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Dual-resolution molecular dynamics simulation of antimicrobials in biomembranes

Dual-resolution molecular dynamics simulation of antimicrobials in biomembranes
Dual-resolution molecular dynamics simulation of antimicrobials in biomembranes
Triclocarban and triclosan, two potent antibacterial molecules present in many consumer products, have been subject to growing debate on a number of issues, particularly in relation to their possible role in causing microbial resistance. In this computational study, we present molecular-level insights into the interaction between these antimicrobial agents and hydrated phospholipid bilayers (taken as a simple model for the cell membrane). Simulations are conducted by a novel ‘dual-resolution’ molecular dynamics approach which combines accuracy with efficiency: the antimicrobials, modelled atomistically, are mixed with simplified (coarse-grain) models of lipids and water. A first set of calculations is run to study the antimicrobials' transfer free energies and orientations as a function of depth inside the membrane. Both molecules are predicted to preferentially accumulate in the lipid headgroup–glycerol region; this finding, which reproduces corresponding experimental data, is also discussed in terms of a general relation between solute partitioning and the intramembrane distribution of pressure. A second set of runs involves membranes incorporated with different molar concentrations of antimicrobial molecules (up to one antimicrobial per two lipids). We study the effects induced on fundamental membrane properties, such as the electron density, lateral pressure and electrical potential profiles. In particular, the analysis of the spontaneous curvature indicates that increasing antimicrobial concentrations promote a ‘destabilizing’ tendency towards non-bilayer phases, as observed experimentally. The antimicrobials' influence on the self-assembly process is also investigated. The significance of our results in the context of current theories of antimicrobial action is discussed.

triclocarban, triclosan, phospholipid, multi-scale, self-assembly, spontaneous curvature
1742-5689
Orsi, Mario
62904259-9a93-4d02-8ce6-d8ef53dfcbf1
Noro, Massimo G.
87828c14-2822-494d-a664-97245d20f43c
Essex, Jonathan W.
1f409cfe-6ba4-42e2-a0ab-a931826314b5
Orsi, Mario
62904259-9a93-4d02-8ce6-d8ef53dfcbf1
Noro, Massimo G.
87828c14-2822-494d-a664-97245d20f43c
Essex, Jonathan W.
1f409cfe-6ba4-42e2-a0ab-a931826314b5

Orsi, Mario, Noro, Massimo G. and Essex, Jonathan W. (2010) Dual-resolution molecular dynamics simulation of antimicrobials in biomembranes. Journal of the Royal Society Interface. (doi:10.1098/rsif.2010.0541).

Record type: Article

Abstract

Triclocarban and triclosan, two potent antibacterial molecules present in many consumer products, have been subject to growing debate on a number of issues, particularly in relation to their possible role in causing microbial resistance. In this computational study, we present molecular-level insights into the interaction between these antimicrobial agents and hydrated phospholipid bilayers (taken as a simple model for the cell membrane). Simulations are conducted by a novel ‘dual-resolution’ molecular dynamics approach which combines accuracy with efficiency: the antimicrobials, modelled atomistically, are mixed with simplified (coarse-grain) models of lipids and water. A first set of calculations is run to study the antimicrobials' transfer free energies and orientations as a function of depth inside the membrane. Both molecules are predicted to preferentially accumulate in the lipid headgroup–glycerol region; this finding, which reproduces corresponding experimental data, is also discussed in terms of a general relation between solute partitioning and the intramembrane distribution of pressure. A second set of runs involves membranes incorporated with different molar concentrations of antimicrobial molecules (up to one antimicrobial per two lipids). We study the effects induced on fundamental membrane properties, such as the electron density, lateral pressure and electrical potential profiles. In particular, the analysis of the spontaneous curvature indicates that increasing antimicrobial concentrations promote a ‘destabilizing’ tendency towards non-bilayer phases, as observed experimentally. The antimicrobials' influence on the self-assembly process is also investigated. The significance of our results in the context of current theories of antimicrobial action is discussed.

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More information

Published date: 3 December 2010
Keywords: triclocarban, triclosan, phospholipid, multi-scale, self-assembly, spontaneous curvature

Identifiers

Local EPrints ID: 179779
URI: http://eprints.soton.ac.uk/id/eprint/179779
ISSN: 1742-5689
PURE UUID: 71d94987-9d5f-47bf-8958-1de6268b67ef
ORCID for Jonathan W. Essex: ORCID iD orcid.org/0000-0003-2639-2746

Catalogue record

Date deposited: 05 Apr 2011 10:30
Last modified: 26 Nov 2019 02:02

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