©cmbi 2002 structure validation murphy’s law: everything that can go wrong, will go wrong,...
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©CMBI 2002
Structure validation
Murphy’s law:
Everything that can go wrong, will go wrong, especially with things as complicated as protein structures.
MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
©CMBI 2002
Why ?
Why does a sane (?) human being spend fourteen years to search for millions of errors in the PDB?
MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
©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.
MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
©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.
MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
©CMBI 2002
How difficult can it be?
MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
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How difficult can it be?
MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
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X-ray specific
MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
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X-ray specific
MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
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PlanarityMurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
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How wrong is wrong?MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
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Improbable thingsMurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
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Contact Probability
MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
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Contact Probability
MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
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DACA
MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
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DACA
MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
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DACA
MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
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DACA
MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
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DACA
MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
©CMBI 2002
Contact probability box
MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
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Using contact probability
MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
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His, Asn, Gln ‘flips’MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
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Where are the protons?
MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
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Hydrogen bond network
MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
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Hydrogen bond force field
MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
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Hydrogen bond force field
MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
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A typical case: 5TIM
MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
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15% should be flipped
MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
©CMBI 2002
Little things hurt bigMurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
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Other errors
MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
©CMBI 2002
Your best checks:MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
DACABackbone normalityand
©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).
MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions
©CMBI 2002
Acknowledgements:
Rob Hooft
MurphyIntroductionX-rayNMRScoresDACAFlipsAdministrationConclusions