1. ©CMBI 2002 Structure validation Murphy’s law: Everything that can go wrong, will go wrong, especially with things as complicated as protein structures. Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

2. ©CMBI 2002 Why ? Why does a sane (?) human being spend fourteen years to search for millions of errors in the PDB? Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

3. ©CMBI 2002 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. Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

4. ©CMBI 2002 What do we check? Administrative errors. Crystal-specific errors. NMR-specific errors. Really wrong things. Improbable things. Things worth looking at. Ad hoc things. Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

5. ©CMBI 2002 How difficult can it be? Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

6. ©CMBI 2002 How difficult can it be? Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

7. ©CMBI 2002 X-ray specific Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

8. ©CMBI 2002 X-ray specific Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

9. ©CMBI 2002 Planarity Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

10. ©CMBI 2002 How wrong is wrong? Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

11. ©CMBI 2002 Improbable things Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

12. ©CMBI 2002 Contact Probability Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

13. ©CMBI 2002 Contact Probability Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

14. ©CMBI 2002 DACA Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

15. ©CMBI 2002 DACA Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

16. ©CMBI 2002 DACA Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

17. ©CMBI 2002 DACA Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

18. ©CMBI 2002 DACA Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

19. ©CMBI 2002 Contact probability box Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

20. ©CMBI 2002 Using contact probability Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

21. ©CMBI 2002 His, Asn, Gln ‘flips’ Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

22. ©CMBI 2002 Where are the protons? Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

23. ©CMBI 2002 Hydrogen bond network Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

24. ©CMBI 2002 Hydrogen bond force field Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

25. ©CMBI 2002 Hydrogen bond force field Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

26. ©CMBI 2002 Little things hurt big Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

27. ©CMBI 2002 Other errors Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

28. ©CMBI 2002 Your best checks: Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions DACA Backbone normality and 

29. ©CMBI 2002 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). Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions

30. ©CMBI 2002 Acknowledgements: Rob Hooft Murphy Introduction X-ray NMR Scores DACA Flips Administration Conclusions