A new procedure for generating and refining protein structures that satisfy constraints derived from two-di mensional data includes an internal coordinate Monte Carlo search algorithm for conformational sampling and a simple target function with terms for describing the structural information contained in 2-D NMR spectra. Solution structures of the peptide neutrophil defensin NP-5, generated with a metric matrix distance geometry algorithm, are refined with the Monte Carlo procedure, leading to structures with interproton distances that are closer to the bounds observed in the NMR data and have improved local geometry. In model studies, an α- helical peptide is rapidly folded from an extended chain when NMR distance constraints corresponding to an α- helix are used as input parameters. The ab initio folding of NP-5 from an extended chain and possible application to studying protein folding pathways are discussed. Cal culations were carried out with the program package IMPACT (Integrated Modeling Program Using Applied Chemical Theory), under development. An overview of IMPACT is presented.