Protein-ligand dissociation rate constant from all-atom simulation

Ekaterina Maximova, Eugene Postnikov, Anastasia Lavrova, Vladimir Farafonov, Dmitry Nerukh

Research output: Preprint or Working paperPreprint


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.
Original languageEnglish
Publication statusPublished - 26 Aug 2021

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© 2021 The Authors. This work is licensed under a CC BY 4.0 License.


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