CDOCKER is a molecular docking method based on CHARMm's position, which can produce highly accurate docking results.
Taking the binding of natural ibuprofen ligand molecules to the COX-1 receptor as a point, the obtained docking conformation is compared with the natural conformation of the ligand in the crystal structure obtained by X-ray diffraction.
In the Files Explorer, find and double-click to open Samples| Tutorals| Receptor-Ligand Interations|1EQG.dsv.
Open a three-dimensional protein structure with active sites in the branch window. (Figure 1)
Figure 1 Three-dimensional structure of protein
In the Tools Explorer, expand Receptor-Ligand Interactions|Define and Edit Binding Site, and then click Show/Hide Residues Outside Sphere and Show/Hide Sphere. Expand the menu bar View|Transform and click Fit To Screen to display the amino acid at the binding site in the center of the window. (Figure 2)
Figure 2 Protein active site amino acids
Find and double-click to open the Samples|Tutorials|Receptol-Ligand Interactions|1EQG-ibuprofen-conf.sd. file. A molecule of ibuprofen with an institutional image will open. (Figure 3)
Figure 3 Small molecule structure of ligand
In the Tools Explorer, expand Receptor-Ligand Interactions|Dock Ligands and click Dock Ligands(CDOCKER) to open the corresponding parameter panel. In the parameter panel, set Input Receptor to 1EQG:1EQG. The parameter Input Ligands is set to 1EQG-ibuptrofen-conf:All. Click the Input Site Sphere parameter and select the coordinate and radius of the sphere from the drop-down list. Expand the Top Hits parameter and set Pose Chister Radius to 0.5. The RMSD threshold is set to 0.5 Angstroms to ensure that the docking conformation is as diverse as possible. The rest of the parameters default (Figure 4) , click Run to run.
Figure 4 CDOCKER parameter settings
After completion, in Jobs Explorer, double-click the completed molecular docking task to open the Report interface, and click View Results to open the docking result.
In the Tools Explorers, expand Receptor-Ligand Interactions|View Interactions and click Ligand Interacitions. In the view window, the non-bonded interaction between the amino acid residues of the receptor protein and the ligand docking poses will be shown by dotted lines of different colors, and only the residues that participate in the interaction with the ligand will be displayed (Figure 5).
Figure 5 shows the non-bonded interaction between protein and ligand
Click Interaction Options under the above View Interaction panel to expand the window (Figure 6). All the non-bonding interaction types in DS listed in this window, where the black display indicates the non-bonding interaction between the protein and the ligand.
Figure 6 Panel parameters
Click Step through Ligands under the View Interaction tool panel above to observe the non-bonding interaction between different docking conformations and the same protein.
Click View|Tool panels in the menu bar and check View Interaction (advanced). Select and display the ligand to be described (such as the first Ibuprofen conformation), in the Tools Explorers, expand Receptor-Ligand Interactions | View Interactions, and click Define Ligand. Then expand Receptor-Ligand Interactions | View Interactions (Advanced) and click Show 2D Diagram. You can see that the two-dimensional plan view of the ligand-protein interaction is opened in a new window, so that we can more intuitively observe the interaction between the two and the key amino acids and groups (Figure 7).
Figure 7 Two-dimensional plan view of ligand-protein interaction
In Jobs Explorer, stand alone under the task bar (click on the + in front of it) Docked Ligands link. The docking ligand will open in a new molecular window. Press and hold CTRL+G to display the molecular graphics window. Expand the menu bar File|Insert From, click File..., select Samples|Tutorials|Receptor-Ligand Interactions|1EQG-ibupronfen.sd. Insert ibuprofen's natural crystal structure 1EQG-ibuprofen.sd in the same window. In the table view, set the Visible and Visibility Locked of the Ibuprofen molecule in the last row to True. Hold down CTRL+Down and observe the comparison between each ligand file and the natural crystal structure of ibuprofen (Figure 8).
Figure 8 Comparison of docking ligand and ibuprofen natural structure crystals