Ion accumulation in a protein nanocage: finding noisy temporal sequences using a genetic algorithm

Many pathogenic bacteria are able to survive attack by the host's immune system because of antioxidant systems that mitigate the effects of reactive oxygen species. Dps is a hollow 12-subunit protein nanocage that prevents oxidative damage by oxidizing and sequestering intracellular Fe²⁺; the resulting Fe³⁺ forms an iron oxyhydroxide nanoparticle in the cage interior. Charged sites on the protein nanocage create an electrostatic gradient that guides ions through well-defined pores that connect the cage interior with the surrounding solution and toward nucleation sites on the cage interior. In this study, we use all-atom molecular dynamics to simulate the motion of simple cations into the dodecameric cage formed by the Dps protein from Listeria monocytogenes. Ion trajectories are analyzed by using a novel, to our knowledge, genetic algorithm to determine the temporal sequence of ion-protein interactions. Ions enter Dps through well-defined pores at the ferritinlike C₃ axes, with negatively-charged residues on the outside of the cage forming a fairly well-defined entrance pathway. This method of trajectory analysis may be broadly applicable in situations where the spatial localization of ions or other small molecules is electrostatically driven by a biomolecule.