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Journal:Proteins:3

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Revision as of 11:07, 6 May 2023 by Joel L. Sussman (Talk | contribs)
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Do Newly Born orphan proteins resemble Never Born proteins? A study using three deep learning algorithms

Newly Born proteins, or orphan proteins, have no sequence homology to other proteins and occur in single species or within a taxonomically restricted gene family

Never Born proteins are random polypeptides with amino acid content similar to that of native proteins.

Can recently developed AI/Deep Learning tools for predicting 3D protein structures like:

  • AlphaFold2 (AF2)
  • RoseTTAFold (RTF)
  • Evolutionary Scale Modeling (ESM-2)

be useful to see if Newly Born proteins are similar to Never Born proteins? AF2 and RTF predict, by default, five top models, while ESM-2 predicts only one model. Morphing between the top models of AF2 and those of RTF give a visual feeling of how similar these 5 models are for each method.

Sequences of the Never Born proteins by Tretyachenko et al.[1] showed that some folded into compact structures, e.g., as seen for Sequences #1856 and #6387.

RTF-1856 ESM-1856 AF2-1856
RTF-6387 ESM-6387 AF2-6387

Other never born proteins experimentally appear to belong to the category of intrinsically disordered proteins (IDPs)[2], e.g., as seen for Sequence #3703.

RTF-3703 ESM-3703 AF2-3703
Image:ESM 35.jpg.jpg

References

  1. Tretyachenko V, Vymětal J, Bednárová L, Kopecký V Jr, Hofbauerová K, Jindrová H, Hubálek M, Souček R, Konvalinka J, Vondrášek J, Hlouchová K. Random protein sequences can form defined secondary structures and are well-tolerated in vivo. Sci Rep. 2017 Nov 13;7(1):15449. PMID:29133927 doi:10.1038/s41598-017-15635-8
  2. Dunker AK, Silman I, Uversky VN, Sussman JL. Function and structure of inherently disordered proteins. Curr Opin Struct Biol. 2008 Dec;18(6):756-64. Epub 2008 Nov 17. PMID:18952168 doi:10.1016/j.sbi.2008.10.002


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