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Antibodies 2018, 7(3), 25; https://doi.org/10.3390/antib7030025

Molecular Recognition between Aβ-Specific Single-Domain Antibody and Aβ Misfolded Aggregates

1
Department of Chemical & Biomolecular Engineering, the University of Akron, Akron, OH 44325, USA
2
Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA
3
Sackler Institute of Molecular Medicine, Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
*
Authors to whom correspondence should be addressed.
Received: 31 May 2018 / Revised: 6 July 2018 / Accepted: 9 July 2018 / Published: 13 July 2018
(This article belongs to the Special Issue Computational Antibody and Antigen Design)
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Abstract

Aβ is the toxic amyloid polypeptide responsible for Alzheimer’s disease (AD). Prevention and elimination of the Aβ misfolded aggregates are the promising therapeutic strategies for the AD treatments. Gammabody, the Aβ-Specific Single-domain (VH) antibody, recognizes Aβ aggregates with high affinity and specificity and reduces their toxicities. Employing the molecular dynamics simulations, we studied diverse gammabody-Aβ recognition complexes to get insights into their structural and dynamic properties and gammabody-Aβ recognitions. Among many heterogeneous binding modes, we focused on two gammabody-Aβ recognition scenarios: recognition through Aβ β-sheet backbone and on sidechain surface. We found that the gammabody primarily uses the complementarity-determining region 3 (CDR3) loop with the grafted Aβ sequence to interact with the Aβ fibril, while CDR1/CDR2 loops have very little contact. The gammabody-Aβ complexes with backbone binding mode are more stable, explaining the gammabody’s specificity towards the C-terminal Aβ sequence. View Full-Text
Keywords: single-domain antibodies; Aβ peptide; amyloid antibody; Alzheimer’s disease; antibody recognition single-domain antibodies; Aβ peptide; amyloid antibody; Alzheimer’s disease; antibody recognition
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Zhang, M.; Zheng, J.; Nussinov, R.; Ma, B. Molecular Recognition between Aβ-Specific Single-Domain Antibody and Aβ Misfolded Aggregates. Antibodies 2018, 7, 25.

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