bi026011h_si_001.pdf (27.14 kB)
Early Steps of the Intramolecular Signal Transduction in Rhodopsin Explored by Molecular Dynamics Simulations†
journal contribution
posted on 2002-07-30, 00:00 authored by Ute F. Röhrig, Leonardo Guidoni, Ursula RothlisbergerWe 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-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 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-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, 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.