Protein-Ligand Dissociation Rate Constant from All-Atom Simulation

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

Результат исследований: Научные публикации в периодических изданияхстатьярецензирование

Аннотация

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.

Язык оригиналаанглийский
Страницы (с-по)10631-10636
Число страниц6
ЖурналJournal of Physical Chemistry Letters
Том12
Номер выпуска43
DOI
СостояниеОпубликовано - 4 ноя 2021

Предметные области Scopus

  • Материаловедение (все)
  • Физическая и теоретическая химия

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