Abstract
Linear cationic α-helical antimicrobial peptides are referred to as one of the most likely substitutes for common antibiotics, due to their relatively simple structures (≤40 residues) and various antimicrobial activities against a wide range of pathogens. Of those, HP(2–20) was isolated from Helicobacter pylori ribosomal protein. To reveal a mechanical determinant that may mediate the antimicrobial activities, we examined the mechanical properties and structural stabilities of HP(2–20) and its four analogues of same chain length by steered molecular dynamics simulation. The results indicated the following: the resistance of H-bonds to the tensile extension mediated the early extensive stage; with the loss of H-bonds, the tensile force was dispensed to prompt the conformational phase transition; and Young's moduli (N/m2) of the peptides were about 4∼8×109. These mechanical features were sensitive to the variation of the residue compositions. Furthermore, we found that the antimicrobial activity is rigidity-enhanced, that is, a harder peptide has stronger antimicrobial activity. It suggests that the molecular spring constant may be used to seek a new structure-activity relationship for different α-helical peptide groups. This exciting result was reasonably explained by a possible mechanical mechanism that regulates both the membrane pore formation and the peptide insertion.
Highlights
Antimicrobial peptides (AMPs), an innate immune component ubiquitous among plants and animals, are variously active against a wide range of pathogens, such as gram-positive bacteria, gramnegative bacteria, fungi and protozoa [1,2,3]
For the action of AMPs, a rational theme is that, as the peptides meet a target cell, the positive charges are beneficial for them to be captured and bound to the cellular membrane by electrostatic affinity [10]; the bound peptides interact with the cellular membrane by their hydrophobic face [11], and may undergo a conformational phase transition in the framework of the cellular membrane via electrostatic, hydrophobic or other affinities [9]; but, the membrane pore or channel formation, which causes dysfunction of the cell, occurs just as the accumulation of the bound peptides on the cellular membrane has arrived at a stoichiometric threshold [12]; and the membrane disruption is induced, or the peptides would directly enter the membrane to access and inhibit intracellular targets [1,9]
There should be a mechanical mechanism that regulates the formation of the pore or slot in cellular membrane
Summary
Antimicrobial peptides (AMPs), an innate immune component ubiquitous among plants and animals, are variously active against a wide range of pathogens, such as gram-positive bacteria, gramnegative bacteria, fungi and protozoa [1,2,3]. They are proposed as one of the most likely substitutes for common antibiotics, to confront an increasingly serious threat to human health caused by antibiotic-resistant bacterial infection [4,5,6]. Previous works were focused mainly on biochemical and biophysical aspects instead of mechanical correspondence in the interaction of the peptides and cellular membrane
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