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Part A (From Pranam)
- Sign up for HuggingFace (we will be using PepMLM: https://huggingface.co/ChatterjeeLab/PepMLM-650M)
- 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
Sequence for SOD1 A4V:
MATKVVCVLKGDGPVQGIINFEQKESNGPVKVWGSIKGLTEGLHGFHVHEFGDNTAGCTSAGPHFNPLSRKHGGPKDEERHVGDLGNVTADKDGVADVSIEDSVISLSGDHCIIGRTLVVHEKADDLGKGGNEESTKTGNAGSRLACGVIGIAQ
- 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)
| Binder |
Pseudo Perplexity |
| WRYPAAAAAHKE |
6.9570456 |
| WRVPAAAARWKX |
8.47874258 |
| WHYGPTAVEHKX |
11.9239867 |
| WRYGAAGAAWKK |
7.52798743 |
-
To your list, add this known SOD1-binding peptide to your list: FLYRWLPSRRGG [from -https://genesdev.csh
| Peptide 1 |
WRYPAAAAAHKE |
| Peptide 2 |
WRVPAAAARWKX |
| Peptide 3 |
WHYGPTAVEHKX |
| Peptide 4 |
WRYGAAGAAWKK |
| Peptide 5 |
FLYRWLPSRRGG |
-
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
- 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.
Peptide 1: WRYPAAAAAHKE
Predictions:
3D structure
Plots:
