SCOREPOSE

Overview

SCOREPOSE scores poses in a database in the context of a single receptor using the Chemgauss4 scoring function. Poses may also optionally be optimized vs. Chemgauss4.

Note

SCOREPOSE does not dock molecules, it only rescores and optionally optimizes molecules within the context of a receptor site.

Input Preparation

Ligand Preparation

The ligand input to SCOREPOSE should already be docked into the receptor site. For the purposes of this document, we’ll call the file(s) of poses to be scored the database file(s), or dbase file(s). Supported formats of the database file include SDF, MOL2 and PDB. SCOREPOSE determines the database file format from the file extension, .sdf or .mol for SDF, .mol2 for MOL2, .pdb or .ent for PDB. Gzip compressed files of these same formats are allowed as well. SCOREPOSE will interpret infile.sdf.gz as a gzip’ed SDF file.

Note

Note that even though all these formats are supported, using SDF, PDB or MOL2 can result in a loss of speed due to the I/O penalty of these formats. We recommend using Gzipped OEB format for maximum speed.

By default SCOREPOSE will interpret conformers in the database file(s) as part of a single multi-conformer molecule as long as they:

  • Are contiguous in the input file.
  • Have the same numbers of atoms and bonds in the same order
  • Have identical atom and bond properties with their order correspondent in the subsequent connection table
  • Have the same atom and bond stereochemistry

While this may appear to be a restrictive list, many programs write multi-conformer molecules into SDF or MOL2 files such that the above rules will be satisfied. If the conformers are named differently, (i.e. they have a conformer number appended to the base name like acetsali_1, acetsali_2), SCOREPOSE will still consider them part of a single multi-conformer molecule if the criteria above are met. For file formats that are not inherently multi-conformer, this behavior can be turned off or modified with the -conftest command-line switch.

Receptor Preparation

SCOREPOSE requires the receptor file that the ligands in the database were docked to. This should generally already be available if the ligands were docked with FRED or HYBRID. If the ligands were docked with another program a receptor can be created using one of the following programs.

Program Type Description
make_receptor GUI Interactive GUI for creating a receptor.
pdb2receptor Command Line Creates a receptor from a PDB file with a protein-ligand complex.
apopdb2receptor Command Line Creates a receptor from a PDB file with apo protein (i.e., no ligand).
receptor_setup Command Line Creates a receptor from a molecule file with a protein and a separate file with either the structure of a bound ligand or a box enclosing the active site.

Note

Receptors can also be created using the OpenEye Docking Toolkit (see the Docking Toolkit documentation).

Parameter List

Input

-receptor : Receptor file(s).

-dbase : Poses to rescore.

-conftest : Conformer test.

-molnames : Molecule names file.

-param : Parameter file.

Score Options

-optimize : Optimize poses before scoring.

Output Files

-rescored_mol_output_file : Output file for rescored poses.

-score_file : Text scores file.

-report_file : Text report file.

-settings_file : Text settings file.

-status_file : Text status file.

Output Options

-hitlist_size : Number of top scoring molecules to retain.

-sort_poses : Re-order poses of each molecule by rescored value.

-annotate_scores : Add VIDA score annotations.

-score_tag : Override the default score tag.

-save_component_scores : Save breakdown of scores by component.

-no_extra_output_files : Suppress default writing of extra output files.

-no_dots : Suppress default writing of dots.

-prefix <value> [Default: rescore]

This flag prefixes all default output filenames with the specified value.

Note

This flag does not affect output filenames explicitly set by the user.

Note

Values in parenthesis are default values.

Parameter Details

Input

-receptor <receptor file> [No Default: Required Parameter]

Receptor file to rescore poses with.

[ Aliases = -rec ]

-dbase <input filename1> [<input filename2> ...] [No Default: Required Parameter]

File(s) containing ligand poses to rescore (see section Ligand Preparation).

The following file formats are supported.

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

More than one file can be specified.

[ Aliases = -database, -in ]

-param <parameter filename> [No Default]

A parameter file is a text file that lists parameter settings to be used during a run. If a parameter is specified both on the command line and in the parameter file, the value specified on the command line is used.

The format of the parameter file is as follows:

  • One parameter per line
  • For non-list parameters one key-value pair per line. (e.g., -receptor rec.oeb.gz).
  • For list parameters a key followed by all the values (e.g., -dbase lig1.oeb.gz ligs2.oeb.gz)
  • Boolean parameters must be listed as a key followed by true or false (e.g. -annotate_poses true).
  • The parameter file may not contain the -param parameter.
  • Lines begining with # are considered comments
-conftest <test type> [Default: isomeric]

Note

This flag has no effect when the database format is OEBinary

When non-OEBinary database file(s) (see parameter -dbase) are read a test is applied to determine if subsequent molecules in the database file(s) are conformers of the same molecule. This flag controls how that conformer test is applied.

The following test types are recognized

Test Type Subsequent molecules are conformers if they
isomeric Have the same numbers of atoms and bonds in the same order. Each atom and bond has identical properties with its order correspondent in the subsequent connection table. Have the same atom and bond stereochemistry.
absolute Have the same numbers of atoms and bonds in the same order. Each atom and bond has identical properties with its order correspondent in the subsequent connection table.
canonical Have the same absolute (non-isomeric) graph.
none Subsequent molecules never treated as a conformer. Database is effectively single conformer.
-molnames <input filename> [No Default]

This parameter specifies a text file containing a list of molecule names (one name per line in the file). If this parameter is set then only molecules in the database file(s) (see parameter -dbase) with names that match those in the text files will be read in.

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

Score Options

-optimize <level> [No Default]

If this parameter is specified each pose will be optimized with a systematic solid body optimization with a resolution given by the table below.

Level Translational Stepsize Rotational Stepsize
High 0.5 Ångström 0.5 Ångström
Standard 0.5 Ångström 0.75 Ångström
Low 0.75 Ångström 1.0 Ångström

If this parameter is not specified poses will not be optimized prior to scoring.

[ Aliases : -opt ]

Output Files

-rescored_mol_output_file <output filename> [Default: scored.oeb.gz]

File rescored molecules will be written to. The file format is controlled by the extension of the filename. The following output formats are supported.

Format Extension
OEBinary .oeb
SDF .sdf
Gzipped OEBinary .oeb.gz
Gzipped SDF .sdf.gz

Scores will be attached as SD data to each pose with the tag FRED Chemgauss4 Score, unless the -score_tag option is used to specify another tag.

By default the top 500 scoring molecules will be outputted to this file (see -hitlist_size flag).

Note

If this flag is not set by the user the default filename (i.e., scored.oeb.gz) will be automatically prefixed with the setting of the -prefix flag.

[ Aliases = -docked_file, -docked, -out ]

-score_file <filename> [Default: score.txt]

Specifies a tab separated text file with the name and scores of the molecules.

Note

If this flag is not set by the user the default filename (i.e., score.txt) will be automatically prefixed with the setting of the -prefix flag.

[ Aliases : -score ]

-report_file <filename> [Default: report.txt]

Specifies a file that a text report of the run will be written to.

Note

If this flag is not set by the user the default filename (i.e., report.txt) will be automatically prefixed with the setting of the -prefix flag.

[ Aliases : -report ]

-settings_file <filename> [Default: settings.param]

Writes the settings of all parameters of the run to the specified output file. The settings will be listed in plain text with one parameter name follow by its value(s). This format is compatible with the format of parameter files, and therefore a settings file from a previous run can be passed to the -param flag to re-run the program with the same settings.

Note

If this flag is not set by the user the default filename (i.e., settings.param) will be automatically prefixed with the setting of the -prefix flag.

[ Aliases : -settings ]

-status_file <filename> [Default: status.txt]

If this parameter is set then the status of the run will be written to the given output file every few seconds (the previous contents of the file will be overwritten) during the run.

Note

If this flag is not set by the user the default filename (i.e., status.txt) will be automatically prefixed with the setting of the -prefix flag.

[ Aliases : -status ]

Output Options

-hitlist_size <num> [Default: 500]

This parameter controls whether docked molecules are outputted as they are docked or in an internal hitlist and outputted at the end of the run.

If -hitlist_size is zero the run will be in serial mode, i.e. each molecule will be outputted as it is docked (unsorted). For single processor runs this will be the order the molecules appear in the database file(s). For MPI runs the order will not be strictly the order the molecules appear in the database file(s).

If -hitlist_size is non-zero a sorted internal hitlist of docked molecules that will be maintained and outputted at the end of the run. The maximum size of the hitlist is -hitlist_size. If more than this number of molecules are docking during the run only the top scoring molecules will be outputted and the rest will be discarded.

There is no formal limit on the number of molecule that can be sorted and outputted at the end of the run. However, retaining a large number of molecules significantly increases the memory requirements. A good rule of thumb is that the setting total number of poses retained should not be larger than 10,000.

[ Aliases = -hitlist_size, -hitlist ]

-sort_poses [Default: false]

If this option is selected the poses of each molecule will be sorted by score.

If the molecules in the database do not have multiple poses this flag has no effect.

[ Aliases = -sortposes ]

-score_tag <tag> [No Default]

This parameter overrides the default SD Data Tag used to store molecule scores (the default is FRED Chemgauss4 Score).

[ Aliases = -scoretag ]

-annotate_scores [Default: false]

If the value of this flag is set to true VIDA score annotations will be added to the processed molecules. These annotations are visible in VIDA (OpenEye’s molecular visualization program) and show a per atom breakdown of the score.

Note

The docked molecule output file format (see -docked_molecule_file) must be OEBinary when using score annotations.

[ Aliases = -annotate ]

-save_component_scores [Default: false]

If the value of this flag is set to true individual components of the total score will be saved to SD data on each pose and appear in the score file (see -score_file).

[ Aliases = -component_scores, -component ]

-no_extra_output_files [Default: false]

When set the only default output to the program will be the docked structure file (see -rescored_mol_output_file).

Using this flag suppresses the default output of the following

Output Default file Parameter
text score file score.txt -score_file
report file report.txt -report_file
settings file scorepose.param -settings_file
status file status.txt -status_file

Only default output is suppressed. If any of these output parameters are explicitly set by the users the relevant output file will still be written even if this switch is turned on.

[ Aliases = -no_extra, -noextra, -noextraoutputfiles, -no_extra_output, -noextraoutput ]

-no_dots [Default: false]
When this flag is set to true, a dot is being written to standard error for each docking molecule (or x in the case of a failure). Setting this flag to false to suppress dot/x writing.

[ Aliases = -nodots ]