Insight into the impact of environments on structure of chimera C3 of human β-defensins 2 and 3 from molecular dynamics simulations

Abstract

C3 is a chimera from human β-defensins 2 and 3 and possesses higher antimicrobial activity compared with its parental molecules, so it is an attractive candidate for clinical application of antimicrobial peptides. In continuation with the previous studies, molecular dynamics (MD) simulations were carried out for further investigating the effect of ambient environments (temperature and bacterial membrane) on C3 dynamics. Our results reveal that C3 has higher flexibility, larger intensity of motion, and more relevant secondary structural changes at 363 K to adapt the high temperature and maintain its antimicrobial activity, comparison with it at 293 K; when C3 molecule associates with the bacterial membrane, it slightly fluctuates and undergoes local conformational changes; in summary, C3 molecule demonstrates stable conformations under these environments. Furthermore, MD results analysis show that the hydrophobic contacts, the hydrogen bonds, and disulfide bonds in the peptide are responsible for maintaining its stable conformation. In addition, our simulation shows that C3 peptides can make anionic lipids clustered in the bacterial membrane; it means that positive charges and pronounced regional cationic charge density of C3 are most key factors for its antimicrobial activity.