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Molecular dynamics simulations of bacterial outer membrane lipid extraction: Adequate sampling?

Molecular dynamics simulations of bacterial outer membrane lipid extraction: Adequate sampling?
Molecular dynamics simulations of bacterial outer membrane lipid extraction: Adequate sampling?

The outer membrane of Gram-negative bacteria is almost exclusively composed of lipopolysaccharide in its outer leaflet, whereas the inner leaflet contains a mixture of phospholipids. Lipopolysaccharide diffuses at least an order of magnitude slower than phospholipids, which can cause issues for molecular dynamics simulations in terms of adequate sampling. Here, we test a number of simulation protocols for their ability to achieve convergence with reasonable computational effort using the MARTINI coarse-grained force-field. This is tested in the context both of potential of mean force (PMF) calculations for lipid extraction from membranes and of lateral mixing within the membrane phase. We find that decoupling the cations that cross-link the lipopolysaccharide headgroups from the extracted lipid during PMF calculations is the best approach to achieve convergence comparable to that for phospholipid extraction. We also show that lateral lipopolysaccharide mixing/sorting is very slow and not readily addressable even with Hamiltonian replica exchange. We discuss why more sorting may be unrealistic for the short (microseconds) timescales we simulate and provide an outlook for future studies of lipopolysaccharide-containing membranes.

0021-9606
Shearer, Jonathan
44810f0c-f875-465e-be3b-810155814bc5
Marzinek, Jan K.
64e75d21-98b8-44d8-96f7-5076859e13ec
Bond, Peter J.
08f46940-85e8-44c4-a368-d94342a10fd6
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394
Shearer, Jonathan
44810f0c-f875-465e-be3b-810155814bc5
Marzinek, Jan K.
64e75d21-98b8-44d8-96f7-5076859e13ec
Bond, Peter J.
08f46940-85e8-44c4-a368-d94342a10fd6
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394

Shearer, Jonathan, Marzinek, Jan K., Bond, Peter J. and Khalid, Syma (2020) Molecular dynamics simulations of bacterial outer membrane lipid extraction: Adequate sampling? Journal of Chemical Physics, 153 (4), [044122]. (doi:10.1063/5.0017734).

Record type: Article

Abstract

The outer membrane of Gram-negative bacteria is almost exclusively composed of lipopolysaccharide in its outer leaflet, whereas the inner leaflet contains a mixture of phospholipids. Lipopolysaccharide diffuses at least an order of magnitude slower than phospholipids, which can cause issues for molecular dynamics simulations in terms of adequate sampling. Here, we test a number of simulation protocols for their ability to achieve convergence with reasonable computational effort using the MARTINI coarse-grained force-field. This is tested in the context both of potential of mean force (PMF) calculations for lipid extraction from membranes and of lateral mixing within the membrane phase. We find that decoupling the cations that cross-link the lipopolysaccharide headgroups from the extracted lipid during PMF calculations is the best approach to achieve convergence comparable to that for phospholipid extraction. We also show that lateral lipopolysaccharide mixing/sorting is very slow and not readily addressable even with Hamiltonian replica exchange. We discuss why more sorting may be unrealistic for the short (microseconds) timescales we simulate and provide an outlook for future studies of lipopolysaccharide-containing membranes.

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Accepted/In Press date: 10 July 2020
e-pub ahead of print date: 29 July 2020
Published date: July 2020

Identifiers

Local EPrints ID: 444825
URI: http://eprints.soton.ac.uk/id/eprint/444825
ISSN: 0021-9606
PURE UUID: c141999d-9831-4232-b7f0-726abdb331c5
ORCID for Syma Khalid: ORCID iD orcid.org/0000-0002-3694-5044

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Date deposited: 05 Nov 2020 17:34
Last modified: 18 Feb 2021 17:09

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