How are 3D macromolecular structures obtained?
- Empirical determination
- X-ray crystallography (83% of PDB entries)
- Solution NMR spectroscopy (15% of PDB entries)
- Electron microscopy or diffraction (0.3% of PDB entries)
- Comparative ("Homology") Modeling.
- Need for empirical template
limits it to ~20% of cases.
- Errors in sequence alignment of target with template
give errors in the model.
- Insertions, deletions cannot be reliably modeled.
- Can be reliable for main chain fold, surface/buried; side-chain positions unreliable.
- ~70% success when >=60% sequence identity.
- ~10% failure rate even when >=90% sequence identity.
- Ab initio theoretical modeling.
- Secondary structure: ~70% accuracy.
- Tertiary structure: accuracy too low for most purposes:
"For roughly 40% of proteins shorter than 150 amino acids [<15 kD] ...,
one of the five most commonly recurring models ...
has sufficient global similarity to the true structure to recognize it ...."
& Sali, 2001).
- Biannual competitions:
- Docking competition:
Eric Martz, University of Massachusetts, July 2003