Insights into lipid-protein interactions from computer simulations

TY - JOUR

T1 - Insights into lipid-protein interactions from computer simulations

AU - Tieleman, D. P.

AU - Sejdiu, B. I.

AU - Cino, E. A.

AU - Smith, P.

AU - Barreto-Ojeda, E.

AU - Khan, H. M.

AU - Corradi, V.

N1 - Funding Information: This work was supported by the Natural Sciences and Engineering Research Council (Canada), the Canadian Institutes for Health Research, MITACS, and the Canada Research Chairs Program. Funding Information: Calculations presented in this work were carried out in part on Compute Canada facilities, supported by the Canada Foundation for Innovation and partners. E. B-O was supported by a Mitacs Globalink Research Award from Mitacs Canada in partnership with Campus France; P. S. was supported by a UK-Canada Mitacs Globalink doctoral exchange award. Publisher Copyright: © 2021, The Author(s).

PY - 2021/12

Y1 - 2021/12

N2 - Lipid-protein interactions play an important direct role in the function of many membrane proteins. We argue they are key players in membrane structure, modulate membrane proteins in more subtle ways than direct binding, and are important for understanding the mechanism of classes of hydrophobic drugs. By directly comparing membrane proteins from different families in the same, complex lipid mixture, we found a unique lipid environment for every protein. Extending this work, we identified both differences and similarities in the lipid environment of GPCRs, dependent on which family they belong to and in some cases their conformational state, with particular emphasis on the distribution of cholesterol. More recently, we have been studying modes of coupling between protein conformation and local membrane properties using model proteins. In more applied approaches, we have used similar methods to investigate specific hypotheses on interactions of lipid and lipid-like molecules with ion channels. We conclude this perspective with some considerations for future work, including a new more sophisticated coarse-grained force field (Martini 3), an interactive visual exploration framework, and opportunities to improve sampling.

AB - Lipid-protein interactions play an important direct role in the function of many membrane proteins. We argue they are key players in membrane structure, modulate membrane proteins in more subtle ways than direct binding, and are important for understanding the mechanism of classes of hydrophobic drugs. By directly comparing membrane proteins from different families in the same, complex lipid mixture, we found a unique lipid environment for every protein. Extending this work, we identified both differences and similarities in the lipid environment of GPCRs, dependent on which family they belong to and in some cases their conformational state, with particular emphasis on the distribution of cholesterol. More recently, we have been studying modes of coupling between protein conformation and local membrane properties using model proteins. In more applied approaches, we have used similar methods to investigate specific hypotheses on interactions of lipid and lipid-like molecules with ion channels. We conclude this perspective with some considerations for future work, including a new more sophisticated coarse-grained force field (Martini 3), an interactive visual exploration framework, and opportunities to improve sampling.

KW - Lipid-protein interactions

KW - Martini

KW - Membrane proteins

KW - Molecular dynamics simulations

UR - http://www.scopus.com/inward/record.url?scp=85118487348&partnerID=8YFLogxK

U2 - 10.1007/s12551-021-00876-9

DO - 10.1007/s12551-021-00876-9

M3 - Review article

AN - SCOPUS:85118487348

SN - 1867-2450

VL - 13

SP - 1019

EP - 1027

JO - Biophysical Reviews

JF - Biophysical Reviews

IS - 6

ER -