Simulations of octapeptin-outer membrane interactions reveal conformational flexibility is linked to antimicrobial potency
Xukai Jiang, Kai Yang, Bing Yuan, Bin Gong, Lin Wan, Nitin A Patil, James D Swarbrick, Kade D Roberts, Falk Schreiber, Lushan Wang, Tony Velkov, Jian Li
Journal of Biological Chemistry | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2020
The octapeptins are lipopeptide antibiotics that are structurally similar to polymyxins yet retain activity against polymyxin-resistant Gram-negative pathogens, suggesting they might be used to treat recalcitrant infections. However, the basis of their unique activity is unclear because of the difficulty in generating high-resolution experimental data of the interaction of antimicrobial peptides with lipid membranes. To elucidate these structure-activity relationships, we employed all-atom molecular dynamics simulations with umbrella sampling to investigate the conformational and energetic landscape of octapeptins interacting with bacterial outer membrane (OM). Specifically, we examined the ..View full abstract
Awarded by NIAID, National Institutes of Health
Awarded by HPC Cloud Platform (National Key Research and Development Project) at Shandong University (China)
This work was supported by NIAID, National Institutes of Health Grant R01 AI132154 (to J. L. and T. V.). X. J. is recipient of the 2019 Faculty Bridging Fellowship from Monash University. J. L. is an Australia National Health Medical Research Council Principal Research Fellow. The simulations were performed on the supercomputer at Monash University (Australia) and the HPC Cloud Platform (National Key Research and Development Project 2016YFB0201702) at Shandong University (China). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.