Department of Chemical and Biomolecular Engineering, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States.
Center of Computation and Theory of Soft Materials, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States.
J Phys Chem B. 2023 Sep 28;127(38):8176-8184. doi: 10.1021/acs.jpcb.3c05598. Epub 2023 Sep 18.
Electrostatic interactions contribute critically to the kinetic pathways and thermodynamic outcomes of peptide self-assembly involving one or more than one charged amino acids. While it is well understood in protein folding that those amino acids with acidic/basic side chains could shift their ps when placed in a hydrophobic microenvironment, to what extent aggregation of monomeric peptide units from the bulk solution could alter their charged status and how this change in p values would reciprocally impact their assembly outcomes. Here, we design and analyze two solution systems containing peptide amphiphiles with hydrocarbon chains of different lengths to determine the factor of deprotonation on assembly. Our results suggest that models of supramolecular nanofibers with uniformly distributed, fully charged amino acids are oversimplified. We demonstrate, with molecular dynamics simulations, and validate with experimental results that asymmetric, different protonation states of the peptides lead to distinct nanostructures after self-assembly. The results give estimates on the electrostatic interactions in peptide amphiphiles required for their self-assembly and shed light on modeling molecular assembly systems containing charged amino acids.
静电相互作用对涉及一个或多个带电氨基酸的肽自组装的动力学途径和热力学结果起着至关重要的作用。虽然在蛋白质折叠中已经很好地理解了那些具有酸性/碱性侧链的氨基酸在置于疏水环境时可以改变它们的 p 值，但单体肽单元从本体溶液中聚集到何种程度会改变它们的带电状态，以及这种 p 值的变化将如何反过来影响它们的组装结果。在这里，我们设计和分析了两个含有不同长度烃链的肽两亲物的溶液体系，以确定组装过程中的去质子化因素。我们的结果表明，具有均匀分布的、完全带电的氨基酸的超分子纳米纤维模型过于简单化。我们通过分子动力学模拟进行了演示，并通过实验结果进行了验证，表明在自组装后，肽的不对称、不同的质子化状态会导致不同的纳米结构。这些结果对肽两亲物自组装所需的静电相互作用进行了估计，并为含有带电氨基酸的分子组装系统的建模提供了启示。
