Distance Constraints

Distance constraints (upper and lower bounds) can be entered using a simple language which specifies the site atom (from) and the ligand atom (to) which will be the targets of the constraint. During the refinement stages the distance constraint will be treated together with the other distance bounds. By default, user specified distance bounds have the same weight as all other bounds but it is possible to change the scaling (relative to other distance bounds) using the SCALE_CONSTRAINTS_1ST, SCALE_CONSTRAINT_2ND and SCALE_CONSTRAINTS_3RD keywords in the dock command file (cmd.cex). By default, these are all set to 1.

The site atom for a distance constraint is specified as "res n [chainid] atom atomname" where n is the residue number followed by an optional chain id (as per the PDB file) and atomname is the name. The ligand atom can either be specified by the "res n [chainid] atom name" string or by a SMARTS substructural pattern (see the SMARTS documentation at www.daylight.com if you need to learn about the SMARTS language). Examples of simple distance constraint specifications:

A full example constraints file is included in the dock subdirectory (constraints.cex). To use it, edit the file to specify your own constraints, leaving the header records intact. Then include the constraints file in the input to dock (for example by appending it to the commands file, cmd.cex).

In the case of a SMARTS pattern, the ligand atom which matches the first atom specified in the SMARTS pattern will be the target for the constraint. In the case of multiple matches of the pattern within the ligand, for each structure generated, the ligand target atom will be chosen randomly from the possible matches. The SMARTS patterns make it easy to run through a number of ligands, applying appropriate constraints without having to specify the exact atoms in each ligand. It is also possible to specify "vector bindings" with the vbind command (see constraints.cex for examples). This allows names to be given to SMARTS patterns which then can be used like atom specifiers in further SMARTS patterns. This allows for rather complicated substructures to be specified (see the SMARTS documentation, www.daylight.com, for further details regarding vector bindings).

Note that, since the distance constraints are applied together with all other distance bounds, it is possible that some of the generated dockings will not meet the constraint bounds, since they may be overridden by other conflicting terms (for example, fitting into the site). By increasing the weight on the constraints, it is possible to emphasize them more, but placing too high of a weight on them might distort ligand geometry. Some experimentation may be needed, depending on the problem. Note also that any atom pair specified in a distance constraint is ignored in the non-bonded energy calculations in the docking.