Strength of FeS Bonds and Hydrogen Bonds in Small Molecule Inhibitors of Bacterioferritin: QM/MM and Local Mode...

In this study, we computationally investigated the strength of FeS chemical bonds in heme groups and hydrogen bonds in bacterioferritin (BR) from Pseudomonas aeruginosa in the presence of small molecular inhibitors. The investigations were based on QM/MM calculations in both the ferric and ferrous oxidation states of BR, followed by Local Mode Analysis, with initial coordinates taken from available experimental x-ray structures of BR with ligands. Our results show that the FeS chemical bonds in both oxidation states were stronger, shorter, more covalent, and generally less polar than in the gas phase. In the ferrous state of the protein, the FeS bonds tended to be weaker, shorter, less covalent, and less polar than in the ferric state. On average, the hydrogen bonds in both oxidation states of the protein were stronger than a hydrogen bond in a water dimer, highlighting the influence of the protein environment on these interactions.