Doctor of Philosophy (PhD)


Physics and Astronomy

Document Type



Vast amount of experimental data in structural biology has been generated, collected and accumulated in the last few decades. This rich dataset is an invaluable mine of knowledge, from which deep insights can be obtained and practical applications can be developed. To achieve that goal, we must be able to manage such "Big Data'' in science and investigate them expertly. Molecular docking is a field that can prominently make use of the large structural biology dataset. As an important component of rational drug design, molecular docking is used to perform large-scale screening of putative associations between small organic molecules and their pharmacologically relevant protein targets. Given a small molecule (ligand), a molecular docking program simulates its interaction with the target protein, and reports the probable conformation of the protein-ligand complex, and the relative binding affinity compared against other candidate ligands. This dissertation collects my contributions in several aspects of molecular docking. My early contribution focused on developing a novel metric to quantify the structural similarity between two protein-ligand complexes. Benchmarks show that my metric addressed several issues associated with the conventional metric. Furthermore, I extended the functionality of this metric to cross different systems, effectively utilizing the data at the proteome level. After developing the novel metric, I formulated a scoring function that can extract the biological information of the complex, integrate it with the physics components, and finally enhance the performance. Through collaboration, I implemented my model into an ultra-fast, adaptive program, which can take advantage of a range of modern parallel architectures and handle the demanding data processing tasks in large scale molecular docking applications.



Document Availability at the Time of Submission

Release the entire work immediately for access worldwide.

Committee Chair

Jarrell, Mark