The broad objectives of the proposed research are to develop and apply methodology for the determination of the molecular structures of peptides and proteins in solution and in lipid bilayers. The ultimate aims of this work include the understanding of (a) certain structure:function relationships of naturally-occurring peptides and some proteins, (b) some mechanisms of cation transport through membranes, and (c) the molecular architecture of certain membrane-embedded and membrane-attached proteins. A major effort will be directed to the determination of bicyclic peptide conformations in solution and in lipid bilayers both in the presence and absence of metal ions. Another part of the effort will involve the use of synthetic peptide fragments of membrane proteins in order to understand their molecular conformations. A third part of our effort will be directed towards understanding the conformation of pre-, pro-, and leader protein sequences through the use of synthetic peptide models. To obtain these objectives use will be made of proton and 13C nuclear magnetic resonance spectroscopy as well as circular dichroism spectroscopy. The scientific disciplines involved in this work include chemistry, biochemistry, biophysics, and biophysical chemistry. Ultimately, it is hoped that, by gaining an understanding of the molecular conformations of proteins, it will be possible to modify their actions in ways beneficial to health.
