Lammers Sven, Lutz Stephan, Meuwly Markus
Chemistry Department, University of Basel, Klingelbergstrasse 80, CH-4056 Basel, Switzerland.
J Comput Chem. 2008 May;29(7):1048-63. doi: 10.1002/jcc.20864.
A force field-inspired method based on fitted, high-quality multidimensional potential energy surfaces to follow proton transfer (PT) reactions in molecular dynamics simulations is presented. In molecular mechanics with proton transfer (MMPT) a system is partitioned into a region where proton transfer takes place and the remaining degrees of freedom which are treated with a conventional force field. The implementation of the method and applications to specific chemically and biologically relevant scenarios are presented. MMPT is developed in view of two primary areas in mind: to follow the molecular dynamics of proton transfer in the condensed phase on realistic time scales and to adapt the shape (morphing) of the potential energy surface for specific applications. MMPT is applied to PT in protonated ammonia dimer, double proton transfer in 2-pyridone-2-hydroxypyridine, and the first step of PT from a protein side-chain towards a buried [3Fe4S] cluster in ferredoxin I. Specific findings of the work include the fundamental role of the N-N vibration as the gating mode for PT in NH4+...NH3 and the qualitative understanding of PT from the protein to a metastable active-site water molecule in Ferredoxin I.
提出了一种基于拟合的高质量多维势能面的力场启发式方法，用于在分子动力学模拟中跟踪质子转移（PT）反应。在质子转移分子力学（MMPT）中，系统被划分为发生质子转移的区域和用传统力场处理的其余自由度。介绍了该方法的实现及其在特定化学和生物学相关场景中的应用。开发MMPT主要考虑两个方面：在现实时间尺度上跟踪凝聚相中质子转移的分子动力学，以及针对特定应用调整势能面的形状（变形）。MMPT应用于质子化氨二聚体中的质子转移、2-吡啶酮-2-羟基吡啶中的双质子转移以及铁氧化还原蛋白I中从蛋白质侧链向埋藏的[3Fe4S]簇的质子转移的第一步。该工作的具体发现包括N-N振动作为NH4+...NH3中质子转移的门控模式的基本作用，以及对铁氧化还原蛋白I中从蛋白质到亚稳态活性位点水分子的质子转移的定性理解。
