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

Area of Science:

• Computational Biochemistry
• Molecular Dynamics Simulations
• Biophysics

Background:

• Molecular oxygen (O2) is vital for cellular respiration, necessitating detailed simulations of its biological pathways.
• All-atom (AA) molecular dynamics (MD) simulations provide high detail but are computationally expensive for large systems.
• Coarse-grained (CG) simulations offer a computationally efficient alternative for larger scales, but a CG model for O2 was previously unavailable.

Purpose of the Study:

• To develop and validate a coarse-grained (CG) model for molecular oxygen (O2) suitable for integration with the Martini 3 force field.
• To assess the model's accuracy in reproducing O2's diffusion, membrane permeability, and protein binding characteristics compared to AA simulations and experimental data.

Main Methods:

• Selection of a CG O2 model (TC3 bead) from the Martini 3 force field based on physical and chemical properties.
• Calculation of diffusion constants in water and hexadecane.
• Determination of O2 permeability across phospholipid and cholesterol-containing membranes.
• Simulation of O2 binding to the T4 lysozyme L99A protein.
• Comparison of CG simulation results with AA simulations and experimental data.

Main Results:

• The developed CG O2 model demonstrated semiquantitative agreement with AA simulation data and experimental findings for diffusion and membrane permeation.
• The model successfully replicated O2's binding behavior within hydrophobic protein cavities, consistent with AA simulations.
• The CG O2 model is compatible with the Martini 3 force field, enabling its use in larger biological simulations.

Conclusions:

• The new CG O2 model provides a computationally efficient and accurate representation of molecular oxygen's behavior in biological systems.
• This model facilitates large-scale simulations of O2 transport and cellular respiration, advancing our understanding of oxygen's role in biology.
• The compatibility with Martini 3 expands the toolkit for simulating complex biomolecular systems involving oxygen.