Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Another piece of the membrane puzzle: extending slipids further
Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry.
2013 (English)In: Journal of Chemical Theory and Computation, ISSN 1549-9618, E-ISSN 1549-9626, Vol. 9, no 1, 774-784 p.Article in journal (Refereed) Published
Abstract [en]

To be able to model complex biological membranes in a more realistic manner, the force field Slipids (Stockholm lipids) has been extended to include parameters for sphingomyelin (SM), phosphatidylglycerol (PG), phosphatidylserine (PS) lipids, and cholesterol. Since the parametrization scheme was faithful to the scheme used in previous editions of Slipids, all parameters are consistent and fully compatible. The results of careful validation of a number of key structural properties for one and two component lipid bilayers are in excellent agreement with experiments. Potentials of mean force for transferring water across binary mixtures of lipids and cholesterol were also computed in order to compare water permeability rates to experiments. In agreement with experimental and simulation studies, it was found that the permeability and partitioning of water is affected by cholesterol in lipid bilayers made of saturated lipids to the largest extent. With the extensions of Slipids presented here, it is now possible to study complex systems containing many different lipids and proteins in a fully atomistic resolution in the isothermic-isobaric (NPT) ensemble, which is the proper ensemble for membrane simulations.

Place, publisher, year, edition, pages
2013. Vol. 9, no 1, 774-784 p.
National Category
Physical Chemistry
Research subject
Physical Chemistry
Identifiers
URN: urn:nbn:se:su:diva-88329DOI: 10.1021/ct300777pISI: 000313378700077OAI: oai:DiVA.org:su-88329DiVA: diva2:611786
Funder
Swedish Research CouncilEU, FP7, Seventh Framework Programme, 261523
Note

AuthorCount:2;

Available from: 2013-03-18 Created: 2013-03-12 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Computer Simulations of Heterogenous Biomembranes
Open this publication in new window or tab >>Computer Simulations of Heterogenous Biomembranes
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Molecular modeling has come a long way during the past decades and in the current thesis modeling of biological membranes is the focus. The main method of choice has been classical Molecular Dynamics simulations and for this technique a model Hamiltonian, or force field (FF), has been developed for lipids to be used for biological membranes. Further, ways of more accurately simulate the interactions between solutes and membranes have been investigated.

A FF coined Slipids was developed and validated against a range of experimental data (Papers I-III). Several structural properties such as area per lipid, scattering form factors and NMR order parameters obtained from the simulations are in good agreement with available experimental data. Further, the compatibility of Slipids with amino acid FFs was proven. This, together with the wide range of lipids that can be studied, makes Slipids an ideal candidate for large-scale studies of biologically relevant systems.

A solute's electron distribution is changed as it is transferred from water to a bilayer, a phenomena that cannot be fully captured with fixed-charge FFs.  In Paper IV we propose a scheme of implicitly including these effects with fixed-charge FFs in order to more realistically model water-membrane partitioning. The results are in good agreement with experiments in terms of free energies and further the differences between using this scheme and the more traditional approach were highlighted.

The free energy landscape (FEL) of solutes embedded in a model membrane is explored in Paper V. This was done using biased sampling methods with a reaction coordinate that included intramolecular degrees of freedom (DoF). These DoFs were identified in different bulk liquids and then used in studies with bilayers. The FELs describe the conformational changes necessary for the system to follow the lowest free energy path. Besides this, the pitfalls of using a one-dimensional reaction coordinate are highlighted.

Place, publisher, year, edition, pages
Stockholm: Department of Materials and Environmental Chemistry (MMK), Stockholm University, 2014. 82 p.
Keyword
Molecular simulation, force field development, biological membranes, free energy calculations, rational drug design, solute-membrane interactions
National Category
Physical Chemistry
Research subject
Physical Chemistry
Identifiers
urn:nbn:se:su:diva-101297 (URN)978-91-7447-875-4 (ISBN)
Public defence
2014-04-04, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 13:00 (English)
Opponent
Supervisors
Available from: 2014-03-13 Created: 2014-03-04 Last updated: 2015-01-21Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Jämbeck, Joakim P. M.Lyubartsev, Alexander P.
By organisation
Physical Chemistry
In the same journal
Journal of Chemical Theory and Computation
Physical Chemistry

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 82 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf