Relationship between hot spot residues and ligand binding hot spots in protein-protein interfaces.

ABSTRACT: In the context of protein-protein interactions, the term "hot spot" refers to a residue or cluster of residues that makes a major contribution to the binding free energy, as determined by alanine scanning mutagenesis. In contrast, in pharmaceutical research, a hot spot is a site on a target protein that has high propensity for ligand binding and hence is potentially important for drug discovery. Here we examine the relationship between these two hot spot concepts by comparing alanine scanning data for a set of 15 proteins with results from mapping the protein surfaces for sites that can bind fragment-sized small molecules. We find the two types of hot spots are largely complementary; the residues protruding into hot spot regions identified by computational mapping or experimental fragment

SUBMITTER: Zerbe BS 

PROVIDER: S-EPMC3623692 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature