Validation of archived chemical shifts through atomic coordinates

Abstract

The public archives containing protein information in the form of NMR chemical shift data at the BioMagResBank (BMRB) and of 3D structure coordinates at the Protein Data Bank are continuously expanding. The quality of the data contained in these archives, however, varies. The main issue for chemical shift values is that they are determined relative to a reference frequency. When this reference frequency is set incorrectly, all related chemical shift values are systematically offset. Such wrongly referenced chemical shift values, as well as other problems such as chemical shift values that are assigned to the wrong atom, are not easily distinguished from correct values and effectively reduce the usefulness of the archive. We describe a new method to correct and validate protein chemical shift values in relation to their 3D structure coordinates. This method classifies atoms using two parameters: the per-atom solvent accessible surface area (as calculated from the coordinates) and the secondary structure of the parent amino acid. Through the use of Gaussian statistics based on a large database of 3220 BMRB entries, we obtain per-entry chemical shift corrections as well as Z scores for the individual chemical shift values. In addition, information on the error of the correction value itself is available, and the method can retain only dependable correction values. We provide an online resource with chemical shift, atom exposure, and secondary structure information for all relevant BMRB entries (http://www.ebi.ac.uk/pdbe/nmr/vasco) and hope this data will aid the development of new chemical shift-based methods in NMR.

Figure 1

Chemical shift corrections from the TALOS database compared with the VASCO—calculated correction for C^α atoms (top left), C atoms (top right), N atoms (bottom left), and H^α atoms (bottom right).

Figure 2

Histogram showing the distribution of the chemical shift corrections for aliphatic carbon atoms.

Figure 3

Chemical shift corrections for the aliphatic carbon atoms for selected NMR laboratories. The (median, average) corrections are listed behind the laboratory identifier.

Figure 4

Variation of proton chemical shift correction for BMRB entry 7014 with increasing numbers of chemical shifts removed.