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Design and Analysis of Nucleic Acid Reaction Pathways


Wolfe, Brian Robert (2014) Design and Analysis of Nucleic Acid Reaction Pathways. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/G4XZ-ZF47.


Nucleic acids are a useful substrate for engineering at the molecular level. Designing the detailed energetics and kinetics of interactions between nucleic acid strands remains a challenge. Building on previous algorithms to characterize the ensemble of dilute solutions of nucleic acids, we present a design algorithm that allows optimization of structural features and binding energetics of a test tube of interacting nucleic acid strands. We extend this formulation to handle multiple thermodynamic states and combinatorial constraints to allow optimization of pathways of interacting nucleic acids. In both design strategies, low-cost estimates to thermodynamic properties are calculated using hierarchical ensemble decomposition and test tube ensemble focusing. These algorithms are tested on randomized test sets and on example pathways drawn from the molecular programming literature. To analyze the kinetic properties of designed sequences, we describe algorithms to identify dominant species and kinetic rates using coarse-graining at the scale of a small box containing several strands or a large box containing a dilute solution of strands.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:DNA;RNA;nucleic acid design;RNA folding;DNA folding;DNA design;inverse folding;molecular programming
Degree Grantor:California Institute of Technology
Division:Biology and Biological Engineering
Major Option:Bioengineering
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Pierce, Niles A.
Thesis Committee:
  • Winfree, Erik (chair)
  • Murray, Richard M.
  • Miller, Thomas F.
  • Pierce, Niles A.
Defense Date:6 May 2014
Record Number:CaltechTHESIS:03272014-193400848
Persistent URL:
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:8173
Deposited By: Brian Wolfe
Deposited On:29 May 2014 21:39
Last Modified:08 Nov 2023 00:43

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