Three Dimensional Structures of Carbohydrates and Glycoinformatics: An Overview
01 Jan 2018-pp 55-87
TL;DR: In this article, a 3D structural database for sialic acid-containing oligosaccharides (3DSDSCAR) was developed based on molecular dynamics simulation results, which can be used to study not only the structure and conformation but also the interaction of carbohydrates with its conjugated forms.
Abstract: Carbohydrates are regarded as the interesting molecules of nature because of their structural diversity and functional characteristics. The nature of existence of carbohydrates in varied forms and conformations is crucial in understanding their functional features in living systems. The dynamical behavior of carbohydrates in free or bound state with other biological molecules influences their functional role in biological systems. In N- and O-glycosylation, sequence, structure, and conformation of carbohydrates play a vital role. Hence, necessity arises for the complete understanding of the three-dimensional structures of carbohydrates. One of the theoretical ways of studying the structural and conformational aspect of carbohydrates is by molecular dynamics simulation. Not only the structure and conformation but also the interaction of carbohydrates with its conjugated forms can be investigated. The resources for carbohydrates in the form of databases available are discussed. Sialic acid-containing oligosaccharides which have an important role in molecular recognition phenomena are attributed to their sequence, structure, and conformational diversity. A three-dimensional structural database for sialic acid-containing carbohydrates (3DSDSCAR) developed based on molecular dynamics simulation results is discussed in detail. Glycoinformatics, knowledge about carbohydrates or glycans, is still a field of informatics to be explored more.
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TL;DR: This review is dedicated to approaches of chemo- and glyco-informatics towards 3D structural data generation, deposition and processing in regard to carbohydrates and their derivatives.
Abstract: Analysis and systematization of accumulated data on carbohydrate structural diversity is a subject of great interest for structural glycobiology. Despite being a challenging task, development of computational methods for efficient treatment and management of spatial (3D) structural features of carbohydrates breaks new ground in modern glycoscience. This review is dedicated to approaches of chemo- and glyco-informatics towards 3D structural data generation, deposition and processing in regard to carbohydrates and their derivatives. Databases, molecular modeling and experimental data validation services, and structure visualization facilities developed for last five years are reviewed.
22 citations
TL;DR: The Review leads the reader through the detailed presentations of the applications of computational modeling of carbohydrates and complex glycans, as exemplified by carbohydrate-active enzymes, transporters, lectins, antibodies, and glycosaminoglycan binding proteins.
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.
17 citations
TL;DR: Sarma et al. as mentioned in this paper performed molecular dynamics simulations for two trisaccharides HMOs (2'-FL and 3-FL) for 250 ns and the conformational models were subsequently substantiated by three replicate simulations.
Abstract: Human breast milk contains free oligosaccharides (Human Milk Oligosaccharides-HMOs) that help to protect breastfed infants against a variety of infectious diseases and act as decoy receptors. In breast milk, HMOs are the third most abundant compounds after lactose and lipids. Structural and conformational models of HMOs are quite crucial to studying the interaction with proteins and molecular recognition phenomenon. Molecular dynamics simulations for two trisaccharides HMOs (2'-FL and 3-FL) were carried out for 250 ns and the conformational models were subsequently substantiated by three replicate simulations. The conformer models of HMOs 2'-FL and 3-FL were deposited in the 3-Dimensional Structural Database for Sialic acid-containing CARbohydrates (3DSDSCAR) database website (www.3dsdscar.in). HMOs were then docked into the active site of norovirus capsid protein and are simulated for 100 ns duration. Each complex system was stabilized by direct and water-mediated hydrogen bonding interactions. Binding free energy calculations predict two possible binding modes for each complex system. The conformational flexibility and binding stability of the complex systems were calculated. The protein folding/unfolding and compactness seem to be better for the two HMOs. From a general perspective, we found that both 2'-FL and 3-FL exhibited higher binding efficacy towards norovirus capsid protein and according to the structural stability, 3-FL might be used as a preventive inhibitor for norovirus infection.Communicated by Ramaswamy H. Sarma.
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References
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TL;DR: A brief description of the origin and early uses of biomolecular simulations is presented, some recent studies that illustrate the utility of such simulations are outlined and their ever-increasing potential for contributing to biology is discussed.
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TL;DR: Examples are given of changes that occur in the carbohydrates of soluble and cell-surface glycoproteins during differentiation, growth and malignancy, which further highlight the important role of these substances in health and disease.
Abstract: During the last decade, there have been enormous advances in our knowledge of glycoproteins and the stage has been set for the biotechnological production of many of them for therapeutic use. These advances are reviewed, with special emphasis on the structure and function of the glycoproteins (excluding the proteoglycans). Current methods for structural analysis of glycoproteins are surveyed, as are novel carbohydrate-peptide linking groups, and mono- and oligo-saccharide constituents found in these macromolecules. The possible roles of the carbohydrate units in modulating the physicochemical and biological properties of the parent proteins are discussed, and evidence is presented on their roles as recognition determinants between molecules and cells, or cell and cells. Finally, examples are given of changes that occur in the carbohydrates of soluble and cell-surface glycoproteins during differentiation, growth and malignancy, which further highlight the important role of these substances in health and disease.
803 citations