61.1.1. RUNNING THE PROGRAM GLUE

Move to the tutorial glue01 directory.

Run the GLUE programme by typing Glue& on your terminal. The GLUE interface will appear.

Select from Menu Bar:

Receptor->Receptor a window appears.

On the "Receptor Analysis Identification" section click on the Browse bar and import the 1ABE.bspc file. After the importation all the others fields inside the Binding Site Precalculations will be automatically filled-in. Since we have prepared everything for you, click on Old configuration and Continue.

The following window will appear:

All the information for the docking should be already present inside the "Docking Parameters" window. Complete the window by selecting the "Ligand File Format" >> kout. This is the standard GRID format for molecules. Select "Ligands List filename" >> press on Browse bar and select ara.list->OK now press Continue, a window will appear.

Click on Unique Site. This allow GLUE to evaluate the interaction energy between the Target and the Ligand located only in the precise position as defined by the User.

Unset Binding Optimization and then click on Start Computation.

GLUE's computing the intermolecular interaction energy between the Ligand and the Target when the Ligand coordinates are those determined (experimental or coming from other docking procedures). The corresponding value in kcal/mol will be printed on the main GLUE window.

Now we are going to compute the interaction energy between the Ligand and the Target, but in this case we activate the Binding Optimization option. In order to do this, from the main GLUE window, click on:

Docking->Docking a window appears, then click on Continue. The following window will appear:

Set Binding Optimization ON and then click on Start Computation. The new interaction energy value will be printed on the main GLUE window.

Compare the present position of ara.kout with the previous one. Compare the energies. The binding optimization allow GLUE to "relax" the TARGET-LIGAND complex. The procedure works eliminating bad steric interaction and maximizing actractive forces in order to locate the ligand in the local minimum of the interaction energy function.

At this point, we are intersted to find all possible interaction sites for ligand ara.kout inside the L-Arabinose Binding Protein. In order to do this, from menu bar of GLUE programme select:

Docking->Docking a window appears, then click on Continue. The following window will appear:

On the "Initial starting Solutions" section, unset Unique Site, set "Prune level" to 1, activate Visualize Docking Dynamics and then click on Start Computations. A graphic empty window will appear. Add the ligand (for reference) in the window:

Molecules->Molecules Manager->Add select ara.kout, click OK->Quit and then View->Full View

The X-ray ligand molecule will be used only as a reference for graphic comparison. Change its style by: Molecules->Mol. Style->Sticks->Quit and Molecules->Mol. Colour->by atom type->Quit

Start the docking by pressing:

Docking->Start Computations

When the computation is terminated, the best docked solutions, based on energy criteria, will be those reported on the screen. Compare the best docked structure with the crystallographic one.

Exit from the graphic window by typing File->Return to Main Applications

In the blue window of GLUE the energies of the docked solutions are labeled. The best energy, corresponding to the best solution, is of -0.987 Kcal/mol.

You have now completed your first Tutorial for GLUE. Well done!! Please, continue with the GLUE tutorial 02.