Date of Award


Degree Name

Doctor of Philosophy



First Advisor

Dr. Yirong Mo

Second Advisor

Dr. John B. Miller

Third Advisor

Dr. Donald R. Schreiber

Fourth Advisor

Dr. Susan R. Stapleton


Computer simulation plays a crucial role in interpreting, unifying and guiding experimental observations. In this dissertation, molecular dynamics (MD) simulations and the block-localized wavefunction (BLW) method have been used to explore the chemical and biological processes.

Detailed MD simulations were performed to study the transportation of NH4+, NH3 and H2O through the Escherichia coli ammonium transporter (AmtB) membrane protein. A periplasmic recruitment vestibule was identified and the entrance of an NH4+ into this vestibule requires only 3.1 kcal/mol. In the end of this vestibule, the phenyl ring of Phe107 dynamically opens and a hydrogen bond wire between NH4+ and the carboxylate group of Asp160 via two water molecules was observed. Thus, deprotonation might occur in this vestibule, with Asp160 as the probable proton acceptor. Further MD simulations were performed on the D160A mutant and compared the NH4+ transport capability with that of native AmtB. The results showed that D160 is responsible for the recognition and binding of NH4+ in AmtB. Moreover, this conclusion is endorsed by results from quantum mechanics/molecular mechanics (QM/MM) simulations on the deprotonation of NH4+. Finally, a detailed mechanism of NH4+/NH3 transport is summarized.

MD simulations were performed on phosphotriesterase (PTE), focusing on the docking process for paraoxon with PTE. One Zn2 cation (second Zn cation in the active site) binding site was identified. At the binding site, the arrangement of the ligands of Zn2 cation changes from an approximately trigonal pyramidal arrangement to an octahedral arrangement. After the binding site, a sharp increase of energy is observed. Thus, the binding site is a good stable point for the second step simulation on the catalytic mechanism.

The BLW approach is an ab initio valence bond (VB) method incorporating the efficiency of molecular orbital (MO) theory. It is particularly useful in the quantification of the intra-molecular electron delocalization effect and the intermolecular charge-transfer effect. An extension of the BLW method to the density functional theory level is described. Several applications are presented on the nature of π-cation interaction between cations and benzene, charge transfer in the solvation of MenNH4-n + (n=1∼3), and the interchain conductivity in Poly(p-phenylene) (PPP).


5th Advisor: Dr. Brian C. Tripp

Access Setting

Dissertation-Open Access

Included in

Chemistry Commons