title: Simulating the antimicrobial mechanism of human β-defensin-3 with coarse-grained molecular dynamics.
abstract: Human β-defensin-3 (HβD-3) is an endogenous antimicrobial peptide with potent and broad killing activity against various microorganisms, and thus, it is an attractive candidate for the development of novel peptide antibiotics, but its antimicrobial mechanism remains elusive. To characterize the mechanism, we used multi-microsecond coarse-grained simulations with the MARTINI force field. These simulations show HβD-3 peptides can form oligomers on the surface of bacterial membrane and make anionic lipids (POPG) clustered. Furthermore, two kinds of regions (one is composed of pure POPG lipids, and the other is enriched in POPE lipids) are formed in the membrane; on the border of them, there are some obvious defects, which result in the membrane disruption. By contrast, the simulations also reveal that the contacts between the HβD-3 peptides and mammalian membrane are not stable. These results provide biophysical insights into HβD-3 selectivity and suggest a possible antimicrobial mechanism.
authors.affiliation: a State Key Laboratory of Theoretical and Computational Chemistry , Institute of Theoretical Chemistry, Jilin University , Changchun 130023 , People's Republic of China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhao
authors.affiliation: b College of Chemistry and Biology , Beihua University , Jilin 132013 , People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yu
authors.affiliation: a State Key Laboratory of Theoretical and Computational Chemistry , Institute of Theoretical Chemistry, Jilin University , Changchun 130023 , People's Republic of China.
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.affiliation: a State Key Laboratory of Theoretical and Computational Chemistry , Institute of Theoretical Chemistry, Jilin University , Changchun 130023 , People's Republic of China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Li
authors.affiliation: a State Key Laboratory of Theoretical and Computational Chemistry , Institute of Theoretical Chemistry, Jilin University , Changchun 130023 , People's Republic of China.
authors.forename: Xuri
authors.initials: X
authors.lastname: Huang
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D023083:beta-Defensins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; C422950:DEFB103A protein, human; D008051:Lipid Bilayers; D023083:beta-Defensins
keywords: antimicrobial mechanism; coarse-grained; human β-defensin-3; molecular dynamics