Can AutoDock be used for "Blind Docking"?Up to table of contents
This FAQ applies to: AutoDock 3, AutoDock 4
Yes, AutoDock can be used when the location of the binding site is unknown. This is often referred to as "blind docking", when all that is known is the structure of the ligand and the macromolecule.
It will be necessary to set up the dockings to search the entire surface of the protein (or other macromolecule) of interest. This can be achieved using AutoGrid to create very large grid maps, with the maximum number of points in each dimension, and if necessary, creating sets of adjacent grid map volumes that cover the macromolecule. The third-party tool BDT can be used to set up such sets of grid maps.
Several authors have used AutoDock to perform blind docking (see 1.-6.); for instance, Hetenyi et al. published two papers showing that AutoDock can be used to perform blind docking of peptides to proteins, and drug-sized molecules to proteins.
- Hetenyi, C. and van der Spoel, D. (2002) Efficient docking of peptides to proteins without prior knowledge of the binding site. Protein Science, 11(7): 1729-1737.
- Kovacs, M., Toth, J., Hetenyi, C., Malnasi-Csizmadia, A., and Sellers, J.R. (2004) Mechanism of blebbistatin inhibition of myosin II. Journal of Biological Chemistry, 279(34): 35557-35563.
- Bikadi, Z., Hazai, E., Zsila, F., and Lockwood, S.F. (2006) Molecular modeling of non-covalent binding of homochiral (3S,3 ' S)-astaxanthin to matrix metalloproteinase-13 (MMP-13). Bioorganic & Medicinal Chemistry, 14(16): 5451-5458.
- Hazai, E., Bikadi, Z., Zsila, F., and Lockwood, S.F. (2006) Molecular modeling of the non-covalent binding of the dietary tomato carotenoids lycopene and lycophyll, and selected oxidative metabolites with 5-lipoxygenase. Bioorganic & Medicinal Chemistry, 14(20): 6859-6867.
- Hetenyi, C. and van der Spoel, D. (2006) Blind docking of drug-sized compounds to proteins with up to a thousand residues. FEBS Letters, 580(5): 1447-1450.
- Iorga, B., Herlem, D., Barre, E., and Guillou, C. (2006) Acetylcholine nicotinic receptors: finding the putative binding site of allosteric modulators using the "blind docking" approach. Journal of Molecular Modeling, 12(3): 366-372.