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J Mol Graph Model. 2020 Mar;95:107502. doi: 10.1016/j.jmgm.2019.107502. Epub 2019 Nov 27.

Charge-based interactions of antimicrobial peptides and general drugs with lipid bilayers.

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Department of Biochemistry, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia. Electronic address:
Department of Oncology, University of Alberta, Edmonton, Canada.
Department of Oncology, University of Alberta, Edmonton, Canada; Department of Physics, University of Alberta, Edmonton, Canada; DIMEAS, Politecnico di Torino, Corso Duca degli Abruzzi, 24, Torino, TO, 10129, Italy.


Membrane-active agents (MAAs), such as antimicrobial peptides (AMPs) and chemotherapy drugs (CDs), induce ion pores/channels inside lipid bilayer membrane, as confirmed by standard electrophysiology experiments. A novel experimental method is described which detects agents directly at the membrane as confirmed for MAAs, CDs and aptamers. MAAs exhibit characteristic 'charge based' interactions with lipids. Electrostatic (ES) and van der Waals (vdW) contributions to the interaction energies have been estimated using molecular dynamics (MD) simulations. These results are consistent with the screened Coulomb interaction predictions recently developed for lipid bilayer binding of integral AMP channels. Energy- and distance-dependence of MAA-lipid interactions from MD simulations are represented by universal probability functions. A generalized model of MAA-lipid interactions is developed based on the charge and geometrical profiles of the participating lipids and AMPs. The corresponding driving force correlates directly with the stability of MAA-lipid structures as observed in electrophysiology experiments. We conclude that MAAs and similar agents that target lipid membranes exhibit physiological effects mainly due to ES and vdW interactions determined by their charge profiles.


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