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

TY - JOUR

T1 - LipIDens

T2 - simulation assisted interpretation of lipid densities in cryo-EM structures of membrane proteins

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.

N1 - Publisher Copyright: © 2023, The Author(s).

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.

UR - http://www.scopus.com/inward/record.url?scp=85177832311&partnerID=8YFLogxK

U2 - 10.1038/s41467-023-43392-y

DO - 10.1038/s41467-023-43392-y

M3 - Journal article

C2 - 38012131

AN - SCOPUS:85177832311

SN - 2041-1723

VL - 14

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 7774

ER -