Use of Raman and Raman optical activity to extract atomistic details of saccharides in aqueous solution

Abstract

Sugars are crucial components in biosystems and industrial applications. In aqueous environments, the natural state of short saccharides or charged glycosaminoglycans is floating and wiggling in solution. Therefore, tools to characterize their structure in a native aqueous environment are crucial but not always available. Here, we show that a combination of Raman/ROA and, on occasions, NMR experiments with Molecular Dynamics (MD) and Quantum Mechanics (QM) is a viable method to gain insights into structural features of sugars in solutions. Combining these methods provides information about accessible ring puckering conformers and their proportions. It also provides information about the conformation of the linkage between the sugar monomers, i.e., glycosidic bonds, allowing for identifying significantly accessible conformers and their relative abundance. For mixtures of sugar moieties, this method enables the deconvolution of the Raman/ROA spectra to find the actual amounts of its molecular constituents, serving as an effective analytical technique. For example, it allows calculating anomeric ratios for reducing sugars and analyzing more complex sugar mixtures to elucidate their real content. Altogether, we show that combining Raman/ROA spectroscopies with simulations is a versatile method applicable to saccharides. It allows for accessing many features with precision comparable to other methods routinely used for this task, making it a viable alternative. Furthermore, we prove that the proposed technique can scale up by studying the complicated Raffinose trisaccharide, and therefore, we expect its wide adoption to characterize sugar structural features in solution.

Glycosidic α-linked mannopyranose disaccharides: an NMR spectroscopy and molecular dynamics simulation study employing additive and Drude polarizable force fields

“…A number of studies based on NMR spectroscopy experiments and molecular modeling on mannose-based oligosaccharides have been reported over the years, with the results generally consistent with those obtained in the present study. For example, compounds M2M, M3M and M6M were studied by Palivec et al 114 using Raman spectroscopy combined with molecular modeling using the GLYCAM06 force field. 115 Free energy surfaces and sampling during the MD simulations of the a-(1-2)and a-(1-3)-linkages were similar to the present observations with respect to the highest probability region; however, a wider region of conformational space was sampled in comparison to both the C36 additive and Drude FF, though closer to that obtained with the Drude model with sampling observed in the vicinity of approximately f = 301 and c = 301 in both studies.…”

Emerging Era of Biomolecular Membrane Simulations: Automated Physically-Justified Force Field Development and Quality-Evaluated Databanks

“…Furthermore, publicly available tools and quality measures en-abling quantitative evaluation of MD simulations of other biomolecular systems than lipid bilayers, such as sugars or proteins, are not yet generally available-but there is certainly ongoing work towards providing them. 16,17,108,109 The flexible design of the NMRlipids Databank enables also inclusion of other systems than lipid bilayers in the future.…”