a rigidity-enhanced antimicrobial activity a case for linear cationic α-helical peptide hp(2–20) and its four analogues一个rigidity-enhanced抗菌活性为线性阳离子α-helical肽惠普四(2 - 20)及其类似物.pdfVIP

A Rigidity-Enhanced Antimicrobial Activity: A Case for Linear Cationic a-Helical Peptide HP(2–20) and Its Four Analogues 1 1 1,2 1 Li Liu , Ying Fang , Qingsheng Huang , Jianhua Wu * 1 Institute of Biomechanics and Department of Biomedical Engineering, School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, China, 2 School of life Science, Sun Yat-Sen University, Guangzhou, China Abstract Linear cationic a-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 6109. 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 a-helical peptide groups. This exciting result was reasonably explained by a possible mechanical mechanism that reg