TY - JOUR
T1 - In-Cell Protein-Protein Contacts
T2 - Transient Interactions in the Crowd
AU - Rickard, Meredith M.
AU - Zhang, Yi
AU - Gruebele, Martin
AU - Pogorelov, Taras V.
N1 - Funding Information:
Anton 2 computer time was provided by the Pittsburgh Supercomputing Center (PSC) through Grant R01GM116961 from the National Institutes of Health. The Anton 2 machine at PSC was generously made available by D. E. Shaw Research. T.V.P. acknowledges support from the Department of Chemistry, University of Illinois at Urbana–Champaign. M.R., and M.G. were supported by NSF Grant MCB 1803786. We thank Prof. James Imlay for helpful discussions during model construction and Dr. Christopher Maffeo for assistance with Brownian dynamics.
Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/9/19
Y1 - 2019/9/19
N2 - 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).
AB - 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).
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U2 - 10.1021/acs.jpclett.9b01556
DO - 10.1021/acs.jpclett.9b01556
M3 - Article
C2 - 31483661
AN - SCOPUS:85072508773
VL - 10
SP - 5667
EP - 5673
JO - Journal of Physical Chemistry Letters
JF - Journal of Physical Chemistry Letters
SN - 1948-7185
IS - 18
ER -