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Molecular aspects of the interaction between amphotericin B and a phospholipid bilayer: molecular dynamics studies

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Abstract

Amphotericin B (AmB) is a polyene macrolide antibiotic used to treat systemic fungal infections. The molecular mechanism of AmB action is still only partly characterized. AmB interacts with cell-membrane components and forms membrane channels that eventually lead to cell death. The interaction between AmB and the membrane surface can be regarded as the first (presumably crucial) step on the way to channel formation. In this study molecular dynamics simulations were performed for an AmB–lipid bilayer model in order to characterize the molecular aspects of AmB–membrane interactions. The system studied contained a box of 200 dimyristoylphosphatidylcholine (DMPC) molecules, a single AmB molecule placed on the surface of the lipid bilayer and 8,065 water molecules. Two molecular dynamics simulations (NVT ensemble), each lasting 1 ns, were performed for the model studied. Two different programs, CHARMM and NAMD2, were used in order to test simulation conditions. The analysis of MD trajectories brought interesting information concerning interactions between polar groups of AmB and both DMPC and water molecules. Our studies show that AmB preferentially took a vertical position, perpendicular to the membrane surface, with no propensity to enter the membrane. Our finding may suggest that a single AmB molecule entering the membrane is very unlikely.

Figure The figure presents the whole structure of the system simulated—starting point. AmB is presented as a space-filling model, DMPC molecules—green sticks, water molecules—red sticks

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Acknowledgments

The authors acknowledge financial support by the State Committee for Scientific Research, Warsaw (Poland), grant number 6P05F00321, and by Gdansk University of Technology, internal grant. We would like to thank the Computational Center TASK, Gdansk (Poland) for granting CPU time on their mainframe machines. We also would like to thank Ms. Malgorzata Grabska (former diploma student) for help in setting up pilot simulations at the early stages of this project.

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Authors and Affiliations

  1. Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdansk University of Technology, Narutowicza St 11/12, 80-952, Gdansk, Poland

    Kamil Sternal, Jacek Czub & Maciej Baginski

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  1. Kamil Sternal
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  2. Jacek Czub
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  3. Maciej Baginski
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Correspondence to Maciej Baginski.

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Sternal, K., Czub, J. & Baginski, M. Molecular aspects of the interaction between amphotericin B and a phospholipid bilayer: molecular dynamics studies. J Mol Model 10, 223–232 (2004). https://doi.org/10.1007/s00894-004-0190-0

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  • DOI: https://doi.org/10.1007/s00894-004-0190-0

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