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dc.contributor.authorJones, Stephanie Ing,author.en_US
dc.date.accessioned2019-05-16T20:55:27Z
dc.date.available2019-05-16T20:55:27Z
dc.date.created2019en_US
dc.identifieraleph-005271419en_US
dc.identifier.urihttps://repository.tcu.edu/handle/116099117/25367
dc.descriptionPh. D.Texas Christian University2019en_US
dc.descriptionDepartment of Chemistry and Biochemistry; advisor, Benjamin G. Janesko.en_US
dc.descriptionIncludes bibliographical references.en_US
dc.descriptionOnline resource; title from PDF title page (viewed July 16, 2019).en_US
dc.description.abstractThere are two different aspects to this project, design and tool, which are later combined and applied to a final project to study protein binding sites. The first design aspects focus on building a receptor that will bind to trimethylamine N-oxide (TMAO) in the body. Studies have shown that higher levels of TMAO increases the risk of cardiovascular diseases (CVD) and atherosclerosis. Here, a receptor is computationally built based on the binding between TorT and TMAO. The second design project is on lignin. In the pulping and biorefinery processes, lignin is disposed as a waste stream after lignocelluloses other components (hemicellulose and cellulose) are extracted. Substituent effects of β-o-4 linkages were studied on lignin models along two reaction pathways: SN2 and E1. The last design project is on warfarin, which is the medicine of choice when it comes to treating blood clots since 1955.^One of the many reasons for dosage variance is due to the makeup of each patients vitamin K epoxide reductase (VKOR) enzyme, which has been shown to mutate. To this day, human VKOR (hVKOR) has not been crystallized, and there have been ongoing disagreements on its structure and warfarins binding site. This study predicts hVKOR structure and the docking site for warfarin. The tool used here is the orbital overlap distance function D(r2), which quantifies the size of molecular orbitals of system being studied. Chemically hard species with tightly bound electrons tend to have a smaller D(r2) than a soft species with loosely bound electrons. Here, the orbital overlap distance is tested on F centers, which are singly occupied electron systems. Orbital overlap distance function is also applied onto protein binding sites and ligands.^Typical analysis of protein molecules involves electrostatic and hydrophobic interaction maps, but the addition of the orbital overlap distance would be a useful tool to rationalize noncovalent interactions in a proteins active site. In this study, a combination of D(r2) and molecular electrostatic potential are used to rationalize noncovalent interactions in a proteins active site. These studies can then be applied to designing an alternative drug to warfarin; where D(r2) can justify whether warfarin and vitamin K 2,3-epoxide would bind to the predicted binding site.en_US
dc.format.extent1 online resource (xviii, 120 pages) :en_US
dc.format.mediumFormat: Onlineen_US
dc.language.isoengen_US
dc.relation.ispartofTexas Christian University dissertationen_US
dc.relation.ispartofUMI thesis.en_US
dc.relation.ispartofTexas Christian University dissertation.en_US
dc.subject.lcshMolecular orbitals.en_US
dc.subject.lcshMolecules Models.en_US
dc.subject.lcshProtein binding.en_US
dc.titleOrbital overlap as a tool in computational design of molecules /en_US
dc.typeTexten_US
local.academicunitDepartment of Chemistry and Biochemistry
local.subjectareaChemistry and Biochemistry


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