Accurate QM/MM Molecular Dynamics for Periodic Systems in GPU4PYSCF with Applications to Enzyme Catalysis

CH Li and GKL Chan, JOURNAL OF CHEMICAL THEORY AND COMPUTATION, 21, 803-816 (2025).

DOI: 10.1021/acs.jctc.4c01698

We present an implementation of the quantum mechanics/molecular mechanics (QM/MM) method for periodic systems using GPU accelerated QM methods, a distributed multipole formulation of the electrostatics, and a pseudobond treatment of the QM/MM boundary. We demonstrate that our method has well-controlled errors, stable self-consistent QM convergence, and energy-conserving dynamics. We further describe an application to the catalytic kinetics of chorismate mutase. Using an accurate hybrid functional reparametrized to coupled cluster energetics, our QM/MM simulations highlight the sensitivity in the calculated rate to the choice of quantum method, quantum region selection, and local protein conformation. Our work is provided through the open-source PySCF package using acceleration from the GPU4PySCF module.

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