How should I prepare a ligand for docking with AutoDock?Up to table of contents
This FAQ applies to: AutoDock 3, AutoDock 4
Where can I obtain 3D coordinates for my ligand? What do I have to do before I can use AutoDock?
Steps to Generate a Ligand Input File for AutoDock
- Convert a 1D description (SMILES string, e.g.) or 2D description (from a molecule sketching program such as ChemDraw, Ghemical or PRODRG) of the ligand into 3D coordinates. Pay attention to the stereoisomeric form, especially chirality.
- Alternatively, obtain the structure of the ligand from a database.
- Generate the correct tautomeric form. If this is not known, all tautomers should be generated and docked independently.
- Add all the hydrogen atoms, to make sure all the valencies of the heavy atoms are satisfied.
- Compute partial charges for the ligand using your preferred method and level of theory.
- AutoDock 3 and AutoDock 4 use the United Atom model. This means only polar hydrogens are included in the coordinates file. A molecule with all hydrogens can be converted into a United Atom model using AutoDockTools (ADT)'s "Edit > Hydrogens > Merge Non-Polar" menu option.
- The ligand needs torsion information to be added depending on which torsions are to be treated as rotatable during the docking. Then it needs to be saved in PDBQ format for AutoDock 3, and PDBQT format for AutoDock 4. There are more details on how to do this using ADT in the tutorials, "Using AutoDock 3.0.5 with AutoDockTools", "Using AutoDock 4 with AutoDockTools" and "Using AutoDock for Virtual Screening".
Obtaining 3D Coordinates for a LigandThere are a variety of ways of obtaining coordinates for a small organic molecule ('ligand')—this list is by no means exhaustive:
- CSD (Commercial, Cambridge Structural Database) — this is the "world repository of small molecule crystal structures".
- PDB — (Free) — RCSB Protein Data Bank — great if you are looking for a structure of a small molecule in complex with a protein or other macromolecule.
- ZINC (Free) — ZINC Is Not Commercial! — "a free database of commercially-available compounds for virtual screening. ZINC contains over 4.6 million compounds in ready-to-dock, 3D formats".
- Chemical Drawing Software
- ChemDraw (Commercial, available from CambridgeSoft)
- Corina (Commercial, available from Molecular Networks GmbH) — note there is an Online Demo available, too.
- Discovery Studio (Commercial, available from Accelrys)
- Ghemical (Free software) — runs in X11 on Linux and Mac OS X; great for sketching and energy minimisation.
- Ghemical-GMS (Free software) — can also be used to generate input for GAMESS.
- PRODRG (Free web service) — produces AutoDock 3 PDBQ files, which can be converted into PDBQT files for AutoDock 4.
Requirements for AutoDock
- AutoDock 3 requires 3D coordinates and partial charges for all the heavy atoms and polar hydrogens in the ligand; these must be given in PDBQ format.
- AutoDock 4 requires 3D coordinates, partial charges and AutoDock 4 atom types for all the heavy atoms and polar hydrogens in the ligand; these must be given in PDBQT format.
- Using AutoDock 3.0.5 with AutoDockTools
- This tutorial teaches you how to use AutoDockTools 3.0.5 to set up AutoGrid grid map calculations, how to set up AutoDock dockings, and how to analyse your docking results.
- Using AutoDock 4 with AutoDockTools
- This tutorial teaches you how to use AutoDockTools to set up AutoGrid 4 grid map calculations, how to set up AutoDock 4 dockings, and how to analyse your docking results.
- Using AutoDock 3 for Virtual Screening
- This teaches you not only how to use AutoDock 3 to perform virtual screening, but also a lot about using UNIX to organize and process large numbers of files, skills that are transferable to many other problems. There are two PDF files, the first contains slides describing some background to virtual screening and the overall process, and a second PDF file with step-by-step instructions. The latter includes instructions on how to download the necessary input files. When we teach this tutorial, we require that you have attended the "Using AutoDock with AutoDockTools" tutorial. NOTE: the tutorial currently refers to an incorrect CVSROOT location. The correct location should be: setenv CVSROOT :pserver:firstname.lastname@example.org:/opt/cvs
by morris — last modified 2007-12-18 22:05