Tutorial on Molecular Latent Space Simulators (LSSs): Spatially and Temporally Continuous Data-Driven Surrogate Dynamical Models of Molecular Systems.

Abstract

The inherently serial nature and requirement for short integration time steps in the numerical integration of molecular dynamics (MD) calculations place strong limitations on the accessible simulation time scales and statistical uncertainties in sampling slowly relaxing dynamical modes and rare events. Molecular latent space simulators (LSSs) are a data-driven approach to learning a surrogate dynamical model of the molecular system from modest MD training trajectories that can generate synthetic trajectories at a fraction of the computational cost. The training data may comprise single long trajectories or multiple short, discontinuous trajectories collected over, for example, distributed computing resources. Provided the training data provide sufficient sampling of the relevant thermodynamic states and dynamical transitions to robustly learn the underlying microscopic propagator, an LSS furnishes a global model of the dynamics capable of producing temporally and spatially continuous molecular trajectories. Trained LSS models have produced simulation trajectories at up to 6 orders of magnitude lower cost than standard MD to enable dense sampling of molecular phase space and large reduction of the statistical errors in structural, thermodynamic, and kinetic observables. The LSS employs three deep learning architectures to solve three independent learning problems over the training data: (i) an encoding of the high-dimensional MD into a low-dimensional slow latent space using state-free reversible VAMPnets (SRVs), (ii) a propagator of the microscopic dynamics within the low-dimensional latent space using mixture density networks (MDNs), and (iii) a generative decoding of the low-dimensional latent coordinates back to the original high-dimensional molecular configuration space using conditional Wasserstein generative adversarial networks (cWGANs) or denoising diffusion probability models (DDPMs). In this software tutorial, we introduce the mathematical and numerical background and theory of LSS and present example applications of a user-friendly Python package software implementation to alanine dipeptide and a 28-residue beta-beta-alpha (BBA) protein within simple Google Colab notebooks.