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, CombineReceptors will make a single receptor using both ligands that may be a better target for predicting some ligands.
When given multiple receptors, CombineReceptors 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:
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.
To run CombineReceptors, simply provide a list of known receptors:
First, make some receptors:
> mkdir receptors > pdb2receptor -pdb renin/2IL2.pdb.gz -receptor receptors/2IL2_b.rec.oeb.gz -ligand_residue CIT501A > pdb2receptor -pdb renin/2IL2.pdb.gz -receptor receptors/2IL2_a.rec.oeb.gz -ligand_residue LIX402B > pdb2receptor -pdb renin/2IL2.pdb.gz -receptor receptors/2IL2_c.rec.oeb.gz -ligand_residue LIX401A > pdb2receptor -pdb renin/2IKO.pdb.gz -receptor receptors/2IKO.rec.oeb.gz -ligand_residue 7IG601A > pdb2receptor -pdb renin/2IKU.pdb.gz -receptor receptors/2IKU_a.rec.oeb.gz -ligand_residue LIY336A > pdb2receptor -pdb renin/2IKU.pdb.gz -receptor receptors/2IKU_b.rec.oeb.gz -ligand_residue LIY336B
> combine_receptors -receptors receptors/*
On Microsoft Windows systems, you need to expand 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
Again, on Microsoft Windows systems, you need to expand 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
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.
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
List of receptors to combine. If a file is not a receptor, combine_receptors will halt.
Clashes allowed between the ligand and protein of a receptor. There are three levels:
|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]
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.
Controls the name of the default param file.
[default = combine_receptors]
Write the merged receptors to the directory specified (the directory must already exist).
Indicate that your receptors are pre-aligned and do not change their alignment on pain of death.
[default = false]
Show that matching status of every receptor pair (whether it is merged or not)
[default = false]