Reduction Potential Properties of Electron Transfer Proteins

Abstract

Electron transfer reactions play an important role in biological processes such as photosynthesis, respiration, and nitrogen fixation. Here, the electron transfer properties of iron-sulfur (Fe-S) proteins and blue copper proteins are investigated. The reduction potentials of these proteins determine the driving forces for their electron transfer. The most important determinant of the reduction potential is the primary coordination sphere, or the type and number of metal ion(s) and the geometry of the redox site with its coordinating ligands. However, for a given redox site, the reduction potentials can vary by ~1 V for non-homologous proteins and ~0.3 V for homologous proteins. Therefore, the protein matrix and solvent environment around the redox site are important factors that are responsible for tuning the reduction potential to serve a variety of biological functions.

Here, a method for calculating the reduction potentials of metalloproteins is presented in which the redox site or inner sphere contribution is calculated by density functional theory (DFT) and the protein and solvent environment or outer sphere contribution is calculated by Poisson-Boltzmann (PB) continuum electrostatics. Reduction potentials calculated using the DFT+PB method are in good agreement with the experimental values for and the nine Fe-S clusters in respiratory complex I. Moreover, the method used here is a useful computational tool to study other questions about complex I. In addition, the method is being extended to the blue copper proteins.

The protein matrix and surrounding solution are investigated in a long 10 microsecond molecular dynamics simulation of 2[4Fe-4S] ferredoxin, a small electron shuttle protein, at very dilute ionic concentration (~0.04 M KCl) similar to the conditions of the rate measurement. The potassium ions form a “cloud” favoring the product due to the arrangement of negatively charged groups of the protein, which suggests a possible mechanism for an electron shuttle protein. Finally, since most of the computer time for molecular dynamics simulations is spent calculating water-water interactions, a fast and efficient water model was developed for biological simulations.