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 E m 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 Fx 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.