Analysis of tractable allosteric sites in G protein-coupled receptors.

ABSTRACT: Allosteric modulation of G protein-coupled receptors represent a promising mechanism of pharmacological intervention. Dramatic developments witnessed in the structural biology of membrane proteins continue to reveal that the binding sites of allosteric modulators are widely distributed, including along protein surfaces. Here we restrict consideration to intrahelical and intracellular sites together with allosteric conformational locks, and show that the protein mapping tools FTMap and FTSite identify 83% and 88% of such experimentally confirmed allosteric sites within the three strongest sites found. The methods were also able to find partially hidden allosteric sites that were not fully formed in X-ray structures crystallized in the absence of allosteric ligands. These results confirm tha

SUBMITTER: Wakefield AE 

PROVIDER: S-EPMC6467999 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature