Overview

DOCK operates in two modes: SINGLE ligand and SEARCH. In SINGLE ligand mode, one ligand molecule is input and all orientations meeting user-defined criteria concerning score and number of bad contacts are output. In SEARCH mode, a database of ligands is input. The top-scoring ligands are output in their highest-scoring orientations.

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, Bodian, and Kuntz, 1992). In addition, certain algorithmic shortcomings of earlier versions were overcome. Versions 2.0 and higher are particularly useful for macromolecular docking (Shoichet and Kuntz, 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 preorganized 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.

Another feature allows investigation of particular regions of orientation space in greater detail if high-scoring dockings are found to occupy them. This is done by expanding the bins which define the regions. We refer to this as "focusing" or "zooming" since it automatically magnifies the importance of certain regions during the docking procedure. Please note that this functionality, although it remains available, is no longer supported and has not been tested for compatibility with new features.

Version 3.0 retained the matching features of version 2.0, and introduced options for scoring (Meng, Shoichet, and Kuntz, 1992). Besides the simple contact scores mentioned above, one can also obtain molecular mechanics interaction energies using grid files calculated by chemgrid. 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 ASCII (MOL2) format (Tripos Associates). 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.

Version 3.5 adds several features, which are previewed in the What's New section. The chemical matching functionality required a change in the formats of the ligand database and sphere cluster files - these changes are described in the Chemical Matching section. Another major addition to version 3.5 is the development of a keyword format input for the INDOCK and DOCKOPT files, described below. The original format for these files is also accepted.