Determination from NMR data

W. Braun, Q. Rev. Biophys., 19, 115 (1987). Distance Geometry and Related Methods for Protein Structure Determination from NMR Data. 

Restrained Molecular Dynamics Procedure for Protein Tertiary Structure Determination from NMR Data A lac Repressor Headpiece Structure Based on Information on /-Coupling and from Presence and Absence of NOEs. 

The overall approach to determining the structure of a protein is to use computational power to take into account concurrently (1) the known sequence of the amino acids in the protein (2) the known molecular structure of each of those amino acid residues, including bond distances and angles (3) the known planar structure of the peptide group (4) internuclear distances and interresidue bond angles, as determined from NMR data (5) correlations of chemical shifts and structural features and (6) minimization of energy and avoidance of unreasonable atomic contacts. There are a number of ways to handle the computations and to derive the molecular structure, but all of them depend critically on the data supplied by NMR. 

It follows from the data presented in Fig. 12 that at temperatures below 0 °C a strong decrease of the Ag amplitude is observed. This decrease is due to freezing of part of the water. For sample 1 (Table 6) with the highest porostiy the drop of AJ is greatest. Below -1 °C the amount of unfrozen water depends linearly (in the first approximation) on temperature at - 6 it is about 50% of the content at -1 °C. In accordance with a previously developed method of calculation the amount of ice in a phenolic foam was determined from NMR data (Table 7). 

The order parameters of aliphatic hydrocarbons solubilized in a lamellar liquid crystal were determined from NMR data. The variation of order parameters along the hydrocarbon chain with varying amounts of hydrocarbon solubilized supports a model with the main part of the hydrocarbon forming a layer between the amphiphilic layers with only a small amount of it penetrating between the amphiphilic molecules. 

The number of complexes for which the AG have been determined from NMR data is rather limited, making it difficult to establish clear trends (Table 5). For many compounds, the exchange is too fast on the NMR time scale to distinguish separate signals for the terminal and bridging hydrogens, even at low temperatures. Compounds of Group 3 and 4 transition metals... 

J. De Vlieg, R. Boelens, R. M. Scheek, R. Kaptein, and W. F. van Gunsteren, hr. J. Chem., 27, 181 (1986). Restrained Molecular Dynamics Procedure for Protein Tertiary Structure Determination from NMR Data A lac Repressor Headpiece Structure Based on Information on J-Coupling and from Presence and Absence of NOE s. 

Another principal difficulty is that the precise effect of local dynamics on the NOE intensity cannot be determined from the data. The dynamic correction factor [85] describes the ratio of the effects of distance and angular fluctuations. Theoretical studies based on NOE intensities extracted from molecular dynamics trajectories [86,87] are helpful to understand the detailed relationship between NMR parameters and local dynamics and may lead to structure-dependent corrections. In an implicit way, an estimate of the dynamic correction factor has been used in an ensemble relaxation matrix refinement by including order parameters for proton-proton vectors derived from molecular dynamics calculations [72]. One remaining challenge is to incorporate data describing the local dynamics of the molecule directly into the refinement, in such a way that an order parameter calculated from the calculated ensemble is similar to the measured order parameter. 

Molecular modeling is an indispensable tool in the determination of macromolecular structures from NMR data and in the interpretation of the data. Thus, state-of-the-art molecular dynamics simulations can reproduce relaxation data well [9,96] and supply a model of the motion in atomic detail. Qualitative aspects of correlated backbone motions can be understood from NMR structure ensembles [63]. Additional data, in particular residual dipolar couplings, improve the precision and accuracy of NMR structures qualitatively [12]. 

The magnitude of the preference for the formation of the less substituted enamine from unsymmetrical ketones as expressed by the general rule given above is not entirely clear. House and Schellenbaum 48) have reported that 2-methylcyclohexanone and pyrrolidine produce a product mixture of tetra- and trisubstituted enamines in a ratio of 15 85. The estimate of this ratio was made from NMR data. In contrast Stork and co-workers (9) report the formation of 100% trisubstituted enamine as determined by NMR spectroscopy. 

In Section 4.1.4.1, we develop the estimation of the relaxation distribution functions from NMR data. These are used to determine porosity and saturation distributions. In Section 4.1.4.2, we develop the estimation of permeability distri-... 

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). 

The structures in aqueous solution of both AP-A [46] and AP-B [47] have been solved using high-resolution NMR data. Structures have also been determined for the Type 1 toxin ATX la [48] and the Type 2 toxin Sh I [49,50] from NMR data. The main secondary structure element in each of these structures is a... 

Laing, L. G., and Hall, K. B. (1996). A model of the iron responsive element RNA hairpin loop structure determined from NMR and thermodynamic data. Biochemistry 35, 13586-13594. 

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