In-Cell Protein-Protein Contacts: Transient Interactions in the Crowd

Meredith M. Rickard, Yi Zhang, Martin Gruebele, Taras V. Pogorelov

Research output: Contribution to journalArticlepeer-review


Proteins in vivo are immersed in a crowded environment of water, ions, metabolites, and macromolecules. In-cell experiments highlight how transient weak protein-protein interactions promote (via functional "quinary structure") or hinder (via competitive binding or "sticking") complex formation. Computational models of the cytoplasm are expensive. We tackle this challenge with an all-atom model of a small volume of the E. coli cytoplasm to simulate protein-protein contacts up to the 5 μs time scale on the special-purpose supercomputer Anton 2. We use three CHARMM-derived force fields: C22*, C36m, and C36mCU (with CUFIX corrections). We find that both C36m and C36mCU form smaller contact surfaces than C22*. Although CUFIX was developed to reduce protein-protein sticking, larger contacts are observed with C36mCU than C36m. We show that the lifespan Δt of protein-protein contacts obeys a power law distribution between 0.03 and 3 μs, with ∼90% of all contacts lasting <1 μs (similar to the time scale for downhill folding).

Original languageEnglish (US)
Pages (from-to)5667-5673
Number of pages7
JournalJournal of Physical Chemistry Letters
Issue number18
StatePublished - Sep 19 2019

ASJC Scopus subject areas

  • General Materials Science
  • Physical and Theoretical Chemistry


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