Accurate QM/MM Molecular Dynamics for Periodic Systems in GPU4PySCF with Applications to Enzyme Catalysis

Creators: Li, Chenghan¹; Chan, Garnet K.¹

1. California Institute of Technology

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Abstract

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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Acknowledgement

This work was primarily supported by the US Department of Energy, Office of Science, Basic Energy Sciences, through Award No. DE-SC0023318. GKC acknowledges additional support in the conceptualization phase from the Dreyfus Foundation, under the program Machine Learning in the Chemical Sciences and Engineering, and from the Simons Investigator program.

Contributions

C.L. and G.K.C. formulated the project. C.L. carried out the implementation and calculations. C.L. and G.K.C. discussed the results and interpretation and wrote the manuscript.

Supplemental Material

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.jctc.4c01698.

Details on multipolar Ewald and pseudobond parametrization, additional computational details on chorismate mutase, rate calculations, and statistical error analysis (PDF)

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