DOI

10.17077/etd.a6nq41cg

Document Type

Thesis

Date of Degree

Spring 2018

Degree Name

MS (Master of Science)

Degree In

Biochemistry

First Advisor

Adrian H. Elcock

First Committee Member

Todd Washington

Second Committee Member

Catherine Musselman

Third Committee Member

Marc Wold

Fourth Committee Member

Michael Schnieders

Fifth Committee Member

Daniel Quinn

Abstract

The bacterium Escherichia coli uses DNA-segregating machinery known as the ParMRC system to ensure the stable inheritance of low copy-number plasmids by daughter cells during cell division. In this system, ParM, an actin-like protein, forms a filamentous spindle between ParR/parC complexes that are assembled on sister plasmids; segregation of the plasmids is achieved by growth of the ParM filaments and the resulting push of plasmids to opposite cell poles. Studies combining in vitro biochemical assays live cell fluorescence microscopy and cryo-electron microscopy has led to deep mechanistic insights into the action of the ParMRC system. It is thought that ParM filaments (attached to the ParR/parC complexes) elongate through a mechanism of “insertional polymerization,” where the growth of the ParM filament occurs preferentially at the end associated with the ParR/parC complex. Owing to good structural information available in the literature, ParMRC serves as an interesting model system for molecular dynamics simulations. These simulations may provide a better insight into the insertional polymerization mechanism of ParMRC system.

My current study focuses on the development of a computational model, a long-term goal, to perform molecular simulations of the ParMRC system. My work here covers the progress of my study by including two main components of the ParMRC system: 1) modeling and molecular simulations to study the elongation and pairing of ParM single and double filaments respectively; and 2) Homology modeling of ParR. Encouragingly, molecular simulations of ParM single and double filaments recapitulated some of the experimental elements of ParM and provided us with some interesting observations. We anticipate that the work presented here may serve as a good start to perform molecular simulations of the ParMRC system.

Pages

ix, 40 pages

Bibliography

Includes bibliographical references (pages 38-40).

Copyright

Copyright © 2018 Venkata R. Sanaboyana

Included in

Biochemistry Commons

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