https://pages.htgaa.org/2026a/moola-mutondo/homework/week-05-hw-protein-design-part-ii/index.htmlPart 1: Generate Binders with PepMLM Sequence Retrieval MATKAVCVLKGDGPVQGIINFEQKESNGPVKVWGSIKGLTEGLHGFHVHEFGDNTAGCTSAGPHFNPLSRKHGGPKDEERHVGDLGNVTADKDGVADVSIEDSVISLSGDHCIIGRTLVVHEKADDLGKGGNEESTKTGNAGSRLACGVIGIAQ Mutated with A4V MATKVVCVLKGDGPVQGIINFEQKESNGPVKVWGSIKGLTEGLHGFHVHEFGDNTAGCTSAGPHFNPLSRKHGGPKDEERHVGDLGNVTADKDGVADVSIEDSVISLSGDHCIIGRTLVVHEKADDLGKGGNEESTKTGNAGSRLACGVIGIAQ Binder Pseudo Perplexity Seq1 HHVPVVVLRHKX 16.326572 Seq2 WRYYAAVARWKE 13.897447 Seq3 HRYYPAAARWKX 8.531565 Control FLYRWLPSRRGG 20.63523127283615 Part 2: Evaluate Binders with AlphaFold3 Navigate to the AlphaFold Server: alphafoldserver.com For each peptide, submit the mutant SOD1 sequence followed by the peptide sequence as separate chains to model the protein-peptide complex. Record the ipTM score and briefly describe where the peptide appears to bind. Does it localize near the N-terminus where A4V sits? Does it engage the β-barrel region or approach the dimer interface? Does it appear surface-bound or partially buried? In a short paragraph, describe the ipTM values you observe and whether any PepMLM-generated peptide matches or exceeds the known binder. Sequence 1 HHVPVVVLRHKX The sequence was submitted without the last X because it was flagged as an illegal character (it could stand for various amino acids). The peptide appears to be interacting with ipTM = 0.22 pTM = 0.85 pTM = 0.85 suggests the overall fold is very reliable, while ipTM = 0.22 says the predicted interaction/interface between chains is very poor. This means the protein’s global shape looks strong and likely meaningful, this is in line with it being a known and well illucidated human protein. It seems like a case where AlphaFold is confident about folding, but not about binding geometry.Hugoen