title: Ion accumulation in a protein nanocage: finding noisy temporal sequences using a genetic algorithm.
abstract: 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 Fe(2+); the resulting Fe(3+) 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 C(3) 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.
authors.affiliation: Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT, USA. jolleycraig@gmail.com
authors.forename: Craig C
authors.initials: CC
authors.lastname: Jolley
authors.forename: Trevor
authors.initials: T
authors.lastname: Douglas
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D007477:Ions / Q000378:metabolism; D008089:Listeria monocytogenes / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D049329:Nanostructures / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013997:Time Factors
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C083911:DPS protein, Bacteria; D007477:Ions