Martini 3 Limitations in Phospholipid Flip-Flop
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F25%3A00142337" target="_blank" >RIV/00216224:14740/25:00142337 - isvavai.cz</a>
Result on the web
<a href="https://pubs.acs.org/doi/10.1021/acs.jctc.5c00994" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jctc.5c00994</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jctc.5c00994" target="_blank" >10.1021/acs.jctc.5c00994</a>
Alternative languages
Result language
angličtina
Original language name
Martini 3 Limitations in Phospholipid Flip-Flop
Original language description
Phospholipid membranes serve as essential barriers in biological systems, and protein-mediated lipid flip-flop is a crucial process for lipid homeostasis in membranes, which is vital for various cellular functions. These phenomena can be studied using the Martini coarse-grained force field, a valuable tool for membrane simulations that balances computational efficiency with chemical accuracy while capturing key membrane properties. However, the accuracy of the newer Martini 3 force field in describing energetics of phospholipid flip-flop remains unknown. Here, we show dramatic differences in the free energy barriers of lipid flip-flop when simulated with Martini 3, Martini 2.2, and CHARMM36m force fields. Using umbrella sampling simulations of six phospholipids (POPC, DPPA, POPE, POPG, POPS, and DPTAP) in the POPC membrane, we demonstrate that Martini 3 predicts significantly lower flip-flop barriers compared to all-atom simulations and the older Martini 2.2 version, with particularly severe underestimation for the positively charged lipid (DPTAP). For DPTAP, we identified that altered Lennard-Jones parameters between choline and alkyl tail beads likely contribute to this discrepancy, as evidenced by our systematic parameter testing. These findings highlight limitations in the current Martini 3 parametrization that should be considered when studying processes involving molecular transport across membranes and suggest potential refinements to improve the model's accuracy for such phenomena. To complete the picture, we also discuss the energetics of flip-flops of phospholipids with various lipid tail lengths (DLPC, DMPC, DPPC, DSPC) and lipid tail saturation (DOPC).
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10403 - Physical chemistry
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Chemical Theory and Computation
ISSN
1549-9618
e-ISSN
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Volume of the periodical
21
Issue of the periodical within the volume
19
Country of publishing house
US - UNITED STATES
Number of pages
7
Pages from-to
9227-9233
UT code for WoS article
001579181000001
EID of the result in the Scopus database
2-s2.0-105018675174