Deciphering Ca^<b>2+</b> permeation and valence selectivity in Ca_V1: Molecular dynamics simulations reveal the three-ion knock-on mechanism.

ABSTRACT: Voltage-gated calcium (Ca[Formula: see text]) channels are pivotal in cellular signaling due to their selective calcium ion permeation upon membrane depolarization. While previous studies have established the highly selective permeability of Ca[Formula: see text] channels, the detailed molecular mechanism remains elusive. Here, we use extensive atomistic molecular dynamics simulations to elucidate the mechanisms governing ion permeation and valence selectivity in Ca[Formula: see text]1 channels. Employing the electronic continuum correction method, we simulated a calcium conductance of approximately 9 to 11 pS, aligning closely with experimental measurement. Our simulations uncovered a three-ion knock-on mechanism critical for efficient calcium ion permeation, necessitating the binding of

SUBMITTER: Xue L 

PROVIDER: S-EPMC12146731 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature