Nuclear Overhauser effect interproton distances

L. Nilsson, G. M, Close, A, M. Gronenbom, A. T. Brunger, and M. Karplus,/. Mol. Biol., 188,455 (1986). Structure refinement of Oligonucleotides by Molecular Dynamics with Nuclear Overhauser Effect Interproton Distance Restraints Application to 5 d(CGTACG)2. 

Structure Refinement of Oligonucleotides by Molecular Dynamics with Nuclear Overhauser Effect Interproton Distance Restraints Application to 5 d(CGTACG). 

The basis for the determination of solution conformation from NMR data lies in the determination of cross relaxation rates between pairs of protons from cross peak intensities in two-dimensional nuclear Overhauser effect (NOE) experiments. In the event that pairs of protons may be assumed to be rigidly fixed in an isotopically tumbling sphere, a simple inverse sixth power relationship between interproton distances and cross relaxation rates permits the accurate determination of distances. Determination of a sufficient number of interproton distance constraints can lead to the unambiguous determination of solution conformation, as illustrated in the early work of Kuntz, et al. (25). While distance geometry algorithms remain the basis of much structural work done today (1-4), other approaches exist. For instance, those we intend to apply here represent NMR constraints as pseudoenergies for use in molecular dynamics or molecular mechanics programs (5-9). 

Also of interest is the density functional theory (DFT) (B3LYP/3-21G level) study of the 1,3,5-dithiazine bicyclic derivative 8, whose optimized geometry shows interproton distances that are in good agreement with observed nuclear magnetic resonance (NMR) nuclear Overhauser effect (NOE) values <2003SL1731>. 

NMR structures of d(CGCGAATTCGCG) have been reported by Nerdal et al. (39) and Lane et al. (40) based on 2D-NOESY data. Nerdal et al, proposed a highly underwound structure with kinks at the primary and secondary roll points and at the ApT step. Lane et al. propose an NMR structure much closer to that of conventional B DNA. The limit of the nuclear Overhauser effect to interproton distances -4.5 A makes unequivocal determination of the helix parameters in an... 

Basic data obtained from NMR studies consist of distance and torsion angle restraints. Once resonances have been assigned, nuclear Overhauser effect (NOE) contacts are selected and their intensities are used to calculate interproton distances. Information on torsion angles are based on the measurement of coupling constants and analysis of proton chemical shifts. Together, this information is used to formulate a nonlinear optimization problem, the solution of which should provide the correct protein structure. Typically, a hybrid energy function of the following form is employed ... 

The nuclear Overhauser effect (NOE) is another important NMR parameter used in conformational analysis because the magnitude of the NOE is inversely proportional to the sixth power of the interproton distance in space (/noe° NOE spectroscopy (NOESY) is two-dimensional experiment that may be run routinely in which the NOE is manifested as a crosspeak between two resonances indicating that the two protons are near in space. 

Figure 6-31 The enhancement factor t as a function of the effective correlation lime Tc for the standard nuclear Overhauser experiment (NOE) and for the spin-lock, or rotating-coordinate, (ROE) variant. The curves were calculated for an interproton distance of 2.0 A and a spectrometer frequency of 500 MHz, (Reproduced from F. J. M. van de Ven, Multidimensional NMR in Liquids, VCH, New York,...

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