Three-dimensional correlated accordion NMR spectroscopy of proteins

Abstract

A major step toward the protein structure determination by nuclear magnetic resonance (NMR) spectroscopy is the assignment of multidimensional NMR signals that provide through-bond and through-space inter-atomic correlations. Ambiguities often occur during the assignment process due to resonance degeneracy, which challenges high resolution and larger size protein structure determination. Here, we present a method that will significantly improve the efficiency and accuracy of the NMR signal assignment. The method is based on a correlated accordion principle that, when incorporated into conventional three-dimensional (3D) heteronuclear NMR experiments, allows the retrieval of additional frequency correlation information at high resolution. We show that 3D spectra derived from this method are as effective as the impractical high resolution four-dimensional (4D) spectra with substantially reduced signal ambiguity as compared to their conventional counterparts. The approach promises increased accuracy and size of protein structures determined by NMR.