1. Open LeadIT and load a receptor, either by "Receptor|Load and Prepare" or by opening an already prepared receptor in a so-called "project file" (*.fxx file).
2. Change to Hyde by clicking the "Thumbs up" icon.
   
3. Load the reference ligand into Hyde - or load another ligand from file. It is also possible to select a ligand from a docking library in your project file.
   
4. In this example, we load the reference ligand, MTX. If you are unsure about the structure of the ligand loaded, you can make minor changes with the ligand editor.
   
   Please note: The editor is in alpha status and will be under further development. Use at your own risk.
5. Press the Hyde button to start the assessment.
   
6. Hyde now starts optimizing the interactions of the ligand and then scores it. Once finished, the optimized ligand will be displayed in Hyde colors (red, white, green); the Hyde score and ligand efficiency are neatly displayed right next to it.
   
   Please note that the bar (resp. for affinity) and the fist (resp. for ligand efficiency) depict two different values. With the eye icon next to the edit button (the pencil) you can turn the original or optimized ligand off and on.
7. If you would like to know explicit score contributions for particular atoms, simply click on the atom you would like to explore, and a table below the overall score value expands with the atom's name, its Hyde contribution, and the ligand's and receptor's individual desolvation and interaction terms.
   
8. Once done with affinity assessment, the optimized structure of the ligand after the assessment can be exported to an SD or mol2 file via the "Save" button underneath the "Load" button.
   Of course, any Hyde assessment can be done from a FlexX docking or a ReCore core replacement, linking or merging. Thus, a quick plausibility check can be done on a newly designed structure in LeadIT.

If we tempted you to get more information, please check out the Hyde web site or write to us.