QM/MM simulation on P450 BM3 enzyme catalysis mechanism and quantum chemistry calculations on transition metal dimers

This dissertation is composed of two parts. Chapter 1 is a brief introduction to the computational methods used in the following chapters.;Chapters 2 to 5 are the first part. The system studied in the first part is the metalloprotein P450 BM3. Based on a binding structure generated by induced fit modeling (IFD) of the protein-ligand complex, the reaction path for hydrogen atom abstraction in P450 BM3 was studied by means of mixed quantum mechanics and molecular mechanics (QM/MM) method to determine the structures and energetics. QM/MM results proved that the IFD structure is suitable for hydrogen atom abstraction at the omega-1 position. The electronic structures obtained are similar to those observed in P450 cam. The barrier for the hydrogen abstraction step from QM/MM modeling is 13.3 kcal/mol in quartet and 15.6 kcal/mol in doublet. Quantum chemistry calculations of two QM models were employed to describe the core chemistry of active site with and without the protein pocket and water shell, as well as to evaluate the effect of the MM region in the catalysis. Although there is some strain energy present in the ligand, the activation barrier is not dramatically affected. A crystal water molecule, HOH502, plays a role as catalyst and decreases the activation barrier by about 2 kcal/mol and reaction energy by about 3--4 kcal/mol. The factors stabilizing the sulfur atom in Cys400 were discussed and preliminary results of QM model calculations to evaluate these factors were summarized. In order to achieve reactive chemistry at the remaining experimentally observed positions in the hydrocarbon tail of the ligand, other structures would have to be utilized as a starting point for the reaction. Finally, the present results still leave open the question of whether DFT methods provide an accurate computation of the barrier height in the P450 hydrogen atom abstraction reaction.;Chapter 6 is the second part. In this chapter, the experimental data and density functional theory (DFT) calculation results of the first row transition metal dimers are summarized. Experimental results mainly included bond lengths, disassociation energies and atomic configurations at dissociation limits. DFT calculations were focused on the functional B3LYP. Ground state electronic configurations were searched using different basis sets and disassociation energies were calculated. These results were used to evaluate the performance of DFT and to be used to set up corrections in density functional theory - localized orbital correction model.