sokrypton / sokrypton/ColabFold

Predicted structure is way different from the RSCB PDB structure.

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Description

Hi, First of all, thank you for such amazing open source efforts. Also, I am very, very new to this domain, just started learning about protein structure prediction and folding.

While doing experiments with I used this random example of insulin complex [pdb_00008ez0] and I downloaded it's fasta sequence:

>8EZ0_1|Chains A, B|Insulin receptor|Mus musculus (10090)
HLYPGEVCPGMDIRNNLTRLHELENCSVIEGHLQILLMFKTRPEDFRDLSFPKLIMITDYLLLFRVYGLESLKDLFPNLTVIRGSRLFFNYALVIFEMVHLKELGLYNLMNITRGSVRIEKNNELCYLATIDWSRILDSVEDNYIVLNKDDNEECGDVCPGTAKGKTNCPATVINGQFVERCWTHSHCQKVCPTICKSHGCTAEGLCCHKECLGNCSEPDDPTKCVACRNFYLDGQCVETCPPPYYHFQDWRCVNFSFCQDLHFKCRNSRKPGCHQYVIHNNKCIPECPSGYTMNSSNLMCTPCLGPCPKVCQILEGEKTIDSVTSAQELRGCTVINGSLIINIRGGNNLAAELEANLGLIEEISGFLKIRRSYALVSLSFFRKLHLIRGETLEIGNYSFYALDNQNLRQLWDWSKHNLTITQGKLFFHYNPKLCLSEIHKMEEVSGTKGRQERNDIALKTNGDQASCENELLKFSFIRTSFDKILLRWEPYWPPDFRDLLGFMLFYKEAPYQNVTEFDGQDACGSNSWTVVDIDPPQRSNDPKSQTPSHPGWLMRGLKPWTQYAIFVKTLVTFSDERRTYGAKSDIIYVQTDATNPSVPLDPISVSNSSSQIILKWKPPSDPNGNITHYLVYWERQAEDSELFELDYCLKGLKLPSRTWSPPFESDDSQKHNQSEYDDSASESSSSPKTDSQILKELEESSFRKTFEDYLHNVVFVPRPSRKRRSLEEVGNVTATTLTLPDFPNVSSTIVPTSQEEHRPFEKVVNKESLVISGLRHFTGYRIELQACNQDSPDERCSVAAYVSARTMPEAKADDIVGPVTHEIFENNVVHLMWQEPKEPNGLIVLYEVSYRRYGDEELHLCVSRKHFALERGCRLRGLSPGNYSVRVRATSLAGNGSWTEPTYFYVTDYLDVPSNIAKIIIGPLIFVFLFSVVIGSIYLFLRKRQPDGPMGPLYASSNPEYLSASDVFPSSVYVPDEWEVPREKITLLRELGQGSFGMVYEGNAKDIIKGEAETRVAVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLLGVVSKGQPTLVVMELMAHGDLKSHLRSLRPDAENNPGRPPPTLQEMIQMTAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMSPESLKDGVFTASSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYLDPPDNCPERLTDLMRMCWQFNPKMRPTFLEIVNLLKDDLHPSFPEVSFFYSEENKAPESEELEMEFEDMENVPLDRSSHCQREEAGGREGGSSLSIKRTYDEHIPYTHMNGGKKNGRVLTLPRSNPS
>8EZ0_2|Chains C[auth D], D[auth E], E[auth F], F[auth G]|Insulin|Homo sapiens (9606)
MALWMRLLPLLALLALWGPDPAAAFVNQHLCGSHLVEALYLVCGERGFFYTPKTRREAEDLQVGQVELGGGPGAGSLQPLALEGSLQKRGIVEQCCTSICSLYQLENYCN

And I ran this command:

colabfold_batch --templates --amber insulin_sample.fasta results/

Everything ran successfully, I got a descent pLDDT score of 77.1, and I downloaded this PDB:

8EZ0_2_Chains_C_auth_D___D_auth_E___E_auth_F___F_auth_G__Insulin_Homo_sapiens__9606__relaxed_rank_001_alphafold2_ptm_model_1_seed_000.pdb

which to my knowledge is the most stable predicted structure. However when I visualize the PDB, I get something like this

Image

Green one is the visualization of the generated structure and the complex structure in the back is the actual from RSCB PDB.

My question is:

  1. What am I doing wrong here? Am I interpreting things differently?
  2. Did my input fasta is wrong, should I have used : for multimers?
  3. Anything else I have to be aware of in general when I am doing prediction of complex molecules or multimers?

Because the same thing happened in the case of hemoglobin complex as well.

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Research direction

Reproduce the issue with the supplied insulin_sample.fasta and colabfold_batch --templates --amber insulin_sample.fasta results/. Compare the generated 8EZ0_2...pdb with RCSB structure 8EZ0, then determine whether the sequence format or multimer syntax explains the difference. Done means documenting the cause and the correct input or interpretation guidance.

Written by the indexing model from the issue text.

Assessment

Tech stack
jupyter-notebook
Domain
bioinformatics, machine-learning
Issue type
Bug
Difficulty
4/5
Estimated time
3-5 days
Activity status
Stale
Clarity
Mostly clear
Newbie friendliness
30/100

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