Carbohydrate force fields

Abstract

Carbohydrates present a special set of challenges to the generation of force fields. First, the tertiary structures of monosaccharides are complex merely by virtue of their exceptionally high number of chiral centers. In addition, their electronic characteristics lead to molecular geometries and electrostatic landscapes that can be challenging to predict and model. The monosaccharide units can also interconnect in many ways, resulting in a large number of possible oligosaccharides and polysaccharides, both linear and branched. These larger structures contain a number of rotatable bonds, meaning they potentially sample an enormous conformational space. This article briefly reviews the history of carbohydrate force fields, examining and comparing their challenges, forms, philosophies, and development strategies. Then it presents a survey of recent uses of these force fields, noting trends, strengths, deficiencies, and possible directions for future expansion.

Ganglioside-Lipid and Ganglioside-Protein Interactions Revealed by Coarse-Grained and Atomistic Molecular Dynamics Simulations

“…81,83 Although atomistic simulations are the most detailed approach possible at the moment, sampling, in particular inside the bilayer environment, is a significant limitation. In addition, anomeric and exoanomeric effects 85 and CH-π interactions 86 are difficult to model and may affect the reliability of the atomistic simulations of saccharides.…”

Recent advances in employing molecular modelling to determine the specificity of glycan-binding proteins

“…Force fields for carbohydrates in many of the popular software packages have reached a generally reliable level of predictive accuracy, and continue to be refined [72]. Advances in high-performance computing, and particularly in the development of algorithms for use on graphics processing units (GPUs), are allowing MD simulations to be performed for significantly longer periods, and on larger systems, than was previously feasible with CPU-based implementations.…”

Optimizing Solute–Solute Interactions in the GLYCAM06 and CHARMM36 Carbohydrate Force Fields Using Osmotic Pressure Measurements

“…This can be especially difficult to achieve, however, when there is a scarcity of experimental data that can be directly compared to measurements from MD. 12 One way to establish a quantitative link between the thermodynamics of simulated and experimental intermolecular interactions is to perform simulations that measure the osmotic pressure of solutes in concentrated solutions. Murad et al 25–28 and Luo and Roux 29 have described a practical simulation method for doing this in which virtual walls are experienced by solute molecules that are not seen by solvent molecules.…”