LipIDens: simulation assisted interpretation of lipid densities in cryo-EM structures of membrane proteins

T. Bertie Ansell; Wanling Song; Claire E. Coupland; Loic Carrique; Robin A. Corey; Anna L. Duncan; C. Keith Cassidy; Maxwell M.G. Geurts; Tim Rasmussen; Andrew B. Ward; Christian Siebold; Phillip J. Stansfeld; Mark S.P. Sansom

doi:10.1038/s41467-023-43392-y

LipIDens: simulation assisted interpretation of lipid densities in cryo-EM structures of membrane proteins

T. Bertie Ansell, Wanling Song, Claire E. Coupland, Loic Carrique, Robin A. Corey, Anna L. Duncan, C. Keith Cassidy, Maxwell M.G. Geurts, Tim Rasmussen, Andrew B. Ward, Christian Siebold, Phillip J. Stansfeld, Mark S.P. Sansom^*

^*Corresponding author af dette arbejde

Institut for Kemi

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

12 Citationer (Scopus)

Abstract

Cryo-electron microscopy (cryo-EM) enables the determination of membrane protein structures in native-like environments. Characterising how membrane proteins interact with the surrounding membrane lipid environment is assisted by resolution of lipid-like densities visible in cryo-EM maps. Nevertheless, establishing the molecular identity of putative lipid and/or detergent densities remains challenging. Here we present LipIDens, a pipeline for molecular dynamics (MD) simulation-assisted interpretation of lipid and lipid-like densities in cryo-EM structures. The pipeline integrates the implementation and analysis of multi-scale MD simulations for identification, ranking and refinement of lipid binding poses which superpose onto cryo-EM map densities. Thus, LipIDens enables direct integration of experimental and computational structural approaches to facilitate the interpretation of lipid-like cryo-EM densities and to reveal the molecular identities of protein-lipid interactions within a bilayer environment. We demonstrate this by application of our open-source LipIDens code to ten diverse membrane protein structures which exhibit lipid-like densities.

Originalsprog	Engelsk
Artikelnummer	7774
Tidsskrift	Nature Communications
Vol/bind	14
Nummer	1
ISSN	2041-1723
DOI	https://doi.org/10.1038/s41467-023-43392-y
Status	Udgivet - nov. 2023

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10.1038/s41467-023-43392-yLicens: CC BY

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Ansell, T. B., Song, W., Coupland, C. E., Carrique, L., Corey, R. A., Duncan, A. L., Cassidy, C. K., Geurts, M. M. G., Rasmussen, T., Ward, A. B., Siebold, C., Stansfeld, P. J., & Sansom, M. S. P. (2023). LipIDens: simulation assisted interpretation of lipid densities in cryo-EM structures of membrane proteins. Nature Communications, 14(1), Artikel 7774. https://doi.org/10.1038/s41467-023-43392-y

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title = "LipIDens: simulation assisted interpretation of lipid densities in cryo-EM structures of membrane proteins",

abstract = "Cryo-electron microscopy (cryo-EM) enables the determination of membrane protein structures in native-like environments. Characterising how membrane proteins interact with the surrounding membrane lipid environment is assisted by resolution of lipid-like densities visible in cryo-EM maps. Nevertheless, establishing the molecular identity of putative lipid and/or detergent densities remains challenging. Here we present LipIDens, a pipeline for molecular dynamics (MD) simulation-assisted interpretation of lipid and lipid-like densities in cryo-EM structures. The pipeline integrates the implementation and analysis of multi-scale MD simulations for identification, ranking and refinement of lipid binding poses which superpose onto cryo-EM map densities. Thus, LipIDens enables direct integration of experimental and computational structural approaches to facilitate the interpretation of lipid-like cryo-EM densities and to reveal the molecular identities of protein-lipid interactions within a bilayer environment. We demonstrate this by application of our open-source LipIDens code to ten diverse membrane protein structures which exhibit lipid-like densities.",

author = "Ansell, {T. Bertie} and Wanling Song and Coupland, {Claire E.} and Loic Carrique and Corey, {Robin A.} and Duncan, {Anna L.} and Cassidy, {C. Keith} and Geurts, {Maxwell M.G.} and Tim Rasmussen and Ward, {Andrew B.} and Christian Siebold and Stansfeld, {Phillip J.} and Sansom, {Mark S.P.}",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = nov,

doi = "10.1038/s41467-023-43392-y",

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AU - Ansell, T. Bertie

AU - Song, Wanling

AU - Coupland, Claire E.

AU - Carrique, Loic

AU - Corey, Robin A.

AU - Duncan, Anna L.

AU - Cassidy, C. Keith

AU - Geurts, Maxwell M.G.

AU - Rasmussen, Tim

AU - Ward, Andrew B.

AU - Siebold, Christian

AU - Stansfeld, Phillip J.

AU - Sansom, Mark S.P.

PY - 2023/11

Y1 - 2023/11

N2 - Cryo-electron microscopy (cryo-EM) enables the determination of membrane protein structures in native-like environments. Characterising how membrane proteins interact with the surrounding membrane lipid environment is assisted by resolution of lipid-like densities visible in cryo-EM maps. Nevertheless, establishing the molecular identity of putative lipid and/or detergent densities remains challenging. Here we present LipIDens, a pipeline for molecular dynamics (MD) simulation-assisted interpretation of lipid and lipid-like densities in cryo-EM structures. The pipeline integrates the implementation and analysis of multi-scale MD simulations for identification, ranking and refinement of lipid binding poses which superpose onto cryo-EM map densities. Thus, LipIDens enables direct integration of experimental and computational structural approaches to facilitate the interpretation of lipid-like cryo-EM densities and to reveal the molecular identities of protein-lipid interactions within a bilayer environment. We demonstrate this by application of our open-source LipIDens code to ten diverse membrane protein structures which exhibit lipid-like densities.

AB - Cryo-electron microscopy (cryo-EM) enables the determination of membrane protein structures in native-like environments. Characterising how membrane proteins interact with the surrounding membrane lipid environment is assisted by resolution of lipid-like densities visible in cryo-EM maps. Nevertheless, establishing the molecular identity of putative lipid and/or detergent densities remains challenging. Here we present LipIDens, a pipeline for molecular dynamics (MD) simulation-assisted interpretation of lipid and lipid-like densities in cryo-EM structures. The pipeline integrates the implementation and analysis of multi-scale MD simulations for identification, ranking and refinement of lipid binding poses which superpose onto cryo-EM map densities. Thus, LipIDens enables direct integration of experimental and computational structural approaches to facilitate the interpretation of lipid-like cryo-EM densities and to reveal the molecular identities of protein-lipid interactions within a bilayer environment. We demonstrate this by application of our open-source LipIDens code to ten diverse membrane protein structures which exhibit lipid-like densities.

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LipIDens: simulation assisted interpretation of lipid densities in cryo-EM structures of membrane proteins

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