Reactive force fields for proton transfer dynamics

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.