TY - JOUR
T1 - Evaluation of the binding mechanism of human defensin 5 in a bacterial membrane
T2 - A simulation study
AU - Awang, Tadsanee
AU - Chairatana, Phoom
AU - Vijayan, Ranjit
AU - Pongprayoon, Prapasiri
N1 - Funding Information:
Funding: This work was supported by Kasetsart University Research and Development Institute (KURDI, grant no. FF (KU) 25.64), Faculty of Science, Department of Chemistry (BRF policy) and Science Achievement Scholarship of Thailand (SAST). R.V. was supported by UPAR grants (31S243 and 12S006) from the United Arab Emirates University.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/11/1
Y1 - 2021/11/1
N2 - Human α-defensin 5 (HD5) is a host-defense peptide exhibiting broad-spectrum antimicrobial activity. The lipopolysaccharide (LPS) layer on the Gram-negative bacterial membrane acts as a barrier to HD5 insertion. Therefore, the pore formation and binding mechanism remain unclear. Here, the binding mechanisms at five positions along the bacterial membrane axis were investigated using Molecular Dynamics. (MD) simulations. We found that HD5 initially placed at positions 1 to 3 moved up to the surface, while HD5 positioned at 4 and 5 remained within the membrane interacting with the middle and inner leaflet of the membrane, respectively. The arginines were key components for tighter binding with 3-deoxy-d-manno-octulosonic acid (KDO), phosphates of the outer and inner leaflets. KDO appeared to retard the HD5 penetration.
AB - Human α-defensin 5 (HD5) is a host-defense peptide exhibiting broad-spectrum antimicrobial activity. The lipopolysaccharide (LPS) layer on the Gram-negative bacterial membrane acts as a barrier to HD5 insertion. Therefore, the pore formation and binding mechanism remain unclear. Here, the binding mechanisms at five positions along the bacterial membrane axis were investigated using Molecular Dynamics. (MD) simulations. We found that HD5 initially placed at positions 1 to 3 moved up to the surface, while HD5 positioned at 4 and 5 remained within the membrane interacting with the middle and inner leaflet of the membrane, respectively. The arginines were key components for tighter binding with 3-deoxy-d-manno-octulosonic acid (KDO), phosphates of the outer and inner leaflets. KDO appeared to retard the HD5 penetration.
KW - Antimicrobial peptides
KW - Human defensin 5
KW - Lipopolysaccharide
KW - Molecular dynamics simulations
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U2 - 10.3390/ijms222212401
DO - 10.3390/ijms222212401
M3 - Article
C2 - 34830284
AN - SCOPUS:85119103526
SN - 1661-6596
VL - 22
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 22
M1 - 12401
ER -