Access Type

Open Access Dissertation

Date of Award

January 2014

Degree Type


Degree Name




First Advisor

Andrés G. Cisneros


Quantum mechanics (QM) calculations have been demonstrated to give very accurate results in studying a variety of chemical reactions. However, the current computing resources limits its use in large-size systems such as enzymes. Compared to QM, Molecular Mechanics (MM) have an advantage in computing time but disadvantage in accuracy, and MM cannot be used in reactions involving bonding forming and breaking. To combine the advantages of these two types of methods, QM/MM has been introduced to study reactions and processes in large-size systems, and it has been proven to give accurate results with moderate computational expense. When studying enzymatic reactions, a comprehensive understanding of the interactions in an intuitive way is highly instructive. The combined ELF/NCI analysis meets the demand. In this dissertation, we have discussed the applications and development of the combined ELF/NCI analysis and QM/MM method. The combined ELF/NCI analysis has been extended to study two enzymatic reactions in Chapter 2, the synthesis of DNA by Human DNA polymerase λ and the ε subunit of DNA Polymerase III and help reveal the factors that account for the higher reaction barrier for Mg2+ than Mn2+ and different coordination numbers for two metal centers with respect to the interactions. It also has been used to investigate the interactions that result in the unusual seesaw shape of several metal clusters in Chapter 3. QM/MM simulations has been carried out to study the steps after the formation of FeIV-oxo for the repair of 1-methyladinine (1-meA) catalyzed by AlkB. First, the rate-limiting step, the hydrogen abstraction step for the H2O pathway has been fully studied in Chapter 4. The results shed lights on the electronic structure of FeIV-oxo. Residues that may affect the reaction barrier has been obtained by EDA. The combined ELF/NCI analysis also reveals important interactions and their changes along the reaction. We have also proposed and studied a new OH- pathway in Chapter 5. Comparison with the traditional H2O pathway provides more details on the mechanism. The consistency between our theoretical results and experimental findings have been found. In Chapter 6, a newly proposed EDA method, DFT-steric analysis is performed on several types of dimers. Comparison between it and another EDA method CSOV and QTAIM provides a deep understanding of the components of the interactions between monomers from different perspectives.

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