Molecular dynamics simulation of antimicrobial peptide arenicin‐2: β‐Hairpin stabilization by noncovalent interactions

Abstract

Arenicin-2 is a 21 residue antimicrobial cyclic peptide, possessing one disulphide bond between residues Cys(3) and Cys(20). NMR and CD studies suggested that the structure of arenicin-2 in water represented a well formed, but highly twisted beta-hairpin. To investigate the spatial arrangement of the peptide side chains and to get a clear view of its possible amphipathic properties we performed molecular dynamics in explicit water. Four independent trajectories, 50 ns in length, were produced, starting from various initial conformations or by applying different simulation conditions. Arenicin-2 retained its beta-hairpin structure during simulations, although the residues close to strand ends were found to escape from the ideal hairpin conformation. The type I' beta-turn connecting the two strands fluctuated between type IV and II' beta-turn. Conversely, the right-handed twist of the beta-hairpin was well conserved with average twist value 203 degrees +/- 19 degrees per eight residues. Several nonbonded interactions, like hydrophobic interactions between aliphatic side chains, cation/pi-aromatic interactions, CH...pi aromatic bond and water bridges, contributed to the hairpin stabilization.

Combined Systems Approaches Reveal a Multistage Mode of Action of a Marine Antimicrobial Peptide against Pathogenic Escherichia coli and Its Protective Effect against Bacterial Peritonitis and Endotoxemia

“…No folded structures were observed for the linear N4 in the aqueous solution and SDS. N4 may experience some untwisting upon formation of a β-structural pore and form an α-helix, which may be associated with its membrane-directed activity (15). …”

Insights into the structure of the PmrD protein with molecular dynamics simulations

“…Starting conformation was build from the first model of NMR derived bundle of structures using the VMD program [12]. As it has been shown recently, MD results do not differ significantly if a different structure from the NMR bundle is used [10]. The protein was solvated with 9935 TIP3P [13] water molecules using a rectangular box with dimensions 6.33 nm × 7.20 nm × 7.32 nm.…”

“…Such type of complementary investigations have been proved to enlighten our knowledge of peptides/proteins structural properties and to help in better understanding of their action [9]. Recent simulation studies have enlighten our understanding of non-bonded interactions that stabilize secondary peptide structures [10] or promote folding [11]. One of the main targets of this study was to explore the five loop dynamics that connect the six strands region of PmrD'sˇ-barrel structure.…”

Molecular dynamics investigation of cyclic natriuretic peptides: Dynamic properties reflect peptide activity

“…Molecular dynamics (MD) simulations have been demonstrated to be a suitable technique to evaluate conformational ensemble of disordered peptides which consists of a variety of conformations [28][29][30][31]. In the this contribution, we present a molecular dynamics (MD) investigation of NPs in solution starting from their structure bound to the NPR-C [21,23] with the aim of providing a high-resolution atomistic view of their conformational ensemble in solution and of specific interactions that cannot be easily captured by experimental techniques [32][33][34].…”