The membrane permeability of small molecule solutes can be calculated from the transmembrane potential of mean force and diffusivity using the solubility-diffusion model. We have used this model to calculate the membrane permeability of endogenous gasotransmitter molecules NO, CO, and H<sub>2</sub>S. Replica-exchange MD was used to calculate the potential of mean force of permeation. The transmembrane diffusivity was calculated from the velocity autocorrelation function of the restrained solute, using a formalism based on the Generalized Langevin Equation. Force fields were developed and validated using high-level ab initio (CCSD(T)-F12) and ab initio molecular dynamics. The calculated transmembrane nitric oxide diffusivity was found to be in good agreement with experimental EPR measurements using spin-labeled lipids. The membrane permeability of all three gasotransmitters was calculated to be very high (&gt; 1 cm/s), indicating that these molecules can cross membranes freely. This high permeability stems from the hydrophobicity of these gaseous molecules. Hydrophobicity, high rates of diffusion, and acute reactivity are common properties of gasotransmitters.

Membrane permeability of gasotransmitters calculated using the solubility-diffusion model

254th National Meeting (2017)

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