Donnini Serena, Tegeler Florian, Groenhof Gerrit, Grubmüller Helmut
Department of Theoretical and Computational Biophysics, Max Planck Institute for Biophysical Chemistry , Göttingen, Germany.
J Chem Theory Comput. 2011 Jun 14;7(6):1962-1978. doi: 10.1021/ct200061r. Epub 2011 Apr 25.
pH is an important parameter in condensed-phase systems, because it determines the protonation state of titratable groups and thus influences the structure, dynamics, and function of molecules in solution. In most force field simulation protocols, however, the protonation state of a system (rather than its pH) is kept fixed and cannot adapt to changes of the local environment. Here, we present a method, implemented within the MD package GROMACS, for constant pH molecular dynamics simulations in explicit solvent that is based on the λ-dynamics approach. In the latter, the dynamics of the titration coordinate λ, which interpolates between the protonated and deprotonated states, is driven by generalized forces between the protonated and deprotonated states. The hydration free energy, as a function of pH, is included to facilitate constant pH simulations. The protonation states of titratable groups are allowed to change dynamically during a simulation, thus reproducing average protonation probabilities at a certain pH. The accuracy of the method is tested against titration curves of single amino acids and a dipeptide in explicit solvent.
pH是凝聚相系统中的一个重要参数，因为它决定了可滴定基团的质子化状态，从而影响溶液中分子的结构、动力学和功能。然而，在大多数力场模拟协议中，系统的质子化状态（而非其pH值）保持固定，无法适应局部环境的变化。在此，我们提出了一种基于λ动力学方法，在显式溶剂中进行恒定pH分子动力学模拟的方法，该方法在MD软件包GROMACS中实现。在后者中，滴定坐标λ在质子化和去质子化状态之间进行插值，其动力学由质子化和去质子化状态之间的广义力驱动。包含作为pH函数的水合自由能，以促进恒定pH模拟。在模拟过程中，允许可滴定基团的质子化状态动态变化，从而在特定pH下再现平均质子化概率。该方法的准确性通过显式溶剂中单个氨基酸和二肽的滴定曲线进行了测试。
