论文标题

分析理论应用于依赖于本质无序蛋白的序列相位分离的数值技术

Numerical Techniques for Applications of Analytical Theories to Sequence-Dependent Phase Separations of Intrinsically Disordered Proteins

论文作者

Lin, Yi-Hsuan, Wessén, Jonas, Pal, Tanmoy, Das, Suman, Chan, Hue Sun

论文摘要

现在通过液态液相分离(LLP)在很大程度上基础的生物分子冷凝物现在被大量的实验研究广泛认可,它们具有基本的生物学,生物医学和生物物理重要性。面对实验发现,在最近对LLP在这些冷凝物组装和解离的作用的理论研究中,分析制剂成为了强大而可触及的工具。相关的LLP通常涉及,尽管不仅涉及本质上无序的蛋白质参与由其氨基酸序列控制的多价相互作用的蛋白质。对于有兴趣应用这些理论方法的研究人员,在这里,我们为设计用于从分析公式中提取序列依赖的LLP属性的一组计算技术提供了实用指南。所涵盖的数值程序包括基于聚合物理论中随机相位近似的示例,使用复杂的LangeVIN Dynamics的多链异聚体系统对多个组分型LLP的TIE LING的构建,用于确定一般自由能函数的旋缺链和二极管相边界的示例。由于更准确的物理图片通常需要将分析理论与显式链模型预测进行比较,因此还简要概述了一种通常用于序列特异性LLP的粗粒分子动力学模拟的方法。

Biomolecular condensates, physically underpinned to a significant extent by liquid-liquid phase separation (LLPS), are now widely recognized by numerous experimental studies to be of fundamental biological, biomedical, and biophysical importance. In the face of experimental discoveries, analytical formulations emerged as a powerful yet tractable tool in recent theoretical investigations of the role of LLPS in the assembly and dissociation of these condensates. The pertinent LLPS often involves, though not exclusively, intrinsically disordered proteins engaging in multivalent interactions that are governed by their amino acid sequences. For researchers interested in applying these theoretical methods, here we provide a practical guide to a set of computational techniques devised for extracting sequence-dependent LLPS properties from analytical formulations. The numerical procedures covered include those for the determinination of spinodal and binodal phase boundaries from a general free energy function with examples based on the random phase approximation in polymer theory, construction of tie lines for multiple-component LLPS, and field-theoretic simulation of multiple-chain heteropolymeric systems using complex Langevin dynamics. Since a more accurate physical picture often requires comparing analytical theory against explicit-chain model predictions, a commonly utilized methodology for coarse-grained molecular dynamics simulations of sequence-specific LLPS is also briefly outlined.

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