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The free energy of small solute permeation through the E. coli outer membrane has a distinctly asymmetric profile

The free energy of small solute permeation through the E. coli outer membrane has a distinctly asymmetric profile
The free energy of small solute permeation through the E. coli outer membrane has a distinctly asymmetric profile
Permeation of small molecules across cell membranes is a
ubiquitous process in biology and is dependent on the principles of physical
chemistry at the molecular level. Here we use atomistic molecular dynamics
simulations to calculate the free energy of permeation of a range of small
molecules through a model of the outer membrane of Escherichia coli, an
archetypical Gram-negative bacterium. The model membrane contains
lipopolysaccharide (LPS) molecules in the outer leaflet and phospholipids in
the inner leaflet. Our results show that the energetic barriers to permeation
through the two leaflets of the membrane are distinctly asymmetric; the LPS
headgroups provide a less energetically favorable environment for organic
compounds than do phospholipids. In summary, we provide the first
reported estimates of the relative free energies associated with the different
chemical environments experienced by solutes as they attempt to cross the
outer membrane of a Gram-negative bacterium. These results provide key
insights for the development of novel antibiotics that target these bacteria.
1948-7185
3346-3451
Carpenter, Timothy S.
f46feb20-3a47-49e8-8d21-9f24b69c9d0a
Parkin, Jamie
5ddf8295-1355-4c4f-b8c2-cd1a828374dd
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394
Carpenter, Timothy S.
f46feb20-3a47-49e8-8d21-9f24b69c9d0a
Parkin, Jamie
5ddf8295-1355-4c4f-b8c2-cd1a828374dd
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394

Carpenter, Timothy S., Parkin, Jamie and Khalid, Syma (2016) The free energy of small solute permeation through the E. coli outer membrane has a distinctly asymmetric profile. The Journal of Physical Chemistry Letters, 7 (17), 3346-3451. (doi:10.1021/acs.jpclett.6b01399).

Record type: Article

Abstract

Permeation of small molecules across cell membranes is a
ubiquitous process in biology and is dependent on the principles of physical
chemistry at the molecular level. Here we use atomistic molecular dynamics
simulations to calculate the free energy of permeation of a range of small
molecules through a model of the outer membrane of Escherichia coli, an
archetypical Gram-negative bacterium. The model membrane contains
lipopolysaccharide (LPS) molecules in the outer leaflet and phospholipids in
the inner leaflet. Our results show that the energetic barriers to permeation
through the two leaflets of the membrane are distinctly asymmetric; the LPS
headgroups provide a less energetically favorable environment for organic
compounds than do phospholipids. In summary, we provide the first
reported estimates of the relative free energies associated with the different
chemical environments experienced by solutes as they attempt to cross the
outer membrane of a Gram-negative bacterium. These results provide key
insights for the development of novel antibiotics that target these bacteria.

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JPC_PMF_v2_revised - Accepted Manuscript
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More information

Accepted/In Press date: 12 August 2016
e-pub ahead of print date: 12 August 2016
Published date: 1 September 2016
Organisations: Computational Systems Chemistry

Identifiers

Local EPrints ID: 408777
URI: http://eprints.soton.ac.uk/id/eprint/408777
ISSN: 1948-7185
PURE UUID: 0b1a431e-a6cc-44cd-938e-a08d2c1e69d5
ORCID for Syma Khalid: ORCID iD orcid.org/0000-0002-3694-5044

Catalogue record

Date deposited: 27 May 2017 04:03
Last modified: 17 Dec 2019 06:12

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