QUANTITATIVE-EVALUATION OF CROSS-PEAK VOLUMES IN MULTIDIMENSIONAL SPECTRA BY NONLINEAR-LEAST-SQUARES CURVE-FITTING

A procedure for quantitative evaluation of cross-peak volumes in spectra of any order of dimensions is described; this is based on a generalized algorithm for combining appropriate one-dimensional integrals obtained by nonlinear-least-squares curve-fitting techniques. This procedure is embodied in a program, NDVOL, which has three modes of operation: a fully automatic mode, a manual mode for interactive selection of fitting parameters, and a fast reintegration mode. The procedures used in the NDVOL program to obtain accurate volumes for overlapping cross peaks are illustrated using various simulated overlapping cross-peak patterns. The precision and accuracy of the estimates of cross-peak volumes obtained by application of the program to these simulated cross peaks and to a back-calculated 2D NOESY spectrum of dihydrofolate reductase are presented. Examples are shown of the use of the program with real 2D and 3D data. It is shown that the program is able to provide excellent estimates of volume even for seriously overlapping cross peaks with minimal intervention by the user. (C) 1995 Academic Press, Inc.