Week 5 HW: Protein design part 2

  • Design short peptides that bind mutant SOD1.
  • Then decide which ones are worth advancing toward therapy.

Uniprot SOD1 protein sequence:

sp|P00441|SODC_HUMAN Superoxide dismutase [Cu-Zn] OS=Homo sapiens OX=9606 GN=SOD1 PE=1 SV=2 MATKAVCVLKGDGPVQGIINFEQKESNGPVKVWGSIKGLTEGLHGFHVHEFGDNTAGCTS AGPHFNPLSRKHGGPKDEERHVGDLGNVTADKDGVADVSIEDSVISLSGDHCIIGRTLVV HEKADDLGKGGNEESTKTGNAGSRLACGVIGIAQ

Apply A4V mutation: (ignoring Methionine) The Bolded V used to be A MATKVVCVLKGDGPVQGIINFEQKESNGPVKVWGSIKGLTEGLHGFHVHEFGDNTAGCTS AGPHFNPLSRKHGGPKDEERHVGDLGNVTADKDGVADVSIEDSVISLSGDHCIIGRTLVV HEKADDLGKGGNEESTKTGNAGSRLACGVIGIAQ

Pepmlm

Generated peptides and their perplexity score:

  • KRYPAAGIELKE - 17
  • WSYPPTAAEHWK - 15
  • WSYPWAAAKHAX - 12
  • WHYYWYAARRKX - 11
  • FLYRWLPSRRGG - 20

Perplexity is how well a probability model predicts a sample. Perplexity can be unbounded, but the closer to 1 the more well the language model predicts a sample. our scores are quite close pepmlm peptides pepmlm peptides

Alphafold

For the FLYRWLPSRRGG peptide: iPTM score - 0.36