The focus of my research is to understand the molecular mechanisms by which different factors, such as membrane lipids, ligands and mutations, modulate the structure, dynamics and function of rhodopsin, the G protein-coupled receptor that mediates scotopic vision.
Lipids effects on rhodopsin
Using microsecond-scale all-atom molecular dynamics simulations we have studied the effect of membrane lipids on rhodopsin along its photocycle. Our work suggest that phospholipids alter rhodopsin's structure and dynamics via both ligand-like and bulk-like effects.
GPCR activation has remained elusive for standard simulation techniques due to its intrinsic timescales. We have implemented simple models (Go models) to try to bridge this gap. In these structure-based models, only native-like interactions are present, thus producing smoothed energy landscapes by construction where water and membrane interactions are implicitly accounted for. We are currently using this approach as a platform to study rhodopsin activation/deactivation, state interconversion in equilibrium and functionally relevant point-mutations.
In collaboration with the Feller lab, we are studying the effects of substitutions in rhodopsin's ligand (retinal) on the structure and dynamics of the receptor. In particular, we are interested on C9-methyl and C13-methyl substitutions, which have been shown to respectively decrease and increase the activity of the protein.
Department of Biochemistry and Biophysics
University of Rochester, Medical Center, Box 712
Rochester, NY 14642