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Molecular Dynamics Simulations of Human Beta-Defensin Type 3 Crossing Different Lipid Bilayers

Rabeta Yeasmin, Ann M. Brewer, Lela R Fine, Liqun Zhang

2021ACS Omega18 citationsDOIOpen Access PDF

Abstract

-direction were observed. Although reorientation of lipid heads toward the hBD-3 tetramer was observed based on the density profile calculation, the order parameter calculation shows that hBD-3 disrupts 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-l-serine (POPS) lipids more significantly and makes it less ordered than on 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipids. Calculating the free energy of hBD-3 through different lipid bilayers, it was found that generally hBD-3 encounters a lower energy barrier through negatively charged lipid membranes than the zwitterionic membrane. hBD-3 in different forms needs to overcome a lower energy barrier crossing the combined POPC+POPS bilayer through the POPS leaflet than through the POPC leaflet. Besides that, the potential of mean force result suggests that hBD-3 forms an oligomer translocating negatively charged lipid membranes at a low concentration. This study supplied new insight into the antibacterial mechanism of hBD-3 through different membranes.

Topics & Concepts

Molecular dynamicsTetramerLipid bilayerMembraneChemistryDimerBeta defensinUmbrella samplingMonomerDefensinCrystallographyPeptideAntimicrobial peptidesBiophysicsComputational chemistryBiochemistryBiologyOrganic chemistryPolymerEnzymeAntimicrobial Peptides and ActivitiesLipid Membrane Structure and BehaviorRNA Interference and Gene Delivery
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