Amber free energy tools : Interoperable software for free energy simulations using generalized quantum mechanical/molecular mechanical and machine learning potentials

Tao, Yujun and Giese, Timothy J. and Ekesan, Şölen and Zeng, Jinzhe and Aradi, Bálint and Hourahine, Ben and Aktulga, Hasan Metin and Götz, Andreas W. and Merz, Kenneth M. and York, Darrin M. (2024) Amber free energy tools : Interoperable software for free energy simulations using generalized quantum mechanical/molecular mechanical and machine learning potentials. Journal of Chemical Physics, 160 (22). 224104. ISSN 0021-9606 (https://doi.org/10.1063/5.0211276)

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Abstract

We report the development and testing of new integrated cyberinfrastructure for performing free energy simulations with generalized hybrid quantum mechanical/molecular mechanical (QM/MM) and machine learning potentials (MLPs) in Amber. The Sander molecular dynamics program has been extended to leverage fast, density-functional tight-binding models implemented in the DFTB+ and xTB packages, and an interface to the DeePMD-kit software enables the use of MLPs. The software is integrated through application program interfaces that circumvent the need to perform “system calls” and enable the incorporation of long-range Ewald electrostatics into the external software’s self-consistent field procedure. The infrastructure provides access to QM/MM models that may serve as the foundation for QM/MM–ΔMLP potentials, which supplement the semiempirical QM/MM model with a MLP correction trained to reproduce ab initio QM/MM energies and forces. Efficient optimization of minimum free energy pathways is enabled through a new surface-accelerated finite-temperature string method implemented in the FE-ToolKit package. Furthermore, we interfaced Sander with the i-PI software by implementing the socket communication protocol used in the i-PI client–server model. The new interface with i-PI allows for the treatment of nuclear quantum effects with semiempirical QM/MM–ΔMLP models. The modular interoperable software is demonstrated on proton transfer reactions in guanine-thymine mispairs in a B-form deoxyribonucleic acid helix. The current work represents a considerable advance in the development of modular software for performing free energy simulations of chemical reactions that are important in a wide range of applications.

ORCID iDs

Tao, Yujun, Giese, Timothy J., Ekesan, Şölen, Zeng, Jinzhe, Aradi, Bálint, Hourahine, Ben ORCID logoORCID: https://orcid.org/0000-0002-7667-7101, Aktulga, Hasan Metin, Götz, Andreas W., Merz, Kenneth M. and York, Darrin M.;
CORE (COnnecting REpositories)