Authors: Robert Sheridan, Renee DesJarlais, Irwin Kuntz
The program DOCK is an automatic procedure for docking a molecule into a receptor site. The receptor site is characterized by centers, which may come from SPHGEN or any other source. The molecule being docked is characterized ligand centers, which may be its non-hydrogen atoms or volume-filling spheres calculated in SPHGEN. The ligand centers and receptor centers are matched based on comparison of ligand-center/ligand-center and receptor-center/receptor-center distances. Sets of ligand centers match sets of receptor centers if all the internal distances match, within a value of distance_tolerance. Ligand-receptor pairs are added to the set until at least nodes_minimum pairs have been found. At least three pairs must be found to uniquely determine a rotation/translation matrix that will orient the ligand in the receptor site. A least-squares fitting procedure is used (Ferro, et al Act. Cryst. A. 1977.). Once an orientation has been found, it is evaluated by any of several scoring functions. DOCK may be used to explore the binding modes of an individual molecule, or be used to screen a database of molecules to identify potential ligands.
Authors: Brian Shoichet, Dale Bodian, Irwin Kuntz
DOCK version 2.0 was written to give the user greater control over the thoroughness of the matching procedure, and thus over the number of orientations found and the CPU time required (Shoichet, et al. J. Comp. Chem. 1992). In addition, certain algorithmic shortcomings of earlier versions were overcome. Versions 2.0 and higher are particularly useful for macromolecular docking (Shoichet, et al J. Mol. Biol. 1991) and applications which demand detailed exploration of ligand binding modes. In these cases, users are encouraged to run CLUSTER in conjunction with SPHGEN and DOCK.
To allow for greater control over searches of orientation space, the ligand and receptor centers are pre-organized according to their internal distances. Starting with any given center, all the other centers are presorted into “bins” based on their distance to the first center. All centers are tried in turn as “first” positions, and all the points in a bin which has been chosen for matching are tried sequentially. Ligand and receptor bins are chosen for matching when they have the same distance limits from their respective “first” points. The number of centers in each bin determines how many sets of points in the receptor and the ligand will ultimately be compared. In general, the wider the bins, the greater the number of orientations generated. Thus, the thoroughness of the search is under user control.
Authors: Elaine Meng, Brian Shoichet, Irwin Kuntz
Version 3.0 retained the matching features of version 2.0, and introduced options for scoring (Meng, et al. J. Comp. Chem., 1992). Besides the simple contact scores mentioned above, one can also obtain molecular mechanics interaction energies using grid files calculated by CHEMGRID (which is now superseded by GRID in version 4.0). More information about the ligand and receptor molecules is required to perform these higher-level kinds of scoring. Point charges on the receptor and ligand atoms are needed for electrostatic scoring, and atom-type information is needed for the van der Waals portion of the force field score. Input formats (some of them new in version 3.5) are discussed in various parts of the documentation; one example of a “complete format” (including point charges and atom type information) is SYBYL MOL2 format. Parameterization of the receptor is discussed in the documentation for CHEMGRID. In DOCK, ligand parameters are read in along with the coordinates; input formats are described below. Currently, the options are: contact scoring only, contact scoring plus Delphi electrostatic scoring, and contact scoring plus force field scoring. Atom-type information and point charges are not required for contact scoring only.
Authors: Mike Connolly, Daniel Gschwend, Andy Good, Connie Oshiro, Irwin Kuntz
Version 3.5 added several features: score optimization, degeneracy checking, chemical matching and critical clustering.
Authors: Todd Ewing, Irwin Kuntz
Version 4.0 was a major rewrite and update of DOCK. A new matching engine was developed which is more robust, efficient, and easier to use (Ewing, et al. J. Comput. Chem. 1997). Orientational sampling can now be controlled directly by specifying the number of desired orientations. Additional features include chemical scoring, chemical screening, and ligand flexibility.
Authors: Demetri Moustakas, P. Therese Lang, Scott Pegg, Scott Brozell, Irwin Kuntz
Version 5 was rewritten in C++ in a modular format, which allows for easy implementation of new scoring functions, sampling methods and analysis tools (Moustakas, et al, 2006). Additional new features include MPI parallelization, exhaustive orientation searching, improved conformation searching, GB/SA solvation scoring, and post-screening pose clustering. (Zou, et al. J. Am. Chem. Soc., 1999)
DOCK 6 is an extension of the DOCK 5 code base. It includes the implementation of Hawkins-Cramer-Truhlar GB/SA solvation scoring with salt screening and PB/SA solvation scoring through OpenEye's Zap Library. Additional flexibility has been added to scoring options during minimization. The new code also incorporates DOCK version 3.5.54 scoring features like Delphi electrostatics, ligand desolvation, and receptor desolvation. Finally, DOCK 6 introduces new code that allows access to the NAB library of functions such as receptor flexibility, the full AMBER molecular mechanics scoring function with implicit solvent, conjugate gradient minimization, and molecular dynamics simulation capabilities.