Kim Seowon, Lee Nam-Kyung, Jung Youngkyun, Johner Albert
Department of Physics and Astronomy, Sejong University, Seoul 05006, Republic of Korea.
Supercomputing Center, Korea Institute of Science and Technology Information, Daejeon 34141, Republic of Korea.
Polymers (Basel). 2024 Oct 18;16(20):2928. doi: 10.3390/polym16202928.
Polyampholytes (PAs) exhibit complex behaviors in various environments influenced by their charge distribution. This study focuses on the kinetics of dimerization of PAs, aiming to elucidate the underlying mechanisms and clarify relevant characteristics of the charge sequence. We focus on PAs with non-zero net charges, employing molecular dynamics simulations and theoretical analyses to examine how charge sequences influence the rates of dimer formation and dissociation. Our findings reveal that the charge sequence of tails and the blockiness of the minority charge group markedly influence the kinetics of dimerization: large blockiness and tails with a high number of majority-type charges slow down the dissociation of dimers. Additionally, the presence of an extended (central) block of the majority charge promotes structural diversity. Within dimer states, blocks alternate between intra- and inter-chain contacts. The duration times in the dimer states are significantly longer than the typical dwell times of block inter-contacts, with a notable extension when multiple blocks are engaged. Intrinsically disordered proteins (IDPs) play crucial roles in cellular functions, primarily due to their ability to undergo rapid conformational changes and form transient complexes. These properties largely depend on the sequence of charged residues. We provide insights into the fundamental principles governing the structural and dynamical properties of polyampholytic IDP, emphasizing the importance of sequence-specific effects on both aggregation and dissociation.
聚两性电解质（PAs）在受其电荷分布影响的各种环境中表现出复杂行为。本研究聚焦于PAs的二聚化动力学，旨在阐明其潜在机制并厘清电荷序列的相关特征。我们关注净电荷不为零的PAs，采用分子动力学模拟和理论分析来研究电荷序列如何影响二聚体形成和解离的速率。我们的研究结果表明，尾部的电荷序列和少数电荷基团的块状性显著影响二聚化动力学：高度的块状性以及带有大量多数型电荷的尾部会减缓二聚体的解离。此外，多数电荷的延伸（中心）块的存在促进了结构多样性。在二聚体状态下，块在链内和链间接触之间交替。二聚体状态下的持续时间明显长于块间接触的典型停留时间，当多个块参与时会有显著延长。内在无序蛋白（IDPs）在细胞功能中起着关键作用，主要是因为它们能够经历快速的构象变化并形成瞬时复合物。这些特性在很大程度上取决于带电残基的序列。我们深入探讨了控制聚两性电解质IDP结构和动力学性质的基本原理，强调了序列特异性效应在聚集和解离方面的重要性。
