G protein-coupled receptor activation is proposed to be a dynamical process involving an ensemble of activated states. Using molecular dynamics simulations, we investigated the dynamical processes that occur in the pre-activated and fully activated photointermediates of rhodopsin, Meta I and Meta II. The putative Meta II structure of rhodopsin (3PXO) was embedded into micelles of two different detergents, dodecylmaltoside (DDM) or CHAPS. Within nanoseconds in CHAPS, the rhodopsin binding pocket becomes less accessible to aqueous solution, a hallmark of Meta I. Conversely, the DDM further stabilizes the initial Meta II-like configuration of the protein. Our results show that the less constrictive surrounding allows for faster conformational transitions to occur, leading to a detailed picture of the changes in rhodopsin from Meta I to Meta II. These studies fill crucial gaps in our knowledge of rhodopsin activation and provide a framework for direct comparison to membrane protein studies in detergents.

Probing the Meta I to Meta II equilibrium of rhodopsin activation in detergent micelles with molecular dynamics simulations

245th National Meeting (2013)

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