Molecular interactions between monoclonal oligomer-specific antibody 5E3 and its amyloid beta cognates

PLoS One. 2020 May 29;15(5):e0232266. doi: 10.1371/journal.pone.0232266. eCollection 2020.


Oligomeric amyloid β (Aβ) is currently considered the most neurotoxic form of the Aβ peptide implicated in Alzheimer's disease (AD). The molecular structures of the oligomers have remained mostly unknown due to their transient nature. As a result, the molecular mechanisms of interactions between conformation-specific antibodies and their Aβ oligomer (AβO) cognates are not well understood. A monoclonal conformation-specific antibody, m5E3, was raised against a structural epitope of Aβ oligomers. m5E3 binds to AβOs with high affinity, but not to Aβ monomers or fibrils. In this study, a computational model of the variable fragment (Fv) of the m5E3 antibody (Fv5E3) is introduced. We further employ docking and molecular dynamics simulations to determine the molecular details of the antibody-oligomer interactions, and to classify the AβOs as Fv5E3-positives and negatives, and to provide a rationale for the low affinity of Fv5E3 for fibrils. This information will help us to perform site-directed mutagenesis on the m5E3 antibody to improve its specificity and affinity toward oligomeric Aβ species. We also provide evidence for the possible capability of the m5E3 antibody to disaggregate AβOs and to fragment protofilaments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Peptides / immunology*
  • Antibodies, Monoclonal / immunology*
  • Protein Binding
  • Protein Multimerization*
  • Protein Structure, Quaternary


  • Amyloid beta-Peptides
  • Antibodies, Monoclonal

Grant support

DW, AK, and NRC received funding from the Alberta Prion Research Institute for this project. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.