Loop modeling with ligand in the receptor

[Anonymous]

I have docked ligand in a receptor and now I want to perform a loop modeling. I tried using these flags:
-in::file::extra_res_fa aral.params
-loops::extra_res_fa aral.params
… but rosetta returns; ERROR: Option matching -in:extra_res_fa not found in command line top-level
Without these flags Rosetta returns:
ERROR: unrecognized aa ARE
(ARE is my ligand).

So, how do I get loopmodel to recognize my ligand?

Thanks,
Christoffer

[Anonymous]

Try it as in:file:extra_res_fa (single colons instead of double colons). The error indicates the “file” part disappeared for some reason. Also try it with no prefixes (just extra_res_fa).

[Anonymous]

Thanks, that helped somewhat. But there is still some troubles.

protocols.looprelax: ==== Loop protocol: =================================================
protocols.looprelax: remodel perturb_kic
protocols.looprelax: intermedrelax no
protocols.looprelax: refine refine_kic
protocols.looprelax: relax fastrelax
core.chemical: can not find a residue type that matches the residue AREat position 296

ERROR: switch_to_residue_type_set fails

ERROR:: Exit from: src/core/chemical/util.cc line: 573

[Anonymous]

The perturbation step of loop modeling occurs in centroid mode – a reduced sidechain representation. Reading between the lines a bit, this error almost certainly means there’s no valid centroid representation of your ligand (since you didn’t create one), so when the perturbation step tries to run it can’t make a centroid version of your protein and it crashes.

Here’s two things to try:
A) skip the perturbation step (“-remodel no” or something similar). This may reduce the sampling the protocol does, although I think with KIC it’s not really an issue.
Try adding your ligand to the centroid residue type set. Look for a flag called -extra_res_cen and pass it your ligand file. (Try passing it the fullatom ligand parameter file you already have and cross your fingers. If that doesn’t work, you’ll have to make a centroid parameter file, I have no idea how to do that.)

[Anonymous]

With -extra_res_cen it gives me the error below. I get the same if I use -remodel no.

protocols.looprelax: ==== Loop protocol: =================================================
protocols.looprelax: remodel perturb_kic
protocols.looprelax: intermedrelax no
protocols.looprelax: refine refine_kic
protocols.looprelax: relax fastrelax

ERROR: unrecognized atom_type_name aroC
ERROR:: Exit from: src/core/chemical/AtomTypeSet.hh line: 76

[Anonymous]

I assume you’re familiar with The Matrix.

The Blue Pill: option A above, skip the centroid perturbation step. -remodel no wasn’t input quite right somehow, because it still says “remodel perturb_kic”. Can you post the options file you tried?

The Red Pill: look at the files (rosetta_database)/chemical/atom_type_sets/fa_standard/atom_properties.txt, chemical/atom_type_sets/centroid/atom_properties.txt, and your params file. You’ll notice your params file has atom types listed in the fa_standard atom types, NOT listed in the centroid atom types. Try modifying either centroid/atom_properties to include your ligand’s atom types (copy them from the fa_standard atom types), or modifying a copy of your ligand paramter file to use only the centroid atom types (sort of limited). This can be made to work eventually but it’s going to be a fair amount of trial and error.

(It may also be informative to compare some of the centroid and fa_standard residue types; sub in residue_type_sets for atom_type_sets).

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