Paper Citing NAMD - Abstract
Laghaei, Rozita; Kowallis, William; Evans, Deborah G.; Coalson, Rob D.
Calculation of Iron Transport through Human H-chain Ferritin
JOURNAL OF PHYSICAL CHEMISTRY A, 118:7442-7453, SEP 4 2014
Influx of ferrous ions from the cytoplasm through 3-fold pores in the shell of ferritin protein is computed using a 3-dimensional Poisson-Nernst-Planck electrodiffusion model, with inputs such as the pore structure and the diffusivity profile of permeant Fe2+ ions extracted from all-atom molecular dynamics (MD) simulations. These calculations successfully reproduce experimental estimates of the transit time of Fe2+ through the ferritin coat, which is on the millisecond time scale and hence much too long to be directly simulated via all-atom MD. This is also much longer than the typical time scale for ion transit in standard membrane spanning ion channels whose pores bear structural similarity to that of the 3-fold ferritin pore. The slow time scale for Fe2+ transport through ferritin pores is traced to two features that distinguish the ferritin pore system from standard ion channels, namely, (i) very low concentration of cytoplasmic Fe2+ under physiological conditions and (ii) very small internal diffusion coefficients for ions inside the ferritin pore resulting from factors that include the divalent nature of Fe2+ and two rings of negatively charged amino acids surrounding a narrow geometric obstruction within the ferritin pore interior.
