Computational Approach for Probing Redox Potential for Iron-Sulfur Clusters in Photosystem I

Photosystem I is a light-driven electron transfer device. Available X-ray crystal structure from Thermosynechococcus elongatus showed that electron transfer pathways consist of two nearly symmetric branches of cofactors converging at the first iron-sulfur cluster F_X, which is followed by two terminal iron-sulfur clusters F_A and F_B. Experiments have shown that F_X has lower oxidation potential than F_A and F_B, which facilitates the electron transfer reaction. Here, we use density functional theory and Multi-Conformer Continuum Electrostatics to explain the differences in the midpoint Em potentials of the F_X, F_A and F_B clusters. Our calculations show that F_X has the lowest oxidation potential compared to F_A and F_B due to strong pairwise electrostatic interactions with surrounding residues. These interactions are shown to be dominated by the bridging sulfurs and cysteine ligands, which may be attributed to the shorter average bond distances between the oxidized Fe ion and ligating sulfurs for F_X compared to F_A and F_B. Moreover, the electrostatic repulsion between the 4Fe-4S clusters and the positive potential of the backbone atoms is lowest for F_X compared to both F_A and F_B. These results agree with the experimental measurements from the redox titrations of low-temperature EPR signals and of room temperature recombination kinetics.