Characterizing changes in the rate of protein-protein dissociation upon interface mutation using hotspot energy and organization.

ABSTRACT: Predicting the effects of mutations on the kinetic rate constants of protein-protein interactions is central to both the modeling of complex diseases and the design of effective peptide drug inhibitors. However, while most studies have concentrated on the determination of association rate constants, dissociation rates have received less attention. In this work we take a novel approach by relating the changes in dissociation rates upon mutation to the energetics and architecture of hotspots and hotregions, by performing alanine scans pre- and post-mutation. From these scans, we design a set of descriptors that capture the change in hotspot energy and distribution. The method is benchmarked on 713 kinetically characterized mutations from the SKEMPI database. Our investigations show that, wit

SUBMITTER: Agius R 

PROVIDER: S-EPMC3764008 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature