Carbohydrates play an important role in many biological and pathological events. While there is significant potential utility for carbohydrate recognition receptors, design is often challenged by the low specificity and affinity due to the structural similarity between different monosaccharides. Recent studies have shown that aromatic oligoamide foldamer helices can selectively encapsulate fructose demonstrating that foldamers can be used as a synthetic receptor for carbohydrates. A library of the aryl amide monomers units are available to design and build helical foldamers, however, the effect of sequence on foldamer structure can only be qualitatively predicted. As a result, design of these foldamers requires iterative labor-intensive organic synthesis to explore sequence space and achieve high affinity and selectivity for carbohydrate binding partners. Computational tools can be used to accelerate this process. We employ computational approaches including molecular dynamics coupled with simulated annealing to predict the structure of the folder-carbohydrate complex. To ensure accuracy in MD simulations of foldamers, we re-parameterized the existing force field and optimized parameters for a series of aryl amide foldamer monomer units. We have benchmarked and optimized our structure prediction protocol using complex structures determined by x-ray crystallography and NMR. While MD simulations reliably predict the correct structure, they reveal additional binding modes not seen in the crystal structure. Scoring schemes used to rank the binding modes are currently being developed.<br/>

Computational structure prediction of arylamide foldamer helices encapsulating monosaccharides

2019 Fall National Meeting

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