Postdoctoral research associate
Theoretical chemistry division
Fukui Institute for Fundamental Chemistry, Kyoto University
34-4 Takano Nishihiraki-cho, Sakyo-ku, Kyoto 606-8103
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
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.