Predicting the Structures of Glycans, Glycoproteins, and Their Complexes

Abstract

Complex carbohydrates are ubiquitous in nature, and together with proteins and nucleic acids they comprise the building blocks of life. But unlike proteins and nucleic acids, carbohydrates form nonlinear polymers, and they are not characterized by robust secondary or tertiary structures but rather by distributions of well-defined conformational states. Their molecular flexibility means that oligosaccharides are often refractory to crystallization, and nuclear magnetic resonance (NMR) spectroscopy augmented by molecular dynamics (MD) simulation is the leading method for their characterization in solution. The biological importance of carbohydrate-protein interactions, in organismal development as well as in disease, places urgency on the creation of innovative experimental and theoretical methods that can predict the specificity of such interactions and quantify their strengths. Additionally, the emerging realization that protein glycosylation impacts protein function and immunogenicity places the ability to define the mechanisms by which glycosylation impacts these features at the forefront of carbohydrate modeling. This review will discuss the relevant theoretical approaches to studying the three-dimensional structures of this fascinating class of molecules and interactions, with reference to the relevant experimental data and techniques that are key for validation of the theoretical predictions.

Induction of Rare Conformation of Oligosaccharide by Binding to Calcium-dependent Bacterial Lectin: X-ray Crystallography and Modelling Study

“…In the β anomer, a minor population (13%) of α -syn conformation was predicted from a 5 ns MD simulation [40]. We note, however, that this percentage is dependent both, on the force-field type and version and on the length of simulation, all variables that have been improved since [41]. The β amide bond dihedral was found by NMR to be predominantly in trans (98%) with a high barrier of 19-20 kcal/mol to conversion to β cis [21].…”

Materials science based on synthetic polysaccharides

“…Moreover, the conformation of most polysaccharides in solution remains elusive, as the intrinsic flexibility of polysaccharides limits the use of conventional techniques, that produce averaged information. MD simulations can help the prediction of oligosaccharide conformation in water, 23 but a lack of validation standards has slowed down the development of reliable simulation packages. In recent years, new force fields, optimized for carbohydrates, have become more accurate and user friendly.…”

Blood Type Diets (BTD) and Aging: An Overview

“…The main carbohydrates included in human diet are polysaccharides in the form of starches, with variable chain length, monosaccharides and disaccharides (sucrose and lactose) [80]. There are other nonstarchy carbohydrates, normally called dietary fibres, that do not possess either α or α glycosidic bonds and are hence not hydolysable by the human digestive enzymes [1,4,6,81]. Indeed, non-digestible plant fibers can be divided into insoluble (cellulose, hemicellulose and lignin) and soluble (gums and pectins) fibers [82].…”

“…It is a well-established fact, now, that complex carbohydrates are ubiquitous in nature [1]. Carbohydrates are also called glycans to underline the functional diversity and complexity of their structural composition [2].…”