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Searching for riboswitches in the human genome and estimation of them as a potential drug target with insilico case studies

2023
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Advisor: Prof. Dr. Kemal Turhan

Abstract (EN)

Riboswitches are genetic regulatory structures usually located at the 5' end regions of mRNA. The most distinctive feature of riboswitches is that they directly recognize a physiological signal and affect the regulation of specific genes by shifts in RNA structure. The current release of Rfam database contains 40 families of riboswitches. As riboswitches have developed different molecular determinants to bind specific effectors, they have attracted attention not only for their ideal feedback mechanisms, but also for their potential to serve as new drug targets. On the other hand, riboswitches have important roles in regulating vital pathways in the cell through feedback mechanisms. Because of these properties, riboswitches have been considered as potential new targets for antibiotic design, theoretically and practically, in order to find a solution to multidrug resistance (MDR). This study has two purposes. Our primary aim is to identify gene sequences in the human genome that show significant compatibility with riboswitch structures available in the literature and to reveal the unknown functions of these gene sequences. In this direction, close to the boundary matches were obtained with the lysine riboswitch, which can be considered significant in certain regions of the human genome. The second aim of our study is to create a pipeline that organizes virtual screening analysis processes in which riboswitch RNA family members are considered as potential drug targets, using publicly available data from the "Rfam" biological database. The pipeline we created as a result of the study succeeded in obtaining the results of the virtual screening of the V. Vulnificus genome. When the obtained virtual screening results are examined considering the Lipinski rule, It can be said that the molecule with the accession ID "ZINC000004097280" is similar to "Ciprofloxacin" and the molecule with the access ID "ZINC000040394717" is similar to "Ceftazidime". "Ceftazidime" and "Ciprofloxacin" are among the drugs used in the treatment of diseases caused by the V. Vulnificus organism. Molecules with the ZINC accession identity that we have found similarity do not have a known use in the literature yet. In this respect, a contribution has been made to the literature.

Author

Dr. Nihat Burak Zihni

How to Cite

Nihat Burak Zihni (Doctorate thesis). Searching for riboswitches in the human genome and estimation of them as a potential drug target with insilico case studies, 2023, Karadeniz Technical University.

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