Dissertation Defenses

Doctoral Dissertation Announcement

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Candidate: Yuchun Lin

Degree of: Doctor of Philosophy

Department: Chemistry

Title: An Exploration of the Chemical and Biological Processes through Molecular Dynamics Simulation and Block-Localized Wavefunction Method

Committee:
Dr. Yirong Mo, Chair
Dr. John B. Miller
Dr. Donald R. Schreiber
Dr. Susan R. Stapleton
Dr. Brian C. Tripp

Date: Monday, April 21, 2008 10:00 a.m. – 12:00 p.m.
1728 Wood Hall

Abstract:
Computer simulation plays a crucial role in interpreting, unifying and guiding experimental observations. In this dissertation, molecular dynamics (MD) simulation and block-localized wavefunction (BLW) method have been used to explore the chemical and biological processes.
Detailed MD simulations have been performed to study the transportation of NH4+, NH3 and H2O through the Escherichia coli AmtB membrane protein. A periplasmic recruitment vestibule was identified and the entrance of an NH4+ into this vestibule requires only 3.1kcal/mol. In the end of this vestibule, the phenyl ring of Phe107 dynamically switches to an open state. At this stage, an about 8 Å hydrogen bond wire between NH4+ and the carboxylate group of D160 via two water molecules was observed. Thus, the deprotonation might occur in the extracellular binding site, and D160 is the probable proton acceptor through two water molecules from NH4+. Furthered extensive 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 have also been performed on phosphotriesterase (PTE) in this dissertation. While the engineering on the PTE is the long term goal, only the docking process is present currently. It is accomplished by performing hybrid QM/MM simulations. The results are instructive for the subsequent engineering on the PTE.
Developed by Dr. Yirong Mo, 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 electron delocalization (resonance) effect within a molecule and the charge-transfer effect between molecules. In this dissertation, an extension of the BLW method to the density functional theory level is described. This description is followed by several test applications on the nature of π-cation interaction between a few cations and benzene, charge transfer in the solvation of MenNH4-n+ (n=1~3), and the interchain conductivity in Poly(p-phenylene) (PPP).