CHARMM Additive All-Atom Force Field for Glycosidic Linkages between Hexopyranoses.
CHARMM Additive All-Atom Force Field for Glycosidic Linkages between Hexopyranoses.
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DOI：
10.1021/ct900242e
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发表时间：
2009-08-20
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;Hatcher, Elizabeth;Venable, Richard M.;Pastor, Richard W.;MacKerell, Alexander D., Jr.
我们提出了一个扩展的CHARMM吡喃己糖单糖添加剂的全原子力场，使建模的糖苷连接的吡喃己糖多糖。新的力场参数包括1→1、1→2、1→3、1→4和1→6六吡喃糖糖苷键，以及C1异头碳的O-甲基化，并与CHARMM蛋白质、核酸和脂质的全原子生物分子力场相一致。的参数是开发在一个层次的方式使用模型化合物中包含的关键原子的完整的碳水化合物，特别是O-甲基-四氢吡喃和糖苷连接的二聚体组成的两个分子的四氢吡喃或四氢吡喃和环己烷之一。参数优化的目标数据包括由二糖类似物中的Φ/β糖苷二面角定义的全二维能量表面，如通过MP2/6- 31 G（d）优化结构（MP2/cc-pVTZ//MP2/6- 31 G（d））上的量子力学MP2/cc-pVTZ单点能量所确定的。为了实现Φ/β糖苷二面角的平衡的、可转移的二面角参数，考虑了糖苷键中涉及的环碳原子处的所有可能手性的表面，导致超过5000个MP2/a-pVTZ//MP2/6- 31 G（d）构象能。作为目标数据还包括振动频率、与水分子的对相互作用能和距离，以及分子内几何形状，包括作为糖苷二面角的函数的糖苷价角的畸变。通过比较分子动力学结果与现有的实验数据，在全二糖上验证了模型化合物优化的力场参数。与实验的各种性质（包括晶胞参数和分子内几何形状、水密度以及与糖苷键相关的水核磁共振耦合常数）取得了良好的一致性。新开发的参数允许建模的线性，支链和环状的吡喃己糖糖苷单独和异质系统，包括蛋白质，核酸和/或脂质结合现有的CHARMM生物分子力场。
We present an extension of the CHARMM hexopyranose monosaccharide additive all-atom force field to enable modeling of glycosidic-linked hexopyranose polysaccharides. The new force field parameters encompass 1→1, 1→2, 1→3, 1→4, and 1→6 hexopyranose glycosidic linkages, as well as O-methylation at the C1 anomeric carbon, and are developed to be consistent with the CHARMM all-atom biomolecular force fields for proteins, nucleic acids, and lipids. The parameters are developed in a hierarchical fashion using model compounds containing the key atoms in the full carbohydrates, in particular O-methyl-tetrahydropyran and glycosidic-linked dimers consisting of two molecules of tetrahyropyran or one of tetrahydropyran and one of cyclohexane. Target data for parameter optimization include full two-dimensional energy surfaces defined by the Φ/Ψ glycosidic dihedral angles in the disaccharide analogs as determined by quantum mechanical MP2/cc-pVTZ single point energies on MP2/6-31G(d) optimized structures (MP2/cc-pVTZ//MP2/6-31G(d)). In order to achieve balanced, transferable dihedral parameters for the Φ/Ψ glycosidic dihedral angles, surfaces for all possible chiralities at the ring carbon atoms involved in the glycosidic linkages are considered, resulting in over 5000 MP2/cc-pVTZ//MP2/6-31G(d) conformational energies. Also included as target data are vibrational frequencies, pair interaction energies and distances with water molecules, and intramolecular geometries including distortion of the glycosidic valence angle as a function of the glycosidic dihedral angles. The model-compound optimized force field parameters are validated on full disaccharides through comparison of molecular dynamics results to available experimental data. Good agreement is achieved with experiment for a variety of properties including crystal cell parameters and intramolecular geometries, aqueous densities, and aqueous NMR coupling constants associated with the glycosidic linkage. The newly-developed parameters allow for the modeling of linear, branched, and cyclic hexopyranose glycosides both alone and in heterogenous systems including proteins, nucleic acids and/or lipids when combined with existing CHARMM biomolecular force fields.
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影响因子：
3
作者：
BROOKS, BR;BRUCCOLERI, RE;KARPLUS, M
通讯作者：
KARPLUS, M
影响因子：
3
作者：
Guvench, Olgun;Greene, Shannon N.;Kamath, Ganesh;Brady, John W.;Venable, Richard M.;Pastor, Richard W.;Mackerell, Alexander D., Jr.
通讯作者：
Mackerell, Alexander D., Jr.
影响因子：
5.5
作者：
Hatcher, Elizabeth R.;Guvench, Olgun;MacKerell, Alexander D., Jr.
通讯作者：
MacKerell, Alexander D., Jr.
影响因子：
4.4
作者：
FELLER, SE;ZHANG, YH;BROOKS, BR
通讯作者：
BROOKS, BR
影响因子：
3.4
作者：
Feller, SE;Yin, DX;MacKerell, AD
通讯作者：
MacKerell, AD