Protein–Ligand Dissociation Rate Constant from All-Atom Simulation

Ekaterina Maximova, Eugene B. Postnikov, Anastasia I. Lavrova, Vladimir Farafonov, Dmitry Nerukh

Research output: Contribution to journalArticlepeer-review


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, in which a random artificial force applied to the ligand facilitates its dissociation. We have suggested a novel approach to extrapolate such obtained dissociation times to the zero-force limit assuming never before attempted universal exponential dependence of the bond strength on the applied force, allowing direct comparison with experimentally measured values. We have found that our calculated dissociation time was equal to 36.1 s with statistically significant values distributed in the interval of 0.2–72.0 s, which quantitatively matches the experimental value of 50 ± 8 s despite the extrapolation over 9 orders of magnitude in time.
Original languageEnglish
Pages (from-to)10631–10636
Number of pages6
JournalJournal of Physical Chemistry Letters
Issue number43
Early online date27 Oct 2021
Publication statusPublished - 4 Nov 2021

Bibliographical note

Funding Information:
We acknowledge the use of Athena at HPC Midlands+, which was funded by the EPSRC on Grant EP/P020232/1, in this research, as part of the HPC Midlands+ consortium. V.F. expresses his gratitude to the Ministry of Education and Science of Ukraine for financial support in the project “Molecular docking for express identification of new potential drugs” (0119U002550). The collaboration was supported by the program H2020-MSCA-RISE-2018, project AMR-TB, Grant ID: 823922.


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