Li Chun Hua, Ma Xiao Hui, Chen Wei Zu, Wang Cun Xin
College of Life Science and Bioengineering, Beijing University of Technology, Beijing, China.
Proteins. 2003 Jul 1;52(1):47-50. doi: 10.1002/prot.10382.
An efficient soft docking algorithm is described for predicting the mode of binding between an antibody and its antigen based on the three-dimensional structures of the molecules. The basic tools are the "simplified protein" model and the docking algorithm of Wodak and Janin. The side-chain flexibility of Arg, Lys, Asp, Glu, and Met residues on the protein surface is taken into account. A combined filtering technique is used to select candidate binding modes. After energy minimization, we calculate a scoring function, which includes electrostatic and desolvation energy terms. This procedure was applied to targets 04, 05, and 06 of CAPRI, which are complexes of three different camelid antibody VHH variable domains with pig alpha-amylase. For target 06, two native-like structures with a root-mean-square deviation < 4.0 A relative to the X-ray structure were found within the five top ranking structures. For targets 04 and 05, our procedure produced models where more than half of the antigen residues forming the epitope were correctly predicted, albeit with a wrong VHH domain orientation. Thus, our soft docking algorithm is a promising tool for predicting antibody-antigen recognition.
描述了一种有效的软对接算法，用于基于分子的三维结构预测抗体与其抗原之间的结合模式。基本工具是“简化蛋白质”模型以及沃达克（Wodak）和雅南（Janin）的对接算法。考虑了蛋白质表面精氨酸（Arg）、赖氨酸（Lys）、天冬氨酸（Asp）、谷氨酸（Glu）和甲硫氨酸（Met）残基的侧链灵活性。使用组合过滤技术来选择候选结合模式。在能量最小化之后，我们计算一个评分函数，该函数包括静电能和去溶剂化能项。此程序应用于蛋白质-配体相互作用预测挑战赛（CAPRI）的目标04、05和06，它们是三种不同骆驼科动物抗体VHH可变结构域与猪α-淀粉酶的复合物。对于目标06，在排名前五的结构中发现了两个与X射线结构的均方根偏差<4.0 Å的类似天然结构。对于目标04和05，我们的程序生成的模型中，形成表位的抗原残基有一半以上被正确预测，尽管VHH结构域方向错误。因此，我们的软对接算法是预测抗体-抗原识别的一个有前途的工具。
