# EquiBind: Geometric Deep Learning for Drug Binding Structure Prediction

arXiv: https://arxiv.org/abs/2202.05146 · HTML: https://mlsanity.com/paper/2202.05146/

## Key facts

- Cited by 144 papers in the map (data through 14 Oct 2026).
- Builds on 21 of its 69 references that are in the map.
- First posted on arXiv 7 Feb 2022.

## Builds on (most cited first, 21 of 21)

- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [Group Equivariant Convolutional Networks](https://mlsanity.com/paper/1602.07576/) (2016)
- [E(n) Equivariant Graph Neural Networks](https://mlsanity.com/paper/2102.09844/) (2021)
- [Tensor field networks: Rotation- and translation-equivariant neural networks for 3D point clouds](https://mlsanity.com/paper/1802.08219/) (2018)
- [E(3)-Equivariant Graph Neural Networks for Data-Efficient and Accurate Interatomic Potentials](https://mlsanity.com/paper/2101.03164/) (2021)
- [SE(3)-Transformers: 3D Roto-Translation Equivariant Attention Networks](https://mlsanity.com/paper/2006.10503/) (2020)
- [Learning from Protein Structure with Geometric Vector Perceptrons](https://mlsanity.com/paper/2009.01411/) (2020)
- [Geometric and Physical Quantities Improve E(3) Equivariant Message Passing](https://mlsanity.com/paper/2110.02905/) (2021)
- [Graph Matching Networks for Learning the Similarity of Graph Structured Objects](https://mlsanity.com/paper/1904.12787/) (2019)
- [Learning Gradient Fields for Molecular Conformation Generation](https://mlsanity.com/paper/2105.03902/) (2021)
- [GeoMol: Torsional Geometric Generation of Molecular 3D Conformer Ensembles](https://mlsanity.com/paper/2106.07802/) (2021)
- [Learning Neural Generative Dynamics for Molecular Conformation Generation](https://mlsanity.com/paper/2102.10240/) (2021)
- [Independent SE(3)-Equivariant Models for End-to-End Rigid Protein Docking](https://mlsanity.com/paper/2111.07786/) (2021)
- [Structure-aware Interactive Graph Neural Networks for the Prediction of Protein-Ligand Binding Affinity](https://mlsanity.com/paper/2107.10670/) (2021)
- [Protein-Ligand Scoring with Convolutional Neural Networks](https://mlsanity.com/paper/1612.02751/) (2016)
- [DeepAffinity: Interpretable Deep Learning of Compound-Protein Affinity through Unified Recurrent and Convolutional Neural Networks](https://mlsanity.com/paper/1806.07537/) (2018)
- [AtomNet: A Deep Convolutional Neural Network for Bioactivity Prediction in Structure-based Drug Discovery](https://mlsanity.com/paper/1510.02855/) (2015)
- [End-to-End Learning on 3D Protein Structure for Interface Prediction](https://mlsanity.com/paper/1807.01297/) (2018)
- [Generating 3D Molecular Structures Conditional on a Receptor Binding Site with Deep Generative Models](https://mlsanity.com/paper/2010.14442/) (2020)
- [Combining docking pose rank and structure with deep learning improves protein-ligand binding mode prediction](https://mlsanity.com/paper/1910.02845/) (2019)
- [Structure-aware generation of drug-like molecules](https://mlsanity.com/paper/2111.04107/) (2021)

## Built on by (most cited first, 30 of 144)

- [DiffDock: Diffusion Steps, Twists, and Turns for Molecular Docking](https://mlsanity.com/paper/2210.01776/) (2022)
- [Torsional Diffusion for Molecular Conformer Generation](https://mlsanity.com/paper/2206.01729/) (2022)
- [Structure-based Drug Design with Equivariant Diffusion Models](https://mlsanity.com/paper/2210.13695/) (2022)
- [3D Equivariant Diffusion for Target-Aware Molecule Generation and Affinity Prediction](https://mlsanity.com/paper/2303.03543/) (2023)
- [Everything is Connected: Graph Neural Networks](https://mlsanity.com/paper/2301.08210/) (2023)
- [PiFold: Toward effective and efficient protein inverse folding](https://mlsanity.com/paper/2209.12643/) (2022)
- [A Comprehensive Survey on Deep Graph Representation Learning](https://mlsanity.com/paper/2304.05055/) (2023)
- [MolGenSurvey: A Systematic Survey in Machine Learning Models for Molecule Design](https://mlsanity.com/paper/2203.14500/) (2022)
- [Learning Hierarchical Protein Representations via Complete 3D Graph Networks](https://mlsanity.com/paper/2207.12600/) (2022)
- [Navigating the Design Space of Equivariant Diffusion-Based Generative Models for De Novo 3D Molecule Generation](https://mlsanity.com/paper/2309.17296/) (2023)
- [Structure-based drug design with geometric deep learning](https://mlsanity.com/paper/2210.11250/) (2022)
- [Efficient and Equivariant Graph Networks for Predicting Quantum Hamiltonian](https://mlsanity.com/paper/2306.04922/) (2023)
- [Geometry-Complete Diffusion for 3D Molecule Generation and Optimization](https://mlsanity.com/paper/2302.04313/) (2023)
- [On the Scalability of GNNs for Molecular Graphs](https://mlsanity.com/paper/2404.11568/) (2024)
- [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)
- [Fractional Denoising for 3D Molecular Pre-training](https://mlsanity.com/paper/2307.10683/) (2023)
- [IGB: Addressing The Gaps In Labeling, Features, Heterogeneity, and Size of Public Graph Datasets for Deep Learning Research](https://mlsanity.com/paper/2302.13522/) (2023)
- [Harmonic Self-Conditioned Flow Matching for Multi-Ligand Docking and Binding Site Design](https://mlsanity.com/paper/2310.05764/) (2023)
- [A Survey of Geometric Graph Neural Networks: Data Structures, Models and Applications](https://mlsanity.com/paper/2403.00485/) (2024)
- [Interpretable Geometric Deep Learning via Learnable Randomness Injection](https://mlsanity.com/paper/2210.16966/) (2022)
- [Deep Confident Steps to New Pockets: Strategies for Docking Generalization](https://mlsanity.com/paper/2402.18396/) (2024)
- [Towards Predicting Equilibrium Distributions for Molecular Systems with Deep Learning](https://mlsanity.com/paper/2306.05445/) (2023)
- [Tx-LLM: A Large Language Model for Therapeutics](https://mlsanity.com/paper/2406.06316/) (2024)
- [Evaluating Self-Supervised Learning for Molecular Graph Embeddings](https://mlsanity.com/paper/2206.08005/) (2022)
- [Graph Neural Networks for Molecules](https://mlsanity.com/paper/2209.05582/) (2022)
- [DisCo-Diff: Enhancing Continuous Diffusion Models with Discrete Latents](https://mlsanity.com/paper/2407.03300/) (2024)
- [Equivariance via Minimal Frame Averaging for More Symmetries and Efficiency](https://mlsanity.com/paper/2406.07598/) (2024)
- [Unsupervised Protein-Ligand Binding Energy Prediction via Neural Euler's Rotation Equation](https://mlsanity.com/paper/2301.10814/) (2023)
- [Rank Collapse Causes Over-Smoothing and Over-Correlation in Graph Neural Networks](https://mlsanity.com/paper/2308.16800/) (2023)

## Abstract (arXiv)

Predicting how a drug-like molecule binds to a specific protein target is a core problem in drug discovery. An extremely fast computational binding method would enable key applications such as fast virtual screening or drug engineering. Existing methods are computationally expensive as they rely on heavy candidate sampling coupled with scoring, ranking, and fine-tuning steps. We challenge this paradigm with EquiBind, an SE(3)-equivariant geometric deep learning model performing direct-shot prediction of both i) the receptor binding location (blind docking) and ii) the ligand's bound pose and orientation. EquiBind achieves significant speed-ups and better quality compared to traditional and recent baselines. Further, we show extra improvements when coupling it with existing fine-tuning techniques at the cost of increased running time. Finally, we propose a novel and fast fine-tuning model that adjusts torsion angles of a ligand's rotatable bonds based on closed-form global minima of the von Mises angular distance to a given input atomic point cloud, avoiding previous expensive differential evolution strategies for energy minimization.