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Atomistic simulations of an antimicrobial molecule interacting with a model bacterial membrane

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Abstract

The dynamics of an antimicrobial molecule (end-only oligo(p-phenylene ethynylene) or EO-OPE-1 (C3)) interacting with a model bacterial membrane is simulated using all-atom molecular dynamics. It is found that the molecule spontaneously adheres to the membrane at the membrane–water interface, but no insertion into the bilayer was observed within the nanosecond simulation time. However, when the simulations start from an inserted configuration, this molecule aligns with the lipid molecules in the membrane and interacts strongly through electrostatic interactions with the anionic phosphoryl groups of the lipid molecules. Due to the hydrophobic mismatch between the molecule and lipids, the inserted molecule induces the deformation of the membrane in the form of local thinning. When more than one molecule were inserted, self-assembling was observed on a nanosecond scale. However, no transmembrane pore formation was observed, due presumably to the hydrophobic backbone of the molecule. Implications in the biocidal action of this molecule are discussed.

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Acknowledgments

This work is partially supported by the Defense Threat Reduction Agency (HDTRA1-11-1-0004). We thank David Keller and David Whitten for many stimulating discussions. Y.L. thanks Dr. Jianyi Ma for discussing the calculation of the diffusion coefficient.

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Authors and Affiliations

  1. Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, NM, 87131, USA

    Yongle Li & Hua Guo

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  1. Yongle Li
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  2. Hua Guo
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Correspondence to Hua Guo.

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Li, Y., Guo, H. Atomistic simulations of an antimicrobial molecule interacting with a model bacterial membrane. Theor Chem Acc 132, 1303 (2013). https://doi.org/10.1007/s00214-012-1303-y

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