posit Usage

posit works best when fitting to a collection of co-crystal ligands, however, it can be used for a single ligand targets. Each pose that posit generates is analyzed with a simple heuristic and marked with a probability (seen below).

The structures output by posit are annotated with information about the best-fit receptor and with various metrics describing the details of the pose. These details are stored in SDDATA and can be viewed with most molecular structure viewers.

The details are as follows:

Name Description
Docking Input Order The input order from the original file
Result GREAT, GOOD, MEDIOCRE or POOR detailing the quality of the result
POSIT receptor title the name of the receptor (taken from the original protein)
POSIT receptor filename the filename of the original receptor
POSIT::Probability Estimated probability of being within 2 Ångström RMSD of the real structure (assuming binding)
POSIT::Method The underlying method used (SHAPEFIT, HYBRID, FRED)
Dock Type The docking type used (which is POSIT in this case)

These values are also written to the report file in a tab separated format, see -prefix for details.

The probability that the computed pose is a correct pose is generate as described in Predicting the Quality of the Pose.

The values in the Result field are as follows:

Result Meaning
GREAT Computed pose is likely (75%-100%) probability) to be within 2.0 Å of experimentally-derived pose.
GOOD Computed pose may be (50%-75%) probability) to be within 2.0 Å of experimentally-derived pose.
MEDIOCRE Take with a grain of salt (33%-50%) probability)
POOR Take with a huge grain of salt (<33% probability)

By default, POOR poses are not written out, they are rejected as unsuitable. The number of rejected molecules is recorded in the status file.

Command Line Interface

A description of the command line interface can be obtained by executing posit with the --help option.

> posit --help

will generate the following output:

Help functions:
  posit --help simple      : Get a list of simple parameters
  posit --help all         : Get a complete list of parameters
  posit --help <parameter> : Get detailed help on a parameter
  posit --help html        : Create an html help file for this program

Required Parameters

-receptor <filenames>

List of receptors used to predict the pose of the input molecules. Receptors must include a bound ligand.

Multiple receptors can be input:

> posit -receptor rec*.oeb

Will use all files that start with rec and end with .oeb.

> posit -receptor  receptors.lst

Will use all receptors files specified in the receptors.lst file. If any entry in the specified file is not a valid receptor, posit will halt.

Supported -receptor file formats are:

File type Extension
OEBinary .oeb .oeb.gz
list .lst

Multiple receptor files and list files can be used simultaneously.

Note

This option also is aliased to -receptors which was used in POSIT 1.0.

-in <filename>

Input molecules to pose-predict. If 3D molecules are input, the original conformations are retained for optimization as well as the expanded conformational ensemble.

Note

This option also aliases to -lig which was used in POSIT 1.0 For more alias details, please use the command:

> posit --help in

posit uses an internal conformation sampling to generate high-quality conformations. However, input ring structures (chair/boat) may not be reproduced as posit may choose a lower energy ring template during the sampling process.

Supported input file formats are:

File type Extension
OEBinary .oeb .oeb.gz
SDF .sdf .mol .sdf.gz .mol.gz
MOL2 .mol2 .mol2.gz
PDB .pdb .ent .pdb.gz .ent.gz
MacroModel .mmod .mmod.gz
Smiles .smi .smi.gz .ism.gz
-dbase <filename>

Input molecules to pose-predict. 3D molecules must be input as conformational expansion is not performed prior to fitting.

Note

For more alias details, please use the command:

> posit --help dbase

Note

-dbase is the fastest way to run posit on large datasets. The expected input is a pre-generated database of OMEGA generated conformers. It is recommended, above two rotatable bonds, to generate 100 conformers per rotatable bond when running OMEGA:

> omega2 -in renin/all.smi -out all.oeb.gz -rangeIncrement 1 \
   -maxConfRange 200,200,300,400,500,600,700,800,900,1000,1100,1200,1300,1400,1500,1600

Supported input file formats are:

File type Extension
OEBinary .oeb .oeb.gz
SDF .sdf .mol .sdf.gz .mol.gz
MOL2 .mol2 .mol2.gz
PDB .pdb .ent .pdb.gz .ent.gz
-conftest

Set the desired test to convert the input single-molecule database into a stream of multi-conformer molecules. Internally posit analyzes multi-conformer molecules as a whole and will only report on result for each molecule.

The settings for this flag have the following meaning:

none:
No conformer test is done, database is treated as single conformer
isomeric:

Molecules are conformers if they:

  • Have the same numbers of atoms and bonds in the same order
  • Each atom and bond must have identical properties with its order correspondent in the subsequent connection table
  • Have the same atom and bond stereochemistry
absolute:

Molecules are conformers if they:

  • Have the same numbers of atoms and bonds in the same order
  • Each atom and bond must have identical properties with its order correspondent in the subsequent connection table
canonical:
Molecules are conformers if they have the same absolute (non-isomeric) graph

Note

The default conformer test setting is isomeric.

-molnames

This flag specifies a text file with the names of one or more molecules in supplied to the -dbase flag. If specified, only molecules with matching names will be read by the -dbase flag. If this flag is not specified all molecules will be read normally. Molecules names should be listed one per line.

The general purpose of this flag is to provide an easy mechanism for reading a few specific molecules that are contained in a large database, without having to extract those molecules by hand from the database.

Multiprocessing Parameters

Execute Options

-param
The argument for this flag is the name of a file containing control parameters. The control parameter file acts to either replace or augment the command line interface. All parameters necessary for program execution may be provided in the control parameter file, although any command given explicitly on the command line will supersede options found in the parameter file. The application generates a new parameter file containing the full set of execution parameters upon every execution. The name of the parameter file is created by combining the prefix base name with the ‘.param’ extension.
-mpi_np <n>
Specifies the number of processors n when the application is run in MPI mode.
-mpi_hostfile <filename>
Specifies the name of the file containing processors configuration. For every host this file should contain a line host_name slots=n where n is the number of processors on the host.

Dock Options

-ignore_nitrogen_stereo

When examining the ligands to pose predict for stereo, ignore any missing nitrogen chirality. (This is normally caused by time averaging of crystal structures).

When expanding stereo, nitrogen stereo centers will not be assigned.

Note

posit may complain about stereo centers being changed by the optimization, this is more likely when ignoring nitrogen stereo centers since the optimization may decide a different stereo configuration is optimal.

For compatibility with POSIT 1.0 this command is aliased to -ignoreNitrogenStereo

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.

The -expandMissingStereo option has been dropped, posit now always expands missing stereo.

Output Files

posit writes docked structure results to a single file, -docked_molecule_file – Ligand only output in one file.

The following output formats are removed in POSIT 3.1.0:

  • -outcomplexes - Interleaved complex output in one file
  • -outreceptors - One file for each receptor matched containing all ligands that were fit to the receptor

By default, not all poses may be written to the output, to see where ligands were placed, consult the log file for more details. To control this behavior use the -outputall flag, which writes all output to the file specified by -out in order of input molecule.

-docked_molecule_file <filename>

If specified, this flag overrides the default name of the docked molecule output file. Only .oeb, .oeb.gz, .sdf and .sdf.gz formats are allows as the poses best fit receptor and various other optimization results are tagged to the SD data of the molecule.

Note

The default file is posit_docked.oeb.gz, or <-prefix>_docked.oeb.gz if the -prefix flag is specified.

Ligands are written to the output file based on the desired sort order (see the -sortby flag).

Note

This command is aliased to -out which was the name used in POSIT 1.0

-undocked_molecule_file

If specified this flag overrides the default name for the undocked molecule file.

Note

The default filename is posit_undocked.oeb.gz, or <-prefix>_undocked.oeb.gz if -prefix is specified.

-score_file

If specified overrides the default name of the output text file containing the scores of the docked molecules.

Note

The default filename is posit_score.txt or <-prefix>_score.txt if the -prefix flag is specified.

-report_file

If specified overrides the default output filename for the report file.

Note

The default filename for the report file is posit_report.txt or <-prefix>_report.txt if the -prefix flag is specified.

-status_file

If specified overrides the default filename for the status file.

Note

The default status file name is posit_status.txt or <-prefix>_status.txt if the -prefix flag is specified.

-reject_file

If specified overrides the default filename for the reject file.

The reject file is a tab separated file containing the input ligand number, the ligand title and the reason for the ligand being undocked.

Example output:

Ligand #        Title#Status
0       lig1    No conformers above minimum probability
1       lig2    No conformers above minimum probability
2       lig3    No conformers above minimum probability
3       lig4    No conformers above minimum probability

Note

The default status file name is posit_rejected.txt or <-prefix>_rejected.txt if the -prefix flag is specified.

-settings_file

If specified overrides the default output filename for the setting file.

Note

The default settings filename is posit_settings.param or <-prefix>_settings.param if the -prefix flag is specified.

-clashed_molecule_file <filename>

Occasionally posit rejects ligands that probably have the correct binding mode but also display uncorrectable clashes. If this flag is set, clashed molecules will be written to this file in no specific output order.

It is important to be aware that because these are likely binding modes there is a chance that the clashed poses are still correct but the protein has reconfigured to accept the clashed pose.

The following output formats are removed in POSIT 3.1.0:

  • -clashcomplexes - Interleaved complex output in one file
  • -clashreceptors - One file for each receptor matched containing all ligands that were fit to the receptor

Note

This command is aliased to -clash which was the name used in POSIT 1.0

Output Options

-hitlist_size

The hit size controls the number of molecules output by posit. If the hit list size is 0, a temporary file is created in order to sort the results for output.

In all cases, the output file is sorted by the current value of the -sortby command line argument.

-sortby

-sortby specifies the order in which to sort the output results. The two available sort orders are:

Allowed Clash Description
probability Sort results in order from highest pose probability to lowest.
asinput Sort the results in input order

[default = asinput]

-minimum_probability

By default posit only outputs relatively probable poses. To output all poses, set -minimum_probability to 0.

[default = 0.33]

-allowed_clashes

Clashes allowed at the end of optimization. There are three levels:

Allowed Clash Description
noclashes No clashes are allowed. Actually there is a little wiggle room here less than 0.2 Ångström penetration is not considered a clash.
mildclashes Mild clashes are allowed (>= 0.2 Ångström < 0.65 Ångström interpenetration)
allclashes All clashes are allowed.

The clash ranges have been tuned to account for average coordinate error in a sampling of PDB files, they are intended to be used as guidelines and may not be indicative of some clash states.

Note

If any of the receptors themselves have clashing ligands, a warning will be generated but posit will automatically be set to accept the receptor ligand by adjusting the clash setting appropriately.

All poses that are accepted by the probability calculation yet clash with the protein are written to the fail file (if specified).

[default = mildclashes]

-force_planar_aromatic

Add a planar potential to aromatic rings, this attempts to keep aromatic systems planar. This mostly affects molecules that require high strain to match the bound ligand.

Note

For compatibility with POSIT 1.0 this command is aliased to -forcePlanarAromatic.

[default = true]

-num_poses

Number of alternative poses to retain for each docked molecule. The default is to only output the most probable pose.

[default = 1]

-score_tag
Overrides the default tag used to attach the score to the output molecules
-no_extra_output_files
Suppress the default output of the score, status, settings, report and undocked files.
-no_dots
Suppress writing a dot (.) to standard error for each docking molecule (or x in the case of a failure).
-prefix
The text passed to this parameter will be preappended to all default output filenames (it does not affect output filenames explicitly set by the users).
-outputall
Shorthand to write all output including clashed or non probable molecules.

Options removed from POSIT 1.0

-alternatePoseRMSD
RMSD for alternate poses
-alternatePoses
Output alternate poses as well as best pose
-cleanupWithProtein
Use the protein to drive placement of the ligands
-mcs
Add the MCS (Maximum Common Substructure) alignment to the initial overlays
-minInitialProbability
If the initial TanimotoCombo is below this value, skip optimization
-minInitialTanimotoCombo
If the initial TanimotoCombo is below this value, skip optimization
-minTanimotoCombo
The minimum TanimotoCombo to assert a good match. Anything less will be rejected.
-probabilityStop
If a receptor is found with this probability or higher, stop searching receptors.
-scatter
Use the scattering function of the target as opposed to a molecular Gaussian
-selectReceptorBy
One of: pathsim, maccssim, initialTanimotoCombo, finalTanimocoCombo, probability
-strain
Maximum delta strain to allow based on estimated minimum stain.

Example Commands

The example commands in this section can be run with files found in the example/posit/3.1.0.2 directory under the top-level installation directory.

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

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.