# Fast and Accurate Blind Flexible Docking

arXiv: https://arxiv.org/abs/2502.14934 · HTML: https://mlsanity.com/paper/2502.14934/

## Key facts

- Cited by 2 papers in the map (data through 14 Oct 2026).
- Builds on 14 of its 46 references that are in the map.
- First posted on arXiv 20 Feb 2025.

## Builds on (most cited first, 14 of 14)

- [A Comprehensive Survey on Graph Neural Networks](https://mlsanity.com/paper/1901.00596/) (2019)
- [Diffusion Models: A Comprehensive Survey of Methods and Applications](https://mlsanity.com/paper/2209.00796/) (2022)
- [E(n) Equivariant Graph Neural Networks](https://mlsanity.com/paper/2102.09844/) (2021)
- [DiffDock: Diffusion Steps, Twists, and Turns for Molecular Docking](https://mlsanity.com/paper/2210.01776/) (2022)
- [Professor Forcing: A New Algorithm for Training Recurrent Networks](https://mlsanity.com/paper/1610.09038/) (2016)
- [EquiBind: Geometric Deep Learning for Drug Binding Structure Prediction](https://mlsanity.com/paper/2202.05146/) (2022)
- [TorchDrug: A Powerful and Flexible Machine Learning Platform for Drug Discovery](https://mlsanity.com/paper/2202.08320/) (2022)
- [State-specific protein-ligand complex structure prediction with a multi-scale deep generative model](https://mlsanity.com/paper/2209.15171/) (2022)
- [E3Bind: An End-to-End Equivariant Network for Protein-Ligand Docking](https://mlsanity.com/paper/2210.06069/) (2022)
- [Deep Confident Steps to New Pockets: Strategies for Docking Generalization](https://mlsanity.com/paper/2402.18396/) (2024)
- [FABind: Fast and Accurate Protein-Ligand Binding](https://mlsanity.com/paper/2310.06763/) (2023)
- [Re-Dock: Towards Flexible and Realistic Molecular Docking with Diffusion Bridge](https://mlsanity.com/paper/2402.11459/) (2024)
- [FABind+: Enhancing Molecular Docking through Improved Pocket Prediction and Pose Generation](https://mlsanity.com/paper/2403.20261/) (2024)
- [Multi-task Bioassay Pre-training for Protein-ligand Binding Affinity Prediction](https://mlsanity.com/paper/2306.04886/) (2023)

## Built on by (most cited first, 2 of 2)

- [Reference-guided Policy Optimization for Molecular Optimization via LLM Reasoning](https://mlsanity.com/paper/2603.05900/) (2026)
- [The Docking Game: Loop Self-Play for Fast, Dynamic, and Accurate Prediction of Flexible Protein-Ligand Binding](https://mlsanity.com/paper/2508.05006/) (2025)

## Abstract (arXiv)

Molecular docking that predicts the bound structures of small molecules (ligands) to their protein targets, plays a vital role in drug discovery. However, existing docking methods often face limitations: they either overlook crucial structural changes by assuming protein rigidity or suffer from low computational efficiency due to their reliance on generative models for structure sampling. To address these challenges, we propose FABFlex, a fast and accurate regression-based multi-task learning model designed for realistic blind flexible docking scenarios, where proteins exhibit flexibility and binding pocket sites are unknown (blind). Specifically, FABFlex's architecture comprises three specialized modules working in concert: (1) A pocket prediction module that identifies potential binding sites, addressing the challenges inherent in blind docking scenarios. (2) A ligand docking module that predicts the bound (holo) structures of ligands from their unbound (apo) states. (3) A pocket docking module that forecasts the holo structures of protein pockets from their apo conformations. Notably, FABFlex incorporates an iterative update mechanism that serves as a conduit between the ligand and pocket docking modules, enabling continuous structural refinements. This approach effectively integrates the three subtasks of blind flexible docking-pocket identification, ligand conformation prediction, and protein flexibility modeling-into a unified, coherent framework. Extensive experiments on public benchmark datasets demonstrate that FABFlex not only achieves superior effectiveness in predicting accurate binding modes but also exhibits a significant speed advantage (208 ×) compared to existing state-of-the-art methods. Our code is released at https://github.com/tmlr-group/FABFlex.