Jussupow Alexander, Bartley Divya, Lapidus Lisa J, Feig Michael
Department of Biochemistry and Molecular Biology, East Lansing, MI 48824, USA.
Department of Physics and Astronomy Michigan State University, East Lansing, MI 48824, USA.
bioRxiv. 2024 Nov 1:2024.10.29.620916. doi: 10.1101/2024.10.29.620916.
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 parameterized 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 multi-scale approaches for modeling biomolecular interactions that span from residue-level to atomistic resolution.
生物分子相互作用在许多生物过程中至关重要，包括复合物形成和相分离过程。粗粒度计算模型对于通过模拟研究此类过程特别有价值。在此，我们展示了COCOMO2，这是一种更新的基于残基的粗粒度模型，其适用性从内在无序肽扩展到折叠蛋白。这是通过引入表面暴露缩放因子来实现的，该因子根据溶剂可及性调整相互作用强度，从而能够在不增加计算成本的情况下更逼真地模拟涉及折叠结构域的相互作用。COCOMO2直接根据溶解度和相分离数据进行参数化，以提高其在预测更广泛生物分子系统的浓度依赖性相分离方面的性能，与原始版本相比。COCOMO2实现了新的应用，包括研究涉及内在无序蛋白与折叠结构域的凝聚物以及复杂组装过程的研究。COCOMO2还为开发从残基水平到原子分辨率的生物分子相互作用多尺度建模方法提供了扩展基础。
