CryptoSite: Expanding the Druggable Proteome by Characterization and Prediction of Cryptic Binding Sites.

ABSTRACT: Many proteins have small-molecule binding pockets that are not easily detectable in the ligand-free structures. These cryptic sites require a conformational change to become apparent; a cryptic site can therefore be defined as a site that forms a pocket in a holo structure, but not in the apo structure. Because many proteins appear to lack druggable pockets, understanding and accurately identifying cryptic sites could expand the set of drug targets. Previously, cryptic sites were identified experimentally by fragment-based ligand discovery and computationally by long molecular dynamics simulations and fragment docking. Here, we begin by constructing a set of structurally defined apo-holo pairs with cryptic sites. Next, we comprehensively characterize the cryptic sites in terms of their seq

SUBMITTER: Cimermancic P 

PROVIDER: S-EPMC4794384 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature