CHARMM additive all-atom force field for carbohydrate derivatives and its utility in polysaccharide and carbohydrate-protein modeling

By Olgun Guvench, S. Mallajosyula, E. P. Raman, Elizabeth Hatcher, Kenno Vanommeslaeghe, T. J. Foster, Francis W Jamison, Alexander D. MacKerell. Journal of Chemical Theory and Computation, 2011

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Monosaccharide derivatives such as xylose, fucose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GlaNAc), glucuronic acid, iduronic acid, and N-acetylneuraminic acid (Neu5Ac) are important components of eukaryotic glycans. The present work details development of force-field parameters for these monosaccharides and their covalent connections to proteins via O-linkages to serine or threonine sidechains and via N-linkages to asparagine sidechains. The force field development protocol was designed to explicitly yield parameters that are compatible with the existing CHARMM additive force field for proteins, nucleic acids, lipids, carbohydrates, and small molecules. Therefore, when combined with previously developed parameters for pyranose and furanose monosaccharides, for glycosidic linkages between monosaccharides, and for proteins, the present set of parameters enables the molecular simulation of a wide variety of biologically-important molecules such as complex carbohydrates and glycoproteins. Parametrization included fitting to quantum mechanical (QM) geometries and conformational energies of model compounds, as well as to QM pair interaction energies and distances of model compounds with water. Parameters were validated in the context of crystals of relevant monosaccharides, as well NMR and/or x-ray crystallographic data on larger systems including oligomeric hyaluronan, sialyl Lewis X, O- and N-linked glycopeptides, and a lectin:sucrose complex. As the validated parameters are an extension of the CHARMM all-atom additive biomolecular force field, they further broaden the types of heterogeneous systems accessible with a consistently-developed force-field model.

Subfields: Materials Chemistry, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9107146664efa61a94d1255696bd0fe01f7d7c7b

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Citations in the corpus

• Nano-engineering of construction materials using molecular dynamics simulations: Prospects and challenges (2018, methodology): “The forcefields including CHARMM [117] and GROMOS [118] are commonly applied.”
• Predicting binding free energies: Frontiers and benchmarks (2016, background): “It is also worth noting that, because the CDs are glucose polymers, they may be best modeled with dedicated carbohydrate force fields [22, 72, 94, 195], rather than generalized small molecule force fields.”