# PROflow: An iterative refinement model for PROTAC-induced structure prediction

arXiv: https://arxiv.org/abs/2405.06654 · HTML: https://mlsanity.com/paper/2405.06654/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 15 of its 44 references that are in the map.
- First posted on arXiv 10 Apr 2024.

## Builds on (most cited first, 15 of 15)

- [Flow Matching for Generative Modeling](https://mlsanity.com/paper/2210.02747/) (2022)
- [Neural Ordinary Differential Equations](https://mlsanity.com/paper/1806.07366/) (2018)
- [Improving and generalizing flow-based generative models with minibatch optimal transport](https://mlsanity.com/paper/2302.00482/) (2023)
- [DiffDock: Diffusion Steps, Twists, and Turns for Molecular Docking](https://mlsanity.com/paper/2210.01776/) (2022)
- [Flow Matching on General Geometries](https://mlsanity.com/paper/2302.03660/) (2023)
- [Torsional Diffusion for Molecular Conformer Generation](https://mlsanity.com/paper/2206.01729/) (2022)
- [e3nn: Euclidean Neural Networks](https://mlsanity.com/paper/2207.09453/) (2022)
- [EquiBind: Geometric Deep Learning for Drug Binding Structure Prediction](https://mlsanity.com/paper/2202.05146/) (2022)
- [AlphaFold Meets Flow Matching for Generating Protein Ensembles](https://mlsanity.com/paper/2402.04845/) (2024)
- [Independent SE(3)-Equivariant Models for End-to-End Rigid Protein Docking](https://mlsanity.com/paper/2111.07786/) (2021)
- [Equivariant Flow Matching with Hybrid Probability Transport](https://mlsanity.com/paper/2312.07168/) (2023)
- [E3Bind: An End-to-End Equivariant Network for Protein-Ligand Docking](https://mlsanity.com/paper/2210.06069/) (2022)
- [End-to-End Learning on 3D Protein Structure for Interface Prediction](https://mlsanity.com/paper/1807.01297/) (2018)
- [Harmonic Self-Conditioned Flow Matching for Multi-Ligand Docking and Binding Site Design](https://mlsanity.com/paper/2310.05764/) (2023)
- [DiffDock-PP: Rigid Protein-Protein Docking with Diffusion Models](https://mlsanity.com/paper/2304.03889/) (2023)

## Abstract (arXiv)

Proteolysis targeting chimeras (PROTACs) are small molecules that trigger the breakdown of traditionally ``undruggable'' proteins by binding simultaneously to their targets and degradation-associated proteins. A key challenge in their rational design is understanding their structural basis of activity. Due to the lack of crystal structures (18 in the PDB), existing PROTAC docking methods have been forced to simplify the problem into a distance-constrained protein-protein docking task. To address the data issue, we develop a novel pseudo-data generation scheme that requires only binary protein-protein complexes. This new dataset enables PROflow, an iterative refinement model for PROTAC-induced structure prediction that models the full PROTAC flexibility during constrained protein-protein docking. PROflow outperforms the state-of-the-art across docking metrics and runtime. Its inference speed enables the large-scale screening of PROTAC designs, and computed properties of predicted structures achieve statistically significant correlations with published degradation activities.