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Atomic Scale Structural Studies of Macromolecular Assemblies by Solid-state Nuclear Magnetic Resonance Spectroscopy
Published on: September 17, 2017
A probabilistic approach for validating protein NMR chemical shift assignments
Bowei Wang1, Yunjun Wang, David S Wishart
1Shanghai American School Pudong, 201201, San Jia Gang, Pudong, Shanghai, People's Republic of China.
Journal of Biomolecular NMR
|May 7, 2010
Summary
Protein NMR chemical shift assignments often contain errors. A new structure-independent method, PANAV, validates and corrects mis-assigned and mis-referenced protein NMR data, improving accuracy before structural determination.
Area of Science:
- Biomolecular NMR Spectroscopy
- Structural Biology
- Computational Chemistry
Background:
- A significant percentage of protein chemical shift assignments in databases like BMRB contain errors.
- Existing software often addresses only mis-assignments or mis-referencing, not both.
- Current methods requiring 3D structure coordinates are suboptimal as errors should be fixed pre-structure determination.
Purpose of the Study:
- To develop a structure-independent protocol for identifying and correcting protein NMR chemical shift mis-assignments and mis-referencing.
- To provide a tool that validates and corrects assigned protein chemical shifts prior to 3D structure determination.
Main Methods:
- A novel structure-independent protocol utilizing residue-specific and secondary structure-specific chemical shift distributions.
- Analysis based on small (3-6 residue) fragments to identify mis-assigned resonances.
- Implementation into a Java program (PANAV) and a web server.
Main Results:
- The developed method effectively identifies mis-assigned protein NMR resonances.
- The protocol successfully re-references mis-referenced chemical shift assignments.
- PANAV demonstrates comparable or superior performance to existing error-detection programs.
Conclusions:
- The new structure-independent protocol offers a robust solution for validating and correcting protein NMR chemical shifts.
- PANAV provides a valuable, freely accessible tool for the biomolecular NMR community.
- Addressing chemical shift assignment errors early streamlines the protein structure determination process.
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