RosettaCommons - Small Molecules

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Problem with sugar parameters

Martin Floor — Sat, 07 Oct 2023 17:17:30 +0000

Hi, everyone.

I encountered a weird relax-optimization output in a structure containing sugars. The output structure has hydrogens in close contact (~1.2 Å) from a sugar molecule and a serine residue. In this reported case, I use the -include_sugars flag, but I've observed the same behaviour with custom params generated for glucose in another system, in which I found hydrogens in close contact with a tyrosine. It seems to be an issue of the Hpol atom type, which allows this to happen for a hitherto unidentified reason. The attached relaxed PDB (truncated at the C-terminus to fit the 512kb limit for uploading, which is a bit low for PDB if you ask me) shows the interaction between hydrogens from residue GLC5 (chain B) and SER105 (chain A).

Any clue on this behaviour will be appreciated.

Attachment	Size
hydrogens_kissing.png	444.28 KB
1BAG_relaxed.pdb	511.3 KB

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EMERALD method not working, Rosetta version not available for download

seba — Thu, 04 May 2023 15:14:30 +0000

Hi,

I am trying to reproduce the the results from this paper 'Automatic and accurate ligand structure determination guided by cryo-electron microscopy maps', but when I try to run the script from the paper (de3mo) i'm getting the following error:

File: src/utility/options/OptionCollection.cc:1467
Option matching -in:file:override_database_params not found in command line top-level context

AN INTERNAL ERROR HAS OCCURED. PLEASE SEE THE CONTENTS OF ROSETTA_CRASH.log FOR DETAILS

I have installed the last version of Rosetta available for download - 2022.49 released on March 19, 2023,

In the paper is mentioned that it should work using weekly releases after February 5, 2023 (version 2023.6 or later) but when I tried to download this version i'm getting the folowing error

Not Found

The requested URL /downloads/academic/2023/wk6 was not found on this server.

Apache/2.2.15 (Red Hat) Server at www.rosettacommons.org Port 443

Any help making this work is higly apreciated.

Thank you.

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relax protein with multi-conformer bound ligand

xfradera — Thu, 12 Jan 2023 17:10:08 +0000

I am working with a protein with a bound small molecule (non-covalent). I've managed in creating parameters for the ligand and relaxing the complex following this workflow: https://new.rosettacommons.org/demos/latest/public/relax_around_chemically_bound_ligand/README

Next I'd like to do the same but including some ligand flexibility. I've generated conformers and new parameters, but when I try to relax the complex, the ligand coordinates are wrong. Not sure if there is something that I should do differently.

For context, I'm allowing a limited set of conformational flexibility to my ligand - just sample one small substituent exposed to solvent and generate aprox. 5 conformers. I would like my ligand core to stay in place and sample different conformations for the substituent. Is this possible? Is there an example of a workflow like this?

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Trehalose

jpfuenzalidawx — Thu, 08 Sep 2022 07:49:15 +0000

Hi, I am having trouble minimizing a protein that contains trehalose. Unfortunately, Rosetta does not like trehalose and always deforms it.

I have no problems with glucose, that's weird because trehalose is a glucose disaccharide. I am using the flag -include_sugars and the relaxed structure has unrealistic energies because it forces the formation of non-existing bonds. The main problem is that rosetta assumes it is ->2)-alpha-D-GlucP

Trehalose: C12H22O11 // Iupac: Glc(a1-1a)Glc// Wikipedia: 1-α-Glucopyranosyl-1-α-glucopyranosid

Could you please share some ideas to solve this issue?

thanks in advance

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PDB weird to PDB rosetta friendly

jpfuenzalidawx — Fri, 02 Sep 2022 11:43:38 +0000

Dear all,

I want to relax a protein with a ligand in a specific position using the simple "relax.linuxgccrelease" program. However, I found that if the atom names (third column at the PDB) are not as expected, the output "relaxed" PDB shows a weird ligand (it looks more like an insect than a molecule), regardless if the ligand is already parameterized in Rosetta (Sorbitol [SOR] in this case). Once the atom names are fixed, the relaxed structures make sense.

I managed to transform my original molecule with OpenBabel and to edit the different fields with PyMol scripting, but finding the correct naming of the atoms is not trivial (I have to do it by hand and I need to test hundred of molecules with my protein).

Does someone know a way of doing this automatically? (see my files below)

Regards,

Attachment	Size
rosettacommons_example.txt	6.64 KB

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Ligand Docking with ROSETTA

sc19 — Thu, 14 Jul 2022 08:32:29 +0000

Hi,

I have been trying to perform Ligand Docking with the ROSETTA software. I describe what I have done:

1. First, I have the ligands in sdf/mol2 format one per file. I add hydrogens to these and create the params files with the "molfile_to_params.py" script.

2. Second, I clean the protein (no ligands or cofactors) and add H to the protein.

3. Third, I concatenate the protein with each ligand in a different file for each ligand (the ligand has chain identifier X, the protein A).

4. Fourth, I prepare the "flags" and "xml" file (both attached as .txt files). The start_from point is specified since the ligands are not in the binding pocket.

5. Then, I perform the ligand docking with these files for each ligand with these command: $ROSETTA/source/bin/rosetta_scripts.linuxgccrelease @flags -in:file:s protein_ligand1.pdb -in:file:extra_res_fa params_ligands/ligand1.params -parser:protocol ligand_docking.xml

However, the results I get are with ligands having strange bonds (as attached in picture).

Could you point me out what am I doing wrong?

Thank you

Attachment	Size
flags.txt	367 bytes
It is used with the .xml extension, but changed to txt so it can be uploaded.	2.93 KB
ligand2_conformer1.png	253.06 KB

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Docking

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-ignore_unrecognized_res doesn't work

e3lm — Fri, 06 May 2022 21:47:48 +0000

Hi, I'm minimizing structures in a list of PDB's using the -l option. Some structures have different ligands which I'd like to ignore or skip. The -ignore_unrecognized_res doesn't work. Minimize got bumped out trying to fill in missing atoms. Apparently it did not see or understand the flag.

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Chemically Modified Residues

Weekly releases for commercial users?

rjacak — Tue, 22 Mar 2022 14:48:27 +0000

Hi Steven, Rocco, et al.,

Would it be possible to have the weekly releases for commercial users restarted? The last weekly release available (for commercial users, maybe commercial and academic users?) is Rosetta 2021.16, with a release date of Friday, April 23, 2021. I know there have been bug fixes and other minor improvements made to apps that I am using and it would be great to have access to those. If weekly releases are unlikely to restart anytime soon, would it be possible to have the source code changes of bug fixes merged into main (master) posted somewhere so that licensees can patch the source themselves?

Thanks,
-Ron

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Fragment Generation

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Pose is full atom and mover expects centroid, how do I handle it the best?

hlinn — Thu, 27 Jan 2022 13:55:49 +0000

I'm trying to use pyrosetta.rosetta.protocols.quantum_annealing.ExternalPackerResultLoader for a project of side-chain packing small peptides with a fixed backbone. I've gotten as far as building the Mover: instantiate the mover, giving it rebuild info and the string with selected rotamers.

The problem I run into comes when I try to apply it to the starting pose; I get a warning:

core.io.silent: [ WARNING ] Number of atoms in pose and silent file disagree! Attempting to continue ...
core.io.silent: [ WARNING ]    (in residue ALA:NtermProteinFull at 1 and atm_seqpos of 1  natoms_pose=7  natoms_struct=12  tag="empty")
core.io.silent: [ WARNING ] Likely explanations:
core.io.silent: [ WARNING ] 	1. You are trying to extract, with residue type set A, a silent file created with residue type set B.
core.io.silent: [ WARNING ] 	2. You have specified a database with -database that is out of sync with your chosen executable.
core.io.silent: [ WARNING ] 	3. You have used different environment flags (e.g. -restore_talaris_behavior/-restore_pre_talaris_behavior) than the silent file was generated with.
core.io.silent: [ WARNING ] 	4. The database has been updated since your silent file was made, meaning the definition of this RT has drifted.

I've narrowed it down to explanation 1: the pose is full atom, and the mover, when applied, changes the pose to centroid representation.

The question is now how to best handle it:

1. Change the pose to centroid, apply the mover, then back to full atom to compare. But according to this tutorial: "Converting from full atom to centroid and back will not give you back the same structure, as sidechain building in Rosetta is not deterministic." Would it work anyways in this case?

2. Is there a way of changing the mover's silent file type to full atom? (I tried googling to no avail)

3. I'm comparing the final pose from the external packer with a pose packed by pyrosetta that is full atom. Is it the best idea to change just everything into centroid and score it that way?

Or is there another better way?

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PyRosetta - General

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