Department of Chemistry and Biochemistry, University of Delaware, Newark Delaware 19716, USA.
J Phys Chem B. 2011 Jan 20;115(2):249-61. doi: 10.1021/jp108642r. Epub 2010 Dec 17.
Tautomerization of amino acids between the neutral form (NF) and the zwitterionic form (ZW) in water has been extensively studied, often using glycine as a model to understand this fundamental process. In spite of many advanced studies, the tautomerization reaction remains poorly understood because of the intrinsic complexities of the system, including multiple accessible reaction pathways, charge transfer, and variations of solvation structure. To establish an accurate model that can be used for molecular dynamics simulations, a ReaxFF reactive force field has been developed for glycine. A training set for the ReaxFF hydrocarbon potential was augmented with several glycine conformers and glycine-water complexes. The force field parameters were optimized to reproduce the quantum mechanically derived energies of the species in the training set. The optimized potential could accurately describe the properties of gas-phase glycine. It was applied to investigate the effect of solvation on the conformational distribution of glycine. Molecular dynamics simulations indicated significant differences in the dominant conformers in the gas phase and in water. This suggests that the tautomerization of glycine occurs through a conformational isomerization followed by the proton transfer event. The direct reaction mechanism of the NF → ZW proton transfer reaction in water, as well as mechanisms mediated by one or two water molecules, were investigated using molecular dynamics simulations. The results suggest that the proton transfer reaction is most likely mediated by a single water molecule. The ReaxFF potential developed in this work provides an accurate description of proton transfer in glycine and thus provides a useful methodology for simulating proton transfer reactions in organic molecules in the aqueous environment.
氨基酸在中性形式（NF）和两性离子形式（ZW）之间的互变异构已经在水中得到了广泛的研究，通常使用甘氨酸作为模型来理解这一基本过程。尽管进行了许多高级研究，但由于系统的固有复杂性，包括多个可访问的反应途径、电荷转移和溶剂化结构的变化，互变异构反应仍然理解得很差。为了建立一个可用于分子动力学模拟的准确模型，已经为甘氨酸开发了 ReaxFF 反应力场。ReaxFF 碳氢化合物势的训练集增加了几个甘氨酸构象体和甘氨酸-水复合物。力场参数经过优化，以再现训练集中物种的量子力学衍生能量。优化后的势能可以准确描述气相甘氨酸的性质。它被应用于研究溶剂化对甘氨酸构象分布的影响。分子动力学模拟表明，在气相和水中，主要构象体存在显著差异。这表明甘氨酸的互变异构通过构象异构化然后质子转移事件发生。使用分子动力学模拟研究了 NF → ZW 质子转移反应在水中的直接反应机制以及由一个或两个水分子介导的机制。结果表明，质子转移反应最有可能由单个水分子介导。本工作中开发的 ReaxFF 势能提供了对甘氨酸中质子转移的准确描述，从而为模拟水相有机分子中的质子转移反应提供了有用的方法。
