Simulations of Membrane-Disrupting Peptides I: Alamethicin Pore Stability and Spontaneous Insertion.

ABSTRACT: An all-atom molecular dynamics simulation of the archetype barrel-stave alamethicin (alm) pore in a 1,2-dioleoyl-sn-glycero-3-phosphocholine bilayer at 313 K indicates that ?7 ?s is required for equilibration of a preformed 6-peptide pore; the pore remains stable for the duration of the remaining 7 ?s of the trajectory, and the structure factors agree well with experiment. A 5 ?s simulation of 10 surface-bound alm peptides shows significant peptide unfolding and some unbinding, but no insertion. Simulations at 363 and 413 K with a -0.2 V electric field yield peptide insertion in 1 ?s. Insertion is initiated by the folding of residues 3-11 into an ?-helix, and mediated by membrane water or by previously inserted peptides. The stability of five alm pore peptides at 413 K with a -0.2 V electric field demonstrates a significant preference for a transmembrane orientation. Hence, and in contrast to the cationic antimicrobial peptide described in the following article, alm shows a strong preference for the inserted over the surface-bound state.

SUBMITTER: Perrin BS 

PROVIDER: S-EPMC5034365 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature