https://pages.htgaa.org/2026a/tianyi-terry-luo/homework/week-05-hw-protein-design-part-ii/index.htmlPart A: SOD1 Binder Peptide Design (From Pranam) Part 1: Generate Binders with PepMLM Sequnce: MATKVVCVLKGDGPVQGIINFEQKESNGPVKVWGSIKGLTEGLHGFHVHEFGDNTAGCTSAGPHFNPLSRKHGGPKDEERHVGDLGNVTADKDGVADVSIEDSVISLSGDHCIIGRTLVVHEKADDLGKGGNEESTKTGNAGSRLACGVIGIAQ Binder Pseudo Perplexity WRYYVAAVALWX 16.2395343215211 WHYYAVAAEWKX 13.6945052943038 WLVPAAAAAHGK 7.93406338297721 WRYGPVAVRHWK 14.3797355975152 FLYRWLPSRRGG 20.6352312728361 Part 2: Evaluate Binders with AlphaFold3 “PepMLM outputs X; substituted X→A for AlphaFold input.” Binder ipTM Score WRYYVAAVALWA 0.34 WHYYAVAAEWKA 0.23 WLVPAAAAAHGK 0.48 WRYGPVAVRHWK 0.36 FLYRWLPSRRGG 0.38 Across the five AlphaFold3 complex predictions, ipTM values ranged from 0.23 to 0.48. The known binder FLYRWLPSRRGG gave ipTM = 0.38 and appeared weakly defined, remaining largely surface-adjacent/partially detached rather than buried in a clear pocket, with no obvious localization near the N-terminus where A4V sits. Three PepMLM peptides (WHYYAVAAEWKA, 0.23; WRYYVAAVALWA, 0.34; WRYGPVAVRHWK, 0.36) similarly showed low-confidence interfaces, tending to lie loosely on the β-barrel exterior instead of concentrating at the A4V region. In contrast, WLVPAAAAAHGK produced the strongest prediction (ipTM = 0.48) and appeared more plausibly docked along a β-barrel/loop-adjacent surface, making it the only PepMLM-generated peptide that exceeded the known binder’s ipTM in this set. Part 3: Evaluate Properties of Generated Peptides in the PeptiVerseHugoen