RosettaCommons / RosettaCommons/PyRosetta.notebooks

Declare_chemical_bond between 2 SG atoms on the sidechain of 2 Cys residues

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Jupyter Notebook
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Description

I want to cyclize my 14-mer peptide in the complex with another protein. I received the complex from AlphaFold-2 multimer model, and the peptide was linear there. I want to form a disulfide bond between 2 SG atoms on these 2 Cys at 2 ends of the peptide to cyclize that peptide before local docking using Rosetta. However, I faced this error:

File: /home/benchmark/rosetta/source/src/core/conformation/Conformation.cc:1756
[ ERROR ] UtilityExitException
ERROR: CYS:NtermProteinFull doesnt have connection at SG

The script I used to declare bond is here:

from pyrosetta import *
init()

pose = pose_from_pdb("/rosetta/Son/project/znrf3/inputs/global_dock/30_2.pdb")
SG_B1_resID = pose.pdb_info().pdb2pose('B', 1)
SG_B14_resID = pose.pdb_info().pdb2pose('B', 14)
pose.conformation().declare_chemical_bond(SG_B1_resID, "SG" , SG_B14_resID, "SG")

I tried to change SG into C and N, it worked. So I was stuck here. I tried to cyclize it with simple_cycpep_predict of Rosetta and it worked but the conformation changed, which is the thing I don't want.

What should I do to solve this problem? Thank you

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First steps

  1. Read the whole issue, then the project's contributing guide.
  2. Comment on the issue to say you are picking it up — it saves two people doing the same work.
  3. Fork the repository and make your change on a branch.
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Research direction

Start with the provided PyRosetta script and the connection error at src/core/conformation/Conformation.cc:1756, then compare the SG bond declaration with the successful C/N experiment and the simple_cycpep_predict approach. Done means identifying a supported way to declare the disulfide bond between the two Cys SG atoms while preserving the peptide conformation.

Written by the indexing model from the issue text.

Assessment

Tech stack
jupyter-notebook, python
Domain
bioinformatics
Issue type
Bug
Difficulty
4/5
Estimated time
3-5 days
Activity status
Stale
Clarity
Needs clarification
Newbie friendliness
25/100

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