Experimental Protein Structure Verification by Scoring with a Single, Unassigned NMR Spectrum

[nmrlearner]

Experimental Protein Structure Verification by Scoring with a Single, Unassigned NMR Spectrum

Publication date: Available online 10 September 2015
Source:Structure

Author(s): Joseph*M. Courtney, Qing Ye, Anna*E. Nesbitt, Ming Tang, Marcus*D. Tuttle, Eric*D. Watt, Kristin*M. Nuzzio, Lindsay*J. Sperling, Gemma Comellas, Joseph*R. Peterson, James*H. Morrissey, Chad*M. Rienstra

Standard methods for de novo protein structure determination by nuclear magnetic resonance (NMR) require time-consuming data collection and interpretation efforts. Here we present a qualitatively distinct and novel approach, called Comparative, Objective Measurement of Protein Architectures by Scoring Shifts (COMPASS), which identifies the best structures from a set of structural models by numerical comparison with a single, unassigned 2D 13C-13C NMR spectrum containing backbone and side-chain aliphatic signals. COMPASS does not require resonance assignments. It is particularly well suited for interpretation of magic-angle spinning solid-state NMR spectra, but also applicable to solution NMR spectra. We demonstrate COMPASS with experimental data from four proteins—GB1, ubiquitin, DsbA, and the extracellular domain of human tissue factor—and with reconstructed spectra from 11 additional proteins. For all these proteins, with molecular mass up to 25*kDa, COMPASS distinguished the correct fold, most often within 1.5*Å root-mean-square deviation of the reference structure.
Graphical abstract


Teaser

Courtney et*al. have developed an algorithm that scores protein structural models against a previously unanalyzed NMR spectrum. This method, named COMPASS, does not require chemical shift assignments and identifies the correct structure in most cases within 1.5*Å RMSD of the reference structure.





More...