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Flow perturbation to accelerate Boltzmann sampling

Author

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  • Xin Peng

    (Beijing University of Posts and Telecommunications)

  • Ang Gao

    (Beijing University of Posts and Telecommunications)

Abstract

Flow-based generative models have been employed for Boltzmann sampling tasks, but their application to high-dimensional systems is hindered by the significant computational cost of obtaining the Jacobian of the flow. We introduce a flow perturbation method that bypasses this bottleneck by injecting stochastic perturbations into the flow, delivering orders-of-magnitude speed-ups. Unlike the Hutchinson estimator, our approach is inherently unbiased in Boltzmann sampling. Notably, this method significantly accelerates Boltzmann sampling of a Chignolin mutant with all atomic Cartesian coordinates explicitly represented, while delivering more accurate results than the Hutchinson estimator.

Suggested Citation

  • Xin Peng & Ang Gao, 2025. "Flow perturbation to accelerate Boltzmann sampling," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62039-8
    DOI: 10.1038/s41467-025-62039-8
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    References listed on IDEAS

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    1. Pierre Del Moral & Arnaud Doucet & Ajay Jasra, 2006. "Sequential Monte Carlo samplers," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 68(3), pages 411-436, June.
    2. Joseph L. Watson & David Juergens & Nathaniel R. Bennett & Brian L. Trippe & Jason Yim & Helen E. Eisenach & Woody Ahern & Andrew J. Borst & Robert J. Ragotte & Lukas F. Milles & Basile I. M. Wicky & , 2023. "De novo design of protein structure and function with RFdiffusion," Nature, Nature, vol. 620(7976), pages 1089-1100, August.
    3. Josh Abramson & Jonas Adler & Jack Dunger & Richard Evans & Tim Green & Alexander Pritzel & Olaf Ronneberger & Lindsay Willmore & Andrew J. Ballard & Joshua Bambrick & Sebastian W. Bodenstein & David , 2024. "Addendum: Accurate structure prediction of biomolecular interactions with AlphaFold 3," Nature, Nature, vol. 636(8042), pages 4-4, December.
    4. John B. Ingraham & Max Baranov & Zak Costello & Karl W. Barber & Wujie Wang & Ahmed Ismail & Vincent Frappier & Dana M. Lord & Christopher Ng-Thow-Hing & Erik R. Van Vlack & Shan Tie & Vincent Xue & S, 2023. "Illuminating protein space with a programmable generative model," Nature, Nature, vol. 623(7989), pages 1070-1078, November.
    5. Kevin E. Wu & Kevin K. Yang & Rianne Berg & Sarah Alamdari & James Y. Zou & Alex X. Lu & Ava P. Amini, 2024. "Protein structure generation via folding diffusion," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    6. Josh Abramson & Jonas Adler & Jack Dunger & Richard Evans & Tim Green & Alexander Pritzel & Olaf Ronneberger & Lindsay Willmore & Andrew J. Ballard & Joshua Bambrick & Sebastian W. Bodenstein & David , 2024. "Accurate structure prediction of biomolecular interactions with AlphaFold 3," Nature, Nature, vol. 630(8016), pages 493-500, June.
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