Efficient Generation of Conformer Ensembles Using Internal Coordinates and a Generative Directional Graph Convolution Neural Network.

Abstract

We present a neural-network-based high-throughput molecular conformer-generation algorithm. A chemical graph-convolutional network is trained to predict low-energy conformers in internal coordinate representation (bond lengths, bond, and torsion angles), starting from two-dimensional (2D) chemical topology. Generative neural network (NN) architecture performs denoising from torsion space, producing conformer ensembles with populations that are well correlated with torsion energy profiles. Short force-field-based energy minimization is applied to refine final conformers. All computation-intensive stages of the algorithm are GPU-optimized. The procedure (termed GINGER) is benchmarked on a commonly used test set of bioactive three-dimensional (3D) conformers from the PDB. We demonstrate highly competitive results in conformer recovery and throughput rates suitable for giga-scale compound library processing. A web server that allows interactive conformer ensemble generation by GINGER and their viewing is made freely available at https://www.molsoft.com/gingerdemo.html.