The overlap of small molecule and protein binding sites within families of protein structures.

ABSTRACT: Protein-protein interactions are challenging targets for modulation by small molecules. Here, we propose an approach that harnesses the increasing structural coverage of protein complexes to identify small molecules that may target protein interactions. Specifically, we identify ligand and protein binding sites that overlap upon alignment of homologous proteins. Of the 2,619 protein structure families observed to bind proteins, 1,028 also bind small molecules (250-1000 Da), and 197 exhibit a statistically significant (p<0.01) overlap between ligand and protein binding positions. These "bi-functional positions", which bind both ligands and proteins, are particularly enriched in tyrosine and tryptophan residues, similar to "energetic hotspots" described previously, and are significantly less

SUBMITTER: Davis FP 

PROVIDER: S-EPMC2816688 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature