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Modeling the Interaction of Dodecylphosphocholine Micelles with the Anticoccidial Peptide PW2 Guided by NMR Data
Laboratory of Toxinology, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 21045-900, Brazil
Institute of Medical Biochemistry, National Center of Nuclear Magnetic Resonance Jiri Jonas, Federal University of Rio de Janeiro - Institute of Structural Biology and Bioimaging, Rio de Janeiro 21941-920, Brazil
* Author to whom correspondence should be addressed.
Received: 19 July 2013; in revised form: 5 August 2013 / Accepted: 7 August 2013 / Published: 20 August 2013
Abstract: Antimicrobial peptides are highly dynamic entities that acquire structure upon binding to a membrane interface. To better understand the structure and the mechanism for the molecular recognition of dodecylphosphocholine (DPC) micelles by the anticoccidial peptide PW2, we performed molecular dynamics (MD) simulations guided by NMR experimental data, focusing on strategies to explore the transient nature of micelles, which rearrange on a millisecond to second timescale. We simulated the association of PW2 with a pre-built DPC micelle and with free-DPC molecules that spontaneously forms micelles in the presence of the peptide along the simulation. The simulation with spontaneous micelle formation provided the adequate environment which replicated the experimental data. The unrestrained MD simulations reproduced the NMR structure for the entire 100 ns MD simulation time. Hidden discrete conformational states could be described. Coulomb interactions are important for initial approximation and hydrogen bonds for anchoring the aromatic region at the interface, being essential for the stabilization of the interaction. Arg9 is strongly attached with phosphate. We observed a helix elongation process stabilized by the intermolecular peptide-micelle association. Full association that mimics the experimental data only happens after complete micelle re-association. Fast micelle dynamics without dissociation of surfactants leads to only superficial binding.
Keywords: molecular dynamics simulation; NMR; structure; antimicrobial; membrane; micelles; peptide structure
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Gomes-Neto, F.; Valente, A.P.; Almeida, F.C.L. Modeling the Interaction of Dodecylphosphocholine Micelles with the Anticoccidial Peptide PW2 Guided by NMR Data. Molecules 2013, 18, 10056-10080.
Gomes-Neto F, Valente AP, Almeida FCL. Modeling the Interaction of Dodecylphosphocholine Micelles with the Anticoccidial Peptide PW2 Guided by NMR Data. Molecules. 2013; 18(8):10056-10080.
Gomes-Neto, Francisco; Valente, Ana P.; Almeida, Fabio C.L. 2013. "Modeling the Interaction of Dodecylphosphocholine Micelles with the Anticoccidial Peptide PW2 Guided by NMR Data." Molecules 18, no. 8: 10056-10080.