Biophysics colloquium with Alan Grossfield from University of Rochester Medical Center.
Abstract: G protein-coupled receptors (GPCRs) are integral membrane proteins critical to a variety of signaling tasks. Roughly one fourth of all drugs target GPCRs, underscoring their biomedical importance. Rhodopsin, the dim-light receptor in the mammalian vision system, has been studied extensively by both experimental and computational means. However, much remains to be learned about the mechanism of rhodopsin. For this reason, my group used molecular modeling techniques to understand the relationship between structure, dynamics, and environment in controlling rhodopsin function. We utilized microsecond-scale all-atom molecular dynamics simulations of rhodopsin and opsin to explore the role played by the ligand, in hopes of better understanding the mechanism of allostery. Additionally, we used coarse-grained molecular dynamics, a faster but less detailed approach, to explore the interactions between rhodopsin and the surrounding lipid matrix, an unusual composition rich in polyunsaturated lipid chains and cholesterol. The results confirm our belief believe that there is no such thing as the "best" modeling method, but rather different techniques are optimal under various circumstances, depending on the scientific question.