This award supports Carol A. Venanzi of the Department of Chemistry, New Jersey Institute of Technology, for collaboration with Jean-Luc Fauchere of the Department of Biotechnology, Swiss Federal Institute of Technology, Zurich and Michel Vallotton, Division of Endocrinology, University Hospital, Geneva. The objective of their research is to obtain an understanding of the relative contributions of the structural and electrostatic components of molecular recognition to the host-guest complexation process. The model system to be studied is a cyclic analog of adrenocorticotropic hormone (ACTH). This molecule was chosen because it can act as both a host (enzyme mimic) and a guest (hormone mimic). The U.S. investigator will use molecular modeling techniques combined with molecular dynamics simulations to provide information on the molecular recognition features of the proposed mimic, such as the orientation of the catalytic components as compared to chymotrypsin and the effect of solvent on conformation. The Swiss investigators will synthesize and test the biological activity of the target molecule. The advantage of the collaboration is that the investigators bring to the project distinctly complementary skills in computer modelling and experimental research along with an understanding and an appreciation of each other's methods. The proposed research addresses a challenging and important area of molecular chemical physics. The results will contribute to a better understanding of the structure and biocatalytic activity of enzymes by providing information on the mechanism of substrate recognition at the enzyme active site, as well as information on the requirements for molecular recognition at the hormone receptor. The successful synthesis of enzyme and hormone mimics will contribute greatly to the creation of cheaper and perhaps better substitutes for these biomaterials.
