Vina-Carb: Improving Glycosidic Angles during Carbohydrate Docking.
Vina-Carb: Improving Glycosidic Angles during Carbohydrate Docking.
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DOI：
10.1021/acs.jctc.5b00834
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发表时间：
2016-02-09
影响因子：
5.5
通讯作者：
Woods RJ
中科院分区：
文献类型：
--
作者：
Nivedha AK;Thieker DF;Makeneni S;Hu H;Woods RJ
分子对接程序主要设计用于将刚性药物样片段对齐到大分子的结合位点中，并且当应用于柔性碳水化合物分子时经常显示出较差的性能。寡糖内柔性的关键来源是糖苷键。最近，碳水化合物固有（CHI）能量函数的报道，试图量化的糖苷扭转角的偏好。在目前的工作中，CHI能量函数已被纳入AutoDock维纳（ADV）评分函数，随后被称为Vina-Carb（VC）。已经引入了两个用户可调节的参数，即，影响CHI能量惩罚的幅度的CHI能量权重项（chi_coeff）和否定低于指定值的CHI能量惩罚的CHI截止项（chi_cutoff）。由101种蛋白质-碳水化合物复合物和29种载脂蛋白结构组成的数据集用于VC的开发和测试，包括抗体、凝集素和碳水化合物结合模块。占分子内能量的糖苷键的寡糖在对接导致VC产生可接受的结构在前五名排名的姿势在74%的系统测试，相比ADV的成功率为55%。酶系统，以说明潜在的应用VC的蛋白质，可能会扭曲糖配体的糖苷键结合后。VC代表了准确预测蛋白质-碳水化合物复合物结构的重要一步。此外，所描述的方法在概念上适用于填充明确定义的构象状态的任何类别的配体。
Molecular docking programs are primarily designed to align rigid, drug-like fragments into the binding sites of macromolecules and frequently display poor performance when applied to flexible carbohydrate molecules. A critical source of flexibility within an oligosaccharide is the glycosidic linkages. Recently, Carbohydrate Intrinsic (CHI) energy functions were reported that attempt to quantify the glycosidic torsion angle preferences. In the present work, the CHI-energy functions have been incorporated into the AutoDock Vina (ADV) scoring function, subsequently termed Vina-Carb (VC). Two user-adjustable parameters have been introduced, namely, a CHI- energy weight term (chi_coeff) that affects the magnitude of the CHI-energy penalty and a CHI-cutoff term (chi_cutoff) that negates CHI-energy penalties below a specified value. A data set consisting of 101 protein–carbohydrate complexes and 29 apoprotein structures was used in the development and testing of VC, including antibodies, lectins, and carbohydrate binding modules. Accounting for the intramolecular energies of the glycosidic linkages in the oligosaccharides during docking led VC to produce acceptable structures within the top five ranked poses in 74% of the systems tested, compared to a success rate of 55% for ADV. An enzyme system was employed in order to illustrate the potential application of VC to proteins that may distort glycosidic linkages of carbohydrate ligands upon binding. VC represents a significant step toward accurately predicting the structures of protein–carbohydrate complexes. Furthermore, the described approach is conceptually applicable to any class of ligands that populate well-defined conformational states.
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