Exploring Biomolecular Interactions Through Single-Molecule Force Spectroscopy and Computational Simulation

Doctoral thesis English OPEN
Yang, Darren (2016)
  • Publisher: Harvard University
  • Subject: Biophysics, General | Biology, Molecular | Physics, General

Molecular interactions between cellular components such as proteins and nucleic acids govern the fundamental processes of living systems. Technological advancements in the past decade have allowed the characterization of these molecular interactions at the single-molecule level with high temporal and spatial resolution. Simultaneously, progress in computer simulation has enabled theoretical research at the atomistic level, assisting in the interpretation of experimental results. This thesis combines single-molecule force spectroscopy and simulation to explore inter- and intra-molecular interactions. Specifically, we investigate the interaction between RecA and DNA to elucidate the underlying molecular mechanism of the DNA homologous recombination process. We also evaluate the stability of the von Willebrand Factor (vWF) A2 domain to determine the molecular origins of von Willebrand Diseases (vWD). This thesis also describes the development and application of a new single-molecule technique that combines the centrifuge force microscope (CFM) with DNA self-assembled mechanical switches to enable massively parallel repeating force measurements of molecular interactions.
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