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

Abstract

We have investigated geometries and excitation energies of bovine rhodopsin and some of its mutants by hybrid quantum mechanical/molecular mechanical (QM/MM) calculations in ONIOM scheme, employing B3LYP and BLYP density functionals as well as DFTB method for the QM part and AMBER force field for the MM part. QM/MM geometries of the protonated Schiff-base 11-cisretinal with B3LYP and DFTB are very similar to each other. TD-B3LYP/MM excitation energy calculations reproduce the experimental absorption maximum of 500 nm in the presence of native rhodopsin environment and predict spectral shifts due to mutations within 10 nm, whereas TD-BLYP/ MM excitation energies have red-shift error of at least 50 nm. In the wild-type rhodopsin, Glu113 shifts the first excitation energy to blue and accounts for most of the shift found. Other amino acids individually contribute to the first excitation energy but their net effect is small. The electronic polarization effect is essential for reproducing experimental bond length alternation along the polyene chain in protonated Schiff-base retinal, which correlates with the computed first excitation energy. It also corrects the excitation energies and spectral shifts in mutants, more effectively for deprotonated Schiff-base retinal than for the protonated form. The protonation state and conformation of mutated residues affect electronic spectrum significantly. The present QM/MM calculations estimate not only the experimental excitation energies but also the source of spectral shifts in mutants.

Comparison of the isomerization mechanisms of human melanopsin and invertebrate and vertebrate rhodopsins

“…As also observed in hMeOp and sqRh, nonpolar amino acids are mainly located around the β-ionone ring. In line with previous results (40)(41)(42)), the Rh model shows that the largest electrostatic effect is due to the putative E113 counterion (SI Appendix, Fig. S6).…”

Evolutionary replacement of UV vision by violet vision in fish

“…It should be noted that the absolute max s calculated by using this method often deviate from the comparable experimental values, but the max -shifts generally match with the experimental values (24). Here, the visual pigments with unprotonated and protonated SBRs have max s of 391-417 and 441-463 nm, respectively, which are significantly higher than the comparable experimental values (Table 1).…”

“…The geometries were optimized at pure AMBER96 force field level (http://ambermd.org) after including H atoms and were further refined by hybrid quantum mechanical/molecular mechanical (QM/MM) calculations in the ONIOM (Our own N-layer Integrated molecular Orbital ϩ molecular Mechanics) electronic embedding scheme (QM ϭ B3LYP; MM ϭ AMBER) (24). The QM portion consists of the 11-cis-retinal, Schiff-base N-H moiety, and Glu-113 along with hydrogen link atoms.…”

“…However, the MM portion is more stable with deprotonated SBR. To evaluate the relative stabilities of unprotonated and protonated SBRs, we performed B3LYP/AMBER ground-state energy calculations (24). The maxs of SWS1 pigments were evaluated from the TD-B3LYP/AMBER excitation energies at their B3LYP/AMBER-optimized structures (24).…”

Predicting solvatochromic shifts and colours of a solvated organic dye: The example of nile red

“…QM/MM approaches have been successfully applied to to the modelling of chromophores in complex environments, such as pigments in pigment-protein complexes [3][4][5]. However, recent work has shown that a range of properties of interest of systems embedded in complex environments, including the absorption properties of small solvated dyes, require the explicit inclusion of large parts of the embedding environment into the QM region in order to obtain consistently converged results [6][7][8][9][10][11].…”