# Flow-Matching Based Refiner for Molecular Conformer Generation

arXiv: https://arxiv.org/abs/2510.04878 · HTML: https://mlsanity.com/paper/2510.04878/

## Key facts

- Cited by 1 papers in the map (data through 14 Oct 2026).
- Placed in Flow matching, time series and science, one of 14 directions in Diffusion models.
- Builds on 32 of its 43 references that are in the map.
- First posted on arXiv 6 Oct 2025.

## Placed in

- Diffusion models / [Flow matching, time series and science](https://mlsanity.com/diffusion/flow-matching-time-series-and-science/)

## Builds on (most cited first, 30 of 32)

- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [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)
- [SDXL: Improving Latent Diffusion Models for High-Resolution Image Synthesis](https://mlsanity.com/paper/2307.01952/) (2023)
- [Flow Straight and Fast: Learning to Generate and Transfer Data with Rectified Flow](https://mlsanity.com/paper/2209.03003/) (2022)
- [Elucidating the Design Space of Diffusion-Based Generative Models](https://mlsanity.com/paper/2206.00364/) (2022)
- [Image Super-Resolution via Iterative Refinement](https://mlsanity.com/paper/2104.07636/) (2021)
- [Building Normalizing Flows with Stochastic Interpolants](https://mlsanity.com/paper/2209.15571/) (2022)
- [Denoising Diffusion Restoration Models](https://mlsanity.com/paper/2201.11793/) (2022)
- [Stochastic Interpolants: A Unifying Framework for Flows and Diffusions](https://mlsanity.com/paper/2303.08797/) (2023)
- [Improving and generalizing flow-based generative models with minibatch optimal transport](https://mlsanity.com/paper/2302.00482/) (2023)
- [SiT: Exploring Flow and Diffusion-based Generative Models with Scalable Interpolant Transformers](https://mlsanity.com/paper/2401.08740/) (2024)
- [Representation Alignment for Generation: Training Diffusion Transformers Is Easier Than You Think](https://mlsanity.com/paper/2410.06940/) (2024)
- [Directional Message Passing for Molecular Graphs](https://mlsanity.com/paper/2003.03123/) (2020)
- [GeoDiff: a Geometric Diffusion Model for Molecular Conformation Generation](https://mlsanity.com/paper/2203.02923/) (2022)
- [Improving Diffusion Models for Inverse Problems using Manifold Constraints](https://mlsanity.com/paper/2206.00941/) (2022)
- [Equivariant message passing for the prediction of tensorial properties and molecular spectra](https://mlsanity.com/paper/2102.03150/) (2021)
- [Multisample Flow Matching: Straightening Flows with Minibatch Couplings](https://mlsanity.com/paper/2304.14772/) (2023)
- [Q-Diffusion: Quantizing Diffusion Models](https://mlsanity.com/paper/2302.04304/) (2023)
- [Torsional Diffusion for Molecular Conformer Generation](https://mlsanity.com/paper/2206.01729/) (2022)
- [Deblurring via Stochastic Refinement](https://mlsanity.com/paper/2112.02475/) (2021)
- [GEOM: Energy-annotated molecular conformations for property prediction and molecular generation](https://mlsanity.com/paper/2006.05531/) (2020)
- [Learning Gradient Fields for Molecular Conformation Generation](https://mlsanity.com/paper/2105.03902/) (2021)
- [GeoMol: Torsional Geometric Generation of Molecular 3D Conformer Ensembles](https://mlsanity.com/paper/2106.07802/) (2021)
- [DiffuseVAE: Efficient, Controllable and High-Fidelity Generation from Low-Dimensional Latents](https://mlsanity.com/paper/2201.00308/) (2022)
- [Swallowing the Bitter Pill: Simplified Scalable Conformer Generation](https://mlsanity.com/paper/2311.17932/) (2023)
- [ET-Flow: Equivariant Flow-Matching for Molecular Conformer Generation](https://mlsanity.com/paper/2410.22388/) (2024)
- [Improved Noise Schedule for Diffusion Training](https://mlsanity.com/paper/2407.03297/) (2024)
- [On Error Propagation of Diffusion Models](https://mlsanity.com/paper/2308.05021/) (2023)
- [Molecular machine learning with conformer ensembles](https://mlsanity.com/paper/2012.08452/) (2020)

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

- [Rethinking Refinement: Correcting Generative Bias without Noise Injection](https://mlsanity.com/paper/2601.21182/) (2026)

## Abstract (arXiv)

Low-energy molecular conformers generation (MCG) is a foundational yet challenging problem in drug discovery. Denoising-based methods include diffusion and flow-matching methods that learn mappings from a simple base distribution to the molecular conformer distribution. However, these approaches often suffer from error accumulation during sampling, especially in the low SNR steps, which are hard to train. To address these challenges, we propose a flow-matching refiner for the MCG task. The proposed method initializes sampling from mixed-quality outputs produced by upstream denoising models and reschedules the noise scale to bypass the low-SNR phase, thereby improving sample quality. On the GEOM-QM9 and GEOM-Drugs benchmark datasets, the generator-refiner pipeline improves quality with fewer total denoising steps while preserving diversity.