Computational Studies of the Primary Phototransduction Event in Visual Rhodopsin

Abstract

This Account addresses recent advances in the elucidation of the detailed molecular rearrangements due to the primary photochemical event in rhodopsin, a prototypical G-protein-coupled receptor (GPCR) responsible for the signal transmission cascade in the vertebrate vision process. The reviewed studies provide fundamental insight on long-standing problems regarding the assembly and function of the individual residues and bound water molecules that form the rhodopsin active site, a center that catalyzes the 11-cis/all-trans isomerization of the retinyl chromophore in the primary step of the phototransduction mechanism. Emphasis is placed on the authors' recent computational studies, based on state-of-the-art quantum mechanics/molecular mechanics (QM/MM) hybrid methods, addressing the structural refinement of the retinyl chromophore binding site in high-resolution X-ray structures of bovine visual rhodopsin, the energy storage mechanism, and the molecular origin of spectroscopic changes due to the primary photochemical event.

Spectral Tuning in Visual Pigments: An ONIOM(QM:MM) Study on Bovine Rhodopsin and its Mutants

“…NMR parameters calculated at B3LYP/MM level are also more consistent with experiment for the 6-s-cis conformation. 12 These results suggest that 6-strans conformation will appear only very rarely during protein dynamics. Hence, we have considered only 6-s-cis conformation in this study.…”

QM/MM investigation of structure and spectroscopic properties of a vanadium-containing peroxidase

“…On the other hand, incorporating individual residues from the first layer in the QM region (while the others in the first layer remain with zero charge) only results in a finer tuning effect. This is in contrast with protein active sites driven by photochemical events, in which a particular residue close the chromophore tunes most of the excitation, while the rest of the protein produces a finer tuning effect [66,67]. A close analysis of the contribution of individual residues (see Table 4) shows that Arg360 and Arg490 are the most important factors influencing the electronic absorption.…”

Fragment-Molecular-Orbital-Method-Based ab Initio NMR Chemical-Shift Calculations for Large Molecular Systems

“…Therefore, in regard to the total number of residues sequentially along the polypeptide (counted from the residue where the chemical shifts are calculated to the residue at Table 6. Quality of Absolute Anisotropic NMR Shielding Constants (in ppm) of 13 C R , 13 C , 15 the FMO boundary), the number is larger in the R-helix than in the -sheet. In other words, if the same cutoff distance is used for the R-helix and the -sheet, the effect of the FMO boundary is larger for the -sheet than for the R-helix.…”

“…For example, the maximum error of 15 N isotropic shielding constants relative to the conventional ab initio values is 1.16-2.19 ppm with a mean error of 0.33-0.51 ppm (Table 1) in the case of the FMO1(merged)/ model I calculation of the R-helix with the 6-31G(d) basis set. The maximum absolute error of 15 N isotropic shielding constants is about 300%-400% larger than the other errors of the 15 N isotropic shielding constants for the R-helix.…”