# Active learning for affinity prediction of antibodies

arXiv: https://arxiv.org/abs/2406.07263 · HTML: https://mlsanity.com/paper/2406.07263/

## Key facts

- Cited by 4 papers in the map (data through 14 Oct 2026).
- Builds on 13 of its 37 references that are in the map.
- First posted on arXiv 11 Jun 2024.

## Builds on (most cited first, 13 of 13)

- [Automatic chemical design using a data-driven continuous representation of molecules](https://mlsanity.com/paper/1610.02415/) (2016)
- [GuacaMol: Benchmarking Models for De Novo Molecular Design](https://mlsanity.com/paper/1811.09621/) (2018)
- [Bayesian Optimization in a Billion Dimensions via Random Embeddings](https://mlsanity.com/paper/1301.1942/) (2013)
- [Constrained Bayesian Optimization with Noisy Experiments](https://mlsanity.com/paper/1706.07094/) (2017)
- [Accelerating Bayesian Optimization for Biological Sequence Design with Denoising Autoencoders](https://mlsanity.com/paper/2203.12742/) (2022)
- [Multi-Information Source Optimization](https://mlsanity.com/paper/1603.00389/) (2016)
- [High-Dimensional Bayesian Optimisation with Variational Autoencoders and Deep Metric Learning](https://mlsanity.com/paper/2106.03609/) (2021)
- [Combining Latent Space and Structured Kernels for Bayesian Optimization over Combinatorial Spaces](https://mlsanity.com/paper/2111.01186/) (2021)
- [LIMO: Latent Inceptionism for Targeted Molecule Generation](https://mlsanity.com/paper/2206.09010/) (2022)
- [Genetic algorithms are strong baselines for molecule generation](https://mlsanity.com/paper/2310.09267/) (2023)
- [Autonomous discovery in the chemical sciences part I: Progress](https://mlsanity.com/paper/2003.13754/) (2020)
- [AntBO: Towards Real-World Automated Antibody Design with Combinatorial Bayesian Optimisation](https://mlsanity.com/paper/2201.12570/) (2022)
- [MFBind: a Multi-Fidelity Approach for Evaluating Drug Compounds in Practical Generative Modeling](https://mlsanity.com/paper/2402.10387/) (2024)

## Built on by (most cited first, 4 of 4)

- [Robust Bayesian Optimisation with Unbounded Corruptions](https://mlsanity.com/paper/2511.15315/) (2025)
- [Active learning for energy-based antibody optimization and enhanced screening](https://mlsanity.com/paper/2409.10964/) (2024)
- [Is Sequence Information All You Need for Bayesian Optimization of Antibodies?](https://mlsanity.com/paper/2509.24933/) (2025)
- [BOAT: Navigating the Sea of In Silico Predictors for Antibody Design via Multi-Objective Bayesian Optimization](https://mlsanity.com/paper/2604.13980/) (2026)

## Abstract (arXiv)

The primary objective of most lead optimization campaigns is to enhance the binding affinity of ligands. For large molecules such as antibodies, identifying mutations that enhance antibody affinity is particularly challenging due to the combinatorial explosion of potential mutations. When the structure of the antibody-antigen complex is available, relative binding free energy (RBFE) methods can offer valuable insights into how different mutations will impact the potency and selectivity of a drug candidate, thereby reducing the reliance on costly and time-consuming wet-lab experiments. However, accurately simulating the physics of large molecules is computationally intensive. We present an active learning framework that iteratively proposes promising sequences for simulators to evaluate, thereby accelerating the search for improved binders. We explore different modeling approaches to identify the most effective surrogate model for this task, and evaluate our framework both using pre-computed pools of data and in a realistic full-loop setting.