DrugPred: A Structure-Based Approach To Predict Protein Druggability Developed Using an Extensive Nonredundant Data Set

Agata Krasowski, Daniel Muthas, Aurijit Sarkar, Stefan Schmitt, Ruth Brenk

    Research output: Contribution to journalArticle

    49 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)2829-2842
    Number of pages14
    JournalJournal of Chemical Information and Modeling
    Volume51
    Issue number11
    DOIs
    Publication statusPublished - Nov 2011

    Keywords

    • BINDING-SITES
    • THYMIDINE PHOSPHORYLASE
    • DISCOVERY
    • TARGETS
    • DRUGS
    • DESIGN
    • INHIBITORS
    • GENOMICS
    • DOCKING
    • EXPLORATION

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