MD Simulations of a 5-HT_2A Receptor Model in DOPC Membranes

Abstract

This work presents MD calculations on a model 5-HT_2A G protein-coupled receptor embedded in DOPC membrane bilayers at different lipid:protein ratios. The primary purpose is to evaluate physical properties of the system to probe membrane dynamics and the solvation interactions. This showed several kinds of apparent cooperativity phenomena in distributions, lipid dynamics, and hydrogen bond interactions. The integral protein appears to cause a disordered condensation of the local lipid structure which does not extend far beyond the surface layer of lipids. This, and changes in the lipid-protein interaction profiles give a start toward understanding membrane-protein selectivity. The presence of a partially immobilized surface layer of lipids may generally slow down kinetics of solute-solute interactions in similar liquid-crystal membranes. A hydration algorithm was also applied to the GPCR model producing a detailed water structure in some of the internal cavities, including in the areas proposed for ligand binding. Other properties examined included the distributions of lipid groups, the membrane electrostatic potential, and some of the short-time protein dynamics.