Encapsulated membrane proteins: a simplified system for molecular simulation

Sarah C. Lee, Syma Khalid, Naomi L. Pollock, Timothy J. Knowles, Karen Edler, Alice J. Rothnie, Owen R.T. Thomas, Timothy R. Dafforn*

*Corresponding author for this work

Research output: Contribution to journalReview article

Abstract

Over the past 50 years there has been considerable progress in our understanding of biomolecular interactions at an atomic level. This in turn has allowed molecular simulation methods employing full atomistic modeling at ever larger scales to develop. However, some challenging areas still remain where there is either a lack of atomic resolution structures or where the simulation system is inherently complex.
An area where both challenges are present is that of membranes containing membrane proteins. In this review we analyse a new practical approach to membrane protein study that offers a potential new route to high resolution structures and the possibility to simplify simulations.
These new approaches collectively recognise that preservation of the interaction between the membrane protein and the lipid bilayer is often essential to maintain structure and function. The new methods preserve these interactions by producing nano-scale disc shaped particles that include bilayer and the chosen protein. Currently two approaches lead in this area: the MSP system that relies on peptides to stabilise the discs, and SMALPs where an amphipathic styrene maleic acid copolymer is used. Both methods greatly enable protein production and hence have the potential to accelerate atomic resolution structure determination as well as providing a simplified format for simulations of membrane protein dynamics.
Original languageEnglish
JournalBBA -Biomembranes
VolumeIn press
Early online date3 Mar 2016
DOIs
Publication statusE-pub ahead of print - 3 Mar 2016

Fingerprint

Membrane Proteins
Lipid bilayers
Styrene
Lipid Bilayers
Membrane Lipids
Proteins
Copolymers
Membranes
Peptides

Bibliographical note

© 2016, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/

Funding: BBSRC (TD - BB/M018261/1, BB/J017310/1, BB/J010812/1, BB/K004441/1, BB/I020349/1).

Keywords

  • styrene maleic acid lipid particle
  • membrane scaffold proteins
  • SMALPs
  • MSP
  • amphipols
  • detergent-free
  • nanodiscs
  • lipid bilayer
  • membrane proteins

Cite this

Lee, S. C., Khalid, S., Pollock, N. L., Knowles, T. J., Edler, K., Rothnie, A. J., ... Dafforn, T. R. (2016). Encapsulated membrane proteins: a simplified system for molecular simulation. BBA -Biomembranes, In press. https://doi.org/10.1016/j.bbamem.2016.02.039
Lee, Sarah C. ; Khalid, Syma ; Pollock, Naomi L. ; Knowles, Timothy J. ; Edler, Karen ; Rothnie, Alice J. ; Thomas, Owen R.T. ; Dafforn, Timothy R. / Encapsulated membrane proteins : a simplified system for molecular simulation. In: BBA -Biomembranes. 2016 ; Vol. In press.
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Lee, SC, Khalid, S, Pollock, NL, Knowles, TJ, Edler, K, Rothnie, AJ, Thomas, ORT & Dafforn, TR 2016, 'Encapsulated membrane proteins: a simplified system for molecular simulation', BBA -Biomembranes, vol. In press. https://doi.org/10.1016/j.bbamem.2016.02.039

Encapsulated membrane proteins : a simplified system for molecular simulation. / Lee, Sarah C.; Khalid, Syma; Pollock, Naomi L.; Knowles, Timothy J.; Edler, Karen; Rothnie, Alice J.; Thomas, Owen R.T.; Dafforn, Timothy R.

In: BBA -Biomembranes, Vol. In press, 03.03.2016.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Encapsulated membrane proteins

T2 - a simplified system for molecular simulation

AU - Lee, Sarah C.

AU - Khalid, Syma

AU - Pollock, Naomi L.

AU - Knowles, Timothy J.

AU - Edler, Karen

AU - Rothnie, Alice J.

AU - Thomas, Owen R.T.

AU - Dafforn, Timothy R.

N1 - © 2016, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ Funding: BBSRC (TD - BB/M018261/1, BB/J017310/1, BB/J010812/1, BB/K004441/1, BB/I020349/1).

PY - 2016/3/3

Y1 - 2016/3/3

N2 - Over the past 50 years there has been considerable progress in our understanding of biomolecular interactions at an atomic level. This in turn has allowed molecular simulation methods employing full atomistic modeling at ever larger scales to develop. However, some challenging areas still remain where there is either a lack of atomic resolution structures or where the simulation system is inherently complex.An area where both challenges are present is that of membranes containing membrane proteins. In this review we analyse a new practical approach to membrane protein study that offers a potential new route to high resolution structures and the possibility to simplify simulations.These new approaches collectively recognise that preservation of the interaction between the membrane protein and the lipid bilayer is often essential to maintain structure and function. The new methods preserve these interactions by producing nano-scale disc shaped particles that include bilayer and the chosen protein. Currently two approaches lead in this area: the MSP system that relies on peptides to stabilise the discs, and SMALPs where an amphipathic styrene maleic acid copolymer is used. Both methods greatly enable protein production and hence have the potential to accelerate atomic resolution structure determination as well as providing a simplified format for simulations of membrane protein dynamics.

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KW - membrane scaffold proteins

KW - SMALPs

KW - MSP

KW - amphipols

KW - detergent-free

KW - nanodiscs

KW - lipid bilayer

KW - membrane proteins

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U2 - 10.1016/j.bbamem.2016.02.039

DO - 10.1016/j.bbamem.2016.02.039

M3 - Review article

C2 - 26946242

VL - In press

JO - BBA -Biomembranes

JF - BBA -Biomembranes

SN - 0005-2736

ER -