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OD Walkthrough

www.opendiscovery.org.uk

Version: 1.0a

Contacts: gareth.price@warwick.ac.uk; a.marsh@warwick.ac.uk

Example 1: Statin + HMG-CoA Reductase

You can follow along with this example by downloading the initial PDB from here. Before starting, watch the video tutorial provided by the authors of AutoDock Vina, here.

Preparing the files

We first need to split the crystal structure of the complex into separate receptor and ligand files. Open up the file 1T02.pdb in your favourite text editor and look at the file. The first section are REMARKS about the structure:

Delete all the header lines, up to line 765 which is the first atom of the structure.

Copy all lines with ATOM at the start into its own file, named hmg_coa.pdb. Include the TER statement in line 5529. Then, copy the subsequent lines starting with HETATM and LVA in the the fourth column into its own file, LVA.pdb:

Now, put hmg_coa.pdb into a 'receptor' folder and LVA.pdb into a 'pdb' folder. Next, we need to prepare the receptor protein (hmg_coa.pdb).

Open up AutoDockTools, and follow the steps in the image below. Make sure to remember the coordinates and dimensions. Make sure Spacing (Angstrom) is set to 1.000.

Open a new file and enter the box coordinates and dimensions such as:

center_x = 83.033
center_y = 125.978
center_z = 106.748

size_x = 16
size_y = 14
size_z = 14

Save it as hmg_coa.conf.

You should have a folder that looks like:

Running ODScreen

We can now run ODScreen. First, let's check that everything is installed properly. In terminal, cd to the Protocol Folder (i.e. the folder with odscreen.py, odparam.py etc.) and run python odcheck.py. Check that there are no Failures, and follow the installation guides if there are. Now, we can run the screening protocol. Navigate to the folder where hmg_coa.conf is located (from before). Now we can run odscreen.py. Make sure you use the correct path to the odscreen.py file.

python /protocolfolder/odscreen.py -d . -r hmg_coa -i pdb -c hmg_coa.conf

This is the result:

# ----------------------------------------- #
#              OPEN DISCOVERY               #
#             Screening Module              #
# ----------------------------------------- #
# Version:  1.0                             #
# URL:      www.opendiscovery.org.uk        #
# Contacts: gareth.price@warwick.ac.uk      #
#           a.marsh@warwick.ac.uk           #
# ----------------------------------------- #
# LigDir: /Desktop/example-statin           #
#           Receptor Name: hmg_coa          #
#              Input Type: pdb              #
#             Conf: hmg_coa.conf            #
#             Exhaustivness: 20             #
# ----------------------------------------- #
#  Time Started: Mon, 22 Jul 2013 00:15:20  #
# ----------------------------------------- #


                PDB -> SMILES
            Writing smiles/LVA.txt


                    IMAGES
            Writing images/LVA.svg


                     MOL
             Writing mol/LVA.mol


                     MOL2
            Writing mol2/LVA.mol2


                 MINIMISATION
                Minimising LVA


               PDBQT PREPARATION
              Writing LVA.pdbqt


                   SCREENING
                Processing LVA


                  EXTRACTING
           Processing results/LVA/


                  PDB -> MOL2
        Writing results-mol2/LVA.mol2


                  SUMMARISING
               Summarising LVA


               MAKING COMPLEXES
                 Writing LVA


# ----------------------------------------- #
#                  FINSHED                  #
#         Time Taken: 231.40 seconds        #
# ----------------------------------------- #

The resulting files are:

From this point on you can analyse the results. A starting point is to look at the binding energies, sorted and summarised in the sum