2010/03/17

Diagonal-free signals

Members of the NMR Platform and the Structural Biology Unit lead by Tammo Diercks have developed a new pulse sequence that improves the acquisition of spatial restrains (NOEs), a required step during the protein structure determination by NMR spectroscopy. This finding has been recently published as a communication in the Journal of the American Chemical Society.

NMR spectroscopy is widely used for the investigation of the structure of matter as well as of other properties. Unlike other techniques, the information is usually obtained after analyzing a multitude of spectra, each of them providing a different bit of information. This is possible because NMR is very versatile, allowing the acquisition of many different experiments (the so-called pulse sequences). A pulse sequence is a combination of radiofrequency pulses and short delays and, when carefully designed, it can remove spurious signals and select the signal of interest.

The NOESY experiment is pivotal because it is the only pulse sequence that can provide information on the spatial organization of the atoms (inter-atomic distances). Actually, protein structure determination heavily relies on the accurate determination of NOEs. The main problem in this experiment is the contamination of the spectrum with the autocorrelation signals (diagonal peaks) that yield no information, complicate the spectrum and limit the sensitivity. In this new implementation, Diercks and co-workers have been able to virtually eliminate the signal arising from the diagonal peaks. The upgraded experiment is cleaner and more informative because it shows NOE peaks that before were overlapped with the diagonal. By including the TROSY methodology, the procedure is especially suitable for studying very large proteins and it is expected that it will become the standard method for obtaining this kind of data.