| 1. |
Toshifumi Mori, Theoretical study on the role of dynamics during enzyme catalysis, Pure and Applied Chemistry International Conference 2024, 2024.01. |
| 2. |
森 俊文, Theoretical study on the role of protein conformational dynamics during enzyme catalysis, 令和5年度化学系学協会東北大会および日本化学会東北支部80周年記念国際会議(物理化学コロキウム), 2023.09. |
| 3. |
Toshifumi Mori, Bridging the gap between static and dynamic reaction mechanisms in enzyme catalysis, Multi-scale Molecular Dynamics Simulation and Machine Learning of Biomolecular Systems Workshop, 2023.08. |
| 4. |
Toshifumi Mori, Dissecting the heterogeneous dynamics of proteins during folding and catalysis, Telluride Science Research Center Protein Dynamics Workshop 2023, 2023.07. |
| 5. |
Toshifumi Mori, Elucidating the Role of Dynamics During Enzyme Catalysis using Molecular Simulations, 7th International Symposium of Quantum Beam Science at Ibaraki University, 2022.12. |
| 6. |
森 俊文, Role of dynamics in conformational transitions and functions of biomolecules, 日本化学会第102春季大会, 2022.03, Structural fluctuations and conformational transitions of proteins have been realized to be essential for protein functions. Yet, how these dynamic aspects of proteins contribute to functions often remains elusive. We have been working towards understanding how enzymes adapt to different stages of the catalytic cycle by adjusting their conformations, and have been focusing on unveiling the conformational dynamics of enzymes. In this talk, by mainly focusing on the peptidyl-prolyl isomerization reaction catalyzed by Pin1, we discuss the molecular mechanism of catalytic reaction from two perspectives. Molecular dynamics simulations with replica exchange umbrella sampling and transition path sampling methods are applied to reveal the static and dynamic mechanisms of the reaction, respectively. From a static view, enzyme lowers the free energy barrier of isomerization with rearrangements in ligand-enzyme interactions along the reaction coordinate . From the dynamic view, on the contrary, the isomerization occurs in a short timescale, which turns out to be too rapid for the ligand-enzyme interactions to reorganize to equilibrium . These results indicate that the dynamics of the enzyme plays a role prior to the reaction step by preparing a reactive environment, i.e., as conformational excited states. The origin of these slow protein dynamics, which has also been discussed by an NMR experiment , and how it seemingly couples to the enzymatic reaction cycle will also be discussed.. |
