Group Final Project
- Group Formed
- Proposal: https://docs.google.com/document/d/1ENvPHhRbBgtl0ERrfqmomJKxPg68nfvCugrPQrDdM7o/edit?tab=t.0
- Documentation: https://pages.htgaa.org/2026a/ritika-saha/homework/week-05-hw-protein-design-part-ii/index.html
By: 2026a-nourelden-rihan, 2026a-ritika-saha, 2026a-rahul-yaji, 2026a-keerthana-gunaretnam
- We decided to focus on the main area of increasing the stability of the MS2 phage lysis protein L, with a possible secondary goal of reducing the dependency on host DnaJ, while still maintaining the lysis action.
- The tools AlphaFold, Clustal Omega, BLAST, ESM, and ESMFold were discussed.
- BLAST can pull out homologous lysis proteins from the databases.
- Clustal Omega can create MSAs to identify essential L48-S49 residues, and the pore-forming regions that must not be mutated.
- ESM can create mutation heatmaps, which can guide the use of ESMFold to obtain highest score foldings in mutatable regions.
- AlphaFold Multimer predicts whether the subunits of our protein can successfully create a pore in the host membrane, and also to check whether N-terminus can break the interaction with DnaJ.
- We also identified a few pitfalls, with majors ones dealing with limited training datasets, that may not be properly aligned towards creating a transmembrane lysis protein.
- Some other pitfalls include the lack of proper annotations for amurins; the possibility of an over-stable protein to form non-functional aggregates; and the vulnerability of modified protein to host proteases.