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dc.contributor.advisor Donald, Bruce R en_US
dc.contributor.advisor Tian, Jingdong en_US
dc.contributor.author Reza, Faisal en_US
dc.date.accessioned 2010-05-10T19:53:06Z
dc.date.available 2012-05-01T04:30:05Z
dc.date.issued 2010 en_US
dc.identifier.uri http://hdl.handle.net/10161/2278
dc.description Dissertation en_US
dc.description.abstract <p>Interactions between nucleic acid substrates and the proteins and enzymes that bind and catalyze them are ubiquitous and essential for reading, writing, replicating, repairing, and regulating the genomic code by the proteomic machinery. In this dissertation, computational molecular engineering furthered the elucidation of spatial-temporal interactions of natural nucleic acid binding proteins and enzymes and the creation of synthetic counterparts with structure-function interactions at predictive proficiency. We examined spatial-temporal interactions to study how natural proteins can process signals and substrates. The signals, propagated by spatial interactions between genes and proteins, can encode and decode information in the temporal domain. Natural proteins evolved through facilitating signaling, limiting crosstalk, and overcoming noise locally and globally. Findings indicate that fidelity and speed of frequency signal transmission in cellular noise was coordinated by a critical frequency, beyond which interactions may degrade or fail. The substrates, bound to their corresponding proteins, present structural information that is precisely recognized and acted upon in the spatial domain. Natural proteins evolved by coordinating substrate features with their own. Findings highlight the importance of accurate structural modeling. We explored structure-function interactions to study how synthetic proteins can complex with substrates. These complexes, composed of nucleic acid containing substrates and amino acid containing enzymes, can recognize and catalyze information in the spatial and temporal domains. Natural proteins evolved by balancing stability, solubility, substrate affinity, specificity, and catalytic activity. Accurate computational modeling of mutants with desirable properties for nucleic acids while maintaining such balances extended molecular redesign approaches. Findings demonstrate that binding and catalyzing proteins redesigned by single-conformation and multiple-conformation approaches maintained this balance to function, often as well as or better than those found in nature. We enabled access to computational molecular engineering of these interactions through open-source practices. We examined the applications and issues of engineering nucleic acid binding proteins and enzymes for nanotechnology, therapeutics, and in the ethical, legal, and social dimensions. Findings suggest that these access and applications can make engineering biology more widely adopted, easier, more effective, and safer.</p> en_US
dc.format.extent 11061162 bytes
dc.format.mimetype application/pdf
dc.language.iso en_US
dc.subject Engineering, Biomedical en_US
dc.subject Computer Science en_US
dc.subject Biology, Bioinformatics en_US
dc.subject binding protein en_US
dc.subject computational biology en_US
dc.subject molecular engineering en_US
dc.subject nucleic acid en_US
dc.subject protein design en_US
dc.subject synthetic biology en_US
dc.title Computational Molecular Engineering Nucleic Acid Binding Proteins and Enzymes en_US
dc.type Dissertation en_US
dc.department Biomedical Engineering en_US
duke.embargo.months 24 en_US

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