Principal objectives of this research are elucidation of the catalytic mechanism of pepsin and other acid proteases and determination of solution structure and dynamics of structural elements of the enzymes. NMR methods form the backbone of our approach, which will proceed along 2 major lines: a study of substrate (inhibitor)-enzyme interactions and direct observation of nuclei on the macromolecules. 1H and 19F relaxation times and chemical shifts of inhibitors will be measured to yield rate constants and an indication of substrate orientation in the active site. 1H, 19F and 13C F.T. nmr will be used for direct observation of macromolecule nuclei. The major thrust will be directed at identifying in the spectra groups in the active site, where several aromatic residues are known to play key roles. The response of enzyme resonances to inhibitor binding will provide details of the enzyme substrate interaction. Porcine pepsin and the acid protease from R. chinensis will be the main species used.