A probabilistic approach for validating protein NMR chemical shift assignments

[nmrlearner]

Abstract It has been estimated that more than 20% of the proteins in the BMRB are improperly referenced and that about 1% of all chemical shift assignments are mis-assigned. These statistics also reflect the likelihood that any newly assigned protein will have shift assignment or shift referencing errors. The relatively high frequency of these errors continues to be a concern for the biomolecular NMR community. While several programs do exist to detect and/or correct chemical shift mis-referencing or chemical shift mis-assignments, most can only do one, or the other. The one program (SHIFTCOR) that is capable of handling both chemical shift mis-referencing and mis-assignments, requires the 3D structure coordinates of the target protein. Given that chemical shift mis-assignments and chemical shift re-referencing issues should ideally be addressed prior to 3D structure determination, there is a clear need to develop a structure-independent approach. Here, we present a new structure-independent protocol, which is based on using residue-specific and secondary structure-specific chemical shift distributions calculated over small (3â??6 residue) fragments to identify mis-assigned resonances. The method is also able to identify and re-reference mis-referenced chemical shift assignments. Comparisons against existing re-referencing or mis-assignment detection programs show that the method is as good or superior to existing approaches. The protocol described here has been implemented into a freely available Java program called â??Probabilistic Approach for protein Nmr Assignment Validation (PANAV)â?? and as a web server (http://redpoll.pharmacy.ualberta.ca/PANAV) which can be used to validate and/or correct as well as re-reference assigned protein chemical shifts.

• Content Type Journal Article
• DOI 10.1007/s10858-010-9407-y
• Authors
  • Bowei Wang, Shanghai American School Pudong 201201 San Jia Gang, Pudong, Shanghai Peopleâ??s Republic of China
  • Yunjun Wang, Mesolight LLC, 4607Â*W 61st St. Little Rock AK 72209 USA
  • David S. Wishart, University of Alberta Departments of Computing Science and Biological Sciences Edmonton AL T6G 2E8 Canada

• • Journal Journal of Biomolecular NMR
  • Online ISSN 1573-5001
  • Print ISSN 0925-2738
  • Journal Volume Volume 47
  • Journal Issue Volume 47, Number 2

Source: Journal of Biomolecular NMR