POSIT provides a simple program for automatically generating receptors from a protein and a ligand. It can generate receptors by providing the ligand and protein pre-split or by providing the full complex and specifying the residues of the bound ligand.
All receptors created by make_pose_receptor are accepted by any of the OEDocking suite of docking tools.
If a crystallographic 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.
When using the -auto flag, If the complex has multiple bound ligands, multiple receptors will be generated for each bound ligand (even if they are copies of the same ligand).
A description of the command line interface can be obtained by executing make_pose_receptor with the --help option.
> make_pose_receptor --help
will generate the following output:
Help functions: make_pose_receptor --help simple : Get a list of simple parameters make_pose_receptor --help all : Get a complete list of parameters make_pose_receptor --help <parameter> : Get detailed help on a parameter make_pose_receptor --help html : Create an html help file for this program
The output receptor file. Note that all receptors must be stored in OEB formats so any extension given will be forced to be OEB.
If -ligand is given, a receptor will be generated with the supplied ligand. As a sanity check, if the ligand overlaps the protein, the receptor will fail with a warning and list the clashing residues.
Either -ligand or -residue are required to create a complex. If neither are supplied, then make_pose_receptor will attempt to find a bound ligand and print out the -residue string for the suggested ligand.
If residues are supplied, the matching residues will be used as the ligand portion of the molecule. Residues are supplied as comma separated list of ligand residues.
The easiest way to find what to enter for the -residue flag is to simply run make_pose_receptor with only a -prot flag.
Automatically extract receptors using all non-covalent ligands.
> make_pose_receptor -prot 1Y6A.pdb.gz Found ligands: 1. CCS(=O)(=O)c1ccc(c(c1)Nc2ncc(o2)c3cccc(c3)c4ccccn4)OC To extract ligand, add command line switch: -residue AAZA201A or -residue 1
Note that, as a convenience, you can simply select the ligand by number as well.
Residues may be comma separated, for example AAZA201A,AAZA201B to indicate that the ligand is actually two residues.
[default = false]
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 (>= 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]
Controls the name of the default param file.
[default = make_pose_receptor]
The example commands in this section can be run with files found in the example/posit/184.108.40.206 directory under the top-level installation directory.
To use these examples, enter the renin directory
> make_pose_receptor -prot renin/2IKO.pdb.gz
You will see the following output (Banner omitted)
Found ligands: 1. CCc1c(c(nc(n1)N)N)c2ccc(cc2)NCc3cc(cc(c3)F)F To extract ligand, add command line switch: -residue 7IG601A or -residue 1
What make_receptor is indicating is its best guess at which portion of the molecule is the ligand. Simply copy this command line switch to your command:
> make_pose_receptor -prot renin/2IKO.pdb.gz -out 2IKO.rec.oeb.gz \ -residue 7IG601A
> make_pose_receptor -prot 2IKO.pdb.gz -out 2IKO.rec.oeb.gz -residue 1
And the indicated residues will be used to separate the ligand from the protein.
When the following command line is executed, notice that the ligand is detected as clashing with the protein:
> make_pose_receptor -prot renin/2IKU.pdb.gz -out renin/receptors/2IKU_a.rec.oeb.gz \ -residue LIY336A -allowedClashes noclashes
Protein (RENINLIY336A): Writing to receptor receptors/2IKU_a.rec.oeb.gz Adding LIY336B CCc1c(c(nc(n1)N)N)c2ccc3c(c2)N(C(CC3)c4ccccc4)CCCOC as an extra molecule Warning: Receptor ligand LIY336A clashes with the proteins To force output please use command line switch -allowedClashes mildclashes Note that POSIT should most likely be run with the same switch. Warning: No receptors written.
make_pose_receptor gives the appropriate command line in order to create the receptor, again it is advisable to visually inspect the complex and the original electron density if available.
In this case the following command will generate the desired receptor (note that mild clashes is the default allowable clash level).
> make_pose_receptor -prot renin/2IKU.pdb.gz -out renin/receptors/2IKU_a.rec.oeb.gz \ -residue LIY336A -allowedClashes mildclashes
In a pinch, simply use the -auto option to make receptors from all non-covalent, structures that aren’t metals, waters or ions in the supplied protein. Each output receptor filename will be annotate with the residue number. For example:
> make_pose_receptor –prot renin/2IKO.pdb.gz -auto
Here, the residue information 7IG601A has been appended to the output filename.