Identification of distant drug off-targets by direct superposition of binding pocket surfaces.

ABSTRACT: Correctly predicting off-targets for a given molecular structure, which would have the ability to bind a large range of ligands, is both particularly difficult and important if they share no significant sequence or fold similarity with the respective molecular target ("distant off-targets"). A novel approach for identification of off-targets by direct superposition of protein binding pocket surfaces is presented and applied to a set of well-studied and highly relevant drug targets, including representative kinases and nuclear hormone receptors. The entire Protein Data Bank is searched for similar binding pockets and convincing distant off-target candidates were identified that share no significant sequence or fold similarity with the respective target structure. These putative target off-t

SUBMITTER: Schumann M 

PROVIDER: S-EPMC3877058 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature