Reweighted Autoencoded Variational Bayes for Enhanced Sampling (RAVE)

TL;DR

RAVE is a novel deep learning-based iterative method that enhances molecular sampling by identifying physically meaningful reaction coordinates, leading to more efficient simulations and accurate thermodynamic estimates.

Contribution

It introduces a physically interpretable reaction coordinate extraction within an iterative deep learning framework for enhanced molecular sampling.

Findings

Successfully applied to complex potentials and ligand binding free energy calculations.

Achieves at least twenty times faster convergence compared to traditional methods.

Provides reliable and interpretable reaction coordinates for enhanced sampling.

Abstract

Here we propose the Reweighted Autoencoded Variational Bayes for Enhanced Sampling (RAVE) method, a new iterative scheme that uses the deep learning framework of variational autoencoders to enhance sampling in molecular simulations. RAVE involves iterations between molecular simulations and deep learning in order to produce an increasingly accurate probability distribution along a low-dimensional latent space that captures the key features of the molecular simulation trajectory. Using the Kullback-Leibler divergence between this latent space distribution and the distribution of various trial reaction coordinates sampled from the molecular simulation, RAVE determines an optimum, yet nonetheless physically interpretable, reaction coordinate and optimum probability distribution. Both then directly serve as the biasing protocol for a new biased simulation, which is once again fed into the deep learning module with appropriate weights accounting for the bias, the procedure continuing until estimates of desirable thermodynamic observables are converged. Unlike recent methods using deep learning for enhanced sampling purposes, RAVE stands out in that (a) it naturally produces a physically interpretable reaction coordinate, (b) is independent of existing enhanced sampling protocols to enhance the fluctuations along the latent space identified via deep learning, and (c) it provides the ability to easily filter out spurious solutions learned by the deep learning procedure. The usefulness and reliability of RAVE is demonstrated by applying it to model potentials of increasing complexity, including computation of the binding free energy profile for a hydrophobic ligand-substrate system in explicit water with dissociation time of more than three minutes, in computer time at least twenty times less than that needed for umbrella sampling or metadynamics.