Molecular Modeling of Mechanical Stresses On Proteins In Glassy Carbohydrate-Water Matrices

Proteins are stabilized in carbohydrate-water solutions and in amorphous solids, but the mechanism of stabilization is not well understood and processes such as lyophilization remain largely empirical. In order to understand the properties of proteins in glassy matrices, simulation techniques were developed to investigate microscopic mechanical stresses, acting on atomic or whole-protein length scales, and the inherent structures of the protein. Microscopic mechanical stresses are shown to correlate with the secondary structure of the protein ubiquitin and with the heptad structure motif in a model coiled-coil protein. The introduction of a known stabilizing carbohydrate in solution, α,α-trehalose, non-monotonically alters the microscopic mechanical stresses of the protein and volume contraction of the protein upon vitrification. The goals of this project are to relate mechanical stresses to protein structure, and ultimately develop a bioinformatics capability for the engineering of protein stability in glassy matrices of varying carbohydrate-water composition.