Protein dynamics chemical shifts

Tjandra N, Szabo A and Bax A 1996 Protein backbone dynamics and N-15 chemical shift anisotropy from quantitative measurement of relaxation interference effected. Am. Chem. Soc. 118 6986-91... 

Fushman, D. and D. Cowburn, Nuclear magnetic resonance relaxation in determination of residue-specific 1SN chemical shift tensors in proteins in solution protein dynamics, structure, and applications of transverse relaxation optimized spectroscopy, in Methods Enzymol. T. James, U. Schmitz, and V. Doetsch, Editors. 2001. p.109-126. 

In addition to being used for structural determinations of protein targets, NMR is increasingly being used to examine the dynamic interactions of ligand-receptor binding. Two NMR properties are particularly important chemical shift and nuclear spin relaxation. 

Abstract In recent years NMR methods have been developed that enable the observation of proteins inside living bacterial cells. Because of the sensitivity of the chemical shift to environmental changes these in-ceU NMR experiments can be used to study protein conformation, molecular interaction or dynamics in a protein s natmal surrounding. Detection of proteins in the bacterial cytoplasm relies on labeling of the protein of interest with NMR active isotopes. This review describes different labeling techniques based on either imiform i5n or labeling as well as amino acid specific labeling schemes. In addition potential applications of these in-cell NMR experiments and their limitations are discussed. 

Also, one would be remiss if one did not at least mention the various analytical and diagnostic NMR techniques that have come into prominent use over the last decade, particularly with respect to their applications to drug discovery. Because of the sensitivity of its chemical shift to local environment, 19F NMR has increasingly been used as a probe in the study of structure and dynamics of small molecules, proteins, and other biological systems.32-36... 

Chemical shifts (CSs) are the most common NMR parameters obtained as the result of the assignment process as a prerequisite of all subsequent analyses. As a consequence, large data sets of CSs and their analyses are available therefore, their relation to protein structure and dynamics is well documented. The basic observation is that CSs, especially Ha and Ca values depend heavily on the local conformation of the peptide chain. This relationship can be further refined by additional factors such as the spatial environment of these atoms. Currently, applications such as SHIFTX47 are capable of calculating CSs from 3D protein structures and, as a reversal, protein folds can be reconstructed solely on the basis of CS information.48 49 Moreover, internal dynamics of proteins can be estimated solely on the basis of CSs.50 51... 

In combination, the 2D NMR spectroscopy allows the determination of resonance frequency (w,), chemical shift (6), relaxation times (T] and T2) for each NMR active atoms, coupling constant (J) between adjacent atoms, and parameters of Overhauser enhancement experiments (NOE). These data make a basis for establishing chemical structure and measurement of dynamics of the molecules under investigation. The main trends in recent NMR research on protein and enzymes involve the development and employment of the following methods 1) NMR spectroscopy with maximal high... 

Finally, NMR-derived distance information as well as information about dihedral angles (obtained from chemical shifts) is incorporated into structure calculations performed using molecular dynamics and simulated annealing programs such as CNS (48) and XPLOR-NIH (49) to calculate the protein stmcture. 

---