How do I start IFD in the Prime stage with preexisting Glide results? I want to include Glide constraints in my IFD run.

If you want to use options not available through IFD, such as addition of metal, hydrophobic, or positional constraints, you can run a separate Glide job instead of running the initial docking through IFD. To use the results of a separate Glide run, follow this procedure:

1. Be sure to prepare the protein yourself with the Protein Preparation Wizard. Also check the protein preparation procedure in the Induced Fit Docking manual and the Protein Preparation Guide.
2. If you want to mutate receptor side chains to ALA in your Glide job, you need to do it manually. You can use one of the following approaches:
   
   
   • Mutate the residues to ALA in the Build panel, and then change the residue name back to the original residue name.
   • Delete all the side chain atoms beyond the CB, and then apply hydrogen treatment to the CB so that it has three hydrogens.
   Both methods produce ALA sidechains while retaining the original residue name, which is required in order for Prime to rebuild the full residue during the optimization stage of IFD.
3. Run Grid Generation and serial Glide docking jobs with the desired constraints or other options, saving multiple poses per ligand (the IFD default is 20) and applying IFD scalings (0.5 for the ligand, and 0.7/0.5 for the receptor with/without mutations). You need to run this initial job serially because IFD uses the lignum Glide property to determine which poses were generated from a particular ligand. Running Glide in parallel results in duplicated lignum values, and this would interfere with IFD's ligand and pose tracking.
4. Set up an IFD job in Maestro as if you were running all stages from the beginning. That is, set job options, put the receptor or complex in the Workspace, define the grid box center, set the Prime refinement and redocking parameters, and so on. You will comment out the Initial Glide docking stage, so the settings for this stage don't matter. For the Ligands to be docked, browse for the ligand file used as input for the Glide job.
5. Write the job files instead of starting the IFD job, with the Write button.
6. Edit the jobname.inp file:
   
   
   • Comment out the STAGE PPREP section, the STAGE TRIM_SIDECHAINS section and the first STAGE GLIDE_DOCKING section.
   • For the INPUT_FILE (at the top), change the reference from jobname_rec.mae to your glidejob_pv.mae file.
7. Run the job from the command line:

   $SCHRODINGER/ifd jobname.inp
   

You can monitor the job's progress in the jobname.log file, or in the Monitor panel. The results can be seen in the jobname_results.prj project, or in the structure output file jobname-out.mae.

Keywords: Maestro

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