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Multiscale simulations of the antimicrobial peptide maculatin 1.1: water permeation through disordered aggregates
Daniel L Parton1, Elena V Akhmatskaya, Mark S P Sansom
1Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom.
Abstract:
The antimicrobial peptide maculatin 1.1 (M1.1) is an amphipathic α-helix that permeabilizes lipid bilayers. In coarse-grained molecular dynamics (CG MD) simulations, M1.1 has previously been shown to form membrane-spanning aggregates in DPPC bilayers. In this study, a simple multiscale methodology has been applied to allow sampling of important regions of the free energy surface at higher resolution. Thus, by back-converting the CG configurations to atomistic representations, it is shown that water is able to permeate through the M1.1 aggregates. Investigation of aggregate stoichiometry shows that at least six peptides are required for water permeation. The aggregates are dynamically disordered structures, and water flux occurs through irregular, fluctuating channels. The results are discussed in relation to experimental data and other simulations of antimicrobial peptides.
Insights
Antimicrobial peptide maculatin 1.1 (M1.1) aggregates allow water permeation through lipid bilayers. At least six M1.1 peptides form disordered channels, enabling water flux and offering insights into antimicrobial peptide mechanisms.
Area of Science:
- Biophysics
- Computational Biology
- Biochemistry
Background:
- Antimicrobial peptides (AMPs) are crucial for innate immunity.
- Maculatin 1.1 (M1.1) is an amphipathic α-helical AMP known to permeabilize lipid bilayers.
- Previous coarse-grained molecular dynamics (CG MD) simulations showed M1.1 forming membrane aggregates.
Purpose of the Study:
- To investigate water permeation through M1.1 aggregates using a multiscale simulation methodology.
- To determine the minimum number of M1.1 peptides required for water permeation.
- To characterize the structure and dynamics of M1.1 aggregates and associated water channels.
Main Methods:
- Application of a multiscale simulation methodology combining coarse-grained (CG) and atomistic representations.
- Molecular dynamics (MD) simulations to analyze peptide-lipid interactions and aggregate formation.
- Free energy surface sampling at higher resolution.
Main Results:
- Water permeation through M1.1 aggregates in DPPC bilayers was confirmed.
- A minimum of six M1.1 peptides are necessary for significant water permeation.
- M1.1 aggregates form dynamically disordered structures with irregular, fluctuating water channels.
Conclusions:
- M1.1 aggregates can facilitate water transport across lipid membranes.
- The study provides a detailed molecular-level understanding of M1.1-induced membrane permeation.
- Findings contribute to the broader understanding of antimicrobial peptide mechanisms and membrane interactions.
