J Chem Inf Model - CSAR data set release 2012: ligands, affinities, complexes, and docking decoys.

Tópicos

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{ compound(1573) activ(1297) structur(1058) }
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{ activ(1138) subject(705) human(624) }
{ can(981) present(881) function(850) }
{ activ(1452) weight(1219) physic(1104) }
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Resumo

A major goal in drug design is the improvement of computational methods for docking and scoring. The Community Structure Activity Resource (CSAR) has collected several data sets from industry and added in-house data sets that may be used for this purpose ( www.csardock.org). CSAR has currently obtained data from Abbott, GlaxoSmithKline, and Vertex and is working on obtaining data from several others. Combined with our in-house projects, we are providing a data set consisting of 6 protein targets, 647 compounds with biological affinities, and 82 crystal structures. Multiple congeneric series are available for several targets with a few representative crystal structures of each of the series. These series generally contain a few inactive compounds, usually not available in the literature, to provide an upper bound to the affinity range. The affinity ranges are typically 3-4 orders of magnitude per series. For our in-house projects, we have had compounds synthesized for biological testing. Affinities were measured by Thermofluor, Octet RED, and isothermal titration calorimetry for the most soluble. This allows the direct comparison of the biological affinities for those compounds, providing a measure of the variance in the experimental affinity. It appears that there can be considerable variance in the absolute value of the affinity, making the prediction of the absolute value ill-defined. However, the relative rankings within the methods are much better, and this fits with the observation that predicting relative ranking is a more tractable problem computationally. For those in-house compounds, we also have measured the following physical properties: logD, logP, thermodynamic solubility, and pK(a). This data set also provides a substantial decoy set for each target consisting of diverse conformations covering the entire active site for all of the 58 CSAR-quality crystal structures. The CSAR data sets (CSAR-NRC HiQ and the 2012 release) provide substantial, publically available, curated data sets for use in parametrizing and validating docking and scoring methods.

Resumo Limpo

major goal drug design improv comput method dock score communiti structur activ resourc csar collect sever data set industri ad inhous data set may use purpos wwwcsardockorg csar current obtain data abbott glaxosmithklin vertex work obtain data sever other combin inhous project provid data set consist protein target compound biolog affin crystal structur multipl congener seri avail sever target repres crystal structur seri seri general contain inact compound usual avail literatur provid upper bound affin rang affin rang typic order magnitud per seri inhous project compound synthes biolog test affin measur thermofluor octet red isotherm titrat calorimetri solubl allow direct comparison biolog affin compound provid measur varianc experiment affin appear can consider varianc absolut valu affin make predict absolut valu illdefin howev relat rank within method much better fit observ predict relat rank tractabl problem comput inhous compound also measur follow physic properti logd logp thermodynam solubl pka data set also provid substanti decoy set target consist divers conform cover entir activ site csarqual crystal structur csar data set csarnrc hiq releas provid substanti public avail curat data set use parametr valid dock score method

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