Intramolecular H-bonds govern the recognition of a flexible peptide by an antibody
Intramolecular H-bonds govern the recognition of a flexible peptide by an antibody
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DOI：
10.1093/jb/mvy032
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发表时间：
2018-07-01
影响因子：
2.7
通讯作者：
Tsumoto, Kouhei
中科院分区：
文献类型：
--
作者：
Miyanabe, Kazuhiro;Akiba, Hiroki;Tsumoto, Kouhei
分子识别是基本上每个生物过程核心的基本事件。特别地，分子间H-键已被认为是抗体-抗原相互作用中的关键稳定力，导致精确的特异性和高亲和力。虽然同样丰富，分子内氢键的作用是远远不够清楚，并没有得到普遍承认。在此，我们已经进行了分子水平的研究，剖析了分子内的H-键的柔性肽的抗体识别的贡献。我们发现，分子内氢键可能有一个深刻的，多方面的和有利的影响，结合亲和力高达2千卡摩尔（-1）的自由能。总的来说，我们的研究结果表明，抗体被微调，以识别在溶液中的柔性肽的瞬时稳定结构，其中分子内H-键起着关键作用。
Molecular recognition is a fundamental event at the core of essentially every biological process. In particular, intermolecular H-bonds have been recognized as key stabilizing forces in antibody-antigen interactions resulting in exquisite specificity and high affinity. Although equally abundant, the role of intramolecular H-bonds is far less clear and not universally acknowledged. Herein, we have carried out a molecular-level study to dissect the contribution of intramolecular H-bonds in a flexible peptide for the recognition by an antibody. We show that intramolecular H-bonds may have a profound, multifaceted and favorable effect on the binding affinity by up to 2 kcal mol(-1) of free energy. Collectively, our results suggest that antibodies are fine tuned to recognize transiently stabilized structures of flexible peptides in solution, for which intramolecular H-bonds play a key role.