Vila-Viçosa Diogo, Reis Pedro B P S, Baptista António M, Oostenbrink Chris, Machuqueiro Miguel
Centro de Química e Bioquímica, Departamento de Química e Bioquímica , Faculdade de Ciências, Universidade de Lisboa , 1749-016 Lisboa , Portugal.
University of Lisboa , Faculty of Sciences, BioISI - Biosystems & Integrative Sciences Institute , Lisboa , Portugal.
J Chem Theory Comput. 2019 May 14;15(5):3108-3116. doi: 10.1021/acs.jctc.9b00030. Epub 2019 Apr 3.
Solution pH is a physicochemical property that has a key role in cellular regulation, and its impact at the molecular level is often difficult to study by experimental methods. In this context, several theoretical methods were developed to study pH effects in macromolecules. The stochastic titration constant-pH molecular dynamics method (CpHMD) was developed by coupling molecular sampling methods, which are appropriate to study the conformational ensemble of biomolecules, with continuum electrostatics approaches, which properly describe pH-dependent protonation states. However, in difficult cases, the protonation sampling can be too slow for the commonly accessible computational times. In this work, we combined a pH replica exchange scheme with this CpHMD method and explored several optimization strategies and possible limitations.
溶液pH值是一种在细胞调节中起关键作用的物理化学性质，其在分子水平上的影响通常很难通过实验方法进行研究。在此背景下，人们开发了几种理论方法来研究大分子中的pH效应。随机滴定恒定pH分子动力学方法（CpHMD）是通过将适用于研究生物分子构象系综的分子采样方法与能恰当描述pH依赖质子化状态的连续介质静电学方法相结合而开发的。然而，在困难的情况下，质子化采样对于通常可达到的计算时间来说可能太慢。在这项工作中，我们将pH复制交换方案与这种CpHMD方法相结合，并探索了几种优化策略和可能的局限性。
