Computational investigation of the role of disordered regions in enzymatic reactions

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K15737
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43020:Structural biochemistry-related
• Research Institution: Institute of Physical and Chemical Research
• 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)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: IDR / Protein dynamics / enhanced sampling

Outline of Final 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 that IDR induces 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.

Free Research Field

Computational Biochemistry

Academic Significance and Societal Importance of the Research Achievements

Enzymes are the best catalysts that accelerate chemical reactions. This project clarify the role of disorder and propose a computational approach to study disorder-function paradigm in Enzymes. A new method was also proposed and applied to study structure changes in Spike protein of SARS-CoV-2