The development of very high-field magnets, cryogenic probes, and relaxation-optimized pulse sequences have dramatically increased the size and complexity of biomacromolecules amenable to study by NMR spectroscopy. In contrast, the computational methods most commonly used to analyze NMR data have remained essentially unchanged for more than 2 decades. These methods have well-documented shortcomings, for example requiring a nearly 4-fold increase in the amount of data that must be collected in a three-dimensional (3D)experiment at 900 MHz in order to achieve the same frequency resolution as an experiment at 500 MHz. In practice this requirement is rarely met, limiting the potential resolution of high-field experiments. A number of modern methods of spectrum analysis have been developed that avoid these shortcomings, but they have not found routine application in NMR. Obstacles to their use include nonintuitive adjustable parameters and the complexity of the available software. In addition, the methods are all nonlinear, and thus prudent application requires careful error analysis. We propose to develop software to enable new applications of maximum entropy reconstruction in biomolecular NMR. The applications include nonuniform sampling in the time domain, to reduce data collection requirements while improving resolution, and deconvolution for performing """"""""virtual decoupling"""""""". In addition to software to support multidimensional experiments and efficient computation using loosely-coupled clusters of computers, we will develop new tools for error analysis. We plan to develop a facile user interface, documentation, tutorials, and tools to support interoperability with other software packages, in order to make these advanced data processing and analysis capabilities accessible to non-experts in the broader biomolecular NMR community. The application of modern spectrum analysis in biomolecular NMR will enable the full potential of modern magnets, probes, and pulse sequences to be realized for solving challenging problems in structural biology. ? ?
| Hoch, Jeffrey C (2017) Beyond Fourier. J Magn Reson 283:117-123 |
| Hoch, Jeffrey C; Maciejewski, Mark W; Mobli, Mehdi et al. (2014) Nonuniform sampling and maximum entropy reconstruction in multidimensional NMR. Acc Chem Res 47:708-17 |
| Schuyler, Adam D; Maciejewski, Mark W; Stern, Alan S et al. (2013) Formalism for hypercomplex multidimensional NMR employing partial-component subsampling. J Magn Reson 227:20-4 |
| Maciejewski, Mark W; Mobli, Mehdi; Schuyler, Adam D et al. (2012) Data sampling in multidimensional NMR: fundamentals and strategies. Top Curr Chem 316:49-77 |
| Gorbatyuk, Vitaliy Y; Schiller, Martin R; Gorbatyuk, Oksana I et al. (2012) N-terminal Dbl domain of the RhoGEF, Kalirin. J Biomol NMR 52:269-76 |
| Mobli, Mehdi; Maciejewski, Mark W; Schuyler, Adam D et al. (2012) Sparse sampling methods in multidimensional NMR. Phys Chem Chem Phys 14:10835-43 |
| Maciejewski, Mark W; Fenwick, Matthew; Schuyler, Adam D et al. (2011) Random phase detection in multidimensional NMR. Proc Natl Acad Sci U S A 108:16640-4 |
| Schuyler, Adam D; Maciejewski, Mark W; Arthanari, Haribabu et al. (2011) Knowledge-based nonuniform sampling in multidimensional NMR. J Biomol NMR 50:247-62 |
| Bobenchik, April M; Choi, Jae-Yeon; Mishra, Arunima et al. (2010) Identification of inhibitors of Plasmodium falciparum phosphoethanolamine methyltransferase using an enzyme-coupled transmethylation assay. BMC Biochem 11:4 |
| Mobli, Mehdi; Stern, Alan S; Bermel, Wolfgang et al. (2010) A non-uniformly sampled 4D HCC(CO)NH-TOCSY experiment processed using maximum entropy for rapid protein sidechain assignment. J Magn Reson 204:160-4 |
Showing the most recent 10 out of 16 publications
