Systematic interaction analysis of anti-HIV-1 neutralizing antibodies with high mannose glycans by FMO and MD methods
Systematic interaction analysis of anti-HIV-1 neutralizing antibodies with high mannose glycans by FMO and MD methods
复制标题
通过 FMO 和 MD 方法系统分析抗 HIV-1 中和抗体与高甘露糖聚糖的相互作用
DOI：
10.1002/jcc.26073
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
K. Takano
中科院分区：
文献类型：
--
作者：
M. Kusumoto;K. Ueno-Noto;K. Takano
一系列名为PGT的广谱中和抗体已被证明通过糖蛋白gp120上的高甘露糖直接与人类免疫缺陷病毒1型结合。尽管抗体的氨基酸序列相似，但它们与多糖的亲和力不同。用量子化学碎片分子轨道计算和分子动力学模拟系统地比较了这些抗体之间的糖链-抗体相互作用。复合物活性部位的葡聚糖结构稳定性和总相互作用能以及糖链与抗体之间的结合自由能之间的差异与实验证明的糖链与抗体的亲和力是一致的。末端糖Man D3结构稳定，负责通过静电和分散相互作用与糖-抗体结合。非末端糖如Man 4或Man C的结构稳定性在通过直接氢键相互作用中起着重要作用。©2019威利期刊公司。
A series of broadly neutralizing antibodies called PGT have been shown to be bound directly to human immunodeficiency virus type‐1 via high mannose glycans on glycoprotein gp120. Despite the sequence similarities of amino acids of the antibodies, their affinities to the glycan differ. Glycan–antibody interactions among these antibodies are systematically compared with quantum chemical fragment molecular orbital calculations and molecular dynamics simulations. The differences among structural stability of the glycan in the active site of the complexes and total interaction energies as well as binding free energies between the glycan and antibodies agree well with the experimentally shown affinities of the glycan to the antibodies. The terminal saccharide, Man D3, is structurally stable and responsible for the glycan–antibody binding through electrostatic and dispersion interactions. The structural stability of nonterminal saccharides such as Man 4 or Man C plays substantial roles in the interaction via direct hydrogen bonds. © 2019 Wiley Periodicals, Inc.