Homework — Protein Design Part II

Warning

Mandatory for MIT/Harvard students and Committed Listeners. Due Tue, Mar 11 (before lecture).

Part A — PepMLM peptide design (From Pranam)

Info

Optional for MIT/Harvard; mandatory for Committed Listeners. Due Tue, Mar 11 (start of class).

Create a Hugging Face account → we’ll use PepMLM‑650M: model page.
1. Generate a token: Settings → Tokens (create new).
2. Ensure repo is ChatterjeeLab/PepMLM-650M.
3. Open the PepMLM Colab and make a copy: Colab (linked from the model page).
4. In Colab, choose T4 GPU, run all blocks.
5. When prompted “Input HF token”, paste your token. When asked “Add token as git credential?”, choose No.
Get the amino‑acid sequence for SOD1 on UniProt (ID: P00441). Make the A4V mutation.
Run PepMLM inference and generate 4 peptides (length 12 aa). (2 is acceptable if time‑limited.)
Add a known SOD1‑binding peptide to your list: FLYRWLPSRRGG (see Genes & Development reference).
genesdev.cshlp.org
Use AlphaFold‑Multimer (ColabFold notebook) to model the SOD1:peptide complex.
Open notebook: AlphaFold‑Multimer
- Set model_type = alphafold2_multimer_v3 — shown to recapitulate peptide‑protein binding accurately.
  Ref: Frontiers in Bioinformatics (2022)
After running AF‑Multimer with your 5 peptides (4 generated + 1 known), plot the ipTM scores to compare relative binding confidence.
Write a 1‑paragraph summary of your results.

Info

Mandatory for MIT/Harvard and Committed Listeners. Due Wed, Mar 12 (start of class).

This is computationally heavy — start early.
More details: Final Project Page (external Notion): www.notion.so