Comprehensive analysis of loops at protein-protein interfaces for macrocycle design.

ABSTRACT: Inhibiting protein-protein interactions (PPIs) with synthetic molecules remains a frontier of chemical biology. Many PPIs have been successfully targeted by mimicking α-helices at interfaces, but most PPIs are mediated by nonhelical, nonstrand peptide loops. We sought to comprehensively identify and analyze these loop-mediated PPIs by writing and implementing LoopFinder, a customizable program that can identify loop-mediated PPIs within all of the protein-protein complexes in the Protein Data Bank. Comprehensive analysis of the entire set of 25,005 interface loops revealed common structural motifs and unique features that distinguish loop-mediated PPIs from other PPIs. 'Hot loops', named in analogy to protein hot spots, were identified as loops with favorable properties for mimicry using s

SUBMITTER: Gavenonis J 

PROVIDER: S-EPMC4138238 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature