Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
J Phys Chem Lett. 2023 Sep 28;14(38):8460-8469. doi: 10.1021/acs.jpclett.3c01642. Epub 2023 Sep 18.
Biomolecular condensates are essential for cellular functionality, yet the complex interplay among the diverse molecular interactions that mediate their formation remains poorly understood. Here, using coarse-grained molecular dynamics simulations, we address the contribution of cation-π interactions to the stability of condensates formed via liquid-liquid phase separation. We found greater stabilization of up to 80% via cation-π interactions in condensates formed from peptides with higher aromatic residue content or less charge clustering. The contribution of cation-π interactions to droplet stability increases with increasing ionic strength, suggesting a trade-off between cation-π and electrostatic interactions. Cation-π interactions, therefore, can compensate for reduced electrostatic interactions, such as occurs at higher salt concentrations and in sequences with less charged residue content or clustering. Designing condensates with desired biophysical characteristics therefore requires quantification not only of the individual interactions but also cross-talks involving charge-charge, π-π, and cation-π interactions.
生物分子凝聚物对于细胞功能至关重要，但介导其形成的各种分子相互作用之间的复杂相互作用仍知之甚少。在这里，我们使用粗粒度分子动力学模拟，研究了阳离子-π 相互作用对通过液-液相分离形成的凝聚物稳定性的贡献。我们发现，在由芳香族残基含量较高或电荷聚集较少的肽形成的凝聚物中，阳离子-π 相互作用的稳定性最大可提高 80%。阳离子-π 相互作用对液滴稳定性的贡献随离子强度的增加而增加，这表明阳离子-π 和静电相互作用之间存在权衡。因此，阳离子-π 相互作用可以补偿静电相互作用的减少，例如在较高盐浓度下以及在电荷残基含量或聚集较少的序列中。因此，设计具有所需生物物理特性的凝聚物不仅需要定量分析单个相互作用，还需要定量分析涉及电荷-电荷、π-π 和阳离子-π 相互作用的交叉对话。
