Quantum Mechanical/Molecular Mechanical Simulations Model Retinal Dynamics during Membrane Activation of Rhodopsin

Abstract

G-protein coupled receptors (GPCRs) - a superfamily of integral proteins that initiate signaling cascades upon ligand binding - are the most sought-after class of therapeutic targets. Solid-state 2H NMR spin relaxation times can be used to investigate the conformational dynamics in the membrane-bound state, but interpreting these data remains difficult. Here, in the case with the GPCR rhodopsin, we combine both quantum mechanics (QM) and molecular mechanics (MM) approaches [4] to study the rotational dynamics of the retinylidene methyl groups of the bound cofactor.