Abstract: Disclosed is a method of determining two-dimensional nuclear- or rotating frame-Overhauser effect spectroscopy intensities for a ligand-enzyme system having flexible active cites, wherein the ligand-enzyme system has at least 3 conformational states. The first step is inputing data into a modeling computer of coordinates for each molecule on the enzyme and ligand, kinetic data, correlation times, and concentrations of ligand and enzyme. Next, a K matrix is created from the kinetic data, and an an R matrix is derived from the correlation times and the coordinates. A dynamic matrix D is created by summing the K and R matrices. This D matrix is symmetrized and diagonalized. Spectroscopy intensities are then derived from the symmetrized and diagonalized D matrix.