Intramolecular H-bonds govern the recognition of a flexible peptide by an antibody
- 30 March 2018
- journal article
- research article
- Published by Oxford University Press (OUP) in The Journal of Biochemistry
- Vol. 164 (1), 65-76
- https://doi.org/10.1093/jb/mvy032
Abstract
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.Keywords
Funding Information
- Photon Factory Advisory Committee (2013G378, 2014G190)
- Innovative R&D on Science and Technology
- FIRST
- JSPS
- Platform for Drug Discovery, Informatics, and Structural Life Science
- MEXT
- JSPS
- Grants-in-Aid for Scientific Research (25249115, 15K06962)
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