Modeling and simulation of the equilibrium and nonequilibrium dynamics of DNA

DNA is a long and slender polyelectrolyte that facilitates the storage, retrieval and transfer of genetic information in living cells. The cell processes by which genetic information is stored, copied or transcribed induce forces and torques in DNA that alter its structure. These structural changes are dynamic and are capable of both inhibiting and facilitating some of these cell processes. Attempts have been made to understand the underlying dynamics of the formation and dissipation of these structures by means of novel experiments. In these experiments, single molecules of DNA are subjected to forces and torques similar to the ones they would experience within the cell in order to characterize the dynamics of the structural changes that occur as DNA responds to these influences. Novel as these experiments are, they do not permit a direct observation of these structural changes and have had to resort to indirect means of characterizing them. DNA is so slender (2nm in diameter) that current equipment are not capable of directly viewing the dynamics of the structural changes that occur in a single molecule. Experiments have had to rely on attached artifacts (such as micron sized paramagnetic beads attached to DNA and/or fluorescent particles) to predict the dynamics of these structural changes. It is believed that these artifacts obscure the observed dynamics due to their sheer size compared to that of DNA. To help make more direct predictions of the structural changes that occur in DNA, we have adapted a model of DNA based on the wormlike-chain polymer model our systems of interest. This model was adapted from earlier models used for Brownian Dynamics simulations of DNA processes such as site juxtaposition. Our version of the model offers the distinct advantage of being capable of accounting for interactions with either fixed or moving boundaries. Our model accounts for the elastic and electrostatic properties of DNA as well as its hydrodynamic interactions. Our model also accounts for the entropic forces arising from the Brownian interaction of the DNA and the fluid particles. This model is capable of resolving some of the dynamics that occur at the long length and time scales considered in these studies but cannot be captured by current experiments. Using this model, we have been able to get around the computational effort involved in carrying out all-atom molecular dynamics simulations while obtaining results and predictions for structural changes that occur at functionally relevant length and time scales. This dissertation highlights some of my major contributions to the computational study of DNA dynamics and kinetics using the model just described.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Mechanical Engineering

Grantor

Texas Tech University

Year dc:date.issued

2015

Author dc:creator

• Ivenso, Ikenna Dominic

Chair dc:contributor.committeechair

• Lillian, Todd

Committee members dc:contributor.committeemember

• Barhorst, Alan
• Blawzdziewicz, Jerzy
• Huang, Juyang
• Sanati, Mahdi

• Computational biophysics
• Mechanobiology

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/2346/66129

OAI identifier oai:identifier

oai:ttu-ir.tdl.org:2346/66129