Antimicrobial peptide structure and function simulation
Antimicrobial peptides are oligopeptides encountered in both prokaryotes and eukaryotes as part of innate immune responses. In animals, they are found mostly in the tissues and organs that are exposed to airborne pathogens. Over 5 000 different antimicrobial peptides have been discovered or synthesised. Although antimicrobial peptides have great potential to serve as antibiotics, their mechanism of action remains poorly understood. The EU-funded AMDERM (The action mechanism of human antimicrobial peptide dermcidin) project worked on the antimicrobial peptide dermcidin (DCD), which is secreted by the human sweat glands. DCD consists of 48 amino acids and exhibits broad-spectrum antimicrobial activities in human sweat. Researchers investigated the selective mechanism of DCD anti-bacterial activity. They discovered that DCD formed ion channels on bacterial membranes, thereby destroying the resting potential of cells and causing cell death. Using multi-scale computer simulations and electrophysiology experiments, they evaluated the effect of membrane composition on DCD activity. By changing the lipid bilayer thicknesses and abundance in cholesterol, they observed that the orientation of DCD critically depended on membrane composition and thickness. Orientation also affected channel ion conductivity and hence DCD function: the thinner the membrane, the larger the tilt angle of DCD in the membrane, the larger the conductance and therefore the greater the activity. Although experimental validation is pending, these in silico findings provided unprecedented evidence on the mechanism of DCD action. While they could potentially be used towards the design and optimisation of DCD-based new antibiotics, further research would be essential to unveil the role of DCD against specific groups of pathogenic bacteria.
Keywords
Antimicrobial peptide, dermcidin, sweat gland, ion channel, membrane, computer simulation, ion conductivity
