Computational construction and analysis of DNA and RNA

UnrestrictedProper understanding of nucleic acid structure and function is critical as nucleic acids emerge as major targets and therapeutic mediators of physiological changes. Efficient, repeatable, and flexible computational construction methods for nucleic acids are largely unavailable, in part due to the magnitude of such a challenge. In this thesis, a novel suite of programs has been developed for construction, manipulation, and analysis of nucleic acids. This suite contains the following programs: NASDAC (Nucleic Acids: Structure, Dynamics, And Conformations), NASNIC (Nucleic Acid Structural Nomenclature Interpreter for Conformations), NASNOX (Nucleic Acid Structure modification: NitrOXide labels), and a higher-level program called NATCAR (Nucleic Acids: Topology, Conformation, Analysis, Refinement) through which all programs are launched. NASDAC is the primary engine of nucleic acid structure assembly, and NASNIC employs an original nucleic acid nomenclature named NAUTILIS (Nucleic Acids: Universal Topological Input Line System) to generate inputs for branched nucleic acids (for example slipped-strand DNA (S-DNA)) for computational studies. Similarly, NASNOX has been used to generate data for branched nucleic acids with spin labels used in electron paramagnetic resonance. NATCAR and NASNOX were used to examine known duplex DNA and RNA structures and predict structures for 3-way junctions, such as that in the dimerized phi 29 packaging RNA (pRNA) sequence, a component of the powerful phi 29 DNA-packaging motor. A discussion of NATSCAPE (Nucleic Acids: Topology, Sequence, Common Axis, and Parameter Extractor), a novel program to convert pdb structure files into NASDAC input, is included in the final section of the thesis