With support from the Organic Dynamics Program, Dr. Gellman will evaluate the contribution made by hydrogen bonds that involve amide groups toward determining the overall conformational stability of globular proteins. The project utilizes small, flexible molecules that contain a limited number of amide groups to dissect the contribution of this one particular class of non-covalent interaction. Results obtained from this work are expected to afford increased understanding of the factors that determine three-dimensional protein structure and, accordingly, that direct the biological function (enzymatic, regulatory or structural) of a globular protein. Conformational preferences in the various model systems will be studied spectroscopically under conditions in which internal hydrogen bonds are energetically significant. Conformational preferences observed in a series of closely related oligoamides should provide information about the manner in which hydrogen bond strength is affected by the spatial orientation of the bonding partners. This analysis also should reveal the manner in which hydrogen bonds are affected by other internal non-covalent interactions, and also how they are affected by the environment (e.g., solvent).
