Deep learning path-like collective variable for enhanced sampling molecular dynamics

Abstract

Several enhanced sampling techniques rely on the definition of collective variables to effectively explore free energy landscapes. Existing variables that describe the progression along a reactive pathway offer an elegant solution but face a number of limitations. In this paper, we address these challenges by introducing a new path-like collective variable called the `Deep-locally-non-linear-embedding', which is inspired by principles of the locally linear embedding technique and is trained on a reactive trajectory. The variable mimics the ideal reaction coordinate by automatically generating a non-linear combination of features through a differentiable generalized autoencoder that combines a neural network with a continuous k-nearest-neighbor selection. Among the key advantages of this method is its capability to automatically choose the metric for searching neighbors and to learn the path from state A to state B without the need to handpick landmarks a priori. We demonstrate the effectiveness of DeepLNE by showing that the progression along the path variable closely approximates the ideal reaction coordinate in toy models such as the Müller-Brown-potential and alanine dipeptide. We then use it in molecular dynamics simulations of an RNA tetraloop, where we highlight its capability to accelerate transitions and converge the free energy of folding.