Experimental and computational characterization of dynamic biomolecular interaction systems involving glycolipid glycans

On cell surfaces, carbohydrate chains that modify proteins and lipids mediate various biological functions, which are exerted not only through carbohydrate-protein interactions but also through carbohydrate-carbohydrate interactions. These glycans exhibit considerable degrees of conformational variability and often form clusters providing multiple binding sites. The integration of nuclear magnetic resonance spectroscopy and molecular dynamics simulation has made it possible to delineate the dynamical structures of carbohydrate chains. This approach has facilitated the remodeling of oligosaccharide conformational space in the prebound state to improve protein-binding affinity and has been applied to visualize dynamic carbohydrate-carbohydrate interactions that control glycoprotein-glycoprotein complex formation. Functional glycoclusters have been characterized by experimental and computational approaches applied to various model membranes and artificial self-assembling systems. This line of investigation has provided dynamic views of molecular assembling on glycoclusters, giving mechanistic insights into physiological and pathological molecular events on cell surfaces as well as clues for the design and creation of molecular systems exerting improved glycofunctions. Further development and accumulation of such studies will allow detailed understanding and artificial control of the glycosynapse foreseen by Dr. Sen-itiroh Hakomori.

Automated summary

Carbohydrate chains on cell surfaces play important roles in mediating various biological functions through both carbohydrate-protein and carbohydrate-carbohydrate interactions. The combination of nuclear magnetic resonance spectroscopy and molecular dynamics simulation allows for the investigation of the dynamical structures of these carbohydrate chains. This approach has been used to improve protein-binding affinity by remodeling the conformational space of oligosaccharides and to visualize dynamic carbohydrate-carbohydrate interactions. Understanding and controlling these processes have implications for designing molecular systems with improved glycofunctions.