Shigehiko HAYASHI Postdoctoral research associate Theoretical chemistry division Fukui Institute for Fundamental Chemistry, Kyoto University 34-4 Takano Nishihiraki-cho, Sakyo-ku, Kyoto 606-8103 JAPAN Tel. +81-75-711-7647 Fax. +81-75-781-4757 E-mail: hayashi@fukui.kyoto-u.ac.jp

Projects:

On-the-fly ab initio QM/MM molecular dynamics simulation of photo-isomerization of the retinal chromophore in bacteriorhodopsin

Retinal proteins are photoreceptors found in many living organisms. They possess a common chromophore, retinal, that upon absorption of light isomerizes and, thereby, triggers biological functions ranging from light energy conversion to phototaxis and vision. The photoisomerization of retinal is extremely fast, highly selective inside the protein matrix, and characterized through optimal sensitivity to incoming light. The study has succeeded in simulating the in situ isomerization dynamics of retinal in bacteriorhodopsin, a microbial retinal protein that functions as a light driven proton pump, in an ab initio quantum mechanical description. The simulation combines ab initio multi-electronic state molecular dynamics of a truncated retinal chromophore model with molecular mechanics of the protein motion and unveils in complete detail the photoisomerization process. The results illustrate the essential role of the protein for the characteristic kinetics and high selectivity of the photoisomerization: the protein arrests inhomogeneous photoisomerization paths and funnels them into a single path that initiates the functional process. Supported by comparison with dynamic spectral modulations observed in femtosecond spectroscopy, the results identify the principal molecular motion during photoisomerization.

Early intermediates of bacteriorhodopsin's photocycle

Bacteriorhodopsin (bR) residing in the purple membrane of Halobacterium salinarum functions as a light-driven proton pump to produce a proton gradient across the membrane. Upon absorption of light, a retinal chromophore in bR undergoes an isomerization, initiating a photocycle during which bR completes the active proton transport event. The photocycle comprises a series of intermediates and involves protein structural changes, which are coupled to proton transfer between key residues in the channel. By means of combined ab initio quantum mechanical/molecular mechanical and molecular dynamics simulations, we have modeled the early intermediate states of the photocycle, K and KL, to elucidate how the early intermediates store the photon energy and utilize it to enable bR to pump a proton during the relaxation process.

Spectral tuning in retinal proteins

The rhodopsin receptors reside in the cell membrane, and function as sensors of light. These proteins consist of an apoprotein (opsin) and a retinal chromophore covalently bound to the apoprotein by a protonated Schiff base linkage to a lysine residue. While the protonated form of retinal Schiff base absorbs at about 440 nm in organic solvents, its maximal absorption is drastically changed after binding to the apoprotein, an effect known as 'opsin shift'. A fundamental challenge in vision research has been the elucidation of the physical mechanisms by which the protein matrix adjusts the maximal absorption of the chromophore, using the molecule retinal to detect light at different wavelengths. The spectral tuning in two very homologous rhodopsins, sensory rhodopsin II and bacteriorhodopsin, is investigated by means of a combined ab initio quantum mechanical/molecular mechanical calculation.

ATP hydrolysis reaction in F₁-ATP synthase

Photoactivation in a visual receptor rhodopsin

Publications:

On the mechanism of ATP hydrolysis in F₁-ATPase. Markus Dittrich, Shigehiko Hayashi, and Klaus Schulten. Biophysical Journal, 85:2253-2266, 2003.

Molecular dynamics simulation of bacteriorhodopsin's photoisomerization using ab initio forces for the excited chromophore. Shigehiko Hayashi, Emad Tajkhorshid, and Klaus Schulten. Biophysical Journal, 85:1440-1449, 2003.

Molecular dynamics investigation of primary photoinduced events in the activation ofrhodopsin.Jan Saam, Emad Tajkhorshid, Shigehiko Hayashi, and Klaus Schulten. Biophys. J., 83:3097-3112, 2002.

Structural Changes during the Formation of Early Intermediates in the Bacteriorhodopsin Photocycle. Shigehiko Hayashi, Emad Tajkhorshid, and Klaus Schulten. Biophys. J., 83:1281-1297, 2002.

Structure and spectral tuning mechanism of photo-sensory protein sRII (pR). Shigehiko Hayashi, Emad Tajkhorshid, and Klaus Schulten. Biophysics (Seibutsu-Butsuri) 42:127-130, 2002 (in Japanese).

Structural determinants of spectral tuning in retinal proteins - bacteriorhodopsin vs sensory rhodopsin II. Shigehiko Hayashi, Emad Tajkhorshid, Eva Pebay-Peyroula, Antoine Royant, Ehud M. Landau, Javier Navarro, and Klaus Schulten. Journal of Physical Chemistry B, 105:10124-10131, 2001, featuring the cover page of the journal.

Proton transfer in bacteriorhodopsin: structure, excitation, IR spectra, and potential energy surface analyses by an ab initio QM/MM Method. Shigehiko Hayashi and Iwao Ohmine. Journal of Physical Chemistry B, 104:10678-10691, 2000.

Solvent effect on intramolecular long-range electron-transfer reactions between porphyrin and benzoquinone in an acetonitrile solution: molecular dynamics calculations of reaction rate ronstants. Shigehiko Hayashi and Shigeki Kato. Journal of Physical Chemistry A, 102:3333-3342, 1998.

Theoretical study of intramolecular long-range electron transfer reactions between porphyrin and benzoquinone: ab initio calculations of electronic coupling element. Shigehiko Hayashi and Shigeki Kato. Journal of Physical Chemistry A, 102:2878-2887, 1998.

Reaction dynamics of charge-transfer state formation of 4-(N,N-dimethylamino)benzonitrile in a methanol solution: theoretical analyses. Shigehiko Hayashi, Koji Ando, and Shigeki Kato. Journal of Physical Chemistry, 99:955-964, 1995.

Electronic structures of poly-cations and -anions of C60. Possible mechanisms of organic ferromagnetism. K. Yamaguchi, S. Hayashi, M. Okumura, M. Nakano, and W. Mori. Chemical Physics Letters, 226:372-380, 1994.

Education:

1988-1992 Hokkaido University, Japan. Awarded B.S. in chemistry.

1992-1994 Kyoto University, Japan. Awarded M.S. in chemistry.

1994-1997 Kyoto University, Japan. Awarded Ph.D. in chemistry.

Research and professional experience:

1996-1998 Research fellow of the Japan society for the promotion of science at Kyoto University, Japan, working with Professor S. Kato.

1998-2001 Research fellow of the Japan society for the promotion of science at Nagoya University, Japan, working with Professor I. Ohmine.

2000-2001 Visiting postdoctral research associate at University of Illinois at Urbana-Champaign, working with Professor K. Schulten.

2001-2003 Postdoctral research associate at University of Illinois at Urbana-Champaign, working with Professor K. Schulten.

2003-present Postdoctral research associate at Fukui Institute for fundamental chemistry, Kyoto Univ.