Minoru Sugihara

Exploring the Opsin shift with ab initio methods: Geometry and counterion effects on the electronic spectrum of retinal

To study the effect of the charged chromophore environment on the absorption spectrum of rhodopsin, we have calculated excited state energies of chromophore models using multi-configurational second-order perturbation theory. Taking advantage of the recently solved crystal structures of rhodopsin we have considered different chromophore geometries and their interaction with the Glu113 counterion, water and Glu181 in different protonation states. We observe a strongly blueshifted S1 state upon inclusion of Glu113/water to the wave function; the effect of the additional carboxyl group appears to be overbalanced by the complex counterion.

Structural elements of the signal propagation pathway in squid rhodopsin and bovine rhodopsin.

Squid and bovine rhodopsins are G-protein coupled receptors (GPCRs) that activate Gq- and Gt-type G-proteins, respectively. To understand the structural elements of the signal propagation pathway, we performed molecular dynamics (MD) simulations of squid and bovine rhodopsins plus a detailed sequence analysis of class A GPCRs. The computations indicate that although the geometry of the retinal is similar in bovine and squid rhodopsins, the important interhelical hydrogen bond networks are different. In squid rhodopsin, an extended hydrogen bond network that spans ∼13 Å to Tyr315 on the cytoplasmic site is present regardless of the protonation state of Asp80. In contrast, the extended hydrogen bond network is interrupted at Tyr306 in bovine rhodopsin. Those differences in the hydrogen bond network may play significant functional roles in the signal propagation from the retinal binding site to the cytoplasmic site, including transmembrane helix (TM) 6 to which the G-protein binds. The MD calculations demonstrate that the elongated conformation of TM6 in squid rhodopsin is stabilized by salt bridges formed with helix (H) 9. Together with the interhelical hydrogen bonds, the salt bridges between TM6 and H9 stabilize the protein conformation of squid rhodopsin and may hinder the occurrence of large conformational changes that are observed upon activation of bovine rhodopsin.

A First-Principles Study of 11-Cis-Retinal: Modelling the Chromophore-Protein Interaction In Rhodopsin

The 11- cis -retinal protonated Schiff base is the chromophore of rhodopsin, the photoreceptor in the vertebrate eye. The photochemical isomerization from 11- cis to the all- trans form triggers a series of enzymatic reactions known as the visual cascade which eventually leads to a neural signal. Experiments such as resonance Raman, NMR etc., have shown that 11- cis -retinal is probably highly twisted in the protein pocket. Because detailed knowledge about the kind of interaction with the protein is missing, a theoretical description of the chromophore conformation is difficult. In the simulations the results of which will be presented here, we assume that the retinal chromophore, as a consequence of the steric fit into the protein binding pocket, undergoes a specific kind of conformational change.The structure we obtain is in good agreement with the experimentally observed highly twisted conformation of the chromophore backbone.

9-Demethylrhodopsin: theoretical evidence for a relaxed batho intermediate.

The 9-methyl group of retinal is crucial for the photoreaction of rhodopsin. On the basis of the results of QM/MM simulations, we propose that the primary function of the methyl group is not to properly align the chromophore in the ground state, but that it is a prerequisite for the peculiarly twisted and strained chromophore observed in the batho state. With the methyl group firmly anchored in the protein binding pocket the protein, at the cost of the incipient photon energy, manages to increase the strain energy stored in the chromophore by 25%, which may be crucial for driving the subsequent transformations.

Ab initio, tight-binding and QM/MM calculations of the rhodopsin chromophore in its binding pocket.

We present results of ab initio and combined ab initio and force field calculations for the conformational changes of the rhodopsin chromophore in its binding pocket subject to various constraints like the inclusion of a water molecule near the counterion Glu113. Furthermore, the influence of other charged groups on the stability of the protonated Schiff base is investigated as well as the role of the amino acid threonine (Thr94). The calculations yield a stable protonated Schiff base and a highly twisted conformation of the chromophore which is in agreement with the latest refined set of structure data.

A Molecular-Dynamics Study of the Rhodopsin Chromophore Using Ultrasoft Pseudopotentials

We investigate the eect of dierent environments on the chromophore of the protein rhodopsin by using the Vienna ab initio simulation package which is based on Density Functional Theory with a plane wave basis set and the implementation of Vanderbilt’s ultrasoft pseudopotentials. We have calculated the energy dependence of 11-cis-retinal on the C11C12 double bond twist angle in the ground state and our results show that the isomerization in the ground state of the retinal chromophore is more dicult in the presence of the counter ion than without it.

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

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.

AB INITIO MOLECULAR-DYNAMICS SIMULATIONS OF ADSORPTION OF DYE MOLECULES AT SURFACES

Max-Planck Institut fu¨r Polymerforschung, 55128 Mainz, GermanyE-mail: hmeyer@mpip-mainz.mpg.deY. SAKAMOTODepartment of Physics, Osaka University, Toyonaka, Osaka 560-0043, JapanE-mail: sakamoto@phys.sci.osaka-u.ac.jpJ. HAFNERInstitut fu¨r Materialphysik, Universtit¨at Wien, 1090 Wien, AustriaE-mail:Juergen.Hafner@univie.ac.atV. BUSSInstitut fu¨r Physikalische und Theoretische Chemie,Universit¨at Duisburg, 47048 Duisburg, GermanyE-mail:theobuss@uni-duisburg.de