EquiDock

What is EquiDock?

EquiDock predicts how two proteins bind together. Given the 3D structures of two unbound proteins, it outputs a docked complex showing their predicted binding pose.

The method uses SE(3)-equivariant graph neural networks, which means the predicted complex is always identical regardless of how the input structures are oriented. Rotate the inputs however you like, and the output remains consistent. This mathematical property makes predictions reliable and reproducible.

Developed at MIT and ETH Zurich, EquiDock was published as a spotlight paper at ICLR 2022. It runs 80-500x faster than traditional docking software by avoiding heavy sampling and refinement steps. The tradeoff is that it assumes rigid binding: neither protein changes shape upon contact.

How does EquiDock work?

EquiDock combines three techniques to predict binding poses:

Keypoint prediction: An attention mechanism identifies representative points on each protein that likely participate in binding. These keypoints approximate where the binding interface will form.

Optimal transport alignment: The model matches keypoints between the two proteins using optimal transport, finding correspondences between binding regions.

Differentiable Kabsch: Given matched keypoints, the algorithm computes the optimal rotation and translation to superimpose one protein onto the other, producing the final docked complex.

The neural network architecture extends Graph Matching Networks with E(3)-equivariant coordinate updates. Each protein is represented as a graph where nodes are residues and edges connect nearby residues. The network exchanges information both within each protein graph and between the two graphs to learn the binding transformation.

How to use EquiDock online

ProteinIQ provides GPU-accelerated EquiDock predictions directly in the browser.

Inputs

Input	Description
Receptor	PDB/ENT file or RCSB PDB ID. Typically the larger protein. Up to 1000 residues and 50 MB per file.
Ligand	PDB/ENT file or RCSB PDB ID. Typically the smaller protein. Up to 1000 residues and 50 MB per file.

Both proteins should be unbound structures (not already in a complex). The tool expects standard ATOM records with backbone atoms (N, CA, C).

Settings

Setting	Description
Model variant	DIPS (default): trained on ~42,000 complexes for general use. DB5: optimized for the Docking Benchmark 5 dataset.
Remove clashes	Optional native postprocessing to reduce steric clashes. Off by default; enabling it increases runtime.

Results

EquiDock produces one docked complex per receptor-ligand pair:

Output	Description
Complex PDB file	The receptor and transformed ligand in the predicted binding pose
Input PDB files	The prepared receptor and ligand used for docking
Run log	The selected model, clash-removal mode, number of complexes, and outcome; downloadable as run.log

The Data tab shows the pose rank, filename, and download. Rank identifies the output order and is not a confidence score. Use the Viewer to inspect the complex and the Files tab to download the complex, prepared inputs, and run log.

Limitations

EquiDock performs rigid docking only. Both proteins retain their input conformations. For proteins that undergo significant conformational changes upon binding, consider flexible docking methods.

The method predicts a single binding mode per pair. It does not model:

• Conformational flexibility or induced fit
• Allosteric effects
• Multiple simultaneous binding sites

Review the predicted interface and any remaining clashes alongside available experimental evidence.