Investigating the Effects of the POPC-POPG Lipid Bilayer Composition on PAP248-286 Binding Using CG Molecular Dynamics Simulations.

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  • Author(s): Agrawal N;Agrawal N;Agrawal N; Parisini E; Parisini E; Parisini E
  • Source:
    The journal of physical chemistry. B [J Phys Chem B] 2023 Oct 26; Vol. 127 (42), pp. 9095-9101. Date of Electronic Publication: 2023 Oct 16.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: American Chemical Society Country of Publication: United States NLM ID: 101157530 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-5207 (Electronic) Linking ISSN: 15205207 NLM ISO Abbreviation: J Phys Chem B Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, D.C. : American Chemical Society, c1997-
    • Subject Terms:
      Lipid Bilayers*/chemistry ; HIV Infections*; Humans ; Molecular Dynamics Simulation ; Histidine ; Peptides/chemistry ; Phosphatidylcholines/chemistry ; Phosphatidylglycerols/chemistry
    • Abstract:
      PAP248-286 is a fusogenic peptide derived from prostatic acid phosphatase, commonly found in human semen, and is known to mediate HIV fusion with cell membranes. In this study, we performed 120 independent coarse-grained molecular dynamics simulations to investigate the spontaneous binding of PAP248-286 monomers, considering both charged and neutral histidine (His) residues, to membrane bilayers composed of different lipid compositions: 100% POPC, 70% POPC-30% POPG, and 50% POPC-50% POPG. Our simulations revealed that PAP248-286 displayed spontaneous binding to the membrane, with increased binding observed in the presence of anionic lipid POPG. Specifically, in systems containing 30% and 50% POPG lipids, monomer residues, particularly in the systems containing charged histidine (His) residues, exhibited prolonged binding with the membrane. Furthermore, our simulations indicated that PAP248-286 adopted a parallel orientation with the membrane, exposing its positively charged residues to the lipid bilayer. Interestingly, systems containing charged His residues showed a higher lipid occupancy around the peptide. These findings are consistent with previous experimental data, suggesting that PAP248-286 binding is enhanced in membranes with charged His residues, resembling the conditions found in the acidic vaginal pH environment. The results of our study provide further insights into the molecular mechanisms underlying the membrane binding of PAP248-286, contributing to our understanding of its potential role in HIV fusion and infection.
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    • Accession Number:
      0 (Lipid Bilayers)
      4QD397987E (Histidine)
      0 (Peptides)
      0 (Phosphatidylcholines)
      0 (Phosphatidylglycerols)
    • Publication Date:
      Date Created: 20231016 Date Completed: 20231027 Latest Revision: 20231101
    • Publication Date:
      20240514
    • Accession Number:
      PMC10614185
    • Accession Number:
      10.1021/acs.jpcb.3c05385
    • Accession Number:
      37843472