CHARMM Additive All-Atom Force Field for Phosphate and Sulfate Linked to Carbohydrates.
CHARMM Additive All-Atom Force Field for Phosphate and Sulfate Linked to Carbohydrates.
复制标题
DOI：
10.1021/ct200792v
复制
发表时间：
2012-02-14
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：
Mallajosyula, Sairam S.;Guvench, Olgun;Hatcher, Elizabeth;MacKerell, Alexander D., Jr.
提出的是CHARMM加性全原子碳水化合物力场的扩展，以使与碳水化合物连接的磷酸盐和硫酸盐的建模成为可能。使用模型化合物中含有的关键原子在充分的碳水化合物的参数开发在一个层次的方式。参数优化的目标数据包括由己吡喃糖单糖磷酸盐和硫酸盐的磷酸盐/硫酸盐模型化合物类似物中的糖苷二面角对定义的全二维能量表面，如通过MP2/6-31+G（d）优化结构上的量子力学（QM）MP2/cc-pVTZ单点能量所确定的。为了实现二面角的平衡、可转移的二面角参数，在参数化过程中包括所有可能的异头和构象状态的表面。此外，模拟生理相关系统的单和双阴离子带电状态进行了研究的磷酸盐。这导致超过7000个MP2/cc-pVTZ//MP2/6- 31 G+（d）模型化合物构象能，其补充有QM几何形状，是参数化的主要目标数据。针对从剑桥结构数据库（CSD）和更大系统获得的相关单糖衍生物的晶体验证参数，所述单糖衍生物即非共价结合至普列克底物蛋白同源性（PH）结构域的肌醇-（三/四/五）磷酸酯和溶液中的寡聚硫酸软骨素以及与组织蛋白酶K蛋白复合的寡聚硫酸软骨素。
Presented is an extension of the CHARMM additive all-atom carbohydrate force field to enable the modeling of phosphate and sulfate linked to carbohydrates. The parameters are developed in a hierarchical fashion using model compounds containing the key atoms in the full carbohydrates. Target data for parameter optimization included full two-dimensional energy surfaces defined by the glycosidic dihedral angle pairs in the phosphate/sulfate model compound analogs of hexopyranose monosaccharide phosphates and sulfates, as determined by quantum mechanical (QM) MP2/cc-pVTZ single point energies on MP2/6-31+G(d) optimized structures. In order to achieve balanced, transferable dihedral parameters for the dihedral angles, surfaces for all possible anomeric and conformational states were included during the parametrization process. In addition, to model physiologically relevant systems both the mono- and di-anionic charged states were studied for the phosphates. This resulted in over 7000 MP2/cc-pVTZ//MP2/6-31G+(d) model compound conformational energies which, supplemented with QM geometries, were the main target data for the parametrization. Parameters were validated against crystals of relevant monosaccharide derivatives obtained from the Cambridge Structural Database (CSD) and larger systems, namely inositol-(tri/tetra/penta) phosphates non-covalently bound to the pleckstrin homology (PH) domain and oligomeric chondroitin sulfate in solution and in complex with cathepsin K protein.
登录
查看更多内容
影响因子：
19
作者：
Corvera, S;Czech, MP
通讯作者：
Czech, MP
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
作者：
Basma, M;Sundara, S;Woods, RJ
通讯作者：
Woods, RJ
影响因子：
11.4
作者：
Cronin, TC;DiNitto, JP;Lambright, DG
通讯作者：
Lambright, DG
影响因子：
16
作者：
Ferguson, KM;Kavran, JM;Lemmon, MA
通讯作者：
Lemmon, MA