论文标题
生物分子冷凝物的统计力学通过空腔方法
Statistical mechanics of biomolecular condensates via cavity methods
论文作者
论文摘要
生命系统中相位分离的物理机制可以发挥关键的生理作用,并且最近成为强化研究的重点。这种现象在生物领域中强烈的异质性和无序性质提出了困难的建模挑战,这些挑战需要基于假定自由能景观的平均野外方法。我们在这项工作中采取的替代途径是解决通过空腔方法从微观相互作用开始计算这些系统中分区功能的完整统计力学问题。我们首先在简单的二进制案例上说明了该过程,然后我们将其成功应用于三元系统,在该系统中,幼稚的平均场近似值被证明不足。然后,我们证明了与晶格模型模拟的一致性,以最终将我们的理论与水溶液中核苷酸和聚赖氨酸的缔合脱混混合,将我们的理论与凝聚酸盐形成的实验进行对比。以这种方式,提供了不同类型的证据来支持腔体方法作为生物分子凝结定量建模的理想工具,从而在准确考虑显微动力学空间方面与基于其分析障碍的快速计算结果之间具有最佳的平衡。
Physical mechanisms of phase separation in living systems can play key physiological roles and have recently been the focus of intensive studies. The strongly heterogeneous and disordered nature of such phenomena in the biological domain poses difficult modeling challenges that require going beyond mean field approaches based on postulating a free energy landscape. The alternative pathway we take in this work is to tackle the full statistical mechanics problem of calculating the partition function in these systems, starting from microscopic interactions, by means of cavity methods. We illustrate the procedure first on the simple binary case, and we then apply it successfully to ternary systems, in which the naive mean field approximations are proved inadequate. We then demonstrate the agreement with lattice model simulations, to finally contrast our theory also with experiments of coacervate formation by associative de-mixing of nucleotides and poly-lysine in aqueous solution. In this way, different types of evidence are provided to support cavity methods as ideal tools for quantitative modeling of biomolecular condensation, giving an optimal balance between the accurate consideration of spatial aspects of the microscopic dynamics and the fast computational results rooted in their analytical tractability.