Molecular dynamics simulations suggest possible activation and deactivation pathways in the hERG channel.

ABSTRACT: The elusive activation/deactivation mechanism of hERG is investigated, a voltage-gated potassium channel involved in severe inherited and drug-induced cardiac channelopathies, including the Long QT Syndrome. Firstly, the available structural data are integrated by providing a homology model for the closed state of the channel. Secondly, molecular dynamics combined with a network analysis revealed two distinct pathways coupling the voltage sensor domain with the pore domain. Interestingly, some LQTS-related mutations known to impair the activation/deactivation mechanism are distributed along the identified pathways, which thus suggests a microscopic interpretation of their role. Split channels simulations clarify a surprising feature of this channel, which is still able to gate when a cut i

SUBMITTER: Costa F 

PROVIDER: S-EPMC8873449 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature