Generation of molecular conformations using generative adversarial neural networks†

Abstract

The accurate determination of a molecule's accessible conformations is key to the success of studying its properties. Traditional computational methods for exploring the conformational space of molecules such as molecular dynamics simulations, however, require substantial computational resources and time. Recently, deep generative models have made significant progress in various fields, harnessing their powerful learning capabilities for complex data distributions. This makes them highly applicable in molecular conformation generation. In this study, we developed ConfGAN, a conformation generation model based on conditional generative adversarial networks. We designed an efficient molecular-motif graph representation, treating molecules composed of functional groups, capturing interactions between groups, and providing rich chemical prior knowledge for conformation generation. During adversarial training, the generator network takes molecular graphs as input and attempts to generate stable conformations with minimal potential energy. The discriminator provides feedback based on energy differences, guiding the generation of conformations that comply with chemical rules. This model explicitly encodes molecular knowledge, ensuring the physical plausibility of generated conformations. Through extensive evaluation, ConfGAN has demonstrated superior performance compared to existing deep learning-based models. Furthermore, conformations generated by ConfGAN have demonstrated potential applications in related fields such as molecular docking and electronic property calculations.