Elucidating the druggable interface of protein-protein interactions using fragment docking and coevolutionary analysis.

ABSTRACT: Protein-protein interactions play a central role in cellular function. Improving the understanding of complex formation has many practical applications, including the rational design of new therapeutic agents and the mechanisms governing signal transduction networks. The generally large, flat, and relatively featureless binding sites of protein complexes pose many challenges for drug design. Fragment docking and direct coupling analysis are used in an integrated computational method to estimate druggable protein-protein interfaces. (i) This method explores the binding of fragment-sized molecular probes on the protein surface using a molecular docking-based screen. (ii) The energetically favorable binding sites of the probes, called hot spots, are spatially clustered to map out candidate bi

SUBMITTER: Bai F 

PROVIDER: S-EPMC5167203 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature