TY - JOUR
T1 - Covariance nuclear magnetic resonance methods for obtaining protein assignments and novel correlations
AU - Kancherla, Aswani K.
AU - Frueh, Dominique P.
N1 - Funding Information:
We thank Bradley Harden, Indrani Pal, and Subrata Mishra for helpful discussions. Research in the Frueh Laboratory is supported by NIH grant R01 GM104257 and our equipment benefitted from grant S10 RR029191.
Funding Information:
his Diplome de Chimie from the Universite de Lausanne in 1997 (faculty prize 1995, math excellence 1992). He then joined the laboratory of Geof- frey Bodenhausen to develop novel solution NMR methods with a focus on protein dynamics and obtained his PhD from the EPFL in 2002. He was a postdoctoral fellow with a Swiss National Science Foundation fellowship (2002-2003) and went to Harvard Medical School, Boston, MA to work with Gerhard Wagner and Christopher T Walsh, and was later promoted as an Instructor and Research Associate (2007-2010). In 2010, he joined the Department of Biophysics and Biophysical Chemistry at the Johns Hopkins School of Medicine, Baltimore, MD, and was promoted to associate professor in 2016. His laboratory studies the molecular mechanisms of nonribosomal peptide synthetases and develops NMR methods for studies of large and/or dynamic proteins.
Publisher Copyright:
© 2018 Wiley Periodicals, Inc.
PY - 2017/3
Y1 - 2017/3
N2 - Protein nuclear magnetic resonance (NMR) assignment can be a tedious and error-prone process, and it is often a limiting factor in biomolecular NMR studies. Challenges are exacerbated in larger proteins, disordered proteins, and often alpha-helical proteins, owing to an increase in spectral complexity and frequency degeneracies. Here, several multidimensional spectra must be inspected and compared in an iterative manner before resonances can be assigned with confidence. Over the last 2 decades, covariance NMR has evolved to become applicable to protein multidimensional spectra. The method, previously used to generate new correlations from spectra of small organic molecules, can now be used to recast assignment procedures as mathematical operations on NMR spectra. These operations result in multidimensional correlation maps combining all information from input spectra and providing direct correlations between moieties that would otherwise be compared indirectly through reporter nuclei. Thus, resonances of sequential residues can be identified and side-chain signals can be assigned by visual inspection of 4D arrays. This review highlights advances in covariance NMR that permitted to generate reliable 4D arrays and describes how these arrays can be obtained from conventional NMR spectra.
AB - Protein nuclear magnetic resonance (NMR) assignment can be a tedious and error-prone process, and it is often a limiting factor in biomolecular NMR studies. Challenges are exacerbated in larger proteins, disordered proteins, and often alpha-helical proteins, owing to an increase in spectral complexity and frequency degeneracies. Here, several multidimensional spectra must be inspected and compared in an iterative manner before resonances can be assigned with confidence. Over the last 2 decades, covariance NMR has evolved to become applicable to protein multidimensional spectra. The method, previously used to generate new correlations from spectra of small organic molecules, can now be used to recast assignment procedures as mathematical operations on NMR spectra. These operations result in multidimensional correlation maps combining all information from input spectra and providing direct correlations between moieties that would otherwise be compared indirectly through reporter nuclei. Thus, resonances of sequential residues can be identified and side-chain signals can be assigned by visual inspection of 4D arrays. This review highlights advances in covariance NMR that permitted to generate reliable 4D arrays and describes how these arrays can be obtained from conventional NMR spectra.
KW - correlation maps
KW - covariance NMR
KW - methyl resonance assignments
KW - multidimensional NMR spectra
KW - protein sequence-specific resonance assignments
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U2 - 10.1002/cmr.a.21437
DO - 10.1002/cmr.a.21437
M3 - Article
C2 - 30288152
AN - SCOPUS:85053372070
SN - 1546-6086
VL - 46A
JO - Concepts in Magnetic Resonance Part A: Bridging Education and Research
JF - Concepts in Magnetic Resonance Part A: Bridging Education and Research
IS - 2
M1 - e21437
ER -