Ab initio prediction of specific phospholipid complexes and membrane association of HIV-1 MPER antibodies by multi-scale simulations.

ABSTRACT: A potent class of HIV-1 broadly neutralizing antibodies (bnAbs) targets the envelope glycoprotein's membrane proximal exposed region (MPER) through a proposed mechanism where hypervariable loops embed into lipid bilayers and engage headgroup moieties alongside the epitope. We address the feasibility and determinant molecular features of this mechanism using multi-scale modeling. All-atom simulations of 4E10, PGZL1, 10E8, and LN01 docked onto HIV-like membranes consistently form phospholipid complexes at key complementarity-determining region loop sites, solidifying that stable and specific lipid interactions anchor bnAbs to membrane surfaces. Ancillary protein-lipid contacts reveal surprising contributions from antibody framework regions. Coarse-grained simulations effectively capture anti

SUBMITTER: Maillie CA 

PROVIDER: S-EPMC11975376 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature