Thomas Young Centre and Department of Chemical Engineering, University College London, London WC1E 7JE, U.K.
Université de Montpellier, Centre de Biologie Structurale (CBS), CNRS, INSERM, 34090 Montpellier, France.
J Phys Chem Lett. 2023 Feb 23;14(7):1748-1755. doi: 10.1021/acs.jpclett.2c03512. Epub 2023 Feb 9.
The nucleation of protein condensates is a concentration-driven process of assembly. When modeled in the canonical ensemble, condensation is affected by finite-size effects. Here, we present a general and efficient route for obtaining ensemble properties of protein condensates in the macroscopic limit from finite-sized nucleation simulations. The approach is based on a theoretical description of droplet nucleation in the canonical ensemble and enables estimation of thermodynamic and kinetic parameters, such as the macroscopic equilibrium density of the dilute protein phase, the surface tension of the condensates, and nucleation free energy barriers. We apply the method to coarse-grained simulations of NDDX4 and FUS-LC, two phase-separating disordered proteins with different physicochemical characteristics. Our results show that NDDX4 condensate droplets, characterized by lower surface tension, higher solubility, and faster monomer exchange dynamics compared to those of FUS-LC, form with negligible nucleation barriers. In contrast, FUS-LC condensates form via an activated process over a wide range of concentrations.
蛋白质凝聚核的成核是一个浓度驱动的组装过程。在正则系综中模拟时，凝聚受到有限尺寸效应的影响。在这里，我们提出了一种从有限尺寸成核模拟中获得宏观极限下蛋白质凝聚物系综特性的通用且高效的方法。该方法基于在正则系综中液滴成核的理论描述，能够估计热力学和动力学参数，例如稀蛋白质相的宏观平衡密度、凝聚物的表面张力和成核自由能垒。我们将该方法应用于 NDDX4 和 FUS-LC 的粗粒化模拟，这两种相分离的无序蛋白质具有不同的物理化学特性。我们的结果表明，与 FUS-LC 相比，NDDX4 凝聚物液滴具有更低的表面张力、更高的溶解度和更快的单体交换动力学，其成核势垒可以忽略不计。相比之下，FUS-LC 凝聚物通过一个广泛的浓度范围内的激活过程形成。
