Docking will be performed with three different programs: Autodock-4, Autodock-Vina, and Glide.

• Obtain/prepare a library of ligands to dock.
  • One option to do so is the ZINC website where you can ebter a ligand (either as a SMILES string or sketch it and run a similarity serach to get a list of ligands that you can download - ask for the ligands in .mol2 format.
  • There are several libraries in the directory /sc/orga/projects/liglib. A (somewhat outdated) desccripton of these directories is at the URL ihttp://inka.mssm.edu/~mezei/molmod/lig_lib.html

  For Autodock, the ligands have to be in mol2 format, and be placed in a separate directory, one file per ligand. For Glide, the ligands have to be in a single file, in SDF or .mae (Schordinger's Maestro) format.

  The script set fullscreen has a program aggregate that combines individual mol2 files into s single file and program splitmol that splits a single file into separate ligand files.

• Select a protein as a target, copy its PDB file in a new dirctory where all dockings will be run
• Copy all files from ~mezeim01/fullscreen to the directory where the PDB and PDBQT files are.
• Docking with Autodock-4 and Autodock-Vina:
  • Prepare it for docking with Autodock-4 and Autodock-Vina using AutoDockTools (ADT). Follow this link for a tutorial on using ADT. This preparation involves the following steps:
    • Read in the protein
    • Add hydrogens (polar only) or remove non-polar hydrogens (Edit menu)
    • Assign Autodock4 types (Edit menu)
    • Assign Gasteiger charges (Edit menu)
    • Use the Grid menu to determine the size and position of the grid box. This menu should put on the screen a box that you can manipulate (translate or scale) with (virtual) dials. Note the grid center and size; you will need it later (also for Glide!).
    • Save the protein as a PDBQT file (this format includes charges and the ATD4 types)
    • If the total charge is not an integral number, use Simulaid to find the residues with non-integral charges. If the deviations are a few hundredth then you can let Simulaid fix it; otherwise fix them manually. This latter may happpen when residues are incomplete or atom names are not recognized or bonds are not considered by ADT.
  • Execute the script fullscreen.csh.
    Select Autodock-4 - the script will later lets you run Autodock-Vina as well.
    Among others, it will prompt you for the target file name, the ligand file directory and the information about the docking grid. It will finish with submitting the jobs.
  • Once the dockings finished, run the script getdir.csh for all three programs - this should generate .dir files for each, containig a list of docking result (log) files.
• Docking with Glide:
  • Execute the script fullscreen.csh.
    
  • The file containing the ligands should be in .sdf format (to be converted to .mae by the script).
  • The grid center and size should be taken from the Autodock setup

• For each of the three programs, run dockres - it will provide a lot of information about the top-scoring ligands.

• Run the program compligset to find out the concensus top-scoring ligands
• If you dock your ligands to two different proteins, compligset can find ligands that are selectove to one or the other.

Last modified: 12/03/2017

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