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Validation of a Coarse-Grained Martini 3 Model for Molecular Oxygen

Davoudi, Samaneh ; Vainikka, Petteri A. LU ; Marrink, Siewert J. and Ghysels, An (2025) In Journal of Chemical Theory and Computation 21(1). p.428-439
Abstract

Molecular oxygen (O2) is essential for life, and continuous effort has been made to understand its pathways in cellular respiration with all-atom (AA) molecular dynamics (MD) simulations of, e.g., membrane permeation or binding to proteins. To reach larger length scales with models, such as curved membranes in mitochondria or caveolae, coarse-grained (CG) simulations could be used at much lower computational cost than AA simulations. Yet a CG model for O2 is lacking. In this work, a CG model for O2 is therefore carefully selected from the Martini 3 force field based on criteria including size, zero charge, nonpolarity, solubility in nonpolar organic solvents, and partitioning in a phospholipid membrane.... (More)

Molecular oxygen (O2) is essential for life, and continuous effort has been made to understand its pathways in cellular respiration with all-atom (AA) molecular dynamics (MD) simulations of, e.g., membrane permeation or binding to proteins. To reach larger length scales with models, such as curved membranes in mitochondria or caveolae, coarse-grained (CG) simulations could be used at much lower computational cost than AA simulations. Yet a CG model for O2 is lacking. In this work, a CG model for O2 is therefore carefully selected from the Martini 3 force field based on criteria including size, zero charge, nonpolarity, solubility in nonpolar organic solvents, and partitioning in a phospholipid membrane. This chosen CG model for O2 (TC3 bead) is then further evaluated through the calculation of its diffusion constant in water and hexadecane, its permeability rate across pure phospholipid- and cholesterol-containing membranes, and its binding to the T4 lysozyme L99A protein. Our CG model shows semiquantitative agreement between CG diffusivity and permeation rates with the corresponding AA values and available experimental data. Additionally, it captures the binding to hydrophobic cavities of the protein, aligning well with the AA simulation of the same system. Thus, the results show that our O2 model approximates the behavior observed in the AA simulations. The CG O2 model is compatible with the widely used multifunctional Martini 3 force field for biological simulations, which will allow for the simulation of large biomolecular systems involved in O2’s transport in the body.

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type
Contribution to journal
publication status
published
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in
Journal of Chemical Theory and Computation
volume
21
issue
1
pages
12 pages
publisher
The American Chemical Society (ACS)
external identifiers
  • pmid:39807536
  • scopus:85214909211
ISSN
1549-9618
DOI
10.1021/acs.jctc.4c01348
language
English
LU publication?
yes
id
acd5bb7a-6e2e-4b5a-a814-20f538be472d
date added to LUP
2025-03-10 11:52:47
date last changed
2025-07-14 22:40:23
@article{acd5bb7a-6e2e-4b5a-a814-20f538be472d,
  abstract     = {{<p>Molecular oxygen (O<sub>2</sub>) is essential for life, and continuous effort has been made to understand its pathways in cellular respiration with all-atom (AA) molecular dynamics (MD) simulations of, e.g., membrane permeation or binding to proteins. To reach larger length scales with models, such as curved membranes in mitochondria or caveolae, coarse-grained (CG) simulations could be used at much lower computational cost than AA simulations. Yet a CG model for O<sub>2</sub> is lacking. In this work, a CG model for O<sub>2</sub> is therefore carefully selected from the Martini 3 force field based on criteria including size, zero charge, nonpolarity, solubility in nonpolar organic solvents, and partitioning in a phospholipid membrane. This chosen CG model for O<sub>2</sub> (TC3 bead) is then further evaluated through the calculation of its diffusion constant in water and hexadecane, its permeability rate across pure phospholipid- and cholesterol-containing membranes, and its binding to the T4 lysozyme L99A protein. Our CG model shows semiquantitative agreement between CG diffusivity and permeation rates with the corresponding AA values and available experimental data. Additionally, it captures the binding to hydrophobic cavities of the protein, aligning well with the AA simulation of the same system. Thus, the results show that our O<sub>2</sub> model approximates the behavior observed in the AA simulations. The CG O<sub>2</sub> model is compatible with the widely used multifunctional Martini 3 force field for biological simulations, which will allow for the simulation of large biomolecular systems involved in O<sub>2</sub>’s transport in the body.</p>}},
  author       = {{Davoudi, Samaneh and Vainikka, Petteri A. and Marrink, Siewert J. and Ghysels, An}},
  issn         = {{1549-9618}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{428--439}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{Journal of Chemical Theory and Computation}},
  title        = {{Validation of a Coarse-Grained Martini 3 Model for Molecular Oxygen}},
  url          = {{http://dx.doi.org/10.1021/acs.jctc.4c01348}},
  doi          = {{10.1021/acs.jctc.4c01348}},
  volume       = {{21}},
  year         = {{2025}},
}