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

Ansell, T. B.; Song, W.; Coupland, C. E.; Carrique, L.; Corey, R. A.; Duncan, A. L.; Cassidy, C. K.; Guerts, M. M. G.; Rasmussen, T.; Ward, A. B.; Siebold, C.; Stansfeld, P. J.; Sansom, M.

doi:10.1101/2022.06.30.498233

bioRxiv · 10.1101/2022.06.30.498233

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

Ansell, T. B.·Song, W.·Coupland, C. E.·Carrique, L.·Corey, R. A.·Duncan, A. L.·Cassidy, C. K.·Guerts, M. M. G.·Rasmussen, T.·Ward, A. B.·Siebold, C.·Stansfeld, P. J.·Sansom, M.

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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. The LipIDens code is open-source and embedded within a notebook format to assist automation and usability.

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Ansell, T. B., Song, W., Coupland, C. E., Carrique, L., Corey, R. A., Duncan, A. L., Cassidy, C. K., Guerts, M. M. G., Rasmussen, T., Ward, A. B., Siebold, C., Stansfeld, P. J., Sansom, M.. 2022-07-01. LipIDens: Simulation assisted interpretation of lipid densities in cryo-EM structures of membrane proteins.. https://doi.org/10.1101/2022.06.30.498233

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