CoChat
Sign Up
PreprintCited by 31Advanced Electron Microscopy Techniques and ApplicationsProtein Structure and DynamicsLipid Membrane Structure and Behavior

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

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

Open access
Ansell, T. Bertie, Song, Wanling, Coupland, Claire E., Carrique, Loic, Corey, Robin A., Duncan, Anna L., Cassidy, C. Keith, Geurts, Maxwell M. G., Rasmussen, Tim, Ward, Andrew B., Siebold, Christian, Stansfeld, Phillip J., Sansom, Mark S. P.·2022·Nature Communications
DOI 10.1101/2022.06.30.498233PMC PMC10682427

Preprint — published as 10.1038/s41467-023-43392-y

Open this paper in CoChat — free accountOpen PDF

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.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1101/2022.06.30.498233

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 77

  1. 2020, Changes in membrane protein structural biology, Biology, 9, 1
  2. 10.1073/pnas.2009385117 · DOI
  3. 10.1038/s41586-020-2829-0 · DOI
  4. 2021, Structural mechanism of heat-induced opening of a temperature-sensitive TRP channel, Nat. Struct. Mol. Biol, 28, 564, 10.1038/s41594-021-00615-4 · DOI
  5. 10.1038/s41467-019-13889-6 · DOI · Paper page
  6. 2021, High-resolution cryo-EM structure of photosystem II reveals damage from high-dose electron beams, Commun. Biol, 4, 1
  7. 10.1371/journal.pbio.3001215 · DOI
  8. Vallese, A. F. et al. Architecture of the human erythrocyte ankyrin-1 complex. bioRxiv 1–64 (2022). · DOI
  9. 10.1126/sciadv.aax2950 · DOI
  10. 2021, Structural insights into the lipid and ligand regulation of serotonin receptors, Nature, 592, 469, 10.1038/s41586-021-03376-8 · DOI
  11. 2021, Cryo-EM structure of type 1 IP3R channel in a lipid bilayer, Commun. Biol, 4, 1
  12. 10.1038/s41467-020-20241-w · DOI · Paper page
  13. 2018, Lipid-Protein Interactions Are Unique Fingerprints for Membrane Proteins, ACS Cent. Sci, 4, 709, 10.1021/acscentsci.8b00143 · DOI
  14. 2019, Emerging Diversity In Lipid-Protein Interactions, Chem. Rev, 119, 5775, 10.1021/acs.chemrev.8b00451 · DOI
  15. 10.1146/annurev-pharmtox-010919-023411 · DOI · Paper page
  16. 10.1016/j.bpj.2019.03.025 · DOI
  17. 2020, Interfacial Binding Sites for Cholesterol on Kir, Kv, K2P, and Related Potassium Channels, Biophys. J, 119, 35, 10.1016/j.bpj.2020.05.028 · DOI
  18. 2011, Equilibrium Sampling in Biomolecular Simulation, Annu Rev Biophys, 40, 41, 10.1146/annurev-biophys-042910-155255 · DOI
  19. 10.1021/bi9013193 · DOI
  20. 2020, Lipid Interactions of a Ciliary Membrane TRP Channel: Simulation and Structural Studies of Polycystin-2, Structure, 28, 169, 10.1016/j.str.2019.11.005 · DOI
  21. 10.1038/s41467-020-20241-w · DOI · Paper page
  22. 2021, ProLint: a web-based framework for the automated data analysis and visualization of lipid–protein interactions, Nucleic Acids Res, 49, W544, 10.1093/nar/gkab409 · DOI
  23. 2021, LiPyphilic: A Python Toolkit for the Analysis of Lipid Membrane Simulations, J. Chem. Theory Comput, 17, 5907, 10.1021/acs.jctc.1c00447 · DOI
  24. 2022, PyLipID: A Python Package for Analysis of Protein-Lipid Interactions from Molecular Dynamics Simulations, J. Chem. Theory Comput, 18, 1188, 10.1021/acs.jctc.1c00708 · DOI
  25. 10.1038/s41592-020-0731-1 · DOI
  26. 10.1002/anie.202112232 · DOI
  27. 10.1016/j.molcel.2021.04.022 · DOI
  28. 10.1101/362970 · DOI
  29. 2018, Molecular Dynamics Simulations of Kir2.2 Interactions with an Ensemble of Cholesterol Molecules, Biophys. J, 115, 1264, 10.1016/j.bpj.2018.07.041 · DOI
  30. 10.1073/pnas.1918387117 · DOI
  31. 10.1126/sciadv.abh2217 · DOI
  32. 2021, Bacterial Analogs to Cholesterol Affect Dimerization of Proteorhodopsin and Modulates Preferred Dimer Interface, J. Chem. Theory Comput, 17, 2502, 10.1021/acs.jctc.0c01174 · DOI
  33. 2021, In silico identification of cholesterol binding motifs in the chemokine receptor CCR3, Membranes, 11, 1
  34. 2019, Structures of the otopetrin proton channels Otop1 and Otop3, Nat. Struct. Mol. Biol, 26, 518, 10.1038/s41594-019-0235-9 · DOI
  35. 10.1073/pnas.2023989118 · DOI
  36. 10.1073/pnas.2023989118 · DOI
  37. 10.1016/j.jmb.2019.05.043 · DOI
  38. 10.1038/nrm2330 · DOI · Paper page
  39. 10.1038/s41589-020-0529-6 · DOI
  40. 2018, Understanding the diversity of membrane lipid composition, Nat. Rev. Mol. Cell Biol, 29, 281
  41. 10.1021/ct300646g · DOI · Paper page
  42. 2020, Capturing Biologically Complex Tissue-Specific Membranes at Different Levels of Compositional Complexity, J. Phys. Chem. B, 124, 7819, 10.1021/acs.jpcb.0c03368 · DOI
  43. 2019, Boundary lipids of the nicotinic acetylcholine receptor: Spontaneous partitioning via coarse-grained molecular dynamics simulation, Biochim. Biophys. Acta - Biomembr, 1861, 887, 10.1016/j.bbamem.2019.01.005 · DOI
  44. 2020, Understanding the Link between Lipid Diversity and the Biophysical Properties of the Neuronal Plasma Membrane, Biochemistry, 59, 3010, 10.1021/acs.biochem.0c00524 · DOI
  45. 2021, Investigating the lipid fingerprint of SLC6 neurotransmitter transporters: a comparison of dDAT, hDAT, hSERT, and GlyT2, BBA Adv, 1, 100010, 10.1016/j.bbadva.2021.100010 · DOI
  46. 2021, Relative Affinities of Protein-Cholesterol Interactions from Equilibrium Molecular Dynamics Simulations, J. Chem. Theory Comput, 17, 6548, 10.1021/acs.jctc.1c00547 · DOI
  47. 2020, Structure of the neurotensin receptor 1 in complex with β-arrestin 1, Nature, 579, 303, 10.1038/s41586-020-1953-1 · DOI · Paper page
  48. 2021, CG2AT2: An Enhanced Fragment-Based Approach for Serial Multi-scale Molecular Dynamics Simulations, J. Chem. Theory Comput, 17, 6472, 10.1021/acs.jctc.1c00295 · DOI · Paper page
  49. 10.1002/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.3.CO;2-L · DOI
  50. 2015, Parameters for Martini sterols and hopanoids based on a virtual-site description, J. Chem. Phys, 143, 243152-1-243152-12
  51. 2021, Nonconverged Constraints Cause Artificial Temperature Gradients in Lipid Bilayer Simulations, J. Phys. Chem. B, 125, 9537, 10.1021/acs.jpcb.1c03665 · DOI
  52. 10.1016/0263-7855(96)00018-5 · DOI · Paper page
  53. 10.1021/ct200133y · DOI
  54. 10.1016/J.SOFTX.2015.06.001 · DOI · Paper page
  55. 2019, Computational Modeling of Realistic Cell Membranes, Chem. Rev, 119, 6184, 10.1021/acs.chemrev.8b00460 · DOI
  56. 10.1002/jcc.23354 · DOI
  57. 2021, CG2AT2: An Enhanced Fragment-Based Approach for Serial Multi-scale Molecular Dynamics Simulations, J. Chem. Theory Comput, 17, 6472, 10.1021/acs.jctc.1c00295 · DOI · Paper page
  58. 2015, Parameters for Martini sterols and hopanoids based on a virtual-site description, J. Chem. Phys, 143, 243152-1-243152-12
  59. 2021, Nonconverged Constraints Cause Artificial Temperature Gradients in Lipid Bilayer Simulations, J. Phys. Chem. B, 125, 9537, 10.1021/acs.jpcb.1c03665 · DOI
  60. 2004, Coot: Model-building tools for molecular graphics, Acta Cryst, D60, 2126
  61. 10.1002/pro.3235 · DOI · Paper page
  62. 10.1016/0263-7855(96)00018-5 · DOI · Paper page
  63. 2022, PyLipID: A Python Package for Analysis of Protein-Lipid Interactions from Molecular Dynamics Simulations, J. Chem. Theory Comput, 18, 1188, 10.1021/acs.jctc.1c00708 · DOI
  64. 10.1021/ct200133y · DOI
  65. 10.1016/J.SOFTX.2015.06.001 · DOI · Paper page
  66. 10.1021/ct300646g · DOI · Paper page
  67. 10.1140/epjst/e2019-800186-9 · DOI
  68. 2019, Fat SIRAH: Coarse-Grained Phospholipids to Explore Membrane-Protein Dynamics, J. Chem. Theory Comput, 15, 5674, 10.1021/acs.jctc.9b00435 · DOI
  69. 10.1093/nar/gky1047 · DOI
  70. 10.1016/S0076-6879(03)74020-8 · DOI
  71. 10.1093/nar/gky427 · DOI
  72. 10.1073/pnas.1914677117 · DOI · Paper page
  73. 10.1126/science.abj8754 · DOI · Paper page
  74. 2021, Martini 3: a general purpose force field for coarse-grained molecular dynamics, Nat. Methods, 18, 382, 10.1038/s41592-021-01098-3 · DOI · Paper page
  75. 10.1021/jp071097f · DOI
  76. 10.1021/ct9002114 · DOI
  77. 10.1038/s41592-020-0731-1 · DOI

Metadata

Authors
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.
Affiliations
  • University of Oxford (GB)
  • Centre for Human Genetics (GB)
  • University of Bristol (GB)
  • Aarhus University (DK)
  • University of Würzburg (DE)
  • Scripps Research Institute (US)
  • University of Warwick (GB)
Corresponding author
Sansom, Mark S. P.
ORCID
Venue
Nature Communications
Publisher
openRxiv
Published
2022-07-01
Volume
14
Issue
1
Pages
7774-7774
ISSN
2041-1723 (ISSN-L)
DOI
10.1101/2022.06.30.498233
PMC
PMC10682427
OpenAlex
W4389046776
Cited by
31
References
1
Citations by year
2026: 9 · 2025: 13 · 2024: 8 · 2023: 1
FWCI
2.74
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Warwick Research Archive Portal (University of Warwick) (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Bristol Research (University of Bristol) (submittedVersion, cc-by)
  • Explore Bristol Research (submittedVersion, cc-by)
Funders
  • Ray Thomas Edwards Foundation
  • Wellcome Trust (208361/Z/17/Z, 102164/Z/13/Z)
  • Cancer Research UK (DRCRPG-May23, DRCRPG-May23 / 100002, C20724 / A26752, 26752, A26752, C20724, 100002)
  • Partnership for Advanced Computing in Europe AISBL (2016163984)
  • Medical Research Council (203141/Z/16/Z, MR/S009213/1)
  • Biotechnology and Biological Sciences Research Council (BB/T01508X/1, BB/R002517/1, BB/S003339/1, BB/P01948X/1, BB/R00126X/1, BB/P01948X/2, P01948X, R002517, S003339)
  • H2020 European Research Council (647278)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
Keywords
membrane proteins, protein-lipid interactions, membrane lipid environment
MeSH terms
Membrane Lipids, Membrane Proteins, Protein Conformation, Cryoelectron Microscopy, Molecular Dynamics Simulation

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review