G-protein Design-around Walkthrough
How the live workstream maps to Yongkun's request, what is already complete, and how the team should collaborate on the next rounds.
This module is a second-generation design-around workstream for the VSV-G / Cocal-G 354 overlap matter. It turns an IP-risk question into staged technical evidence: recall candidates, compare sequence and mapped positions, hand off to structure prediction, then feed wet-lab and IP review.
The green/amber/red labels are technical triage signals, not legal FTO conclusions. Any design-around claim still needs a claim-chart review.
| Step | Yongkun request | Current implementation | Status |
|---|---|---|---|
| 1 | Retrieve viral glycoproteins from UniProt, select VSV-G similarity <85%, rank by similarity. | UniProt query mode, FASTA import, VSV-G/Cocal-G identity, 47/354 mapping, risk band, CSV/JSON export. | Done |
| 2 | Predict structures with AlphaFold, compare with VSV-G, then send qualified candidates to packaging tests. | Structure comparison is live: top candidates + Cocal-G are folded (Boltz), TM-scored against the VSV-G crystal (PDB 5OY9 chain A) and Cocal-G, and the VSV-G-weighted structural similarity drives the ranking. VSV-G is weighted higher (it has a crystal; Cocal-G's reference is predicted). | Done |
| 3 | Predict key ligand-binding sites for wet-lab-selected candidates and mutate them while preserving structure. | Planned after wet-lab packaging hits exist; not run before hit selection. | Planned |
| 4 | Use mutants for in-vivo lentivirus testing in the second wet-lab round. | Planned collaboration layer with wet-lab readout ingest and IP/FTO package export. | Planned |
1. Open the module and choose FASTA upload or UniProt query.
2. Optionally upload VSV-G / Cocal-G references for reproducibility.
3. Run the assessment and wait for polling to finish.
4. Download CSV, JSON, and manifest for review.
assessments.csv
Spreadsheet review table
assessments.json
Machine-readable full result
manifest.json
Inputs, references, query, and counts
| Round | Action | Output |
|---|---|---|
| R0 | Run smoke query | Baseline candidate list |
| R1 | Add curated literature FASTA | Higher-quality sequence pool |
| R2 | Run AlphaFold/Boltz batch | Predicted structures |
| R3 | Compare structures to VSV-G | Structure-supported shortlist |
| R4 | Packaging/titer screen | Wet-lab fitness data |
| R5 | Binding-site annotation | Mutation target map |
| R6 | Conservative mutation design | Stable mutant candidates |
| R7 | In-vivo lentivirus test | Final technical evidence |
Domain-coverage field
Add domain-coverage / confidence alongside the live TM-score & RMSD.
Wet-lab ingest
Attach packaging/titer results to candidate ranking.
Ligand-site mutation
Design conservative mutations after wet-lab hit selection.