QM/MM Tutorial Series

QM/MM Tutorial Series – Part 2: Molecular Docking with CB-Dock2

In the previous post, we prepared the protein and ligand files using AutoDock Tools (ADT).

Now it's time to perform the docking.

One platform I've found particularly useful is CB-Dock2, a free web server that combines automatic cavity detection with AutoDock Vina. It identifies potential binding pockets on the protein and predicts how a ligand may bind within them.

Using it is straightforward:
✅ Upload the prepared protein file
✅ Upload the prepared ligand file
✅ Enter your email address (optional) to receive the results
You can then either:
🔹 Search Cavities first to inspect the predicted binding pockets and their locations
or
🔹 Run Auto Blind Docking directly, allowing CB-Dock2 to automatically identify potential binding sites and perform the docking.

The output includes the predicted binding cavity, the best binding pose, and an estimated binding affinity, providing a quick and convenient starting point for protein–ligand studies.

In the next post, we'll move beyond CB-Dock2 and perform docking directly with AutoDock Vina, allowing us to examine multiple binding poses rather than only the top-ranked solution. We'll then use the selected complex as the starting point for building a QM/MM calculation in ORCA.

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