Mechanosensitive Piezo1 and Piezo2 channels produce mechanically-activated intracellular signals that are central to a bewildering number of physiological and pathological processes. Besides mechanical stimuli, Piezo1 is also partially activated by the synthetic small molecule Yoda1. To date, the mechanism by which Yoda1 interacts with and activates Piezo1 is unknown. Here, we used a multi-scale molecular dynamics (MD) simulation of Piezo1, allosteric network analysis and principal component guided free energy calculations, to investigate how Yoda1 interacts with and modulates Peizo1 in absence or presence of mechanical stimuli.

Chemical activation and allosteric modulation of mechanosensitive Piezo1 channel

2019 Fall National Meeting

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