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The physicochemical basis of QSARs for baseline toxicity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: SAR and QSAR in Environmental Research - June 28, 2009 Category: Environmental Health Authors: Mackay D, Arnot JA, Petkova EP, Wallace KB, Call DJ, Brooke LT, Veith GD Tags: SAR QSAR Environ Res Source Type: journals

Use of principal component analysis and a spectral mapping technique for the evaluation of the antifungal activity of anthracene-based synthetic dyes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 t...
Source: SAR and QSAR in Environmental Research - June 28, 2009 Category: Environmental Health Authors: Oros G, Cserháti T Tags: SAR QSAR Environ Res Source Type: journals

Design of topological indices: computer-oriented approach.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 basi...
Source: SAR and QSAR in Environmental Research - June 28, 2009 Category: Environmental Health Authors: Skvortsova MI, Palyulin VA, Zefirov NS Tags: SAR QSAR Environ Res Source Type: journals

Application of the linear interaction energy method for rational design of artemisinin analogues as haeme polymerisation inhibitors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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-L...
Source: SAR and QSAR in Environmental Research - June 28, 2009 Category: Environmental Health Authors: Srivastava M, Singh H, Naik PK Tags: SAR QSAR Environ Res Source Type: journals

QSAR models for P450 (2D6) substrate activity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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) mod...
Source: SAR and QSAR in Environmental Research - June 28, 2009 Category: Environmental Health Authors: Ringsted T, Nikolov N, Jensen GE, Wedebye EB, Niemelä J Tags: SAR QSAR Environ Res Source Type: journals

DFT study on the bromination pattern dependence of electronic properties and their validity in quantitative structure-activity relationships of polybrominated diphenyl ethers.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: SAR and QSAR in Environmental Research - June 28, 2009 Category: Environmental Health Authors: Gu CG, Ju XH, Jiang X, Wang F, Yang SG, Sun C Tags: SAR QSAR Environ Res Source Type: journals

Estimation of molecular diffusivity of pure chemicals in water: a quantitative structure-property relationship study.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 - June 28, 2009 Category: Environmental Health Authors: Gharagheizi F, Sattari M Tags: SAR QSAR Environ Res Source Type: journals

How not to develop a quantitative structure-activity or structure-property relationship (QSAR/QSPR).Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 - June 28, 2009 Category: Environmental Health Authors: Dearden JC, Cronin MT, Kaiser KL Tags: SAR QSAR Environ Res Source Type: journals

Molecular simulation of polycyclic aromatic hydrocarbon sorption to black carbon.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 i...
Source: SAR and QSAR in Environmental Research - June 28, 2009 Category: Environmental Health Authors: Haftka JJ, Parsons JR, Govers HA Tags: SAR QSAR Environ Res Source Type: journals

Using chemical categories to fill data gaps in hazard assessment.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 tox...
Source: SAR and QSAR in Environmental Research - June 28, 2009 Category: Environmental Health Authors: van Leeuwen K, Schultz TW, Henry T, Diderich B, Veith GD Tags: SAR QSAR Environ Res Source Type: journals

Fragment-based prediction of cytochromes P450 2D6 and 1A2 inhibition by recursive partitioning.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 term...
Source: SAR and QSAR in Environmental Research - June 28, 2009 Category: Environmental Health Authors: Burton J, Danloy E, Vercauteren DP Tags: SAR QSAR Environ Res Source Type: journals

Strategic selection of chemicals for testing. Part I. Functionalities and performance of basic selection methods.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: SAR and QSAR in Environmental Research - January 1, 2009 Category: Environmental Health Authors: Aladjov H, Todorov M, Schmieder P, Serafimova R, Mekenyan O, Veith G Tags: SAR QSAR Environ Res Source Type: journals

Comparative PBT screening using (Q)SAR tools within REACH legislation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 - January 1, 2009 Category: Environmental Health Authors: Zachary M, Greenway GM Tags: SAR QSAR Environ Res Source Type: journals

QSAR study of selective I1-imidazoline receptor ligands.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: SAR and QSAR in Environmental Research - January 1, 2009 Category: Environmental Health Authors: Nikolic K, Filipic S, Agbaba D Tags: SAR QSAR Environ Res Source Type: journals

Predicting the vapour pressure of chemicals from structure: a comparison of graph theoretic versus quantum chemical descriptors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: SAR and QSAR in Environmental Research - January 1, 2009 Category: Environmental Health Authors: Basak SC, Mills D Tags: SAR QSAR Environ Res Source Type: journals

Identification of potential influenza virus endonuclease inhibitors through virtual screening based on the 3D-QSAR model.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 comp...
Source: SAR and QSAR in Environmental Research - January 1, 2009 Category: Environmental Health Authors: Kim J, Lee C, Chong Y Tags: SAR QSAR Environ Res Source Type: journals

Modelling the depuration rates of polychlorinated biphenyls in Oncorhynchus mykiss with quantum chemical descriptors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: SAR and QSAR in Environmental Research - January 1, 2009 Category: Environmental Health Authors: Wang L, Liu XH, Wu D, Xu MZ, Sun T, Cui BS, Yang ZF Tags: SAR QSAR Environ Res Source Type: journals

Quantitative structure-property relationship modelling of the degradability rate constant of alkenes by OH radicals in atmosphere.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: SAR and QSAR in Environmental Research - January 1, 2009 Category: Environmental Health Authors: Fatemi MH, Baher E Tags: SAR QSAR Environ Res Source Type: journals

Prediction of chemical carcinogenicity by machine learning approaches.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: SAR and QSAR in Environmental Research - January 1, 2009 Category: Environmental Health Authors: Tan NX, Rao HB, Li ZR, Li XY Tags: SAR QSAR Environ Res Source Type: journals

A modified uncorrelated linear discriminant analysis model coupled with recursive feature elimination for the prediction of bioactivity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 inc...
Source: SAR and QSAR in Environmental Research - January 1, 2009 Category: Environmental Health Authors: Chen X, Liang YZ, Yuan DL, Xu QS Tags: SAR QSAR Environ Res Source Type: journals

Synthesis, antimicrobial activity and QSAR studies of 2,5-disubstituted benzoxazoles.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: SAR and QSAR in Environmental Research - October 16, 2008 Category: Environmental Health Authors: Arisoy M, Temiz-Arpaci O, Yildiz I, Kaynak-Onurdag F, Aki E, Yalcin I, Abbasoglu U Tags: SAR QSAR Environ Res Source Type: journals

Application of QSARs and VFARs to the rapid risk assessment process at US EPA.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 - October 16, 2008 Category: Environmental Health Authors: Moudgal CJ, Young D, Nichols T, Martin T, Harten P, Venkatapathy R, Stelma G, Siddhanti S, Baier-Anderson C, Wolfe M Tags: SAR QSAR Environ Res Source Type: journals

Identification of mechanisms of toxic action for skin sensitisation using a SMARTS pattern based approach.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 assignmen...
Source: SAR and QSAR in Environmental Research - October 16, 2008 Category: Environmental Health Authors: Enoch SJ, Madden JC, Cronin MT Tags: SAR QSAR Environ Res Source Type: journals

Molecular graph fingerprint: a new molecular structural characterization method for the modelling and prediction of chromatographic retention behaviour of several persistent organic pollutants.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 advant...
Source: SAR and QSAR in Environmental Research - October 16, 2008 Category: Environmental Health Authors: Yang S, Tian F, Li Z Tags: SAR QSAR Environ Res Source Type: journals

QSPR checking and validation: a case study with hydroxy radical reaction rate constant.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: SAR and QSAR in Environmental Research - October 16, 2008 Category: Environmental Health Authors: Hawkins DM, Kraker JJ, Basak SC, Mills D Tags: SAR QSAR Environ Res Source Type: journals

An evaluation of the implementation of the Cramer classification scheme in the Toxtree software.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 tox...
Source: SAR and QSAR in Environmental Research - October 16, 2008 Category: Environmental Health Authors: Patlewicz G, Jeliazkova N, Safford RJ, Worth AP, Aleksiev B Tags: SAR QSAR Environ Res Source Type: journals

ExPlain: finding upstream drug targets in disease gene regulatory networks.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 a...
Source: SAR and QSAR in Environmental Research - October 16, 2008 Category: Environmental Health Authors: Kel A, Voss N, Valeev T, Stegmaier P, Kel-Margoulis O, Wingender E Tags: SAR QSAR Environ Res Source Type: journals

Prediction of atmospheric degradation data for POPs by gene expression programming.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 h...
Source: SAR and QSAR in Environmental Research - October 16, 2008 Category: Environmental Health Authors: Luan F, Si HZ, Liu HT, Wen YY, Zhang XY Tags: SAR QSAR Environ Res Source Type: journals

Mode of action-based classification and prediction of activity of uncouplers for the screening of chemical inventories.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: SAR and QSAR in Environmental Research - October 16, 2008 Category: Environmental Health Authors: Spycher S, Netzeva TI, Worth AP, Escher BI Tags: SAR QSAR Environ Res Source Type: journals

Prediction of chemical toxicity with local support vector regression and activity-specific kernels.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 Toxicit...
Source: SAR and QSAR in Environmental Research - October 16, 2008 Category: Environmental Health Authors: Maunz A, Helma C Tags: SAR QSAR Environ Res Source Type: journals

Toxmatch-a new software tool to aid in the development and evaluation of chemically similar groups.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 releva...
Source: SAR and QSAR in Environmental Research - April 1, 2008 Category: Environmental Health Authors: Patlewicz G, Jeliazkova N, Gallegos Saliner A, Worth AP Tags: SAR QSAR Environ Res Source Type: journals

Estimation of bioconcentration factors using molecular electro-topological state and flexibility.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: SAR and QSAR in Environmental Research - April 1, 2008 Category: Environmental Health Authors: Wang Y, Li Y, Ding J, Jiang Z, Chang Y Tags: SAR QSAR Environ Res Source Type: journals

On novel representation of proteins based on amino acid adjacency matrix.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 - April 1, 2008 Category: Environmental Health Authors: Randic M, Novic M, Vracko M Tags: SAR QSAR Environ Res Source Type: journals

Representation of proteins as walks in 20-D space.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: SAR and QSAR in Environmental Research - April 1, 2008 Category: Environmental Health Authors: Novic M, Randic M Tags: SAR QSAR Environ Res Source Type: journals

Online resource for theoretical study of hydration of biopolymers.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 us...
Source: SAR and QSAR in Environmental Research - April 1, 2008 Category: Environmental Health Authors: Sobolev EV, Sobolev OV, Tikhonov DA Tags: SAR QSAR Environ Res Source Type: journals

QSAR studies using the parashift system.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 - April 1, 2008 Category: Environmental Health Authors: Livingstone DJ, Clark T, Ford MG, Hudson BD, Whitley DC Tags: SAR QSAR Environ Res Source Type: journals

Characterisation of the chemical and biological properties of molecules with QSAR/QSPR and chemical grouping, and its application to a group of alkyl ethers.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 an...
Source: SAR and QSAR in Environmental Research - April 1, 2008 Category: Environmental Health Authors: Niska H, Tuppurainen K, Skon JP, Mallett AK, Kolehmainen M Tags: SAR QSAR Environ Res Source Type: journals

Homology modelling of the Apis mellifera nicotinic acetylcholine receptor (nAChR) and docking of imidacloprid and fipronil insecticides and their metabolites.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 t...
Source: SAR and QSAR in Environmental Research - April 1, 2008 Category: Environmental Health Authors: Rocher A, Marchand-Geneste N Tags: SAR QSAR Environ Res Source Type: journals

Quantitative structure-affinity relationship of 5-HT(1A) receptor ligands by the classification tree method.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 - April 1, 2008 Category: Environmental Health Authors: Kuz'min VE, Polischuk PG, Artemenko AG, Makan SY, Andronati SA Tags: SAR QSAR Environ Res Source Type: journals

Prediction of drug solubility from molecular structure using a drug-like training set.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 =...
Source: SAR and QSAR in Environmental Research - April 1, 2008 Category: Environmental Health Authors: Huuskonen J, Livingstone DJ, Manallack DT Tags: SAR QSAR Environ Res Source Type: journals

Quantitative structure-affinity relationship of 5-HT1A receptor ligands by the classification tree method.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 - April 1, 2008 Category: Environmental Health Authors: Kuz'min VE, Polischuk PG, Artemenko AG, Makan SY, Andronati SA Tags: SAR QSAR Environ Res Source Type: journals

Structure-related clustering of gene expression fingerprints of thp-1 cells exposed to smaller polycyclic aromatic hydrocarbons.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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; dibenzot...
Source: SAR and QSAR in Environmental Research - April 1, 2008 Category: Environmental Health Authors: Wan B, Yarbrough JW, Schultz TW Tags: SAR QSAR Environ Res Source Type: journals

Molecular dynamics simulations of the enzyme Catechol-O-Methyltransferase: methodological issues.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 tha...
Source: SAR and QSAR in Environmental Research - January 1, 2008 Category: Environmental Health Authors: Bunker A, Männistö P, St Pierre JF, Róg T, Pomorski P, Stimson L, Karttunen M Tags: SAR QSAR Environ Res Source Type: journals

Prediction of pH-dependent aqueous solubility of Histone Deacetylase (HDAC) inhibitors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 A...
Source: SAR and QSAR in Environmental Research - January 1, 2008 Category: Environmental Health Authors: Kouskoumvekaki I, Hansen NT, Björkling F, Vadlamudi SM, Jónsdóttir SO Tags: SAR QSAR Environ Res Source Type: journals

Fast tools for calculation of atomic charges well suited for drug design.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 reproductio...
Source: SAR and QSAR in Environmental Research - January 1, 2008 Category: Environmental Health Authors: Shulga DA, Oliferenko AA, Pisarev SA, Palyulin VA, Zefirov NS Tags: SAR QSAR Environ Res Source Type: journals

Decision trees versus support vector machine for classification of androgen receptor ligands.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 atom...
Source: SAR and QSAR in Environmental Research - January 1, 2008 Category: Environmental Health Authors: Panaye A, Doucet JP, Devillers J, Marchand-Geneste N, Porcher JM Tags: SAR QSAR Environ Res Source Type: journals

Prediction of PAH mutagenicity in human cells by QSAR classification.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 i...
Source: SAR and QSAR in Environmental Research - January 1, 2008 Category: Environmental Health Authors: Papa E, Pilutti P, Gramatica P Tags: SAR QSAR Environ Res Source Type: journals

QSAR and pharmacophore analysis on amides against drug-resistant S. aureus.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 poss...
Source: SAR and QSAR in Environmental Research - January 1, 2008 Category: Environmental Health Authors: Yildiz I, Ertan T, Bolelli K, Temiz-Arpaci O, Yalcin I, Aki E Tags: SAR QSAR Environ Res Source Type: journals

Ligand-specific scoring functions: improved ranking of docking solutions.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: SAR and QSAR in Environmental Research - January 1, 2008 Category: Environmental Health Authors: Pyrkov TV, Priestle JP, Jacoby E, Efremov RG Tags: SAR QSAR Environ Res Source Type: journals

Computer-aided prediction of QT-prolongation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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-traini...
Source: SAR and QSAR in Environmental Research - January 1, 2008 Category: Environmental Health Authors: Filz O, Lagunin A, Filimonov D, Poroikov V Tags: SAR QSAR Environ Res Source Type: journals