Regularized Molecular Conformation Fields

Abstract

Predicting energetically favorable 3-dimensional conformations of organic molecules from molecular graph plays a fundamental role in computer-aided drug discovery research. However, effectively exploring the high-dimensional conformation space to identify (meta) stable conformers is anything but trivial. In this work, we introduce RMCF, a novel framework to generate a diverse set of low-energy molecular conformations through sampling from a regularized molecular conformation field. We develop a data-driven molecular segmentation algorithm to automatically partition each molecule into several structural building blocks to reduce the modeling degrees of freedom. Then, we employ a Markov Random Field to learn the joint probability distribution of fragment configurations and inter-fragment dihedral angles, which enables us to sample from different low-energy regions of a conformation space. Our model constantly outperforms state-of-the-art models for the conformation generation task on the GEOM-Drugs dataset. We attribute the success of RMCF to modeling in a regularized feature space and learning a global fragment configuration distribution for effective sampling. The proposed method could be generalized to deal with larger biomolecular systems.