1. Structure validation Everything that can go wrong, will go wrong, especially with things as complicated as protein structures. Everything that can go wrong, will go wrong, especially with things as complicated as protein structures.

2. Why ? Why does a sane (?) human being spend fourteen years to search for millions of errors in the PDB?

3. Because: Everything we know about proteins comes from PDB files. If a template is wrong the model will be wrong. Errors become less dangerous when you know about them.

4. What do we check? Administrative errors. Crystal-specific errors. NMR-specific errors. Really wrong things. Improbable things. Things worth looking at. Ad hoc things.

5. How difficult can it be?

7. Contact Probability

9. DACA

10. DACA

11. DACA

12. DACA

13. DACA

14. Contact probability box

15. Using contact probability

16. Other errors

17. His, Asn, Gln ‘flips’

18. Where are the protons?

19. Hydrogen bond network

20. Hydrogen bond force field

22. A typical case: 5TIM

24. 15% should be flipped

25. Little things hurt big

26. Improbable things

27. Your best check:

28. Planarity

29. How wrong is wrong?

30. Conclusions Everything that could go wrong has gone wrong. Errors are on a ‘sliding scale’. Error detection can detect a lot, but surely not everything (yet).

31. Acknowledgements: Rob Hooft