The MKHetDict utility generates PDB format heterogen (small-molecule) dictionary files that are used by reduce to add hydrogens to ligand and cofactor atoms. Each non-standard residue will have an entry in the dictionary. The reduce option -db <dict.txt> ensures these residues will be protonated, as long as the “het-dict” is a .txt file and the input structure file is provided to reduce in .pdb format.
Reduce [Word-1999] is open source software from the Richardson laboratory at Duke University. It is free to license and available for download available at kinemage.biochem.duke.edu. Windows Vista or Windows 7 users should use the latest version as some Windows versions of reduce do not process the heterogen dictionary correctly. This software is described here for your convenience only, you are free to use any software you prefer to add and optimize hydrogens.
OpenEye has not been involved in the development of reduce and does not provide support for reduce.
The usual workflow is to make a “het-dict” and then use it to generate a protonated output file (reduce writes the protonated structure to standard output, in the example below this is redirected to the file molH.pdb with the ‘>’ operator).
> mkhetdict mol.pdb mol_hetdict.txt > reduce -db mol_hetdict.txt -build -rotexist mol.pdb >molH.pdb
If MKHetDict chooses a different tautomer or ionization state than the one you feel is appropriate, the hetdict.txt file can be modified in a text editor before running reduce.
Below is an example heterogen dictionary made by MKHetDict. Although this file contains only one entry, structures with more than one type of small-molecule will contain multiple entries, one per type. Each CONECT record identifies an atom, specifies how many other atoms it is bonded to, and enumerates each bonded atom. Each atom is listed in multiple places, as the parent atom and again as a bonded neighbor. When editing this file, care must be taken to maintain the column positions in the file—blank spaces are significant. Also, when atoms are added or removed from an entry, be sure to update the total number of atoms on the lines that begin with RESIDUE and HET.
RESIDUE BFS 33 CONECT C1 3 C2 C6 C CONECT C2 3 C1 C3 O2 CONECT C3 3 C2 C4 H3 CONECT C4 3 C3 C5 H4 CONECT C5 3 C4 C6 F5 CONECT C6 3 C1 C5 H6 CONECT C 3 C1 N O CONECT CE1 4 CE2 C1' N HE1 CONECT CE2 4 CE1 HE21 HE22 HE23 CONECT C1' 3 CE1 C2' C6' CONECT C2' 3 C1' C3' H2' CONECT C3' 3 C2' C4' H3' CONECT C4' 3 C3' C5' BR4 CONECT C5' 3 C4' C6' H5' CONECT C6' 3 C1' C5' H6' CONECT N 3 C CE1 HN CONECT O 1 C CONECT O2 2 C2 H2 CONECT F5 1 C5 CONECT BR4 1 C4' CONECT HN 1 N CONECT H3 1 C3 CONECT H4 1 C4 CONECT H6 1 C6 CONECT HE1 1 CE1 CONECT HE21 1 CE2 CONECT HE22 1 CE2 CONECT HE23 1 CE2 CONECT H2' 1 C2' CONECT H3' 1 C3' CONECT H5' 1 C5' CONECT H6' 1 C6' CONECT H2 1 O2 END HET BFS 33
A description of the command line interface can be obtained by executing MKHetDict with the --help option.
> mkhetdict --help
will generate the following output:
Help functions: mkhetdict --help simple : Get a list of simple parameters mkhetdict --help all : Get a complete list of parameters mkhetdict --help defaults : List the defaults for all parameters mkhetdict --help <parameter> : Get detailed help on a parameter mkhetdict --help html : Create an html help file for this program mkhetdict --help versions : List the toolkits and versions used in the application
[keyless parameter 2]
Output PDB format small-molecule dictionary file.
Must have the extension .txt for reduce to recognize it.
Do not adjust heterogen molecules for neutral pKa. At times, this adjustment can either delete a hydrogen or rename one in a way that will cause reduce to produce inappropriate extra hydrogens. Turning it off may leave the molecule in a state that is not canonical but will not have these pathologies.