Metastable States in the Hinge-Bending Landscape of an Enzyme in an Atomistic Cytoplasm Simulation

Premila P. Samuel Russell, Andrew K. Maytin, Meredith M. Rickard, Matthew C. Russell, Taras V. Pogorelov, Martin Gruebele

Research output: Contribution to journalArticlepeer-review


Many enzymes undergo major conformational changes to function in cells, particularly when they bind to more than one substrate. We quantify the large-amplitude hinge-bending landscape of human phosphoglycerate kinase (PGK) in a human cytoplasm. Approximately 70 μs of all-atom simulations, upon coarse graining, reveal three metastable states of PGK with different hinge angle distributions and additional substates. The “open” state was more populated than the “semi-open” or “closed” states. In addition to free energies and barriers within the landscape, we characterized the average transition state passage time of ≈0.3 μs and reversible substrate and product binding. Human PGK in a dilute solution simulation shows a transition directly from the open to closed states, in agreement with previous SAXS experiments, suggesting that the cell-like model environment promotes stability of the human PGK semi-open state. Yeast PGK also sampled three metastable states within the cytoplasm model, with the closed state favored in our simulation.

Original languageEnglish (US)
Pages (from-to)940-946
Number of pages7
JournalJournal of Physical Chemistry Letters
Issue number4
StatePublished - Feb 1 2024

ASJC Scopus subject areas

  • General Materials Science
  • Physical and Theoretical Chemistry


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