How are 3D macromolecular structures obtained?
(Peitsch et al., 1998)
Ab initio theoretical modeling.
- X-ray crystallography
(88% of PDB entries)
- Solution NMR spectroscopy
(11% of PDB entries)
- Electron microscopy or diffraction (0.5% of PDB entries)
- Comparative ("Homology") Modeling.
- Need for empirical template
limits it to ~40% of domain sequences.
- Errors in sequence alignment of target with template
give errors in the model.
- Insertions, deletions, disordered template regions 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.
- Secondary structure: ~70% accuracy.
- Tertiary structure: accuracy too low for most purposes:
- 2005: In about 1/4 of domains <85 residues, predictions are within 1.5 Å
of the true structure (Bradley, Misura & Baker, 2005).
(Cf. independent determinations of the same protein, ~0.5 Å.)
- ~150 CPU-days needed per prediction. Orders of magnitude more computing power would be needed
for large proteins.
- Biannual competitions:
- Docking competition:
Eric Martz, University of Massachusetts, 2003. Most recent update: May 2012.