General Graph Neural Network Based Implicit Solvation Model for Organic Molecules in Water

Abstract

The dynamical behavior of small molecules in their environment can be studied with molecular dynamics (MD) simulations to gain deeper insight on an atomic level and thus complement and rationalize the interpretation of experimental findings. Such approaches are of great value in various areas of research, e.g., in the development of new therapeutics. The accurate description of solvation effects in such simulations is thereby key and has in consequence been an active field of research since the introduction of MD. Until today the most accurate approaches involve computationally expensive explicit solvent simulations, while widely applied models using an implicit solvent description suffer from reduced accuracy. Recently, machine learning (ML) approaches that provide a probabilistic representation of solvation effects have been proposed as potential alternatives. However, the associated computational costs and minimal or lacking transferability used to render them unusable in practice. Here, we report the first example of a transferable ML-based implicit solvent model trained on a diverse set of 3’000’000 molecular structures that can be applied to organic small molecules for simulations in water. Extensive testing against reference calculations demonstrated that the model delivers on par accuracy with explicit solvent simulations while providing up to 18-fold increase in sampling rate.