CHARMM additive all-atom force field for carbohydrate derivatives and its utility in polysaccharide and carbohydrate-protein modeling.
CHARMM additive all-atom force field for carbohydrate derivatives and its utility in polysaccharide and carbohydrate-protein modeling.
复制标题
DOI：
10.1021/ct200328p
复制
发表时间：
2011-10-11
影响因子：
5.5
通讯作者：
MacKerell, Alexander D., Jr.
中科院分区：
文献类型：
--
作者：
Guvench, Olgun;Mallajosyula, Sairam S.;Raman, E. Prabhu;Hatcher, Elizabeth;Vanommeslaeghe, Kenno;Foster, Theresa J.;Jamison, Francis W., II;MacKerell, Alexander D., Jr.
单糖衍生物如木糖、岩藻糖、N-乙酰葡糖胺（GlcNAc）、N-乙酰半乳糖胺（GlaNAc）、葡糖醛酸、艾杜糖醛酸和N-乙酰神经氨酸（Neu 5Ac）是真核生物聚糖的重要组分。本工作的详细发展力场参数为这些单糖和它们的共价连接蛋白质通过O-连接丝氨酸或苏氨酸侧链和通过N-连接天冬酰胺侧链。力场开发方案旨在明确产生与蛋白质、核酸、脂质、碳水化合物和小分子的现有CHARMM加性力场兼容的参数。因此，当与先前开发的吡喃糖和呋喃糖单糖、单糖之间的糖苷键和蛋白质的参数相结合时，本参数集能够对多种生物学上重要的分子如复杂的碳水化合物和糖蛋白进行分子模拟。参数化包括拟合模型化合物的量子力学（QM）几何形状和构象能，以及QM对相互作用能和模型化合物与水的距离。参数进行了验证的背景下，晶体的相关单糖，以及NMR和/或X-射线晶体学数据的较大系统，包括低聚透明质酸，唾液酸刘易斯X，O-和N-连接的糖肽，和凝集素：蔗糖复合物。由于验证的参数是CHARMM全原子添加剂生物分子力场的扩展，它们进一步拓宽了可使用一致开发的力场模型访问的非均质系统的类型。
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.
登录
查看更多内容
影响因子：
5.6
作者：
Almond, A;DeAngelis, PL;Blundell, CD
通讯作者：
Blundell, CD
影响因子：
--
作者：
Durier, V;Tristram, F;Vergoten, G
通讯作者：
Vergoten, G
影响因子：
4.3
作者：
Fernandez-Tejada, Alberto;Corzana, Francisco;Peregrina, Jesus M.
通讯作者：
Peregrina, Jesus M.
影响因子：
16.8
作者：
Banerji, Suneale;Wright, Alan J.;Jackson, David G.
通讯作者：
Jackson, David G.
影响因子：
3
作者：
BROOKS, BR;BRUCCOLERI, RE;KARPLUS, M
通讯作者：
KARPLUS, M