CoarsenConf: Equivariant Coarsening with Aggregated Attention for Molecular Conformer Generation
This work addresses the challenge of efficiently generating low-energy 3D molecular structures for cheminformatics and drug discovery, potentially accelerating virtual screenings and structural exploration.
The paper tackled the problem of molecular conformer generation by introducing CoarsenConf, an SE(3)-equivariant hierarchical variational autoencoder that coarse-grains molecular graphs based on torsional angles and uses aggregated attention to restore fine-grained coordinates, resulting in more accurate conformer ensembles compared to prior generative models.
Molecular conformer generation (MCG) is an important task in cheminformatics and drug discovery. The ability to efficiently generate low-energy 3D structures can avoid expensive quantum mechanical simulations, leading to accelerated virtual screenings and enhanced structural exploration. Several generative models have been developed for MCG, but many struggle to consistently produce high-quality conformers. To address these issues, we introduce CoarsenConf, which coarse-grains molecular graphs based on torsional angles and integrates them into an SE(3)-equivariant hierarchical variational autoencoder. Through equivariant coarse-graining, we aggregate the fine-grained atomic coordinates of subgraphs connected via rotatable bonds, creating a variable-length coarse-grained latent representation. Our model uses a novel aggregated attention mechanism to restore fine-grained coordinates from the coarse-grained latent representation, enabling efficient generation of accurate conformers. Furthermore, we evaluate the chemical and biochemical quality of our generated conformers on multiple downstream applications, including property prediction and oracle-based protein docking. Overall, CoarsenConf generates more accurate conformer ensembles compared to prior generative models.