Multifaceted Computational Modeling in Glycoscience

Abstract

Glycoscience assembles all the scientific disciplines involved in studying various molecules and macromolecules containing carbohydrates and complex glycans. Such an ensemble involves one of the most extensive sets of molecules in quantity and occurrence since they occur in all microorganisms and higher organisms. Once the compositions and sequences of these molecules are established, the determination of their three-dimensional structural and dynamical features is a step toward understanding the molecular basis underlying their properties and functions. The range of the relevant computational methods capable of addressing such issues is anchored by the specificity of stereoelectronic effects from quantum chemistry to mesoscale modeling throughout molecular dynamics and mechanics and coarse-grained and docking calculations. The Review leads the reader through the detailed presentations of the applications of computational modeling. The illustrations cover carbohydrate−carbohydrate interactions, glycolipids, and N-and O-linked glycans, emphasizing their role in SARS-CoV-2. The presentation continues with the structure of polysaccharides in solution and solid-state and lipopolysaccharides in membranes. The full range of protein-carbohydrate interactions is presented, as exemplified by carbohydrate-active enzymes, transporters, lectins, antibodies, and glycosaminoglycan binding proteins. A final section features a list of 150 tools and databases to help address the many issues of structural glycobioinformatics. CONTENTS 5.1. N-and O-Linked Glycans 5.2. Structure and Dynamics of SARS-CoV-2 5.3. Structure, Function, and Dynamics of Glycolipids 6. Polysaccharides 6.1. Polysaccharides in Solution 6.2. Polysaccharides in the Solid-State 6.3. Lipolysaccharides in Membranes 7. Protein Carbohydrate Interactions 7.1. Presentation: Synopsis of the Protein Families 7.2. Insights into Glycosyltransferases 7.3. Insights into Glycosyl Hydrolases 7.4. Enzymatic Degradation of Polysaccharides in the Solid-State

Multivalent glycocyclopeptides: conjugation methods and biological applications

“…While the potential of these structures to interact with lectins or to stimulate immunity against tumor cells was clearly demonstrated, the selectivity remains the major issue to overcome. The utilization of advanced computational modelling methods 155 is undoubtedly a key tool to achieve this purpose by driving the design of glycomimetics or non-carbohydrate druglike lectin inhibitors capable to target secondary binding pockets of these proteins. 156,157 Besides this, the heterogenous expression of glycans at the surface of both normal and cancer cells is a crucial aspect to consider, making the design of multivalent systems much more complex than the simple multimerization of glycans on a scaffold.…”

The In Silico Characterization of Monocotyledonous α-l-Arabinofuranosidases on the Example of Maize

“…All models of maize proteins, AtARAF1 of A. thaliana , structures of fungal MgGH51, and bacterial Tx-Abf with replacement of catalytic acid/base E with Q and wild type enzyme were subjected to molecular docking with a number of substrates ( Table 2 ). In silico prediction of the specificity of glycoside hydrolases to a particular substrate is effective [ 78 ], as has already been demonstrated, including for the α- l -arabinofuranosidases of GH51 [ 79 ]. However, the results of such modeling should be treated with caution, since they are derived from predicted protein structures.…”

Primary Structure of Glycans by NMR Spectroscopy

“…Current complementary analytical techniques to NMR for the structural elucidation of glycans , are, e.g., infrared spectroscopy (IR), , liquid chromatography (LC), capillary electrophoresis (CE), and mass spectrometry (MS). , The conformation of carbohydrates and three-dimensional (3D) structure of glycans are interlinked to the determination of the “primary structure” of a glycan molecule and some aspects and potential caveats will also be touched upon. − …”