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

Autor: Ansell TB; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK., Song W; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.; MSD R&D Innovation Centre, 120 Moorgate, London, EC2M 6UR, UK., Coupland CE; Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK.; Molecular Medicine Program, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada., Carrique L; Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK., Corey RA; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.; School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK., Duncan AL; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.; Department of Chemistry, Aarhus University, Lagelsandsgade 140, 8000, Aarhus C, Denmark., Cassidy CK; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.; Department of Physics and Astronomy, University of Missouri-Columbia, Columbia, MO, 65211, USA., Geurts MMG; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK., Rasmussen T; Biocenter and Rudolf-Virchow-Zentrum, Universität Würzburg, Haus D15, Josef-Schneider-Str. 2, 97080, Würzburg, Germany., Ward AB; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA., Siebold C; Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK., Stansfeld PJ; School of Life Sciences & Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK., Sansom MSP; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK. mark.sansom@bioch.ox.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Nov 27; Vol. 14 (1), pp. 7774. Date of Electronic Publication: 2023 Nov 27.
DOI: 10.1038/s41467-023-43392-y
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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