Theoretical and Computational Chemistry

DeepWEST: Deep learning of kinetic models with the Weighted Ensemble Simulation Toolkit for enhanced sampling



Recent advances in computational power and algorithms have made molecular dynamics (MD) simulations reach greater timescales. However, for observing conformational transitions associated with biomolecular processes, MD simulations still have limitations. Several enhanced sampling techniques seek to address this challenge, including the weighted ensemble (WE) method, which samples transition between metastable states using many weighted trajectories to estimate kinetic rate constants. However, initial sampling of the potential energy surface has a significant impact on the performance of WE, i.e., convergence and efficiency. We thereby introduce deep-learned kinetic modeling approaches that extract statistically relevant information from short MD trajectories to provide a well-sampled initial state distribution for WE simulation. This hybrid approach overcomes any statistical bias to the system as it runs short unbiased MD trajectories and identifies meaningful metastable states of the system. It is shown to provide a more refined free energy landscape closer to steady-state that could efficiently sample kinetic properties such as rate constants.

Version notes

Revisions proposed by the reviewers after submitting to the JCTC journal.


Thumbnail image of DeepWEST_revision.pdf

Supplementary weblinks

GitHub for DeepWEST project
DeepWEST package