Free energy and kinetics of cAMP permeation through connexin26 via applied voltage and milestoning.

ABSTRACT: The connexin family is a diverse group of highly regulated wide-pore channels permeable to biological signaling molecules. Despite the critical roles of connexins in mediating selective molecular signaling in health and disease, the basis of molecular permeation through these pores remains unclear. Here, we report the thermodynamics and kinetics of binding and transport of a second messenger, adenosine-3',5'-cyclophosphate (cAMP), through a connexin26 hemichannel (Cx26). First, inward and outward fluxes of cAMP molecules solvated in KCl solution were obtained from 4 μs of ± 200 mV simulations. These fluxes data yielded a single-channel permeability of cAMP and cAMP/K⁺ permeability ratio consistent with experimentally measured values. The results from voltage simulations were the

SUBMITTER: Jiang W 

PROVIDER: S-EPMC8391066 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature