title: A probabilistic approach for validating protein NMR chemical shift assignments.
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 (3-6 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 "Probabilistic Approach for protein Nmr Assignment Validation (PANAV)" 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.
authors.affiliation: Shanghai American School Pudong, 201201, San Jia Gang, Pudong, Shanghai, People's Republic of China.
authors.forename: Bowei
authors.initials: B
authors.lastname: Wang
authors.forename: Yunjun
authors.initials: Y
authors.lastname: Wang
authors.forename: David S
authors.initials: DS
authors.lastname: Wishart
mesh_terms: D000595:Amino Acid Sequence; D015233:Models, Statistical; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011506:Proteins / Q000737:chemistry*; D015203:Reproducibility of Results; D012984:Software; D014584:User-Computer Interface
chemical_list: D011506:Proteins
references.citation: J Biomol NMR. 2009 Jun;44(2):95-9
references.pmid: 19436955
references.citation: J Am Chem Soc. 2002 Nov 27;124(47):14075-84
references.pmid: 12440906
references.citation: Biochemistry. 1992 Feb 18;31(6):1647-51
references.pmid: 1737021
references.citation: Science. 1993 Jun 4;260(5113):1491-6
references.pmid: 8502992
references.citation: J Biomol NMR. 2003 Mar;25(3):173-95
references.pmid: 12652131
references.citation: J Biomol NMR. 1991 Sep;1(3):217-36
references.pmid: 1841696
references.citation: J Am Chem Soc. 2009 Oct 7;131(39):13894-5
references.pmid: 19739624
references.citation: J Biomol NMR. 2003 Jul;26(3):215-40
references.pmid: 12766419
references.citation: Biochemistry. 1993 Dec 21;32(50):13818-29
references.pmid: 8268157
references.citation: J Biomol NMR. 2001 Dec;21(4):321-33
references.pmid: 11824752
references.citation: Biochem Cell Biol. 1998;76(2-3):153-63
references.pmid: 9923684
references.citation: J Biomol NMR. 1994 May;4(3):455-8
references.pmid: 8019146
references.citation: Nucleic Acids Res. 2008 Jan;36(Database issue):D402-8
references.pmid: 17984079
references.citation: Protein Sci. 2002 Apr;11(4):852-61
references.pmid: 11910028
references.citation: J Biomol NMR. 2004 Apr;28(4):341-55
references.pmid: 14872126
references.citation: J Biomol NMR. 2007 Nov;39(3):223-7
references.pmid: 17899394
references.citation: J Mol Biol. 1991 Nov 20;222(2):311-33
references.pmid: 1960729
references.citation: J Biomol NMR. 2004 Apr;28(4):327-40
references.pmid: 14872125
references.citation: J Biomol NMR. 1994 Mar;4(2):171-80
references.pmid: 8019132
references.citation: J Biomol NMR. 2005 Feb;31(2):143-8
references.pmid: 15772753
references.citation: Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4685-90
references.pmid: 18326625