Combined experimental and computational studies of the interactions between small molecule ligands and eukaryotic translation initiation factors eIF5B and eIF4E

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dc.contributor.authorChukka, Prakash Amruth Raj
dc.contributor.supervisorThakor, Nehal
dc.contributor.supervisorWetmore, Stacey D.
dc.date.accessioned2022-05-27T17:23:36Z
dc.date.available2022-05-27T17:23:36Z
dc.date.issued2021
dc.degree.levelMastersen_US
dc.description.abstracteIF5B and eIF4E are aberrantly expressed in several cancers, and there is a growing body of literature that recognises their importance in cancer survival. This thesis attempts to study the interactions of small molecule inhibitors with eIF5B and eIF4E by combining cell, molecular, and computational biology techniques. Through western blotting, we identified that ribavirin does not affect the function of eIF5B in BT48 and U343 cells. These results were corroborated by MD simulations, which suggested that the charge on nucleobase of RTP prevents interaction with eIF5B. Using homology modeling and protein validation, the first human eIF5B structure was generated that facilitated the identification of the LWW31 binding site. In addition, MD simulations provided insights into the stability of m7GTP and the binding mode of RBV. Overall, this thesis provides insight into small molecule interactions with eIF5B and eIF4E, which might be beneficial for the future drug design of antineoplastic drugs.en_US
dc.identifier.urihttps://hdl.handle.net/10133/6213
dc.language.isoen_CAen_US
dc.proquest.subject0487en_US
dc.proquest.subject0715en_US
dc.proquest.subject0379en_US
dc.proquestyesYesen_US
dc.publisherLethbridge, Alta. : University of Lethbridge, Dept. of Chemistry and Biochemistry
dc.publisher.departmentDepartment of Chemistry and Biochemistryen_US
dc.publisher.facultyArts and Scienceen_US
dc.relation.ispartofseriesThesis (University of Lethbridge. Faculty of Arts and Science)
dc.subjectmRNA translationen_US
dc.subjectuORFen_US
dc.subjectGlioblastomaen_US
dc.subjectDockingen_US
dc.subjectProtein modelingen_US
dc.subjectAntineoplastic drugs
dc.subject.lcshAntineoplastic agents
dc.subject.lcshComputational chemistry
dc.subject.lcshWestern immunoblotting
dc.subject.lcshEukaryotic cells--Research
dc.subject.lcshLigands
dc.subject.lcshDissertations, Academic
dc.titleCombined experimental and computational studies of the interactions between small molecule ligands and eukaryotic translation initiation factors eIF5B and eIF4Een_US
dc.typeThesisen_US
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