# Learning conformational ensembles of proteins based on backbone geometry

arXiv: https://arxiv.org/abs/2503.05738 · HTML: https://mlsanity.com/paper/2503.05738/

## Key facts

- Cited by 1 papers in the map (data through 14 Oct 2026).
- Builds on 19 of its 60 references that are in the map.
- First posted on arXiv 19 Feb 2025.

## Builds on (most cited first, 19 of 19)

- [Score-Based Generative Modeling through Stochastic Differential Equations](https://mlsanity.com/paper/2011.13456/) (2020)
- [Flow Matching for Generative Modeling](https://mlsanity.com/paper/2210.02747/) (2022)
- [Building Normalizing Flows with Stochastic Interpolants](https://mlsanity.com/paper/2209.15571/) (2022)
- [Improving and generalizing flow-based generative models with minibatch optimal transport](https://mlsanity.com/paper/2302.00482/) (2023)
- [Equivariant message passing for the prediction of tensorial properties and molecular spectra](https://mlsanity.com/paper/2102.03150/) (2021)
- [Flow Matching on General Geometries](https://mlsanity.com/paper/2302.03660/) (2023)
- [SE(3) diffusion model with application to protein backbone generation](https://mlsanity.com/paper/2302.02277/) (2023)
- [SE(3)-Stochastic Flow Matching for Protein Backbone Generation](https://mlsanity.com/paper/2310.02391/) (2023)
- [Equivariant flow matching](https://mlsanity.com/paper/2306.15030/) (2023)
- [AlphaFold Meets Flow Matching for Generating Protein Ensembles](https://mlsanity.com/paper/2402.04845/) (2024)
- [Generating Novel, Designable, and Diverse Protein Structures by Equivariantly Diffusing Oriented Residue Clouds](https://mlsanity.com/paper/2301.12485/) (2023)
- [Generative Modeling of Molecular Dynamics Trajectories](https://mlsanity.com/paper/2409.17808/) (2024)
- [Protein Conformation Generation via Force-Guided SE(3) Diffusion Models](https://mlsanity.com/paper/2403.14088/) (2024)
- [Improved motif-scaffolding with SE(3) flow matching](https://mlsanity.com/paper/2401.04082/) (2024)
- [Str2Str: A Score-based Framework for Zero-shot Protein Conformation Sampling](https://mlsanity.com/paper/2306.03117/) (2023)
- [Structure Language Models for Protein Conformation Generation](https://mlsanity.com/paper/2410.18403/) (2024)
- [Beyond Canonicalization: How Tensorial Messages Improve Equivariant Message Passing](https://mlsanity.com/paper/2405.15389/) (2024)
- [Generating Highly Designable Proteins with Geometric Algebra Flow Matching](https://mlsanity.com/paper/2411.05238/) (2024)
- [Improving AlphaFlow for Efficient Protein Ensembles Generation](https://mlsanity.com/paper/2407.12053/) (2024)

## Built on by (most cited first, 1 of 1)

- [AI-based Methods for Simulating, Sampling, and Predicting Protein Ensembles](https://mlsanity.com/paper/2509.17224/) (2025)

## Abstract (arXiv)

Deep generative models have recently been proposed for sampling protein conformations from the Boltzmann distribution, as an alternative to often prohibitively expensive Molecular Dynamics simulations. However, current state-of-the-art approaches rely on fine-tuning pre-trained folding models and evolutionary sequence information, limiting their applicability and efficiency, and introducing potential biases. In this work, we propose a flow matching model for sampling protein conformations based solely on backbone geometry - BBFlow. We introduce a geometric encoding of the backbone equilibrium structure as input and propose to condition not only the flow but also the prior distribution on the respective equilibrium structure, eliminating the need for evolutionary information. The resulting model is orders of magnitudes faster than current state-of-the-art approaches at comparable accuracy, is transferable to multi-chain proteins, and can be trained from scratch in a few GPU days. In our experiments, we demonstrate that the proposed model achieves competitive performance with reduced inference time, across not only an established benchmark of naturally occurring proteins but also de novo proteins, for which evolutionary information is scarce or absent. BBFlow is available at https://github.com/graeter-group/bbflow.