# BetterBodies: Reinforcement Learning guided Diffusion for Antibody Sequence Design

arXiv: https://arxiv.org/abs/2409.16298 · HTML: https://mlsanity.com/paper/2409.16298/

## 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 18 of its 37 references that are in the map.
- First posted on arXiv 9 Sep 2024.

## Placed in

- Diffusion models / [Flow matching, time series and science](https://mlsanity.com/diffusion/flow-matching-time-series-and-science/)
- Deep reinforcement learning methods / [RL for energy, networks and operations](https://mlsanity.com/deeprl/rl-for-energy-networks-and-operations/)

## Builds on (most cited first, 18 of 18)

- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [Denoising Diffusion Implicit Models](https://mlsanity.com/paper/2010.02502/) (2020)
- [Deep Unsupervised Learning using Nonequilibrium Thermodynamics](https://mlsanity.com/paper/1503.03585/) (2015)
- [Improved Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2102.09672/) (2021)
- [Supervised Contrastive Learning](https://mlsanity.com/paper/2004.11362/) (2020)
- [Addressing Function Approximation Error in Actor-Critic Methods](https://mlsanity.com/paper/1802.09477/) (2018)
- [Offline Reinforcement Learning: Tutorial, Review, and Perspectives on Open Problems](https://mlsanity.com/paper/2005.01643/) (2020)
- [A Minimalist Approach to Offline Reinforcement Learning](https://mlsanity.com/paper/2106.06860/) (2021)
- [Diffusion Policies as an Expressive Policy Class for Offline Reinforcement Learning](https://mlsanity.com/paper/2208.06193/) (2022)
- [Biological Sequence Design with GFlowNets](https://mlsanity.com/paper/2203.04115/) (2022)
- [Protein Design with Guided Discrete Diffusion](https://mlsanity.com/paper/2305.20009/) (2023)
- [Efficient Diffusion Policies for Offline Reinforcement Learning](https://mlsanity.com/paper/2305.20081/) (2023)
- [Design-Bench: Benchmarks for Data-Driven Offline Model-Based Optimization](https://mlsanity.com/paper/2202.08450/) (2022)
- [Towards Understanding and Improving GFlowNet Training](https://mlsanity.com/paper/2305.07170/) (2023)
- [Population-Based Black-Box Optimization for Biological Sequence Design](https://mlsanity.com/paper/2006.03227/) (2020)
- [DiffDock-PP: Rigid Protein-Protein Docking with Diffusion Models](https://mlsanity.com/paper/2304.03889/) (2023)
- [AntBO: Towards Real-World Automated Antibody Design with Combinatorial Bayesian Optimisation](https://mlsanity.com/paper/2201.12570/) (2022)
- [Structured Q-learning For Antibody Design](https://mlsanity.com/paper/2209.04698/) (2022)

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

- [Iterative Distillation for Reward-Guided Fine-Tuning of Diffusion Models in Biomolecular Design](https://mlsanity.com/paper/2507.00445/) (2025)

## Abstract (arXiv)

Antibodies offer great potential for the treatment of various diseases. However, the discovery of therapeutic antibodies through traditional wet lab methods is expensive and time-consuming. The use of generative models in designing antibodies therefore holds great promise, as it can reduce the time and resources required. Recently, the class of diffusion models has gained considerable traction for their ability to synthesize diverse and high-quality samples. In their basic form, however, they lack mechanisms to optimize for specific properties, such as binding affinity to an antigen. In contrast, the class of offline Reinforcement Learning (RL) methods has demonstrated strong performance in navigating large search spaces, including scenarios where frequent real-world interaction, such as interaction with a wet lab, is impractical. Our novel method, BetterBodies, which combines Variational Autoencoders (VAEs) with RL guided latent diffusion, is able to generate novel sets of antibody CDRH3 sequences from different data distributions. Using the Absolut! simulator, we demonstrate the improved affinity of our novel sequences to the SARS-CoV spike receptor-binding domain. Furthermore, we reflect biophysical properties in the VAE latent space using a contrastive loss and add a novel Q-function based filtering to enhance the affinity of generated sequences. In conclusion, methods such as ours have the potential to have great implications for real-world biological sequence design, where the generation of novel high-affinity binders is a cost-intensive endeavor.