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dc.contributor.advisorHarvey, Steve
dc.contributor.authorGossett, John Jared
dc.date.accessioned2014-05-28T19:33:02Z
dc.date.available2014-05-28T19:33:02Z
dc.date.issued2013-04-08
dc.identifier.urihttp://hdl.handle.net/1853/51925
dc.description.abstractThis thesis covers a wide variety of projects within the domain of computational structural biology. Structural biology is concerned with the molecular structure of proteins and nucleic acids, and the relationship between structure and biological function. We used molecular modeling and simulation, a purely computational approach, to study DNA-linked molecular nanowires. We developed a computational tool that allows potential designs to be screened for viability, and then we used molecular dynamics (MD) simulations to test their stability. As an example of using molecular modeling to create experimentally testable hypotheses, we were able to suggest a new design based on pyrrylene vinylene monomers. In another project, we combined experiments and molecular modeling to gain insight into factors that influence the kinetic binding dynamics of fibrin "knob" peptides and complementary "holes." Molecular dynamics simulations provided helpful information about potential peptide structural conformations and intrachain interactions that may influence binding properties. The remaining projects discussed in this thesis all deal with RNA structure. The underlying approach for these studies is a recently developed chemical probing technology called 2'-hydroxyl acylation analyzed by primer extension (SHAPE). One study focuses on ribosomal RNA, specifically the 23S rRNA from T. thermophilus. We used SHAPE experiments to show that Domain III of the T. thermophilus 23S rRNA is an independently folding domain. This first required the development of our own data processing program for generating quantitative and interpretable data from our SHAPE experiments, due to limitations of existing programs and modifications to the experimental protocol. In another study, we used SHAPE chemistry to study the in vitro transcript of the RNA genome of satellite tobacco mosaic virus (STMV). This involved incorporating the SHAPE data into a secondary structure prediction program. The SHAPE-directed secondary structure of the STMV RNA was highly extended and considerably different from that proposed for the RNA in the intact virion. Finally, analyzing SHAPE data requires navigating a complex data processing pipeline. We review some of the various ways of running a SHAPE experiment, and how this affects the approach to data analysis.en_US
dc.language.isoen_USen_US
dc.publisherGeorgia Institute of Technologyen_US
dc.subjectComputational biologyen_US
dc.subjectStructural biologyen_US
dc.subjectMolecular nanowireen_US
dc.subjectRibosomal RNAen_US
dc.subjectSatellite tobacco mosaic virusen_US
dc.subjectSHAPE chemistryen_US
dc.subjectMacromolecular modelingen_US
dc.subjectData analysisen_US
dc.subject.lcshMacromolecules Analysis
dc.subject.lcshComputational biology
dc.subject.lcshBiomolecules Structure
dc.subject.lcshMolecular dynamics
dc.subject.lcshComputer simulation
dc.titleAnalysis of macromolecular structure through experiment and computationen_US
dc.typeDissertationen_US
dc.description.degreePh.D.
dc.contributor.departmentComputer Science
dc.embargo.termsnullen_US
thesis.degree.levelDoctoral
dc.contributor.committeeMemberApostolico, Alberto
dc.contributor.committeeMemberBader, David
dc.contributor.committeeMemberWartell, Roger M.
dc.contributor.committeeMemberWilliams, Loren D.


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