Computational docking of antibody-antigen complexes, opportunities and pitfalls illustrated by influenza hemagglutinin.
Computational docking of antibody-antigen complexes, opportunities and pitfalls illustrated by influenza hemagglutinin.
复制标题
抗体 - 抗原络合物的计算对接，流感血凝素所说明的机会和陷阱。
DOI：
10.3390/ijms12010226
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发表时间：
2011-01-05
影响因子：
5.6
通讯作者：
Varani L
中科院分区：
文献类型：
--
作者：
Pedotti M;Simonelli L;Livoti E;Varani L
抗体在基础研究和制药工业中发挥着越来越重要的作用。由于它们的效率最终取决于它们与抗原的原子相互作用，因此研究这种相互作用对于了解它们如何发挥作用以及从长远来看设计具有所需特性的新分子非常重要。计算对接，从其分离的组分预测复合物的构象的过程，正在成为一种快速和负担得起的技术，用于抗体-抗原复合物的结构表征。在这篇手稿中，我们首先描述了不同的计算策略的建模抗体和对接其复合物，然后预测两种抗体的结合流感血凝素的茎区，一个重要的药物靶标。其目的有两个：在一个一般性的说明，我们想说明的优点和缺陷的计算对接与一个实际的例子，使用不同的方法和比较的结果，已知的实验结构。更具体地说，我们想评估对接是否可以成功地表征与具有未知结构的其他抗体的相同流感表位的结合，这对药物和生物学研究具有实际意义。这篇论文清楚地表明，一些计算对接预测可以非常准确，但算法往往无法区分它们与不准确的解决方案。因此，使用快速获得的实验数据来验证计算结果至关重要。
Antibodies play an increasingly important role in both basic research and the pharmaceutical industry. Since their efficiency depends, in ultimate analysis, on their atomic interactions with an antigen, studying such interactions is important to understand how they function and, in the long run, to design new molecules with desired properties. Computational docking, the process of predicting the conformation of a complex from its separated components, is emerging as a fast and affordable technique for the structural characterization of antibody-antigen complexes. In this manuscript, we first describe the different computational strategies for the modeling of antibodies and docking of their complexes, and then predict the binding of two antibodies to the stalk region of influenza hemagglutinin, an important pharmaceutical target. The purpose is two-fold: on a general note, we want to illustrate the advantages and pitfalls of computational docking with a practical example, using different approaches and comparing the results to known experimental structures. On a more specific note, we want to assess if docking can be successful in characterizing the binding to the same influenza epitope of other antibodies with unknown structure, which has practical relevance for pharmaceutical and biological research. The paper clearly shows that some of the computational docking predictions can be very accurate, but the algorithm often fails to discriminate them from inaccurate solutions. It is of paramount importance, therefore, to use rapidly obtained experimental data to validate the computational results.
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影响因子：
3
作者：
Cheng TM;Blundell TL;Fernandez-Recio J
通讯作者：
Fernandez-Recio J
影响因子：
3
作者：
Fanelli, F;Ferrari, S
通讯作者：
Ferrari, S
影响因子：
5.6
作者：
CHOTHIA, C;LESK, AM
通讯作者：
LESK, AM
影响因子：
5.6
作者：
AlLazikani, B;Lesk, AM;Chothia, C
通讯作者：
Chothia, C
影响因子：
5.6
作者：
Chaudhury, Sidhartha;Gray, Jeffrey J.
通讯作者：
Gray, Jeffrey J.