Application of asymmetric statistical potentials to antibody-protein docking
Application of asymmetric statistical potentials to antibody-protein docking
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DOI：
10.1093/bioinformatics/bts493
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发表时间：
2012-10-15
期刊：
影响因子：
5.8
通讯作者：
Kozakov, Dima
中科院分区：
文献类型：
--
作者：
Brenke, Ryan;Hall, David R.;Kozakov, Dima
动机：用于抗体蛋白质抗原复合物预测的有效对接算法是迈向设计生物制剂和疫苗的重要第一步。我们最近开发了一种新的基于知识的互动电位，称为诱饵作为参考状态（DARS），并根据快速傅立叶变换相关方法将DARS纳入了Docking Program Piper。尽管Piper是CAPRI蛋白对接实验最新一轮的表现最好的表现，但与其他类型的配合物相比，对接抗体蛋白抗原对的准确性要少得多，尽管将基于序列的信息纳入了羊皮纸的位置。抗体蛋白质抗原复合物的分析揭示了这些界面内固有的不对称性。具体而言，苯丙氨酸，色氨酸和酪氨酸残基高度填充了抗体的副群，而不是抗原的表位。抗原的表位：由于无法使用对称的成对潜能对这种不对称性进行充分的建模，因此我们已经去除了对称性的通常假设。在假设抗体上的特定原子与抗原蛋白上的相同原子不同的假设下，从抗体蛋白质复合物中提取了相互作用统计。新电位的使用显着提高了抗体蛋白质抗原复合物的对接性能，即使没有有关果汁膜位置的任何序列信息。我们注意到，不对称电位捕获了抗体 - 蛋白质抗原界面中复杂环境固有的多体相互作用的影响。
Motivation: An effective docking algorithm for antibody-protein antigen complex prediction is an important first step toward design of biologics and vaccines. We have recently developed a new class of knowledge-based interaction potentials called Decoys as the Reference State (DARS) and incorporated DARS into the docking program PIPER based on the fast Fourier transform correlation approach. Although PIPER was the best performer in the latest rounds of the CAPRI protein docking experiment, it is much less accurate for docking antibody-protein antigen pairs than other types of complexes, in spite of incorporating sequence-based information on the location of the paratope. Analysis of antibody-protein antigen complexes has revealed an inherent asymmetry within these interfaces. Specifically, phenylalanine, tryptophan and tyrosine residues highly populate the paratope of the antibody but not the epitope of the antigen.Results: Since this asymmetry cannot be adequately modeled using a symmetric pairwise potential, we have removed the usual assumption of symmetry. Interaction statistics were extracted from antibody-protein complexes under the assumption that a particular atom on the antibody is different from the same atom on the antigen protein. The use of the new potential significantly improves the performance of docking for antibody-protein antigen complexes, even without any sequence information on the location of the paratope. We note that the asymmetric potential captures the effects of the multi-body interactions inherent to the complex environment in the antibody-protein antigen interface.