Atomistic Details of Charge/Space Competition in the Ca²⁺ Selectivity of Ryanodine Receptors

Ryanodine receptors (RyRs) are ion channels responsible for the fast release of Ca2+ from sarco/endoplasmic reticulum to cytosol and show a selectivity over monovalent cations. By utilizing recently developed multisite model in molecular dynamic simulations, we that multiple cations accumulate upper filter RyRs, small size high valence make it preferable K+ competition space this confined region negative electrostatic potential. The presence significantly increases energy barrier permeation, while has little impact on permeation. Our results provide atomistic details charge/space mechanism which ensures robustness their function. could be utilized protein- nanoengineering species.