Charge-Governed Solvation Behaviour of Novel AMPs
Résumé
Antimicrobial peptides (AMPs) are regarded as a promising alternative to conventional 1 antimicrobials, but their mechanism of action is not completely understood. Using long-scale 2 molecular dynamics simulations, we investigate the behavior of two newly isolated AMPs from 3 the fraction with molecular weight (MW) below 3 kDa of the mucus of Helix aspersa in mono-and 4 multicomponent solutions, prior to their engagement with the pathogenic membrane. In both 5 instances, the peptide monomers form clusters consisting of a non-polar hydrophobic nucleus 6 surrounded by charged and polar residues exposed to the solvent. We consider the so-formed 7 structures to be the ideal transport and coalescence system-locking the hydrophobic uncharged 8 residues in the cluster core prevents interaction with the largely uncharged eukaryotic membranes, 9 while positioning the charged residues on the cluster surface enables electrostatic interaction with 10 the bacterial surface. In addition, the amphiphilic structure of the aggregates promotes peptide 11 folding, which increases the local concentration of AMPs delivered to the target membrane in a 12 functionally active conformation.
Domaines
Sciences du Vivant [q-bio]
Origine : Fichiers produits par l'(les) auteur(s)