具有短、长空间作用的类蛋白质杂聚物序列特异性相分离的解析表示和场论模拟
Analytical Formulation and Field-Theoretic Simulation of Sequence-Specific Phase Separation of Proteinlike Heteropolymers with Short- and Long-Spatial-Range Interactions
摘要：
通过扩展具有长程库仑作用的杂聚物的无规相近似（RPA）和场论模拟（FTS），将氨基酸残基间短程疏水作用的基本效应考虑在内，建立了生物分子凝聚体研究中内在无序蛋白（IDPs）的序列相关液液相分离（LLPS）理论.为此，短程效应的Yukawa相互作用来自成对残基-残基接触能的本征值分解的多个非静电荷。链排除体积由不可压缩性约束提供。平均场近似导致一个有效的弗洛里$χ$参数，它与RPA，占接触相互作用的影响氨基酸组合物和序列模式的影响，远程静电在IDP LLPS，而FTS的基础上制定提供了完整的序列依赖性的短期和长期的相互作用。这里通过在几种不同的氨基酸相互作用方案以及一组共享相同组成的不同模型疏水-极性序列的背景下应用于天然IDP变体来说明这种通用方法。粗粒度显链分子动力学模拟验证了该方法的有效性。
英文摘要：
A theory for sequence dependent liquid-liquid phase separation (LLPS) of intrinsically disordered proteins (IDPs) in the study of biomolecular condensates is formulated by extending the random phase approximation (RPA) and field-theoretic simulation (FTS) of heteropolymers with spatially long-range Coulomb interactions to include the fundamental effects of short-range, hydrophobic-like interactions between amino acid residues. To this end, short-range effects are modeled by Yukawa interactions between multiple nonelectrostatic charges derived from an eigenvalue decomposition of pairwise residue-residue contact energies. Chain excluded volume is afforded by incompressibility constraints. A mean-field approximation leads to an effective Flory $χ$ parameter, which, in conjunction with RPA, accounts for the contact-interaction effects of amino acid composition and the sequence-pattern effects of long-range electrostatics in IDP LLPS, whereas FTS based on the formulation provides full sequence dependence for both short- and long-range interactions. This general approach is illustrated here by applications to variants of a natural IDP in the context of several different amino-acid interaction schemes as well as a set of different model hydrophobic-polar sequences sharing the same composition. Effectiveness of the methodology is verified by coarse-grained explicit-chain molecular dynamics simulations.
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