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18.6 Protein-Protein Docking
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[ ODA | Setup | P-P Set Project | P-P Receptor Setup | P-P Ligand Setup | Epitope | P-P Maps | P-P Batch | Results | Refinement ]

Here we describe the steps for protein-protein docking. An example is described using a complex of subtilisin and chymotrypsin (PDB code:2sni). The example will re-dock the ligand ( PDB code entry 2ci2) into the receptor molecule (PDB code 2st1) and then determine how accurately the molecules are docked by comparison with the complex 2sni. The structure of 2sni is shown below with the ligand displayed in green and the receptor in yellow.

18.6.1 Optimal Docking Area


The ICM Optimal Docking Area method is a useful way of prediciting likely protein-protein interaction interfaces. If you do not have mutational data or other experimental data which indicates the likely protein-protein docking site this method will be useful. This procedure can save you time during the docking procedure by focusing your docking only on areas on the receptor and ligand most likely to interact.

Theory

ODA (Optimal Docking Areas) is a new method to predict protein-protein interaction sites on protein surfaces. It identifies optimal surface patches with the lowest docking desolvation energy values as calculated by atomic solvation parameters (ASP) derived from octanol/water transfer experiments and adjusted for protein-protein docking. The predictor has been benchmarked on 66 non-homologous unbound structures, and the identified interactions points (top 10 ODA hot-spots) are correctly located in 70% of the cases (80% if we disregard NMR structures).

To display the optimal docking area.

ODA Example with a subtilisin-chymotrypsin complex.

As an example we will determine whether the ICM-ODA method can accurately predict the binding surface of the complex between subtilisin and chymotrypsin. This example is used in the protein-protein docking tutorial below as well.

This complex has been solved experimentally and has PDB id 2sni.

Calculate the ODA for each subunit (Tools/3D Predict / Protein Interface by ODA).

ODA for subtilisin and ODA for chymotrypsin - red colored spheres indicate a region highly likely to be involved in protein-protein interaction, blue coloring is unlikely to be involved in protein-protein interaction. A clickable table is also displayed with ODA values.

18.6.2 Protein-Protein Docking Procedure


To begin the protein-protein docking procedure:

  1. Read in the PDB files for 2ci2 (ligand) 2st1 (receptor) and 2sni (complex for comparison). For instructions on how to load a PDB structure into ICM please click here.
  2. Convert all three PDB files into ICM objects.
  3. Delete all waters and sulfate ions, you can keep the calcium ions if you wish.

Now go onto the first step of the protein-protein docking protocol which is to Set Project name.

NOTE: All the protein-proteing docking options can be found in the GUI menu Docking/Protein-Protein.

18.6.3 Protein-Protein Set Project


Docking/Protein-protein/Set Project

Start the protein-protein docking project setup by defining the project name:

Now setup the receptor.

18.6.4 Protein-Protein Receptor Setup


Docking/Protein-protein/Receptor setup

Now setup the ligand.

18.6.5 Protein-Protein Ligand Setup


Docking/Protein-protein/Ligand setup

Now select an initial point of interest on the receptor referred to as epitope selection (NOTE: This step is optional. If you do not wish to select an initial point of interest junp to the make maps section. It is recommended to narrow down the docking interaction site as much as possible by selecting epitoptes. Protein-protein interaction sites can be predicted by ODA or experimental data or based on a reference complex.

18.6.6 Epitope Selection


Docking/Protein-protein/Epitope selection

Select an initial point of interest on the receptor for the docking simulation. You may want to check biological data or a reference complex or predict interaction sites using ODA before doing this step. If you do not know the docking interface location you should setup multiple docking runs for different epitopes on the receptor.

NOTE: If you are unsure which epitopes you have selected they are listed in the DOCKING_PROJECT_NAME.tab file in the first two fields called I_selLigPos (receptor epitopes) and I_selLigRot (ligand epitopes).

The next step is to make the maps of the receptor.

18.6.7 Protein-Protein Make Receptor Maps


Docking/Protein-protein/Make Receptor Maps

Now run the docking simulation.

18.6.8 Protein-Protein Docking Batch


The docking can be run on your local machine or in PBS.

To run on your local machine:

Docking/Protein-protein/Docking Batch/Local Machine

To run in PBS:

Docking/Protein-protein/Docking Batch/PBS

You can check the docking progress by going to Windows/Background Jobs. Once the docking has finished a dialog window will be displayed telling you that the docking job is complete - Click OK and a results table will be displayed. Read the next section on how to view the results.

Error messages are reported at the end of the DOCKING_Project.ou output file. You can also see details about any errors by clicking on the Details button in the dialog window which is displayed once the docking run is finished.

18.6.9 Display Grid Docking Results


Once the docking is finished you should see a table A table as shown below will be displayed. You can sort the table by Energy (ener) by right clicking on the column header and select sort.

To display the complexes:

If no docking table is displayed you can process the results by:

The output columns represent:

All your docking data is saved so if you want to return to view the table at a later date please use the following commands in the command line.


read object "DOCK1_rec" # read receptor (if not read yet)
display a_DOCK1_rec.      # display receptor (if not displayed yet)
read object "DOCK1_lig" # read ligand object
display a_         # display this ligand
read table  "DOCK1_gd.Var" # read table of the ligand conformations. Click on table rows to view ligand conformations

18.6.10 Complex Refinement


You can refine a complex by:

Once the simulation has finished you can view the results by:


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