COCOMO2: A Coarse-Grained Model for Interacting Folded and Disordered Proteins

Jussupow, Alexander; Bartley, Divya; Lapidus, Lisa J.; Feig, Michael

doi:10.1021/acs.jctc.4c01460

Title: COCOMO2: A Coarse-Grained Model for Interacting Folded and Disordered Proteins

Journal Article · 05 February 2025 · Journal of Chemical Theory and Computation

DOI: https://doi.org/10.1021/acs.jctc.4c01460 · OSTI ID:2511324

Jussupow, Alexander ^[1]; Bartley, Divya ^[1];

^[1];

^[1]

Michigan State University, East Lansing, MI (United States)

Biomolecular interactions are essential in many biological processes, including complex formation and phase separation processes. Coarse-grained computational models are especially valuable for studying such processes via simulation. Here, we present COCOMO2, an updated residue-based coarse-grained model that extends its applicability from intrinsically disordered peptides to folded proteins. This is accomplished with the introduction of a surface exposure scaling factor, which adjusts interaction strengths based on solvent accessibility, to enable the more realistic modeling of interactions involving folded domains without additional computational costs. COCOMO2 was parametrized directly with solubility and phase separation data to improve its performance on predicting concentration-dependent phase separation for a broader range of biomolecular systems compared to the original version. COCOMO2 enables new applications including the study of condensates that involve IDPs together with folded domains and the study of complex assembly processes. COCOMO2 also provides an expanded foundation for the development of multiscale approaches for modeling biomolecular interactions that span from residue-level to atomistic resolution.

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Research Organization:: Michigan State University, East Lansing, MI (United States)

Sponsoring Organization:: National Institutes of Health (NIGMS); National Science Foundation (NSF); USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: SC0023395

OSTI ID:: 2511324

Journal Information:: Journal of Chemical Theory and Computation, Journal Name: Journal of Chemical Theory and Computation Journal Issue: 4 Vol. 21; ISSN 1549-9618

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Molecular interactions
Molecular mechanics
Monomers
Peptides and proteins
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Title: COCOMO2: A Coarse-Grained Model for Interacting Folded and Disordered Proteins

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