combine_receptors¶

Overview¶

In many cases ligands from different receptors may be combined to yield more productive posing targets. For example, if, when the two proteins are aligned, two ligands overlap but occupy different spaces in the binding pocket, combine_receptors will make a single receptor using both ligands that may be a better target for predicting some ligands.

When given multiple receptors, combine_receptors will find the best matched pair for each input receptor. The best matched pair is the combination of two ligands that overlap but have a large difference in shape.

For each set of combined ligands, two receptors are output, one for each input protein. This also helps when analyzing clashes.

Output names are automatically generated so that if two receptors are merged, say A_receptor.oeb.gz and B_receptor.oeb.gz, two outputs are formed:

combine_receptors_A_receptor_merged_B_receptor.oeb.gz

combine_receptors_B_receptor_merged_A_receptor.oeb.gz

For example, consider the merged receptors shown in figures Merged receptors and Matched to merged receptor.

Merged Receptors: Merging the receptors 2IKO and 2IKU capture more potential interaction constraints than either does alone¶

Matched to Merged Receptors: REN9 is correctly predicted by the merged receptor¶

If a combined ligand has significant clashes with the protein a warning will also be output with the recommended setting when running posit. Serious clashes will not be output unless the user specifies the -allowedClashes option.

Example Commands¶

To run combine_receptors, simply provide a list of known receptors:

First, make some receptors:

> spruce -in renin/2IKO.pdb.gz
> spruce -in renin/2IKU.pdb.gz

To convert output OEDesignUnit files into OEBinary files:

> du2oebreceptor -in rec_2IKO_ABCDEFsym1__DU__7IG_A-601.oedu -out rec_2IKO_ABCDEFsym1__DU__7IG_A-601.oeb.gz
> du2oebreceptor -in rec_2IKO_ABCDEFsym2__DU__7IG_A-601.oedu -out rec_2IKO_ABCDEFsym2__DU__7IG_A-601.oeb.gz
...
> du2oebreceptor -in rec_2IKU_ABCDEF__DU__LIY_A-336.oedu -out rec_2IKU_ABCDEF__DU__LIY_A-336.oeb.gz
> du2oebreceptor -in rec_2IKU_ABCDEF__DU__LIY_B-336.oedu -out rec_2IKU_ABCDEF__DU__LIY_B-336.oeb.gz
...

> combine_receptors -receptors rec_*.oeb.gz

Note

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

> combine_receptors -receptors rec_2IKO_ABCDEFsym1__DU__7IG_A-601.oeb.gz  rec_2IKO_ABCDEFsym2__DU__7IG_A-601.oeb.gz rec_2IKO_ABCDEFsym3__DU__7IG_A-601.oeb.gz  rec_2IKU_ABCDEF__DU__LIY_A-336.oeb.gz rec_2IKU_ABCDEF__DU__LIY_B-336.oeb.gz rec_2IKU_ABCDEF__DU__LIY_C-336.oeb.gz rec_2IKU_ABCDEF__DU__LIY_D-336.oeb.gz rec_2IKU_ABCDEF__DU__LIY_E-336.oeb.gz rec_2IKU_ABCDEF__DU__LIY_F-336.oeb.gz

The merged receptor files will be named combine_receptors_rec_*:

Wrote combined receptor:combine_receptors_rec_2IKU_ABCDEF__DU__LIY_E-336_merged_rec_2IKO_ABCDEFsym1__DU__7IG_A-601.oeb.gz
Wrote combined receptor:combine_receptors_rec_2IKO_ABCDEFsym2__DU__7IG_A-601_merged_rec_2IKU_ABCDEF__DU__LIY_E-336.oeb.gz ShapeTanimoto of merged ligands:0.690121
...

It is often useful to first collect the receptors ready for combining into a directory, and place the merged receptors into another directory which must already exist, to do this, simply use the -outputdir option.

> combine_receptors -receptors receptors/*.oeb.gz -outputdir merged

Note

Again, on Microsoft Windows systems, you need to expand the wildcard (this will be omitted for all future examples).

If a merged ligand has an unallowable clash with a protein, it will not result in a receptor.

Command Line Help¶

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

> combine_receptors --help

will generate the following output (omitting the OpenEye banner for space)

Help functions:
  combine_receptors --help simple      : Get a list of simple parameters
  combine_receptors --help all         : Get a complete list of parameters
  combine_receptors --help defaults    : List the defaults for all parameters
  combine_receptors --help <parameter> : Get detailed help on a parameter
  combine_receptors --help html        : Create an html help file for this program
  combine_receptors --help versions    : List the toolkits and versions used in the application

Required Parameters¶

-receptors <filenames>¶: List of receptors to combine. If a file is not a receptor, combine_receptors will halt.

Optional Parameters¶

-allowedClashes¶

Clashes allowed between the ligand and protein of a receptor. 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 (greater than 0.2 Ångström and less than 0.65 Ångström)
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.

By default, receptors are not output if serious clashes exist between the specified ligand and protein. By specifying -allowedClashes allclashes all clashing receptors will be output.

[default = mildclashes]

-param <filename>¶: Defines the control parameter file. This file can contain a collection of parameters which can be used instead of writing each parameter to the command-line. In addition, the parameter file written by any posit run (see -prefix below), can be used with the -param flag in subsequent posit_ executions. Any command given explicitly on the command line will supersede any command found in a file specified with the -param parameter.

-prefix¶

Controls the name of the default param file.

[default = combine_receptors]

-outputdir¶: Write the merged receptors to the directory specified (the directory must already exist).

-verbose¶

Show that matching status of every receptor pair (whether it is merged or not)

[default = false]