Appendix D: Stereochemical restraints for ligands

Content

• Background
• Script requirements
• Script input
• Script output
• Additional information

Background

The script $BDG_home/bin/buster/SmilesGUI, described here, is provided for the generation of the stereochemical restraints based on a SMILES string, in the TNT format. It also generates a PDB file with atom labels matching those used in the TNT dictionary. Finally, the interactive script can generate another script, suitable for automation of the process.

Script requirements

The following environment variables need to be set:

	variable name	notes
	BDG_java	the java binary must implement the version 1.3 or above of the run-time environment
	DY_LICENSEDATA	a valid licence for the Daylight's Toolkit (and optionally RUBICON). Beware of the spelling !
	DY_ROOT	point to the root of the Daylight's distribution (usually /usr/local/daylight/v473). This environment variable is not strictly speaking mandatory if one does not use RUBICON, but it is useful for finding all kind of files.
	LD_LIBRARY_PATH	must contain the location of libBalls.so, i.e. $BDG_home/bin/irixn32_exe or $BDG_home/bin/linux_exe and the location of the Daylight Toolkit shared libraries, usually $DY_ROOT/lib.

The script builds the CLASSPATH for the java program $BDG_home/lib/java/SmilesGUI.class.

Script input

1. a 3-character name for the ligand (e.g. for 2-methyl-2,4-pentanediole one can choose "MPD" - notice that this name MUST match the one the ligand has in the PDB file);

2. a SMILES string;

3. [an optional 3D model of the ligand in PDB format, provided that the atoms order in the PDB file is identical to that in the SMILES string];

4. an output directory to write the output files.

Script output

1. the stereochemical restraints describing the ligand in TNT format,
2. a tentative 3D model for the ligand (identical to the input model when provided, otherwise generated by Daylight's RUBICON program),

3. an assessement of the stereochemical quality of the 3D model,

4. a script suitable for generation of TNT dictionaries and PDB models from the command-line.

Additional information

There are a few caveats to keep in mind when using the $BDG_bin/buster/SmilesGUI script:

• The SMARTS patterns used to generate the TNT dictionary do not define a target value and its esd, but a interval for the allowed values of the stereochemistry. The script will take the target values as the center of this interval. While this does not really affects the bond distances and bond angles restraints, torsion angles target sometimes take unexpected values. This is because the allowed interval covers a wide range of angles.

• The torsion angle SMARTS patterns are not defined in the interval of 0 to 360 deg, but from 0 to 180 deg. TNT dictionaries for torsion angles can span the full range from 0 to 360 deg.

Please consult the documentation from the java GUI for more details about the program operation.