sokrypton / sokrypton/ColabFold

Aberrant 3D modeling of a multiprotein complex leads to the formation of a covalent interprotein bond Arginine - Leucine

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Description

I attempted to model a missense mutation in the NUF2 peptide located in the NDC80 protein complex. The substitution of a leucine at position 303 by an arginine in the NUF2 peptide leads to a covalent interprotein bond with the leucine opposite on the NDC80 protein at position 463. This interaction would therefore reinforce the quaternary structure of this complex.
Unless I am mistaken, this type of interaction cannot take place and I expected rather a destructuring of the region.

On the attached figure showing the modeling leading to the covalent bond between NUF2 and NDC80, NUF2 appears in green and NDC80 in yellow.

Could you explain to me where this issue comes from? Are there any parameters to change?

AlphaFold2.ipynb
{
"num_queries": 1,
"use_templates": false,
"use_amber": false,
"msa_mode": "MMseqs2 (UniRef+Environmental)",
"model_type": "AlphaFold2-multimer-v2",
"num_models": 5,
"num_recycles": 3,
"model_order": [
1,
2,
3,
4,
5
],
"keep_existing_results": false,
"rank_by": "multimer",
NDC80CPLXL303R_9AC43_UNRELAXED_RANK_1_MODEL_1 PDB (2)
"pair_mode": "unpaired+paired",
"host_url": "https://api.colabfold.com",
"stop_at_score": 100.0,
"recompile_padding": 1.0,
"recompile_all_models": false,
"commit": "1f2d963e7705b0d8c847980e4b1c44243127febb",
"version": "1.2.0"
}

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First steps

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  3. Fork the repository and make your change on a branch.
  4. Open a pull request that references the issue number.

Research direction

Start with the attached AlphaFold2.ipynb configuration and the reported NUF2 L303R/NDC80 L463 model image. Examine the AlphaFold2-multimer-v2 run and its reported covalent interprotein bond; done means determining whether the result is a modeling artifact and whether the listed parameters can account for it.

Written by the indexing model from the issue text.

Assessment

Tech stack
jupyter-notebook
Domain
bioinformatics
Issue type
Bug
Difficulty
5/5
Estimated time
Over a week
Activity status
Stale
Clarity
Needs clarification
Newbie friendliness
20/100

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