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Torsional Diffusion for Molecular Conformer Generation

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arxiv 2206.01729 v2 pith:ZOJJIJ4B submitted 2022-06-01 physics.chem-ph cs.LGq-bio.BM

classification physics.chem-phcs.LGq-bio.BM
keywords diffusionconformertorsionalcheminformaticsgenerationlearningmachinemethods
verification ladder T0 review T1 audit T2 compute T3 formal
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Molecular conformer generation is a fundamental task in computational chemistry. Several machine learning approaches have been developed, but none have outperformed state-of-the-art cheminformatics methods. We propose torsional diffusion, a novel diffusion framework that operates on the space of torsion angles via a diffusion process on the hypertorus and an extrinsic-to-intrinsic score model. On a standard benchmark of drug-like molecules, torsional diffusion generates superior conformer ensembles compared to machine learning and cheminformatics methods in terms of both RMSD and chemical properties, and is orders of magnitude faster than previous diffusion-based models. Moreover, our model provides exact likelihoods, which we employ to build the first generalizable Boltzmann generator. Code is available at https://github.com/gcorso/torsional-diffusion.

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Cited by 4 Pith papers

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    Feynman-Kac particle steering, previously diffusion-only, is derived for conditional flow matching and used to generate chirality-correct chemical transition states.

  3. Applications of Modular Co-Design for De Novo 3D Molecule Generation

    cs.LG 2025-05 conditional novelty 6.0 of 10

    A new transformer architecture with joint continuous and discrete denoising improves 3D molecule generation and moves generated structures closer to low-energy physical minima.

  4. Graph Neural Networks in Modern AI-aided Drug Discovery

    q-bio.BM 2025-06 conditional novelty 1.0 of 10

    A comprehensive model-centric review of graph neural network methods and applications in AI-aided drug discovery, from molecular representation to synthesis planning.

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