Abstract
dc:description.abstractThrombin is a critical drug target for chemotherapeutic and antithrombotic therapy development. Although many experiments have demonstrated that thrombin is a multifunctional allosteric enzyme, the exact mechanism of thrombin's allostery is still unclear and widely debated. This dissertation describes my application of molecular dynamics simulations and various quantitative methods to uncover thrombin's allostery. It discusses thrombin's allosteric responses upon different factors including ion conditions, mutations, and ligation statuses. My in-depth atomic-level investigation presents experimentally consistent results and also provides mechanistic insights into thrombin's functional switch. Several novel testable predictions further the understanding of thrombin's substrate recognition process and allosteric pathways. Finally, the work concludes with future directions of investigating the allosteric network of thrombin.
Degree
thesis:*- Grantor dc:publisher
- Wake Forest University
- Year dc:date.issued
- 2018
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Xiao, Jiajie
Subjects
dc:subject × 1Rights
- Language dc:language.iso
- en
Identifiers
dc:identifier.*- Handle dc:identifier.uri
- http://hdl.handle.net/10339/92371
- OAI identifier oai:identifier
- oai:wakespace.lib.wfu.edu:10339/92371