Markov state models of proton- and pore-dependent activation in a pentameric ligand-gated ion channel.

ABSTRACT: Ligand-gated ion channels conduct currents in response to chemical stimuli, mediating electrochemical signaling in neurons and other excitable cells. For many channels, the details of gating remain unclear, partly due to limited structural data and simulation timescales. Here, we used enhanced sampling to simulate the pH-gated channel GLIC, and construct Markov state models (MSMs) of gating. Consistent with new functional recordings, we report in oocytes, our analysis revealed differential effects of protonation and mutation on free-energy wells. Clustering of closed- versus open-like states enabled estimation of open probabilities and transition rates, while higher-order clustering affirmed conformational trends in gating. Furthermore, our models uncovered state- and protonation-dependent

SUBMITTER: Bergh C 

PROVIDER: S-EPMC8635979 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature