Team Leader
Yuji Sugita D.Sci.

Laboratory for Biomolecular Function Simulation

[Concurrent appointment to BDR ended in March 2025. He continues his research at RIKEN Pioneering Research Institute. ]

E-mailsugita@riken.jp

Overview
Selected Publications
Members
News
Lab Website

We study biomolecular function using computer simulations on Fugaku or other supercomputers

In our laboratory, we carry out molecular dynamics simulations on Fugaku or other supercomputers to elucidate the relationships between structure, dynamics, and function in biomacromolecules, such as proteins, nucleic acids, glycans, and lipid molecules. We develop various free-energy calculation methods to evaluate free-energy differences between two thermodynamic states in biomacromolecules for understanding biomolecular functions more quantitatively. The developed methods are installed into the GENESIS software, which is a freeware available to everyone. We thus contribute not only to the basic life science but also to in-silico drug discovery.

Research Theme

Effects of intracellular crowding on the dynamics of protein and water interactions
Simulations and data analysis of large-scale protein structural changes
Slow dynamics using Brownian dynamics simulations

Selected Publications

Chong SH, Oshima H, Sugita Y.
Allosteric changes in the conformational landscape of Src kinase upon substrate binding.
Journal of Molecular Biology (2024) doi: 10.1016/j.jmb.2024.168871

Jung J, Yagi K, Tan C, et al.
GENESIS 2.1: High-Performance Molecular Dynamics Software for Enhanced Sampling and Free-Energy Calculations for Atomistic, Coarse-Grained, and Quantum Mechanics/Molecular Mechanics Models.
Journal of Physical Chemistry. B 128(25), 6028-6048 (2024) doi: 10.1021/acs.jpcb.4c02096

Chyży P, Kulik M, Shinobu A, et al.
Molecular dynamics in multidimensional space explains how mutations affect the association path of neomycin to a riboswitch.
Proceedings of the National Academy of Sciences of the United States of America 121(15), e2317197121 (2024) doi: 10.1073/pnas.2317197121

Shinobu A, Re S, Sugita Y.
Practical Protocols for Efficient Sampling of Kinase-Inhibitor Binding Pathways Using Two-Dimensional Replica-Exchange Molecular Dynamics.
Frontiers in Molecular Biosciences 9, 878830 (2022) doi: 10.3389/fmolb.2022.878830

Matsubara D, Kasahara K, Dokainish HM, et al.
Modified Protein-Water Interactions in CHARMM36m for Thermodynamics and Kinetics of Proteins in Dilute and Crowded Solutions.
Molecules 27(17), 5726 (2022) doi: 10.3390/molecules27175726

Oshima H, Sugita Y.
Modified Hamiltonian in FEP Calculations for Reducing the Computational Cost of Electrostatic Interactions
Journal of Chemical Information and Modeling 62(11), 2846-2856 (2022) doi: 10.1021/acs.jcim.1c01532

Fujiyama K, Kato N, Re S, et al.
Molecular Basis for Two Stereoselective Diels-Alderases that Produce Decalin Skeletons*.
Angewandte Chemie 60(41), 22401-22410 (2021) doi: 10.1002/anie.202106186

Kasahara K, Re S, Nawrocki G, et al.
Reduced efficacy of a Src kinase inhibitor in crowded protein solution.
Nature Communications 12(1), 4099 (2021) doi: 10.1038/s41467-021-24349-5

Shinobu A, Kobayashi C, Matsunaga Y, Sugita Y.
Coarse-Grained Modeling of Multiple Pathways in Conformational Transitions of Multi-Domain Proteins.
Journal of Chemical Information and Modeling 61(5), 2427-2443 (2021) doi: 10.1021/acs.jcim.1c00286

Re S, Oshima H, Kasahara K, et al.
Encounter Complexes and Hidden Poses of Kinase-Inhibitor Binding on the Free-Energy Landscape.
Proceedings of the National Academy of Sciences of the United States of America 116, 18404-18409 (2019) doi: 10.1073/pnas.1904707116