combine_receptors Usage

In many cases ligands from different receptors may be combined to yield more productive posing targets. For example, if, when the 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:

  • A_receptor_merged_B_receptor.oeb.gz
  • 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

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

Merged receptors

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.

Command Line Interface

A description of the command line interface can be obtained by executing combine_receptors 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 <parameter> : Get detailed help on a parameter
  combine_receptors --help html        : Create an html help file for this program

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 (>= 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.

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 make_pose_receptor 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).
-prealigned

Indicate that your receptors are pre-aligned and do not change their alignment on pain of death.

[default = false]

-verbose

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

[default = false]

Example Commands

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

First, make some receptors:

> mkdir receptors
> make_pose_receptor -prot renin/2IL2.pdb.gz -out receptors/2IL2_b.rec.oeb.gz -residues CIT501A
> make_pose_receptor -prot renin/2IL2.pdb.gz -out receptors/2IL2_a.rec.oeb.gz -residues LIX402B
> make_pose_receptor -prot renin/2IL2.pdb.gz -out receptors/2IL2_c.rec.oeb.gz -residues LIX401A
> make_pose_receptor -prot renin/2IKO.pdb.gz -out receptors/2IKO.rec.oeb.gz -residues 7IG601A
> make_pose_receptor -prot renin/2IKU.pdb.gz -out receptors/2IKU_a.rec.oeb.gz -residues LIY336A
> make_pose_receptor -prot renin/2IKU.pdb.gz -out receptors/2IKU_b.rec.oeb.gz -residues LIY336B
> combine_receptors -receptors receptors/*

Note

On Microsoft Windows systems, you may have to expand out the wildcard:

> combine_receptors -receptors receptors/2IL2_b.rec.oeb.gz receptors/2IL2_a.rec.oeb.gz \
        receptors/2IL2_c.rec.oeb.gz receptors/2IKO.rec.oeb.gz receptors/2IKU_a.rec.oeb.gz \
        receptors/2IKU_b.rec.oeb.gz

In this case, there were only two good merges which results in four output files, one for each reference frame. For example if protein A can be combined with protein B, then A_merge_B and B_merge_A will be written. :

Wrote combined receptor:merged/2IKO.rec_7IG601A._merge_2IKU_a.rec_LIY336A.oeb.gz ShapeTanimoto:0.6..
Wrote combined receptor:merged/2IKU_a.rec_LIY336A._merge_2IKO.rec_7IG601A.oeb.gz
Wrote combined receptor:merged/2IKU_a.rec_LIY336A._merge_2IKO.rec_7IG601A.oeb.gz ShapeTanimoto:0.6..
Wrote combined receptor:merged/2IKO.rec_7IG601A._merge_2IKU_a.rec_LIY336A.oeb.gz

It is often useful to place the merged receptors into a different directory, to do this, simply use the -outputdir option.

> combine_receptors -receptors receptors/* -outputdir merged

Note

Again, on some Microsoft Windows systems, you may have to expand out the wildcard (this will be omitted for all future examples):

> combine_receptors -receptors receptors/2IL2_b.rec.oeb.gz receptors/2IL2_a.rec.oeb.gz \
        receptors/2IL2_c.rec.oeb.gz receptors/2IKO.rec.oeb.gz receptors/2IKU_a.rec.oeb.gz \
        receptors/2IKU_b.rec.oeb.gz -outputdir merged

combine_receptors deals with clashes identically to make_pose_receptor. If a merged ligand has an unallowable clash with a protein, it will not result in a receptor. An example output is as follows:

Warning: Combined ligand: 2IKU_LIY336A.oeb.gz clashes with protein in 2IKO_7IG601A.oeb.gz
       To force output please use command line switch -allowedClashes mildclashes
       Note that POSIT should most likely be run with the same switch.
Warning: Combined ligand: 2IKO_7IG601A.oeb.gz clashes with protein in 2IKU_LIY336A.oeb.gz
       To force output please add the  command line switch -allowedClashes mildclashes
       it is recommended that POSIT be run with the same switch.
Warning: Combined ligand: 2IKO_7IG601A.oeb.gz clashes with protein in 2IKU_LIY336A.oeb.gz
       To force output please use command line switch -allowedClashes mildclashes
       Note that POSIT should most likely be run with the same switch.
Warning: Combined ligand: 2IKU_LIY336A.oeb.gz clashes with protein in 2IKO_7IG601A.oeb.gz
       To force output please add the  command line switch -allowedClashes mildclashes
       it is recommended that POSIT be run with the same switch.
Warning: All potential mergings clashed with the merged protein.

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