trans
the new FlexX Release 3 - part 1: protein preparation
trans
contact
impressum
legal notice
print this page
BioSolveIT
The Premier Scientific Solution Provider
trans
In this issue we focus on the workflow required to prepare a protein for ligand docking. Here we describe some of the hidden features that may not appear evident at first glance or are not totally obvious.

To obtain a more thorough guide to the GUI you can go to the Help drop down menu in the GUI and click on the Quick Guide to obtain more detailed instructions on how to use the GUI. Use these tips and tricks to supplement the instructions taken from there and if you wish take a look at the online tutorial movie. If you have any difficulties please feel free to contact us. Also in the Help menu you can find FlexX Reference this will provide you with the command line version of the FlexX documentation.

workflow
  1. In the Protein drop down menu obtain your favourite or the latest protein-ligand complex of your choice by downloading it directly from the PDB or load it from a file. Next define your binding site for docking in the Receptor menu by selecting Define or simply load your definition from mol2. A wizard will pop-up after you click Define and guide you through the receptor preparation stage.
  2. Select the protein chain for docking using the boxes provided (highlighted below) or simply just click on the desired protein chain in the 3D box view containing the chain. You can manipulate this 3D box view in an identical fashion as the normal view i.e. use the roller ball or move your mouse while holding shift and the right mouse button to zoom in and out.
  3. Define your binding site by selecting your reference ligand. You can in/decrease the size of your binding site definition by changing the radius size (circled below). An interesting feature is that the atoms in the binding site definition are highlighted in the 3D box view and these change as you change your binding site definition. Have a go; change the size of your binding site definition.
  4. Adjust the atom assignment of several chemical groups using your chemical knowledge. A list of amino acids that are to be considered are shown. Click on your choice in the highlighted section below in the 3D box view to change between amino acids.
  5. Protonation, H-torsions and tautomers can be crucial in docking runs. A list of amino acids in the binding site are listed in this section and can be manipulated by clicking on them in the Chain/AA column (highlighted below). Here you must pay attention and use your chemical knowledge to change the amino acids assignments marked with an !. You can complete this section by using the roller ball to scroll through the available options - watch as your molecule physically changes before your eyes in the 3D box view.
  6. By clicking the Next button you will continue through to name your tailored binding site definition for docking. To complete the protein preparation click on the Finish button. However, if you wish to revise or review any of the sections you have previously visited simply click on any of the titled sections highlighted below.
  7. Upon clicking Finish the GUI will calculate a binding surface for your defined binding site. This can be switched off if undesired by clicking on the Binding Site Surface box in the tree view highlighted below. All of the tree view sections can be manipulated to gain the desired 3D view of your protein-ligand complex. I.e. click on the Water box to view the water molecules in the complex which have previously not been visible.
  8. At any point in time during protein preparation or later during or after the docking procedure (pharmacophore selection, results analysis -see Part 2 in the next Tips and Tricks) you can save your work as a FlexX project. Under File select Save Project As to save your existing work as an .fxx FlexX project file. You can take a look at some project example files provided with the GUI!
  9. The binding site definition can be exported as a Pipeline Pilot xml file using the Export drop down menu and selecting Docking (highlighted below). Once you've saved a binding site as a Pipeline Pilot xml file simply open up Pipeline Pilot and drag and drop the file into Pipeline Pilot. Assign parameters, connect the FlexX docking module to the binding site xml file and you're all set to perform FlexX docking within your existing pipelines.
  10. Other export options include a mol2 file export for the receptor also under the Export drop down menu under Receptor (circled above).
Last modified Thursday, 02. Feb 2012 23:19 CET by WebMaster