Molecular Simulation of the Effect of Cholesterol on Lipid-Mediated Protein-Protein Interactions

Experiments and molecular simulations have shown that the hydrophobic mismatch between proteins and membranes contributes significantly to lipid mediated protein protein interactions In this article we discuss the effect of cholesterol on lipid mediated protein protein interactions as function of hydrophobic mismatch protein diameter and protein cluster size lipid tail length and temperature To do so we study a mesoscopic model of a hydrated bilayer containing lipids and cholesterol in which proteins are embedded with a hybrid dissipative particle dynamics Monte Carlo method We propose a mechanism by which cholesterol affects protein interactions protein induced cholesterol enriched or cholesterol depleted lipid shells surrounding the proteins affect the lipid mediated protein protein interactions Our calculations of the potential of mean force between proteins and protein clusters show that the addition of cholesterol dramatically reduces repulsive lipid mediated interactions between proteins (protein clusters) with positive mismatch but does not affect attractive interactions between proteins with negative mismatch Cholesterol has only a modest effect on the repulsive interactions between proteins with different mismatch