Distance constraint data

In order to integrate the NMR distance constraint data into a molecular mechanics minimization routine, we have chosen a smooth approximation of the above function... 

Table II Distance Constraint Data for Globoside Dissolve in Me2SO-d6, D20 ...

Even when initial structures were refined in the absence of distance constraint data, geometries change significantly. values for these minimum energy structures along with the additional minimum energy structures are presented in Table VI. Ball and... 

In the basic metric matrix implementation of the distance constraint technique [16] one starts by generating a distance bounds matrix. This is an A X y square matrix (N the number of atoms) in which the upper bounds occupy the upper diagonal and the lower bounds are placed in the lower diagonal. The matrix is Ailed by information based on the bond structure, experimental data, or a hypothesis. After smoothing the distance bounds matrix, a new distance matrix is generated by random selection of distances between the bounds. The distance matrix is converted back into a 3D confonnation after the distance matrix has been converted into a metric matrix and diagonalized. A new distance matrix... 

Figure 18.20 The two-dimensional NMR spectrum shown in Figure 18.17 was used to derive a number of distance constraints for different hydrogen atoms along the polypeptide chain of the C-terminal domain of a cellulase. The diagram shows 10 superimposed structures that all satisfy the distance constraints equally well. These structures are all quite similar since a large number of constraints were experimentally obtained. (Courtesy of P. Kraulis, Uppsala, from data published in P. Kraulis et ah. Biochemistry 28 7241-7257, 1989, by copyright permission of the American Chemical Society.)...

In de novo three-dimensional structure determinations of proteins in solution by NMR spectroscopy, the key conformational data are upper distance limits derived from nuclear Overhauser effects (NOEs) [11, 14]. In order to extract distance constraints from a NOESY spectrum, its cross peaks have to be assigned, i.e. the pairs of hydrogen atoms that give rise to cross peaks have to be identified. The basis for the NOESY assignment... 

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). 

In order to incorporate distance constraints derived from two-dimensional crossrelaxation data in a molecular mechanics program, we have chosen to treat the constraints as a pseudoenergy function. This function should ideally reflect the distance dependence of cross relaxation rates. Previously, we had proposed a function of the form (40) ... 

In expression 7, iij is the distance to be determined a j is the corresponding cross peak intensity, ao is the cross peak intensity corresponding to a rigidly fixed pair of protons on the same saccharide residue, and tq is the distance between them. In Table II, we present a list of distance constraints and their associated errors which were determined from the ratio of cross peak intensities in the NOESY data set shown in Figure 3. 

RMS deviations (in A) for twenty-seven distance constraints corresponding to observed connectivities in NOESY data set on globoside... 

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