Lecture (03/04)

<aside> <img src="/icons/slide_green.svg" alt="/icons/slide_green.svg" width="40px" /> Lecture slides will be shared here after the class!

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<aside> <img src="/icons/video-camera_yellow.svg" alt="/icons/video-camera_yellow.svg" width="40px" /> Lecture recording

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Recitation (03/05)

<aside> <img src="/icons/slide_green.svg" alt="/icons/slide_green.svg" width="40px" /> Recitation slides Part 1:

MS2-Phage_homeworkdiscussion (1).pptx

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<aside> <img src="/icons/video-camera_yellow.svg" alt="/icons/video-camera_yellow.svg" width="40px" /> Recitation recording

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Homework

<aside> ⚠️ Please read through the full assignment before you get started. This assignment is mandatory for MIT/Harvard students and Committed Listeners. Due March 11 before lecture

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<aside> <img src="/icons/push-pin_green.svg" alt="/icons/push-pin_green.svg" width="40px" /> Key Links: http://docs.google.com/spreadsheets/d/1AsYRLlrRLd6I8abxNHfuz1OtFTSqYZ87_kefBMsxhMo/edit?gid=0#gid=0

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Part A (From Pranam)

<aside> ⚠️ Optional for MIT/Harvard Students, mandatory for Committed Listeners. Due at the start of class March 11

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1. Sign up for HuggingFace (we will be using PepMLM: https://huggingface.co/ChatterjeeLab/PepMLM-650M)
   1. Once you login, go to the page (https://huggingface.co/settings/tokens). Click +Create new token.
   2. Make sure you type the full name ChatterjeeLab/PepMLM-650M when searching for repos. Click save token and you will see the newly token (copy that).
   3. Go to the page (https://huggingface.co/ChatterjeeLab/PepMLM-650M) and find their Colab Notebook (link).
   4. Make a copy to your Google Drive, choose T4 GPU and run each block.
   5. When running into the block Input HF token , a pop-up will show Enter your token (input will not be visible):. Paste your token and Add token as git credential? (Y/n) choose n.
2. Find the amino acid sequence for SOD1 in UniProt (ID: P00441), a protein when mutated, can cause Amyotrophic lateral sclerosis (ALS). In fact, the A4V (when you change position 4 from Alanine to Valine) causes the most aggressive form of ALS, so make that change in the sequence
3. Enter your mutated SOD1 sequence into the PepMLM inference API and generate 4 peptides of length 12 amino acids (Step 5 takes a while so you can also just pick 1 or 2 peptides)
4. To your list, add this known SOD1-binding peptide to your list: FLYRWLPSRRGG [from -https://genesdev.cshlp.org/content/22/11/1451]
5. Go to AlphaFold-Multimer (https://colab.research.google.com/github/sokrypton/ColabFold/blob/main/AlphaFold2.ipynb). This is similar to what you did for homework last week but instead for a protein-peptide complex
   1. Set model_type: alphafold2_multimer_v3 (this model has been shown to recapitulate peptide-protein binding accurately: https://www.frontiersin.org/articles/10.3389/fbinf.2022.959160/full). * Add your query sequence - Its the SOD1Sequence:PeptideSequence.
6. After running AlphaFold-Multimer with your 5 peptides alongside your mutated SOD1 sequence, plot the ipTM scores, which measures the relative confidence of the binding region.
7. Provide a 1 paragraph write-up of your results

Part B (Final Project: L-Protein Mutants)

<aside> ⚠️ Mandatory for MIT/Harvard Students and Committed Listeners. Due at the start of class March 12

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<aside> <img src="/icons/exclamation-mark_red.svg" alt="/icons/exclamation-mark_red.svg" width="40px" /> This homework requires computation that might take you a while to run. So please get started early.

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<aside> <img src="/icons/push-pin_green.svg" alt="/icons/push-pin_green.svg" width="40px" /> Key Links: You can read more about the final project in the Final Project Page.

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