Mechanism of Molecular Oxygen Diffusion in a Hypoxia-Sensing Prolyl Hydroxylase Using Multiscale Simulation

Mechanism of Molecular Oxygen Diffusion in a Hypoxia-Sensing Prolyl Hydroxylase Using Multiscale Simulation. J Am Chem Soc. 2020 Feb 5;142(5):2253-2263. doi: 10.1021/jacs.9b09236.
A general multiscale molecular simulation approach for the calculation of diffusion rates and the determination of pathways by which O2 gas can reach the active site of oxygenases is presented and applied to the PHD2 oxygenase. PHD2 provides a direct link between O2 availability and the hypoxic response in humans. The mechanism by which O2 gas reaches the protein active site is important to understand the function of these enzymes in diverse physiological roles and their links to disease, and it is crucial in the development of inhibitors.