TY - JOUR
T1 - Capturing Biologically Complex Tissue-Specific Membranes at Different Levels of Compositional Complexity
AU - Ingólfsson, Helgi I.
AU - Bhatia, Harsh
AU - Zeppelin, Talia
AU - Bennett, W. F.Drew
AU - Carpenter, Kristy A.
AU - Hsu, Pin Chia
AU - Dharuman, Gautham
AU - Bremer, Peer Timo
AU - Schiøtt, Birgit
AU - Lightstone, Felice C.
AU - Carpenter, Timothy S.
N1 - Funding Information:
This work was partially funded by Laboratory Directed Research and Development at the Lawrence Livermore National Laboratory (16-FS-007). This work has been supported in part by the Joint Design of Advanced Computing Solutions for Cancer (JDACS4C) program established by the U.S. Department of Energy (DOE) and the National Cancer Institute (NCI) of the National Institutes of Health (NIH) and by the Independent Research Fund, Denmark (FNU grants 4002-00502B and 7014-00192B). For computing time, we thank Livermore Computing (LC), Livermore Institutional Grand Challenge, and the Centre for Scientific Computing Aarhus and Abacus 2.0. We thank the entire JDACS4C Pilot 2 team, particularly Frantz Jean-Francois and Andrew Stephen of Frederick National Laboratory for Cancer Research, for their helpful discussion. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344, Los Alamos National Laboratory under Contract DEAC5206NA25396, Oak Ridge National Laboratory under Contract DE-AC05-00OR22725, and Frederick National Laboratory for Cancer Research under Contract HHSN261200800001E, Release number LLNL-JRNL-808886.
PY - 2020/9/10
Y1 - 2020/9/10
N2 - Plasma membranes (PMs) contain hundreds of different lipid species that contribute differently to overall bilayer properties. By modulation of these properties, membrane protein function can be affected. Furthermore, inhomogeneous lipid mixing and domains of lipid enrichment/depletion can sort proteins and provide optimal local environments. Recent coarse-grained (CG) Martini molecular dynamics efforts have provided glimpses into lipid organization of different PMs: an "Average"and a "Brain"PM. Their high complexity and large size require long simulations (∼80 μs) for proper sampling. Thus, these simulations are computationally taxing. This level of complexity is beyond the possibilities of all-atom simulations, raising the question - what complexity is needed for "realistic"bilayer properties? We constructed CG Martini PM models of varying complexity (63 down to 8 different lipids). Lipid tail saturations and headgroup combinations were kept as consistent as possible for the "tissues'"(Average/Brain) at three levels of compositional complexity. For each system, we analyzed membrane properties to evaluate which features can be retained at lower complexity and validate eight-component bilayers that can act as reliable mimetics for Average or Brain PMs. Systems of reduced complexity deliver a more robust and malleable tool for computational membrane studies and allow for equivalent all-atom simulations and experiments.
AB - Plasma membranes (PMs) contain hundreds of different lipid species that contribute differently to overall bilayer properties. By modulation of these properties, membrane protein function can be affected. Furthermore, inhomogeneous lipid mixing and domains of lipid enrichment/depletion can sort proteins and provide optimal local environments. Recent coarse-grained (CG) Martini molecular dynamics efforts have provided glimpses into lipid organization of different PMs: an "Average"and a "Brain"PM. Their high complexity and large size require long simulations (∼80 μs) for proper sampling. Thus, these simulations are computationally taxing. This level of complexity is beyond the possibilities of all-atom simulations, raising the question - what complexity is needed for "realistic"bilayer properties? We constructed CG Martini PM models of varying complexity (63 down to 8 different lipids). Lipid tail saturations and headgroup combinations were kept as consistent as possible for the "tissues'"(Average/Brain) at three levels of compositional complexity. For each system, we analyzed membrane properties to evaluate which features can be retained at lower complexity and validate eight-component bilayers that can act as reliable mimetics for Average or Brain PMs. Systems of reduced complexity deliver a more robust and malleable tool for computational membrane studies and allow for equivalent all-atom simulations and experiments.
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U2 - 10.1021/acs.jpcb.0c03368
DO - 10.1021/acs.jpcb.0c03368
M3 - Article
C2 - 32790367
AN - SCOPUS:85090870663
VL - 124
SP - 7819
EP - 7829
JO - The journal of physical chemistry. B
JF - The journal of physical chemistry. B
SN - 1520-5207
IS - 36
ER -