Running SZMAP Stabilization Calculations

Assuming the input structures have been prepared as described above, SZMAP grids can be calculated for the region around the ligand as follows:

> szmap -mpi_np 4 -prefix 4std_stbl -stbl -p 4STD_ABC__DU__BFS_A-173.oedu -excludeDUsolvent

or

> szmap -mpi_np 4 -prefix 4std_stbl -stbl -p 4STD_A__DU__BFS_A-173_target.oeb.gz -l 4STD_A__DU__BFS_A-173_ligand.oeb.gz

Note

The option -excludeDUsolvent is needed to exclude structural waters from the stabilization calculation if the input is using a design unit.

Stabilization calculations can also be performed with a dataset of pre-posed non-native ligands, using the commands below.

> szmap -mpi_np 4 -prefix 4std_stbl -stbl -p 4STD_ABC__DU__BFS_A-173.oedu -excludeDUsolvent -l posed_ligands.oeb

Calculations for complex, apo, and ligand grids will be done (requiring about 40 minutes for this example on Linux using four 2.8GHz processors) and then further processed to yield (complex - apo - ligand) stabilization grids, describing where water is stabilizing or destabilizing the binding reaction. The output consists of the calculated grids in an .oeb.gz file, along with a parameter file and a log file, all with names prefixed with “4std_stbl”.

To run on only a single processor, drop the -mpi_np # option. More information on options can be found in chapter SZMAP.

Note

SZMAP (and GamePlan) will check for missing hydrogens and missing partial charges and halt if they are missing on the protein, but that will typically not be a problem if the input is an OEDesignUnit. It also shouldn’t be a problem with the ligand read from an OEDesignUnit, however, if a ligand is passed with missing partial charges, they will be assigned AM1BCC charges and Zap9 radii. If reading from a PDB, sometimes, OEChem will have a different opinion about the charge or bond order than what you expect. For example, if your structure has significantly nonterminal geometry around an aromatic or double bond, OEChem may try to treat it as a single bond. The option -warn_if_missing_hydrogens will allow you to run SZMAP and GamePlan despite OEChem thinking there are hydrogens that are not explicitly in your structure. But you may also need to change the formal charge of a polar group before running pch, either in VIDA’s builder or by modifying the structure file using a text editor.