Thermodynamics of antimicrobial lipopeptide binding to membranes: origins of affinity and selectivity.

ABSTRACT: The development of novel antibiotic drugs is one of the most pressing biomedical problems due to the increasing number of antibiotic-resistant pathogens. Antimicrobial peptides and lipopeptides are a promising category of candidates, but the molecular origins of their antimembrane activity is unclear. Here we explore a series of recently developed antimicrobial lipopeptides, using coarse-grained molecular-dynamics simulations and free energy methods to uncover the thermodynamics governing their binding to membranes. Specifically, we quantify C16-KGGK's binding affinity to the two types of membrane by umbrella sampling. We also examined the origin of C16-KGGK's selectivity for bacterial versus mammalian membranes by systematically varying the peptide sequence and salt concentration. Our dat

SUBMITTER: Lin D 

PROVIDER: S-EPMC4213737 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature