Coarse-Grained Molecular Dynamics Provides Insight into the Interactions of Lipids and Cholesterol with Rhodopsin

Abstract

Protein function is a complicated interplay between structure and dy- namics, which can be heavily influenced by environmental factors and conditions. This is particularly true in the case ofmembrane proteins, such as the visual receptor rhodopsin. It has been well documented that lipid headgroups, polyunsaturated tails, and the concentration of cholesterol in membranes all play a role in the function of rhodopsin. Recently, we used all-atom simulations to demonstrate that different lipid species have preferential interactions and possible binding sites on rhodopsin’s surface, consistent with experiment. However, the limited timescales of the simulations meant that the statistical uncertainty of these results was substantial. Accordingly, we present here 32 independent 1.6?s coarse-grained simulations exploring lipids and cholesterols surrounding rhodopsin and opsin, in lipid bilayers mimicking those found naturally. Our results agree with those found experimentally and in previous simu- lations, but with far better statistical certainty. The results demonstrate the value of combining all-atom and coarse-grained models with experiment to provide a well-rounded view of lipid-protein interactions.