Efficient Training of Neural Network Potentials for Chemical and Enzymatic Reactions by Continual Learning.

Machine learning (ML) methods have emerged as an efficient surrogate for high-level electronic structure theory, offering precision and computational efficiency. However, the vast conformational and chemical space remains challenging when constructing a general force field. Training data sets typically cover only a limited region of this space, resulting in poor extrapolation performance. Traditional strategies must address this problem by training models from scratch using old and new data sets. In addition, model transferability is crucial for general force field construction. Existing ML force fields, designed for closed systems with no external environmental potential, exhibit limited transferability to complex condensed phase systems such as enzymatic reactions, resulting in inferior performance and high memory costs. Our ML/MM model, based on the Taylor expansion of the electrostatic operator, showed high transferability between reactions in several simple solvents. This work extends the strategy to enzymatic reactions to explore the transferability between more complex heterogeneous environments. In addition, we also apply continual learning strategies based on memory data sets to enable autonomous and on-the-fly training on a continuous stream of new data. By combining these two methods, we can efficiently construct a force field that can be applied to chemical reactions in various environmental media.