2024 DOCK tutorial 3 with PDBID 1Y0X

Introduction

1. Setting up your environment
2. Downloading a protein from the PDB database
3. Determining if there are any missing loops in the structure and if they need to be modeled
4. Preparing the ligand
5. Preparing the protein
6. Finding the binding site of the protein

Preparation of the ligand and protein

1. Evaluate the structure to determine if there are any missing loops
2. Prepare the protein structure
3. Prepare the ligand structure

Evaluating the Structure

1. Select an atom at near the start of the missing section (hold the ctrl button while clicking it)
2. Select another atom near the binding site (hold ctrl + shift while clicking the second atom)
3. Go to Tools → Structure Analysis → Distances

Preparing the Protein file

1. Select an atom on the protein
2. Press the up arrow until the entire protein is selected
3. Go to Select → Invert (all models). This will change the selection from the protein to everything else in the structure
4. Go to Actions → Atoms/Bonds → Delete
5. Save the structure with a new file name (i.e. 4s0v_protein_only.pdb). Your pdb file will now look similar to this:
6. Adding hydrogens
7. Adding charge
8. Click on one atom anywhere on the protein
9. Click on Select → Zone. This will cause the following dialogue box to appear:

Preparing the Ligand File

1. Select an atom on the ligand
2. Press the up arrow until the entire ligand is selected (you may have to press the up arrow many times)
3. Go to Select → Invert (all models). This will change the selection from the ligand to everything else in the structure
4. Go to Actions → Atom/Bonds → Delete
5. Save the structure with a new file name (i.e. 4s0v_ligand_only.pdb). The image will look similar to this:

1. Add hydrogens
2. Add charges

Creating the Protein Binding Site Surface

Binding Site Spheres

1. scp selected_spheres.sph to your local computer
2. Close any open sessions you have in Chimera
3. In Chimera open selected_spheres.sph
4. In the current session, open the original protein/ligand complex (4s0v.pdb)
5. You should see the spheres located within the binding site of the protein, similar to:

1. Hold down ctrl and click on a sphere
2. Press the up arrow until all spheres are selected
3. Actions → Atoms/Bonds → hide
4. Verify the ligand is where the spheres were