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Dissertation/Thesis Abstract

Disrupted Pathways: Generating Tunable Macromolecular Assembly Pathways
by Briggs, Koan E. M., Ph.D., University of Kansas, 2018, 120; 13419290
Abstract (Summary)

What follows is a pathway; a sequence of individual events, which together form a story. Yet it is still only a small part of what has come before. Biological structures also have individual stories; each composed of simple events in sequence. One story does not tell the whole, for that we must observe many stories, sample them if you will. Together, they bring understanding.

Assembly is an emergent property of many individual binding events. Through this, all of the structures that make up life are created. Understanding the regime of possibilities provides insight into both the breadth and tendencies of the system. Cells contain numerous types of individual proteins many of which come together to form larger complexes. I will begin by introducing the elementary building blocks of those protein complexes. An introductory example will provide the first perspective, it will form common ground and allow the telling of the larger story with a shared perspective. Then a case study, a real biological complex and how understanding the progression of its pathways provided insight into the states which it reached. With the elementary operations described, I will move on to laying out the landscape of possible pathways; first for a specific case and then the structure of the assembly pathways themselves. Thus, providing a novel framework for the understanding of the stochastic space of protein complex assembly. Finally, I will provide an example of how making changes in the possible assembly pathways leads to non-intuitive changes in the conclusion of the protein complexes’ stories.

Indexing (document details)
Advisor: Fischer, Christopher J., Deeds, Eric J.
Commitee: Hawley, Steven A., Murray, Michael J., Shi, JiCong
School: University of Kansas
Department: Physics & Astronomy
School Location: United States -- Kansas
Source: DAI-B 80/07(E), Dissertation Abstracts International
Subjects: Computational physics, Physics, Biophysics
Keywords: Assembly networks, Combinatorial optimization, Graph optimization, Molecular biophysics, Numerical optimization, Protein complex assembly
Publication Number: 13419290
ISBN: 978-0-438-89779-3
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