期刊
PROTEIN SCIENCE
卷 30, 期 7, 页码 1371-1379出版社
WILEY
DOI: 10.1002/pro.4094
关键词
coarse‐ grained model; hydropathy scales; liquid‐ liquid phase separation; molecular simulation; physics‐ based model
资金
- Division of Materials Research [2004796]
- National Institute of General Medical Sciences [R01GM136917, R01NS116176]
- National Science Foundation [TG-MCB-120014]
- U.S. Naval Research Laboratory
- Office of Naval Research
- Division Of Materials Research
- Direct For Mathematical & Physical Scien [2004796] Funding Source: National Science Foundation
The study presents improvements to the hydropathy scale model for simulating sequence-specific behavior of intrinsically disordered proteins, including liquid-liquid phase separation. By using the Urry hydropathy scale and introducing new model parameters, accurate simulations of protein LLPS can be achieved.
We present improvements to the hydropathy scale (HPS) coarse-grained (CG) model for simulating sequence-specific behavior of intrinsically disordered proteins (IDPs), including their liquid-liquid phase separation (LLPS). The previous model based on an atomistic hydropathy scale by Kapcha and Rossky (KR scale) is not able to capture some well-known LLPS trends such as reduced phase separation propensity upon mutations (R-to-K and Y-to-F). Here, we propose to use the Urry hydropathy scale instead, which was derived from the inverse temperature transitions in a model polypeptide with guest residues X. We introduce two free parameters to shift (Delta) and scale (mu) the overall interaction strengths for the new model (HPS-Urry) and use the experimental radius of gyration for a diverse group of IDPs to find their optimal values. Interestingly, many possible (Delta, mu) combinations can be used for typical IDPs, but the phase behavior of a low-complexity (LC) sequence FUS is only well described by one of these models, which highlights the need for a careful validation strategy based on multiple proteins. The CG HPS-Urry model should enable accurate simulations of protein LLPS and provide a microscopically detailed view of molecular interactions.
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