11-cis-Retinal Protonated Schiff Base:  Influence of the Protein Environment on the Geometry of the Rhodopsin Chromophore

Abstract

Density functional theory (DFT) calculations based on the self-consistent-charge tight-binding approximation have been performed to study the influence of the protein pocket on the 3-dimensional structure of the 11-cis-retinal Schiff base (SB) chromophore. Starting with an effectively planar chromophore embedded in a protein pocket consisting of the 27 next-nearest amino acids, the relaxed chromophore geometry resulting from energy optimization and molecular dynamics (MD) simulations has yielded novel insights with respect to the following questions: (i) The conformation of the beta-ionone ring. The protein pocket tolerates both conformations, 6-s-cis and 6-s-trans, with a total energy difference of 0.7 kcal/mol in favor of the former. Of the two possible 6-s-cis conformations, the one with a negative twist angle (optimized value: -35 degrees ) is strongly favored, by 3.6 kcal/mol, relative to the one in which the dihedral is positive. (ii) Out-of-plane twist of the chromophore. The environment induces a nonplanar helical deformation of the chromophore, with the distortions concentrated in the central region of the chromophore, from C10 to C13. The dihedral angle between the planes formed by the bonds from C7 to C10 and from C13 to C15 is 42 degrees. (iii) The absolute configuration of the chromophore. The dihedral angle about the C12-C13 bond is +170 degrees from planar s-cis, which imparts a positive helicity on the chromophore, in agreement with earlier considerations based on theoretical and spectroscopic evidence.

Mechanism of a proton pump analyzed with computer simulations

“…The active-site geometries of a set of conformers with protonated retinal Schiff base/negatively charged D85, and, respectively, with neutral Schiff base/neutral D85, were almost identical when QM/MM optimized using either SCC-DFTB or B3LYP/6-31G** for the QM region; the optimized relative energies agreed to within 2 kcal/mol (0.8 kcal/mol with SCC-DFTB/MM, and 2.6 kcal/mol with B3LYP6-31G**/MM) [22]. The geometry of the twisted 11-cis retinal in the binding pocket of bovine rhodopsin obtained from SCC-DFTB computations was also in good agreement with the experimental NMR data [54].…”

“…2c, d), by the interaction with the negatively charged counterion [54,67,68] (black and blue/cyan curves in Fig. 2), and by pronounced twists around double bonds [38].…”

“…The bond alternation is reduced by protonation of the Schiff base [46] (Fig. 2c, d) and increased due to the interaction with the counterion [54,[67][68][69] (black, blue, and light blue curves in Fig. 2c).…”

QM/MM Study of the NMR Spectroscopy of the Retinyl Chromophore in Visual Rhodopsin

“…The reported studies include calculations based on classical molecular dynamics simulations, [73][74][75] ab initio restricted Hartree-Fock (RHF) calculations of reducedmodel systems, 76,52 and QM/MM computations. 16,30,[77][78][79][80] The 1 H and 13 C NMR spectra reported in this paper are based on the atomistic computational models of rhodopsin and bathorhodopsin developed in previous work, 16 in an effort to provide an explicit and rigorous description of the influence of the opsin environment on the 1 H and 13 C NMR chemical shifts of the retinyl chromophore. The models are able to predict the energy storage and electronic excitation energies for the dark and product states in very good agreement with experimental data.…”

Computational Studies of the Primary Phototransduction Event in Visual Rhodopsin

“…1,2,[5][6][7][20][21][22] In particular, recent DFT QM/MM studies 1,2 have addressed the elucidation of chromophoreopsin interactions responsible for phototransduction and energy storage through 11-cis/all-trans isomerization, a problem that has been largely elusive to first-principles examinations. Some of the fundamental questions are as follows: What are the molecular rearrangements responsible for 11-cis/all-trans isomerization in the rhodopsin binding pocket?…”