标题： 液滴生长，奥斯特瓦尔德规则，以及融合在肌动蛋白中的秩序出现 显示英文标题

标题： Droplet growth, Ostwald's rule, and emergence of order in Fused in Sarcoma

摘要： FUS-LC（由214个残基组成）的低复杂度区域发生相分离，形成致密的液态相，该相早期形成并缓慢成熟，在长时间尺度上达到有序的凝胶状状态。 成熟后，核心-1（由N端的57个残基（39-95）组成）变得结构化，导致非多态性纤维的形成。 截短的FUS-LC-C（残基110-214）构建体形成一种纤维，其中核心-2（残基112-150）采用$\beta$-片层结构。 使用FUS-LC的粗粒度单体SOP-IDP模型模拟，我们预测C端（核心-3）的残基155-190迅速形成，随后是核心-2，最后是核心-1。 核心的形成时间尺度及其稳定性呈反比关系，这符合奥斯特瓦尔德阶段规则的预期。 无偏见的多链模拟显示，两相中的化学势相等，计算出的致密相和稀释相的密度与实验结果一致。 通过成核机制形成的致密相，随着时间推移通过类似于奥斯特瓦尔德熟化的过程粗化。 AlphaFold对核心-3结构的预测和模拟显示，$\beta$-链在液滴形成早期出现在核心-3区域，并驱动FUS-LC组装的启动。 这里介绍的技术是通用的，可以用于研究其他IDPs（如TDP-43）的组装，因为TDP-43与FUS-LC有许多相似之处。 显示英文摘要

摘要： The low complexity domain of Fused in Sarcoma (FUS-LC consisting of 214 residues) undergoes phase separation, resulting in a dense liquid-like phase that forms early and slowly matures to reach ordered gel-like state on long time scales. Upon maturation, core-1, comprising of the 57 residues (39-95) in the N-terminus become structured, resulting in the formation of a non-polymorphic fibril. The truncated FUS-LC-C (residues 110-214) construct forms a fibril in which core-2 (residues 112-150) adopts a $\beta$-sheet structure. Using coarse-grained monomer SOP-IDP model simulations of FUS-LC, we predict that residues 155-190 in the C-terminal (core-3) form rapidly, followed by core-2, and finally core-1. The time scale of formation of the cores and their stabilities are inversely correlated, as anticipated by the Ostwald's rule of stages. Unbiased multichain simulations show that the chemical potentials in the two phases are equal and the calculated densities of the dense and dilute phases are in agreement with experiments. The dense phase, which forms by a nucleation mechanism, coarsens over time by a process that is reminiscent of Ostwald ripening. AlphaFold predictions of the core-3 structure and the simulations show that $\beta$-strand emerges in the core-3 region early during the droplet formation, and drives the initiation of FUS-LC assembly. The techniques introduced here are general and could be used to probe assembly of other IDPs such as TDP-43, which shares many features with FUS-LC.