Nagoya University · 생화학·유전·분자생물학
Kazuhiro J. Fujimoto 교수의 연구실은 광학적 및 전자적 성질을 가진 단백질, 특히 레티날 기반 색소 단백질(예: 로돕신, 바크시오로돕신, 색소 수용체 등)의 광흡수 메커니즘을 고도로 정밀한 양자역학적 계산(예: SAC-CI, QM/MM, TDFI)을 통해 규명하는 데 초점을 맞추고 있습니다. 특히 색소 단백질의 스펙트럼 조정 메커니즘, 에너지 전달 및 전자 상호작용의 원리를 전자구조 이론과 결합하여 분석하며, 생물학적 기능과 분자 구조 간의 상관관계를 해명하고자 합니다. 또한, 약리학적 작용 메커니즘(예: 안정제의 K(ATP) 채널 조절)에 이르기까지 분자 수준의 기전 규명에도 기여하고 있습니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
The excited states of the three retinal proteins, bovine rhodopsin (Rh), bacteriorhodopsin (bR), and sensory rhodopsin II (sRII) were studied using the symmetry-adapted cluster-configuration interaction (SAC-CI) and combined quantum mechanical and molecular mechanical (QM/MM) methods. The computed absorption energies are in good agreement with the experimental ones for all three proteins. The spectral tuning mechanism was analyzed in terms of three contributions: molecular structures of the chro
Electronic coupling of excitation-energy transfer (EET) in a retinal (RET) protein, xanthorhodopsin (xR), was studied theoretically. The protein, functioning as a light driven proton pump, contains a carotenoid antenna, salinixanthin (SXN), to collect light energy for an RET chromophore through EET. The pseudo-Coulombic interaction (PCI) between the donor SXN and the acceptor RET molecules was calculated by a transition density fragment interaction (TDFI) method, which overcomes difficulty arisi
Isoflurane facilitated the opening of the sarcolemmal K(ATP) channel in the intact cell, but not in an excised, inside-out patch. The isoflurane effect was not due to a direct interaction with the K(ATP) channel protein, but required an intracellular component, likely including the translocation of specific protein kinase C isoforms. This suggests that the sarcolemmal K(ATP) channel may have a significant role in anesthetic-induced preconditioning.
A transition-density-fragment interaction (TDFI) combined with a transfer integral (TI) method is proposed. The TDFI method was previously developed for describing electronic Coulomb interaction, which was applied to excitation-energy transfer (EET) [K. J. Fujimoto and S. Hayashi, J. Am. Chem. Soc. 131, 14152 (2009)] and exciton-coupled circular dichroism spectra [K. J. Fujimoto, J. Chem. Phys. 133, 124101 (2010)]. In the present study, the TDFI method is extended to the exchange interaction, an
A density-fragment interaction (DFI) approach for large-scale calculations is proposed. The DFI scheme describes electron density interaction between many quantum-mechanical (QM) fragments, which overcomes errors in electrostatic interactions with the fixed point-charge description in the conventional quantum-mechanical/molecular-mechanical (QM/MM) method. A self-consistent method, which is a mean-field treatment of the QM fragment interactions, was adopted to include equally the electron densit
Abstract Human red (HR), green (HG), and blue (HB) cone pigments are responsible for human color vision, and their photoabsorption wavelengths spread uniquely over the three primary colors. These pigments, however, include only one common chromophore, retinal. Here, we report physical basis of the color tuning in human vision on the basis of SAC-CI calculations for excited states of the cone pigments. The dominant origin of the red–green–blue distinction lies in differences in electrostatic inte
A transition charge, dipole, and quadrupole from electrostatic potential (TrESP-CDQ) method for electronic coupling calculations is proposed. The TrESP method is based on the classical description of electronic Coulomb interaction between transition densities for individual molecules. In the original TrESP method, only the transition charge interactions were considered as the electronic coupling. In the present study, the TrESP method is extended to include the contributions from the transition
A transition-density-fragment interaction (TDFI) method for exciton-coupled circular dichroism (ECCD) spectra is proposed. The TDFI method was previously developed for excitation-energy transfer, which led to the successful estimation of the electronic coupling energy between donor and accepter molecules in xanthorhodopsin [K. J. Fujimoto and S. Hayashi, J. Am. Chem. Soc. 131, 14152 (2009)]. In the present study, the TDFI scheme is extended to the ECCD spectral calculation based on the matrix me
The crystallochromy of the red and yellow solids of tetracenes was theoretically investigated using the transition-density-fragment interaction combined with transfer integral method [K. J. Fujimoto, J. Chem. Phys. 137, 034101 (2012)]. The calculated absorption and fluorescence energies were in good agreement with the experimental values for both solids. The spectral tuning mechanism was analyzed in terms of three contributions: side-chain conformational effect, electrostatic solid-state effect,
Protein-ligand docking is an optimization problem, which aims to identify the binding pose of a ligand with the lowest energy in the active site of a target protein. In this study, we employed a novel optimization algorithm called fitness learning-based artificial bee colony with proximity stimuli (FlABCps) for docking. Simulation results revealed that FlABCps improved the success rate of docking, compared to four state-of-the-art algorithms. The present results also showed superior docking perf
We propose a novel machine-learning-based scoring function for drug discovery that incorporates ligand and protein structural information into a knowledge-based PMF score. Molecular docking, a simulation method for structure-based drug design (SBDD), is expected to reduce the enormous costs associated with conventional experimental methods in terms of rational drug discovery. Molecular docking has two main purposes: to predict ligand-binding structures for target proteins and to predict protein-
