Thesis (Ph. D.)--University of Oregon, 2006. / Typescript. Includes vita and abstract. Includes bibliographical references (leaves 115-121). Also available for download via the World Wide Web; free to University of Oregon users.

Ph D.

It is of interest to know where in the genome DNA binding proteins act in order to effect their gene regulatory function. For many sequence specific DNA binding proteins we plan to predict the location of their action by having a model of their affinity to short DNA sequences. Existing and new models of protein sequence specificty are investigated and their ability to predict genomic locations is evaluated. Public data from a micro-fluidic experiment is used to fit a matrix model of binding specificity for a single transcription factor. Physical association and disassociation constants from the experiment enable a biophysical interpretation of the data to be made in this case. The matrix model is shown to provide a better fit to the experimental data than a model initially published with the data. Public data from 172 protein binding micro-array experiments is used to fit a new type of model to 82 unique proteins. Each experiment provides measurements of the binding specificity of an individual protein to approximately 40000 DNA probes. Statistical, `DNA word', models are assessed for their ability to predict held back data and perform very well in many cases. Where available, ChIP-seq data from the ENCODE project is used to assess the ability of a selection of the DNA word models to predict ChIP-seq peaks and how they compare to matrix models in doing so. This $\textit{in vitro}$ data is the closest proxy to the true sites of the proteins' regulatory action that we have.

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Thesis (Ph. D.)--University of Missouri--Columbia, 2001. / Typescript. Vita. Includes bibliographical references (leaves 326-347). Also available on the Internet.

Call number: LD2668 .T4 1956 L66 / Master of Science

published_or_final_version / Zoology / Doctoral / Doctor of Philosophy

published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy

A dissertation submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfillment of the requirements for the Master of Science degree. 2 November 2017. / Screening methodologies have identified specific targets that could serve as potential therapeutic markers in cancer drug design, and the Retinoblastoma binding protein 6 (RBBP6) which is predominately expressed in lung and breast cancers is one critical protein identified. This study seeks to understand the 3D structure of RBBP6 domains, with emphasis on cancer. Three of these domains have been studied in this project, i.e. the Domain With No Name (DWNN), RING Finger, and the p53-binding domain. The ubiquitin-like structure of the DWNN has implicated this domain as a ubiquitin-like modifier of other proteins such as p53, whilst the RING Finger domain has intrinsic E3 Ligase activity like MDM2 the prototypical negative regulator of p53. The DWNN and RING Finger domains have resolved solution NMR structures, whilst the p53-binding domain has none. Thus, the first initiative undertaken was to model the RBBP6 p53-binding domain using I-TASSER and eThread-Modeller web-severs. Our results demonstrated that this domain mainly constitutes of alpha-helices and loop structures. Structural quality validations of both I-TASSER and eThread-Modeller models were further assessed using Swiss-Model and ProSA (Protein structure analysis) web-servers. Analyses were focussed on specific statistical parameters (Anolea, DFire, QMEAN, ProCheck and the ProSA Z-score). Results from these analyses show that the first I-TASSER model is the best possible representation of the RBBP6 p53-binding domain depicting minimal deviation from native state. Furthermore, screening and docking studies were performed using Schrödinger-Maestro v10.7: Glide SP and drug-like molecules that would potentially serve as agonist or antagonist of RBBP6 were identified. / MT 2018