Week 5: Protein Design Part II

Week 5 cover Week 5 cover

Context
This week extends protein design with a peptide-binder workflow. You’ll generate short peptides with PepMLM, then model peptide–protein complexes with AlphaFold-Multimer and interpret ipTM scores. :contentReference[oaicite:0]{index=0}

Protein cartoon Protein cartoon

Goals

  • Use PepMLM to propose peptide binders for a chosen target (here: SOD1). :contentReference[oaicite:1]{index=1}
  • Predict peptide–target complexes with AlphaFold-Multimer and compare ipTM. :contentReference[oaicite:2]{index=2}
  • Summarize results and pick candidates for follow-up.

Part A — PepMLM → AlphaFold-Multimer (protein–peptide)

Warning

Read this whole assignment before starting. You’ll need a Hugging Face token and a GPU runtime for Colab. :contentReference[oaicite:3]{index=3}

Step 1 — Set up PepMLM (Hugging Face)

Step 2 — Prepare the target sequence (SOD1)

Step 3 — Generate candidate peptides

  • Run the PepMLM Colab and generate 4 peptides of length 12 for the mutated SOD1.
  • Add this known SOD1-binding peptide to your set: FLYRWLPSRRGG (from the literature). :contentReference[oaicite:6]{index=6}

Step 4 — Structure modeling with AlphaFold-Multimer

Step 5 — Compare and interpret

  • Plot ipTM for all candidates (higher ≈ more confident interface) and note interface details (contacts, pose variety).
  • Short write-up: 1 paragraph on which peptide(s) you’d pursue and why (ipTM, pose, chemistry). :contentReference[oaicite:9]{index=9}
Tip

Minimal report for Part A

  • Table of peptides (PepMLM 3–4 + literature peptide), the edited SOD1 sequence (A4V), and ipTM per complex.
  • 2–3 annotated screenshots from your top model(s).
  • One-paragraph conclusion + next steps (e.g., mutate peptide residues; re-score with more seeds).

Part B — Final Project (L-Protein mutants)

This is a compute-heavier follow-up for your final project—start early and keep logs of settings, seeds, and runtimes. (Details per course brief.) :contentReference[oaicite:10]{index=10}

Submission checklist

  • SOD1 A4V sequence (source + edit noted). :contentReference[oaicite:11]{index=11}
  • List of peptides (PepMLM outputs + FLYRWLPSRRGG reference). :contentReference[oaicite:12]{index=12}
  • ipTM plot across candidates; top models’ screenshots. :contentReference[oaicite:13]{index=13}
  • 1-paragraph summary of findings & next steps.

References / Tools