AUTO DOCK

1. Opening the protein pdb file.

Go to File/Read Molecule.

Read in a pdb file for a protein that has no hydrogen atoms.  

Here it call as dhp_noh.pdb.   

Before you read in the pdb file open it and change the iron atom from FE to Fe.   

In general, all element must have the same appearance as in the periodic table for use in Autodock.  

The protein will look as below.

2. Assign polar hydrogens and save the file as a pdbqt file.

Go to Edit/Hydrogens/Add.

Select “Polar Only”.   

This means O and N atoms which is polar will get an H.  

C-H which is non polar will be treated as a unit in the electrostatic calculation.

Now we need to write the file type for the Autodock calculation.  

It has a pdbqt extension.

Go to Grid/Macromolecule/Choose.

Make sure the molecule is highlighted and click on “Select Molecule”

Write the file as a pdbqt on the menu that appears. 

   3. Determine a grid center and grid dimensions for the Autodock calculation. 

      Edit the pdbqt file using an editor like UltraEdit.  

      Here we want to identify some location in the protein that will serve as the center of the grid.   

      I will choose the Fe atom since I am most interested in the heme.   

      You could also choose the center of mass of the protein.   

       Recall that you can find the center of mass in VMD using the commands 

      Ø  set OBJECT [atomselect top prot]

      Ø  measure center $OBJECT

 

Next we choose Grid/Grid Box

The Grid menu appears.

 

Adjust the Spacing to 1.00 so the grid is in even increments of 1.00 Angstrom.

Input the center of the grid and then adjust the grid size.   

The grid dimensions can range from 1 to 40 Angstroms.

The 18 x 18 x 18 grid is appropriate to focus on the heme itself.

 

The 32 x 40 x 30 grid covers essential the whole protein. 

4. Read in the substrate from a pdb file and then generate the pdbqt file.

Next we need to read in the substrate.   

First, we want to check the substrate file to make sure that the atom types have the appropriate names.  

 For example, bromine needs to be Fe and not FE.

To load the substrate into Autodock Tools use the Ligand/Input/Open menu selection.

We choose tbp.pdb.

‘

‘Hide the protein and center the substrate (just for appearance).

When the ligand is read into the program, it automatically is assigned charges. 

To write the ligand as an output file use Ligand/Output and then select to write it as a pdbqt file.

Aside from writing the pdbqt files, the Autodock Tools interface does not generate the configuration file for “vina” the docking routine. 

5. Edit the configuration file to prepare to run Vina.

Along the way you need to save the information you have obtained, such as the center of mass and grid box and write that information in a very simple configuration file shown below.

The output will be put in all.pdbqt as a series of 10 different structures of the substrate. 

The exhaustiveness tells the program how hard to search.   

In our case the molecule is very simple and the protein is relatively small so we set the exhaustiveness to the maximum value of 16.

6. Dock the substrate using Vina.

To run vina, go to the Command Prompt.

Navigate to the appropriate directory.

One clever trick is to put the vina program (which you download from the Autodock website) into the Windows/system32 directory.  

From the directory where the program is you type.

      Ø  copy vina.exe c:\windows\system32

Then you may type vina anywhere on your system and it will run the vina program.  If you type

      Ø  vina

You get a kind of help menu.

To run the program using the configuration file config.txt you type.

      Ø  vina –config config.txt –log log.txt

Note use two dashes - -, not one.  Once vina starts running you will see the progress on the screen.   

It typically takes only a few minutes for our system.

You can read in the final pdbqt structure using the Read/Molecule command and it will show you all of your docked structures.   

The green substrate remains from previous work.   

We could also delete it if we want to put the protein in the center of the screen.

An important final step is to read your docked inhibitor molecules into VMD and check that the molecular bonds are all in order. 
Sometimes atoms get switched or minus signs get deleted during translation of file types between pdbqt and pdb. 
A common error that we have observed is for the CAG and CAH carbon atoms to be reversed in the docked inhibitor. 
Then the bonds look like a zig-zag across the phenyl ring. 
You may fix this quick simply by editing the pdb file and reversing the CAG and CAH atom names.