Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India.
PLoS Comput Biol. 2022 May 9;18(5):e1010067. doi: 10.1371/journal.pcbi.1010067. eCollection 2022 May.
Phase separation of biomolecules could be mediated by both specific and non-specific interactions. How the interplay between non-specific and specific interactions along with polymer entropy influences phase separation is an open question. We address this question by simulating self-associating molecules as polymer chains with a short core stretch that forms the specifically interacting functional interface and longer non-core regions that participate in non-specific/promiscuous interactions. Our results show that the interplay of specific (strength, ϵsp) and non-specific interactions (strength, ϵns) could result in phase separation of polymers and its transition to solid-like aggregates (mature state). In the absence of ϵns, the polymer chains do not dwell long enough in the vicinity of each other to undergo phase separation and transition into a mature state. On the other hand, in the limit of strong ϵns, the assemblies cannot transition into the mature state and form a non-specific assembly, suggesting an optimal range of interactions favoring mature multimers. In the scenario where only a fraction (Nfrac) of the non-core regions participate in attractive interactions, we find that slight modifications to either ϵns or Nfrac can result in dramatically altered self-assembled states. Using a combination of heterogeneous and homogeneous mix of polymers, we establish how this interplay between interaction energies dictates the propensity of biomolecules to find the correct binding partner at dilute concentrations in crowded environments.
生物分子的相分离可以由特异性和非特异性相互作用介导。非特异性和特异性相互作用以及聚合物熵的相互作用如何影响相分离是一个悬而未决的问题。我们通过模拟自缔合分子作为聚合物链来解决这个问题，其中短的核心延伸形成特异性相互作用的功能界面，而较长的非核心区域参与非特异性/混杂相互作用。我们的结果表明，特异性（强度，ϵsp）和非特异性相互作用（强度，ϵns）的相互作用可能导致聚合物的相分离及其向类似固体的聚集体（成熟状态）的转变。在没有ϵns的情况下，聚合物链不会在彼此附近停留足够长的时间以经历相分离并转变为成熟状态。另一方面，在强ϵns的极限下，组装体不能转变为成熟状态并形成非特异性组装体，这表明相互作用的最佳范围有利于成熟的多聚体。在只有一部分（Nfrac）非核心区域参与吸引力相互作用的情况下，我们发现 ϵns 或 Nfrac 的微小变化都可能导致自组装状态的显著改变。通过使用异质和同质聚合物的组合，我们确定了这种相互作用能量之间的相互作用如何决定生物分子在拥挤环境中在稀浓度下找到正确结合伴侣的倾向。
