AlphaSpace: Fragment-Centric Topographical Mapping To Target Protein-Protein Interaction Interfaces.

ABSTRACT: Inhibition of protein-protein interactions (PPIs) is emerging as a promising therapeutic strategy despite the difficulty in targeting such interfaces with drug-like small molecules. PPIs generally feature large and flat binding surfaces as compared to typical drug targets. These features pose a challenge for structural characterization of the surface using geometry-based pocket-detection methods. An attractive mapping strategy--that builds on the principles of fragment-based drug discovery (FBDD)--is to detect the fragment-centric modularity at the protein surface and then characterize the large PPI interface as a set of localized, fragment-targetable interaction regions. Here, we introduce AlphaSpace, a computational analysis tool designed for fragment-centric topographical mapping (FCTM)

SUBMITTER: Rooklin D 

PROVIDER: S-EPMC4550072 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature