Cyclotides are cyclic antimicrobial peptides (APs) that offer promising features for the development of efficient pharmaceutical therapies because of their bioavailability, stability and broad range of biological activities (Antitumor, Antimicrobial, Anti-HIV and Insecticidal). However, their efficiency as therapeutic agent is still hampered by lack of molecular details of their mechanism of action on biological membranes and other potential molecular targets. Specifically, data on the residues, domains and conformational changes on membrane is limited. We have used unconstrained all-atom molecular dynamics (MD) simulation to investigate the interactions between a representative cyclotide (kalata B1) and bilayers of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) lipids and 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) lipids. The intra- and inter-molecular potential between the biomolecules are described using amber and the S-lipids force fields. After analysis of 100 ns simulations we determined that kalata B1 is attracted to the surface of both lipid layers through close contact interactions. We also found supporting evidence of preferential binding on POPE layer as opposed to POPC mainly due to stronger electrostatic interactions. Kalata B1 in the last 60 ns of the simulation remains in close contact with the lipid headgroups of POPE using 3 amino acid residues (VAL, ASN, THR). This initial data suggest that these surface interactions promote peptide distribution similar to the carpet model mechanism of interaction.

Do cyclotides bind lipid bilayers: All atom molecular dynamics simulations of kalata B1 and POPE/POPC lipids

248th National Meeting (2014)

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