A group of PHS supported principal investigators and other biomedical researchers request funds to purchase an Apollo DN 10000 personal supercom- puter workstation and to upgrade an existing peptide synthesizer with an automation module. A large fraction of the work proposed involves the use of short peptide sequences which mimic the function of the entire parent regulatory protein in provoking a biological response in a receptor protein (Prof. Dratz, Jesaitis, Helgerson, and Starkey). Conformational energy calculations will be carried out on these peptides to predict structure. Direct information on the active conformations of the peptides bound to their receptors will be provided by TR-NOSEY 2D NMR measurements coupled with distance geometry, conformational energy calculations (XPLOR and AMBER), and color graphics. Modified peptides will be then synthesized to be """"""""locked"""""""" into the proposed active conformations (Prof. Livinghouse, Dratz, Jesaitis, Helgerson, and Starkey). These peptides will be tested for increased efficacy (lower Km) in provoking the biological response and the actual conformation determined by COSY, NOSEY, and ROSEY 2D NMR. This work will be extended to studies of active conformations of oligosaccaharides and chemically modified oligosaccharides (Prof. Starkey and Hood). Other projects to be carried out using the computer requested include ab initio calculations of electronic structure and dynamics to investigate mechanisms of photodamage in nucleic acids and amino acids (Prof. Callis); calculations of conformational energies for improved synthesis of bioactive small molecules (Professors Livinghouse); and statistical analysis of large three dimensional data sets for environmental and epidemiological problems (Prof. Goodman). Users will communicate via a local area Ethernet installed in Chemistry and a broadband video link which is in place to other points on the MSU campus.
