Lecture 4:Targeted or site specific docking by PyRx| find binding pocket residues| interpret result

🎯 Topic: Targeted Docking — From Binding Site to Complex Generation

Step 1: Identifying the Binding Pocket Residues
To perform targeted docking, we first need to identify the active or binding site of the protein. You can do this using:

Tools like CASTp or discovery studio to predict pocket residues based on surface geometry.

Literature or PDB data: If your protein-ligand complex is known, check the original article or co-crystallized ligand in the PDB file.

Visualization tools like PyMOL or Chimera: Use these to inspect where the ligand binds or where conserved residues are located.

Once identified, note the residue numbers and chain ID for targeted docking.
Example: Binding pocket residues might be listed like this: ASP34, HIS57, SER195 in chain A.

Step 2: Performing Targeted Docking
Now that you know the binding site:

Set a grid box around the binding pocket in tools like AutoDock Vina or PyRx.

Keep the box size slightly larger than the pocket to allow some flexibility.

If you are using AutoDock Tools, define the grid center based on the binding residues or known ligand position.

Step 3: Interpreting the Docking Results
After running docking:

Check the binding affinity values (in kcal/mol). Lower values mean stronger binding.

Look at the RMSD values — a value close to 0 indicates that the pose is similar to the best pose.

Open the top docking poses in PyMOL or Discovery Studio to analyze interactions.

Look for:

Hydrogen bonds

Hydrophobic contacts

π-π stacking

Salt bridges

You can also use LigPlot+ or Discovery Studio Visualizer to generate 2D interaction maps.

Step 4: Generating the Protein-Ligand Complex
Once you select the best docking pose:

Load both the receptor PDB and ligand (from docking output) in PyMOL.

Save as a single complex using the “Save Molecule As” option.

You can now use this complex for further analysis or simulations.

Now you have your protein-ligand complex file!


"In this video, we explored how to identify binding pocket residues, perform targeted docking, interpret docking scores and interactions, and generate the final protein-ligand complex. These steps are essential in structure-based drug discovery and help you understand how molecules interact at the atomic level.