Examination of Molecular Recognition in Protein-Ligand Interactions

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).

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biology and Biomedical Sciences: Computational and Systems Biology

Year dc:date.available

2010

Author dc:creator

• Tang, Yat

Contributors dc:contributor

• Garland Marshall

• Chemistry
• Biochemistry
• Biophysics
• General
• Biology
• Microbiology
• antibiotics
• computational chemistry
• drug design
• molecular modeling
• molecular recognition
• protein-ligand

Language dc:language

English (en)

DOI

https://doi.org/10.7936/K74747VH

OAI identifier oai:identifier

oai:openscholarship.wustl.edu:etd-1340