AUTODOCK is a script driven program to dock flexible ligands to a crystallographic
protein structure.

AUTODOCK runs on Linux machines; the executable is in:

/programs/autodock/linux/dist305/src/autodock/autodock3 

The local documentation is available from the author's web site:

http://www.scripps.edu/mb/olson/doc/autodock/documentation.html 
or from a local source
/joule2/programs/autodock/dist305/doc/html/documentation.html 

you can download examples from :
http://www.scripps.edu/mb/olson/doc/autodock/examples.html

For beginners, it is much easier to access autodock through AutoDockTools (ADT).
AutoDockTools is a graphical user interface. Here is a dry overview.
http://www.scripps.edu/~sanner/python/adt/autotoolsoverview.html

A very HELPFUL TUTORIAL can be obtained in PDF format from 
http://www.scripps.edu/pub/olson-web/doc/autodock/pdf/UsingAutoDockWithADT.pdf
or a different tutorial in html format which includes screenshots
http://www.scripps.edu/~sanner/python/adt/Tutorial/

MIKE'S NOTES ON AUTODOCKING

STEP 1. Log on to a linux computer:

STEP 2. In your working directory, copy a PDB file containing the macromolecule of interest. In this example we will copy the pdb file pdb1rx3.ent to macro.pdb.

cp /pdb/pdb1rx3.ent macro.pdb

STEP 3. Get a PDB file containing your ligand of interest. You might create it in WebLabViewer, or retrieve it from the HIC-Up database of ligands. http://alpha2.bmc.uu.se/hicup/. For this example, you could use the methotrexate molecule, MTX. http://xray.bmc.uu.se/hicup/MTX/

STEP 4. In your working directory

source /joule2/programs/autodock/mglTools_v1.5_recompile/rel.1.1/i86Linux2/bin/initPython

STEP 5. Read in the coordinates of your macromolecule using the following menu items: File -> ReadMolecule. Select: macro.pdb. Molecule will be displayed in GUI. (See page 7, step 1 of the HELPFUL TUTORIAL in PDF format, linked above)

STEP 6. Add hydrogens to macromolecule with the following menu items: Edit --> Hydrogens --> Add. Select: polar only, no bond order, yes. Hydrogens will appear in GUI. (See page 10, Step 7 in tutorial)

STEP 7. Write out the coordinates of the hydrogenated protein. File-->Save-->Write PDB--> save as macro_h.pdb (See page 11, step 8 in tutorial).

STEP 8. Convert the PDB coordinates of the ligand into pdbq format. Open a web browser to access the PRODRG server: http://davapc1.bioch.dundee.ac.uk/programs/prodrg/prodrg.html. Using your mouse, copy and paste your coordinates for the ligand into the PRODRG server window. Full charge:no. On the results page, find "autodock 3.0 pdbq format." Click on the link. Use the mouse to cut and paste the results into ligand.pdbq in your working directory.

STEP 9. Read in the ligand PDBQ file. Ligand-->Input Molecule-->Read Molecule. Ligand will show in center of screen, probably obscured by protein atoms. To turn off annoying protein atoms -->Show/hide. Select protein. (Page 12, 2nd paragraph of tutorial). Use SHIFT middle mouse button drag to zoom back. (See page 8 of tutorial).

STEP 10. Define Rigid Root of Ligand. Ligand-->Define Rigid Root-->Automated. See green sphere appear sitnifying the choice of root atom.

STEP 11. Define Rotatable Bonds. Ligand-->Rotatable Bonds-->Define Rotatable Bonds. Move the annoying popup window out of the way to see which bonds are rotatable (green) and which are not (red). If OK, click "done". (See page 14, step 3 of tutorial).

STEP 12. Write out Ligand PDBQ file. Ligand-->Write-->PDBQ Call it ligand.out.pdbq. (See page 14, step 5 of the tutorial).

STEP 13. Select the macromolecule for the grid calculation. Grid-->Macromolecule-->Choose Macromolecule. Choose macro. You might get a message indicating that you have a non-integral charge and that the charge was corrected. That's just fine. In this case you will be prompted to write out a new pdbqs file, macro_h_corrected.pdbqs (see page 16, step 1 of tutorial).

STEP 14. Select map type (in other words, select the ligand). Its a map of the macromolecule, but its contents will depend on the atom types in the ligand. Go figure. Grid-->Set Map Type-->Choose Ligand. Select ligand. Click accept.

STEP 15. Select Grid dimensions. Grid-->Set Grid. You'll get a window with dials to adjust the dimensions of a rectangular box. Be sure to turn on the appearance of the macromolecule if you turned it off earlier. Go to the Grid spacing dial, and increase to maximum, 1.0Angstrom in order to make it run faster. Use smaller grid spacings if you want more "accuracy." Then, adjust the x, y, and z dials individually. You should see an image of a semi-transparent box increase its dimensions as you adjust the dials. Make it cover the whole molecule or the part of the molecule you are interested in. If the box does not appear to change size, select a dimension, save it, then open the window again to see the new box size. (See pages 18-20, step 2 of tutorial).

STEP 16. Write out a grid parameter file (macro_ligand.gpf). This is an instruction file for autogrid to use to calculate the macromolecule grid. Grid-->Write GPF. (See page 20, step 3 of tutorial).

STEP 17. You can view the .gpf file you just made. Grid-->Edit GPF.

STEP 18. Run Autogrid. Run-->Start AutoGrid. Nice 5. Run. (See page 21 of tutorial). You should get a message "autogrid3: successful Completion" in the terminal window. It might take 1-5 minutes, depending on the number of grid points it has to calculate.

STEP 19. Select macromolecule to be used as docking target. Docking-->Set Macromolecule-->Select Macromolecule Filename. Select macro.pdbqs. Click open. (See page 23, step 1 of tutorial).

STEP 20. Select ligand to be used for docking. Docking-->Set Ligand Parameters-->Choose Ligand. Click on ligand name. (See page 23, step 2 of tutorial).

STEP 21. Select Docking algorithm. Docking-->Set Search Parameters-->Genetic Algorithm Parameters. You can choose SA-the original Monte Carlo simulated annealing; GA, a traditional Darwinian genetic algorithm; LS, local search; and GA-LS, (a.k.a LGA) which is a hybrid genetic algorithm with local search (Lamarkian). (See page 24, step 3 of tutorial).

STEP 22.Set more parameters if you are adventurous. Docking-->Set Docking Run Parameters. specify number of retries, step size, output format, cluster analysis. Usually accept default. (See page 24, step 4 of tutorial).

STEP 23. Write a docking parameter file (.dpf). Docking-->Write DPF-->macro_ligand.dpf. Save (See page 24, step 5 of tutorial).

STEP 24. Waste time by editing .dpf file. Docking-->Edit DPF. (See page 24, step 6 of tutorial).

STEP 25. Run Autodock! Run-->Start AutoDock. Can finish in less than a minute. Should get a message "autodock3: Successful Completion". (See page 25 of tutorial).

STEP 26a. Load the docking solutions. Analyze --->Docking Logs --->Read Docking Log. (See page 27 of tutorial).

STEP 26b. View the individual docking solutions. Analyze-->Conformations-->Show Conformations. You'll get a window, you can slide the slider through the 10 different solutions. You'll see each docking site separately. (see page 29 of tutorial).

STEP 27. View all the docked ligands at once to see how clustered the solutions are on the surface of the macromolecule. Analyze-->Molecules-->Visualize Dockings as Spheres. (see page 36 of tutorial).

STEP 28. To get the coordinates of docked ligand in PDB format, type get-docked macro_ligand.dlg. You'll get a pdb file with 10 docked ligands. You'll have to split the file into individual molecules yourself, if you want.