# AntibodyFlow: Normalizing Flow Model for Designing Antibody Complementarity-Determining Regions

arXiv: https://arxiv.org/abs/2406.13162 · HTML: https://mlsanity.com/paper/2406.13162/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 13 of its 39 references that are in the map.
- First posted on arXiv 19 Jun 2024.

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

- [Semi-Supervised Classification with Graph Convolutional Networks](https://mlsanity.com/paper/1609.02907/) (2016)
- [Graph Attention Networks](https://mlsanity.com/paper/1710.10903/) (2017)
- [Auto-Encoding Variational Bayes](https://mlsanity.com/paper/1312.6114/) (2013)
- [Variational Inference with Normalizing Flows](https://mlsanity.com/paper/1505.05770/) (2015)
- [NICE: Non-linear Independent Components Estimation](https://mlsanity.com/paper/1410.8516/) (2014)
- [E(n) Equivariant Graph Neural Networks](https://mlsanity.com/paper/2102.09844/) (2021)
- [Bidirectional LSTM-CRF Models for Sequence Tagging](https://mlsanity.com/paper/1508.01991/) (2015)
- [GraphAF: a Flow-based Autoregressive Model for Molecular Graph Generation](https://mlsanity.com/paper/2001.09382/) (2020)
- [MoFlow: An Invertible Flow Model for Generating Molecular Graphs](https://mlsanity.com/paper/2006.10137/) (2020)
- [Iterative Refinement Graph Neural Network for Antibody Sequence-Structure Co-design](https://mlsanity.com/paper/2110.04624/) (2021)
- [Semismooth Newton Coordinate Descent Algorithm for Elastic-Net Penalized Huber Loss Regression and Quantile Regression](https://mlsanity.com/paper/1509.02957/) (2015)
- [Variational auto-encoding of protein sequences](https://mlsanity.com/paper/1712.03346/) (2017)
- [A random coordinate descent algorithm for optimization problems with composite objective function and linear coupled constraints](https://mlsanity.com/paper/1302.3074/) (2013)

## Abstract (arXiv)

Therapeutic antibodies have been extensively studied in drug discovery and development in the past decades. Antibodies are specialized protective proteins that bind to antigens in a lock-to-key manner. The binding strength/affinity between an antibody and a specific antigen is heavily determined by the complementarity-determining regions (CDRs) on the antibodies. Existing machine learning methods cast in silico development of CDRs as either sequence or 3D graph (with a single chain) generation tasks and have achieved initial success. However, with CDR loops having specific geometry shapes, learning the 3D geometric structures of CDRs remains a challenge. To address this issue, we propose AntibodyFlow, a 3D flow model to design antibody CDR loops. Specifically, AntibodyFlow first constructs the distance matrix, then predicts amino acids conditioned on the distance matrix. Also, AntibodyFlow conducts constraint learning and constrained generation to ensure valid 3D structures. Experimental results indicate that AntibodyFlow outperforms the best baseline consistently with up to 16.0% relative improvement in validity rate and 24.3% relative reduction in geometric graph level error (root mean square deviation, RMSD).