Model-independent refinement of interproton distances generated from 1H NMR overhauser intensities

Abstract

A recursive method to refine interproton distances compatible with two-dimensional nuclear Overhauser effect (NOESY) experiments has been tested. Convergence does not depend on the initial estimate of the parameters. Hence, no approximate initial structure of the molecule is required: the iterative process can be started from the experimentally measured NOESY cross-peak volumes, supplemented with arbitrary cross-peak and autopeak values to obtain an initial NOESY matrix. The relaxation matrix is calculated from the NOESY matrix, and its diagonal elements ( ϱ i ) are adjusted at each iteration until the difference between theoretical and experimental cross peaks is a minimum. The improvement comes from using interproton distances calculated from the off-diagonal ( σ ij ) elements to generate ϱ i values. The method was applied to alumichrome, a rigid cyclohexapeptide of virtually identical solution and crystallographic structures. The experimental data consisted of the integrated volumes of NOESY cross peaks at 500 MHz. Convergence was tested by resorting to different initial conditions, one of them being a NOESY matrix in which the experimentally unobserved off diagonal elements were set equal to zero and the diagonal elements to 0.5. The iterations rapidly converge, in all cases, to a set of distances whose root-mean-squares deviation (rmsd) from the crystallographic distances is < 0.05 Å. The acronym MIDGE (model-independent distance generation) for the procedure is proposed.