School of Physics, University College Dublin, Belfield, Dublin 4, Ireland.
Institute for Discovery, University College Dublin, Belfield, Dublin 4, Ireland.
J Phys Chem B. 2021 May 27;125(20):5233-5242. doi: 10.1021/acs.jpcb.1c01939. Epub 2021 May 14.
The self-assembling propensity of amyloid peptides such as diphenylalanine (FF) allows them to form ordered, nanoscale structures, with biocompatible properties important for biomedical applications. Moreover, piezoelectric properties allow FF molecules and their aggregates (e.g., FF nanotubes) to be aligned in a controlled way by the application of external electric fields. However, while the behavior of FF nanostructures emerges from the biophysical properties of the monomers, the detailed responses of individual peptides to both temperature and electric fields are not fully understood. Here, we study the temperature-dependent conformational dynamics of FF peptides solvated in explicit water molecules, an environment relevant to biomedical applications, by using an enhanced sampling method, replica exchange molecular dynamics (REMD), in conjunction with applied electric fields. Our simulations highlight and overcome possible artifacts that may occur during the setup of REMD simulations of explicitly solvated peptides in the presence of external electric fields, a problem particularly important in the case of short peptides such as FF. The presence of the external fields could overstabilize certain conformational states in one or more REMD replicas, leading to distortions of the underlying potential energy distributions observed at each temperature. This can be overcome by correcting the REMD initial conditions to include the lower-energy conformations induced by the external field. We show that the converged REMD data can be analyzed using a Markovian description of conformational states and show that a rather complex, 3-state, temperature-dependent conformational dynamics in the absence of electric fields collapses to only one of these states in the presence of the electric fields. These details on the temperature- and electric-field-dependent thermodynamic and kinetic properties of small FF amyloid peptides can be useful in understanding and devising new methods to control their aggregation-prone biophysical properties and, possibly, the structural and biophysical properties of FF molecular nanostructures.
具有二苯丙氨酸（FF）等自组装倾向的淀粉样肽能够形成有序的纳米结构，具有生物相容性，这对于生物医学应用很重要。此外，压电特性使得 FF 分子及其聚集体（例如 FF 纳米管）能够在外电场的作用下以受控的方式排列。然而，尽管 FF 纳米结构的行为源自单体的生物物理特性，但单个肽对温度和电场的详细响应尚未完全了解。在这里，我们通过使用增强采样方法， replica exchange 分子动力学（REMD），并结合外加电场，研究了在明确溶剂水分子环境中 FF 肽的温度依赖性构象动力学。我们的模拟突出并克服了在存在外加电场的情况下，对明确溶剂化肽的 REMD 模拟进行设置时可能出现的人为因素，对于 FF 等短肽，这是一个特别重要的问题。外部场的存在可能会使一个或多个 REMD 副本中的某些构象状态过度稳定，从而导致在每个温度下观察到的潜在能量分布发生扭曲。通过修正 REMD 的初始条件以包含外部场诱导的较低能量构象，可以克服此问题。我们表明，可以使用构象状态的马尔可夫描述来分析收敛的 REMD 数据，并表明在不存在电场的情况下，相当复杂的、与温度相关的 3 态构象动力学在存在电场的情况下会坍缩为这些状态之一。这些关于小 FF 淀粉样肽的温度和电场依赖性热力学和动力学特性的详细信息对于理解和设计控制其易于聚集的生物物理特性的新方法可能有用，并且可能对 FF 分子纳米结构的结构和生物物理特性有用。
