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

[Image: see text] 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...

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Autores principales: Agrawal, Nikhil, Parisini, Emilio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614185/
https://www.ncbi.nlm.nih.gov/pubmed/37843472
http://dx.doi.org/10.1021/acs.jpcb.3c05385
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author Agrawal, Nikhil
Parisini, Emilio
author_facet Agrawal, Nikhil
Parisini, Emilio
author_sort Agrawal, Nikhil
collection PubMed
description [Image: see text] 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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spelling pubmed-106141852023-10-31 Investigating the Effects of the POPC–POPG Lipid Bilayer Composition on PAP248–286 Binding Using CG Molecular Dynamics Simulations Agrawal, Nikhil Parisini, Emilio J Phys Chem B [Image: see text] 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. American Chemical Society 2023-10-16 /pmc/articles/PMC10614185/ /pubmed/37843472 http://dx.doi.org/10.1021/acs.jpcb.3c05385 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Agrawal, Nikhil
Parisini, Emilio
Investigating the Effects of the POPC–POPG Lipid Bilayer Composition on PAP248–286 Binding Using CG Molecular Dynamics Simulations
title Investigating the Effects of the POPC–POPG Lipid Bilayer Composition on PAP248–286 Binding Using CG Molecular Dynamics Simulations
title_full Investigating the Effects of the POPC–POPG Lipid Bilayer Composition on PAP248–286 Binding Using CG Molecular Dynamics Simulations
title_fullStr Investigating the Effects of the POPC–POPG Lipid Bilayer Composition on PAP248–286 Binding Using CG Molecular Dynamics Simulations
title_full_unstemmed Investigating the Effects of the POPC–POPG Lipid Bilayer Composition on PAP248–286 Binding Using CG Molecular Dynamics Simulations
title_short Investigating the Effects of the POPC–POPG Lipid Bilayer Composition on PAP248–286 Binding Using CG Molecular Dynamics Simulations
title_sort investigating the effects of the popc–popg lipid bilayer composition on pap248–286 binding using cg molecular dynamics simulations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614185/
https://www.ncbi.nlm.nih.gov/pubmed/37843472
http://dx.doi.org/10.1021/acs.jpcb.3c05385
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