Quantum machine learning corrects classical forcefields: Stretching DNA base pairs in explicit solvent

In order to improve the accuracy of molecular dynamics simulations, classical forcefields are supplemented with a kernel-based machine learning method trained on quantum-mechanical fragment energies. As an example application, a potential-energy surface is generalized for a small DNA duplex, taking into account explicit solvation and long-range electron exchange-correlation effects. A long-standing problem in molecular science is that experimental studies of the structural and thermodynamic behavior of DNA under tension are not well confirmed by simulation; study of the potential energy vs extension taking into account a novel correction shows that leading classical DNA models have excessive stiffness with respect to stretching. This discrepancy is found to be common across multiple forcefields. The quantum correction is in qualitative agreement with the experimental thermodynamics for larger DNA double helices, providing a candidate explanation for the general and long-standing discrepancy between single molecule stretching experiments and classical calculations of DNA stretching. The new dataset of quantum calculations should facilitate multiple types of nucleic acid simulation, and the associated Kernel Modified Molecular Dynamics method (KMMD) is applicable to biomolecular simulations in general. KMMD is made available as part of the AMBER22 simulation software. (C) 2022 Author(s).

Automated summary

To improve the accuracy of molecular dynamics simulations, classical forcefields are supplemented with a kernel-based machine learning method trained on quantum-mechanical fragment energies. The study finds that classical DNA models have excessive stiffness when it comes to stretching, which is not confirmed by experimental studies. Quantum correction provides a better explanation for the discrepancy between single molecule stretching experiments and classical calculations of DNA stretching. This research is important for nucleic acid simulations and biomolecular simulations in general.