DP/MM: A Hybrid Model for Zinc–Protein Interactions in Molecular Dynamics

Zinc-containing proteins are vital for many biological processes, yet accurately modeling them using classical force fields is hindered by complicated polarization and charge transfer effects. This study introduces DP/MM, a hybrid force field scheme that utilizes a deep potential model to correct the atomic forces of zinc ions and their coordinated atoms, elevating them from MM to QM levels of accuracy. Trained on the difference between MM and QM atomic forces across diverse zinc coordination groups, the DP/MM model faithfully reproduces structural characteristics of zinc coordination during simulations, such as the tetrahedral coordination of Cys₄ and Cys₃His₁ groups. Furthermore, DP/MM allows water exchange in the zinc coordination environment. With its unique blend of accuracy, efficiency, flexibility, and transferability, DP/MM serves as a valuable tool for studying structures and dynamics of zinc-containing proteins and also represents a pioneering approach in the evolving landscape of machine learning potentials for molecular modeling.