Computational studies of electron transfer proteins: Rubredoxin-type proteins and ferredoxin

Iron-sulfur proteins are an important class of electron transfer proteins found universally in living organisms, serving vital roles in the electron transport chains of cellular energy utilization. Determining the molecular basis of electron transfer properties of these proteins is important in understanding how they promote fast and efficient energy flow in the cell.;The reduction potential of an electron transfer protein is one of its most important properties since its sign and magnitude affects the direction and rate of electron transfer between redox sites. Homologous iron-sulfur proteins with the same redox site exhibit a broad range of reduction potentials, and thus serve as ideal models for unraveling how the protein tunes the reduction potential of its redox site. Here, the determinants responsible for the high reduction potential of rubredoxin-like domain of rubrerythrin relative to rubredoxin were identified using a bioinformatic sequence/electrostatic structure analysis and molecular dynamics simulations. In addition, the biologically relevant dimer of rubrerythrin was identified as the dimer with a calculated reduction potential in good agreement with experiment using a combination of a quantum mechanical calculation of the redox site and a Poisson-Boltzmann calculation of the interaction between the redox site and the surrounding environment. This approach is being developed into a general method for identifying biologically relevant oligomers of redox-active proteins.;The reorganization energy of an electron transfer protein due to the polarization of the protein and solvent around the redox site is another important property because the polarization creates the activation barrier for electron transfer and thus affects the electron transfer rate. Here, the intramolecular electron transfer in the 2[4Fe-4S] ferredoxins was investigated using molecular dynamics simulations. The reorganization in response to the electron transfer occured mostly in picoseconds, much faster than most biological electron transfers, which implies electron transfer chains may be viewed as a series of equilibrium transfers. In addition, the polarization due to the surrounding solvent was very large but highly coupled to that of the protein and its counterions. Thus, although dynamics of the counterions and protein were slow individually, the net time scale of the reorganization was fast.