Your browser doesn't support javascript.
loading
Molecular dynamics simulations of bacterial outer membrane lipid extraction: Adequate sampling?
Shearer, Jonathan; Marzinek, Jan K; Bond, Peter J; Khalid, Syma.
Afiliação
  • Shearer J; School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, United Kingdom.
  • Marzinek JK; Bioinformatics Institute (BII), Agency for Science, Technology and Research (ASTAR), 30 Biopolis Street, Matrix #07-01, 138671, Singapore.
  • Bond PJ; Bioinformatics Institute (BII), Agency for Science, Technology and Research (ASTAR), 30 Biopolis Street, Matrix #07-01, 138671, Singapore.
  • Khalid S; School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, United Kingdom.
J Chem Phys ; 153(4): 044122, 2020 Jul 28.
Article em En | MEDLINE | ID: mdl-32752683
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Membrana Externa Bacteriana / Lipídeos Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Membrana Externa Bacteriana / Lipídeos Idioma: En Ano de publicação: 2020 Tipo de documento: Article