New Vistas on the Recruiting of Ferrous Iron and Dioxygen by Ferritins: A Case Study of the Escherichia coli 24-mer Ferritin by All-Atom Molecular Dynamics in Aqueous Medium.

It is shown here that Fe2+ and O2 ligands are displaced from the ferroxidase center of the C1 four-helix bundle of E. coli 24-mer ferritin under molecular dynamics (MD) aided by a randomly oriented external force applied to the ligand. Under these conditions, ligand egress toward the external aqueous medium occurs preferentially from the same four-helix bundle, in the case of O2 , or other bundle, in the case of Fe2 . Viewing ligand egress from the protein as the microscopic reverse of ligand influx into the protein under unbiased MD, these findings challenge current views that preferential gates for recruitment of Fe2+ are 3-fold channels with human ferritin, or the short path from the ferroxidase center to H93 with bacterial ferritins.