Inner pore hydration free energy controls the activation of big potassium channels.

ABSTRACT: Hydrophobic gating is an emerging mechanism in regulation of protein ion channels where the pore remains physically open but becomes dewetted to block ion permeation. Atomistic molecular dynamics simulations have played a crucial role in understanding hydrophobic gating by providing the molecular details to complement mutagenesis and structural studies. However, existing studies rely on direct simulations and do not quantitatively describe how the sequence and structural changes may control the delicate liquid-vapor equilibrium of confined water in the pore of the channel protein. To address this limitation, we explore two enhanced sampling methods, namely metadynamics and umbrella sampling, to derive free-energy profiles of pore hydration in both the closed and open states of big potassiu

SUBMITTER: Nordquist EB 

PROVIDER: S-EPMC10111268 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature