title: P-113 peptide: New experimental evidences on its biological activity and conformational insights from molecular dynamics simulations.
abstract: In this article, we report novel and additional results, both experimental and computational, obtained in our laboratories on the peptide P-113. In particular, our experimental results indicate that this peptide is endowed with a high target-cell selectivity towards yeast species, suggesting its potential development as a new drug against oral microbial infections. To provide additional structural insights, we performed several Molecular Dynamics simulations in different conditions. Results suggest that P-113 is a rather compact species presumably because of its highly charged state as emerged from the dramatic increase of internal fluctuation occurring upon point-mutation. The peptide turns out to adopt, in water, a beta-hairpin-like conformation and, in a more hydrophobic environment, is found to be in a (probably slow) equilibrium between α-helix and hairpin conformations. Complexation with Zn(2+) induces a drastic mechanical stabilization, which prevents any conformational organization of the peptide into a biologically active state.
authors.affiliation: Department of Physical and Chemical Sciences, University of L'Aquila, Via Vetoio snc, 67100, L'Aquila, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Di Giampaolo
authors.forename: Carla
authors.initials: C
authors.lastname: Luzi
authors.forename: Bruno
authors.initials: B
authors.lastname: Casciaro
authors.forename: Argante
authors.initials: A
authors.lastname: Bozzi
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Mangoni
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Aschi
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D012996:Solutions; D013816:Thermodynamics; D013997:Time Factors; D014270:Trifluoroethanol / Q000737:chemistry; D014867:Water / Q000737:chemistry; D015003:Yeasts / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D010455:Peptides; D012996:Solutions; D014867:Water; D014270:Trifluoroethanol
keywords: cationic peptide; minimal inhibitory concentration; molecular dynamics; yeasts