Collaborative Research: A General Approach to the Design of Tailor-Made Glycan Recognition Protein Modules.

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Protein-carbohydrate interactions play an important role in several biological processes, such as cell growth and differentiation, signal transduction, apoptosis, and fertilization. From a molecular recognition perspective, glycans are challenging ligands, in that they differ from each other simply by the point of attachment to each other, or by the position of single hydroxyl groups. Further, glycan based biopolymers are flexible and highly hydrated. The objective of this project is to understand at the molecular level protein-glycan interactions in a model system, and to use this knowledge to develop novel glycan recognition proteins through an integrated computational and experimental strategy. Starting from a natural glycan binding protein, cyanovirin, we will explore the sequence space that supports high-affinity binding to the target glycan in parallel, utilizing directed evolution on the experimental side, and fast docking methods as well as explicit solvent molecular dynamics simulations on the computational side.The Broader Impact of this proposal is twofold. First, the project relies on a highly interdisciplinary approach, which offers students at the graduate and undergraduate level a rich training experience. Second, the PIs participate in outreach activities at the high school level both at Iowa and at ASU. At ASU, Ozkan and Ghirlanda participate with this project to the ASU Math and Science Teaching Fellows program run by CRESMET (http://cresmet.asu.edu/MSTF/index.shtml). The program brings high school teachers from disadvantaged schools in the Phoenix area to ASU for research internships combined with intensive training in science education techniques, and establishes a rapport between schools and university that continues through campus visits. Margulis has created a mentor matching program (http://mentor.chem.uiowa.edu/) that through the Upward Bound Program integrates underrepresented high school students in research groups.