Doctoral Dissertations

Date of Award

8-2015

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Life Sciences

Major Professor

Jerome Baudry

Committee Members

Jeremy Smith, Elizabeth Howell, Robert Hinde, Hong Guo

Abstract

The study focuses on understanding the dynamic nature of interactions between molecules and macromolecules. Molecular modeling and simulation technologies are employed to understand how the chemical constitution of the protein, specific interactions and dynamics of its structure provide the basis of its mechanism of function. The structure-dynamics-function relationship is investigated from quantum to macromolecular-assembly level, with applications in the field of rationale drug discovery and in improving efficiency of renewable sources of energy. Results presented include investigating the role of dynamics in the following:

1) In interactions between molecules: analyzing dynamic nature of a specific non-covalent interaction known as “anion-π [pi]” in RmlC protein.

2) In interactions between molecules and macromolecules: defining the structural basis of testosterone activation of GPRC6A.

3) In disrupting the function using specific substrate interactions: incorporating protein dynamics and flexibility in structure-based drug-discovery approach targeting the prothrombinase coagulation complex.

4) In interactions between macromolecules: elucidating the protein-protein binding and dynamics of electron-transport proteins, Ferrodoxin and Cytochrome c6, with Cyanobacterial Photosystem I.

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