Retinal versus 13-demethyl-retinal inside the rhodopsin binding pocket—a QM/MM Study§

Abstract

To probe the effect of the protein environment on the retinal chromophore of rhodopsin, we performed molecular dynamics simulations using combined quantum mechanics/molecular mechanics (QM/MM). The starting geometry of the protein is based on the 2.6Å X-ray structure of bovine rhodopsin of Okada et al. [T. Okada, et al. Proc. Natl. Acad. Sci. USA 99 5982 (2002)]. The wild-type chromophore of rhodopsin according to our calculations shows a highly twisted conformation around the central region, from C10 to C13, due to non-bonded interaction with the protein pocket. The absolute sense of twist of the C11–C12 and C12–C13 bonds is negative (−19 ± 9°) and positive (170 ± 8°), respectively. The 13-demethyl retinal chromophore, in which the methyl group at the C13 position is removed, is less distorted in this region. The C11–C12 bond is less twisted (−15 ± 10°) and the C12–C13 bond is planar (179 ± 9°) . The flattened geometry of this artificial chromophore is supported by spectroscopic evidence.