A Deep Graph Network–Enhanced Sampling Approach to Efficiently Explore the Space of Reduced Representations of Proteins

Abstract

The limits of molecular dynamics (MD) simulations of macromolecules are steadily pushed forward by the relentless development of computer architectures and algorithms. The consequent explosion in the number and extent of MD trajectories induces the need for automated methods to rationalize the raw data and make quantitative sense of them. Recently, an algorithmic approach was introduced by some of us to identify the subset of a protein’s atoms, or mapping, that enables the most informative description of the system. This method relies on the computation, for a given reduced representation, of the associated mapping entropy, that is, a measure of the information loss due to such simplification; albeit relatively straightforward, this calculation can be time-consuming. Here, we describe the implementation of a deep learning approach aimed at accelerating the calculation of the mapping entropy. We rely on Deep Graph Networks, which provide extreme flexibility in handling structured input data and whose predictions prove to be accurate and-remarkably efficient. The trained network produces a speedup factor as large as 105 with respect to the algorithmic computation of the mapping entropy, enabling the reconstruction of its landscape by means of the Wang–Landau sampling scheme. Applications of this method reach much further than this, as the proposed pipeline is easily transferable to the computation of arbitrary properties of a molecular structure.