Toward a structural identification of metastable molecular conformations

Abstract

Interpreting high-dimensional data from molecular dynamics simulations is a persistent challenge. In this paper, we show that for a small peptide, deca-alanine, metastable states can be identified through a neural net based on structural information alone. While processing molecular dynamics data, dimensionality reduction is a necessary step that projects high-dimensional data onto a low-dimensional representation that, ideally, captures the conformational changes in the underlying data. Conventional methods make use of the temporal information contained in trajectories generated through integrating the equations of motion, which forgoes more efficient sampling schemes. We demonstrate that EncoderMap, an autoencoder architecture with an additional distance metric, can find a suitable low-dimensional representation to identify long-lived molecular conformations using exclusively structural information. For deca-alanine, which exhibits several helix-forming pathways, we show that this approach allows us to combine simulations with different biasing forces and yields representations comparable in quality to other established methods. Our results contribute to computational strategies for the rapid automatic exploration of the configuration space of peptides and proteins.