Investigation of Iron Ion Transit in Ferritin by Molecular Dynamics Simulations

S.A. Limon, M. Stepanova
Missouri State University,
United States

Keywords: ferritin, iron ions uptake and release, nano-biological materials, molecular modeling

Summary:

Ferritin is an iron-storage protein with an ability to uptake, mineralize and release iron ions in a controllable manner. This intracellular ubiquitous protein is composed of 24 subunits forming a globular hollow shell allowing for storage of mineralized iron, with several channels responsible for the transit of ions into the shell and out of it. Understanding of detailed molecular functioning of ferritin is required for rational design of biomimetic conjugate nano-biosystems containing ferritin-like constituents. The goal of this work is to understand details of iron ions transit through pertinent channels in the ferritin shell using molecular dynamics (MD) simulations. Three subunits of modified ferritin shell (PDB ID: 5CZU) forming a threefold channel were subjected to molecular dynamics (MD) simulations in explicit water using the Gromacs 5.1.1 package with OPLS-AA force field. Fe2+ ions were added to the system in two configurations, outside and inside of the trimer. Within only 1.4-8.8 ns of production MD simulations, transit of the ions through the threefold channel was observed. In this presentation, results of a thorough investigation of the transit are reported. Molecular mechanisms involved in the ion transit, as observed in MD simulations, provide the long-sought clarification of pathways of Fe2+ uptake and release through threefold channels in ferritin. These findings contribute to ongoing research on applications of ferritin-like proteins for development of novel biomimetic nanomaterials.