title: DrugPred: a structure-based approach to predict protein druggability developed using an extensive nonredundant data set.
abstract: Judging if a protein is able to bind orally available molecules with high affinity, i.e. if a protein is druggable, is an important step in target assessment. In order to derive a structure-based method to predict protein druggability, a comprehensive, nonredundant data set containing crystal structures of 71 druggable and 44 less druggable proteins was compiled by literature search and data mining. This data set was subsequently used to train a structure-based druggability predictor (DrugPred) using partial least-squares projection to latent structures discriminant analysis (PLS-DA). DrugPred performed well in discriminating druggable from less druggable binding sites for both internal and external predictions. The method is robust against conformational changes in the binding site and outperforms previously published methods. The superior performance of DrugPred is likely due to the size and composition of the training set which, in contrast to most previously developed methods, only contains cavities that have evolved to bind a natural ligand.
authors: College of Life Sciences, Division of Biological Chemistry and Drug Discovery, University of Dundee, Dow St, Dundee DD1 5EH, UK.
authors: Agata
authors: A
authors: Krasowski
authors: Daniel
authors: D
authors: Muthas
authors: Aurijit
authors: A
authors: Sarkar
authors: Stefan
authors: S
authors: Schmitt
authors: Ruth
authors: R
authors: Brenk
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods* / Q000706:statistics & numerical data; D057225:Data Mining; D030562:Databases, Protein; D055808:Drug Discovery / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D025341:Principal Component Analysis; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D012984:Software
chemical_list: D008024:Ligands; D011506:Proteins