Week 4: Protein Design Part I

Week 4 hero Week 4 hero

Context
Week 4 focuses on in-silico exploration of proteins and introductory design workflows (no wet lab this week).

Goals for this week

  • Pick a protein of interest (from PDB or literature) and explore its structure.
  • Practice core visualization & analysis tasks (secondary structure, residue types, surfaces).
  • Try a structure prediction or mutational design thought-experiment to see how sequence ↔ structure relates.
  • Capture clear screenshots and short notes you can reuse in Week 5.

Part A — Explore a real structure (PDB)

Use one of these web viewers to open your protein (search by PDB ID or UniProt):

  • RCSB PDB 3D View (Mol*) — interactive rendering, color by secondary structure/residue type, measure distances.
    https://www.rcsb.org/3d-view/
  • iCn3D (NCBI) — web viewer with synced sequence/structure and quick analysis panels (hydrophobicity, H-bonds, pockets).
    https://github.com/ncbi/icn3d

Try these views/tasks

  1. Representations: cartoon / ribbon / ball-and-stick.
  2. Coloring: by secondary structure (helices vs sheets) and by residue type (hydrophobic/hydrophilic).
  3. Sites: identify ligands or pockets; note any catalytic residues or binding motifs.
  4. Screenshots: save at least 3 views (overall fold, active/binding site, colored by residue properties).
Tip

Pro tip: Mol* and iCn3D can export high-res images and shareable states. Keep a consistent background and label key residues for clarity.

Part B — Predict or compare a structure (quick)

If your protein lacks an experimental structure or you want to test variants:

Deliverable ideas

  • Compare the predicted model to a known template (if any): RMSD impression, domain arrangement, confidence (pLDDT/PAE).
  • If you mutate 1–3 residues (e.g., core → larger hydrophobe; surface → polar), what changes do you observe in predicted packing?
Warning

Predictions can be confident but wrong—treat them as hypotheses to guide thinking, not as proof.

Optional — Local tools

Use these if you want more control than web viewers provide.

What to deliver (minimum)

  1. Protein choice (name, organism, PDB or UniProt reference).
  2. 3 screenshots showing:
    • cartoon/ribbon overview;
    • colored by secondary structure (helices vs sheets);
    • colored by residue type (hydrophobic vs hydrophilic) and/or surface/pocket.
  3. Short notes (5–10 bullets): what you learned about fold, interface, and residue distribution.
  4. (Optional) Prediction/variant: brief comparison and what you’d test next.

Handy references