论文标题
蛋白液滴形成的有限尺寸缩放分析
Finite-size scaling analysis of protein droplet formation
论文作者
论文摘要
细胞内部生物分子冷凝物的形成通常涉及本质上无序的蛋白质（IDP），并且其中一些IDP也能够通过液态液相分离自行形成液滴状的密集组件。当模型热力学相变化时，众所周知，有限尺寸的缩放分析可能是有价值的工具。但是，据我们所知，这种方法尚未应用于对依赖序列依赖性生物分子相分离的计算挑战性问题。在这里，我们实施有限尺寸的缩放方法，以研究连续疏水/极性蛋白质模型中两个10珠序列的相行为。结合可逆的显式链蒙特卡洛模拟这些序列，有限尺寸的缩放分析既依赖于渐近较大的系统的理论结果，却是可行的和有益的。尽管这两个序列在低温下形成致密簇，但该分析表明其中只有一个经历液态液相分离。此外，观察到液滴形成的过渡温度被观察到与系统尺寸缓慢收敛，因此即使对于我们最大的系统，过渡也会转移约8％。使用有限尺寸的缩放分析，可以估算和校正此转移。
The formation of biomolecular condensates inside cells often involve intrinsically disordered proteins (IDPs), and several of these IDPs are also capable of forming droplet-like dense assemblies on their own, through liquid-liquid phase separation. When modelings thermodynamic phase changes, it is well-known that finite-size scaling analysis can be a valuable tool. However, to our knowledge, this approach has not been applied before to the computationally challenging problem of modeling sequence-dependent biomolecular phase separation. Here, we implement finite-size scaling methods to investigate the phase behavior of two 10-bead sequences in a continuous hydrophobic/polar protein model. Combined with reversible explicit-chain Monte Carlo simulations of these sequences, finite-size scaling analysis turns out to be both feasible and rewarding, despite relying on theoretical results for asymptotically large systems. While both sequences form dense clusters at low temperature, this analysis shows that only one of them undergoes liquid-liquid phase separation. Furthermore, the transition temperature at which droplet formation sets in, is observed to converge slowly with system size, so that even for our largest systems the transition is shifted by about 8%. Using finite-size scaling analysis, this shift can be estimated and corrected for.
