Seamless QM/MM Simulations via a GROMACS-CP2K Interface

Abstract

Understanding and controlling chemical reactivity in biological systems require atomic-level insight into processes that are often inaccessible to experiments. Hybrid quantum mechanics/molecular mechanics (QM/MM) simulations provide a powerful framework for describing chemical reactions in complex environments, but their practical application remains limited by fragmented software ecosystems, restricted accessibility, and methodological approximations that can compromise accuracy and reproducibility. In particular, many existing QM/MM implementations rely on ad hoc couplings, proprietary software, or truncated treatments of long-range electrostatic interactions. Here, we present a robust and fully periodic QM/MM interface between the open-source molecular dynamics engine GROMACS and the electronic structure theory code CP2K. The implementation enables efficient and reproducible QM/MM molecular dynamics and enhanced sampling simulations with a consistent treatment of long-range electrostatics under periodic boundary conditions. By combining the strengths of two widely used community codes, this interface provides a general and scalable platform for studying chemical reactivity in biological systems and establishes a transparent reference implementation for QM/MM simulations.