Unraveling membrane properties at the organelle-level with LipidDyn

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  • Simone Scrima
  • Matteo Tiberti
  • Alessia Campo
  • Elisabeth Corcelle-Termeau
  • Delphine Judith
  • Mads Møller Foged
  • Knut Kristoffer Bundgaard Clemmensen
  • Sharon A. Tooze
  • Jaattela, Marja
  • Kenji Maeda
  • Matteo Lambrughi
  • Elena Papaleo

Cellular membranes are formed from different lipids in various amounts and proportions depending on the subcellular localization. The lipid composition of membranes is sensitive to changes in the cellular environment, and its alterations are linked to several diseases. Lipids not only form lipid-lipid interactions but also interact with other biomolecules, including proteins. Molecular dynamics (MD) simulations are a powerful tool to study the properties of cellular membranes and membrane-protein interactions on different timescales and resolutions. Over the last few years, software and hardware for biomolecular simulations have been optimized to routinely run long simulations of large and complex biological systems. On the other hand, high-throughput techniques based on lipidomics provide accurate estimates of the composition of cellular membranes at the level of subcellular compartments. Lipidomic data can be analyzed to design biologically relevant models of membranes for MD simulations. Similar applications easily result in a massive amount of simulation data where the bottleneck becomes the analysis of the data. In this context, we developed LipidDyn, a Python-based pipeline to streamline the analyses of MD simulations of membranes of different compositions. Once the simulations are collected, LipidDyn provides average properties and time series for several membrane properties such as area per lipid, thickness, order parameters, diffusion motions, lipid density, and lipid enrichment/depletion. The calculations exploit parallelization, and the pipeline includes graphical outputs in a publication-ready form. We applied LipidDyn to different case studies to illustrate its potential, including membranes from cellular compartments and transmembrane protein domains. LipidDyn is available free of charge under the GNU General Public License from https://github.com/ELELAB/LipidDyn.

OriginalsprogEngelsk
TidsskriftComputational and Structural Biotechnology Journal
Vol/bind20
Sider (fra-til)3604-3614
Antal sider11
ISSN2001-0370
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
E.P. group is supported by Danmarks Frie Forskningsfond, Natural Science, Project 1 (102517), NovoNordisk Fonden Bioscience and Basic Biomedicine (NNF20OC0065262) and Andreas og Grethe Gullev Hansens Fond (to M.L.). M.J. is supported by NovoNordisk Distinguished Investigator Grant - Endocrinology and Metabolism (054296). M.J. and E.P. groups are part of the Center of Excellence for Autophagy, Recycling, and Disease (CARD), which is supported by Danmarks Grundforskningsfond (DNRF125). K.M. is supported by Danmarks Frie Forskningsfond, Sapere Aude (6108–00542B). D.J. and S.A.T. were supported by The Francis Crick Institute which receives its core funding from Cancer Research UK (FC001187), the UK Medical Research Council (FC001187). This research was funded in whole, or in part, by the Wellcome Trust (FC001187).

Funding Information:
The authors would like to thank Valeria Zoni and Stefano Vanni for sharing the protocol and data to test our implementation of the Enrichment class on previously published trajectories. Moreover, the authors would like to thank Matteo Arnaudi, Ludovica Beltrame, Matteo Orlandi, and Mattia Utichi for testing installation and case studies on different architectures. We also thank Dr. Mesut Bilgin and the Lipidomics Core Facility of DCRC for making instruments and materials available for lipidomics experiments.

Publisher Copyright:
© 2022

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