Using metadynamics to build neural network potentials for reactive events: the case of urea decomposition in water

The study of chemical reactions in aqueous media is very important for its implications in several fields of science, from biology to industrial processes. However, modeling these reactions is difficult when water directly participates in the reaction, since it requires a fully quantum mechanical description of the system. Ab-initio molecular dynamics is the ideal candidate to shed light on these processes. However, its scope is limited by a high computational cost. A popular alternative is to perform molecular dynamics simulations powered by machine learning potentials, trained on an extensive set of quantum mechanical calculations. Doing so reliably for reactive processes is difficult because it requires including very many intermediate and transition state config-urations. In this study we used an active learning procedure accelerated by enhanced sampling to harvest such structures and to build a neural-network potential to study the urea decomposition process in water. This allowed us to obtain the free energy profiles of this important reaction in a wide range of temperatures, to discover several novel metastable states, and improve the accuracy of the kinetic rates calculations. Furthermore, we found that the formation of the zwitterionic intermediate has the same probability of occurring via an acidic or a basic pathway, which could be the cause of the insensitivity of reaction rates to the solution pH.

Automated summary

The study of chemical reactions in aqueous media is crucial and challenging due to the involvement of water molecules. Ab-initio molecular dynamics and machine learning potentials offer solutions to model these reactions, but their application is limited by computational cost. In this study, an active learning procedure accelerated by enhanced sampling was used to build a neural-network potential for studying the urea decomposition process in water. The obtained free energy profiles improved the accuracy of kinetic rates calculations, and the formation of the zwitterionic intermediate was found equally probable via an acidic or a basic pathway.