9803535 Colon This study is to investigate how proteins fold, using a histidine-containing protein from E. coli as a model system since its three-dimensional structure is known. Experiments are designed to determine if kinetic intermediates can be detected during the processes of folding and unfolding, and whether basic principles can be derived from such information. The strategy will rely on the application of stopped-flow methods combined with optical spectroscopy and site-directed mutagenesis. The results should be fundamental to the understanding of protein structure and design.