Machine Learning Implicit Solvation for Molecular Dynamics

Abstract

Accurate modeling of the solvent environment for biological molecules is crucial for computational biology and drug design. A popular approach to achieve long simulation time scales for large system sizes is to incorporate the effect of the solvent in a mean-field fashion with implicit solvent models. However, a challenge with existing implicit solvent models is that they often lack accuracy or certain physical properties compared to explicit solvent models, as the many-body effects of the neglected solvent molecules is difficult to model as a mean field. Here, we leverage machine learning (ML) and multi-scale coarse graining (CG) in order to learn implicit solvent models that can approximate the energetic and thermodynamic properties of a given explicit solvent model with arbitrary accuracy, given enough training data. Following the previous ML--CG models CGnet and CGSchnet, we introduce ISSNet, a graph neural network, to model the implicit solvent potential of mean force. ISSNet can learn from explicit solvent simulation data and be readily applied to MD simulations. We compare the solute conformational distributions under different solvation treatments for two peptide systems. The results indicate that ISSNet models can outperform widely-used generalized Born and surface area models in reproducing the thermodynamics of small protein systems with respect to explicit solvent. The success of this novel method demonstrates the potential benefit of applying machine learning methods in accurate modeling of solvent effects for in silico research and biomedical applications.

16 pages, 6 figures

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• chemtrain: Learning Deep Potential Models via Automatic Differentiation and Statistical Physics
• Artificial Intelligence for Science in Quantum, Atomistic, and Continuum Systems
• Implicit Solvent Approach Based on Generalised Born and Transferable Graph Neural Networks for Molecular Dynamics Simulations
• AMARO: All Heavy-Atom Transferable Neural Network Potentials of Protein Thermodynamics
• Data-driven dynamical coarse-graining for condensed matter systems
• Scaling Graph Neural Networks to Large Proteins
• Free energy profiles for chemical reactions in solution from high-dimensional neural network potentials: The case of the Strecker synthesis
• Knowledge Distillation of a Protein Language Model Yields a Foundational Implicit Solvent Model