期刊
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
卷 7, 期 10, 页码 3162-3180出版社
AMER CHEMICAL SOC
DOI: 10.1021/ct200328p
关键词
-
资金
- NIH [GM070855]
- University of New England College of Pharmacy
- Department of Defense
- NPACI Alliance
- Division Of Chemistry
- Direct For Mathematical & Physical Scien [0823198] Funding Source: National Science Foundation
Monosaccharide derivatives such as xylose, fucose, N-acetylglucosarnine (GlcNAc), N-acetylgalactosamine (GlaNAc), glucuronic acid, iduronic acid, and N-acetylneuraminic acid (Neu5Ac) are important components of eukaryotic glycans. The present work details the development of force-field parameters for these monosaccharides and their covalent connections to proteins via O linkages to serine or threonine side chains and via N linkages to asparagine side chains. 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据