Department of Physics and Quantum Theory Project, University of Florida, Gainesville, Florida 32611-8435, USA.
J Phys Chem B. 2012 Aug 2;116(30):8805-11. doi: 10.1021/jp303385x. Epub 2012 Jul 17.
Protonation equilibria in biological molecules modulates structure, dynamics, and function. A pH-replica exchange molecular dynamics (pH-REMD) method is described here to improve the coupling between conformational and protonation sampling. Under a Hamiltonian replica exchange setup, conformations are swapped between two neighboring replicas, which themselves are at different pHs. The method has been validated on a series of biological systems. We applied pH-REMD to a series of model compounds, to an terminally charged ADFDA pentapeptide, and to a heptapeptide derived from the ovomucoid third domain (OMTKY3). In all of those systems, the predicted pK(a) by pH-REMD is very close to the experimental value and almost identical to the ones obtained by constant pH molecular dynamics (CpH MD). The method presented here, pH-REMD, has the advantage of faster convergence properties due to enhanced sampling of both conformation and protonation spaces.
质子化平衡在生物分子中调节结构、动力学和功能。本文描述了一种 pH 复制交换分子动力学 (pH-REMD) 方法，以改善构象和质子化采样之间的耦合。在哈密顿复制交换设置下，构象在两个相邻副本之间交换，副本本身处于不同的 pH 值。该方法已在一系列生物系统中得到验证。我们将 pH-REMD 应用于一系列模型化合物、末端带电荷的 ADFDA 五肽和来源于卵转铁蛋白第三结构域的七肽 (OMTKY3)。在所有这些系统中，pH-REMD 预测的 pK(a) 值非常接近实验值，几乎与通过恒 pH 分子动力学 (CpH MD) 获得的值相同。本文提出的 pH-REMD 方法具有更快的收敛特性的优势，因为它增强了构象和质子化空间的采样。
