The long-range objective is to understand the structure-function relationship of a select few biopolymers by biophysical studies. The conformation of several polypeptides and proteins in solutions will be studied by circular dichroism together with other physicochemical methods. Our working hypothesis that the conformation of polypeptides in surfactant and lipid solutions is dictated by their primary structure will be further tested on amphipathic polypeptides (e.g. fragments of melittin and bacteriorhodopsin) and strongly hydrophobic polypeptides (e.g. signal peptides). Two new projects are initiated: one on two major proteins in cholinergic neurotransmission and the other on metal ion-cyclic peptide complexes. The conformation and enzymic activity of both the asymmetric (soluble) and globular (membrane-bound) forms of acetylcholinesterase and those of acetylcholine receptor and its subunits (Alpha2BetaGammaDelta) from Torpedo californica will be studied. The conformational changes, if any, of the receptor in the presence of agonists and antagonists will be determined. The conformation of reconstituted receptor and enzyme in lipid vesicles will be investigated by various physical methods. Second, a series of diketopiperazines such as c(His)2 and c(Cys-Met) and, later, cyclic hexapeptides will be synthesized. The coordination complexes of these compounds with metal ions such as Cu, Co, Ni, Mn and Fe mimick the active sites of several metalloproteins such as Cu/Zn superoxide dismutase, plastocyanin and azurin. The conformation and possible catalytic activity of these complexes will be related to and compared with those of the corresponding metalloproteins. The proteins and model compounds are chosen for their biological interest and health-related importance.
