Jump to main content
Jump to site search


Exploration of HIV-1 fusion peptide–antibody VRC34.01 binding reveals fundamental neutralization sites

Author affiliations

Abstract

Antibody binding to a vulnerable site of HIV envelope glycoprotein (Env), the eight N-terminal residues of the gp41 fusion peptide, renders robust HIV neutralization. Here, we theoretically investigate HIV-1 fusion peptide binding to the neutralizing antibody N123–VRC34.01. We explore numerous fusion peptide mutations using all-atom molecular dynamics simulation with explicit-solvent models. Simulation results show that the hydrophobic interaction between Ile515 in the HIV-1 fusion peptide and the antibody VRC34.01 Fab plays an important role in antibody binding. Furthermore, we verify by free energy perturbation (FEP) calculations that two point mutations of Ile515Thr or Ile515Ala can dramatically weaken the binding affinity. Our findings provide new insights into fusion peptide–VRC34.01 binding, which can ultimately be utilized to design effective HIV vaccines.

Graphical abstract: Exploration of HIV-1 fusion peptide–antibody VRC34.01 binding reveals fundamental neutralization sites

Back to tab navigation

Supplementary files

Publication details

The article was received on 22 May 2019, accepted on 08 Aug 2019 and first published on 08 Aug 2019


Article type: Paper
DOI: 10.1039/C9CP02909E
Phys. Chem. Chem. Phys., 2019, Advance Article

  •   Request permissions

    Exploration of HIV-1 fusion peptide–antibody VRC34.01 binding reveals fundamental neutralization sites

    M. Feng, D. R. Bell, H. Kang, Q. Shao and R. Zhou, Phys. Chem. Chem. Phys., 2019, Advance Article , DOI: 10.1039/C9CP02909E

Search articles by author

Spotlight

Advertisements