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MOE - DockingTutorial

This tutorial provides instructions for docking ligands into a protein receptor using MOE software. It describes setting up and running a docking simulation to redock a known ligand back into its binding site, as well as docking additional ligands from a database into the receptor binding pocket.

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talal adlan
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© © All Rights Reserved
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Download as PDF, TXT or read online on Scribd
217 views

MOE - DockingTutorial

This tutorial provides instructions for docking ligands into a protein receptor using MOE software. It describes setting up and running a docking simulation to redock a known ligand back into its binding site, as well as docking additional ligands from a database into the receptor binding pocket.

Uploaded by

talal adlan
Copyright
© © All Rights Reserved
Available Formats
Download as PDF, TXT or read online on Scribd
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2.

Docking Tutorial
This tutorial provides a worked example of docking in MOE. The PDE4B
receptor from the structure of PDE4B in complex with rolipram (PDB code
1RO6) will be used as the receptor for docking. Initially, we will dock rolipram
back into the receptor (self-docking) and then, in a second docking run, various
known PDE4B inhibitors will be docked into the PDE4B receptor. For the
second run, we will create a pharmacophore query prior to docking and we
will use it as a filter for docking placement.
MOE Tutorials
Conventions Used in this Tutorial

MOE MOE Window


2. Docking Tutorial
DBV Database Viewer
RHS Right Hand Side Button Bar (MOE Window)

Extracted from the MOE manual In this tutorial, we will assume that you are using a three-button mouse. For
information on using a two-button mouse see Using the Mouse.

Prepare the 1RO6 structure for docking.


Dr. Talal Ahmed Awad
MOE | File | Open | $MOE/sample/mol/1RO6.moe
Ph.D, BioChemistry, M.Sc, Organic Chemistry
Ibn Sina University The original 1RO6 PDB file contained crystallized Zn and Mn metal
Faculty of Clinical Pharmacy ions. CCG processed the 1RO6 pdb file to 1) retain only the waters in
the active site, 2) keep first protein chain, 3) remove Mn metal ion 4)
removed As (arsenic).

Add hydrogens and partial charges to the system with the Protonate3D
application.

MOE | Compute | Protonate3D

Click OK in the prompt to perform the calculation

The calculation will take a few moments. Progress reports are written
to the MOE window. The messages disappear when the calculation is
done. Now draw a Gaussian Contact surface around the binding site.

MOE | Compute | Surfaces and Maps


1
MOE | Compute | Simulations | Dock

1. Verify that the Receptor pull-down menu is set to


Receptor+Solvent and that the Site pull-down menu is set to
Ligand Atoms (the residues close to the ligand atoms will
define the docking site).
2. For simplicity, in this first example we will dock only the
bound ligand. Thus, set the Ligand pull-down menu to
Ligand Atoms.
3. Use the default Placement method: Triangle Matcher.
Set the Color: to Constant and the color to light yellow. Click Apply 4. Set the first scoring function, Rescoring 1 to the default
to draw the surface. Press Isolate to render the binding site and MOE London dG and set the Retain dropdown to 10.
| Render | Backbone | None to remove the backbone rendering. Slide 5. Set the Refinement to Forcefield. The docked poses will be
the TB: slider to ~75 % to increase the back transparency of the energy minimized in the receptor pocket.
surface. 6. Set the refinement scoring function, Rescoring 2 to None and
set the Retain dropdown to 10. With this setting, the final
refined poses will be ranked by the MM/GBVI binding free
energy estimation.

Setup the docking run.


7. Click OK to start docking. When the docking is finished, the
Here we will open the Dock panel and setup the docking options for docked poses and scores will be written to the ‘dock.mdb’
this particular run. Full descriptions of all the Docking parameters can output database.
be found in the Docking chapter.

2
The docking results will appear in a DBV window (dock.mdb). See in
the S field that the docking poses are ranked by the MM/GBVI binding
free energy calculation which is identical to the E_refine score. Also Use the arrows of the Database Browser to browse through some of
note the rmsd field, which is the RMSD of the docking pose compared the poses returned by MOE Dock. Next, we will dock a database of
to the co-crystal ligand position. Use the Database browser to ligands to this receptor and we will filter the poses with a
compare the docking poses to the ligand in the co-crystallized pharmacophore query. Close the Database Browser and close the
structure. docking database (dock.mdb) when finished.

DBV | File | Browser

The Database Browser will sequentially display the docked ligands


of the database in the MOE window. For a better view of the docked
ligand poses, ctrl-click on an atom from the docked ligand in the MOE
window and Render | Color Carbon | Green to color the carbons
green. Then apply Render | Stick and hide hydrogens using RHS |
Hide | Hydrogens. The ligands you browse should appear as shown
in the image below.

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