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

Jussupow, Alexander [Michigan State University, East Lansing, MI (United States)]; Bartley, Divya [Michigan State University, East Lansing, MI (United States)]; Lapidus, Lisa J. [Michigan State University, East Lansing, MI (United States)] (ORCID:0000000331362680); Feig, Michael [Michigan State University, East Lansing, MI (United States)] (ORCID:0000000193806422)

doi:10.1021/acs.jctc.4c01460

DOE OSTI · 2511324

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

Jussupow, Alexander [Michigan State University, East Lansing, MI (United States)]·Bartley, Divya [Michigan State University, East Lansing, MI (United States)]·Lapidus, Lisa J. [Michigan State University, East Lansing, MI (United States)] (ORCID:0000000331362680)·Feig, Michael [Michigan State University, East Lansing, MI (United States)] (ORCID:0000000193806422)

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Abstract

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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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY Molecular interactions Molecular mechanics Monomers Peptides and proteins Phase separation

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Jussupow, Alexander [Michigan State University, East Lansing, MI (United States)], Bartley, Divya [Michigan State University, East Lansing, MI (United States)], Lapidus, Lisa J. [Michigan State University, East Lansing, MI (United States)] (ORCID:0000000331362680), Feig, Michael [Michigan State University, East Lansing, MI (United States)] (ORCID:0000000193806422). 2025-02-05. COCOMO2: A Coarse-Grained Model for Interacting Folded and Disordered Proteins. https://doi.org/10.1021/acs.jctc.4c01460

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