Protein crystallography validation

X-ray crystallography, docking modes can be validated by various NMR techniques NOEs may be observed between the ligand and the receptor protein by heteronuclear-filtered NOE spectroscopy [51], chemical shift changes of protein resonances upon binding can be analyzed by simulation of shifts caused by ring currents and electrostatic effects [52], and saturation transfer difference measurements indicate which part of the ligand is in direct contact with the protein [52]. 

An application of the ROCS program has been reported recently (82). New scaffolds for small molecule inhibitors of the ZipA-FtsZ protein-protein interaction have been found. The shape comparisons are made relative to the bioactive conformation of a HTS hit, determined by X-ray crystallography. A followup X-ray crystallographic analysis also showed that ROCS accurately predicted the binding mode of the inhibitor. This result offers the first experimental evidence that validates the use of ROCS for scaffold hopping purposes. 

Macarthur, M.W., Laskowski, R.A. and Thornton, J.M. (1994) Knowledge-based validation of protein-structure coordinates derived by X-ray crystallography and NMR-spectroscopy. Curr. Opin. Struct. Biol. 4 731-737. 

The PDB is the repository for solved 3-D structures of proteins, peptides, viruses, protein-nucleic acid complexes, nucleic acids, and carbohydrates. Most structures deposited in the PDB are based on X-ray crystallography (approximately 80%) with the remaining structures solved using nuclear magnetic resonance (NMR) techniques. The PDB no longer stores theoretical protein models in the main archive, but it does accept them for storage in a separate theoretical model section where they are neither aimotated nor validated. The PDB staff members annotate and validate the submitted 3-D structures to ensure the information provided to the public is correct. The structures archived at the PDB are provided in two formats, PDB and... 

Using PROVE as a protein model evaluator is beneficial because it provides an alternative method of assessing the validity of proposed structures. As demonstrated by the developers of PROVE, it can predict which structures (and regions of structures) are defective based on resolution, B-factors, and to a lesser extent R-factors, all experimentally derived values that gauge the quality of a structure determined through X-ray crystallography. 

Knowledge-based Validation of Protein Structure Coordinates Derived by X-Ray Crystallography and NMR Spectroscopy. 

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