Tokyo Institute of Technology · Biochemistry, Genetics and Molecular Biology
Professor Akio Kitao's research lab specializes in computational biophysics and molecular dynamics, focusing on the conformational dynamics, energy landscapes, and free energy calculations of biomolecules such as proteins and protein-ligand complexes. The lab develops advanced simulation methodologies—such as the jumping-among-minima (JAM) model, principal component analysis (PCA), Markov state models (MSM), and parallel cascade selection molecular dynamics (PaCS-MD)—to uncover the hierarchical motions and molecular mechanisms underlying protein folding, allostery, and ligand binding. Their work bridges atomistic simulations with experimental data, particularly in understanding complex phenomena like bacterial flagellar supercoiling and the dynamics of intrinsically disordered proteins such as p53. The lab also pioneers software tools for accurate free energy calculations, emphasizing the role of specific residues in protein stability and function.
Figures are computed from collected data and may differ slightly.
We have investigated energy landscape of human lysozyme in its native state by using principal component analysis and a model, jumping-among-minima (JAM) model. These analyses are applied to 1 nsec molecular dynamics trajectory of the protein in water. An assumption embodied in the JAM model allows us to divide protein motions into intra-substate and inter-substate motions. By examining intra-substate motions, it is shown that energy surfaces of individual conformational substates are nearly har
Principal component analysis (PCA) is used to reduce the dimensionalities of high-dimensional datasets in a variety of research areas. For example, biological macromolecules, such as proteins, exhibit many degrees of freedom, allowing them to adopt intricate structures and exhibit complex functions by undergoing large conformational changes. Therefore, molecular simulations of and experiments on proteins generate a large number of structure variations in high-dimensional space. PCA and many PCA-
Bacterial flagellar filament is a macromolecular assembly consisting of a single protein, flagellin. Bacterial swimming is controlled by the conformational transitions of this filament between left- and right-handed supercoils induced by the flagellar motor torque. We present a massive molecular dynamics simulation that was successful in constructing the atomic-level supercoil structures consistent with various experimental data and further in elucidating the detailed underlying molecular mechan
Recently, we efficiently generated dissociation pathways of a protein-ligand complex without applying force bias with parallel cascade selection molecular dynamics (PaCS-MD) and showed that PaCS-MD in combination with the Markov state model (MSM) yielded a binding free energy comparable to experimental values. In this work, we applied the same procedure to a complex of MDM2 protein and the transactivation domain of p53 protein (TAD-p53), the latter of which is known to be very flexible in the un
Abstract Effects of different treatments of the degrees of freedom of bond length stretching and bond angle bending in computational analysis of conformational dynamics of proteins and polypeptides are assessed. More specifically, the normal mode analysis of conformational dynamics of α‐helix of deca‐alanine has been carried out both in the dihedral angle space (DAS) and in the Cartesian coordinate space (CCS). Almost perfect one‐to‐one correspondence has been found between normal modes in the C
We developed a software package for improved free energy calculation, in which spherical solvent boundary potential, cell multipole method, and Nosé-Hoover equation are employed. The performance of the developed software package is demonstrated in the case of valine to alanine mutation of the 57th residue in chymotrypsin inhibitor 2. By using this package, we obtained results quantitatively comparable to experimental results. By the free energy component analysis, it is shown that leucine 51, ar
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEffects of solvent on the conformation and the collective motions of a protein. 3. Free energy analysis by the extended RISM theoryAkio Kitao, Fumio Hirata, and Nobuhiro GoCite this: J. Phys. Chem. 1993, 97, 39, 10231–10235Publication Date (Print):September 1, 1993Publication History Published online1 May 2002Published inissue 1 September 1993https://pubs.acs.org/doi/10.1021/j100141a053https://doi.org/10.1021/j100141a053research-articleACS Publications
Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter Facebook Reddit LinkedIn Tools Icon Tools Reprints and Permissions Cite Icon Cite Search Site Citation Akio Kitao, Ryuhei Harada, Yasutaka Nishihara, Duy Phuoc Tran; Parallel cascade selection molecular dynamics for efficient conformational sampling and free energy calculation of proteins. AIP Conf. Proc. 6 December 2016; 1790 (1): 020013. https://doi.org/10.1063/1.4968639 Downl
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