CoarsenConf: Equivariant Coarsening with Aggregated Attention for Molecular Conformer Generation
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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 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 autoregressive generation of large molecules. Furthermore, our work expands current conformer generation benchmarks and introduces new metrics to better evaluate the quality and viability of generated conformers. We demonstrate that CoarsenConf generates more accurate conformer ensembles compared to prior generative models and traditional cheminformatics methods.
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