RIKEN Center for Computational Science Computational Biophysics Research Team

Team Leader: Yuji Sugita (D.Sc.)

Japanese Page

Research Summary

We perform molecular dynamics (MD) simulations to elucidate the structure, dynamics and function of biological macromolecules in various intracellular environments. Unlike dilute solutions, the cytoplasm is a crowded environment with huge number of proteins, nucleic acids and metabolites. Biological membranes also contain various lipid molecules, cholesterol and membrane proteins, and act as a platform for many biological phenomena. In order to understand biomolecular dynamics in such environments, we have developed multi-scale MD simulations using coarse-grained models, all-atom models, and QM/MM models We have developed GENESIS software for multi-scale MD simulations with enhanced sampling methods, free energy calculations, and data-driven molecular dynamics. Large-scale simulations are performed using the Fugaku supercomputer and other systems to study molecular dynamics in the intracellular environments.

Main Research Fields

Chemistry

Related Research Fields

Complex Systems
Mathematical & Physical Sciences
Biological Sciences

Keywords

Molecular Dynamics
Protein Dynamics
Free Energy Calculation
Machine Learning
Parallelization

Selected Publications

1.Jung J., Tan C., and Sugita Y.:
"GENESIS CGDYN: large-scale coarse-grained MD simulation with dynamic load balancing for heterogeneous biomolecular systems"
Nature Comm. 15, 3370 (2024).
2.Jung J., Yagi K., Tan C., Oshima H., Mori T., Yu I., Matsunaga Y., Kobayashi C., Ito S., Ugarte La Torre D., and Sugita Y.:
"GENESIS 2.1: High-Performance Molecular Dynamics Software for Enhanced Sampling and Free-Energy Calculations for Atomistic, Coarse-Grained, and QM/MM models"
J. Phys. Chem. B 128, 6028-6048 (2024).
3.Ugarte La Torre D., Takada S., and Sugita, Y.:
"Extension of the iSoLF implicit-solvent coarse-grained model for multicomponent lipid bilayers"
J. Chem. Phys. 159, 075101 (2023).
4.Jung J., Kobayashi C., and Sugita Y.:
"Acceleration of generalized replica exchange with solute tempering simulations of large biological systems on massively parallel supercomputer"
J. Comp. Chem, 44, 1740-1749 (2023).
5.Mizutani A., Tan C., Sugita Y., and Takada S.:
"Micelle-like clusters in phase-separated Nanog condensates: A molecular simulation study"
PLoS Comp. Biol. 19, e1011321 (2023).
6.Matsunaga Y., Kamiya M., Oshima H., Jung J., Ito S., and Sugita Y.:
"Use of multistate Bennett acceptance ratio method for free-energy calculations from enhanced sampling and free-energy perturbation"
Biophys. Rev.14, 1-10 (2022).
7.Zhang Y., Kobayashi C., Cai X., Watanabe S., Tsutsumi A., Kikkawa M., Sugita Y., and Inaba K.:
"Multiple sub state structures of SERCA2b reveal conformational overlap at transition steps during the catalytic cycle"
Cell reports 41, 111760 (2022).
8.Kobayashi C., Matsunaga Y., Jung J., and Sugita Y.:
"Structural and energetic analysis of metastable intermediate states in the E1P–E2P transition of Ca2+-ATPase"
Proc. Natl. Acad. Sci. USA, 118, e2105507118 (2021).
9.Jung J., Kasahara K., Kobayashi C., Oshima H., Mori T., and Sugita Y.:
"Optimized Hydrogen Mass Repartitioning Scheme Combined with Accurate Temperature/Pressure Evaluations for Thermodynamic and Kinetic Properties of Biological Systems"
J. Chem. Theory Comput. 17, 5312-5321 (2021).
10.Mori T., Jung J., Kobayashi C., Dokainish H.M, Re, Yuji Sugita.:
"Elucidation of Interactions Regulating Conformational Stability and Dynamics of SARS-CoV-2 S-Protein"
Biophys. J. 120, 1060-1071 (2021).