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Center for Nonlinear Studies |
Sugar Folding: A Novel Structural Prediction Tool for Complex Carbohydrates in Solution
Carbohydrates are powerful biological markers and involved in numerous molecular recognition phenomena such as inflammatory processes, cancer metastasis, bacterial and viral infections, as well as other carbohydrate-mediated events. The three dimensional structure determination of sugars in solution is crucial to understand these phenomena and perform carbohydrate-based drug designs such as developing new antibiotics, HIV and cancer vaccines. We have developed an automated tool for the systematic prediction of conformations of complex carbohydrates in solution. The prediction tool consists of a ring perception module that automatically detects rotatable dihedrals, an exhaustive systematic search in dihedral space, a substructure matching algorithm for query- ing allowed conformations of previously studied substructures stored in a database of conformers, the optimization of allowed structures using gas phase or implicit solvation models (by interfacing to molecular packages), the calculation of NMR observables such as NOEs and RDCs in order to make a ranking of structures, and final explicit solvent MD simulations in order to refine structures and evaluate thermal averages around the global free energy minimum basin and adjacent accessible phase space regions. We have successfully applied our tool to study simple disaccharides, human milk oligosaccharides, and complex bacterial lipopolysaccharides.
Host: Gnana Gnanakaran, T-10