Exploring the interstitial atom in the FeMo cofactor of nitrogenase: insights from QM and QM/MM calculations.

Density functional theory and combined quantum mechanics and molecular mechanics (QM/MM) calculations have been used to explore structural features of the FeMo cofactor with an interstitial atom X (X = N, C, or O) and its interactions with CO and N 2. Predicted frequencies of the metal-bound CO, QM/MM-optimized geometries, and calculated redox potentials of the FeMo cofactor with different central ligands show that the oxygen atom is the candidate for the interstitial atom. Calculations on the interactions of the FeMo cofactor with CO and N 2 reveal that there is a remarkable dependence of the binding energy on the binding site and the interstitial atom. Generally, the Fe2 site of the FeMo cofactor has stronger interactions with CO and N 2 than Fe6, and both the Fe2 and Fe6 sites in the N-centered and O-centered clusters of the FeMo cofactor can effectively bind N 2 while the coordination of N 2 to the Fe6 site of the C-centered active cluster is unfavorable energetically. Present results indicate that the protein environment is important for computational characterization of the structure of the FeMo cofactor and properties of the metal-bound CO and N 2 are sensitive to the interstitial atom.