Delineating the Dynamic Conformations of Oligosaccharides by Combining Molecular Simulation and NMR Spectroscopy

抄録

Oligosaccharides are highly flexible molecules with significant degrees of freedom in their structures. To gain insights into the molecular basis of their biological functions, it is important to describe the conformational dynamics of oligosaccharides. The combination of molecular simulations and nuclear magnetic resonance (NMR) spectroscopy is an effective method for quantitatively interpreting the dynamic behaviors of oligosaccharides. In NMR analyses, paramagnetic-tagging of oligosaccharides provides information on their overall conformations; paramagnetism-assisted NMR methods can facilitate the validation of oligosaccharide dynamical structures originally derived from molecular dynamics simulations. Using this approach, the dynamic conformations of a series of sialyl oligosaccharides found in gangliosides and high-mannose-type oligosaccharides involved in the glycoprotein quality control system were revealed. The quantitative descriptions of their conformational spaces also provided the dynamic views of oligosaccharide–lectin interactions, which complemented static insights from crystallographic analyses. Understanding the oligosaccharide–lectin binding process enables the design of oligosaccharides with enhanced affinity and specificity for target proteins.