# Torsional-GFN: a conditional conformation generator for small molecules

arXiv: https://arxiv.org/abs/2507.11759 · HTML: https://mlsanity.com/paper/2507.11759/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 12 of its 24 references that are in the map.
- First posted on arXiv 15 Jul 2025.

## Builds on (most cited first, 12 of 12)

- [Gaussian Error Linear Units (GELUs)](https://mlsanity.com/paper/1606.08415/) (2016)
- [GFlowNet Foundations](https://mlsanity.com/paper/2111.09266/) (2021)
- [Torsional Diffusion for Molecular Conformer Generation](https://mlsanity.com/paper/2206.01729/) (2022)
- [GEOM: Energy-annotated molecular conformations for property prediction and molecular generation](https://mlsanity.com/paper/2006.05531/) (2020)
- [Biological Sequence Design with GFlowNets](https://mlsanity.com/paper/2203.04115/) (2022)
- [Iterated Denoising Energy Matching for Sampling from Boltzmann Densities](https://mlsanity.com/paper/2402.06121/) (2024)
- [GFlowNets and variational inference](https://mlsanity.com/paper/2210.00580/) (2022)
- [A theory of continuous generative flow networks](https://mlsanity.com/paper/2301.12594/) (2023)
- [VarGrad: A Low-Variance Gradient Estimator for Variational Inference](https://mlsanity.com/paper/2010.10436/) (2020)
- [Transferable Boltzmann Generators](https://mlsanity.com/paper/2406.14426/) (2024)
- [An Empirical Study of the Effectiveness of Using a Replay Buffer on Mode Discovery in GFlowNets](https://mlsanity.com/paper/2307.07674/) (2023)
- [Towards equilibrium molecular conformation generation with GFlowNets](https://mlsanity.com/paper/2310.14782/) (2023)

## Abstract (arXiv)

Generating stable molecular conformations is crucial in several drug discovery applications, such as estimating the binding affinity of a molecule to a target. Recently, generative machine learning methods have emerged as a promising, more efficient method than molecular dynamics for sampling of conformations from the Boltzmann distribution. In this paper, we introduce Torsional-GFN, a conditional GFlowNet specifically designed to sample conformations of molecules proportionally to their Boltzmann distribution, using only a reward function as training signal. Conditioned on a molecular graph and its local structure (bond lengths and angles), Torsional-GFN samples rotations of its torsion angles. Our results demonstrate that Torsional-GFN is able to sample conformations approximately proportional to the Boltzmann distribution for multiple molecules with a single model, and allows for zero-shot generalization to unseen bond lengths and angles coming from the MD simulations for such molecules. Our work presents a promising avenue for scaling the proposed approach to larger molecular systems, achieving zero-shot generalization to unseen molecules, and including the generation of the local structure into the GFlowNet model.