Principles which govern surface recognition, intra- and intermolecular assembly and function of peptides and proteins are being studied. Molecular recognition by peptides and proteins underlies essentially all biological functions of these substances, emphasizing the importance of understanding surface organization and dynamics in determining molecular order and function. A major project is in progress to understand the newly described phenomenon that peptides encoded in anti-sense DNA have unexpected and potentially provocative interaction properties, including an ability both to bind to corresponding sense peptides (those encoded in sense DNA) and to elicit antibodies which bind to cellular receptors of sense peptides. An experimental paradigm has been established to characterize sense-antisense peptide binding and used to reveal quantitative properties of this binding process. Separately, underlying principles which determine surface recognition and consequent molecular order are being evaluated by studying the effect of synthetic sequence mutation on the peptide-protein assembly of semisynthetic ribonuclease-S, using high resolution structure of a modeled semisynthetic ribonuclease-S as a starting point. The data are being used to examine rules of protein self-assembly and to establish general guidelines for protein engineering. And a study continues of the neurohypophysial hormones oxytocin and vasopressin and associated neurophysins, which form cooperative peptide-protein complexes that act as storage forms for the polypeptides in neurosecretory granules, and the hormone- neurophysin precursors which also appear to self-associate into forms likely to exist in granules before processing. The nature and structural interrelationships between the self-association and hormone binding surfaces in neurophysins that give rise to cooperative complexes have been studied, using natural hormones and hormone mutants obtained by chemical synthesis. In addition, sequence-variant mutants of precursor have been prepared by semisynthesis and their interaction properties are being studied.
