Abstract

We present mol. dynamics simulations of bovine rhodopsin in a membrane mimetic environment based on the recently refined x-ray structure of the pigment. The interactions between the protonated Schiff base and the protein moiety are explored both with the chromophore in the dark-adapted 11-cis and in the photoisomerized all-trans form. Comparison of simulations with Glu181 in different protonation states strongly suggests that this loop residue located close to the 11-cis bond bears a neg. charge. Restrained mol. dynamics simulations also provide evidence that the protein tightly confines the abs. conformation of the retinal around the C12-C13 bond to a pos. helicity. 11-cis to all-trans isomerization leads to an internally strained chromophore, which relaxes after a few nanoseconds by a switching of the ionone ring to an essentially planar all-trans conformation. This structural transition of the retinal induces in turn significant conformational changes of the protein backbone, esp. in helix VI. Our results suggest a possible mol. mechanism for the early steps of intramol. signal transduction in a prototypical G-protein-coupled receptor. [on SciFinder (R)]

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