GraphVAMPNet, using graph neural networks and variational approach to markov processes for dynamical modeling of biomolecules

Abstract

Finding low dimensional representation of data from long-timescale trajectories of biomolecular processes such as protein-folding or ligand-receptor binding is of fundamental importance and kinetic models such as Markov modeling have proven useful in describing the kinetics of these systems. Recently, an unsupervised machine learning technique called VAMPNet was introduced to learn the low dimensional representation and linear dynamical model in an end-to-end manner. VAMPNet is based on variational approach to Markov processes (VAMP) and relies on neural networks to learn the coarse-grained dynamics. In this contribution, we combine VAMPNet and graph neural networks to generate an end-to-end framework to efficiently learn high-level dynamics and metastable states from the long-timescale molecular dynamics trajectories. This method bears the advantages of graph representation learning and uses graph message passing operations to generate an embedding for each datapoint which is used in the VAMPNet to generate a coarse-grained representation. This type of molecular representation results in a higher resolution and more interpretable Markov model than the standard VAMPNet enabling a more detailed kinetic study of the biomolecular processes. Our GraphVAMPNet approach is also enhanced with an attention mechanism to find the important residues for classification into different metastable states.