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 'Biophysical Journal' source. Fri, 12 Mar 2010 16:29:38 +0100 http://www.medworm.com/index.php?rid=3336112&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197027%26dopt%3DAbstract In conclusion, the oscillatory response of homeostatic controllers may provide new insights into the origin and role of oscillations observed in homeostatically controlled molecular networks. PMID: 20197027 [PubMed - as supplied by publisher] (Source: Biophysical Journal) Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3336112 Wed, 03 Mar 2010 00:00:00 +0100 3336112 http://www.medworm.com/index.php?rid=3336111&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197028%26dopt%3DAbstract Authors: Berndt A, Prigge M, Gradmann D, Hegemann P Channelrhodopsins are light-gated ion channels that mediate vision in phototactic green algae like Chlamydomonas. In neurosciences, channelrhodopsins are widely used to light-trigger action potentials in transfected cells. All known channelrhodopsins preferentially conduct H(+). Previous studies have indicated the existence of an early and a late conducting state within the channelrhodopsin photocycle. Here, we show that for channelrhodopsin-2 expressed in Xenopus oocytes and HEK cells, the two open states have different ion selectivities that cause changes in the channelrhodopsin-2 reversal voltage during a light pulse. An enzyme kinetic algorithm was applied to convert the reversal voltages in various ionic conditions to conductance... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3336111 Wed, 03 Mar 2010 00:00:00 +0100 3336111 http://www.medworm.com/index.php?rid=3336110&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197029%26dopt%3DAbstract Authors: Finol-Urdaneta RK, McArthur JR, Juranka PF, French RJ, Morris CE The actions of alcohols and anesthetics on ion channels are poorly understood. Controversy continues about whether bilayer restructuring is relevant to the modulatory effects of these surface active agents (SAAs). Some voltage-gated K channels (Kv), but not KvAP, have putative low affinity alcohol-binding sites, and because KvAP structures have been determined in bilayers, KvAP could offer insights into the contribution of bilayer mechanics to SAA actions. We monitored KvAP unitary conductance and macroscopic activation and inactivation kinetics in PE:PG/decane bilayers with and without exposure to classic SAAs (short-chain 1-alkanols, cholesterol, and selected anesthetics: halothane, isoflurane, chloroform). At ... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3336110 Wed, 03 Mar 2010 00:00:00 +0100 3336110 http://www.medworm.com/index.php?rid=3336109&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197030%26dopt%3DAbstract Authors: Karashima Y, Prenen J, Talavera K, Janssens A, Voets T, Nilius B The Ca(2+)-permeable cation channel TRPA1 acts as an ionotropic receptor for various pungent compounds and as a noxious cold sensor in sensory neurons. It is unclear what proportion of the TRPA1-mediated current is carried by Ca(2+) ions and how the permeation pathway changes during stimulation. Here, based on the relative permeability of the nonstimulated channel to cations of different size, we estimated a pore diameter of approximately 11 A. Combined patch-clamp and Fura-2 fluorescence recordings revealed that with 2 mM extracellular Ca(2+), and at a membrane potential of -80 mV, approximately 17% of the inward TRPA1 current is carried by Ca(2+). Stimulation with mustard oil evoked an apparent dilatation of th... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3336109 Wed, 03 Mar 2010 00:00:00 +0100 3336109 http://www.medworm.com/index.php?rid=3336108&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197031%26dopt%3DAbstract Authors: Chakrabarti N, Neale C, Payandeh J, Pai EF, Pomès R Magnesium translocation across cell membranes is essential for numerous physiological processes. Three recently reported crystal structures of the CorA magnesium transport system revealed a surprising architecture, with a bundle of giant alpha-helices forming a 60-A-long pore that extends beyond the membrane before widening into a funnel-shaped cytosolic domain. The presence of divalent cations in putative intracellular regulation sites suggests that these structures correspond to the closed conformation of CorA. To examine the nature of the conduction pathway, we performed 110-ns molecular-dynamics simulations of two of these structures in a lipid bilayer with and without regulatory ions. The results show that a 15-A-lo... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3336108 Wed, 03 Mar 2010 00:00:00 +0100 3336108 http://www.medworm.com/index.php?rid=3336107&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197032%26dopt%3DAbstract Authors: Smith HL, Hickey J, Jablin MS, Trujillo A, Freyer JP, Majewski J Neutron reflectometry (NR) was used to examine live mouse fibroblast cells adherent on a quartz substrate in a deuterated phosphate-buffered saline environment at room temperature. These measurements represent the first, to our knowledge, successful visualization and quantization of the interface between live cells and a substrate with subnanometer resolution using NR. NR data, attributable to the adhesion of live cells, were observed and compared with data from pure growth medium. Independently of surface cell density, the average distance between the center of the cell membrane region and the quartz substrate was determined to be approximately 180 A. The membrane region ( approximately 80 A thick) contains the ... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3336107 Wed, 03 Mar 2010 00:00:00 +0100 3336107 http://www.medworm.com/index.php?rid=3336106&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197033%26dopt%3DAbstract Authors: Morozova D, Weiss M Acylation is a frequent means to ensure membrane association of a variety of soluble proteins in living cells. However, many transmembrane proteins are palmitoylated, indicating that this posttranslational modification may also serve as a means to regulate protein trafficking. Based on coarse-grained membrane simulations, we find that protein acylation significantly alters the tilting of transmembrane proteins with respect to the bilayer normal. In addition, the proteins' partitioning behavior and cluster formation ability due to hydrophobic mismatching is strongly altered. Based on our results, we propose that acylation is a potent means to regulate the trafficking of transmembrane proteins along the early secretory pathway. PMID: 20197033 [PubMed - as... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3336106 Wed, 03 Mar 2010 00:00:00 +0100 3336106 http://www.medworm.com/index.php?rid=3336105&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197034%26dopt%3DAbstract Authors: Sayadi M, Tanizaki S, Feig M The conformational sampling of monomeric, membrane-bound phospholamban is described from computer simulations. Phospholamban (PLB) plays a key role as a regulator of sarcoplasmic reticulum calcium ATPase. An implicit membrane model is used in conjunction with replica exchange molecular dynamics simulations to reach mus-ms timescales. The implicit membrane model was also used to study the effect of different membrane thicknesses by scaling the low-dielectric region. The conformational sampling with the membrane model mimicking dipalmitoylphosphatidylcholine bilayers is in good agreement overall with experimental measurements, but consists of a wide variety of different conformations including structures not described previously. The conformational e... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3336105 Wed, 03 Mar 2010 00:00:00 +0100 3336105 http://www.medworm.com/index.php?rid=3336104&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197035%26dopt%3DAbstract Authors: Oreopoulos J, Epand RF, Epand RM, Yip CM Direct visualization of the mechanism(s) by which peptides induce localized changes to the structure of membranes has high potential for enabling understanding of the structure-function relationship in antimicrobial and cell-penetrating peptides. We have applied a combined imaging strategy to track the interaction of a model antimicrobial peptide, PFWRIRIRR-amide, with bacterial membrane-mimetic supported phospholipid bilayers comprised of POPE/TOCL. Our in situ studies revealed rapid reorganization of the POPE/TOCL membrane into localized TOCL-rich domains with a concomitant change in the organization of the membranes themselves, as reflected by changes in fluorescent-membrane-probe order parameter, upon introduction of the peptide. ... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3336104 Wed, 03 Mar 2010 00:00:00 +0100 3336104 http://www.medworm.com/index.php?rid=3336103&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197036%26dopt%3DAbstract Authors: Bécavin C, Barbi M, Victor JM, Lesne A During eukaryotic transcription, RNA-polymerase activity generates torsional stress in DNA, having a negative impact on the elongation process. Using our previous studies of chromatin fiber structure and conformational transitions, we suggest that this torsional stress can be alleviated, thanks to a tradeoff between the fiber twist and nucleosome conformational transitions into an activated state named "reversome". Our model enlightens the origin of polymerase pauses, and leads to the counterintuitive conclusion that chromatin-organized compaction might facilitate polymerase progression. Indeed, in a compact and well-structured chromatin loop, steric hindrance between nucleosomes enforces sequential transitions, thus ensuring that th... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3336103 Wed, 03 Mar 2010 00:00:00 +0100 3336103 http://www.medworm.com/index.php?rid=3336102&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197037%26dopt%3DAbstract We present atomistic simulations, mesoscopic modeling and single-molecule pulling experiments describing DNA dendrimer interactions. All-atom molecular dynamics were used to characterize pulling-force-dependent interactions between DNA and generation-3 PAMAM amine-terminated dendrimers, and a free energy profile and mean forces along the interaction coordinate are calculated. The energy, force, and geometry parameters computed at the atomic level are input for a Monte Carlo model yielding mesoscopic force-extension curves. Actual experimental single-molecule curves obtained with optical tweezers are also presented, and they show remarkable agreement with the virtual curves from our model. The calculations reveal the microscopic origin of the hysteresis observed in the phase transition unde... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3336102 Wed, 03 Mar 2010 00:00:00 +0100 3336102 http://www.medworm.com/index.php?rid=3336101&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197038%26dopt%3DAbstract Authors: Waudby CA, Knowles TP, Devlin GL, Skepper JN, Ecroyd H, Carver JA, Welland ME, Christodoulou J, Dobson CM, Meehan S alphaB-Crystallin is a small heat-shock protein (sHsp) that is colocalized with alpha-synuclein (alphaSyn) in Lewy bodies-the pathological hallmarks of Parkinson's disease-and is an inhibitor of alphaSyn amyloid fibril formation in an ATP-independent manner in vitro. We have investigated the mechanism underlying the inhibitory action of sHsps, and here we establish, by means of a variety of biophysical techniques including immunogold labeling and nuclear magnetic resonance spectroscopy, that alphaB-crystallin interacts with alphaSyn, binding along the length of mature amyloid fibrils. By measurement of seeded fibril elongation kinetics, both in solution and on a ... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3336101 Wed, 03 Mar 2010 00:00:00 +0100 3336101 http://www.medworm.com/index.php?rid=3336100&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197039%26dopt%3DAbstract Authors: Jantz D, Berg JM Engineered transcription factors and endonucleases based on designed Cys(2)His(2) zinc finger domains have proven to be effective tools for the directed regulation and modification of genes. The introduction of this technology into both research and clinical settings necessitates the development of rapid and accurate means of evaluating both the binding affinity and binding specificity of designed zinc finger domains. Using a fluorescence anisotropy-based DNA-binding assay, we examined the DNA-binding properties of two engineered zinc finger proteins that differ by a single amino acid. We demonstrate that the protein with the highest affinity for a particular DNA site need not be the protein that binds that site with the highest degree of specificity. Moreover... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3336100 Wed, 03 Mar 2010 00:00:00 +0100 3336100 http://www.medworm.com/index.php?rid=3336099&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197040%26dopt%3DAbstract Authors: Kuzmanic A, Zagrovic B Root mean-square deviation (RMSD) after roto-translational least-squares fitting is a measure of global structural similarity of macromolecules used commonly. On the other hand, experimental x-ray B-factors are used frequently to study local structural heterogeneity and dynamics in macromolecules by providing direct information about root mean-square fluctuations (RMSF) that can also be calculated from molecular dynamics simulations. We provide a mathematical derivation showing that, given a set of conservative assumptions, a root mean-square ensemble-average of an all-against-all distribution of pairwise RMSD for a single molecular species, <RMSD(2)>(1/2), is directly related to average B-factors (<B>) and <RMSF(2)>(1/2). We show this ... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3336099 Wed, 03 Mar 2010 00:00:00 +0100 3336099 http://www.medworm.com/index.php?rid=3336098&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197041%26dopt%3DAbstract Authors: Aguilar B, Anandakrishnan R, Ruscio JZ, Onufriev AV This work investigates statistical prevalence and overall physical origins of changes in charge states of receptor proteins upon ligand binding. These changes are explored as a function of the ligand type (small molecule, protein, and nucleic acid), and distance from the binding region. Standard continuum solvent methodology is used to compute, on an equal footing, pK changes upon ligand binding for a total of 5899 ionizable residues in 20 protein-protein, 20 protein-small molecule, and 20 protein-nucleic acid high-resolution complexes. The size of the data set combined with an extensive error and sensitivity analysis allows us to make statistically justified and conservative conclusions: in 60% of all protein-small molecule,... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3336098 Wed, 03 Mar 2010 00:00:00 +0100 3336098 http://www.medworm.com/index.php?rid=3336097&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197042%26dopt%3DAbstract Authors: Bocharov EV, Mayzel ML, Volynsky PE, Mineev KS, Tkach EN, Ermolyuk YS, Schulga AA, Efremov RG, Arseniev AS The Eph receptor tyrosine kinases and their membrane-bound ephrin ligands control a diverse array of cell-cell interactions in the developing and adult organisms. During signal transduction across plasma membrane, Eph receptors, like other receptor tyrosine kinases, are involved in lateral dimerization and subsequent oligomerization presumably with proper assembly of their single-span transmembrane domains. Spatial structure of dimeric transmembrane domain of EphA2 receptor embedded into lipid bicelle was obtained by solution NMR, showing a left-handed parallel packing of the transmembrane helices (535-559)(2). The helices interact through the extended heptad repeat motif... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3336097 Wed, 03 Mar 2010 00:00:00 +0100 3336097 http://www.medworm.com/index.php?rid=3336096&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197043%26dopt%3DAbstract This study investigates the effect of the cutoff value used in building the residue network. For small cutoff values, <5 A, the cavities found are very large corresponding almost to the whole protein surface. On the contrary, for large cutoff value, >10.0 A, only very large cavities are detected and the networks look very homogeneous. These findings are useful for practical purposes as well as for identifying protein-like complex networks. Finally, this article shows that the main topological class of residue networks is not reproduced by random networks growing according to Erdös-Rényi model or the preferential attachment method of Barabási-Albert. However, the Watts-Strogatz model reproduces very well the topological class as well as other topological properties of r... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3336096 Wed, 03 Mar 2010 00:00:00 +0100 3336096 http://www.medworm.com/index.php?rid=3336095&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197044%26dopt%3DAbstract We present a method for estimating this contribution, based on perturbation theory using the quasi-harmonic model of Karplus and Kushick as a reference system. The consistency of the method is checked for small model systems. Subsequently we use the method, along with an estimate for the enthalpic contribution due to ligand-receptor interactions, to calculate relative binding affinities. The AMBER force field and generalized Born implicit solvent model is used. Binding affinities were estimated for a test set of 233 protein-ligand complexes for which crystal structures and measured binding affinities are available. In most cases, the ligand conformation in the bound state was significantly different from the most favorable conformation in solution. In general, the correlation between measu... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3336095 Wed, 03 Mar 2010 00:00:00 +0100 3336095 http://www.medworm.com/index.php?rid=3336094&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197045%26dopt%3DAbstract In this report, we apply the phasor representation of fluorescence lifetime imaging data to the quantitative study of ionic concentrations in tissues, overcoming technical problems of tissue thickness, concentration artifacts of ion-sensitive dyes, and calibration across inhomogeneous tissue. We used epidermis as a model system, as Ca(2+) gradients in this organ have been shown previously to control essential biologic processes of differentiation and formation of the epidermal permeability barrier. The approach described here allowed much better localization of Ca(2+) stores than those used in previous studies, and revealed that the bulk of free Ca(2+) measured in the epidermis comes from intracellular Ca(2+) stores such as the Golgi and the endoplasmic reticulum, with extracellular Ca(2+)... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3336094 Wed, 03 Mar 2010 00:00:00 +0100 3336094 http://www.medworm.com/index.php?rid=3336093&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197046%26dopt%3DAbstract Authors: van Oort B, Alberts M, de Bianchi S, Dall'osto L, Bassi R, Trinkunas G, Croce R, van Amerongen H The role of individual photosynthetic antenna complexes of Photosystem II (PSII) both in membrane organization and excitation energy transfer have been investigated. Thylakoid membranes from wild-type Arabidopsis thaliana, and three mutants lacking light-harvesting complexes CP24, CP26, or CP29, respectively, were studied by picosecond-fluorescence spectroscopy. By using different excitation/detection wavelength combinations it was possible for the first time, to our knowledge, to separate PSI and PSII fluorescence kinetics. The sub-100 ps component, previously ascribed entirely to PSI, turns out to be due partly to PSII. Moreover, the migration time of excitations from antenna to ... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3336093 Wed, 03 Mar 2010 00:00:00 +0100 3336093 http://www.medworm.com/index.php?rid=3284667&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159145%26dopt%3DAbstract Authors: Dodla R, Wilson CJ Auto- and cross-correlation methods, when applied to discrete events, can determine periodicity and correlation times within and between event train sequences. However, if the number of available events for analysis is too few, the correlation techniques yield ambiguous and insufficient results. Here we report a technique based on measurements of phases of event times that could detect the periodicity even among very few discrete data points. The results are demonstrated on in vitro neuronal spike time data, and are found to be highly contrasting when compared with the correlation techniques. The technique could become invaluable, for example, for treating in vivo spike time records that often last very short duration, or for determining short timescales in ... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3284667 Wed, 17 Feb 2010 00:00:00 +0100 3284667 http://www.medworm.com/index.php?rid=3284666&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159146%26dopt%3DAbstract Authors: Qiao L, Phipps-Yonas H, Hartmann B, Moran TM, Sealfon SC, Hayot F The pretreatment of human dendritic cells with interferon-beta enhances their immune response to influenza virus infection. We measured the expression levels of several key players in that response over a period of 13 h both during pretreatment and after viral infection. Their activation profiles reflect the presence of both negative and positive feedback loops in interferon induction and interferon signaling pathway. Based on these measurements, we have developed a comprehensive computational model of cellular immune response that elucidates its mechanism and its dynamics in interferon-pretreated dendritic cells, and provides insights into the effects of duration and strength of pretreatment. PMID: 20159146... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3284666 Wed, 17 Feb 2010 00:00:00 +0100 3284666 http://www.medworm.com/index.php?rid=3284665&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159147%26dopt%3DAbstract Authors: Bernal R, Melo F, Pullarkat PA We investigate the mechanical response of PC12 neurites subjected to a drag force imposed by a laminar flow perpendicular to the neurite axis. The curvature of the catenary shape acquired by an initially straight neurite under the action of the drag force provides information on both elongation and tension of the neurite. This method allows us to measure the rest tension and viscoelastic parameters of PC12 neurites and active behavior of neurites. Measurement of oscillations in the strain rate of neurites at constant flow rate provides insight on the response of molecular motors and additional support for the presence of a negative strain-rate sensitivity region in the global mechanical response of PC12 neurites. PMID: 20159147 [PubMed - as s... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3284665 Wed, 17 Feb 2010 00:00:00 +0100 3284665 http://www.medworm.com/index.php?rid=3284664&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159148%26dopt%3DAbstract Authors: Monai H, Omori T, Okada M, Inoue M, Miyakawa H, Aonishi T Under physiological and artificial conditions, the dendrites of neurons can be exposed to electric fields. Recent experimental studies suggested that the membrane resistivity of the distal apical dendrites of cortical and hippocampal pyramidal neurons may be significantly lower than that of the proximal dendrites and the soma. To understand the behavior of dendrites in time-varying extracellular electric fields, we analytically solved cable equations for finite cylindrical cables with and without a leak conductance attached to one end by employing the Green's function method. The solution for a cable with a leak at one end for direct-current step electric fields shows a reversal in polarization at the leaky end, as has ... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3284664 Wed, 17 Feb 2010 00:00:00 +0100 3284664 http://www.medworm.com/index.php?rid=3284663&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159149%26dopt%3DAbstract Authors: Ladoux B, Anon E, Lambert M, Rabodzey A, Hersen P, Buguin A, Silberzan P, Mège RM Traction forces between adhesive cells play an important role in a number of collective cell processes. Intercellular contacts, in particular cadherin-based intercellular junctions, are the major means of transmitting force within tissues. We investigated the effect of cellular tension on the formation of cadherin-cadherin contacts by spreading cells on substrates with tunable stiffness coated with N-cadherin homophilic ligands. On the most rigid substrates, cells appear well-spread and present cadherin adhesions and cytoskeletal organization similar to those classically observed on cadherin-coated glass substrates. However, when cells are cultured on softer substrates, a change in morpholog... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3284663 Wed, 17 Feb 2010 00:00:00 +0100 3284663 http://www.medworm.com/index.php?rid=3284662&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159150%26dopt%3DAbstract Authors: Selhuber-Unkel C, Erdmann T, López-García M, Kessler H, Schwarz US, Spatz JP Spatial patterning of biochemical cues on the micro- and nanometer scale controls numerous cellular processes such as spreading, adhesion, migration, and proliferation. Using force microscopy we show that the lateral spacing of individual integrin receptor-ligand bonds determines the strength of cell adhesion. For spacings >/=90 nm, focal contact formation was inhibited and the detachment forces as well as the stiffness of the cell body were significantly decreased compared to spacings </=50 nm. Analyzing cell detachment at the subcellular level revealed that rupture forces of focal contacts increase with loading rate as predicted by a theoretical model for adhesion clusters. Furthermo... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3284662 Wed, 17 Feb 2010 00:00:00 +0100 3284662 http://www.medworm.com/index.php?rid=3284661&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159151%26dopt%3DAbstract Authors: Kumar M, Mommer MS, Sourjik V Protein mobility affects most cellular processes, such as the rates of enzymatic reactions, signal transduction, and assembly of macromolecular complexes. Despite such importance, little systematic information is available about protein diffusion inside bacterial cells. Here we combined fluorescence recovery after photobleaching with numerical modeling to analyze mobility of a set of fluorescent protein fusions in the bacterial cytoplasm, the plasma membrane, and in the nucleoid. Estimated diffusion coefficients of cytoplasmic and membrane proteins show steep dependence on the size and on the number of transmembrane helices, respectively. Protein diffusion in both compartments is thus apparently obstructed by a network of obstacles, creating the s... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3284661 Wed, 17 Feb 2010 00:00:00 +0100 3284661 http://www.medworm.com/index.php?rid=3284660&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159152%26dopt%3DAbstract Authors: Luo Y, Ergenekan CE, Fischer JT, Tan ML, Ichiye T Based on the crystal structures, three possible sequence determinants have been suggested as the cause of a 285 mV increase in reduction potential of the rubredoxin domain of rubrerythrin over rubredoxin by modulating the polar environment around the redox site. Here, electrostatic calculations of crystal structures of rubredoxin and rubrerythrin and molecular dynamics simulations of rubredoxin wild-type and mutants are used to elucidate the contributions to the increased reduction potential. Asn(160) and His(179) in rubrerythrin versus valines in rubredoxins are predicted to be the major contributors, as the polar side chains contribute significantly to the electrostatic potential in the redox site region. The mutant simulatio... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3284660 Wed, 17 Feb 2010 00:00:00 +0100 3284660 http://www.medworm.com/index.php?rid=3284659&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159153%26dopt%3DAbstract Authors: Hajjar E, Mahendran KR, Kumar A, Bessonov A, Petrescu M, Weingart H, Ruggerone P, Winterhalter M, Ceccarelli M Our aim in this study was to provide an atomic description of ampicillin translocation through OmpF, the major outer membrane channel in Escherichia coli and main entry point for beta-lactam antibiotics. By applying metadynamics simulations, we also obtained the energy barriers along the diffusion pathway. We then studied the effect of mutations that affect the charge and size at the channel constriction zone, and found that in comparison to the wild-type, much lower energy barriers are required for translocation. The expected higher translocation rates were confirmed on the macroscopic scale by liposome-swelling assays. A microscopic view on the millisecond timescale... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3284659 Wed, 17 Feb 2010 00:00:00 +0100 3284659 http://www.medworm.com/index.php?rid=3284658&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159154%26dopt%3DAbstract Authors: Vad BS, Bertelsen K, Johansen CH, Pedersen JM, Skrydstrup T, Nielsen NC, Otzen DE Pardaxin is a 33-amino-acid neurotoxin from the Red Sea Moses sole Pardachirus marmoratus, whose mode of action shows remarkable sensitivity to lipid chain length and charge, although the effect of pH is unclear. Here we combine optical spectroscopy and dye release experiments with laser scanning confocal microscopy and natural abundance (13)C solid-state nuclear magnetic resonance to provide a more complete picture of how pardaxin interacts with lipids. The kinetics and efficiency of release of entrapped calcein is highly sensitive to pH. In vesicles containing zwitterionic lipids (PC), release occurs most rapidly at low pH, whereas in vesicles containing 20% anionic lipid (PG), release occurs m... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3284658 Wed, 17 Feb 2010 00:00:00 +0100 3284658 http://www.medworm.com/index.php?rid=3284657&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159155%26dopt%3DAbstract Authors: Boggara MB, Krishnamoorti R Using the potential of mean constrained force method, molecular dynamics simulations with atomistic details were performed to examine the partitioning and nature of interactions of two nonsteroidal antiinflammatory drugs, namely aspirin and ibuprofen, in bilayers of dipalmitoylphosphatidylcholine. Two charge states (neutral and anionic) of the drugs were simulated to understand the effect of protonation or pH on drug partitioning. Both drugs, irrespective of their charge state, were found to have high partition coefficients in the lipid bilayer from water. However, the values and trends of the free energy change and the location of the minima in the bilayer are seen to be influenced by the drug structure and charge state. In the context of the trans... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3284657 Wed, 17 Feb 2010 00:00:00 +0100 3284657 http://www.medworm.com/index.php?rid=3284656&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159156%26dopt%3DAbstract Authors: Voisinne G, Alexandrou A, Masson JB We propose a Bayesian method to extract the diffusivity of biomolecules evolving freely or inside membrane microdomains. This approach assumes a model of motion for the particle considered, namely free Brownian motion or confined diffusion. In each framework, a systematic Bayesian scheme is provided for estimating the diffusivity. We show that this method reaches the best performances theoretically achievable. Its efficiency overcomes that of widely used methods based on the analysis of the mean-square displacement. The approach presented here also gives direct access to the uncertainty on the estimation of the diffusivity and predicts the number of steps of the trajectory necessary to achieve any desired precision. Its robustness with respe... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3284656 Wed, 17 Feb 2010 00:00:00 +0100 3284656 http://www.medworm.com/index.php?rid=3284655&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159157%26dopt%3DAbstract Authors: Friedrich O, Both M, Weber C, Schürmann S, Teichmann MD, von Wegner F, Fink RH, Vogel M, Chamberlain JS, Garbe C Progressive force loss in Duchenne muscular dystrophy is characterized by degeneration/regeneration cycles and fibrosis. Disease progression may involve structural remodeling of muscle tissue. An effect on molecular motorprotein function may also be possible. We used second harmonic generation imaging to reveal vastly altered subcellular sarcomere microarchitecture in intact single dystrophic mdx muscle cells ( approximately 1 year old). Myofibril tilting, twisting, and local axis deviations explain at least up to 20% of force drop during unsynchronized contractile activation as judged from cosine angle sums of myofibril orientations within mdx fibers. In contr... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3284655 Wed, 17 Feb 2010 00:00:00 +0100 3284655 http://www.medworm.com/index.php?rid=3284654&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159158%26dopt%3DAbstract Authors: Sznitman J, Purohit PK, Krajacic P, Lamitina T, Arratia PE Undulatory locomotion, as seen in the nematode Caenorhabditis elegans, is a common swimming gait of organisms in the low Reynolds number regime, where viscous forces are dominant. Although the nematode's motility is expected to be a strong function of its material properties, measurements remain scarce. Here, the swimming behavior of C. elegans is investigated in experiments and in a simple model. Experiments reveal that nematodes swim in a periodic fashion and generate traveling waves that decay from head to tail. The model is able to capture the experiments' main features and is used to estimate the nematode's Young's modulus E and tissue viscosity eta. For wild-type C. elegans, we find E approximately 3.77 kPa and e... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3284654 Wed, 17 Feb 2010 00:00:00 +0100 3284654 http://www.medworm.com/index.php?rid=3284653&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159159%26dopt%3DAbstract In this study, the calculations using AMBER force field give a qualitatively correct description for the folding of two RNA hairpins, as the calculated PMF confirms the global stability of the folded structures and the resulting relative folding free energy is in quantitative agreement with the experimental result. The hairpin stabilities are also correctly differentiated by the more rapid molecular mechanics-Poisson Boltzmann-surface area approach, but the relative free energy estimated from this method is overestimated. The free energy profile shows that the native state basin and the unfolded state plateau are separated by a wide shoulder region, which samples a variety of native-like structures with frayed terminal basepair. The calculated PMF lacks major barriers that are expected nea... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3284653 Wed, 17 Feb 2010 00:00:00 +0100 3284653 http://www.medworm.com/index.php?rid=3284652&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159160%26dopt%3DAbstract Authors: Fisette O, Morin S, Savard PY, Lagüe P, Gagné SM Dynamic properties of class A beta-lactamase TEM-1 are investigated from molecular dynamics (MD) simulations. Comparison of MD-derived order parameters with those obtained from model-free analysis of nuclear magnetic resonance (NMR) relaxation data shows high agreement for N-H moieties within alpha- and beta-secondary structures, but significant deviation for those in loops. This was expected, because motions slower than the protein global tumbling often take place in loop regions. As previously shown using NMR, TEM-1 is a highly ordered protein. Motions are observed within the Omega loop that could, upon substrate binding, stabilize E166 in a catalytically efficient position as the cavity between the protein core and ... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3284652 Wed, 17 Feb 2010 00:00:00 +0100 3284652 http://www.medworm.com/index.php?rid=3284651&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159161%26dopt%3DAbstract We report a numerical study of the (un)folding routes of the truncated FBP28 WW domain at ambient conditions using a combination of four advanced rare event molecular simulation techniques. We explore the free energy landscape of the native state, the unfolded state, and possible intermediates, with replica exchange molecular dynamics. Subsequent application of bias-exchange metadynamics yields three tentative unfolding pathways at room temperature. Using these paths to initiate a transition path sampling simulation reveals the existence of two major folding routes, differing in the formation order of the two main hairpins, and in hydrophobic side-chain interactions. Having established that the hairpin strand separation distances can act as reasonable reaction coordinates, we employ metady... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3284651 Wed, 17 Feb 2010 00:00:00 +0100 3284651 http://www.medworm.com/index.php?rid=3284650&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159162%26dopt%3DAbstract Authors: Joshi H, Momin F, Haines KE, Dima RI Decomposition of the intrinsic dynamics of proteins into collective motions among distant regions of the protein structure provides a physically appealing approach that couples the dynamics of the system with its functional role. The cellular functions of microtubules (an essential component of the cytoskeleton in all eukaryotic cells) depend on their dynamic instability, which is altered by various factors among which applied forces are central. To shed light on the coupling between forces and the dynamic instability of microtubules, we focus on the investigation of the response of the microtubule subunits (tubulin) to applied forces. We address this point by adapting an approach designed to survey correlations for the equilibrium dynamics... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3284650 Wed, 17 Feb 2010 00:00:00 +0100 3284650 http://www.medworm.com/index.php?rid=3284649&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159163%26dopt%3DAbstract Authors: Folch B, Dehouck Y, Rooman M The goal of controlling protein thermostability is tackled here through establishing, by in silico analyses, the relative weight of residue-residue interactions in proteins as a function of temperature. We have designed for that purpose a (melting-) temperature-dependent, statistical distance potential, where the interresidue distances are computed between the side-chain geometric centers or their functional centers. Their separate derivation from proteins of either high or low thermal resistance reveals the interactions that contribute most to stability in different temperature ranges. Thermostabilizing interactions include salt bridges and cation-pi interactions (especially those involving arginine), aromatic interactions, and H-bonds between neg... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3284649 Wed, 17 Feb 2010 00:00:00 +0100 3284649 http://www.medworm.com/index.php?rid=3284648&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159164%26dopt%3DAbstract Authors: Kato S, Kamikubo H, Hirano S, Yamazaki Y, Kataoka M Rapid molecular collapse mediated by nonlocal interactions is believed to be a crucial event for protein folding. To investigate the role of nonlocal interactions in tertiary structure formation, we performed a nonlocal interaction substitution mutation analysis on staphylococcal nuclease (SNase). Y54 and I139 of wild-type (WT) SNase and Delta140-149 were substituted by cysteine to form intramolecular disulfide bonds, respectively called WT-SS and Delta140-149-SS. Under physiological conditions, the reduced form of Delta140-149-SS appears to assume a denatured structure; in contrast, the oxidized form of Delta140-149-SS forms a native-like structure. From this result, we conclude that the C-terminal region participates in a n... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3284648 Wed, 17 Feb 2010 00:00:00 +0100 3284648 http://www.medworm.com/index.php?rid=3284647&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159165%26dopt%3DAbstract Authors: Zink M, Grubmüller H The mechanical properties of viral shells are crucial determinates for the pathway and mechanism by which the genetic material leaves the capsid during infection and have therefore been studied by atomic force microscopy as well as by atomistic simulations. The mechanical response to forces from inside the capsid are found to be relevant, especially after ion removal from the shell structure, which is generally assumed to be essential during viral infection; however, atomic force microscopy measurements are restricted to probing the capsids from outside, and the primary effect of ion removal is still inaccessible. To bridge this gap, we performed atomistic force-probe molecular dynamics simulations of the complete solvated icosahedral shell of Souther... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3284647 Wed, 17 Feb 2010 00:00:00 +0100 3284647 http://www.medworm.com/index.php?rid=3284646&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159166%26dopt%3DAbstract Authors: Chung HS, Louis JM, Eaton WA Förster resonance energy transfer (FRET) efficiency distributions in single-molecule experiments contain both structural and dynamical information. Extraction of this information from these distributions requires a careful analysis of contributions from dye photophysics. To investigate how mechanisms other than FRET affect the distributions obtained by counting donor and acceptor photons, we have measured single-molecule fluorescence trajectories of a small alpha/beta protein, i.e., protein GB1, undergoing two-state, folding/unfolding transitions. Alexa 488 donor and Alexa 594 acceptor dyes were attached to cysteines at positions 10 and 57 to yield two isomers-donor(10)/acceptor(57) and donor(57)/acceptor(10)-which could not be separated in th... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3284646 Wed, 17 Feb 2010 00:00:00 +0100 3284646 http://www.medworm.com/index.php?rid=3284645&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159167%26dopt%3DAbstract Authors: Ashton L, Dusting J, Imomoh E, Balabani S, Blanch EW By directly monitoring stirred protein solutions with Raman spectroscopy, the reversible unfolding of proteins caused by fluid shear is examined for several natural proteins with varying structural properties and molecular weight. While complete denaturation is not observed, a wide range of spectral variances occur for the different proteins, indicating subtle conformational changes that appear to be protein-specific. A number of significant overall trends are apparent from the study. For globular proteins, the overall extent of spectral variance increases with protein size and the proportion of beta-structure. For two less structured proteins, fetuin and alpha-casein, the observed changes are of relatively low magnitude, de... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3284645 Wed, 17 Feb 2010 00:00:00 +0100 3284645 http://www.medworm.com/index.php?rid=3284644&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159168%26dopt%3DAbstract Authors: Herz J, Siffrin V, Hauser AE, Brandt AU, Leuenberger T, Radbruch H, Zipp F, Niesner RA Chronic inflammation in various organs, such as the brain, implies that different subpopulations of immune cells interact with the cells of the target organ. To monitor this cellular communication both morphologically and functionally, the ability to visualize more than two colors in deep tissue is indispensable. Here, we demonstrate the pronounced power of optical parametric oscillator (OPO)-based two-photon laser scanning microscopy for dynamic intravital imaging in hardly accessible organs of the central nervous and of the immune system, with particular relevance for long-term investigations of pathological mechanisms (e.g., chronic neuroinflammation) necessitating the use of fluorescent ... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3284644 Wed, 17 Feb 2010 00:00:00 +0100 3284644 http://www.medworm.com/index.php?rid=3284643&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159169%26dopt%3DAbstract Authors: Mannoor MS, James T, Ivanov DV, Beadling L, Braunlin W Among the various label-free methods for monitoring biomolecular interactions, capacitive sensors stand out due to their simple instrumentation and compatibility with multiplex formats. However, electrode polarization due to ion gradient formation and noise from solution conductance limited early dielectric spectroscopic measurements to high frequencies only, which in turn limited their sensitivity to biomolecular interactions, as the applied excitation signals were too fast for the charged macromolecules to respond. To minimize electrode polarization effects, capacitive sensors with 20 nm electrode separation were fabricated using silicon dioxide sacrificial layer techniques. The nanoscale separation of the capacitive ele... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3284643 Wed, 17 Feb 2010 00:00:00 +0100 3284643 http://www.medworm.com/index.php?rid=3284642&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159170%26dopt%3DAbstract Authors: Zeng X, Hu H, Zhou HX, Marszalek PE, Yang W In the studies of force-induced conformational transitions of biomolecules, the large timescale difference from experiments presents the challenge of obtaining convergent sampling for molecular dynamics simulations. To circumvent this fundamental problem, an approach combining the replica-exchange method and umbrella sampling (REM-US) was developed to simulate mechanical stretching of biomolecules under equilibrium conditions. Equilibrium properties of conformational transitions can be obtained directly from simulations without further assumptions. To test the performance, we carried out REM-US simulations of atomic force microscope (AFM) stretching and relaxing measurements on the polysaccharide pustulan, a (1-->6)-beta-D-glucan,... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3284642 Wed, 17 Feb 2010 00:00:00 +0100 3284642 http://www.medworm.com/index.php?rid=3263101&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20141747%26dopt%3DAbstract Authors: Jawerth LM, Münster S, Vader DA, Fabry B, Weitz DA We investigate the dependence of fiber brightness on three-dimensional fiber orientation when imaging biopolymer networks with confocal reflection microscopy (CRM) and confocal fluorescence microscopy (CFM). We compare image data of fluorescently labeled type I collagen networks concurrently acquired using each imaging modality. For CRM, fiber brightness decreases for more vertically oriented fibers, leaving fibers above approximately 50 degrees from the imaging plane entirely undetected. As a result, the three-dimensional network structure appears aligned with the imaging plane. In contrast, CFM data exhibit little variation of fiber brightness with fiber angle, thus revealing an isotropic collagen network. Consequently,... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3263101 Wed, 03 Feb 2010 00:00:00 +0100 3263101 http://www.medworm.com/index.php?rid=3263095&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20141748%26dopt%3DAbstract Authors: Mark S, Shlomovitz R, Gov NS, Poujade M, Grasland-Mongrain E, Silberzan P Collective cell migration is of great significance in many biological processes. The goal of this work is to give a physical model for the dynamics of cell migration during the wound healing response. Experiments demonstrate that an initially uniform cell-culture monolayer expands in a nonuniform manner, developing fingerlike shapes. These fingerlike shapes of the cell culture front are composed of columns of cells that move collectively. We propose a physical model to explain this phenomenon, based on the notion of dynamic instability. In this model, we treat the first layers of cells at the front of the moving cell culture as a continuous one-dimensional membrane (contour), with the usual elasticity of... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3263095 Wed, 03 Feb 2010 00:00:00 +0100 3263095 http://www.medworm.com/index.php?rid=3263094&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20141749%26dopt%3DAbstract Authors: Song L, Santos-Sacchi J Outer hair cells boost auditory performance in mammals. This amplification relies on an expansive array of intramembranous molecular motors, identified as prestin, that drive somatic electromotility. By measuring nonlinear capacitance, the electrical signature of electromotility, we are able to assess prestin's conformational state and interrogate the effectiveness of anions on prestin's activity. We find that the affinity of anions depends on the state of prestin that we set with a variety of perturbations (in membrane tension, temperature, and voltage), and that movement into the expanded state reduces the affinity of prestin for anions. These data signify that anions work allosterically on prestin. Consequently, anions are released from prestin's bin... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3263094 Wed, 03 Feb 2010 00:00:00 +0100 3263094 http://www.medworm.com/index.php?rid=3263093&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20141750%26dopt%3DAbstract In this study, we further test this hypothesis of a positive pore potential in CLC-0 and find that the preference for the negatively charged MTS is diminished significantly in modifying the substituted cysteine at a deeper pore position, E166. To examine this conundrum, we study the rates of MTS inhibitions of the E166C current and those of the control mutant current from E166A. The results suggest that the inhibition of E166C by intracellularly applied MTS reagents is tainted by the modification of an endogenous cysteine, C229, located at the channel's dimer interface. After this endogenous cysteine is mutated, CLC-0 resumes its preference for selecting MTSES in modifying E166C, reconfirming the idea that the pore of CLC-0 is indeed built with a positive intrinsic potential. These experim... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3263093 Wed, 03 Feb 2010 00:00:00 +0100 3263093 http://www.medworm.com/index.php?rid=3263092&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20141751%26dopt%3DAbstract Authors: Kurylowicz M, Yu CH, Pomès R We use principal component analysis (PCA) to detect functionally interesting collective motions in molecular-dynamics simulations of membrane-bound gramicidin A. We examine the statistical and structural properties of all PCA eigenvectors and eigenvalues for the backbone and side-chain atoms. All eigenvalue spectra show two distinct power-law scaling regimes, quantitatively separating large from small covariance motions. Time trajectories of the largest PCs converge to Gaussian distributions at long timescales, but groups of small-covariance PCs, which are usually ignored as noise, have subdiffusive distributions. These non-Gaussian distributions imply anharmonic motions on the free-energy surface. We characterize the anharmonic components of ... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3263092 Wed, 03 Feb 2010 00:00:00 +0100 3263092 http://www.medworm.com/index.php?rid=3263091&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20141752%26dopt%3DAbstract In this study of a voltage-gated K channel, we propose what we believe to be a novel pharmacological mechanism for how to regulate channel activity. Charged lipophilic substances can tune channel opening, and consequently excitability, by an electrostatic interaction with the channel's voltage sensors. The direction of the effect depends on the charge of the substance. This was shown by three compounds sharing an arachidonyl backbone but bearing different charge: arachidonic acid, methyl arachidonate, and arachidonyl amine. Computer simulations of membrane excitability showed that small changes in the voltage dependence of Na and K channels have prominent impact on excitability and the tendency for repetitive firing. For instance, a shift in the voltage dependence of a K channel with -5 or... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3263091 Wed, 03 Feb 2010 00:00:00 +0100 3263091 http://www.medworm.com/index.php?rid=3263090&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20141753%26dopt%3DAbstract Authors: Song C, Corry B Four x-ray crystal structures of prokaryotic homologs of ligand-gated ion channels have recently been determined: ELIC from Erwinia chrysanthemi, two structures of a proton-activated channel from Gloebacter violaceus (GLIC1 and GLIC2) and that of the E221A mutant (GLIC1M). The availability of numerous structures of channels in this family allows for aspects of channel gating and ion conduction to be examined. Here, we determine the likely conduction states of the four structures as well as IV curves, ion selectivity, and steps involved in ion permeation by performing extensive Brownian dynamics simulations. Our results show that the ELIC structure is indeed nonconductive, but that GLIC1 and GLIC1M are both conductive of ions with properties different from those... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3263090 Wed, 03 Feb 2010 00:00:00 +0100 3263090 http://www.medworm.com/index.php?rid=3263089&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20141754%26dopt%3DAbstract Authors: Henighan T, Chen A, Vieira G, Hauser AJ, Yang FY, Chalmers JJ, Sooryakumar R A platform of discrete microscopic magnetic elements patterned on a surface offers dynamic control over the motion of fluid-borne cells by reprogramming the magnetization within the magnetic bits. T-lymphocyte cells tethered to magnetic microspheres and untethered leukemia cells are remotely manipulated and guided along desired trajectories on a silicon surface by directed forces with average speeds up to 20 mum/s. In addition to navigating cells, the microspheres can be operated from a distance to push biological and inert entities and act as local probes in fluidic environments. PMID: 20141754 [PubMed - as supplied by publisher] (Source: Biophysical Journal) Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3263089 Wed, 03 Feb 2010 00:00:00 +0100 3263089 http://www.medworm.com/index.php?rid=3263088&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20141755%26dopt%3DAbstract Authors: Ogneva IV, Lebedev DV, Shenkman BS The structural integrity of striated muscle is determined by extra-sarcomere cytoskeleton that includes structures that connect the Z-disks and M-bands of a sarcomere to sarcomeres of neighbor myofibrils or to sarcolemma. Mechanical properties of these structures are not well characterized. The surface structure and transversal stiffness of single fibers from soleus muscle of the rat were studied with atomic force microscopy in liquid. We identified surface regions that correspond to projections of the Z-disks, M-bands, and structures between them. Transversal stiffness of the fibers was measured in each of these three regions. The stiffness was higher in the Z-disk regions, minimal between the Z-disks and the M-bands, and intermediate in the... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3263088 Wed, 03 Feb 2010 00:00:00 +0100 3263088 http://www.medworm.com/index.php?rid=3263087&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20141756%26dopt%3DAbstract Authors: Lignell M, Becker HC We have studied the association of a helix-loop-helix peptide scaffold carrying a benzenesulfonamide ligand to carbonic anhydrase using steady-state and time-resolved fluorescence spectroscopy. The helix-loop-helix peptide, developed for biosensing applications, is labeled with the fluorescent probe dansyl, which serves as a polarity-sensitive reporter of the binding event. Using maximum entropy analysis of the fluorescence lifetime of dansyl at 1:1 stoichiometry reveals three characteristic fluorescence lifetime groups, interpreted as differently interacting peptide/protein structures. We characterize these peptide/protein complexes as mostly bound but unfolded, bound and partly folded, and strongly bound and folded. Furthermore, analysis of the fluoresce... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3263087 Wed, 03 Feb 2010 00:00:00 +0100 3263087 http://www.medworm.com/index.php?rid=3263086&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20141757%26dopt%3DAbstract Authors: Feniouk BA, Kato-Yamada Y, Yoshida M, Suzuki T Subunit varepsilon of bacterial and chloroplast F(O)F(1)-ATP synthase is responsible for inhibition of ATPase activity. In Bacillus PS3 enzyme, subunit varepsilon can adopt two conformations. In the "extended", inhibitory conformation, its two C-terminal alpha-helices are stretched along subunit gamma. In the "contracted", noninhibitory conformation, these helices form a hairpin. The transition of subunit varepsilon from an extended to a contracted state was studied in ATP synthase incorporated in Bacillus PS3 membranes at 59 degrees C. Fluorescence energy resonance transfer between fluorophores introduced in the C-terminus of subunit varepsilon and in the N-terminus of subunit gamma was used to follow the conformational transitio... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3263086 Wed, 03 Feb 2010 00:00:00 +0100 3263086 http://www.medworm.com/index.php?rid=3263085&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20141758%26dopt%3DAbstract Authors: Reddy AS, Wang L, Lin YS, Ling Y, Chopra M, Zanni MT, Skinner JL, De Pablo JJ Amyloid deposits of amylin in the pancreas are an important characteristic feature found in patients with Type-2 diabetes. The aggregate has been considered important in the disease pathology and has been studied extensively. However, the secondary structures of the individual peptide have not been clearly identified. In this work, we present detailed solution structures of rat amylin using a combination of Monte Carlo and molecular dynamics simulations. A new Monte Carlo method is presented to determine the free energy of distinct biomolecular conformations. Both folded and random-coil conformations of rat amylin are observed in water and their relative stability is examined in detail. The former co... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3263085 Wed, 03 Feb 2010 00:00:00 +0100 3263085 http://www.medworm.com/index.php?rid=3263084&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20141759%26dopt%3DAbstract Authors: Rathinavelan T, Zhang L, Picking WL, Weis DD, De Guzman RN, Im W Many Gram-negative bacteria initiate infections by injecting effector proteins into host cells through the type III secretion apparatus, which is comprised of a basal body, a needle, and a tip. The needle channel is formed by the assembly of a single needle protein. To explore the export mechanisms of MxiH needle protein through the needle of Shigella flexneri, an essential step during needle assembly, we have performed steered molecular dynamics simulations in implicit solvent. The trajectories reveal a screwlike rotation motion during the export of nativelike helix-turn-helix conformations. Interestingly, the channel interior with excessive electronegative potential creates an energy barrier for MxiH to enter t... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3263084 Wed, 03 Feb 2010 00:00:00 +0100 3263084 http://www.medworm.com/index.php?rid=3263083&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20141760%26dopt%3DAbstract Authors: Zhulina EB, Leermakers FA Applying self-consistent field theory, we consider a coarse-grained model for the polymerlike projections of neurofilament (NF) proteins that form a brush structure around neurofilaments. We focus on effects of molecular composition, which is the relative occurrence of NF-H, NF-M, and NF-L proteins, on the organization of NF projection domains. We consider NF brushes with selectively truncated projections, and with a varied ratio L:H:M of constituent tails. Our conclusion is that the NF brush structure is remarkably tolerant with respect to the variation in M and H chains. Results compare favorably with experimental data on model animals, provided that due attention is paid on the level of phosphorylation of the KSP repeats. PMID: 20141760 [PubMed... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3263083 Wed, 03 Feb 2010 00:00:00 +0100 3263083 http://www.medworm.com/index.php?rid=3263082&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20141761%26dopt%3DAbstract Authors: Gong H, Freed KF Born-type electrostatic continuum methods have been an indispensable ingredient in a variety of implicit-solvent methods that reduce computational effort by orders of magnitude compared to explicit-solvent MD simulations and thus enable treatment using larger systems and/or longer times. An analysis of the limitations and failures of the Born approaches serves as a guide for fundamental improvements without diminishing the importance of prior works. One of the major limitations of the Born theory is the lack of a liquidlike description of the response of solvent dipoles to the electrostatic field of the solute and the changes therein, a feature contained in the continuum Langevin-Debye (LD) model applied here to investigate how Coulombic interactions depend on... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3263082 Wed, 03 Feb 2010 00:00:00 +0100 3263082 http://www.medworm.com/index.php?rid=3263081&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20141762%26dopt%3DAbstract Authors: Moskalenko AV, Yarova PL, Gordeev SN, Smirnov SV Understanding the structural organization and distribution of proteins in biological cells is of fundamental importance in biomedical research. The use of conventional fluorescent microscopy for this purpose is limited due to its relatively low spatial resolution compared to the size of a single protein molecule. Atomic force microscopy (AFM), on the other hand, allows one to achieve single-protein resolution by scanning the cell surface using a specialized ligand-coated AFM tip. However, because this method relies on short-range interactions, it is limited to the detection of binding sites that are directly accessible to the AFM tip. We developed a method based on magnetic (long-range) interactions and applied it to investigate... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3263081 Wed, 03 Feb 2010 00:00:00 +0100 3263081 http://www.medworm.com/index.php?rid=3263080&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20141763%26dopt%3DAbstract Authors: Rajput J, Rahbek DB, Aravind G, Andersen LH Spectral tuning in the photoactive yellow protein (PYP) is investigated by performing gas-phase absorption measurements on a PYP-model chromophore with two water molecules hydrogen-bonded to it. The photoabsorption maximum shows an unusually large blue shift of 0.71 eV in going from the bare to the hydrogen-bonded chromophore. It is concluded that several interactions within the PYP protein are mutually canceling each other, yielding an absorption maximum that is close to the absorption maximum of the bare chromophore. The system breaks apart upon photoexcitation in the gas phase by releasing the two water molecules, leaving the chromophore itself intact. The hydrogen-bonding interactions thus play an important role in stabilizing th... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3263080 Wed, 03 Feb 2010 00:00:00 +0100 3263080 http://www.medworm.com/index.php?rid=3263076&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20141764%26dopt%3DAbstract Authors: Wu Y, Eghbali M, Ou J, Lu R, Toro L, Stefani E To quantify spatial protein-protein proximity (colocalization) in paired microscopic images of two sets of proteins labeled by distinct fluorophores, we showed that the cross-correlation and the autocorrelation functions of image intensity consisted of fast and slowly decaying components. The fast component resulted from clusters of proteins specifically labeled, and the slow component resulted from image heterogeneity and a broadly-distributed background. To better evaluate spatial proximity between the two specifically labeled proteins, we extracted the fast-decaying component by fitting the sharp peak in correlation functions to a Gaussian function, which was then used to obtain protein-protein proximity index and the Pearson's... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3263076 Wed, 03 Feb 2010 00:00:00 +0100 3263076 http://www.medworm.com/index.php?rid=3194620&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20085716%26dopt%3DAbstract Authors: Krishna V, Ayton GS, Voth GA Coarse-grained models of the HIV-1 CA dimer are constructed based on all-atom molecular dynamics simulations. Coarse-grained representations of the capsid shell, which is composed of approximately 1500 copies of CA proteins, are constructed and their stability is examined. A key interaction between carboxyl and hexameric amino terminal domains is shown to generate the curvature of the capsid shell. It is demonstrated that variation of the strength of this interaction for different subunits in the lattice can cause formation of asymmetric, conical-shaped closed capsid shells, and it is proposed that variations, in the structure of the additional carboxyl-amino terminal binding interface during self-assembly, are important aspects of capsid cone form... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3194620 Wed, 06 Jan 2010 00:00:00 +0100 3194620 http://www.medworm.com/index.php?rid=3194619&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20085717%26dopt%3DAbstract Authors: Yu X, Wang J, Yang JC, Wang Q, Cheng SZ, Nussinov R, Zheng J The peptide self-assembly mimic (PSAM) from the outer surface protein A (OspA) can form highly stable but soluble beta-rich self-assembly-like structures similar to those formed by native amyloid-forming peptides. However, unlike amyloids that predominantly form insoluble aggregates, PSAMs are highly water-soluble. Here, we characterize the conformations of these soluble beta-sheet-rich assemblies. We simulate PSAMs with different-sized beta-sheets in the presence and absence of end-capping proteins using all-atom explicit-solvent molecular dynamics, comparing the structural stability, conformational dynamics, and association force. Structural and free-energy comparisons among beta-sheets with different numbers of la... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3194619 Wed, 06 Jan 2010 00:00:00 +0100 3194619 http://www.medworm.com/index.php?rid=3194618&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20085718%26dopt%3DAbstract Authors: Monine MI, Posner RG, Savage PB, Faeder JR, Hlavacek WS We use flow cytometry to characterize equilibrium binding of a fluorophore-labeled trivalent model antigen to bivalent IgE-FcepsilonRI complexes on RBL cells. We find that flow cytometric measurements are consistent with an equilibrium model for ligand-receptor binding in which binding sites are assumed to be equivalent and ligand-induced receptor aggregates are assumed to be acyclic. However, this model predicts extensive receptor aggregation at antigen concentrations that yield strong cellular secretory responses, which is inconsistent with the expectation that large receptor aggregates should inhibit such responses. To investigate possible explanations for this discrepancy, we evaluate four rule-based models for intera... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3194618 Wed, 06 Jan 2010 00:00:00 +0100 3194618 http://www.medworm.com/index.php?rid=3194617&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20085719%26dopt%3DAbstract Authors: Hill DB, Swaminathan V, Estes A, Cribb J, O'Brien ET, Davis CW, Superfine R Motile cilia are unique multimotor systems that display coordination and periodicity while imparting forces to biological fluids. They play important roles in normal physiology, and ciliopathies are implicated in a growing number of human diseases. In this work we measure the response of individual human airway cilia to calibrated forces transmitted via spot-labeled magnetic microbeads. Cilia respond to applied forces by 1), a reduction in beat amplitude (up to an 85% reduction by 160-170 pN of force); 2), a decreased tip velocity proportionate to applied force; and 3), no significant change in beat frequency. Tip velocity reduction occurred in each beat direction, independently of the direction of app... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3194617 Wed, 06 Jan 2010 00:00:00 +0100 3194617 http://www.medworm.com/index.php?rid=3194616&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20085720%26dopt%3DAbstract Authors: Weiger MC, Ahmed S, Welf ES, Haugh JM It has long been appreciated that spatiotemporal dynamics of cell migration are under the control of intracellular signaling pathways, which are mediated by adhesion receptors and other transducers of extracellular cues. Further, there is ample evidence that aspects of cell migration are stochastic: how else could it exhibit directional persistence over timescales much longer than typical signal transduction processes, punctuated by abrupt changes in direction? Yet the mechanisms by which signaling processes affect those behaviors remain unclear. We have developed analytical methods for relating parallel live-cell microscopy measurements of cell migration dynamics to the intracellular signaling processes that govern them. In this analysis ... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3194616 Wed, 06 Jan 2010 00:00:00 +0100 3194616 http://www.medworm.com/index.php?rid=3194615&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20085721%26dopt%3DAbstract We report insights into the mechanism of SLB formation by vesicle adsorption using temperature-controlled time-resolved fluorescence microscopy at low vesicle concentrations. First, lipid accumulates on the surface at a constant rate up to approximately 0.8 of SLB coverage. Then, as patches of SLB nucleate and spread, the rate of accumulation increases. At a coverage of approximately 1.5 x SLB, excess vesicles desorb as SLB patches rapidly coalesce into a continuous SLB. Variable surface fluorescence immediately before SLB patch formation argues against the existence of a critical vesicle density necessary for rupture. The accelerating rate of accumulation and the widespread, abrupt loss of vesicles coincide with the emergence and disappearance of patch edges. We conclude that SLB edges en... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3194615 Wed, 06 Jan 2010 00:00:00 +0100 3194615 http://www.medworm.com/index.php?rid=3194614&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20085722%26dopt%3DAbstract Authors: Shaklee PM, Bourel-Bonnet L, Dogterom M, Schmidt T Key cellular processes such as cell division, membrane compartmentalization, and intracellular transport rely on motor proteins. Motors have been studied in detail on the single motor level such that information on their step size, stall force, average run length, and processivity are well known. However, in vivo, motors often work together, so that the question of their collective coordination has raised great interest. Here, we specifically attach motors to giant vesicles and examine collective motor dynamics during membrane tube formation. Image correlation spectroscopy reveals directed motion as processive motors walk at typical speeds (< or = 500 nm/s) along an underlying microtubule and accumulate at the tip of the gr... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3194614 Wed, 06 Jan 2010 00:00:00 +0100 3194614 http://www.medworm.com/index.php?rid=3194613&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20085723%26dopt%3DAbstract Authors: Chen G, Tan ZJ, Chen SJ RNAs are highly negatively charged chain molecules. Metal ions play a crucial role in RNA folding stability and conformational changes. In this work, we employ the recently developed tightly bound ion (TBI) model, which accounts for the correlation between ions and the fluctuation of ion distributions, to investigate the ion-dependent free energy landscape for the three-way RNA junction in a 16S rRNA domain. The predicted electrostatic free energy landscape suggests that 1), ion-mediated electrostatic interactions cause an ensemble of unfolded conformations narrowly populated around the maximally extended structure; and 2), Mg(2+) ion-induced correlation effects help bring the helices to the folded state. Nonelectrostatic interactions, such as noncanoni... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3194613 Wed, 06 Jan 2010 00:00:00 +0100 3194613 http://www.medworm.com/index.php?rid=3194612&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20085724%26dopt%3DAbstract Authors: Hay S, Johannissen LO, Sutcliffe MJ, Scrutton NS It is generally accepted that enzymes catalyze reactions by lowering the apparent activation energy by transition state stabilization or through destabilization of ground states. A more controversial proposal is that enzymes can also accelerate reactions through barrier compression-an idea that has emerged from studies of H-tunneling reactions in enzyme systems. The effects of barrier compression on classical (over-the-barrier) reactions, and the partitioning between tunneling and classical reaction paths, have largely been ignored. We performed theoretical and computational studies on the effects of barrier compression on the shape of potential energy surfaces/reaction barriers for model (malonaldehyde and methane/methyl radica... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3194612 Wed, 06 Jan 2010 00:00:00 +0100 3194612 http://www.medworm.com/index.php?rid=3194611&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20085725%26dopt%3DAbstract Authors: Liao JH, Lin YC, Hsu J, Lee AY, Chen TA, Hsu CH, Chir JL, Hua KF, Wu TH, Hong LJ, Yen PW, Chiou A, Wu SH The Escherichia coli Lon protease degrades the E. coli DNA-binding protein HUbeta, but not the related protein HUalpha. Here we show that the Lon protease binds to both HUbeta and HUalpha, but selectively degrades only HUbeta in the presence of ATP. Mass spectrometry of HUbeta peptide fragments revealed that region K18-G22 is the preferred cleavage site, followed in preference by L36-K37. The preferred cleavage site was further refined to A20-A21 by constructing and testing mutant proteins; Lon degraded HUbeta-A20Q and HUbeta-A20D more slowly than HUbeta. We used optical tweezers to measure the rupture force between HU proteins and Lon; HUalpha, HUbeta, and HUbeta-A20D can ... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3194611 Wed, 06 Jan 2010 00:00:00 +0100 3194611 http://www.medworm.com/index.php?rid=3194610&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20085726%26dopt%3DAbstract Authors: Diakova G, Goddard YA, Korb JP, Bryant RG Rotational immobilization of proteins permits characterization of the internal peptide and water molecule dynamics by magnetic relaxation dispersion spectroscopy. Using different experimental approaches, we have extended measurements of the magnetic field dependence of the proton-spin-lattice-relaxation rate by one decade from 0.01 to 300 MHz for (1)H and showed that the underlying dynamics driving the protein (1)H spin-lattice relaxation is preserved over 4.5 decades in frequency. This extension is critical to understanding the role of (1)H(2)O in the total proton-spin-relaxation process. The fact that the protein-proton-relaxation-dispersion profile is a power law in frequency with constant coefficient and exponent over nearly 5 deca... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3194610 Wed, 06 Jan 2010 00:00:00 +0100 3194610 http://www.medworm.com/index.php?rid=3194609&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20085727%26dopt%3DAbstract Authors: Barbosa LR, Ortore MG, Spinozzi F, Mariani P, Bernstorff S, Itri R The combined effects of concentration and pH on the conformational states of bovine serum albumin (BSA) are investigated by small-angle x-ray scattering. Serum albumins, at physiological conditions, are found at concentrations of approximately 35-45 mg/mL (42 mg/mL in the case of humans). In this work, BSA at three different concentrations (10, 25, and 50 mg/mL) and pH values (2.0-9.0) have been studied. Data were analyzed by means of the Global Fitting procedure, with the protein form factor calculated from human serum albumin (HSA) crystallographic structure and the interference function described, considering repulsive and attractive interaction potentials within a random phase approximation. Small-angle x-r... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3194609 Wed, 06 Jan 2010 00:00:00 +0100 3194609 http://www.medworm.com/index.php?rid=3179072&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20074511%26dopt%3DAbstract We report the simplest yet known reactions involving driven phosphorylation-dephosphorylation cycle kinetics with autocatalytic kinase. We show that the noise-induced phenomenon is correlated with free energy dissipation and thus conforms with the open-chemical system theory. A previous reported noise-induced bistability in futile cycles is found to have originated from the kinase synchronization in a bistable system with slow transitions, as reported here. PMID: 20074511 [PubMed - as supplied by publisher] (Source: Biophysical Journal) Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3179072 Wed, 06 Jan 2010 00:00:00 +0100 3179072 http://www.medworm.com/index.php?rid=3179071&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20074512%26dopt%3DAbstract Authors: Watari N, Larson RG To study the swimming of a peritrichous bacterium such as Escherichia coli, which is able to change its swimming direction actively, we simulate the "run-and-tumble" motion by using a bead-spring model to account for: 1), the hydrodynamic and the mechanical interactions among the cell body and multiple flagella; 2), the reversal of the rotation of a flagellum in a tumble; and 3), the associated polymorphic transformations of the flagellum. Because a flexible hook connects the cell body and each flagellum, the flagella can take independent orientations with respect to the cell body. This simulation reproduces the experimentally observed behaviors of E. coli, namely, a three-dimensional random-walk trajectory in run-and-tumble motion and steady clockwise swim... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3179071 Wed, 06 Jan 2010 00:00:00 +0100 3179071 http://www.medworm.com/index.php?rid=3179070&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20074513%26dopt%3DAbstract Authors: Jeon J, Quaranta V, Cummings PT We have developed an off-lattice hybrid discrete-continuum (OLHDC) model of tumor growth and invasion. The continuum part of the OLHDC model describes microenvironmental components such as matrix-degrading enzymes, nutrients or oxygen, and extracellular matrix (ECM) concentrations, whereas the discrete portion represents individual cell behavior such as cell cycle, cell-cell, and cell-ECM interactions and cell motility by the often-used persistent random walk, which can be depicted by the Langevin equation. Using this framework of the OLHDC model, we develop a phenomenologically realistic and bio/physically relevant model that encompasses the experimentally observed superdiffusive behavior (at short times) of mammalian cells. When systemic simul... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3179070 Wed, 06 Jan 2010 00:00:00 +0100 3179070 http://www.medworm.com/index.php?rid=3179069&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20074514%26dopt%3DAbstract Authors: Romo TD, Grossfield A, Pitman MC The recently solved crystallographic structures for the A(2A) adenosine receptor and the beta(1) and beta(2) adrenergic receptors have shown important differences between members of the class-A G-protein-coupled receptors and their archetypal model, rhodopsin, such as the apparent breaking of the ionic lock that stabilizes the inactive structure. Here, we characterize a 1.02 mus all-atom simulation of an apo-beta(2) adrenergic receptor that is missing the third intracellular loop to better understand the inactive structure. Although we find that the structure is remarkably rigid, there is a rapid influx of water into the core of the protein, as well as a slight expansion of the molecule relative to the crystal structure. In contrast to the x-ra... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3179069 Wed, 06 Jan 2010 00:00:00 +0100 3179069 http://www.medworm.com/index.php?rid=3179068&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20074515%26dopt%3DAbstract Authors: Rezáč J, Hobza P, Harris SA We combined atomistic molecular-dynamics simulations with quantum-mechanical calculations to investigate the sequence dependence of the stretching behavior of duplex DNA. Our combined quantum-mechanical/molecular-mechanical approach demonstrates that molecular-mechanical force fields are able to describe both the backbone and base-base interactions within the highly distorted nucleic acid structures produced by stretching the DNA from the 5' ends, which include conformations containing disassociated basepairs, just as well as these force fields describe relaxed DNA conformations. The molecular-dynamics simulations indicate that the force-induced melting pathway is sequence-dependent and is influenced by the availability of noncanonical hy... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3179068 Wed, 06 Jan 2010 00:00:00 +0100 3179068 http://www.medworm.com/index.php?rid=3179067&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20074516%26dopt%3DAbstract Authors: Hein B, Willig KI, Wurm CA, Westphal V, Jakobs S, Hell SW We show far-field fluorescence nanoscopy of different structural elements labeled with an organic dye within living mammalian cells. The diffraction barrier limiting far-field light microscopy is outperformed by using stimulated emission depletion. We used the tagging protein hAGT (SNAP-tag), which covalently binds benzylguanine-substituted organic dyes, for labeling. Tetramethylrhodamine was used to image the cytoskeleton (vimentin and microtubule-associated protein 2) as well as structures located at the cell membrane (caveolin and connexin-43) with a resolution down to 40 nm. Comparison with structures labeled with the yellow fluorescent protein Citrine validates this labeling approach. Nanoscopic movies showing the ... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3179067 Wed, 06 Jan 2010 00:00:00 +0100 3179067 http://www.medworm.com/index.php?rid=3179066&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20074517%26dopt%3DAbstract Authors: Taylor JN, Makarov DE, Landes CF A method to denoise single-molecule fluorescence resonance energy (smFRET) trajectories using wavelet detail thresholding and Bayesian inference is presented. Bayesian methods are developed to identify fluorophore photoblinks in the time trajectories. Simulated data are used to quantify the improvement in static and dynamic data analysis. Application of the method to experimental smFRET data shows that it distinguishes photoblinks from large shifts in smFRET efficiency while maintaining the important advantage of an unbiased approach. Known sources of experimental noise are examined and quantified as a means to remove their contributions via soft thresholding of wavelet coefficients. A wavelet decomposition algorithm is described, and threshold... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3179066 Wed, 06 Jan 2010 00:00:00 +0100 3179066 http://www.medworm.com/index.php?rid=3179065&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20074518%26dopt%3DAbstract Authors: PMID: 20074518 [PubMed - in process] (Source: Biophysical Journal) Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3179065 Wed, 06 Jan 2010 00:00:00 +0100 3179065 http://www.medworm.com/index.php?rid=3049073&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19948113%26dopt%3DAbstract Authors: Li J, Tajkhorshid E The crystal structure of Na(+)-coupled galactose symporter (vSGLT) reports the transporter in its substrate-bound state, with a Na(+) ion modeled in a binding site corresponding to that of a homologous protein, leucine transporter (LeuT). In repeated molecular dynamics simulations, however, we find the Na(+) ion instable, invariably and spontaneously diffusing out of the transporter through a pathway lined by D189, which appears to facilitate the diffusion of the ion toward the cytoplasm. Further analysis of the trajectories and close structural examination, in particular, comparison of the Na(+)-binding sites of vSGLT and LeuT, strongly indicates that the crystal structure of vSGLT actually represents an ion-releasing state of the transporter. The observed... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3049073 Wed, 02 Dec 2009 00:00:00 +0100 3049073 http://www.medworm.com/index.php?rid=3049072&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19948114%26dopt%3DAbstract Authors: Lindemann CB PMID: 19948114 [PubMed - in process] (Source: Biophysical Journal) Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3049072 Wed, 02 Dec 2009 00:00:00 +0100 3049072 http://www.medworm.com/index.php?rid=3049071&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19948115%26dopt%3DAbstract Authors: Cheng Z, Liu F, Zhang XP, Wang W Reversible phosphorylation of proteins is ubiquitous in circadian systems, but the role it plays in generating rhythmicity is not completely understood. A common mechanism for most circadian rhythms involves a negative feedback loop between the positive and negative elements. Here, we built a minimal model for the Neurospora crassa circadian clock based on the core negative feedback loop and the protein FREQUENCY (FRQ)-dependent phosphorylation of the White Collar Complex (WCC). The model can reproduce basic features of the clock, such as the period length, phase relationship, and entrainment to light/dark cycles. We found that the activity of WCC can be controlled by FRQ in a switchlike manner owing to zero-order ultrasensitivity. WCC is inact... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3049071 Wed, 02 Dec 2009 00:00:00 +0100 3049071 http://www.medworm.com/index.php?rid=3049070&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19948116%26dopt%3DAbstract Authors: Müller KP, Erdel F, Caudron-Herger M, Marth C, Fodor BD, Richter M, Scaranaro M, Beaudouin J, Wachsmuth M, Rippe K Heterochromatin protein 1 (HP1) is a central factor in establishing and maintaining the repressive heterochromatin state. To elucidate its mobility and interactions, we conducted a comprehensive analysis on different time and length scales by fluorescence fluctuation microscopy in mouse cell lines. The local mobility of HP1alpha and HP1beta was investigated in densely packed pericentric heterochromatin foci and compared with other bona fide euchromatin regions of the nucleus by fluorescence bleaching and correlation methods. A quantitative description of HP1alpha/beta in terms of its concentration, diffusion coefficient, kinetic binding, and dissociation rate... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3049070 Wed, 02 Dec 2009 00:00:00 +0100 3049070 http://www.medworm.com/index.php?rid=3049069&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19948117%26dopt%3DAbstract This study investigates the hypothesis that the intracellular partitioning of membrane-permeant solutes manifests itself as a partial volume recovery in response to hyperosmotic loading, based on prior theoretical and biomimetic experimental studies. Osmotic loading experiments are performed on immature bovine chondrocytes using culture conditions where regulatory volume responses are shown to be insignificant. Osmotic loading with membrane-permeant glycerol (92 Da) and urea (60 Da) are observed to produce partial volume recoveries consistent with the proposed hypothesis, whereas loading with 1,2-propanediol (76 Da) produces complete volume recovery. Combining these experimental results with the previous theoretical framework produces a measure for the intracellular partition coefficient o... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3049069 Wed, 02 Dec 2009 00:00:00 +0100 3049069 http://www.medworm.com/index.php?rid=3049068&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19948118%26dopt%3DAbstract Authors: Teixeira LR, Merzlyak PG, Valeva A, Krasilnikov OV A mechanism of how polyanions influence the channel formed by Staphylococcus aureus alpha-hemolysin is described. We demonstrate that the probability of several types of polyanions to block the ion channel depends on the presence of divalent cations and the polyanion molecular weight and concentration. For heparins, a 10-fold increase in molecular weight decreases the half-maximal inhibitory concentration, IC(50), nearly 10(4)-fold. Dextran sulfates were less effective at blocking the channel. The polyanions are significantly more effective at reducing the conductance when added to the trans side of this channel. Lastly, the effectiveness of heparins on the channel conductance correlated with their influence on the zeta-potent... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3049068 Wed, 02 Dec 2009 00:00:00 +0100 3049068 http://www.medworm.com/index.php?rid=3049067&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19948119%26dopt%3DAbstract Authors: Heuvingh J, Bonneau S Oxidation of unsaturated lipids is a fundamental process involved in cell bioenergetics as well as in cell death. Using giant unilamellar vesicles and a chlorin photosensitizer, we asymmetrically oxidized the outer or inner monolayers of lipid membranes. We observed different shape transitions such as oblate to prolate and budding, which are typical of membrane curvature modifications. The asymmetry of the shape transitions is in accordance with a lowered effective spontaneous curvature of the leaflet being targeted. We interpret this effect as a decrease in the preferred area of the targeted leaflet compared to the other, due to the secondary products of oxidation (cleaved-lipids). Permeabilization of giant vesicles by light-induced oxidation is observed... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3049067 Wed, 02 Dec 2009 00:00:00 +0100 3049067 http://www.medworm.com/index.php?rid=3049066&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19948120%26dopt%3DAbstract We report here what is believed to be the first electro-optical Pockels signal and image from such a membrane. The electro-optical dephasing distribution within the membrane is imaged and the signal is shown to be linear as a function of the applied voltage. A theoretical analysis taking into account the statistical orientation distribution of the inserted dye molecules allows us to estimate the doped membrane nonlinearity. Ongoing extensions of this work to living cell membranes are discussed. PMID: 19948120 [PubMed - in process] (Source: Biophysical Journal) Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3049066 Wed, 02 Dec 2009 00:00:00 +0100 3049066 http://www.medworm.com/index.php?rid=3049065&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19948121%26dopt%3DAbstract Authors: Colombini B, Nocella M, Benelli G, Cecchi G, Griffiths PJ, Bagni MA Force generation and movement in skeletal muscle result from a cyclical interaction of overlapping myosin and actin filaments that permits the free energy of ATP hydrolysis to be converted into mechanical work. The rapid force recovery that occurs after a step release imposed on a muscle is thought to result from a synchronized tilting of myosin lever arms toward a position of lower free energy (the power stroke). We investigated the power stroke mechanism in intact muscle fibers of Rana esculenta using a fast stretch to detach forcibly cross-bridges. Stretches were applied either with or without a conditioning step release. Cross-bridge rupture tension was not significantly influenced by the release, whereas ... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3049065 Wed, 02 Dec 2009 00:00:00 +0100 3049065 http://www.medworm.com/index.php?rid=3049064&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19948122%26dopt%3DAbstract Authors: Chen J, Neu J, Miyata M, Oster G Mycoplasmas exhibit a novel, substrate-dependent gliding motility that is driven by approximately 400 "leg" proteins. The legs interact with the substrate and transmit the forces generated by an assembly of ATPase motors. The velocity of the cell increases linearly by nearly 10-fold over a narrow temperature range of 10-40 degrees C. This corresponds to an Arrhenius factor that decreases from approximately 45 k(B)T at 10 degrees C to approximately 10 k(B)T at 40 degrees C. On the other hand, load-velocity curves at different temperatures extrapolate to nearly the same stall force, suggesting a temperature-insensitive force-generation mechanism near stall. In this article, we propose a leg-substrate interaction mechanism that explains the intrig... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3049064 Wed, 02 Dec 2009 00:00:00 +0100 3049064 http://www.medworm.com/index.php?rid=3049063&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19948123%26dopt%3DAbstract Authors: Brokaw CJ A regular cycle of dynein-driven sliding, doublet separation, doublet reassociation, and resumption of sliding was previously observed by Aoyama and Kamiya in outer doublet pairs obtained after partial dissociation of Chlamydomonas flagella. In the work presented here, computer programming based on previous simulations of oscillatory bending of microtubules was extended to simulate the cycle of events observed with doublet pairs. These simulations confirm the straightforward explanation of this oscillation by inactivation of dynein when doublets separate and resumption of dynein activity after reassociation. Reassociation is augmented by a dynein-dependent "adhesive force" between the doublets. The simulations used a simple mathematical model to generate velocity-dep... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3049063 Wed, 02 Dec 2009 00:00:00 +0100 3049063 http://www.medworm.com/index.php?rid=3049062&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19948124%26dopt%3DAbstract Authors: Vaiana SM, Best RB, Yau WM, Eaton WA, Hofrichter J Islet amyloid polypeptide (amylin) is the main component in amyloid deposits formed in type II diabetes. We used triplet quenching to probe the dynamics of contact formation between the N-terminal disulfide loop and a C-terminal tryptophan in monomeric amylins from human and rat. Quenching rates measured in the absence of denaturant are four times larger than those in 6 M guanidinium chloride, indicating a decrease in the average end-to-end distance (collapse) at low denaturant concentrations. We were surprised to find an even greater (sevenfold) increase in quenching rates on removal of denaturant for a hydrophilic control peptide containing the disulfide loop compared to the same peptide without the loop (twofold change). Th... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3049062 Wed, 02 Dec 2009 00:00:00 +0100 3049062 http://www.medworm.com/index.php?rid=3049061&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19948125%26dopt%3DAbstract Authors: Jonsson AL, Scott KA, Daggett V The Dynameomics project aims to simulate a representative sample of all globular protein metafolds under both native and unfolding conditions. We have identified protein unfolding transition state (TS) ensembles from multiple molecular dynamics simulations of high-temperature unfolding in 183 structurally distinct proteins. These data can be used to study individual proteins and individual protein metafolds and to mine for TS structural features common across all proteins. Separating the TS structures into four different fold classes (all proteins, all-alpha, all-beta, and mixed alpha/beta and alpha +beta) resulted in no significant difference in the overall protein properties. The residues with the most contacts in the native state lost the mos... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3049061 Wed, 02 Dec 2009 00:00:00 +0100 3049061 http://www.medworm.com/index.php?rid=3049060&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19948126%26dopt%3DAbstract Authors: Daigle R, Rousseau JA, Guertin M, Lagüe P Mycobacterium tuberculosis group I truncated hemoglobin trHbN catalyzes the oxidation of nitric oxide (*NO) to nitrate with a second-order rate constant k approximately 745 muM(-1) s(-1) at 23 degrees C (nitric oxide dioxygenase reaction). It was proposed that this high efficiency is associated with the presence of hydrophobic tunnels inside trHbN structure that allow substrate diffusion to the distal heme pocket. In this work, we investigated the mechanisms of *NO diffusion within trHbN tunnels in the context of the nitric oxide dioxygenase reaction using two independent approaches. Molecular dynamics simulations of trHbN were performed in the presence of explicit *NO molecules. Successful *NO diffusion from the bulk solvent to t... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3049060 Wed, 02 Dec 2009 00:00:00 +0100 3049060 http://www.medworm.com/index.php?rid=3049059&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19948127%26dopt%3DAbstract Authors: Chandler DE, Gumbart J, Stack JD, Chipot C, Schulten K The photosynthetic apparatus of purple bacteria is contained within organelles called chromatophores, which form as extensions of the cytoplasmic membrane. The shape of these chromatophores can be spherical (as in Rhodobacter sphaeroides), lamellar (as in Rhodopseudomonas acidophila and Phaeospirillum molischianum), or tubular (as in certain Rb. sphaeroides mutants). Chromatophore shape is thought to be influenced by the integral membrane proteins Light Harvesting Complexes I and II (LH1 and LH2), which pack tightly together in the chromatophore. It has been suggested that the shape of LH2, together with its close packing in the membrane, induces membrane curvature. The mechanism of LH2-induced curvature is explored via mo... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3049059 Wed, 02 Dec 2009 00:00:00 +0100 3049059 http://www.medworm.com/index.php?rid=3049058&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19948128%26dopt%3DAbstract Authors: Grant CA, Brockwell DJ, Radford SE, Thomson NH Systematic variation of solution conditions reveals that the elastic modulus (E) of individual collagen fibrils can be varied over a range of 2-200 MPa. Nanoindentation of reconstituted bovine Achilles tendon fibrils by atomic force microscopy (AFM) under different aqueous and ethanol environments was carried out. Titration of monovalent salts up to a concentration of 1 M at pH 7 causes E to increase from 2 to 5 MPa. This stiffening effect is more pronounced at lower pH where, at pH 5, e.g., there is an approximately 7-fold increase in modulus on addition of 1 M KCl. An even larger increase in modulus, up to approximately 200 MPa, can be achieved by using increasing concentrations of ethanol. Taken together, these results indicate... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3049058 Wed, 02 Dec 2009 00:00:00 +0100 3049058 http://www.medworm.com/index.php?rid=3049057&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19948129%26dopt%3DAbstract In this study, we quantify this flexibility in terms of persistence length, namely the length scale over which it is rigid. We use single-molecule optical trapping and small-angle x-ray scattering, combined with Monte Carlo simulations to demonstrate that the Kelch ER/K alpha-helix behaves as a wormlike chain with a persistence length of approximately 15 nm or approximately 28 turns of alpha-helix. The ER/K alpha-helix length in proteins varies from 3 to 60 nm, with a median length of approximately 5 nm. Knowledge of its persistence length enables us to define its function as a rigid spacer in a translation initiation factor, as a force transducer in the mechanoenzyme myosin VI, and as a flexible spacer in the Kelch-motif-containing protein. PMID: 19948129 [PubMed - in process] (Source... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3049057 Wed, 02 Dec 2009 00:00:00 +0100 3049057 http://www.medworm.com/index.php?rid=3049056&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19948130%26dopt%3DAbstract Authors: Vorov OK, Livesay DR, Jacobs DJ A complete description of protein structure and function must include a proper treatment of mechanisms that lead to cooperativity. The helix/coil transition serves as a simple example of a cooperative folding process, commonly described by a nucleation-propagation mechanism. The prevalent view is that coil structure must first form a short segment of helix in a localized region despite paying a free energy cost (nucleation). Afterward, helical structure propagates outward from the nucleation site. Both processes entail enthalpy-entropy compensation that derives from the loss in conformational entropy on helix formation with concomitant gain in favorable interactions. Nucleation-propagation models inherently assume that cooperativity arises from ... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3049056 Wed, 02 Dec 2009 00:00:00 +0100 3049056 http://www.medworm.com/index.php?rid=3049055&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19948131%26dopt%3DAbstract Authors: Crane JM, Verkman AS The shorter "M23" isoform of the glial cell water channel aquaporin-4 (AQP4) assembles into orthogonal arrays of particles (OAPs) in cell plasma membranes, whereas the full-length "M1" isoform does not. N-terminal residues are responsible for OAP formation by AQP4-M23 and for blocking of OAP formation in AQP4-M1. In investigating differences in OAP formation by certain N-terminus mutants of AQP4, as measured by freeze-fracture electron microscopy versus live-cell imaging, we discovered reversible, temperature-dependent OAP assembly of certain weakly associating AQP4 mutants. Single-particle tracking of quantum-dot-labeled AQP4 in live cells and total internal reflection fluorescence microscopy showed >80% of M23 in OAPs at 10-50 degrees C compared to &l... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3049055 Wed, 02 Dec 2009 00:00:00 +0100 3049055 http://www.medworm.com/index.php?rid=3049054&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19948132%26dopt%3DAbstract Authors: Moulisová V, Luer L, Hoseinkhani S, Brotosudarmo TH, Collins AM, Lanzani G, Blankenship RE, Cogdell RJ Energy transfer processes in photosynthetic light harvesting 2 (LH2) complexes isolated from purple bacterium Rhodopseudomonas palustris grown at different light intensities were studied by ground state and transient absorption spectroscopy. The decomposition of ground state absorption spectra shows contributions from B800 and B850 bacteriochlorophyll (BChl) a rings, the latter component splitting into a low energy and a high energy band in samples grown under low light (LL) conditions. A spectral analysis reveals strong inhomogeneity of the B850 excitons in the LL samples that is well reproduced by an exponential-type distribution. Transient spectra show a bleach of bot... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3049054 Wed, 02 Dec 2009 00:00:00 +0100 3049054 http://www.medworm.com/index.php?rid=3049053&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19948133%26dopt%3DAbstract Authors: Jang H, Arce FT, Capone R, Ramachandran S, Lal R, Nussinov R In Alzheimer's disease, calcium permeability through cellular membranes appears to underlie neuronal cell death. It is increasingly accepted that calcium permeability involves toxic ion channels. We modeled Alzheimer's disease ion channels of different sizes (12-mer to 36-mer) in the lipid bilayer using molecular dynamics simulations. Our Abeta channels consist of the solid-state NMR-based U-shaped beta-strand-turn-beta-strand motif. In the simulations we obtain ion-permeable channels whose subunit morphologies and shapes are consistent with electron microscopy/atomic force microscopy. In agreement with imaged channels, the simulations indicate that beta-sheet channels break into loosely associated mobile beta-sheet ... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3049053 Wed, 02 Dec 2009 00:00:00 +0100 3049053 http://www.medworm.com/index.php?rid=3049052&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19948134%26dopt%3DAbstract Authors: Wang J, Xu L, Wang E Three-protein circadian oscillations in cyanobacteria sustain for weeks. To understand how cellular oscillations function robustly in stochastic fluctuating environments, we used a stochastic model to uncover two natures of circadian oscillation: the potential landscape related to steady-state probability distribution of protein concentrations; and the corresponding flux related to speed of concentration changes which drive the oscillations. The barrier height of escaping from the oscillation attractor on the landscape provides a quantitative measure of the robustness and coherence for oscillations against intrinsic and external fluctuations. The difference between the locations of the zero total driving force and the extremal of the potential provides a p... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3049052 Wed, 02 Dec 2009 00:00:00 +0100 3049052 http://www.medworm.com/index.php?rid=3009100&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917217%26dopt%3DAbstract Authors: Krammer EM, Ravaud S, Dehez F, Frelet-Barrand A, Pebay-Peyroula E, Chipot C The ADP/ATP carrier (AAC) is a very effective membrane protein that mediates the exchange of ADP and ATP across the mitochondrial membrane. In vivo transport measurements on the AAC overexpressed in Escherichia coli demonstrate that this process can be severely inhibited by high-chloride concentrations. Molecular-dynamics simulations reveal a strong modification of the topology of the local electric field related to the number of chloride ions inside the cavity. Halide ions are shown to shield the positive charges lining the internal cavity of the carrier by accurate targeting of key basic residues. These specific amino acids are highly conserved as highlighted by the analysis of multiple AAC sequences... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3009100 Wed, 18 Nov 2009 00:00:00 +0100 3009100 http://www.medworm.com/index.php?rid=3009099&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917218%26dopt%3DAbstract Authors: Sul B, Iwasa KH The effectiveness of hair bundle motility in mammalian and avian ears is studied by examining energy balance for a small sinusoidal displacement of the hair bundle. The condition that the energy generated by a hair bundle must be greater than energy loss due to the shear in the subtectorial gap per hair bundle leads to a limiting frequency that can be supported by hair-bundle motility. Limiting frequencies are obtained for two motile mechanisms for fast adaptation, the channel re-closure model and a model that assumes that fast adaptation is an interplay between gating of the channel and the myosin motor. The limiting frequency obtained for each of these models is an increasing function of a factor that is determined by the morphology of hair bundles and the co... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3009099 Wed, 18 Nov 2009 00:00:00 +0100 3009099 http://www.medworm.com/index.php?rid=3009098&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917219%26dopt%3DAbstract Authors: Jayasinghe ID, Cannell MB, Soeller C Confocal and total internal reflection fluorescence imaging was used to examine the distribution of caveolin-3, sodium-calcium exchange (NCX) and ryanodine receptors (RyRs) in rat ventricular myocytes. Transverse and longitudinal optical sectioning shows that NCX is distributed widely along the transverse and longitudinal tubular system (t-system). The NCX labeling consisted of both punctate and distributed components, which partially colocalize with RyRs (27%). Surface membrane labeling showed a similar pattern but the fraction of RyR clusters containing NCX label was decreased and no nonpunctate labeling was observed. Sixteen percent of RyRs were not colocalized with the t-system and 1.6% of RyRs were found on longitudinal elements of the... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3009098 Wed, 18 Nov 2009 00:00:00 +0100 3009098 http://www.medworm.com/index.php?rid=3009097&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917220%26dopt%3DAbstract Authors: Cha CY, Oka C, Earm YE, Wakabayashi S, Noma A A new kinetic model of the Na(+)/H(+) exchanger (NHE) was developed by fitting a variety of major experimental findings, such as ion-dependencies, forward/reverse mode, and the turnover rate. The role of NHE in ion homeostasis was examined by implementing the NHE model in a minimum cell model including intracellular pH buffer, Na(+)/K(+) pump, background H(+), and Na(+) fluxes. This minimum cell model was validated by reconstructing recovery of pH(i) from acidification, accompanying transient increase in [Na(+)](i) due to NHE activity. Based on this cell model, steady-state relationships among pH(i), [Na(+)](I), and [Ca(2+)](i) were quantitatively determined, and thereby the critical level of acidosis for cell survival was predicte... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3009097 Wed, 18 Nov 2009 00:00:00 +0100 3009097 http://www.medworm.com/index.php?rid=3009096&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917221%26dopt%3DAbstract We present a hybrid computational-experimental technique, the cell-type transforming clamp, which is designed to overcome such differences by using a calculated compensatory current to convert the macroscopic electrical behavior of an isolated cell into that of a different cell type. We demonstrate the technique's utility by evaluating drug arrhythmogenicity in murine cardiomyocytes that are transformed to behave like human myocytes. Whereas we use the cell-type transforming clamp in this work to convert between mouse and human electrodynamics, the technique could be adapted to convert between the action potential morphologies of any two cell types of interest. PMID: 19917221 [PubMed - in process] (Source: Biophysical Journal) Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3009096 Wed, 18 Nov 2009 00:00:00 +0100 3009096 http://www.medworm.com/index.php?rid=3009095&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917222%26dopt%3DAbstract In conclusion, SLN acts as an ATP-induced phosphate carrier exhibiting a behavior quite similar to that of the unidentified P(i) transporter described previously. No ion-channel activity is exhibited by the T18A mutant of SLN. PMID: 19917222 [PubMed - in process] (Source: Biophysical Journal) Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3009095 Wed, 18 Nov 2009 00:00:00 +0100 3009095 http://www.medworm.com/index.php?rid=3009094&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917223%26dopt%3DAbstract Authors: Brownholland DP, Longo GS, Struts AV, Justice MJ, Szleifer I, Petrache HI, Brown MF, Thompson DH Binary mixtures of C(20)BAS and POPC membranes were studied by solid-state (2)H NMR spectroscopy and small angle x-ray scattering (SAXS) over a wide range of concentrations and at different temperatures. Three specifically deuterated C(20)BAS derivatives--[1',1',20',20'-(2)H(4)]C(20)BAS, [2',2',19',19'-(2)H(4)]C(20)BAS, and [10',11'-(2)H(2)]C(20)BAS--combined with protiated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), as well as membranes containing POPC-d(31) and fully protiated bolalipid, were used in NMR experiments to obtain structural information for the mixtures. The (2)H NMR spectra of [10',11'-(2)H(2)]C(20)BAS/POPC membrane dispersions reveal that the bolalipid ... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3009094 Wed, 18 Nov 2009 00:00:00 +0100 3009094 http://www.medworm.com/index.php?rid=3009093&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917224%26dopt%3DAbstract Authors: Griesbauer J, Wixforth A, Schneider MF Sound waves are excited on lipid monolayers using a set of planar electrodes aligned in parallel with the excitable medium. By measuring the frequency-dependent change in the lateral pressure, we are able to extract the sound velocity for the entire monolayer phase diagram. We demonstrate that this velocity can also be directly derived from the lipid monolayer compressibility, and consequently displays a minimum in the phase transition regime. This minimum decreases from v(0) = 170 m/s for one-component lipid monolayers down to v(m) = 50 m/s for lipid mixtures. No significant attenuation can be detected confirming an adiabatic phenomenon. Finally, our data propose a relative lateral density oscillation of Deltarho/rho approximately 2%, im... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3009093 Wed, 18 Nov 2009 00:00:00 +0100 3009093 http://www.medworm.com/index.php?rid=3009092&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917225%26dopt%3DAbstract Authors: Busto JV, Fanani ML, De Tullio L, Sot J, Maggio B, Goñi FM, Alonso A A combination of lipid monolayer- and bilayer-based model systems has been applied to explore in detail the interactions between and organization of palmitoylsphingomyelin (pSM) and the related lipid palmitoylceramide (pCer). Langmuir balance measurements of the binary mixture reveal favorable interactions between the lipid molecules. A thermodynamically stable point is observed in the range approximately 30-40 mol % pCer. The pSM monolayer undergoes hyperpolarization and condensation with small concentrations of pCer, narrowing the liquid-expanded (LE) to liquid-condensed (LC) pSM main phase transition by inducing intermolecular interactions and chain ordering. Beyond this point, the phase diagram no lo... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3009092 Wed, 18 Nov 2009 00:00:00 +0100 3009092 http://www.medworm.com/index.php?rid=3009091&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917226%26dopt%3DAbstract Authors: Arkhipov A, Yin Y, Schulten K BAR domains are highly conserved protein domains participating in a diversity of cellular processes that involve membrane remodeling. The mechanisms underlying such remodeling are debated. For the relatively well-studied case of amphiphysin N-BAR domain, one suggested mechanism involves scaffolding, i.e., binding of a negatively charged membrane to the protein's positively charged curved surface. An alternative mechanism suggests that insertion of the protein's N-terminal amphipathic segments (N-helices H0) into the membrane leads to bending. Here, we address the issue through all-atom and coarse-grained simulations of multiple amphiphysin N-BAR domains and their components interacting with a membrane. We observe that complete N-BAR domains and BA... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3009091 Wed, 18 Nov 2009 00:00:00 +0100 3009091 http://www.medworm.com/index.php?rid=3009090&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917227%26dopt%3DAbstract In this study, we analyzed the effect of SP-C on the thermodynamic properties of phospholipid membranes containing cholesterol, and the ability of lipid/protein complexes containing cholesterol to form and respread interfacial films capable of producing very low surface tensions upon repetitive compression-expansion cycling. SP-C modulates the effect of cholesterol to reduce the enthalpy associated with the gel-to-liquid-crystalline melting transition in dipalmitoylphosphatidylcholine (DPPC) bilayers, as analyzed by differential scanning calorimetry. The presence of SP-C affects more subtly the effects of cholesterol on the thermotropic properties of ternary membranes, mimicking more closely the lipid composition of native surfactant, where SP-C facilitates the miscibility of the sterol. I... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3009090 Wed, 18 Nov 2009 00:00:00 +0100 3009090 http://www.medworm.com/index.php?rid=3009089&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917228%26dopt%3DAbstract Authors: Cui H, Ayton GS, Voth GA The structure of the endophilin N-terminal amphipathic helix Bin/Amphiphysin/Rvs-homology (N-BAR) domain is unique because of an additional insert helix under the arch of the N-BAR dimer. The structure of this additional helix has not been fully resolved in crystallographic studies, and thus presents a challenge to molecular-level analysis. Large-scale molecular-dynamics simulations were therefore employed to investigate the interaction of a single endophilin N-BAR with a lipid bilayer. Various possible configurations of the additional insert helix under the top of the arch of the endophilin N-BAR were modeled to examine their effect on membrane bending. A residue-residue and residue-lipid headgroup distance analysis, similar to that performed with ele... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3009089 Wed, 18 Nov 2009 00:00:00 +0100 3009089 http://www.medworm.com/index.php?rid=3009088&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917229%26dopt%3DAbstract Authors: Waheed Q, Edholm O It is here shown that there is a considerable system size-dependence in the area compressibility calculated from area fluctuations in lipid bilayers. This is caused by the contributions to the area fluctuations from undulations. This is also the case in experiments. At present, such a contribution, in most cases, is subtracted from the experimental values to obtain a true area compressibility. This should also be done with the simulation values. Here, this is done by extrapolating area compressibility versus system size, down to very small (zero) system size, where undulations no longer exist. The area compressibility moduli obtained from such simulations do not agree with experimental true area compressibility moduli as well as the uncorrected ones from con... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3009088 Wed, 18 Nov 2009 00:00:00 +0100 3009088 http://www.medworm.com/index.php?rid=3009087&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917230%26dopt%3DAbstract Authors: Boucher PA, Morris CE, Joós B Multiconformation membrane proteins are mechanosensitive (MS) if their conformations displace different bilayer areas. Might MS closed-closed transitions serve as tension buffers, that is, as membrane "spandex"? While bilayer expansion is effectively instantaneous, transitions of bilayer-embedded MS proteins are stochastic (thermally activated) so spandex kinetics would be critical. Here we model generic two-state (contracted/expanded) stochastic spandexes inspired by known bacterial osmovalves (MscL, MscS) then suggest experimental approaches to test for spandex-like behaviors in these proteins. Modeling shows: 1), spandex kinetics depend on the transition state location along an area reaction coordinate; 2), increasing membrane concentratio... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3009087 Wed, 18 Nov 2009 00:00:00 +0100 3009087 http://www.medworm.com/index.php?rid=3009086&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917231%26dopt%3DAbstract Authors: Gingras J, Rioux RM, Cuvelier D, Geisse NA, Lichtman JW, Whitesides GM, Mahadevan L, Sanes JR Micropatterned poly(dimethylsiloxane) substrates fabricated by soft lithography led to large-scale orientation of myoblasts in culture, thereby controlling the orientation of the myotubes they formed. Fusion occurred on many chemically identical surfaces in which varying structures were arranged in square or hexagonal lattices, but only a subset of patterned surfaces yielded aligned myotubes. Remarkably, on some substrates, large populations of myotubes oriented at a reproducible acute angle to the lattice of patterned features. A simple geometrical model predicts the angle and extent of orientation based on maximizing the contact area between the myoblasts and patterned topographic s... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3009086 Wed, 18 Nov 2009 00:00:00 +0100 3009086 http://www.medworm.com/index.php?rid=3009085&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917232%26dopt%3DAbstract Authors: Kleimann C, Sischka A, Spiering A, Tönsing K, Sewald N, Diederichsen U, Anselmetti D The binding kinetics of the intercalative binding of Triostin A to lambda-DNA was investigated by measuring the force extension response of the DNA-ligand complexes with an optical tweezers system. These force response curves, containing the information about different binding properties, were analyzed based on a recent method (put forth by another research group) for monointercalators that was extended to bisintercalators. Our binding analysis reveals an exponential dependence of the association constant on the applied external force as well as a decreasing binding site size. In general, our results are in agreement with those for the monointercalator ethidium. However, to explain the hi... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3009085 Wed, 18 Nov 2009 00:00:00 +0100 3009085 http://www.medworm.com/index.php?rid=3009084&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917233%26dopt%3DAbstract Authors: Kenward M, Dorfman KD Deoxyribozymes (DNAzymes) are single-stranded DNA that catalyze nucleic acid biochemistry. Although a number of DNAzymes have been discovered by in vitro selection, the relationship between their tertiary structure and function remains unknown. We focus here on the well-studied 10-23 DNAzyme, which cleaves mRNA with a catalytic efficiency approaching that of RNase A. Using coarse-grained Brownian dynamics simulations, we find that the DNAzyme bends its substrate away from the cleavage point, exposing the reactive site and buckling the DNAzyme catalytic core. This hypothesized transition state provides microscopic insights into experimental observations concerning the size of the DNAzyme/substrate complex, the impact of the recognition arm length, and the ... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3009084 Wed, 18 Nov 2009 00:00:00 +0100 3009084 http://www.medworm.com/index.php?rid=3009083&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917234%26dopt%3DAbstract Authors: Chen CH, Málková S, Pingali SV, Long F, Garde S, Cho W, Schlossman ML X-ray reflectivity measurements are used to determine the configuration of the C2 domain of protein kinase Calpha (PKCalpha-C2) bound to a lipid monolayer of a 7:3 mixture of 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine and 1-stearoyl-2-oleoyl-sn-glycero-3-phosphoserine supported on a buffered aqueous solution. The reflectivity is analyzed in terms of the known crystallographic structure of PKCalpha-C2 and a slab model representation of the lipid layer. The configuration of lipid-bound PKCalpha-C2 is described by two angles that define its orientation, theta = 35 degrees +/- 10 degrees and phi =210 degrees +/- 30 degrees, and a penetration depth (=7.5 +/- 2 A) into the lipid layer. In this struc... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3009083 Wed, 18 Nov 2009 00:00:00 +0100 3009083 http://www.medworm.com/index.php?rid=3009082&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917235%26dopt%3DAbstract Authors: Feng JA, Kao J, Marshall GR Mini-proteins that contain <50 amino acids often serve as model systems for studying protein folding because their small size makes long timescale simulations possible. However, not all mini-proteins are created equal. The stability and structure of FSD-1, a 28-residue mini-protein that adopted the betabetaalpha zinc-finger motif independent of zinc binding, was investigated using circular dichroism, differential scanning calorimetry, and replica-exchange molecular dynamics. The broad melting transition of FSD-1, similar to that of a helix-to-coil transition, was observed by using circular dichroism, differential scanning calorimetry, and replica-exchange molecular dynamics. The N-terminal beta-hairpin was found to be flexible. The FSD-1 apparent... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3009082 Wed, 18 Nov 2009 00:00:00 +0100 3009082 http://www.medworm.com/index.php?rid=3009081&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917236%26dopt%3DAbstract Authors: Li H, Ke H, Ren G, Qiu X, Weng YX, Wang CC The thermal stability of DsbC, a homodimeric protein disulfide isomerase in prokaryotic periplasm, has been studied by using temperature-dependent Fourier transformation infrared and time-resolved infrared spectroscopy coupled with temperature-jump initiation. The infrared absorbance thermal titration curves for thermal-induced unfolding of DsbC in D(2)O exhibit a three-state transition with the first transition midpoint temperature at 37.1 +/- 1.1 degrees C corresponding to dissociation, and the second at >74.5 degrees C corresponding to global unfolding and aggregation. The dissociation midpoint temperature of DsbC in phosphate buffer shifts to 49.2 +/- 0.7 degrees C. Temperature-jump time-resolved infrared spectra in D(2)O shows... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3009081 Wed, 18 Nov 2009 00:00:00 +0100 3009081 http://www.medworm.com/index.php?rid=3009080&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917237%26dopt%3DAbstract Authors: Averett LE, Schoenfisch MH, Akhremitchev BB, Gorkun OV Fibrin, the structural scaffold of blood clots, spontaneously polymerizes through the formation of 'A-a' knob-hole bonds. When subjected to external force, the dissociation of this bond is accompanied by two to four abrupt changes in molecular dimension observable as rupture events in a force curve. Herein, the configuration, molecular extension, and kinetic parameters of each rupture event are examined. The increases in contour length indicate that the D region of fibrinogen can lengthen by approximately 50% of the length of a fibrin monomer before rupture of the 'A-a' interaction. The dependence of the dissociation rate on applied force was obtained using probability distributions of rupture forces collected at different... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3009080 Wed, 18 Nov 2009 00:00:00 +0100 3009080 http://www.medworm.com/index.php?rid=3009079&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917238%26dopt%3DAbstract Authors: Aleksandrov A, Schuldt L, Hinrichs W, Simonson T Tetracycline (Tc) antibiotics have been put to new uses in the construction of artificial gene regulation systems, where they bind to the Tet repressor protein (TetR) and modulate its affinity for DNA. Many Tc variants have been produced, both to overcome bacterial resistance and to achieve a broad range of binding strengths. To better understand TetR-Tc binding, we investigate a library of 16 tetracyclines, using fluorescence experiments and molecular dynamics free energy simulations (MDFE). The relative TetR binding free energies are computed by reversibly transforming one Tc variant into another during the simulation, with no adjustable parameters. The chemical variations involve polar and nonpolar substitutions along one ent... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3009079 Wed, 18 Nov 2009 00:00:00 +0100 3009079 http://www.medworm.com/index.php?rid=3009078&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917239%26dopt%3DAbstract Authors: Bernadó P, Blackledge M Characterization of the conformational properties of unfolded proteins is essential for understanding the mechanisms of protein folding and misfolding. This information is also fundamental to determining the relationship between flexibility and function in the highly diverse families of intrinsically disordered proteins. Here we present a self-consistent model of conformational sampling of chemically denatured proteins in agreement with experimental data reporting on long-range distance distributions in unfolded proteins using small-angle x-ray scattering and nuclear magnetic resonance pulse-field gradient-based measurements. We find that standard statistical coil models, selected from folded protein databases with secondary structural elements rem... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3009078 Wed, 18 Nov 2009 00:00:00 +0100 3009078 http://www.medworm.com/index.php?rid=3009077&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917240%26dopt%3DAbstract Authors: Chuang GY, Kozakov D, Brenke R, Beglov D, Guarnieri F, Vajda S Structures of truncated versions of the influenza A virus M2 proton channel have been determined recently by x-ray crystallography in the open conformation of the channel, and by NMR in the closed state. The structures differ in the position of the bound inhibitors. The x-ray structure shows a single amantadine molecule in the middle of the channel, whereas in the NMR structure four drug molecules bind at the channel's outer surface. To study this controversy we applied computational solvent mapping, a technique developed for the identification of the most druggable binding hot spots of proteins. The method moves molecular probes-small organic molecules containing various functional groups-around the protein surfac... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3009077 Wed, 18 Nov 2009 00:00:00 +0100 3009077 http://www.medworm.com/index.php?rid=3009076&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917241%26dopt%3DAbstract We present a polarimetric two-photon microscopy technique to quantitatively image the local static molecular orientational behavior in lipid and cell membranes. This approach, based on a tunable excitation polarization state complemented by a polarized readout, is easily implementable and does not require hypotheses on the molecular angular distribution such as its mean orientation, which is a main limitation in traditional fluorescence anisotropy measurements. The method is applied to the investigation of the molecular angular distribution in giant unilamellar vesicles formed by liquid-ordered and liquid-disordered micro-domains, and in COS-7 cell membranes. The highest order contrast between ordered and disordered domains is obtained for dyes locating within the membrane acyl chains. ... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=3009076 Wed, 18 Nov 2009 00:00:00 +0100 3009076 http://www.medworm.com/index.php?rid=2960060&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19883578%26dopt%3DAbstract We present a simple and model free approach to extract the force-dependent dissociation rates directly from the force curve data. Simulations show that the dissociation rates at any force are given directly by the ratio of the number of detected rupture events to the time this force was acting on the bond. To calculate these total times of acting forces, all force curve data points of all curves measured are taken into account, which significantly increases the amount of information which is considered for data analysis compared to other methods. Moreover, by providing force-dependent dissociation rates this method allows direct testing and validating of any energy landscape model. PMID: 19883578 [PubMed - in process] (Source: Biophysical Journal) Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=2960060 Wed, 04 Nov 2009 00:00:00 +0100 2960060 http://www.medworm.com/index.php?rid=2960059&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19883579%26dopt%3DAbstract In this study, we demonstrate that a new class of NIR fluorescent dyes, pyrrolopyrrole cyanine dyes, have exceptionally long FLTs ranging from 3 to 4 ns, both in vitro (dimethyl sulfoxide and albumin/water solutions) and in vivo (mice). These results provide a new window for imaging molecular processes, rejecting backscattered light and autofluorescence, and multiplexing imaging information with conventional NIR fluorescent dyes that absorb and emit light at similar wavelengths. PMID: 19883579 [PubMed - in process] (Source: Biophysical Journal) Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=2960059 Wed, 04 Nov 2009 00:00:00 +0100 2960059 http://www.medworm.com/index.php?rid=2960058&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19883580%26dopt%3DAbstract This study suggests that gel distribution in layers of thickness >100 microm and fractional area coated >0.8 is critical in determining the ability of the gel to serve as a barrier to HIV diffusion. PMID: 19883580 [PubMed - in process] (Source: Biophysical Journal) Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=2960058 Wed, 04 Nov 2009 00:00:00 +0100 2960058 http://www.medworm.com/index.php?rid=2960057&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19883581%26dopt%3DAbstract Authors: Pálsson E Starving Dictyostelium cells respond chemotactically to cell-generated waves of cyclic adenosine -3',5'- monophosphate (cAMP) that guide cell aggregation toward a signaling center. In this process, a large number of cells are recruited, resulting in the formation of aggregation territories that are essential for fruiting body formation. The enzyme PdsA phosphodiesterase (PDE), a crucial component of the signaling system, breaks down the external cAMP and can be either membrane-bound or secreted. The existence of two such forms is unusual in cell biology, and it remains to be determined why they have both been maintained through evolution. Here, using a model of the cAMP signaling system, I show that colonies can successfully organize into aggregates over a wider... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=2960057 Wed, 04 Nov 2009 00:00:00 +0100 2960057 http://www.medworm.com/index.php?rid=2960056&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19883582%26dopt%3DAbstract Authors: Fathallah-Shaykh HM, Bona JL, Kadener S Eukaryotic circadian clocks include interconnected positive and negative feedback loops. The clock-cycle dimer (CLK-CYC) and its homolog, CLK-BMAL1, are key transcriptional activators of central components of the Drosophila and mammalian circadian networks, respectively. In Drosophila, negative loops include period-timeless and vrille; positive loops include par domain protein 1. Clockwork orange (CWO) is a recently discovered negative transcription factor with unusual effects on period, timeless, vrille, and par domain protein 1. To understand the actions of this protein, we introduced a new system of ordinary differential equations to model regulatory networks. The model is faithful in the sense that it replicates biological observatio... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=2960056 Wed, 04 Nov 2009 00:00:00 +0100 2960056 http://www.medworm.com/index.php?rid=2960055&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19883583%26dopt%3DAbstract Authors: Tsaneva-Atanasova K, Sherman A K(ir)6.2[AAA] transgenic mouse islets exhibit mosaicism such that approximately 70% of the beta-cells have nonfunctional ATP-sensitive potassium (K(ATP)) channels, whereas the remainder have normal K(ATP) function. Despite this drastic reduction, the glucose dose-response curve is only shifted by approximately 2 mM. We use a previously published mathematical model, in which K(ATP) conductance is increased by rises in cytosolic calcium through indirect effects on metabolism, to investigate how cells could compensate for the loss of K(ATP) conductance. Compensation is favored by the assumption that only a small fraction of K(ATP) channels are open during oscillations, which renders it easy to upregulate the open fraction via a modest elevation of c... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=2960055 Wed, 04 Nov 2009 00:00:00 +0100 2960055 http://www.medworm.com/index.php?rid=2960054&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19883584%26dopt%3DAbstract Authors: Gladnikoff M, Shimoni E, Gov NS, Rousso I The assembly and budding of a new virus is a fundamental step in retroviral replication. Yet, despite substantial progress in the structural and biochemical characterization of retroviral budding, the underlying physical mechanism remains poorly understood, particularly with respect to the mechanism by which the virus overcomes the energy barrier associated with the formation of high membrane curvature during viral budding. Using atomic force, fluorescence, and transmission electron microscopy, we find that both human immunodeficiency virus and Moloney murine leukemia virus remodel the actin cytoskeleton of their host. These actin-filamentous structures assemble simultaneously with or immediately after the beginning of budding, and dis... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=2960054 Wed, 04 Nov 2009 00:00:00 +0100 2960054 http://www.medworm.com/index.php?rid=2960053&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19883585%26dopt%3DAbstract Authors: Zeng S, Li B, Zeng S, Chen S The purpose of this computational study was to investigate the possible role of voltage-gated Ca(2+) channels in spontaneous Ca(2+) oscillations of astrocytes. By incorporating different types of voltage-gated Ca(2+) channels and a previous model, this study reproduced typical Ca(2+) oscillations in silico. Our model could mimic the oscillatory phenomenon under a wide range of experimental conditions, including resting membrane potential (-75 to -60 mV), extracellular Ca(2+) concentration (0.1 to 1500 muM), temperature (20 to 37 degrees C), and blocking specific Ca(2+) channels. By varying the experimental conditions, the amplitude and duration of Ca(2+) oscillations changed slightly (both <25%), while the frequency changed significantly ( appro... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=2960053 Wed, 04 Nov 2009 00:00:00 +0100 2960053 http://www.medworm.com/index.php?rid=2960052&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19883586%26dopt%3DAbstract Authors: Qian J, Wang J, Lin Y, Gao H Focal adhesions are clusters of specific receptor-ligand bonds that link an animal cell to an extracellular matrix. To understand the mechanical responses of focal adhesions, here we develop a stochastic-elasticity model of a periodic array of adhesion clusters between two dissimilar elastic media subjected to an inclined tensile stress, in which stochastic descriptions of molecular bonds and elastic descriptions of interfacial traction are unified in a single modeling framework. We first establish a fundamental scaling law of interfacial traction distribution and derive a stress concentration index that governs the transition between uniform and cracklike singular distributions of the interfacial traction within molecular bonds. Guided by this sca... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=2960052 Wed, 04 Nov 2009 00:00:00 +0100 2960052 http://www.medworm.com/index.php?rid=2960051&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19883587%26dopt%3DAbstract Authors: Yarotskyy V, Elmslie KS N-type and L-type channels have significant gating differences, and we wondered whether some of these differences are linked to the relationship between charge movement and channel opening. The time constants for N-channel closing (tau(Deact)) and Off-gating charge movement (tauQ(Off)) were compared over a range of voltages. tauQ(Off) was significantly larger than tau(Deact) at voltages < -10 mV, and the voltage dependence of the tauQ(Off) was less steep than that for tau(Deact), which suggests that gating charge relaxation does not limit channel closing. Roscovitine, a drug that slows N-channel closing by holding the channel in a high open-probability state, was found to slow both tauQ(Off) and tau(Deact), and thus the time courses of channel closin... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=2960051 Wed, 04 Nov 2009 00:00:00 +0100 2960051 http://www.medworm.com/index.php?rid=2960049&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19883588%26dopt%3DAbstract Authors: Zhu F, Hummer G Pentameric ligand-gated ion channels are an important family of membrane proteins and play key roles in physiological processes, including signal transduction at chemical synapses. Here, we study the conformational changes associated with the opening and closing of the channel pore. Based on recent crystal structures of two prokaryotic members of the family in open and closed states, respectively, mixed elastic network models are constructed for the transmembrane domain. To explore the conformational changes in the gating transition, a coarse-grained transition path is computed that smoothly connects the closed and open conformations of the channel. We find that the conformational transition involves no major rotations of the transmembrane helices, and is inste... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=2960049 Wed, 04 Nov 2009 00:00:00 +0100 2960049 http://www.medworm.com/index.php?rid=2960047&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19883589%26dopt%3DAbstract Authors: Fassioli F, Olaya-Castro A, Scheuring S, Sturgis JN, Johnson NF In bacterial photosynthesis light-harvesting complexes, LH2 and LH1 absorb sunlight energy and deliver it to reaction centers (RCs) with extraordinarily high efficiency. Submolecular resolution images have revealed that both the LH2:LH1 ratio, and the architecture of the photosynthetic membrane itself, adapt to light intensity. We investigate the functional implications of structural adaptations in the energy transfer performance in natural in vivo low- and high-light-adapted membrane architectures of Rhodospirillum photometricum. A model is presented to describe excitation migration across the full range of light intensities that cover states from active photosynthesis, where all RCs are available for charge sepa... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=2960047 Wed, 04 Nov 2009 00:00:00 +0100 2960047 http://www.medworm.com/index.php?rid=2960025&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19883590%26dopt%3DAbstract Authors: Brender JR, Hartman K, Gottler LM, Cavitt ME, Youngstrom DW, Ramamoorthy A In previous in vivo studies, amyloid fibers formed from a peptide ubiquitous in human seminal fluid (semen-derived enhancer of viral infection (SEVI)) were found to dramatically enhance the infectivity of the HIV virus (3-5 orders of magnitude by some measures). To complement those studies, we performed in vitro assays of PAP(248-286), the most active precursor to SEVI, and other polycationic polymers to investigate the physical mechanisms by which the PAP(248-286) promotes the interaction with lipid bilayers. At acidic (but not at neutral) pH, freshly dissolved PAP(248-286) catalyzes the formation of large lipid flocculates in a variety of membrane compositions, which may be linked to the promotion of ... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=2960025 Wed, 04 Nov 2009 00:00:00 +0100 2960025 http://www.medworm.com/index.php?rid=2960005&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19883591%26dopt%3DAbstract Authors: Tielrooij KJ, Paparo D, Piatkowski L, Bakker HJ, Bonn M We study hydrated model membranes, consisting of stacked bilayers of 1,2-dioleoyl-sn-glycero-3-phosphocholine lipids, using terahertz time-domain spectroscopy and infrared spectroscopy. Terahertz spectroscopy enables the investigation of water dynamics, owing to its sensitivity to dielectric relaxation processes associated with water reorientation. By controlling the number of water molecules per lipid molecule in the system, we elucidate how the interplay between the model membrane and water molecules results in different water dynamics. For decreasing hydration levels, we observe the appearance of new types of water dynamics: the collective bulklike dynamics become less pronounced, whereas an increased amount of both ve... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=2960005 Wed, 04 Nov 2009 00:00:00 +0100 2960005 http://www.medworm.com/index.php?rid=2959984&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19883592%26dopt%3DAbstract Authors: Tong J, Briggs MM, Mlaver D, Vidal A, McIntosh TJ Two classes of channel-forming proteins in the eye lens, the water channel aquaporin-0 (AQP-0) and the connexins Cx46 and Cx50, are preferentially located in different regions of lens plasma membranes (1,2). Because these membranes contain high concentrations of cholesterol and sphingomyelin, as well as phospholipids such as phosphatidylcholine with unsaturated hydrocarbon chains, microdomains (rafts) form in these membranes. Here we test the hypothesis that sorting into lipid microdomains can play a role in the disposition of AQP-0 and the connexins in the plane of the membrane. For both crude membrane fractions and proteoliposomes composed of lens proteins in phosphatidylcholine/sphingomyelin/cholesterol lipid bilayers, deter... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=2959984 Wed, 04 Nov 2009 00:00:00 +0100 2959984 http://www.medworm.com/index.php?rid=2959983&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19883593%26dopt%3DAbstract We examined flash-frozen left-ventricle human cardiomyocyte bundles from healthy donors to determine control parameters for isometric tension (P(o)) development and Ca(2+) sensitivity, while simultaneously measuring actomyosin ATPase activity in situ by a fluorimetric technique. P(o) was 17 kN m(-2) and pCa(50%) was 5.99 (28 degrees C, I = 130 mM). ATPase activity increased linearly with tension to 132 muM s(-1). To determine the influence of flash-freezing, we compared the same parameters in both glycerinated and flash-frozen porcine left-ventricle trabeculae. P(o) in glycerinated porcine myocardium was 25 kN m(-2), and maximum ATPase activity was 183 microM s(-1). In flash-frozen porcine myocardium, P(o) was 16 kN m(-2) and maximum ATPase activity was 207 microM s(-1). pCa(50%) was 5.77 ... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=2959983 Wed, 04 Nov 2009 00:00:00 +0100 2959983 http://www.medworm.com/index.php?rid=2959982&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19883594%26dopt%3DAbstract Authors: Bui JM, Gsponer J, Vendruscolo M, Dobson CM The functions of proteins depend on the dynamical behavior of their native states on a wide range of timescales. To investigate these dynamics in the case of the small protein Gbeta1, we analyzed molecular dynamics simulations with the model-free approach of nuclear magnetic relaxation. We found amplitudes of fast timescale motions (sub-tau(c), where tau(c) is the rotational correlation time) consistent with S(2) obtained from spin relaxation measurements as well as amplitudes of slow timescale motions (supra-tau(c)) in quantitative agreement with S(2) order parameters derived from residual dipolar coupling measurements. The slow timescale motions are associated with the large variations of the (3)J couplings that follow transitions ... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=2959982 Wed, 04 Nov 2009 00:00:00 +0100 2959982 http://www.medworm.com/index.php?rid=2959981&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19883595%26dopt%3DAbstract Authors: Bekard IB, Dunstan DE The traditional approach to investigating the partial unfolding and fibrillation of insulin, and proteins at large, has involved use of the dyes 1-anilinonaphthalene-8-sulphonic acid (ANS) and Thioflavin T (ThT), respectively. We compare the kinetic profiles of ThT, ANS, light scattering, and intrinsic Tyr fluorescence during insulin fibrillation. The data reveal that the sequence of structural changes (dimers --> monomers --> partially unfolded monomers --> oligomeric aggregates --> fibrils) accompanying insulin fibrillation can be detected directly using intrinsic Tyr fluorescence. The results indicate that at least two distinguishable structural intermediates precede fibril development. There is no evidence of tyrosinate or dityrosine durin... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=2959981 Wed, 04 Nov 2009 00:00:00 +0100 2959981 http://www.medworm.com/index.php?rid=2959980&cid=s_35858_75_f&fid=35858&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19883596%26dopt%3DAbstract Authors: Vorontsov II, Miyashita O Cyanovirin-N (CVN) is a highly potent anti-HIV carbohydrate-binding agent that establishes its microbicide activity through interaction with mannose-rich glycoprotein gp120 on the virion surface. The m4-CVN and P51G-m4-CVN mutants represent simple models for studying the high-affinity binding site, B(M). A recently determined 1.35 A high-resolution structure of P51G-m4-CVN provided details on the di-mannose binding mechanism, and suggested that the Arg-76 and Glu-41 residues are critical components of high mannose specificity and affinity. We performed molecular-dynamics simulations in solution and a crystal environment to study the role of Arg-76. Network analysis and clustering were used to characterize the dynamics of Arg-76. The results of our exp... Biophysical Journal journals http://www.medworm.com/rss/comments.php?id=2959980 Wed, 04 Nov 2009 00:00:00 +0100 2959980