Macs in Chemistry

Insanely great science

Viewing Docking results in Vortex using Astex Viewer ========================================= I recently wrote a review of ForgeV10 from Cresset in which I actually imported the results into Vortex to do the analysis. There were however two issues with doing this, firstly interpretation of the 3D structures is sometimes difficult, this can be resolved by creating a 2D rendering of the structure. The other issue is trying to interpret the docking pose whilst looking at the analysis of the results in say a Vortex scatter plot. I’ve been working with Mike Hartshorn and the people at Dotmatics who have incorporated [OpenAstexViewer]( (a 3D molecule viewer) into the application and I’d like to highlight the current results. For this functionality you need to download the latest Vortex build from the Dotmatics support site, the latest version comes with OpenAstex Viewer originally developed by Mike Hartshorn whilst he was at Astex Therapeutics (M.J.Hartshorn, JCAMD, 16, 871 (2002)) and it is now available under a GNU LESSER GENERAL PUBLIC LICENSE. You also need to the following short Vortex script to activate the viewer. import com.dotmatics.vortex.plots as plots oav = plots.OpenAstexViewerPlot() oav.setVortexTable(vtable) vtable.addVortexTableListener(oav) oav.loadMolecules() frame = vws.addComponent(oav, "Structures") frame.setSize(java.awt.Dimension(600, 600)) # Make all popup menus heavyweight (i.e. real components) # so that they will appear above the OAV plot. # Gives access to the Detached menu setting amongst other things # which is useful for looking at structure on another monitor. javax.swing.JPopupMenu.setDefaultLightWeightPopupEnabled(0) This script can be downloaded from here []( In the previous review we had a view as shown below, in which the plot shows the similarity score from ForgeV10 versus the Maccs similarity calculated using a Vortex script and the points coloured by biologic activity. Whilst this is a useful way of looking at the data, in order to explain why some of the actives are poorly scored by ForgeV10 we need to look at the docking pose. Whilst we can do this by continually switching back and forth between applications this is a far from ideal situation. full view If you use the script above it inserts an Astex viewer window into the workspace. If you then select a group of points in the scatter plot the corresponding structures are shown overlaid in the Astex Viewer window, the selected points are also automatically selected in the molecular spreadsheet view. This allows you to rapidly and easily compare structures to identify regions of the ligand molecules that might explain differences in activity. structures_only ForgeV10 also uses the protein to provide an excluded volume, this might explain the lack of activity of some molecules to include the protein structure simply right-click on the Astex Viewer plot to bring up a small control panel. In this case we have a single static protein that was used for all ligands, so simply click the appropriate “Configure” button and select the protein. control You can then use the check boxes to configure the display. protein If you have multiple monitors or are displaying using multiple projectors you can click on the Astex Viewer window and then choose “Detached” from the top right “Actions” menu of the main Vortex window and then the Astex Viewer window can be moved independently of the main Vortex window. This is a wonderful way to explore structure-activity and docking results, it can of course be used with any docking/virtual screening program as long the structural output has the resulting docked structures in the same co-ordinate space. Of course not all docking results in a single protein conformation, in some cases the protein side-chains are allowed to move after the initial pose to allow better fitting. In these cases we would want to look at a different protein structure with each ligand. To do this we need to be able to identify which protein is associated with each ligand and which conformation. To do this we create a new field that contains the name of the protein. For example 1RO6_28409_1 ProteinName_LigandID_PoseNumber and the Proteins must named correspondingly 1RO6_28409_1.mol2 etc. So now when you choose the appropriate “Configure” button from the Astex Viewer popup control panel, then chose one of the proteins and you will be presented with a text field describing the path to the protein structures e.g. /dockings/1RO6_40552_5.mol2 edit this to /dockings/${Name}.mol2 When you select a data point, each complex will substitute the value of its name column into the string and load the corresponding protein structure into Astex Viewer. There are a number of Vortex scripting tutorials here and I’ve started a [Vortex scripting exchange here]( There are more hints and tutorials here Updated 8 October 2012