Protein-ligand dissociation rate constant from all-atom simulation


Dissociation of a ligand isoniazid from a protein catalase was investigated using all-atom Molecular Dynamics (MD) simulations. Random Acceleration MD (τ-RAMD) was used where a random artificial force applied to the ligand facilitates its dissociation. We have suggested an approach to extrapolate such obtained dissociation times to the zero-force limit that was never attempted before, thus allowing direct comparison with experimentally measured values. We have found that our calculated dissociation time was equal to 36.1 seconds with statistically significant values distributed in the interval 0.2-72.0 s, that quantitatively matches the experimental value of 50 ± 8 seconds despite the extrapolation over nine orders of magnitude in time.

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Divisions: College of Engineering & Physical Sciences > Aston Institute of Urban Technology and the Environment (ASTUTE)
College of Engineering & Physical Sciences > Systems analytics research institute (SARI)
College of Engineering & Physical Sciences
Additional Information: © 2021 The Authors. This work is licensed under a CC BY 4.0 License.
Last Modified: 27 Dec 2023 10:15
Date Deposited: 27 Sep 2021 13:16
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Related URLs: https://www.res ... le/rs-816562/v1 (Publisher URL)
PURE Output Type: ["eprint_fieldname_pure_output_type_workingpaper/preprint" not defined]
Published Date: 2021-08-26
Authors: Maximova, Ekaterina
Postnikov, Eugene
Lavrova, Anastasia
Farafonov, Vladimir
Nerukh, Dmitry (ORCID Profile 0000-0001-9005-9919)



Version: Published Version

License: Creative Commons Attribution

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