De Novo Design: Sugar Binding

Abstract

De Novo Design: Sugar BindingANNIE MCALLISTER, Kenneth Foreman, Department of Chemistry and Biochemistry, George Mason University.Although nature provides proteins that bind sugars, the exact forces that lead to specific binding or high affinity complexation are poorly understood. De novo design seeks to understand the fundamental chemistry of proteins and particularly what forces drives their intra- and inter- molecular interactions. We have applied de novo design approaches in a virtual setting to model the binding of glucose, ribofuranose, and phosphoribose to a four-helix bundle originally intended to bind heme. Three binding sites were created by modifying the protein sidechains in Chimera to create opportunities for hydrogen bond formation with the sugars. Two sites were made specifically to bind ribose while the third was intended to bind glucose. The sugars were docked and scored in AutoDock. All sites had specificity for one sugar over the others. However, the phosphoribose featured stronger predicted binding in the site designed for ribose than the ribofuranose itself. These results suggest a combination of sterics and well-placed electrostatic interactions drive specificity in protein-sugar interactions.