Skip to content Skip to navigation
University of Warwick
  • Study
  • |
  • Research
  • |
  • Business
  • |
  • Alumni
  • |
  • News
  • |
  • About

University of Warwick
Publications service & WRAP

Highlight your research

  • WRAP
    • Home
    • Search WRAP
    • Browse by Warwick Author
    • Browse WRAP by Year
    • Browse WRAP by Subject
    • Browse WRAP by Department
    • Browse WRAP by Funder
    • Browse Theses by Department
  • Publications Service
    • Home
    • Search Publications Service
    • Browse by Warwick Author
    • Browse Publications service by Year
    • Browse Publications service by Subject
    • Browse Publications service by Department
    • Browse Publications service by Funder
  • Help & Advice
University of Warwick

The Library

  • Login
  • Admin

Relative affinities of protein–cholesterol interactions from equilibrium molecular dynamics simulations

Tools
- Tools
+ Tools

Ansell, T. Bertie, Curran, Luke, Horrell, Michael R., Pipatpolkai, Tanadet, Letham, Suzanne C., Song, Wanling, Siebold, Christian, Stansfeld, Phillip J., Sansom, Mark S. P. and Corey, Robin A. (2021) Relative affinities of protein–cholesterol interactions from equilibrium molecular dynamics simulations. Journal of Chemical Theory and Computation, 17 (10). pp. 6548-6558. doi:10.1021/acs.jctc.1c00547 ISSN 1549-9626.

[img]
Preview
PDF
WRAP-Relative-affinities-protein−cholesterol-interactions-equilibrium-dynamics-simulations-2021.pdf - Published Version - Requires a PDF viewer.
Available under License Creative Commons Attribution 4.0.

Download (3619Kb) | Preview
Official URL: http://dx.doi.org/10.1021/acs.jctc.1c00547

Request Changes to record.

Abstract

Specific interactions of lipids with membrane proteins contribute to protein stability and function. Multiple lipid interactions surrounding a membrane protein are often identified in molecular dynamics (MD) simulations and are, increasingly, resolved in cryo-electron microscopy (cryo-EM) densities. Determining the relative importance of specific interaction sites is aided by determination of lipid binding affinities using experimental or simulation methods. Here, we develop a method for determining protein–lipid binding affinities from equilibrium coarse-grained MD simulations using binding saturation curves, designed to mimic experimental protocols. We apply this method to directly obtain affinities for cholesterol binding to multiple sites on a range of membrane proteins and compare our results with free energies obtained from density-based equilibrium methods and with potential of mean force calculations, getting good agreement with respect to the ranking of affinities for different sites. Thus, our binding saturation method provides a robust, high-throughput alternative for determining the relative consequence of individual sites seen in, e.g., cryo-EM derived membrane protein structures surrounded by an array of ancillary lipid densities.

Item Type: Journal Article
Subjects: Q Science > QP Physiology
Q Science > QR Microbiology
Divisions: Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
SWORD Depositor: Library Publications Router
Library of Congress Subject Headings (LCSH): Lipids -- Metabolism, Membrane proteins , Molecular dynamics, Lipids -- Physiological transport, Membrane lipids, Protein binding
Journal or Publication Title: Journal of Chemical Theory and Computation
Publisher: American Chemical Society (ACS)
ISSN: 1549-9626
Official Date: 12 October 2021
Dates:
DateEvent
12 October 2021Published
15 September 2021Available
3 September 2021Accepted
Volume: 17
Number: 10
Page Range: pp. 6548-6558
DOI: 10.1021/acs.jctc.1c00547
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Copyright Holders: © 2021 The Authors. Published by American Chemical Society
Date of first compliant deposit: 24 September 2021
Date of first compliant Open Access: 28 September 2021
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
208361/Z/17/ZWellcome Trusthttp://dx.doi.org/10.13039/100010269
BB/R00126X/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
C20724/A26752Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
647278European Research Councilhttp://dx.doi.org/10.13039/501100000781
EP/R004722/1[EPSRC] Engineering and Physical Sciences Research Councilhttp://dx.doi.org/10.13039/501100000266
MR/S009213/1[MRC] Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
BB/ P01948X/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
BB/R002517/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
BB/S003339/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
EP/L000253/1[EPSRC] Engineering and Physical Sciences Research Councilhttp://dx.doi.org/10.13039/501100000266
Related URLs:
  • https://creativecommons.org/licenses/by/...

Request changes or add full text files to a record

Repository staff actions (login required)

View Item View Item

Downloads

Downloads per month over past year

View more statistics

twitter

Email us: wrap@warwick.ac.uk
Contact Details
About Us