Example Commands

POSIT always requires a bound-ligand in a receptor to fit against and an output file. The ligand (or ligands) to fit is specified with the -dbase option or the -in option, and the structures to fit are specified with the -receptors. Multiple receptors can be input at a time, in fact this is the preferred mode of running POSIT.

Note

-dbase accepts only 3D molecules, normally generated by OMEGA.

-in accepts most formats and generates 3D conformations when applicable. When in doubt, use the -in option.

Basic Usage

The basic form of running POSIT is to fit against multiple receptors. The best fit receptor will be chosen for the final pose. Assuming that you have made receptors and combined them as shown above:

> posit -receptors renin/receptors/*.oeb.gz renin/merged/*.oeb.gz -in renin/all.smi \
         -docked_molecule_file results.sdf

Note

On Microsoft Windows systems, you need to expand the wildcard:

> posit -receptor renin\receptors\2IL2_b.rec.oeb.gz renin\receptors\2IL2_a.rec.oeb.gz \
      renin\receptors\2IL2_c.rec.oeb.gz renin\receptors\2IKO.rec.oeb.gz \
      renin\receptors\2IKU_a.rec.oeb.gz renin\receptors\2IKU_b.rec.oeb.gz \
      renin\merged\2IKU_a.rec._merge_2IKO.rec.oeb.gz renin\merged\2IKO.rec._merge_2IKU_a.rec.oeb.gz \
      -in renin\all.smi -docked_molecule_file results.sdf

All results are written to the specified output file.

Any predicted ligand that has a good probability but clashes with the protein will either be ignored or, if the -clashed_mol_file output is specified on the command line, it will be output to the specified file.

> posit -receptors renin/receptors/*.oeb.gz renin/merged/*.oeb.gz -in renin/all.smi \
         -docked_molecule_file .sdf

Ignoring Nitrogen Stereo

By default, POSIT ignores nitrogen stereo to make it easier to dock input x-ray models which may be time-averaged resulting in planar nitrogens.

If desired, this flag can be set to false in order to only fit explicit nitrogen stereo:

> posit -receptors renin/receptors/*.oeb.gz renin/merged/*.oeb.gz -in all.smi \
          -docked_molecule_file results.sdf -ignore_nitrogen_stereo false

Note

POSIT 1.0 defaulted to not ignoring nitrogen stereo. This was changed due to the nature of crystallographic structures tending to produce time-averaged planar nitrogens.

Sometimes you may see warnings like the following:

Warning: Input stereochemistry different from output after fitting
in: CCc1c(c(nc([nH+]1)N)N)c2ccc3c(c2)N(CCC3)CCCOC
out: CCc1c(c(nc([nH+]1)N)N)c2ccc3c(c2)[N@](CCC3)CCCOC
Warning: Input stereochemistry different from output after fitting
in: CCc1c(c(nc([nH+]1)N)N)c2ccc3c(c2)N(CCC3)CCCOC
out: CCc1c(c(nc([nH+]1)N)N)c2ccc3c(c2)[N@@](CCC3)CCCOC

These simply serve as a warning that stereochemistry was added or modified during the fitting/optimization process.

Advanced Usage

To run POSIT on absolutely everything and not worry about clashes or probabilities:

> posit -receptors renin/receptors/*.oeb.gz -in renin/ren1.smi \
 -docked_molecule_file results.oeb  -outputall

This runs POSIT and outputs all docked molecules regardless of score in the order they exist in the input file.