Using multiple microenvironments to find similar ligand-binding sites: application to kinase inhibitor binding.

ABSTRACT: The recognition of cryptic small-molecular binding sites in protein structures is important for understanding off-target side effects and for recognizing potential new indications for existing drugs. Current methods focus on the geometry and detailed chemical interactions within putative binding pockets, but may not recognize distant similarities where dynamics or modified interactions allow one ligand to bind apparently divergent binding pockets. In this paper, we introduce an algorithm that seeks similar microenvironments within two binding sites, and assesses overall binding site similarity by the presence of multiple shared microenvironments. The method has relatively weak geometric requirements (to allow for conformational change or dynamics in both the ligand and the pocket) and uses

SUBMITTER: Liu T 

PROVIDER: S-EPMC3248393 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature