Early Steps of the Intramolecular Signal Transduction in Rhodopsin Explored by Molecular Dynamics Simulations<sup>†</sup>
2002-07-30T00:00:00Z (GMT) by
We present molecular 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<i>-cis</i> and in the photoisomerized <i>all-trans</i> form. Comparison of simulations with Glu181 in different protonation states strongly suggests that this loop residue located close to the 11<i>-cis</i> bond bears a negative charge. Restrained molecular dynamics simulations also provide evidence that the protein tightly confines the absolute conformation of the retinal around the C12−C13 bond to a positive helicity. 11<i>-cis</i> to <i>all-trans</i> isomerization leads to an internally strained chromophore, which relaxes after a few nanoseconds by a switching of the ionone ring to an essentially planar <i>all-trans</i> conformation. This structural transition of the retinal induces in turn significant conformational changes of the protein backbone, especially in helix VI. Our results suggest a possible molecular mechanism for the early steps of intramolecular signal transduction in a prototypical G-protein-coupled receptor.