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The adsorption of human defensin 5 on bacterial membranes: simulation studies

  • Tadsanee Awang
  • Prapasiri Pongprayoon
Original Paper

Abstract

Human α-defensin 5 (HD5) is one of the important antimicrobial peptides (AMPs) used against a broad-spectrum of pathogens, especially Gram-negative bacteria. HD5 kills by disrupting and making a pore in the bacterial membrane. The presence of lipopolysaccharide (LPS), located on a membrane surface, is found to have an impact on HD5’s activity, where such binding mechanism in microscopic detail remains unclear. In this work, we therefore employed molecular dynamics (MD) simulations to investigate the binding mechanisms of HD5 on LPS in comparison to a bare DMPC lipid membrane. Two oligomers, dimer and tetramer, are studied here. Apparently, the membrane structure influences the protein binding affinity. HD5 binds tighter to a lipid membrane than LPS. Both dimeric and tetrameric HD5 can penetrate deeply into a phosphate layer in a lipid membrane, whereas only facial contacts are observed for LPS systems. The proteins appear to stay in the polar area instead of diving into a hydrophobic region. Furthermore, it happens in all cases that residues in the active region (A1, T2, R6, R13, R32) contribute to the membrane adsorption. The breakdown of tetramer into two dimers is also found. This implies that the dimer is more favorable for membrane binding. Moreover, both dimeric and tetrameric HD5 can significantly disrupt a LPS layer, whilst no serious distortion of lipid membrane is obtained. This emphasizes the importance of LPS on HD5 activity.

Keywords

Antimicrobial peptides Human defensin 5 LPS Molecular dynamics simulations Host-defense peptide 

Abbreviations

MD

Molecular dynamics

LPS

Lipopolysaccharide

HD5

Human α-defensin 5

DMPC

1,2-dimyristoyl-sn-glycero-3-phosphocholine

Notes

Acknowledgments

We would like to acknowledge the financial support received from the Kasetsart University Research and Development Institute (KURDI), Bangkok, Thailand and from a Science Achievement Scholarship of Thailand (SAST). We also thank Prof Syma Khalid for her kind support.

Supplementary material

894_2018_3812_MOESM1_ESM.docx (338 kb)
ESM 1 (DOCX 337 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Chemistry, Faculty of ScienceKasetsart UniversityBangkokThailand
  2. 2.Computational Biomodelling Laboratory for Agricultural Science and Technology (CBLAST)Kasetsart UniversityBangkokThailand
  3. 3.Center for Advanced Studies in Nanotechnology for Chemical, Food and Agricultural Industries, KU Institute for Advanced StudiesKasetsart UniversityBangkokThailand

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