Characterizing Interhelical Interactions of G-Protein Coupled Receptors with the Fragment Molecular Orbital Method.

ABSTRACT: G-protein coupled receptors (GPCRs) are the largest superfamily of membrane proteins, regulating almost every aspect of cellular activity and serving as key targets for drug discovery. We have identified an accurate and reliable computational method to characterize the strength and chemical nature of the interhelical interactions between the residues of transmembrane (TM) domains during different receptor activation states, something that cannot be characterized solely by visual inspection of structural information. Using the fragment molecular orbital (FMO) quantum mechanics method to analyze 35 crystal structures representing different branches of the class A GPCR family, we have identified 69 topologically equivalent TM residues that form a consensus network of 51 inter-TM interactions,

SUBMITTER: Heifetz A 

PROVIDER: S-EPMC7161079 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature