MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'SAR and QSAR in Environmental Research' source. Sat, 10 Oct 2009 19:36:58 +0100 http://www.medworm.com/index.php?rid=2544269&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19544188%26dopt%3DAbstract Authors: Burton J, Danloy E, Vercauteren DP The evaluation of the ADME (absorption, distribution, metabolism, and excretion) properties of drug candidates is an important stage in drug discovery. To speed up the numerous tests carried out on large databases of compounds, the help of robust and accurate in silico filters is increasingly required. We propose here a method to build predictive and interpretable models for the prediction of cytochrome P450 (CYP) 1A2 and 2D6 inhibition using recursive partitioning (RP), a well-known technique for the construction of decision trees. The originality of the work is the use of several descriptions of the molecules in terms of fragments, i.e. the MACCS keys and five in-house fingerprints based on the electron density properties of fragments, empl... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=2544269 Sun, 28 Jun 2009 02:07:02 +0100 2544269 http://www.medworm.com/index.php?rid=2544267&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19544189%26dopt%3DAbstract Authors: van Leeuwen K, Schultz TW, Henry T, Diderich B, Veith GD Hazard assessments of chemicals have been limited by the availability of test data and the time needed to evaluate the test data. While available data may be inadequate for the majority of industrial chemicals, the body of existing knowledge for most hazards is large enough to permit reliable estimates to be made for untested chemicals without additional animal testing. We provide a summary of the growing use by regulatory agencies of the chemical categories approach, which groups chemicals based on their similar toxicological behaviour and fills in the data gaps in animal test data such as genotoxicity and aquatic toxicity. Although the categories approach may be distinguished from the use of quantitative structure-acti... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=2544267 Sun, 28 Jun 2009 02:07:02 +0100 2544267 http://www.medworm.com/index.php?rid=2544265&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19544190%26dopt%3DAbstract Authors: Haftka JJ, Parsons JR, Govers HA Strong sorption of hydrophobic organic contaminants to soot or black carbon (BC) is an important environmental process limiting the bioremediation potential of contaminated soils and sediments. Reliable methods to predict BC sorption coefficients for organic contaminants are therefore required. A computer simulation based on molecular mechanics using force field methods has been applied in this study to calculate BC sorption coefficients of polycyclic aromatic hydrocarbons (PAHs). The free energy difference between PAHs dissolved in water and in water containing a model structure of BC was calculated by thermodynamic integration of Monte Carlo simulated energies of transfer. The free energies were calculated with a hypothetical reference state ... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=2544265 Sun, 28 Jun 2009 02:07:02 +0100 2544265 http://www.medworm.com/index.php?rid=2544263&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19544191%26dopt%3DAbstract Authors: Dearden JC, Cronin MT, Kaiser KL Although thousands of quantitative structure-activity and structure-property relationships (QSARs/QSPRs) have been published, as well as numerous papers on the correct procedures for QSAR/QSPR analysis, many analyses are still carried out incorrectly, or in a less than satisfactory manner. We have identified 21 types of error that continue to be perpetrated in the QSAR/QSPR literature, and each of these is discussed, with examples (including some of our own). Where appropriate, we make recommendations for avoiding errors and for improving and enhancing QSAR/QSPR analyses. PMID: 19544191 [PubMed - in process] (Source: SAR and QSAR in Environmental Research) SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=2544263 Sun, 28 Jun 2009 02:07:02 +0100 2544263 http://www.medworm.com/index.php?rid=2544261&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19544192%26dopt%3DAbstract Authors: Gharagheizi F, Sattari M A quantitative structure-property relationship (QSPR) study was performed to predict the molecular diffusivity of pure chemicals in water. A genetic-algorithm-based multivariate linear regression (GA-MLR) was applied to select the most statistically effective molecular descriptors for modelling the molecular diffusivity of pure chemicals in water. Based on the selected molecular descriptors, a three-layer feed forward neural network (FFNN) was constructed to predict the property. The obtained results showed that the FFNN was able to predict the molecular diffusivity of pure chemicals in water. PMID: 19544192 [PubMed - in process] (Source: SAR and QSAR in Environmental Research) SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=2544261 Sun, 28 Jun 2009 02:07:02 +0100 2544261 http://www.medworm.com/index.php?rid=2544259&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19544193%26dopt%3DAbstract Authors: Gu CG, Ju XH, Jiang X, Wang F, Yang SG, Sun C With quantum chemical computation of density functional theory (DFT), the electronic properties including the polarisabilities, polarisability anisotropies and quadrupole moments of a total of 209 congeners of polybrominated diphenyl ethers (PBDEs) were evaluated. The electronic properties were shown to be highly dependent on the bromination pattern, i.e. their values changed sensitively with the number and sites of bromination. Being similar to the 2,3,7,8-, 1,4,6,9-chlorination of dioxins, respectively, 3,3',4,4'-, 2,2',5,5'-bromination of PBDEs can impose relatively greater effects on the electronic properties. Some of electronic properties were found to be potent in explaining the variance of toxicity, and the potency was verif... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=2544259 Sun, 28 Jun 2009 02:07:02 +0100 2544259 http://www.medworm.com/index.php?rid=2544257&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19544194%26dopt%3DAbstract Authors: Ringsted T, Nikolov N, Jensen GE, Wedebye EB, Niemelä J Human Cytochrome P450 (CYP) is a large group of enzymes that possess an essential function in metabolising different exogenous and endogenous compounds. Humans have more than 50 different genes encoding CYP enzymes, among these a gene encoding for the CYP isoenzyme 2D6, a CYP able to metabolise drugs and other chemicals. A training set of 747 chemicals primarily based on in vivo human data for the CYP isoenzyme 2D6 was collected from the literature. QSAR models focusing on substrate/non-substrate activity were constructed by the use of MultiCASE, Leadscope and MDL quantitative structure-activity relationship (QSAR) modelling systems. They cross validated (leave-groups-out) with concordances of 71%, 81% and 82%, respe... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=2544257 Sun, 28 Jun 2009 02:07:02 +0100 2544257 http://www.medworm.com/index.php?rid=2544255&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19544195%26dopt%3DAbstract Authors: Srivastava M, Singh H, Naik PK The anti-malarial activity of artemisinin-derived drugs appears to be mediated by an interaction of the drug's endoperoxide bridge with intra-parasitic haeme. The binding affinity of artemisinin analogues with haeme were computed using linear interaction energy with a surface generalised Born (LIE-SGB) continuum solvation model. Low levels of root mean square error (0.348 and 0.415 kcal/mol) as well as significant correlation coefficients (r(2) = 0.868 and 0.892) between the experimental and predicted free energy of binding (FEB) based on molecular dynamics and hybrid Monte Carlo sampling techniques establish the SGB-LIE method as an efficient tool for generating more potent inhibitors of haeme polymerisation inhibition. PMID: 19544195 [PubMe... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=2544255 Sun, 28 Jun 2009 02:07:02 +0100 2544255 http://www.medworm.com/index.php?rid=2544253&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19544196%26dopt%3DAbstract Authors: Skvortsova MI, Palyulin VA, Zefirov NS A novel method is suggested for constructing topological indices (TIs) of molecular graphs which models human logic. This method is described in terms of a block scheme, consisting of the mutually connected elementary blocks. In each block the simple transformations of a molecular graph are fulfilled. A variant of the transformation is selected from the list of possible variants. Every TI is obtained as a result of the sequential execution of a number of operations, corresponding to some 'walk' on the block scheme. This walk can be selected both randomly and by the investigator. The suggested method can serve as a basis for the development of the respective computer program which may be used for the automatic construction of any number of... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=2544253 Sun, 28 Jun 2009 02:07:02 +0100 2544253 http://www.medworm.com/index.php?rid=2544251&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19544197%26dopt%3DAbstract Authors: Oros G, Cserháti T The antifungal activity of 14 anthracene-based synthetic dyes and 6 reference compounds was measured on 36 fungal strains and the data matrix was evaluated separately by principal component analysis (PCA) and using a spectral mapping technique (SPM). The dimensionality of the maps of principal component loadings and variables and the selectivity maps was reduced to two by non-linear mapping. Except for two compounds, the dyes showed marked antifungal activity. Calculations proved that both the strength and selectivity of the biological effect of anthracene-based dyes were highly dependent on the chemical structure of the dye and on the type of fungi. PCA and SPM revealed different aspects of the antifungal activity, therefore, their simultaneous applica... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=2544251 Sun, 28 Jun 2009 02:07:02 +0100 2544251 http://www.medworm.com/index.php?rid=2544249&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19544198%26dopt%3DAbstract Authors: Mackay D, Arnot JA, Petkova EP, Wallace KB, Call DJ, Brooke LT, Veith GD The physico-chemical properties relevant to the equilibrium partitioning (bioconcentration) of chemicals between organisms and their respired media of water and air are reviewed and illustrated for chemicals that range in hydrophobicity. Relationships are then explored between freely dissolved external concentrations such as LC50s and chemical properties for one important toxicity mechanism, namely baseline toxicity or narcosis. The 'activity hypothesis' proposed by Ferguson in 1939 provides a coherent and compelling explanation for baseline toxicity of chemicals in both water- and air-respiring organisms, as well as a reference point for identifying more specific toxicity pathways. From inhalation studie... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=2544249 Sun, 28 Jun 2009 02:07:02 +0100 2544249 http://www.medworm.com/index.php?rid=2321832&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19343582%26dopt%3DAbstract Authors: Chen X, Liang YZ, Yuan DL, Xu QS To meet the requirements of providing accurate, robust, and interpretable prediction of bioactivity, a modified uncorrelated linear discriminant analysis (M-ULDA) model was developed. In addition, a feature selection method called recursive feature elimination (RFE), originally used for support vector machine (SVM), was introduced and modified to fit the scheme of ULDA. From the evaluation of six pharmaceutical datasets, the M-UDLA coupled with RFE showed better or comparable classification accuracy with respect to other well-studied methods such as SVM and decision trees. The RFE used for ULDA has the advantage of increasing the computational speed and provides useful insights into biochemical mechanisms related to pharmaceutical activity by s... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=2321832 Thu, 01 Jan 2009 05:00:00 +0100 2321832 http://www.medworm.com/index.php?rid=2321828&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19343583%26dopt%3DAbstract Authors: Tan NX, Rao HB, Li ZR, Li XY In this paper we report a successful application of machine learning approaches to the prediction of chemical carcinogenicity. Two different approaches, namely a support vector machine (SVM) and artificial neural network (ANN), were evaluated for predicting chemical carcinogenicity from molecular structure descriptors. A diverse set of 844 compounds, including 600 carcinogenic (CG+) and 244 noncarcinogenic (CG-) molecules, was used to estimate the accuracies of these approaches. The database was divided into two sets: the model construction set and the independent test set. Relevant molecular descriptors were selected by a hybrid feature selection method combining Fischer's score and Monte Carlo simulated annealing from a wide set of molecular desc... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=2321828 Thu, 01 Jan 2009 05:00:00 +0100 2321828 http://www.medworm.com/index.php?rid=2321824&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19343584%26dopt%3DAbstract Authors: Fatemi MH, Baher E In this work, the degradability rate constants of 98 alkenes by OH radicals were predicted from theoretically derived descriptors, which were calculated from the molecular structure alone by applying a quantitative structure-property relationship (QSPR) approach. For the selection of the most relevant descriptors, stepwise multiple linear regression (MLR) and genetic algorithms (GAs) were used. Then some linear and nonlinear techniques were used for the investigation of the relation between selected molecular descriptors and the OH radical degradability rate constant. These methods were MLR, artificial neural networks (ANNs) and support vector machines (SVMs). According to the variable selection method and feature mapping techniques, six QSPR models were con... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=2321824 Thu, 01 Jan 2009 05:00:00 +0100 2321824 http://www.medworm.com/index.php?rid=2321820&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19343585%26dopt%3DAbstract Authors: Wang L, Liu XH, Wu D, Xu MZ, Sun T, Cui BS, Yang ZF Using quantum chemical descriptors and partial least squares regression, a quantitative structure-activity relationship (QSAR) model is developed for the depuration rate constants (log k(d)) of 62 polychlorinated biphenyls (PCBs) in juvenile rainbow trout (Oncorhynchus mykiss). The values of the cross-validated regression coefficient (Qcum(2)) and standard deviation (SD) are 0.655 and 0.05, respectively. The high cross-validated coefficient and low standard deviation indicate that the QSAR model is well predictive. In the QSAR model, the following six descriptors are highly significant: QH(+) (the most positive charge of a hydrogen atom), HOF (standard heat of formation), CCR (core-core repulsion), EE (electronic energy), alp... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=2321820 Thu, 01 Jan 2009 05:00:00 +0100 2321820 http://www.medworm.com/index.php?rid=2321814&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19343586%26dopt%3DAbstract Authors: Kim J, Lee C, Chong Y Influenza endonucleases have appeared as an attractive target of antiviral therapy for influenza infection. With the purpose of designing a novel antiviral agent with enhanced biological activities against influenza endonuclease, a three-dimensional quantitative structure-activity relationships (3D-QSAR) model was generated based on 34 influenza endonuclease inhibitors. The comparative molecular similarity index analysis (CoMSIA) with a steric, electrostatic and hydrophobic (SEH) model showed the best correlative and predictive capability (q(2) = 0.763, r(2) = 0.969 and F = 174.785), which provided a pharmacophore composed of the electronegative moiety as well as the bulky hydrophobic group. The CoMSIA model was used as a pharmacophore query in the UNITY ... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=2321814 Thu, 01 Jan 2009 05:00:00 +0100 2321814 http://www.medworm.com/index.php?rid=2321809&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19343587%26dopt%3DAbstract Authors: Basak SC, Mills D In this paper a set of graph theoretic molecular descriptors was used to predict the normal vapour pressure of a collection of 121 chlorinated organic chemicals. The easily calculated topological descriptors resulted in a robust quantitative structure-property relationship (QSPR) model with q(2) of 0.988, which is comparable to a model published previously developed using the computationally expensive density functional theory (DFT) method at the B3LYP level (Becke three-parameter exchange, Lee-Yang-Parr correlation). The addition of computer-intensive quantum chemical descriptors, including polarizability, to the set of topological descriptors did not improve the predictive ability of the model. PMID: 19343587 [PubMed - in process] (Source: SAR and QSAR ... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=2321809 Thu, 01 Jan 2009 05:00:00 +0100 2321809 http://www.medworm.com/index.php?rid=2321803&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19343588%26dopt%3DAbstract Authors: Nikolic K, Filipic S, Agbaba D Selective imidazoline(1)-receptor (I(1)-R) ligands are used clinically to reduce blood pressure. Thus, there is significant interest in developing new imidazoline analogs with high selectivity and affinity for I(1) receptors. A quantitative structure-activity relationship (QSAR) study was carried out on 11 potent I(1)-R ligands (derivatives of imidazoline, oxazoline and pyrroline) using a multiple linear regression (MLR) procedure. The selected compounds have been studied using B3LYP/3-21G(d, p) and B3LYP/6-31G(d, p) methods. Among the 42 descriptors that were considered in generating the QSAR model, three descriptors (partial atomic charges of nitrogen in the heterocyclic moiety (N-2 charge), log D and the dipole moment of the ligands) resulted ... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=2321803 Thu, 01 Jan 2009 05:00:00 +0100 2321803 http://www.medworm.com/index.php?rid=2321796&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19343589%26dopt%3DAbstract In this study the PBT predictions obtained from the more user-friendly PBT Profiler and the Danish(Q)SAR database for the chemicals were compared with the results taken directly from the EPI Suite software. It was found that these widely used (Q)SAR databases might have some errors and examples are provided. It was concluded that extra care must be taken when considering the use of these databases for PBT screening. In addition, to increase the likelihood of a correct prediction, data estimates from various (Q)SAR models relevant to the PBT endpoints must be compared. PMID: 19343589 [PubMed - in process] (Source: SAR and QSAR in Environmental Research) SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=2321796 Thu, 01 Jan 2009 05:00:00 +0100 2321796 http://www.medworm.com/index.php?rid=2321791&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19343590%26dopt%3DAbstract Authors: Aladjov H, Todorov M, Schmieder P, Serafimova R, Mekenyan O, Veith G To develop quantitative structure-activity relationships (QSAR) models capable of predicting adverse effects for large chemical inventories and diverse structures, an interactive approach is presented that includes testing of strategically selected chemicals to expand the scope of a preliminary model to cover a target inventory. The goal of chemical selection in this context is to make the testing more effective in terms of adding maximal new structural information to the predictive model with minimal testing. The aim of this paper is to describe a set of algorithmic solutions and modelling techniques that can be used to efficiently select chemicals for testing to achieve a variety of goals. One purpose of ch... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=2321791 Thu, 01 Jan 2009 05:00:00 +0100 2321791 http://www.medworm.com/index.php?rid=1880056&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18853295%26dopt%3DAbstract Authors: Maunz A, Helma C We propose a new kernel, based on 2-D structural chemical similarity, that integrates activity-specific information from the training data, and a new approach to applicability domain estimation that takes feature significances and activity distributions into consideration. The new kernel provides superior results than the well-established Tanimoto kernel, and activity-sensitive feature selection enhances prediction quality. Validation of local support vector regression models based on this kernel has been preformed with three publicly available datasets from the DSSTox project. One of them (Fathead Minnow Acute Toxicity) has been already modelled by other groups, and serves as a benchmark dataset, the other two (Maximum Recommended Therapeutic Dose, IRIS Lifet... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1880056 Thu, 16 Oct 2008 12:13:12 +0100 1880056 http://www.medworm.com/index.php?rid=1880055&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18853296%26dopt%3DAbstract Authors: Spycher S, Netzeva TI, Worth AP, Escher BI A new approach for classification of uncouplers of oxidative and photophosphorylation, also suitable for screening of large chemical inventories, is introduced. Earlier fragment-based approaches for this mode of toxic action are limited to phenols but weak acids of extremely diverse chemical classes can act as uncouplers. The proposed approach overcomes the limitation to phenolic uncouplers by combining structural fragments with the global information of physico-chemical descriptors. In a top-down approach to reduce the number of candidate chemicals, firstly substructure definitions for the detection of weak acids were applied. Subsequently, conservative physico-chemical thresholds for the two most important properties for the uncoupl... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1880055 Thu, 16 Oct 2008 12:13:12 +0100 1880055 http://www.medworm.com/index.php?rid=1880054&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18853297%26dopt%3DAbstract Authors: Luan F, Si HZ, Liu HT, Wen YY, Zhang XY Quantitative structure-activity relationship models for the prediction of the mean and the maximum atmospheric degradation half-life values of persistent organic pollutants were developed based on the linear heuristic method (HM) and non-linear gene expression programming (GEP). Molecular descriptors, calculated from the structures alone, were used to represent the characteristics of the compounds. HM was used both to pre-select the whole descriptor sets and to build the linear model. GEP yielded satisfactory prediction results: the square of the correlation coefficient r(2) was 0.80 and 0.81 for the mean and maximum half-life values of the test set, and the root mean square errors were 0.448 and 0.426, respectively. The results of this ... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1880054 Thu, 16 Oct 2008 12:13:12 +0100 1880054 http://www.medworm.com/index.php?rid=1880053&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18853298%26dopt%3DAbstract Authors: Kel A, Voss N, Valeev T, Stegmaier P, Kel-Margoulis O, Wingender E Different signal transduction pathways leading to the activation of transcription factors (TFs) converge at key molecules that master the regulation of many cellular processes. Such crossroads of signalling networks often appear as "Achilles Heels" causing a disease when not functioning properly. Novel computational tools are needed for analysis of the gene expression data in the context of signal transduction and gene regulatory pathways and for identification of the key nodes in the networks. An integrated computational system, ExPlain (www.biobase.de) was developed for causal interpretation of gene expression data and identification of key signalling molecules. The system utilizes data from two databases (TR... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1880053 Thu, 16 Oct 2008 12:13:12 +0100 1880053 http://www.medworm.com/index.php?rid=1880052&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18853299%26dopt%3DAbstract Authors: Patlewicz G, Jeliazkova N, Safford RJ, Worth AP, Aleksiev B Risk assessment for most human health effects is based on the threshold of a toxicological effect, usually derived from animal experiments. The Threshold of Toxicological Concern (TTC) is a concept that refers to the establishment of a level of exposure for all chemicals below which there would be no appreciable risk to human health. When carefully applied, the TTC concept can provide a means of waiving testing based on knowledge of exposure limits. Two main approaches exist; the first of these is a General Threshold of Toxicological Concern; the second approach is a TTC in relation to structural information and/or toxicological data of chemicals. The structural scheme most routinely used is that of Cramer and co-work... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1880052 Thu, 16 Oct 2008 12:13:12 +0100 1880052 http://www.medworm.com/index.php?rid=1880051&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18853300%26dopt%3DAbstract Authors: Hawkins DM, Kraker JJ, Basak SC, Mills D Traditionally, QSAR and QSPR models have been fitted by splitting the available compounds into separate learning and validation sets. The model is then fitted to the learning set and assessed using the validation set. Cross-validation (CV) uses all available compounds for both purposes, so that the full body of available information is brought to bear on both the learning and the validation portions of the study. The price paid for this additional information is a substantially greater computational load. A common mistake in using CV is to omit some of the repetitive computations. This mistake leads to substantial bias in the assessment. A hydroxyl radical reaction rate dataset is used to illustrate the superiority of CV and the pitfall... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1880051 Thu, 16 Oct 2008 12:13:12 +0100 1880051 http://www.medworm.com/index.php?rid=1880050&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18853301%26dopt%3DAbstract Authors: Yang S, Tian F, Li Z How to extract and characterize information on molecular microstructures is deemed to be the key task to accurately simulate and predict molecular properties. In terms of atomic attributes, atoms in a molecule are divided into three levels. Based upon that, inter-atomic correlations are mapped to certain reasonable spatial coordinates in virtue of radial distribution function, generating the novel molecular graph fingerprint (MoGF), which essentially provides insight into molecular inner structures. MoGF, committing itself to transformation of molecular structures into characteristic graph curves, shows valuable advantages such as easy calculation, experimental parameters-free, rich information content, and structural significance and intuitive expressions... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1880050 Thu, 16 Oct 2008 12:13:12 +0100 1880050 http://www.medworm.com/index.php?rid=1880049&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18853302%26dopt%3DAbstract Authors: Enoch SJ, Madden JC, Cronin MT Skin sensitisation is a key endpoint under REACH as it is costly and its assessment currently has a high dependency on animal testing. In order to reduce both the cost and the numbers of animals tested, it is likely that (quantitative) structure-activity relationships ((Q)SAR) and read-across methods will be utilised as part of intelligent testing strategies. The majority of skin sensitisers elicit their effect via covalent bond formation with skin proteins. These reactions have been understood in terms of well defined nucleophilic-electrophilic reaction chemistry. Thus, a first step in (Q)SAR analysis is the assignment of a chemical's potential mechanism of action enabling it to be placed in an appropriate reactivity domain. The aim of this stud... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1880049 Thu, 16 Oct 2008 12:13:12 +0100 1880049 http://www.medworm.com/index.php?rid=1880048&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18853303%26dopt%3DAbstract This article summarizes the workshop report by highlighting the importance of continued QSAR research, the current state of VFAR science, and the guidance provided to the National Homeland Security Research Center and National Risk Management Research Laboratory by an expert panel for the continued use and development of computational approaches. PMID: 18853303 [PubMed - in process] (Source: SAR and QSAR in Environmental Research) SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1880048 Thu, 16 Oct 2008 12:13:12 +0100 1880048 http://www.medworm.com/index.php?rid=1880047&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18853304%26dopt%3DAbstract In this study, a new series of 2,5-disubstituted benzoxazoles was synthesized and their structures were elucidated by elemental analysis, MASS, (1)H-NMR, (13)C-NMR and IR spectral data. Newly and previously synthesized 2,5-disubstituted benzoxazole derivatives were evaluated for antibacterial and antifungal activity against standard strains and their drug-resistant isolates. Microbiological results showed that the compounds presented a large spectrum of activity having MIC values of 250-7.8 microg mL(-1) against the tested microorganisms. Among the newly synthesized derivatives 3-22, compound 11 was the most active against Candida krusei out of all; however, it was one dilution less potent than standard drug fluconazole. In addition, all the new and previous compounds were more active than... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1880047 Thu, 16 Oct 2008 12:13:12 +0100 1880047 http://www.medworm.com/index.php?rid=1646248&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18637284%26dopt%3DAbstract This study was undertaken to test the hypothesis that structurally similar PAHs induce similar gene expression profiles. THP-1 cells were exposed to a series of 12 selected PAHs at 50 microM for 24 hours and gene expressions profiles were analyzed using both unsupervised and supervised methods. Clustering analysis of gene expression profiles revealed that the 12 tested chemicals were grouped into five clusters. Within each cluster, the gene expression profiles are more similar to each other than to the ones outside the cluster. One-methylanthracene and 1-methylfluorene were found to have the most similar profiles; dibenzothiophene and dibenzofuran were found to share common profiles with fluorine. As expression pattern comparisons were expanded, similarity in genomic fingerprint dropped of... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1646248 Tue, 01 Apr 2008 04:00:00 +0100 1646248 http://www.medworm.com/index.php?rid=1637902&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18484496%26dopt%3DAbstract Authors: Kuz'min VE, Polischuk PG, Artemenko AG, Makan SY, Andronati SA The influence of molecular structure of 346 ligands on their affinity for 5-HT1A receptors was investigated. It was shown that the effectiveness of the proposed novel approach for interpretation of decision tree models compared favourably with the PLS method. In the context of the proposed approach, molecular fragments and their values of the relative influence on the affinity for 5-HT1A receptors were defined. PMID: 18484496 [PubMed - in process] (Source: SAR and QSAR in Environmental Research) SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1637902 Tue, 01 Apr 2008 04:00:00 +0100 1637902 http://www.medworm.com/index.php?rid=1454699&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18484495%26dopt%3DAbstract Authors: Huuskonen J, Livingstone DJ, Manallack DT Using a training set of 191 drug-like compounds extracted from the AQUASOL database a quantitative structure-property relationship (QSPR) study was conducted employing a set of simple structural and physicochemical properties to predict aqueous solubility. The resultant regression model comprised five parameters (ClogP, molecular weight, indicator variable for aliphatic amine groups, number of rotatable bonds and number of aromatic rings) and demonstrated acceptable statistics (r(2) = 0.87, s = 0.51, F = 243.6, n = 191). The model was applied to two test sets consisting of a drug-like set of compounds (r(2) = 0.80, s = 0.68, n = 174) and a set of agrochemicals (r(2) = 0.88, s = 0.65, n = 200). Using the established general solubility e... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1454699 Tue, 01 Apr 2008 04:00:00 +0100 1454699 http://www.medworm.com/index.php?rid=1454698&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18484496%26dopt%3DAbstract Authors: Kuz'min VE, Polischuk PG, Artemenko AG, Makan SY, Andronati SA The influence of molecular structure of 346 ligands on their affinity for 5-HT(1A) receptors was investigated. It was shown that the effectiveness of the proposed novel approach for interpretation of decision tree models compared favourably with the PLS method. In the context of the proposed approach, molecular fragments and their values of the relative influence on the affinity for 5-HT(1A) receptors were defined. PMID: 18484496 [PubMed - in process] (Source: SAR and QSAR in Environmental Research) SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1454698 Tue, 01 Apr 2008 04:00:00 +0100 1454698 http://www.medworm.com/index.php?rid=1454697&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18484497%26dopt%3DAbstract Authors: Rocher A, Marchand-Geneste N Five homology models for honeybee (Apis mellifera) nicotinic acetylcholine receptor (nAChR) alpha1/beta1, alpha3/beta2, alpha4/beta2, alpha6/beta2 and alpha9/alpha9 subtypes were built from the Torpedo marmorata nAChR X-ray structure. Then, imidacloprid, fipronil and their metabolites were docked into the ligand binding domain (LBD) of these receptors and the corresponding scoring functions were calculated. The binding modes of the docked compounds were carefully analysed. Finally, multivariate analyses were used for deriving structure-activity relationships based on hydrogen bond number and scoring functions between the insecticides and the nAChR models. PMID: 18484497 [PubMed - in process] (Source: SAR and QSAR in Environmental Research) SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1454697 Tue, 01 Apr 2008 04:00:00 +0100 1454697 http://www.medworm.com/index.php?rid=1454696&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18484498%26dopt%3DAbstract This study presents a QSAR/QSPR modelling and chemical grouping (read-across) approach to provide information on the biological properties of a group of aliphatic ethers, with accurate biological predictions restricted to those physico-chemical and (eco)toxicological properties where the performance of QSAR/QSPR has been shown to be acceptable. The mathematical methods used ranged from multivariate regression models to PLS (partial least-squares), SVM (support vector machines) and Sammon's mapping. A novel grouping approach, based on a set of key descriptors, has been proposed to give a compact picture of the structural and biological properties of the compounds, and to provide a more mechanistic basis for the interpretations of chemical groups. Besides being a straightforward case study, ... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1454696 Tue, 01 Apr 2008 04:00:00 +0100 1454696 http://www.medworm.com/index.php?rid=1454695&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18484499%26dopt%3DAbstract This study reports an examination of the use of these descriptions of molecules to model a simple chemical interaction (complex formation) and a diverse set of mutagens. Both of these systems have been modelled successfully and the results are discussed. PMID: 18484499 [PubMed - in process] (Source: SAR and QSAR in Environmental Research) SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1454695 Tue, 01 Apr 2008 04:00:00 +0100 1454695 http://www.medworm.com/index.php?rid=1454694&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18484500%26dopt%3DAbstract Authors: Sobolev EV, Sobolev OV, Tikhonov DA An online resource has been developed for the theoretical study of hydration of biopolymers by the RISM (Reference Interaction Site Model) method, deriving from the integral equation theory of liquids. The online resource is based upon original software developed by the authors and includes all steps in studying a biopolymer with a given spatial structure and force field. It prepares the input data and carries out the RISM calculation yielding the atom-atom correlation functions of the biopolymer with water as solvent. From these functions the algorithm finds atomic partial contributions to the hydration free energy using various free energy expressions from integral equation theory. The calculated results are automatically recorded in a dat... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1454694 Tue, 01 Apr 2008 04:00:00 +0100 1454694 http://www.medworm.com/index.php?rid=1454693&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18484501%26dopt%3DAbstract Authors: Novic M, Randic M A novel representation of proteins was introduced. It is independent of arbitrary decisions with respect to the choice of labels to be assigned to the 20 natural amino acids. The approach is based on an assignment of 20 unit vectors in 20-dimensional vector space to the 20 natural amino acids. Proteins are then represented by a walk, that is, a sequence of steps in the 20-dimensional space analogous to a walk in the (x, y) plane in the case of binary strings. A straightforward numerical characterization of proteins is obtained from the distance matrix associated with the walk representing the protein in 20-dimensional space combining the information on the Euclidean distance between various amino acids in protein sequence. The Line Distance matrix offers addi... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1454693 Tue, 01 Apr 2008 04:00:00 +0100 1454693 http://www.medworm.com/index.php?rid=1454692&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18484502%26dopt%3DAbstract Authors: Randic M, Novic M, Vracko M A novel characterization of proteins is presented based on selected properties of recently introduced 20 x 20 amino acid adjacency matrix of proteins in which matrix elements count the occurrence of all 400 possible pair-wise adjacencies obtained by reading protein primary sequence from the left to the right. In particular we consider the characterization based on the sum and the difference of the rows and the corresponding columns, which characterize proteins by a pair of 20-component vectors. The approach is illustrated on a set of ND6 proteins of eight species. PMID: 18484502 [PubMed - in process] (Source: SAR and QSAR in Environmental Research) SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1454692 Tue, 01 Apr 2008 04:00:00 +0100 1454692 http://www.medworm.com/index.php?rid=1454691&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18484503%26dopt%3DAbstract Authors: Wang Y, Li Y, Ding J, Jiang Z, Chang Y Bioconcentration assessment is important in the scientific evaluation of risks that chemicals may pose to humans and environment and is a current focus of regulatory effort. In this work, a new QSAR model by adopting electronic topological properties and flexibility of chemicals to predict the bioconcentration factor (BCF) in fish was established based on a large number of diverse compounds. Multiple linear regression (MLR) and partial least squares (PLS) were used to build reliable QSARs, which were evaluated with internal five cross-validations [image omitted] and an external validation [image omitted]. The proposed MLR model showed reasonable predictivity of BCF (Q(cv)(2) = 0.79,Q(ex)(2) = 0.79) and included seven molecular descriptors... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1454691 Tue, 01 Apr 2008 04:00:00 +0100 1454691 http://www.medworm.com/index.php?rid=1454690&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18484504%26dopt%3DAbstract Authors: Patlewicz G, Jeliazkova N, Gallegos Saliner A, Worth AP Chemical similarity is a widely used concept in toxicology, and is based on the hypothesis that similar compounds should have similar biological activities. This forms the underlying basis for performing read-across, forming chemical groups and developing (Quantitative) Structure-Activity Relationships ((Q)SARs). Chemical similarity is often perceived as structural similarity but in fact there are a number of other approaches that can be used to assess similarity. A systematic similarity analysis usually comprises two main steps. Firstly the chemical structures to be compared need to be characterised in terms of relevant descriptors which encode their physicochemical, topological, geometrical and/or surface properties. A ... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1454690 Tue, 01 Apr 2008 04:00:00 +0100 1454690 http://www.medworm.com/index.php?rid=1278193&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18311630%26dopt%3DAbstract Authors: Sitzmann M, Filippov IV, Nicklaus MC ()New data, tools and services recently made available on the web server (http://cactus.nci.nih.gov) of the Computer-Aided Drug Design (CADD) Group, NCI, NIH, developed in the context of chemoinformatics and drug development work, are presented. These tools are designed for searching for structures in very large databases of small molecules. One of them is a web service-the Chemical Structure Lookup Service (CSLS)-for very rapid structure lookup in an aggregated collection of more than 80 databases comprising more than 27 million unique structures at the time of this writing. CSLS contains pointers to the entries in toxicology-related databases, catalogues of commercially available samples, drugs, assay results data sets, and databases in s... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1278193 Tue, 01 Jan 2008 05:00:00 +0100 1278193 http://www.medworm.com/index.php?rid=1278192&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18311631%26dopt%3DAbstract Authors: Saxena AK, Alam I, Dixit A, Saxena M G-Protein coupled receptors (GPCRs), one of the most important families of drug targets, belong to the super family of integral membrane proteins characterized by seven transmembrane helices. Because they are difficult to crystallize, the three dimensional structure of these receptors have not yet been determined by X-ray crystallography, except one. In the absence of a 3-D structure, in-silico approaches for solving the structure of this class of proteins are widely used and provide valuable information for structure based drug design. There are several web servers and computer programs available that automate the modelling process of GPCRs. Some of these include Modeller, Swiss-Model server, Homer, etc. Using these tools reliable homology... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1278192 Tue, 01 Jan 2008 05:00:00 +0100 1278192 http://www.medworm.com/index.php?rid=1278191&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18311632%26dopt%3DAbstract Authors: Geronikaki A, Druzhilovsky D, Zakharov A, Poroikov V Some computational tools for medicinal chemistry freely available on the Internet were compared to examine whether the results of prediction obtained with different methods coincided or not. It was shown that the correlation coefficients varied from 0.65 to 0.90 for log P (seven methods), from 0.01 to 0.73 for aqueous solubility (four methods), and from 0.19 to 0.73 for drug-likeness (three methods). While for log P estimates, reasonable average pairwise correlation was found, for aqueous solubility and drug-likeness it was rather poor. Therefore, using computational tools freely available via the Internet, medicinal chemists should evaluate their accuracy versus experimental data for particular series of compounds. In contr... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1278191 Tue, 01 Jan 2008 05:00:00 +0100 1278191 http://www.medworm.com/index.php?rid=1278190&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18311633%26dopt%3DAbstract Authors: Kulkarni SA, Zhu J An integrated framework of data analysis has been proposed to systematically address the determination of the domain of applicability (DA) of some commercial Quantitative Structure Activity Relationship ((Q)SAR) models based on the structure of test chemicals. This framework forms one of the important steps in dealing with the growing concerns on reliability of model-based predictions on toxicity of chemicals specifically in the regulatory context. The present study uses some of the well-known mutagenicity and carcinogenicity models that are available within the Casetox (MultiCASE Inc.) and TOPKAT (Accelrys Software Inc.) programs. The approach enumerated in this paper employs chemoinformatics tools that facilitate comparisons of key structural features as w... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1278190 Tue, 01 Jan 2008 05:00:00 +0100 1278190 http://www.medworm.com/index.php?rid=1278189&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18311634%26dopt%3DAbstract Authors: Kiralj R, Ferreira MM Multidrug resistance activities pECr(50) of diverse strains of pathogenic fungus Penicillium digitatum against seven toxicants were studied by Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA). Fungal growth data (radii, circumferences, surface areas of fungal colonies, radius differences and ratios) in absence and presence of toxicants were used to derive eight new descriptors for 35 fungal strains. This data set was studied by PCA and HCA, and was correlated with the genome descriptor PCR for expression of gene CYP51 by Partial Least Squares (PLS) regression. Both analyses of pECr(50) data and of fungal growth data have identified baseline resistance character, origin and target fruits of the fungal strains. In addition, the ana... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1278189 Tue, 01 Jan 2008 05:00:00 +0100 1278189 http://www.medworm.com/index.php?rid=1278188&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18311635%26dopt%3DAbstract Authors: Chuman H The log P value has been the first choice for the molecular hydrophobicity descriptor in QSAR studies. However, it is still now difficult to understand the partitioning phenomenon in terms of physical chemistry. First, an attempt to understand and predict log P is addressed. We formulated a simple model that expressed by the solvent accessible surface area and the solvation energy difference between aqueous and solvent phases. Next, an application of log P in QSAR analyses of ligand-CYP (Cytochrome P450) interaction was described. Azole compounds are widely used as antifungal agents. We showed that the binding affinity of 18 azole compounds with CYP2B and CYP3A were nicely expressed by the bilinear model of log P. These results suggest that molecular hydrophobicity pl... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1278188 Tue, 01 Jan 2008 05:00:00 +0100 1278188 http://www.medworm.com/index.php?rid=1278187&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18311636%26dopt%3DAbstract Authors: Filz O, Lagunin A, Filimonov D, Poroikov V Drug-induced cardiac arrhythmia is acknowledged as a serious obstacle in successful development of new drugs. Several methods for in silico prediction of acquired long QT syndrome (LQTS) caused by the pharmacological blockade of human hERG K(+) channels are discussed in literature. We propose to use the computer program PASS, which estimates the probabilities of about 3000 biological activities, not only for prediction of hERG blockade and QT-prolongation but also for the analysis of indirect mechanisms of these actions. After addition in the PASS training set of 163 compounds with data on QT-Prolongation and re-training, it was shown that accuracy of prediction was 87.1% and 81.8% for hERG blockade and QT-prolongation, respectively. ... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1278187 Tue, 01 Jan 2008 05:00:00 +0100 1278187 http://www.medworm.com/index.php?rid=1278186&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18311637%26dopt%3DAbstract Authors: Pyrkov TV, Priestle JP, Jacoby E, Efremov RG Molecular docking is a powerful computational method that has been widely used in many biomolecular studies to predict geometry of a protein-ligand complex. However, while its conformational search algorithms are usually able to generate correct conformation of a ligand in the binding site, the scoring methods often fail to discriminate it among many false variants. We propose to treat this problem by applying more precise ligand-specific scoring filters to re-rank docking solutions. In this way specific features of interactions between protein and different types of compounds can be implicitly taken into account. New scoring functions were constructed including hydrogen bonds, hydrophobic and hydrophilic complementarity terms. Thes... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1278186 Tue, 01 Jan 2008 05:00:00 +0100 1278186 http://www.medworm.com/index.php?rid=1278185&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18311638%26dopt%3DAbstract Authors: Yildiz I, Ertan T, Bolelli K, Temiz-Arpaci O, Yalcin I, Aki E Considering the worth of developing new antibacterial agents against drug-resistant Stapylococcus aureus, the present study explores the structure-activity relationships analysis of N-(2-hydroxy-4(or 5)-nitro/aminophenyl)benzamide and phenylacetamide derivatives using classical QSAR and 3D-common-feature pharmacophore hypothese approaches. QSAR analysis revealed that the compounds possessing a methylene group between the phenyl and the carboxyamido moiety played a role for decreasing the activity. On the other side, substituent effects on position R(1) was found important for the activity and holding a substituent possessing a minimum width property on this position like as alkyl groups enhanced the activity. Moreov... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1278185 Tue, 01 Jan 2008 05:00:00 +0100 1278185 http://www.medworm.com/index.php?rid=1278184&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18311639%26dopt%3DAbstract Authors: Papa E, Pilutti P, Gramatica P Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants of high environmental concern. The experimental data of a mutagenicity test on human B-lymphoblastoid cells (alternative to the Ames bacterial test) for a set of 70 oxo-, nitro- and unsubstituted PAHs, detected in particulate matter (PM), were modelled by Quantitative Structure-Activity Relationships (QSAR) classification methods (k-NN, k-Nearest Neighbour, and CART, Classification and Regression Tree) based on different theoretical molecular descriptors selected by Genetic Algorithms. The best models were validated for predictivity both externally and internally. For external validation, Self Organizing Maps (SOM) were applied to split the original data set. The best models, devel... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1278184 Tue, 01 Jan 2008 05:00:00 +0100 1278184 http://www.medworm.com/index.php?rid=1278183&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18311640%26dopt%3DAbstract In this study, a large set of about 200 chemicals covering a broad range of structural classes was considered in order to categorize their relative binding affinity (RBA) to the androgen receptor. Classification of chemicals into four activity groups, with respect to their log RBA value, was carried out in a cascade of recursive partitioning trees, with descriptors calculated from CODESSA software and encoding topological, geometrical and quantum chemical properties. The hydrophobicity parameter (log P), Balaban index, and descriptors relying on charge distribution (maximum partial charge, nucleophilic index on oxygen atoms, charged surface area, etc.) appear to play a major role in the chemical partitioning. Separation of strongly active compounds was rather straightforward. Similarly, ab... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1278183 Tue, 01 Jan 2008 05:00:00 +0100 1278183 http://www.medworm.com/index.php?rid=1278182&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18311641%26dopt%3DAbstract Authors: Shulga DA, Oliferenko AA, Pisarev SA, Palyulin VA, Zefirov NS Two novel approaches to construct empirical schemes for partial atomic charge calculation were proposed. The charge schemes possess important benefits. First, they produce both topologically symmetrical and environment dependent charges. Second, they can be parameterised to reasonably reproduce ab initio molecular electrostatic potential (MEP), which guarantees their successful use in molecular modelling. To validate the approaches, the parameters of the proposed charge schemes were fitted to best reproduce MEP simultaneously on grids around a set of 227 diverse organic compounds. The residual errors in MEP reproduction due to calculated atomic charges were compared to those due to charges from known charge schemes.... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1278182 Tue, 01 Jan 2008 05:00:00 +0100 1278182 http://www.medworm.com/index.php?rid=1278181&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18311642%26dopt%3DAbstract Authors: Kouskoumvekaki I, Hansen NT, Björkling F, Vadlamudi SM, Jónsdóttir SO Recently we developed a model for prediction of pH-dependent aqueous solubility of drugs and drug like molecules. In the present work, the model was applied on a series of novel Histone Deacetylases (HDAC) inhibitors discovered at TopoTarget. The applicability of our model was evaluated on the series of HDAC inhibitors by use of Self-Organizing Maps (SOM) and 2D-projection of the HDAC inhibitors on the chemical space of the training data set of the artificial neural network (ANN) module. The model was refined for the particular chemical space of interest, which led to two modifications in the training data set of the ANN. The performance of the original and the two modified versions of the mod... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1278181 Tue, 01 Jan 2008 05:00:00 +0100 1278181 http://www.medworm.com/index.php?rid=1278180&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18311643%26dopt%3DAbstract Authors: Bunker A, Männistö P, St Pierre JF, Róg T, Pomorski P, Stimson L, Karttunen M Results from extensive 70 ns all-atom molecular dynamics simulations of catechol-O-methyltransferase (COMT) enzyme are reported. The simulations were performed with explicit TIP3P water and Mg(2 +) ions. Four different crystal structures of COMT, with and without different ligands, were used. These simulations are among the most extensive of their kind and as such served as a stability test for such simulations. On the methodological side we found that the initial energy minimization procedure may be a crucial step: particular hydrogen bonds may break, and this can initiate an irreversible loss of protein structure that becomes observable in longer time scales of the order of tens of n... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1278180 Tue, 01 Jan 2008 05:00:00 +0100 1278180 http://www.medworm.com/index.php?rid=1052465&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18038362%26dopt%3DAbstract Comment on "Discriminating toxicant classes by mode of action: 3. Substructure indicators" (M. Nendza and M. Müller, SAR QSAR Environ. Res. 18 155 (2007)). SAR QSAR Environ Res. 2007 Dec;18(7):621-4 Authors: Von Der Ohe PC, Kühne R, Ebert RU, Schüürmann G PMID: 18038362 [PubMed - in process] (Source: SAR and QSAR in Environmental Research) SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1052465 Tue, 27 Nov 2007 14:47:10 +0100 1052465 http://www.medworm.com/index.php?rid=1052464&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18038363%26dopt%3DAbstract Response to Letter to the Editor: Comment on "Discriminating toxicant classes by mode of action: 3. Substructure indicators" (M. Nendza and M. Müller, SAR QSAR Environ. Res. 18 155 (2007)) (P. C. von der Ohe, R. Kühne, R. U. Ebert and G. Schüürmann, SAR QSAR Environ. Res. 18 621 (2007)). SAR QSAR Environ Res. 2007 Dec;18(7):625-8 Authors: Nendza M, Müller M PMID: 18038363 [PubMed - in process] (Source: SAR and QSAR in Environmental Research) SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1052464 Tue, 27 Nov 2007 14:47:08 +0100 1052464 http://www.medworm.com/index.php?rid=1052463&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18038364%26dopt%3DAbstract Authors: Devillers J, Doré JC, Guyot M, Poroikov V, Gloriozova T, Lagunin A, Filimonov D Over the past decade cyanobacteria have become an interesting source of new classes of pharmacologically active natural products. Some cyanobacterial secondary metabolites (CSMs) are also well known for their toxic effects on living species. The PASS (Prediction of Activity Spectra for Substances) computer program, which is able to simultaneously predict more than one thousand biological and toxicological activities from only the structural formulas of the chemicals, was used to predict the biological activity profile of 681 CSMs. Multivariate methods were employed to structure and analyse this wealth of biological and chemical information. PASS predictions were successfully compared to the av... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1052463 Tue, 27 Nov 2007 14:47:07 +0100 1052463 http://www.medworm.com/index.php?rid=1052462&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18038365%26dopt%3DAbstract This study presents a novel approach to toxicity modelling that handles the involved uncertainties using a fuzzy filter, and thus improves the generalization capability of the model. The method is illustrated by considering a data set dealing with the fathead minnow (Pimephales promelas) toxicity of 568 organic compounds. PMID: 18038365 [PubMed - in process] (Source: SAR and QSAR in Environmental Research) SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1052462 Tue, 27 Nov 2007 14:47:05 +0100 1052462 http://www.medworm.com/index.php?rid=1052461&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18038366%26dopt%3DAbstract Authors: Rasulev BF, Saidkhodzhaev AI, Nazrullaev SS, Akhmedkhodzhaeva KS, Khushbaktova ZA, Leszczynski J The relationship between chemical structure and estrogenic activity in a series of terpenoid esters with aromatic and aliphatic acid substituents isolated from Ferula plants, was studied. The fragments of the terpenoid structure that are potentially responsible for estrogenic activity were revealed. A quantitative structure-estrogenic activity study has been carried out using the QSAR approach with use of data derived from quantum-chemical calculations as well as data generated from three-dimensional structures of terpenoids. A number of molecular descriptors was obtained from the density functional theory (DFT) at the B3LYP/6-31G(d, p) level of calculation. Comparative analysis of... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1052461 Tue, 27 Nov 2007 14:47:04 +0100 1052461 http://www.medworm.com/index.php?rid=1052460&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18038367%26dopt%3DAbstract Authors: Fratev F, Piparo EL, Benfenati E, Mihaylova E 3D-QSAR, Docking, Local Binding Energy (LBE) and GRID methods were integrated as a tool for predicting toxicity and studying mechanisms of action. The method was tested on a set of 73 allelochemical-like pesticides, for which acute toxicity (LD(50)) for the rat was available. 3D-QSAR gave a model with high predictive ability and the regression maps indicated the important toxic chemical substituents. Significant ligand-protein residue interactions and oxidation positions in the binding site were found by docking analysis using CYP1A2 homology modelling. The binding energies of the compounds and the important substituents (Local Binding Energy, LBE) were calculated in order to demonstrate quantitatively the substituent contributions... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1052460 Tue, 27 Nov 2007 14:47:02 +0100 1052460 http://www.medworm.com/index.php?rid=1052459&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18038368%26dopt%3DAbstract Authors: Sedykh A, Klopman G An alternate representation of the biodegradation of chemicals (biochemical oxygen demand (BOD) amount instead of BOD-based degradation percentage) allows the derivation of an improved QSAR model. The structural descriptors for this model are related to biodegradation mechanisms. A linear group contribution model of 99 variables was derived from a training set of 1190 chemicals. The squared correlation coefficients for self-prediction and for 20%-off cross-validation were 0.83 and 0.69, respectively. Additional external validation with 62 reported in the literature chemicals resulted in 91% overall correct classification, although ready biodegradable molecules were too few and predicted poorly (two out of five correct). PMID: 18038368 [PubMed - in proce... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1052459 Tue, 27 Nov 2007 14:47:00 +0100 1052459 http://www.medworm.com/index.php?rid=1052458&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18038369%26dopt%3DAbstract Authors: Salum LB, Polikarpov I, Andricopulo AD The estrogen receptor-beta subtype (ERbeta) is an attractive drug target for the development of novel therapeutic agents for hormone replacement therapy. Hologram quantitative structure-activity relationships (HQSAR) were conducted on a series of 6-phenylnaphthalene and 2-phenylquinoline derivatives, employing values of ERbeta binding affinity. A training set of 65 compounds served to derive the models. The best statistical HQSAR model (q(2) = 0.73 and r(2) = 0.91) was generated using atoms, bonds, connections and donor and acceptor as fragment distinction parameters, and fragment size default (4-7) with hologram length of 199. The model was used to predict the binding affinity of an external test set of 16 compounds, and the predicted va... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1052458 Tue, 27 Nov 2007 14:46:59 +0100 1052458 http://www.medworm.com/index.php?rid=1052457&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18038370%26dopt%3DAbstract Authors: Kim JH, Gramatica P, Kim MG, Kim D, Tratnyek PG The aim of this study was to determine the degradability of 26 Alkylphenols (APs) by Chemical Oxygen Demand (COD) and/or 5-day Biochemical Oxygen Demand (BOD(5)), and to describe these data from Quantitative Structure-activity Relationships (QSARs). Statistical analysis techniques, such as Multiple Linear Regression (MLR), Principal Component Regression (PCR), Partial Least-Squares (PLS) Regression and Neural Network (NN) were carried out to calibrate and validate four-descriptor QSAR models using two different types of descriptor sets. Stable MLR-QSAR models using Leave-One-Out (LOO) were obtained with high predictability performance: r(2) = 0.924, [image omitted] = 0.854 for log (1/BOD) model on 24 APs and r(2) = 0.888, [image ... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1052457 Tue, 27 Nov 2007 14:46:57 +0100 1052457 http://www.medworm.com/index.php?rid=1052456&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18038371%26dopt%3DAbstract Authors: García-Domenech R, Alarcón-Elbal P, Bolas G, Bueno-Marí R, Chordá-Olmos FA, Delacour SA, Mouriño MC, Vidal A, Gálvez J Topological indices were used in the prediction of the acute toxicity (intraperitoneal and oral LD(50)) of organophosphorus pesticides on rats. Models with six variables for the prediction of LD(50)-i.p. (r = 0.849, Q(2) = 0.613) and eight variables for LD(50)-oral (r = 0.906, Q(2) = 0.701) were selected. External group and cross-validation by use of leave-n-out tests were also performed in order to assess the stability and the prediction performance of the selected topological models. PMID: 18038371 [PubMed - in process] (Source: SAR and QSAR in Environmental Research) SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1052456 Tue, 27 Nov 2007 14:46:56 +0100 1052456 http://www.medworm.com/index.php?rid=1052455&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18038372%26dopt%3DAbstract Authors: PMID: 18038372 [PubMed - in process] (Source: SAR and QSAR in Environmental Research) SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=1052455 Tue, 27 Nov 2007 14:46:54 +0100 1052455 http://www.medworm.com/index.php?rid=896563&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17654333%26dopt%3DAbstract Authors: Li S, Fedorowicz A, Andrew ME A novel descriptor selection scheme for Support Vector Machine (SVM) classification method has been proposed and its utility demonstrated using a skin sensitisation dataset as an example. A backward elimination procedure, guided by mean accuracy (the average of specificity and sensitivity) of a leave-one-out cross validation, is devised for the SVM. Subsets of descriptors were first selected using a sequential t-test filter or a Random Forest filter, before backward elimination was applied. Different kernels for SVM were compared using this descriptor selection scheme. The Radial Basis Function (RBF) kernel worked best when a sequential t-test filter was adopted. The highest mean accuracy, 84.9%, was obtained using SVM with 23 descriptors. The sen... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896563 Sun, 01 Jul 2007 04:00:00 +0100 896563 http://www.medworm.com/index.php?rid=896562&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17654334%26dopt%3DAbstract Authors: Dimitrov S, Pavlov T, Nedelcheva D, Reuschenbach P, Silvani M, Bias R, Comber M, Low L, Lee C, Parkerton T, Mekenyan O Biodegradation plays a key role in the environmental risk assessment of organic chemicals. The need to assess biodegradability of a chemical for regulatory purposes supports the development of a model for predicting the extent of biodegradation at different time frames, in particular the extent of ultimate biodegradation within a '10 day window' criterion as well as estimating biodegradation half-lives. Conceptually this implies expressing the rate of catabolic transformations as a function of time. An attempt to correlate the kinetics of biodegradation with molecular structure of chemicals is presented. A simplified biodegradation kinetic model was formulated... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896562 Sun, 01 Jul 2007 04:00:00 +0100 896562 http://www.medworm.com/index.php?rid=896561&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17654335%26dopt%3DAbstract Authors: Kulkarni SA, Moir D, Zhu J Alterations in molecular structure are responsible for the differential biological response(s) of a chemical inside a biosystem. Structural and functional parameters that govern a chemical's metabolic course and determine its ultimate outcome in terms of mutagenic/carcinogenic potential are extensively reviewed here. A large number of environmentally-significant organic chemicals are addressed under one or more broadly classified groups each representing one or more characteristic structural feature. Numerous examples are cited to illustrate the influence of key structural and functional parameters on the metabolism and DNA adduction properties of different chemicals. It is hoped that, in the event of limited experimental data on a chemical's bioacti... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896561 Sun, 01 Jul 2007 04:00:00 +0100 896561 http://www.medworm.com/index.php?rid=896560&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17654336%26dopt%3DAbstract Authors: Patlewicz G, Aptula AO, Uriarte E, Roberts DW, Kern PS, Gerberick GF, Kimber I, Dearman RJ, Ryan CA, Basketter DA Skin sensitisation potential is an endpoint that needs to be assessed within the framework of existing and forthcoming legislation. At present, skin sensitisation hazard is normally identified using in vivo test methods, the favoured approach being the local lymph node assay (LLNA). This method can also provide a measure of relative skin sensitising potency which is essential for assessing and managing human health risks. One potential alternative approach to skin sensitisation hazard identification is the use of (Quantitative) structure activity relationships ((Q)SARs) coupled with appropriate documentation and performance characteristics. This represents a major ... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896560 Sun, 01 Jul 2007 04:00:00 +0100 896560 http://www.medworm.com/index.php?rid=896559&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17654337%26dopt%3DAbstract Authors: Raevsky OA, Perlovich GL, Schaper KJ On the basis of octanol solubility data (log S(o)) for 218 structurally diverse solid chemicals it was shown that the exclusive consideration of melting points did not provide satisfactory results in the quantitative prediction of this parameter (s = 0.92). The application of HYBOT physicochemical descriptors separately (s = 0.94) and together with melting points (s = 0.70) in the framework of a common regression model also was not successful, although contributions of volume-related and H-bond terms to solubility in octanol were identified. It was proposed that the main reason for such behaviour was the different crystal lattice interaction of different classes of chemicals. Successful calculations of the solubility in octanol of chemicals... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896559 Sun, 01 Jul 2007 04:00:00 +0100 896559 http://www.medworm.com/index.php?rid=896558&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17654338%26dopt%3DAbstract Authors: Xia XR, Baynes RE, Monteiro-Riviere NA, Riviere JE A system coefficient approach is proposed for quantitative assessment of the solvent effects on membrane absorption from chemical mixtures. The complicated molecular interactions are dissected into basic molecular interaction forces via Abraham's linear solvation energy relationship (LSER). The molecular interaction strengths of a chemical are represented by a set of solute descriptors, while those of a membrane/chemical mixture system are represented by a set of system coefficients. The system coefficients can be determined by using a set of probe compounds with known solute descriptors. Polydimethylsiloxane (PDMS) membrane-coated fibres and 32 probe compounds were used to demonstrate the proposed approach. When a solvent was... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896558 Sun, 01 Jul 2007 04:00:00 +0100 896558 http://www.medworm.com/index.php?rid=896557&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17654339%26dopt%3DAbstract Authors: Alcaro S, Arcone R, Vecchio I, Ortuso F, Gallelli A, Pasceri R, Procopio A, Iannone M The potent herbicide paraquat and three other analogues MPP+, MPDP+ and MPTP have a known toxicological profile linked to the ability to damage dopaminergic neurons. Other biological effects were recently addressed to this class of compounds, including the ability to interact with enzymatic targets involved in the Central Nervous System, such as the acetylcholinesterase (AChE) and the butyrylcholinesterase (BuChE). A combined molecular modelling and enzymatic study focusing onto their interaction against the AChE and BuChE is reported. The former study was performed by docking techniques using target known co-crystallographic models. The latter study was carried out by the widely adopted Ellm... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896557 Sun, 01 Jul 2007 04:00:00 +0100 896557 http://www.medworm.com/index.php?rid=896556&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17654340%26dopt%3DAbstract Authors: Gu CG, Jiang X, Ju XH, Yang XL, Yu GF Density functional theory (DFT) at B3LYP/6-311G** level was employed to optimise the dioxin compounds, i.e., 25 polychlorinated or brominated dibenzo-p-dioxins (PCDDs or PBDDs) and 34 polychlorinated dibenzofurans (PCDFs) involved in this investigation. Three groups of descriptors mainly related to chemical reactivity, molecular overall charge distribution and thermochemical property were calculated. With partial least squares (PLS) analysis and variable importance in the projection (VIP), the least significant descriptors were removed from the quantitative structure-activity relationship (QSAR), which was focused on exploring the influential factors responsible for the variance of binding affinities of dioxins to aryl hydrocarbon receptor... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896556 Sun, 01 Jul 2007 04:00:00 +0100 896556 http://www.medworm.com/index.php?rid=896577&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17514564%26dopt%3DAbstract Authors: Devillers J, Marchand-Geneste N, Doré JC, Porcher JM, Poroikov V A number of chemicals released into the environment have the potential to disturb the normal functioning of the endocrine system. These chemicals termed endocrine disruptors (EDs) act by mimicking or antagonizing the normal functions of natural hormones and may pose serious threats to the reproductive capability and development of living species. Batteries of laboratory bioassays exist for detecting these chemicals. However, due to time and cost limitations, they cannot be used for all the chemicals which can be found in the ecosystems. SAR and QSAR models are particularly suited to overcome this problem but they only deal with specific targets/endpoints. The interest to account for profiles of endocrine act... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896577 Tue, 01 May 2007 04:00:00 +0100 896577 http://www.medworm.com/index.php?rid=896576&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17514565%26dopt%3DAbstract Authors: Jaworska J, Nikolova-Jeliazkova N Chemical category is a regulatory concept facilitating filling safety data gaps. Practically, all chemical management programs like the OECD HPV Program, EU REACH, or the Canadian DSL Categorization are planning to use or are already using categorization approaches to reduce resources including animal testing. The aim of the study was to discuss the feasibility to apply computational structural similarity methods to augment formation of a category. The article discusses also how this understanding can be translated into computer readable format, an ultimate need for practical, broad scope applications. We conclude that for the skin sensitization endpoint, used as a working example, mechanistic understanding expressed as chemical reactivity can... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896576 Tue, 01 May 2007 04:00:00 +0100 896576 http://www.medworm.com/index.php?rid=896575&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17514566%26dopt%3DAbstract Authors: Benfenati E QSAR models have special characteristics depending on the field they are addressing. In the case of QSAR models for regulatory purposes particular requirements should be introduced, to warrant the proper use within a regulatory context. Here the criteria introduced within the European project DEMETRA are presented and discussed. The case discussed here refers to models addressing (eco)toxicological endpoints. Major issues are related to the identification of regulation guidelines, data quality and reproducibility. Further points to be addressed in the model description should be uncertainty and availability of the model, and false negatives, even in the case of regression models. PMID: 17514566 [PubMed - indexed for MEDLINE] (Source: SAR and QSAR in Environment... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896575 Tue, 01 May 2007 04:00:00 +0100 896575 http://www.medworm.com/index.php?rid=896574&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17514567%26dopt%3DAbstract Authors: Tsakovska I, Saliner AG, Netzeva T, Pavan M, Worth AP The proposed REACH regulation within the European Union (EU) aims to minimise the number of laboratory animals used for human hazard and risk assessment while ensuring adequate protection of human health and the environment. One way to achieve this goal is to develop non-testing methods, such as (quantitative) structure-activity relationships ([Q]SARs), suitable for identifying toxicological hazard from chemical structure and physicochemical properties alone. A database containing data submitted within the EU New Chemicals Notification procedure was compiled by the German Bundesinstitut für Risikobewertung (BfR). On the basis of these data, the BfR built a decision support system (DSS) for the prediction of several tox... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896574 Tue, 01 May 2007 04:00:00 +0100 896574 http://www.medworm.com/index.php?rid=896573&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17514568%26dopt%3DAbstract Authors: Basak SC, Natarajan R, Nowak W, Miszta P, Klun JA 2-(2-Hydroxyethyl)-1-piperidinecarboxylic acid 1-methylpropyl ester (Picaridin), and 1-(cyclohex-3-ene-1-ylcarbonyl)-2-methylpiperidine (AI3-37220; 220) are alternatives to DEET (N,N-diethyl-3-methylbenzamide), the most popular mosquito repellent. Picaridin and AI3-37220 exhibit polychiral diastereoisomerism and each has four diastereoisomers due to the presence of two asymmetric centers in their molecules. The diastereoisomers of these compounds have differing degrees of mosquito-repellent activity according to quantitative behavioral assays conducted at the United States Department of Agriculture. An insight into the stereochemical requirements for repellency is of great importance in the development of better repellents. Mol... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896573 Tue, 01 May 2007 04:00:00 +0100 896573 http://www.medworm.com/index.php?rid=896572&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17514569%26dopt%3DAbstract Authors: Tekiner-Gulbas B, Temiz-Arpaci O, Oksuzoglu E, Eroglu H, Yildiz I, Diril N, Aki-Sener E, Yalcin I Previously synthesized 2,5-disubstituted benzoxazole and benzimidazole derivatives, were tested for their genotoxic activity in the Bacillus subtilis rec- assay. The results revealed that 5-methyl-2-(p-aminobenzyl)benzoxazole exhibited the highest genotoxic response, which was comparable to 4-nitroquinoline 1-oxide (4-NQO), the reference agent of classical positive mutagen. Among the other tested compounds, four showed a genotoxic activity. A QSAR study revealed that structural parameters IY(C(2)H(4)) and IY(CH(2)O), indicating the bridge elements between the phenyl moiety and the fused ring system at position 2 and the quantum chemical parameter (DeltaE ), showing the difference ... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896572 Tue, 01 May 2007 04:00:00 +0100 896572 http://www.medworm.com/index.php?rid=896571&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17514570%26dopt%3DAbstract Authors: Carbó-Dorca R The present theoretical study analyses the Quantum QSPR fundamental linear equation predictive power. Two main alternative algorithms, among several possible choices, are fully described in an add one and add many basis, while the other possibilities are only sketched out. It is shown that one can also apply the described Quantum QSPR prediction algorithms to parent problems in the framework of empirical QSPR, based on the molecular space framework. PMID: 17514570 [PubMed - indexed for MEDLINE] (Source: SAR and QSAR in Environmental Research) SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896571 Tue, 01 May 2007 04:00:00 +0100 896571 http://www.medworm.com/index.php?rid=896570&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17514571%26dopt%3DAbstract Authors: Lagunin AA, Zakharov AV, Filimonov DA, Poroikov VV A new QSAR approach based on a Quantitative Neighbourhoods of Atoms description of molecular structures and self-consistent regression was developed. Its prediction accuracy, advantages and limitations were analysed from three sets of published experimental data on acute toxicity: 56 phenylsulfonyl carboxylates for Vibrio fischeri; 65 aromatic compounds for the alga Chlorella vulgaris and 200 phenols for the ciliated protozoan Tetrahymena pyriformis. According to our findings, the proposed approach provides a good correlation and prediction accuracy (r(2) = 0.908 and Q(2) = 0.866) for the set of 56 phenylsulfonyl carboxylates and the 65 aromatic compounds tested on C. vulgaris (r(2) = 0.885, Q(2) = 0.849). For the 200 phenols ... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896570 Tue, 01 May 2007 04:00:00 +0100 896570 http://www.medworm.com/index.php?rid=896569&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17514572%26dopt%3DAbstract Authors: Puzyn T, Falandysz J Molecular descriptors from calculations at the level of Density Functional Theory (B3LYP/6-311++G**) were effectively applied in QSPR estimation of supercooled liquid vapour pressures (P(L)) for individual chloronaphthalene congeners. The estimated values of log P(L) varied from 1.05 Pa to 5.6 x 10(-5) Pa, depending on the number of chlorine substituents present in the molecule and the substitution pattern. Comparison of the five chemometrical methods of modelling (approaches) led to the final conclusion, that the use of relatively simple PLS combined with one of the variable pre-selection algorithms (UVE or GA) seems to be the optimal choice in such computational studies for persistent organic pollutants. The best GA-PLS model was characterized by the val... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896569 Tue, 01 May 2007 04:00:00 +0100 896569 http://www.medworm.com/index.php?rid=896568&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17514573%26dopt%3DAbstract Authors: Kooijman SA, Baas J, Bontje D, Broerse M, Jager T, Van Gestel CA, Van Hattum B The LC(50) of compounds with a similar biological effect, at a given exposure period, is frequently plotted log-log against the octanol-water partition coefficient and a straight line is fitted for interpolation purposes. This is also frequently done for physiological properties, such as the weight-specific respiration rate, as function of the body weight of individuals. This paper focuses on the remarkable observation that theoretical explanations for these relationships also have strong similarities. Both can be understood as result of the covariation of the values of parameters of models of a particular type for the underlying processes, while this covariation follows logically from the model str... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896568 Tue, 01 May 2007 04:00:00 +0100 896568 http://www.medworm.com/index.php?rid=896567&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17514574%26dopt%3DAbstract Authors: Saliner AG, Tsakovska I, Pavan M, Patlewicz G, Worth AP The German Federal Institute for Risk Assessment (BfR) has developed a Decision Support System (DSS) to assess certain hazardous properties of pure chemicals, including skin and eye irritation/corrosion. The BfR-DSS is a rule-based system that could be used for the regulatory classification of chemicals in the European Union. The system is based on the combined use of two predictive approaches: exclusion rules based on physicochemical cut-off values to identify chemicals that do not exhibit a certain hazard (e.g., skin irritation/corrosion), and inclusion rules based on structural alerts to identify chemicals that do show a particular toxic potential. The aim of the present study was to evaluate the structural inclusion r... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896567 Tue, 01 May 2007 04:00:00 +0100 896567 http://www.medworm.com/index.php?rid=896566&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17514575%26dopt%3DAbstract Authors: Roberts DW, Aptula AO, Cronin MT, Hulzebos E, Patlewicz G As part of a European Chemicals Bureau contract relating to the evaluation of (Q)SARs for toxicological endpoints of regulatory importance, we have reviewed and analysed (Q)SARs for skin sensitisation. Here we consider some recently published global (Q)SAR approaches against the OECD principles and present re-analysis of the data. Our analyses indicate that "statistical" (Q)SARs which aim to be global in their applicability tend to be insufficiently robust mechanistically, leading to an unacceptably high failure rate. Our conclusions are that, for skin sensitisation, the mechanistic chemistry is very important and consequently the best non-animal approach currently applicable to predict skin sensitisation potential is w... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896566 Tue, 01 May 2007 04:00:00 +0100 896566 http://www.medworm.com/index.php?rid=896565&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17514576%26dopt%3DAbstract Authors: Trapp S The current European risk assessment for chemicals considers only tap water, while in reality other beverages play an important role. A good part of beverages are made from fruits, for example apple juice and vine. A mathematical model was developed to predict uptake of neutral organic chemicals from soil and air into fruits. The new fruit tree model considers eight compartments, i.e. two soil compartments, fine roots, thick roots, stem, leaves, fruits, and air. Chemical equilibrium, advective transport in xylem and phloem, diffusive exchange to soil and air and growth dilution are the main processes. The parameterization is for a square-meter of an apple orchard. The model predicts that polar, non-volatile compounds will effectively be transported from soil to fruits,... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896565 Tue, 01 May 2007 04:00:00 +0100 896565 http://www.medworm.com/index.php?rid=896564&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17514577%26dopt%3DAbstract Authors: Serafimova R, Todorov M, Nedelcheva D, Pavlov T, Akahori Y, Nakai M, Mekenyan O A multi-dimensional formulation of the COmmon REactivity PAttern (COREPA) modeling approach has been used to investigate chemical binding to the human estrogen receptor (hER). A training set of 645 chemicals included 497 steroid and environmental chemicals (database of the Chemical Evaluation and Research Institute, Japan - CERI) and 148 chemicals to further explore hER-structure interactions (selected J. Katzenellenbogen references). Upgrades of modeling approaches were introduced for multivariate COREPA analysis, optimal conformational generation and description of the local hydrophobicity of chemicals. Analysis of reactivity patterns based on the distance between nucleophilic sites resulted in i... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896564 Tue, 01 May 2007 04:00:00 +0100 896564 http://www.medworm.com/index.php?rid=896591&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17365954%26dopt%3DAbstract Authors: PMID: 17365954 [PubMed - indexed for MEDLINE] (Source: SAR and QSAR in Environmental Research) SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896591 Mon, 01 Jan 2007 05:00:00 +0100 896591 http://www.medworm.com/index.php?rid=896590&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17365955%26dopt%3DAbstract Authors: Kaiser KL This presentation will review the evolution of the workshops from a scientific and personal perspective. From their modest beginning in 1983, the workshops have developed into larger international meetings, regularly held every two years. Their initial focus on the aquatic sphere soon expanded to include properties and effects on atmospheric and terrestrial species, including man. Concurrent with this broadening of their scientific scope, the workshops have become an important forum for the early dissemination of all aspects of qualitative and quantitative structure-activity research in ecotoxicology and human health effects. Over the last few decades, the field of quantitative structure/activity relationships (QSARs) has quickly emerged as a major scientific method ... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896590 Mon, 01 Jan 2007 05:00:00 +0100 896590 http://www.medworm.com/index.php?rid=896589&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17365956%26dopt%3DAbstract Authors: Schultz TW, Ralston KE, Roberts DW, Veith GD, Aptula AO Using abiotic thiol reactivity (EC50) and Tetrahymena pyriformis toxicity (IGC50) data for a group of halo-substituted ketones, esters and amides (i.e. SN2 electrophiles) and related compounds a series of structure-activity relationships are illustrated. Only the alpha-halo-carbonyl-containing compounds are observed to be thiol reactive with the order I > Br > Cl > F. Further comparisons disclose alpha-halo-carbonyl compounds to be more reactive than non-alpha-halo-carbonyl compounds; in addition, the reactivity is reduced when the number of C atoms between the carbonyl and halogen is greater than one. Comparing reactivity among alpha-halo-carbonyl-containing compounds with different beta-alkyl groups shows the g... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896589 Mon, 01 Jan 2007 05:00:00 +0100 896589 http://www.medworm.com/index.php?rid=896588&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17365957%26dopt%3DAbstract Authors: Riviere JE, Brooks JD Significant progress has been made on predicting dermal absorption/penetration of topically applied compounds by developing QSPR models based on linear free energy relations (LFER). However, all of these efforts have employed compounds applied to the skin in aqueous or single solvent systems, a dosing scenario that does not mimic occupational, environmental or pharmaceutical exposure. We have explored using hybrid QSPR equations describing individual compound penetration based on the molecular descriptors for the compound modified by a mixture factor (MF) which accounts for the physicochemical properties of the vehicle/mixture components. The MF is calculated based on percentage composition of the vehicle/mixture components and physical chemical propertie... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896588 Mon, 01 Jan 2007 05:00:00 +0100 896588 http://www.medworm.com/index.php?rid=896587&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17365958%26dopt%3DAbstract Authors: Basak SC, Mills D, Mumtaz MM Quantitative structure-activity relationship (QSAR) models were developed for the prediction of dermal absorption based on experimental log Kp data for a diverse set of 101 chemicals obtained from the literature. Molecular descriptors including topostructural (TS), topochemical (TC), shape or three-dimensional (3D) and quantum chemical (QC) indices were calculated. Based on this information, a generic predictive model was created using the diverse set of 101 compounds. In addition, two submodels were prepared for subsets of 79 cyclic and 22 acyclic chemicals. A modified Gram-Schmidt variable reduction algorithm for descriptor thinning was followed by regression analyses using ridge regression (RR), principal components regression (PCR) and partial ... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896587 Mon, 01 Jan 2007 05:00:00 +0100 896587 http://www.medworm.com/index.php?rid=896586&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17365959%26dopt%3DAbstract This study describes the possibilities of using simple (quantitative) structure-activity relationships ((Q)SARs) to predict whether a molecule may cross the placental membrane. The concept is straightforward, if a molecule is not able to cross the placental barrier, then it will not be a reproductive toxicant. Such a model could be placed at the start of any integrated testing strategy. To develop these models the literature was reviewed to obtain data relating to the transfer of molecules across the placenta. A reasonable number of data were obtained and are suitable for the modelling of the ability of a molecule to cross the placenta. Clearance or transfer indices data were sought due to their ability to eliminate inter-placental variation by standardising drug clearance to the reference... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896586 Mon, 01 Jan 2007 05:00:00 +0100 896586 http://www.medworm.com/index.php?rid=896585&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17365960%26dopt%3DAbstract Authors: Fujita T, Nakagawa Y A series of our SAR and QSAR studies of synthetic moulting hormone agonists, dibenzoylhydrazines (DBH), exhibiting insecticidal/larvicidal activity are reviewed in this article. We prepared a number of analogues where various substituents are introduced into the two benzene rings of DBH and measured their biological activity using various biological systems. Larvicidal activity was against larvae of the rice stem borer Chilo suppressalis and the moulting hormone activity was in terms of the stimulation of N-acetylglucosamine incorporation in a cultured integument system of the same insect species. Binding affinity to the ecdysone receptor was assayed with intact Sf-9 cell lines in which the ADME processes are negligible as well as using receptor proteins o... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896585 Mon, 01 Jan 2007 05:00:00 +0100 896585 http://www.medworm.com/index.php?rid=896584&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17365961%26dopt%3DAbstract Authors: Kolossov E, Stanforth R Assessment of the quality of goodness-of-fit and the confidence in predictivity (prediction power) are the main terms used to define the statistical quality of QSAR models. Three parts of this assessment can be defined as: (1) Measure of goodness-of-fit. (2) Validation of model stability. (3) Predictivity analysis. Currently there are no mandatory requirements for the validation methods to be used and rules for the quantitative confidence estimates. To compare the statistical quality of QSAR models it is necessary to have an overall statistical quality index which will depend on the goodness-of-fit, validation and predictivity results together. To do so it is necessary to define the set of mandatory parameters for all three parts of assessment listed ab... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896584 Mon, 01 Jan 2007 05:00:00 +0100 896584 http://www.medworm.com/index.php?rid=896583&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17365962%26dopt%3DAbstract Authors: Poroikov V, Filimonov D, Lagunin A, Gloriozova T, Zakharov A Toxicity of chemical compound is a complex phenomenon that may be caused by its interaction with different targets in the organism. Two distinct types of toxicity can be broadly specified: the first one is caused by the strong compound's interaction with a single target (e.g. AChE inhibition); while the second one is caused by the moderate compound's interaction with many various targets. Computer program PASS predicts about 2500 kinds of biological activities based on the structural formula of chemical compounds. Prediction is based on the robust analysis of structure-activity relationships for about 60,000 biologically active compounds. Mean accuracy exceeds 90% in leave-one-out cross-validation. In addition to som... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896583 Mon, 01 Jan 2007 05:00:00 +0100 896583 http://www.medworm.com/index.php?rid=896582&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17365963%26dopt%3DAbstract This article provides an overview of ECB activities on computational toxicology, which are intended to promote the development, validation, acceptance and use of (Q)SARs and related estimation methods, both at the European and international levels. PMID: 17365963 [PubMed - indexed for MEDLINE] (Source: SAR and QSAR in Environmental Research) SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896582 Mon, 01 Jan 2007 05:00:00 +0100 896582 http://www.medworm.com/index.php?rid=896581&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17365964%26dopt%3DAbstract Authors: Oberg T The vapour pressure is the most important property of an anthropogenic organic compound in determining its partitioning between the atmosphere and the other environmental media. The enthalpy of vaporisation quantifies the temperature dependence of the vapour pressure and its value around 298 K is needed for environmental modelling. The enthalpy of vaporisation can be determined by different experimental methods, but estimation methods are needed to extend the current database and several approaches are available from the literature. However, these methods have limitations, such as a need for other experimental results as input data, a limited applicability domain, a lack of domain definition, and a lack of predictive validation. Here we have attempted to develop a quan... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896581 Mon, 01 Jan 2007 05:00:00 +0100 896581 http://www.medworm.com/index.php?rid=896580&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17365965%26dopt%3DAbstract We describe graph machines, an alternative approach to traditional machine-learning-based QSAR, which circumvents the problem of designing, computing and selecting molecular descriptors. In that approach, which is similar in spirit to recursive networks, molecules are considered as structured data, represented as graphs. For each example of the data set, a mathematical function (graph machine) is built, whose structure reflects the structure of the molecule under consideration; it is the combination of identical parameterised functions, called "node functions" (e.g. a feedforward neural network). The parameters of the node functions, shared both within and across the graph machines, are adjusted during training with the "shared weights" technique. Model selection is then performed by tradi... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896580 Mon, 01 Jan 2007 05:00:00 +0100 896580 http://www.medworm.com/index.php?rid=896579&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17365966%26dopt%3DAbstract Authors: Nendza M, Müller M Decision support for selecting suitable QSARs for predictive purposes is suggested by a stepwise procedure: The first tier pre-filters the compounds based on substructure indicators for baseline versus excess toxicity. This step, if sufficiently conservative, discriminates chemicals, whose toxicity can be reliably estimated from their log KOW from those, that require further classification by biological and chemical domain. A test set of 115 chemicals from 9 different MOA classes was used to compare the discriminatory power of several classification schemes based on substructure indicators. Performance, evaluated by contingency table statistics, is varied and no single scheme provides sufficient applicability and reliability for pre-filtering chemical i... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896579 Mon, 01 Jan 2007 05:00:00 +0100 896579 http://www.medworm.com/index.php?rid=896578&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17365967%26dopt%3DAbstract Authors: Gramatica P, Pilutti P, Papa E Nitrated Polycyclic Aromatic Hydrocarbons (nitro-PAHs), ubiquitous environmental pollutants, are recognized mutagens and carcinogens. A set of mutagenicity data (TA100) for 48 nitro-PAHs was modeled by the Quantitative Structure-Activity Relationships (QSAR) regression method, and OECD principles for QSAR model validation were applied. The proposed Multiple Linear Regression (MLR) models are based on two topological molecular descriptors. The models were validated for predictivity by both internal and external validation. For the external validation, three different splitting approaches, D-optimal Experimental Design, Self Organizing Maps (SOM) and Random Selection by activity sampling, were applied to the original data set in order to compare th... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896578 Mon, 01 Jan 2007 05:00:00 +0100 896578 http://www.medworm.com/index.php?rid=896596&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17162385%26dopt%3DAbstract Authors: Rosselli FP, Albuquerque CN, Da Silva AB The AM1 semiempirical method was employed to study megazol and 13 of its analogues where their activity against Trypanosoma equiperdum was obtained from in vitro tests. Several molecular properties (descriptors or variables) were calculated for the 14 compounds studied to be correlated with the biological activity. For a practical analysis of large data sets, it is necessary to reduce the dimensionality and select the most relevant descriptors related to the biological activity under study. For this purpose, the following chemometric methods were employed: principal component analysis (PCA), hierarchical cluster analysis (HCA), K-nearest neighbour (KNN), stepwise discriminant analysis (SDA) and soft independent modelling of class analog... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896596 Fri, 01 Dec 2006 05:00:00 +0100 896596 http://www.medworm.com/index.php?rid=896595&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17162386%26dopt%3DAbstract Authors: Tuppurainen K, Korhonen SP, Ruuskanen J A novel method for underdetermined regression problems, multicomponent self-organizing regression (MCSOR), has been recently introduced. Here, its performance is compared with partial least-squares (PLS), which is perhaps the most widely adopted multivariate method in chemometrics. A potpourri of models is presented, and MCSOR appears to provide highly predictive models that are comparable with or better than the corresponding PLS models in large internal (leave-one-out, LOO) and pseudo-external (leave-many-out, LMO) validation tests. The "blind" external predictive ability of MCSOR and PLS is demonstrated employing large melting point, factor Xa, log P and log S data sets. In a nutshell, MCSOR is fast, conceptually simple (employing mul... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896595 Fri, 01 Dec 2006 05:00:00 +0100 896595 http://www.medworm.com/index.php?rid=896594&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17162387%26dopt%3DAbstract Authors: Roy K, Sanyal I, Roy PP Bioconcentration refers to the absorption or uptake of a chemical from the media to an organism's tissues leading to greater concentration in tissues than that in the surrounding environment. Considering the importance of bioconcentration from the viewpoint of ecological safety assessment, a QSPR study was conducted based upon log BCF of 122 non-ionic organic compounds in fish using the recently introduced extended topochemical atom (ETA) indices. In deriving the models, principal component factor analysis (FA) followed by multiple linear regression (MLR), stepwise regression, partial least squares (PLS) and principal component regression analysis (PCRA) were applied as statistical tools. This was repeated with non-ETA (topological and physicochemical) ... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896594 Fri, 01 Dec 2006 05:00:00 +0100 896594 http://www.medworm.com/index.php?rid=896593&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17162388%26dopt%3DAbstract Authors: Randić M, Novic M, Vikić-Topić D, Plavsić D We have introduced novel numerical and graphical representations of DNA, which offer a simple and unique characterization of DNA sequences. The numerical representation of a DNA sequence is given as a sequence of real numbers derived from a unique graphical representation of the standard genetic code. There is no loss of information on the primary structure of a DNA sequence associated with this numerical representation. The novel representations are illustrated with the coding sequences of the first exon of beta-globin gene of half a dozen species in addition to human. The method can be extended to proteins as is exemplified by humanin, a 24-aa peptide that has recently been identified as a specific inhibitor... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896593 Fri, 01 Dec 2006 05:00:00 +0100 896593 http://www.medworm.com/index.php?rid=896592&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17162389%26dopt%3DAbstract Authors: Wan B, Sayler GS, Schultz TW Using flow cytometry, select polycyclic aromatic hydrocarbons (PAHs) were evaluated for induction of apoptosis in human monocytic THP-1 cells. Based on structure, the PAHs were divided into linear and bay-region-containing compounds. Except for fluorene, the linear PAHs failed to induce apoptosis; all of the bay-region-containing PAHs induce apoptosis. The relationship that a bay-region is required to induce apoptosis is supported by results for benzo[a]pyrene (positive) and 2-methylanthracene (negative). The data for bay-region containing, four-ringed PAH compounds reveal that possessing a linear-region of more than two rings diminishes the ability of a PAH to induce apoptosis. Owing to the steric interactions of the hydrogen atoms of the methyl g... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896592 Fri, 01 Dec 2006 05:00:00 +0100 896592 http://www.medworm.com/index.php?rid=896601&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17018425%26dopt%3DAbstract Authors: Koike A The selection of effective features from various descriptors of chemical compounds and the exploitation of the most appropriate classifier is a momentous issue in improving overall accuracies of virtual screening of chemical compounds. In this article, the performance of various feature-selection methods and various classifiers of chemical compound-protein binding affinities are compared by using six series of compounds: cytochrome P450 2C9 inhibitors, multi-drug-resistance reversal compounds, estrogen receptor ligands, inhibitors of human ether-a-go-go-related genes, and ligands of serotonin receptor 5HT1A and 5HT2A. As a result, it was found that the genetic algorithm was superior to the other feature-selection methods, and its combination with Random Forests and Ada... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896601 Sun, 01 Oct 2006 04:00:00 +0100 896601 http://www.medworm.com/index.php?rid=896600&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17050186%26dopt%3DAbstract Authors: Wang XZ, Buontempo FV, Young A, Osborn D Recent literature has demonstrated the applicability of genetic programming to induction of decision trees for modelling toxicity endpoints. Compared with other decision tree induction techniques that are based upon recursive partitioning employing greedy searches to choose the best splitting attribute and value at each node that will necessarily miss regions of the search space, the genetic programming based approach can overcome the problem. However, the method still requires the discretization of the often continuous-valued toxicity endpoints prior to the tree induction. A novel extension of this method, YAdapt, is introduced in this work which models the original continuous endpoint by adaptively finding suitable ranges to describe ... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896600 Sun, 01 Oct 2006 04:00:00 +0100 896600 http://www.medworm.com/index.php?rid=896599&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17050187%26dopt%3DAbstract Authors: Yuan S, Xiao M, Zheng G, Tian M, Lu X A quantitative structure-property relationship (QSPR) model has been developed for the electrochemical degradation of substituted phenols using a support vector machine (SVM). Thirty descriptors, including quantum chemical parameters, steric effect descriptors and half wave potential (E1/2), were used for describing twelve substituted phenols, including mono- and multi-substituent phenols. A leave-one-out (LOO) cross validation procedure resulted in the selection of three descriptors, the total of electron and nuclear energies of the two-center terms for the carbon-chlorine or carbon-nitrogen bond (TE2), the net atomic charges on the chlorine or nitrogen (qx), and the largest negative atomic charge on an atom (q-). The model based on SVM y... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896599 Sun, 01 Oct 2006 04:00:00 +0100 896599 http://www.medworm.com/index.php?rid=896598&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17050188%26dopt%3DAbstract Authors: Delgado EJ, Diaz GA A Quantitative Structure-Property Relationship (QSPR) model for the prediction of surface tension of organic compounds was derived from a data set of 320 chemicals including N, O, F, Cl, Br, and/or S atoms and covering a range of about 14-45 dyn cm-1. The model, only involving six molecular descriptors obtained solely from the chemical structures, yielded an r2 of 0.96. Its predictive capability was estimated from an external test set containing 55 structures not considered in the training set (r2 = 0.94). It was shown that the selected molecular descriptors presented a physical meaning corresponding to the different intermolecular interactions occurring in the bulk solution. The model is applicable to a wider variety of compounds, includes less parameters ... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896598 Sun, 01 Oct 2006 04:00:00 +0100 896598 http://www.medworm.com/index.php?rid=896597&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17050189%26dopt%3DAbstract Authors: Basak SC, Mills D, Gute BD Predictive QSAR models for rat and human tissue : air partition coefficients, namely blood : air, fat : air, brain : air, liver : air, muscle : air, and kidney : air were developed utilizing experimentally determined partition coefficients for 131 chemicals obtained from the literature and molecular descriptors based solely on chemical structure. The descriptors were partitioned into four hierarchical classes, including topostructural, topochemical, 3-dimensional, and ab initio quantum chemical. Three types of regression methodologies--ridge regression, principal components regression, and partial least squares regression--were used comparatively in the development of the structure-based models. In addition to the structure-based models, ordinary lea... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896597 Sun, 01 Oct 2006 04:00:00 +0100 896597 http://www.medworm.com/index.php?rid=896606&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16920659%26dopt%3DAbstract Authors: Pungpo P, Saparpakorn P, Wolschann P, Hannongbua S Ligand- and structure-based design approaches have been applied to an extended series of 74 efavirenz compounds effectively inhibiting wild type (WT) and mutant type (K103N) HIV-1 reverse transcriptase (RT). For ligand-based approach, three dimensional quantitative structure-activity relationship (3D-QSAR) methods, comparative molecular field analysis (CoMFA) and comparative similarity indices analysis (CoMSIA), were performed. The starting geometry of efavirenz was obtained from X-ray crystallographic data. The efavirenz derivatives were constructed and fully optimized by ab-initio molecular orbital method at HF/3-21G level. Reliable QSAR models for high predictive abilities were developed. Regarding WT and K103N inhibitions,... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896606 Tue, 01 Aug 2006 04:00:00 +0100 896606 http://www.medworm.com/index.php?rid=896605&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16920660%26dopt%3DAbstract Authors: Saxena AK, Prathipati P Drug discovery and development research is undergoing a paradigm shift from a linear and sequential nature of the various steps involved in the drug discovery process of the past to the more parallel approach of the present, due to a lack of sufficient correlation between activities estimated by in vitro and in vivo assays. This is attributed to the non-drug-likeness of the lead molecules, which has often been detected at advanced drug development stages. Thus a striking aspect of this paradigm shift has been early/parallel in silico prioritization of drug-like molecular databases (also database pre-processing), in addition to prioritizing compounds with high affinity and selectivity for a protein target. In view of this, a drug-like database useful for... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896605 Tue, 01 Aug 2006 04:00:00 +0100 896605 http://www.medworm.com/index.php?rid=896604&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16920661%26dopt%3DAbstract Authors: Devillers J, Marchand-Geneste N, Carpy A, Porcher JM A number of xenobiotics by mimicking natural hormones can disrupt crucial functions in wildlife and humans. These chemicals termed endocrine disruptors are able to exert adverse effects through a variety of mechanisms. Fortunately, there is a growing interest in the study of these structurally diverse chemicals mainly through research programs based on in vitro and in vivo experimentations but also by means of SAR and QSAR models.The goal of our study was to retrieve from the literature all the papers dealing with structure-activity models on endocrine disruptor xenobiotics. A critical analysis of these models was made focusing our attention on the quality of the biological data, the significance of the molecular descriptors... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896604 Tue, 01 Aug 2006 04:00:00 +0100 896604 http://www.medworm.com/index.php?rid=896603&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16920662%26dopt%3DAbstract Authors: Schultz TW, Carlson RE, Cronin MT, Hermens JL, Johnson R, O'Brien PJ, Roberts DW, Siraki A, Wallace KB, Veith GD Although the literature is replete with QSAR models developed for many toxic effects caused by reversible chemical interactions, the development of QSARs for the toxic effects of reactive chemicals lacks a consistent approach. While limitations exit, an appropriate starting-point for modeling reactive toxicity is the applicability of the general rules of organic chemical reactions and the association of these reactions to cellular targets of importance in toxicology. The identification of plausible "molecular initiating events" based on covalent reactions with nucleophiles in proteins and DNA provides the unifying concept for a framework for reactive toxicity. This ... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896603 Tue, 01 Aug 2006 04:00:00 +0100 896603 http://www.medworm.com/index.php?rid=896602&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16920663%26dopt%3DAbstract Authors: Balaban AT, Mills D, Kodali V, Basak SC Chemical graph complexity depends on many factors, but the main ones are size, branching, and cyclicity. Some molecular descriptors embrace together all these three parameters, which cannot then be disentangled. The topological index J (and its refinements that include accounting for bond multiplicity and the presence of heteroatoms) was designed to compensate in a significant measure for graph size and cyclicity, and therefore it contains information mainly on branching. In order to separate these factors, two new indices (F and G) related with J are proposed, which allow to group together graphs with the same size into families of constitutional formulas differing in their branching and cyclicity. A comparison with other topological in... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896602 Tue, 01 Aug 2006 04:00:00 +0100 896602 http://www.medworm.com/index.php?rid=896613&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16815766%26dopt%3DAbstract Authors: Bauvais C, Barbault F, Zhu Y, Petitjean M, Fan BT A theoretical investigation was carried out on the retention and separation of enantiomeric molecules including nonsteroidal anti-inflammatory drugs, anti-neoplastic compounds and N-derivatized amino acids by capillary electrophoresis using macrocyclic antibiotics, a new class of chiral selectors, as stationary phase. Firstly docking methods were used to study the enantiorecognition in chiral electrophoresis. The molecular dynamics simulations of the two diastereoisomer complexes were then performed in order to understand how these antibiotics recognize the enantiomers. Another approach was applied in this study to establish a quantitative structure-enantioselectivity relationship (QSER) model, able to describe the resolution o... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896613 Thu, 01 Jun 2006 04:00:00 +0100 896613 http://www.medworm.com/index.php?rid=896612&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16815767%26dopt%3DAbstract Authors: Vracko M, Bandelj V, Barbieri P, Benfenati E, Chaudhry Q, Cronin M, Devillers J, Gallegos A, Gini G, Gramatica P, Helma C, Mazzatorta P, Neagu D, Netzeva T, Pavan M, Patlewicz G, Randić M, Tsakovska I, Worth A The OECD has proposed five principles for validation of QSAR models used for regulatory purposes. Here we present a case study investigating how these principles can be applied to models based on Kohonen and counter propagation neural networks. The study is based on a counter propagation network model that has been built using toxicity data in fish fathead minnow for 541 compounds. The study demonstrates that most, if not all, of the OECD criteria may be met when modeling using this neural network approach. PMID: 16815767 [PubMed - indexed for MEDLINE] (Source:... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896612 Thu, 01 Jun 2006 04:00:00 +0100 896612 http://www.medworm.com/index.php?rid=896611&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16815768%26dopt%3DAbstract Authors: Raevsky OA, Grigor'ev VJ, Raevskaja OE, Schaper KJ QSPR analyses of a data set containing experimental partition coefficients in the three systems octanol-water, water-gas, and octanol-gas for 98 chemicals have shown that it is possible to calculate any partition coefficient in the system 'gas phase/octanol/water' by three different approaches: (1) from experimental partition coefficients obtained in the corresponding two other subsystems. However, in many cases these data may not be available. Therefore, a solution may be approached (2), a traditional QSPR analysis based on e.g. HYBOT descriptors (hydrogen bond acceptor and donor factors, SigmaCa and SigmaCd, together with polarisability alpha, a steric bulk effect descriptor) and supplemented with substructural indicator var... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896611 Thu, 01 Jun 2006 04:00:00 +0100 896611 http://www.medworm.com/index.php?rid=896610&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16815769%26dopt%3DAbstract Authors: Giraud F, Loge C, Le Borgne M, Pagniez F, Na YM, Le Pape P A three-dimensional quantitative structure-activity relationship (3D-QSAR) study using Comparative Molecular Similarity Indices Analysis (CoMSIA) was conducted on a series of 3-azolylmethylindoles as anti-leishmanial agents. Evaluation of 24 compounds synthesized in our laboratory served to establish the model. A random search was performed on the library of compounds, and molecules of the training set were aligned on common elements of template molecule 13, one of the most active compounds. The best predictions were obtained from multifit procedure with a CoMSIA model combining steric, electrostatic, hydrophobic and hydrogen bond acceptor fields (q2 = 0.594, r2 = 0.897). The model was validated using an external test ... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896610 Thu, 01 Jun 2006 04:00:00 +0100 896610 http://www.medworm.com/index.php?rid=896609&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16815770%26dopt%3DAbstract Authors: Abshear T, Banik GM, D'Souza ML, Nedwed K, Peng C Over half of the failures in drug development are due to problems with the absorption, distribution, metabolism, excretion, and toxicity, or ADME/Tox properties of a candidate compound. The utilization of in silico tools to predict ADME/Tox and physicochemical properties holds great potential for reducing the attrition rate in drug research and development, as this technology can prioritize candidate compounds in the pharmaceutical R&D pipeline. However, a major concern surrounding the use of in silico ADME/Tox technology is the reliability of the property predictions. Bio-Rad Laboratories, Inc. has created a computational environment that addresses these concerns. This environment is referred to as KnowItAll. Within this p... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896609 Thu, 01 Jun 2006 04:00:00 +0100 896609 http://www.medworm.com/index.php?rid=896608&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16815771%26dopt%3DAbstract Authors: Lukovits I, Fodor J, Gömöry A, István K, Keresztury G, Kótai L The presence and absence of alkane isomers in petroleum and petroleum derivatives depend on the complexity of these structures. It was assumed that the more complex the structure is the less probable it is that that the molecule can be detected in any petroleum derivative. Complexity is a vague concept, which has not been defined in quantitative terms yet, and therefore there is no experimental method, which could be used to determine 'complexity'. Mass spectrometry and infrared spectroscopy in combination with gas chromatography were used to identify the various structural isomers of alkanes in petroleum ether. The isomers were categorised in quantitative terms by using topological indices and ... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896608 Thu, 01 Jun 2006 04:00:00 +0100 896608 http://www.medworm.com/index.php?rid=896607&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16815772%26dopt%3DAbstract Authors: Chen JJ, Tsai CA, Moon H, Ahn H, Young JJ, Chen CH Standard classification algorithms are generally designed to maximize the number of correct predictions (concordance). The criterion of maximizing the concordance may not be appropriate in certain applications. In practice, some applications may emphasize high sensitivity (e.g., clinical diagnostic tests) and others may emphasize high specificity (e.g., epidemiology screening studies). This paper considers effects of the decision threshold on sensitivity, specificity, and concordance for four classification methods: logistic regression, classification tree, Fisher's linear discriminant analysis, and a weighted k-nearest neighbor. We investigated the use of decision threshold adjustment to improve performance of either sensitiv... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896607 Thu, 01 Jun 2006 04:00:00 +0100 896607 http://www.medworm.com/index.php?rid=896620&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16644553%26dopt%3DAbstract Authors: Tekiner-Gulbas B, Temiz-Arpaci O, Yildiz I, Aki-Sener E, Yalcin I Selective topoisomerase II (Topo II) inhibitors have interested to a great extent for the design of new antitumoral compounds in recent years. Comparative molecular similarity indices analysis (CoMSIA) was performed on a series of previously synthesized benzoxazole, benzimidazole, and oxazolo(4,5-b)pyridine derivatives as eukaryotic Topo II inhibitors. A training set of 16 heterocyclic compounds was used to establish the CoMSIA model. They were constructed and geometrically optimized using SYBYL v7.0. The predictive ability of the model was assessed using a test set of 7 compounds. The best model has demonstrated a good fit having r2 value of 0.968 and cross-validated coefficient q2 value as 0.562 including ster... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896620 Sat, 01 Apr 2006 05:00:00 +0100 896620 http://www.medworm.com/index.php?rid=896619&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16644554%26dopt%3DAbstract Authors: Carlsen L QSAR generated data appear as an attractive alternative to experimental data as foreseen in the proposed new chemicals legislation REACH. A preliminary risk assessment for the aquatic environment can be based on few factors, i.e. the octanol-water partition coefficient (Kow), the vapour pressure (VP) and the potential biodegradability of the compound in combination with the predicted no-effect concentration (PNEC) and the actual tonnage in which the substance is produced. Application of partial order ranking, allowing simultaneous inclusion of several parameters leads to a mutual prioritisation of the investigated substances, the prioritisation possibly being further analysed through the concept of linear extensions and average ranks. The ranking uses endpoint values... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896619 Sat, 01 Apr 2006 05:00:00 +0100 896619 http://www.medworm.com/index.php?rid=896618&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16644555%26dopt%3DAbstract Authors: Pavan M, Netzeva TI, Worth AP In the present study, a quantitative structure--activity relationship (QSAR) model has been developed for predicting acute toxicity to the fathead minnow (Pimephales promelas), the aim being to demonstrate how statistical validation and domain definition are both required to establish model validity and to provide reliable predictions. A dataset of 408 heterogeneous chemicals was modelled by a diverse set of theoretical molecular descriptors by using multivariate linear regression (MLR) and Genetic Algorithm-Variable Subset Selection (GA-VSS). This QSAR model was developed to generate reliable predictions of toxicity for organic chemicals not yet tested, so particular emphasis was given to statistical validity and applicability domain. External va... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896618 Sat, 01 Apr 2006 05:00:00 +0100 896618 http://www.medworm.com/index.php?rid=896617&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16644556%26dopt%3DAbstract Authors: Niu JF, Yang ZF, Shen ZY, Wang LL By partial least squares (PLS) regression analysis, a quantitative structure-property relationship (QSPR) model was developed for photodegradation half-life (t1/2) of polychlorinated biphenyls (PCBs) in n-hexane solution under UV irradiation. Quantum chemical descriptors computed by PM3 Hamiltonian were used as predictor variables. The cross-validated value for the optimal QSPR model was 0.589, indicating good predictive capability for log t1/2 values of PCBs in n-hexane. The QSPR results show that standard heat of formation (DeltaHf), total energy (TE), and molecular weight (Mw) have dominant effect on t1/2 values of PCBs in n-hexane. Increasing DeltaHf and TE values or decreasing Mw values of the PCBs leads to decrease of log t1/2 values. In... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896617 Sat, 01 Apr 2006 05:00:00 +0100 896617 http://www.medworm.com/index.php?rid=896616&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16644557%26dopt%3DAbstract Authors: Saparpakorn P, Hannongbua S, Rognan D Nevirapine (Viramune) belongs to the first generation of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Its efficiency is limited by drug resistant mutations, such as K103N and Y181C, so, the aim of this work was to design novel nevirapine analogues insensitive to the K103N and Y181C HIV-1 RT. 360 Nevirapine derivatives were designed using a combinatorial library design approach and these compounds were docked into the binding pocket of mutant HIV-1 RT enzyme structures, using the GOLD program. 124 Compounds having a GoldScore higher than that of nevirapine (55.00 and 52.00 for K103N and Y181C mutants, respectively) were first retrieved and submitted to a topological analysis with the SILVER program. Consequently, 31 compounds p... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896616 Sat, 01 Apr 2006 05:00:00 +0100 896616 http://www.medworm.com/index.php?rid=896615&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16644558%26dopt%3DAbstract Authors: Saliner AG, Netzeva TI, Worth AP (Q)SAR models can be used to reduce animal testing as well as to minimise the testing costs. In particular, classification models have been widely used for estimating endpoints with binary activity. The aim of the present study was to develop and validate a classification-based quantitative structure-activity relationship (QSAR) model for endocrine disruption, based on interpretable mechanistic descriptors related to estrogenic gene activation. The model predicts the presence or absence of estrogenic activity according to a pre-defined cut-off in activity as determined in a recombinant yeast assay. The experimental data was obtained from the literature. A two-descriptor classification model was developed that has the form of a decision tree. Th... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896615 Sat, 01 Apr 2006 05:00:00 +0100 896615 http://www.medworm.com/index.php?rid=896614&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16644559%26dopt%3DAbstract Authors: Piclin N, Pintore M, Wechman C, Roncaglioni A, Benfenati E, Chretien JR Classification models were established on four endpoints, i.e. trout, daphnia, quail and bee, including from 100 to 300 pesticides subdivided into 3 toxicity classes. For each species, five separate sets of molecular descriptors, computed by several software, were compared, including parameters related to 2D or 3D structures. The most relevant descriptors were selected with help of a procedure based on genetic algorithms. Then, structure-activity relationships were built by Adaptive Fuzzy Partition (AFP), a recursive partitioning method derived from Fuzzy Logic concepts.Globally, satisfactory results were obtained for each animal species. The best cross-validation and test set scores reached values of abou... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896614 Sat, 01 Apr 2006 05:00:00 +0100 896614 http://www.medworm.com/index.php?rid=896628&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16513548%26dopt%3DAbstract Authors: Carpy AJ, Marchand-Geneste N Nowadays the in silico scenario for drug design is totally dependent on structural biology and structural bioinformatics. A myriad of free bioinformatics applications and services have been posted on the web. This mini-review mentions web sites that are useful in structure-based drug design. The information is given in a logical manner, following the drug design process i.e. characterization of a protein target, modelling the protein using sequence homology, optimization of the protein structure and finally docking of small ligands into the active site. PMID: 16513548 [PubMed - indexed for MEDLINE] (Source: SAR and QSAR in Environmental Research) SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896628 Wed, 01 Feb 2006 05:00:00 +0100 896628 http://www.medworm.com/index.php?rid=896627&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16513549%26dopt%3DAbstract The objective of this system is the analysis of molecular similarity and diversity through the treatment of structural and physicochemical information. Current needs for chemical databases include the analysis, the management and the retrieval of chemical information. The implementation of eXtended Markup Languages (XML) is proposed as a basis for representing and structuring the chemical information contained in data structures and databases. The adequate descriptor vector and related physicochemical properties have been defined and constructed. The benefits of XML in chemoinformatics are discussed, as well as, the applications of this system in a virtual screening environment. PMID: 16513549 [PubMed - indexed for MEDLINE] (Source: SAR and QSAR in Environmental Research) SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896627 Wed, 01 Feb 2006 05:00:00 +0100 896627 http://www.medworm.com/index.php?rid=896626&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16513550%26dopt%3DAbstract Authors: Paananen J, Wong G Genome based technologies such as sequencing and gene expression profiling using microarrays are creating massive amounts of data. Results from these studies have provided unique insights into targets, biochemical pathways, and biological systems affected by drug or xenobiotic chemical treatments. Moreover, these genomic technologies offer the potential to identify biomarkers for pharmacological development or toxicological prediction. Nonetheless, microarray studies involving a single compound produce useful although limited data. To gain further power from these individual studies, the ability to combine datasets through integration schemes has become imperative. In the current study, we describe and analyze currently available Internet resources designed ... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896626 Wed, 01 Feb 2006 05:00:00 +0100 896626 http://www.medworm.com/index.php?rid=896625&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16513551%26dopt%3DAbstract Authors: Gute BD, Basak SC Three classes of arbitrary quantitative molecular similarity analysis (QMSA) methods have been computed using atom pairs (APs), topological indices (TIs), and principal components (PCs) derived from topological indices. Tailored QMSA models have been developed from TIs selected through ridge regression. K-nearest neighbor (kNN) based estimation has been applied to all of the methods to estimate normal vapor pressure (p(vap)) and water solubility (sol) for a set of 194 chemicals. Results show that the tailored QMSA methods are superior to arbitrary similarity methods in estimating both of these properties for the given set of chemicals. PMID: 16513551 [PubMed - indexed for MEDLINE] (Source: SAR and QSAR in Environmental Research) SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896625 Wed, 01 Feb 2006 05:00:00 +0100 896625 http://www.medworm.com/index.php?rid=896624&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16513552%26dopt%3DAbstract Authors: Mwense M, Wang XZ, Buontempo FV, Horan N, Young A, Osborn D The principle of using a singe model to predict the toxicity of mixtures of chemicals based on the characterisation of the degrees of similarity and dissimilarity of the constituent chemicals using descriptors has been demonstrated in a previous work. The current study introduces a feature extraction technique, independent component analysis, to the method to remove the correlations and dependencies between descriptors and reduce the dimension prior to similarity and dissimilarity calculations. In addition, a goal attainment multi-objective optimisation technique is used for the determination of the fuzzy membership function parameters. For three mixtures, which include a new mixture and two previously studied mixture... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896624 Wed, 01 Feb 2006 05:00:00 +0100 896624 http://www.medworm.com/index.php?rid=896623&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16513553%26dopt%3DAbstract Authors: Panaye A, Fan BT, Doucet JP, Yao XJ, Zhang RS, Liu MC, Hu ZD Prediction of toxicity of 203 nitro- and cyano-aromatic chemicals to Tetrahymena pyriformis was carried out by radial basis function neural network, general regression neural network and support vector machine, in non-linear response surface methodology. Toxicity was predicted from hydrophobicity parameter (log Kow) and maximum superdelocalizability (Amax). Special attention was drawn to prediction ability and robustness of the models, investigated both in a leave-one-out and 10-fold cross validation (CV) processes. The influence that the corresponding changes in the learning sets during these CV processes could have on a common external test set including 41 compounds was also examined. This allowed us to establish ... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896623 Wed, 01 Feb 2006 05:00:00 +0100 896623 http://www.medworm.com/index.php?rid=896622&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16513554%26dopt%3DAbstract Authors: Marchand-Geneste N, Cazaunau M, Carpy AJ, Laguerre M, Porcher JM, Devillers J A model for rainbow trout (Oncorhynchus mykiss) estrogen receptor (rtERa) was built by homology with the human estrogen receptor (hERa). A high level of sequence conservation between the two receptors was found with 64% and 80% of identity and similarity, respectively. Selected endocrine disrupting chemicals were docked into the ligand binding domain (LBD) of rtERa and the corresponding free binding energies Delta(DeltaG(bind)) values were calculated. A Quantitative Structure-Activity Relationship (QSAR) model between the relative binding affinity data and the Delta(DeltaG(bind)) values was derived in order to predict which further organic pollutants are likely to bind to rtERa. PMID: 16513554 [P... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896622 Wed, 01 Feb 2006 05:00:00 +0100 896622 http://www.medworm.com/index.php?rid=896621&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16513555%26dopt%3DAbstract Authors: Mekenyan O, Dimitrov S, Dimitrova N, Dimitrova G, Pavlov T, Chankov G, Kotov S, Vasilev K, Vasilev R The role of metabolism in prioritising chemicals according to their potential adverse health effects is extremely important given the fact that innocuous parents can be transformed into toxic metabolites. Our recent efforts in simulating metabolic activation of chemicals are reviewed in this work. The application of metabolic simulators to predict biodegradation (microbial degradation pathways), bioaccumulation (fish liver metabolism), skin sensitisation (skin metabolism), mutagenicity (rat liver S-9 metabolism) are discussed. The ability of OASIS approach to predict metabolism (toxicokinetics) and toxicity (toxicodynamics) of chemicals resulting from their metabolic activation... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896621 Wed, 01 Feb 2006 05:00:00 +0100 896621 http://www.medworm.com/index.php?rid=896633&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16428129%26dopt%3DAbstract Authors: Chen JJ, Tsai CA, Young JF, Kodell RL This paper investigates the effects of the ratio of positive-to-negative samples on the sensitivity, specificity, and concordance. When the class sizes in the training samples are not equal, the classification rule derived will favor the majority class and result in a low sensitivity on the minority class prediction. We propose an ensemble classification approach to adjust for differential class sizes in a binary classifier system. An ensemble classifier consists of a set of base classifiers; its prediction rule is based on a summary measure of individual classifications by the base classifiers. Two re-sampling methods, augmentation and abatement, are proposed to generate different bootstrap samples of equal class size to build the base cl... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896633 Thu, 01 Dec 2005 05:00:00 +0100 896633 http://www.medworm.com/index.php?rid=896632&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16428130%26dopt%3DAbstract Authors: Dimitrov S, Dimitrova N, Parkerton T, Comber M, Bonnell M, Mekenyan O The base-line modeling concept presented in this work is based on the assumption of a maximum bioconcentration factor (BCF) with mitigating factors that reduce the BCF. The maximum bioconcentration potential was described by the multi-compartment partitioning model for passive diffusion. The significance of different mitigating factors associated either with interactions with an organism or bioavailability were investigated. The most important mitigating factor was found to be metabolism. Accordingly, a simulator for fish liver was used in the model, which has been trained to reproduce fish metabolism based on related mammalian metabolic pathways. Other significant mitigating factors, depending on the chemic... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896632 Thu, 01 Dec 2005 05:00:00 +0100 896632 http://www.medworm.com/index.php?rid=896631&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16428131%26dopt%3DAbstract Authors: Asikainen AH, Ruuskanen J, Tuppurainen KA The performance of the spectroscopic EVA (eigenvalue) and EEVA (electronic eigenvalue) methods was tested with data sets applying coumarin 7-hydroxylation inhibitors (28 compounds) for cytochrome P450 mouse CYP2A5 and human CYP2A6 enzymes and 11ss-, 16a-, and 17a-substituted estradiol derivatives (30 compounds) for the lamb uterine estrogen receptor, and compared with the performance of the classical Hansch-type, CoMFA and GRID/GOLPE methods. Besides the internal predictability, the external predictability of the models was tested with several randomized training and test sets to ensure the validity and reliability of the models. Partial least squares (PLS) regression was employed as a general statistical tool with the EVA and EEVA met... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896631 Thu, 01 Dec 2005 05:00:00 +0100 896631 http://www.medworm.com/index.php?rid=896630&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16428132%26dopt%3DAbstract Authors: Korhonen SP, Tuppurainen K, Laatikainen R, Peräkylä M Self-Organizing Molecular Field Analysis (SOMFA) comes with a built-in regression methodology, the Self-Organizing Regression (SOR), instead of relying on external methods such as PLS. In this article we present a proof of the equivalence between SOR and SIMPLS with one principal component. Thus, the modest performance of SOMFA on complex datasets can be primarily attributed to the low performance of the SOMFA regression methodology. A multi-component extension of the original SOR methodology (MCSOR) is introduced, and the performances of SOR, MCSOR and SIMPLS are compared using several datasets. The results indicate that in general the performance of SOMFA models is greatly improved if SOR is replaced with a more... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896630 Thu, 01 Dec 2005 05:00:00 +0100 896630 http://www.medworm.com/index.php?rid=896629&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16428133%26dopt%3DAbstract Authors: Basak SC, Natarajan R, Mills D, Hawkins DM, Kraker JJ Juvenile hormone (JH) activity of one hundred and eighty 2,4-dienoates reported for the larvae/pupae of six insect species was modeled using 915 atom pairs and 258 global molecular descriptors (topological and geometrical). Ridge regression, principal component regression and partial least square regression methods were used to model each of the JH activities. The use of all of the available parameters did not yield any good models, and extensive predictor trimming was necessary to improve the models. Ridge regression was found to give the best results among the three statistical tools used. The top ten molecular descriptors selected based on the t-statistic for each of the six models were found to be mostly atom pairs cont... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896629 Thu, 01 Dec 2005 05:00:00 +0100 896629 http://www.medworm.com/index.php?rid=896639&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16272041%26dopt%3DAbstract Authors: Sakuratani Y, Yamada J, Kasai K, Noguchi Y, Nishihara T External validation of the biodegradability prediction model CATABOL was conducted using test data of 338 existing chemicals and 1123 new chemicals under the Japanese Chemical Substances Control Law. CATABOL predicts that 1089 chemicals will have a BOD < 60% while 925 (85%) actually have an observed BOD<60%. The percentage of chemicals with an observed BOD value <60% tends to increase as the predicted BOD values decrease. In contrast, 340 chemicals were predicted to have a BOD > or = 60% and 234 (69%) actually had an observed BOD > or = 60%. The prediction of poor biodegradability was more accurate than the predictions of high biodegradability. The features of chemical structures affecting CATABOL predictab... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896639 Sat, 01 Oct 2005 04:00:00 +0100 896639 http://www.medworm.com/index.php?rid=896638&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16272042%26dopt%3DAbstract Authors: Devillers J A new type of environmental QSAR model is presented for the common situation in which the biological activity of molecules mainly depends on their 1-octanol/water partition coefficient (log P). In a first step, a classical regression equation with log P is derived. The residuals obtained with this simple linear equation are then modeled from a supervised artificial neural network including different molecular descriptors as input neurons. Finally, results produced by the linear and nonlinear models are both considered for calculating the activity values, which are compared with the initial actual activity values. A heterogeneous database of 569 organic compounds with 96-h LC50s measured to the fathead minnow (Pimephales promelas), randomly divided into a training s... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896638 Sat, 01 Oct 2005 04:00:00 +0100 896638 http://www.medworm.com/index.php?rid=896637&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16272043%26dopt%3DAbstract Authors: Saçan MT, Ozkul M, Erdem SS QSPR models for water solubility (S), n-octanol/water partition coefficient (K(OW)), and Henry's law constant (H) for polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzo-p-furans (PCDFs) and phthalates have been established based on two different sets of parameters. Those parameters were topology based characteristic root index (CRI) and three semi-empirical molecular descriptors, namely--energies of the highest occupied and the lowest unoccupied molecular orbital (E(HOMO) and E(LUMO)), and dipole moment (mu). The best fit equation found by "forward multiple linear regression" showed that the topology based CRI was the most important parameter for the modelling of solubility and n-octanol/water partition coefficient. For n-octanol/water parti... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896637 Sat, 01 Oct 2005 04:00:00 +0100 896637 http://www.medworm.com/index.php?rid=896636&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16272044%26dopt%3DAbstract In this study, a quantitative structure-property relationship (QSPR) model for the prediction of Henry's law constants of aliphatic hydrocarbons in air-water system has been developed, based on a data-set of 189 compounds. The well-known linear thermodynamic relation between the logarithm of Henry's law constant and solvation free energy has been used for developing the model. It is emphasised that the solvent-accessible surface area (SASA) descriptor is not adequate for predicting the solvation free energy of a wide range of aliphatic hydrocarbons; there are many compounds that have the same solvent-accessible surface area with different solvation free energy. Therefore, we have introduced cavity ovality as a good descriptor of molecular cavity shape factor. The root mean square error (RM... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896636 Sat, 01 Oct 2005 04:00:00 +0100 896636 http://www.medworm.com/index.php?rid=896635&cid=s_36246_55_f&fid=36246&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16272045%26dopt%3DAbstract This article compares two bioconcentration Quantitative Structure Activity Relationships (QSARs) for fish applied in human risk assessments with the mechanistic bioaccumulation model OMEGA and field data. It was found that all models are virtually similar up to a Kow of 10(6). For substances with a Kow higher than 10(6), the fish bioconcentration curve in the risk assessment model EUSES decreases parabolically. In contrast, OMEGA bioaccumulation outcomes approximately show a linear increase, based on mechanistic bioconcentration and biomagnification properties of chemicals. The OMEGA-outcomes are close to the fish bioconcentration outcomes of the risk assessment model CalTOX. For very hydrophobic substances, field accumulation data in freshwater and marine fish species are closer to OMEGA-... SAR and QSAR in Environmental Research journals http://www.medworm.com/rss/comments.php?id=896635 Sat, 01 Oct 2005 04:00:00 +0100 896635