Author's School

Graduate School of Arts & Sciences

Author's Department/Program

Biology and Biomedical Sciences: Computational and Systems Biology

Language

English (en)

Date of Award

January 2010

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

Garland Marshall

Abstract

This dissertation is a compilation of two main projects that were investigated during my thesis research. The first project was a prospective study which identified and characterized drug-like inhibitors of a prototype of bacterial two-component signal transduction response regulator using computational and experimental methods. The second project was the development and validation of a scoring function, PHOENIX, derived using high-resolution structures and calorimetry measurements to predict binding affinities of protein-ligand interactions. Collectively, my thesis research aimed to better understand the underlying driving forces and principles which govern molecular recognition and molecular design. A prospective study coupled computational predictions with experimental validation resulted in the discovery of first-in-class inhibitors targeting a signal transduction module important for bacterial virulence. Development and validation of the PHOENIX scoring function for binding affinity prediction derived using high-resolution structures and calorimetry measurements should guide future molecular recognition studies and endeavors in computer-aided molecular design. To request for an electronic copy of this dissertation, please email the author: yattang at gmail dot com).

Comments

Permanent URL: http://dx.doi.org/10.7936/K74747VH

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