Hi,
I have a crystal structure of rhodopsin that I would like to score, but there is a retinal molecule covalently linked to a Lys residue in that structure. How do I get PyRosetta to read in the pdb file with the retinal correctly?
How does the scoring function treat such modifications?
Thank you!
Tobias
Post Situation:
There's several ways to treat this situation.
First you can treat it as a regular lysine which has a retinal modification to it. This would entail writing a "patch" file for lysine which adds on the atoms and properties for the retinal portion. Much of this work would be done by hand.
The second option is to treat the lysine+retinal as a single non-canonical amino acid. This would involve creating a non-canonical amino acid params file. There's demos which cover this, as well as previous discussions on the forums.
The third way is to treat the lysine and retinal as separate residues, and then use the enzdes/matcher constraint system (https://www.rosettacommons.org/manuals/archive/rosetta3.5_user_guide/d5/...) to enforce a particular covalent geometry between the retinal and the lysine you're interested in. If you put "1" as the "periodicity" of your constraint file, you enforce a covalent restraint between the residue and the ligand.
Which way would work best for you probably depends on what you're trying to accomplish with your modeling job, and how critical the behavior and the geometry of the modified lysine is.
Regarding scoring, it depends on what technique you use, and what part of scoring you're interested in. The atomistic portions of scoring don't care how the residue is composed, so things like LJ and hydrogen bonding aren't much affected. For the patch and enzdes paths, the backbone energy terms are inherited from the parent residue. For the non-canonical route, when you build your params file you can specify how to treat backbone energies. For the internal geometries, you specify a somewhat fixed geometry of the retinal in the patch file, you regenerate the combined lysine-retinal rotamers externally for the non-canonical amino acid route, and you use the existing lysine rotamers combined with supplied retinal rotamers along with the geometric restraints for the geometry of their interaction. (Internal geometries in Rosetta being not so much a scoring consideration but a sampling one.)