Evolutionary Couplings and Molecular Dynamic Simulations Highlight Details of GPCRs Heterodimers' Interfaces.

ABSTRACT: A growing body of evidence suggests that only a few amino acids ("hot-spots") at the interface contribute most of the binding energy in transient protein-protein interactions. However, experimental protocols to identify these hot-spots are highly labor-intensive and expensive. Computational methods, including evolutionary couplings, have been proposed to predict the hot-spots, but they generally fail to provide details of the interacting amino acids. Here we showed that unbiased evolutionary methods followed by biased molecular dynamic simulations could achieve this goal and reveal critical elements of protein complexes. We applied the methodology to selected G-protein coupled receptors (GPCRs), known for their therapeutic properties. We used the structure-prior-assisted direct coupling an

SUBMITTER: Nchourupouo KWT 

PROVIDER: S-EPMC9966702 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature