2021 Fiscal Year Annual Research Report
Computational investigation of the role of disordered regions in enzymatic reactions
| Project/Area Number |
20K15737
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Dokainish Hisham 国立研究開発法人理化学研究所, 開拓研究本部, 特別研究員 (20825575)
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Keywords | IDR / Catalysis / MD simaulation / Enhanced Sampling / Chrosimate Mutase |
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| Outline of Annual Research Achievements |
The role of intrinsically disordered region (IDR) in enzymatic reactions was elucidated, using multiscale computational approach. This includes classical and enhanced sampling molecular dynamics (MD) simulations and Quantum mechanical (QM) calculations. MD results show IDR induce large fluctuation in an engineered Chrosimate Mutase active site, allowing for a necessary substrate reorganization to form reactive complex. QM calculations confirmed the role of IDR in lowering the reaction barrier. The results shed the light on an unrecognized role of structural disorder in enzymatic reactions. Furthermore, new method to enhance domain motion was proposed and applied to study conformational transition in SARS-CoV-2.
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