Free Energy of Membrane Pore Formation and Stability from Molecular Dynamics Simulations
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F25%3A00140546" target="_blank" >RIV/00216224:14740/25:00140546 - isvavai.cz</a>
Result on the web
<a href="https://pubs.acs.org/doi/10.1021/acs.jcim.4c01960" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jcim.4c01960</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jcim.4c01960" target="_blank" >10.1021/acs.jcim.4c01960</a>
Alternative languages
Result language
angličtina
Original language name
Free Energy of Membrane Pore Formation and Stability from Molecular Dynamics Simulations
Original language description
Understanding the molecular mechanisms of pore formation is crucial for elucidating fundamental biological processes and developing therapeutic strategies, such as the design of drug delivery systems and antimicrobial agents. Although experimental methods can provide valuable information, they often lack the temporal and spatial resolution necessary to fully capture the dynamic stages of pore formation. In this study, we present two novel collective variables (CVs) designed to characterize membrane pore behavior, particularly its energetics, through molecular dynamics (MD) simulations. The first CV-termed Full-Path-effectively tracks both the nucleation and expansion phases of pore formation. The second CV-called Rapid-is tailored to accurately assess pore expansion in the limit of large pores, providing quick and reliable method for evaluating membrane line tension under various conditions. Our results clearly demonstrate that the line tension predictions from both our CVs are in excellent agreement. Moreover, these predictions align qualitatively with available experimental data. Specifically, they reflect higher line tension of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) membranes containing 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-l-serine (POPS) lipids compared to pure POPC, the decrease in line tension of POPC vesicles as the 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) content increases, and higher line tension when ionic concentration is increased. Notably, these experimental trends are accurately captured only by the all-atom CHARMM36 and prosECCo75 force fields. In contrast, the all-atom Slipids force field, along with the coarse-grained Martini 2.2, Martini 2.2 polarizable, and Martini 3 models, show varying degrees of agreement with experiments. Our developed CVs can be adapted to various MD simulation engines for studying pore formation, with potential implications in membrane biophysics. They are also applicable to simulations involving external agents, offering an efficient alternative to existing methodologies.
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
10400 - Chemical sciences
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 Information and Modeling
ISSN
1549-9596
e-ISSN
1549-960X
Volume of the periodical
65
Issue of the periodical within the volume
2
Country of publishing house
US - UNITED STATES
Number of pages
13
Pages from-to
908-920
UT code for WoS article
001395263400001
EID of the result in the Scopus database
2-s2.0-85214656624