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Computer Aided Drug Design from a Series of GSK3b Inhibitors: Advancements Towards the Treatment of Bipolar Disorder

Boesger, Hannah
http://orcid.org/0000-0002-5634-369X
http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1650802882861802

Abstract Details

2022, Bachelor of Science (BS), Ohio University, Neuroscience.
Lithium, a therapeutic first introduced in 1952, is still considered the gold standard for treatment of bipolar disorder. Although many new medications have been discovered over the years, lithium is the only therapeutic used exclusively for bipolar disorder-- indicating a separate mechanism of action from antipsychotic and antidepressive treatments (Kaidanovich-Beilin et al., 2011). Genetic and pharmacological studies have shown that lithium’s therapeutic efficacy is at least partially due to inhibition of glycogen synthase kinase-3 beta, or GSK3b (Kaidanovich-Beilin et al., 2011). Development of small molecule therapeutics to target GSK3b with better drug like qualities such as higher affinity and selectivity can lead to advancements in our understanding and treatment of bipolar disorder. This study investigates the structure activity relationship of small molecule GSK3b inhibitors through ab initio calculations, protein kinase sequence alignment, and computational docking studies. We found that although the ATP binding pocket is highly conserved, a proline residue unique to GSK3 may contribute to selectivity of small molecule inhibitors. In addition, small molecule inhibitors may show increased selectivity for GSK3b through preferential SH-π interactions with cysteine residue 199. Finally, docking studies suggest that GSK3b may be too dynamic or ligand-specific for predictive docking. Overall, this work has improved understanding of how small molecule inhibitors may utilize the GSK3b ATP binding pocket and their potential to treat bipolar disorder.
Jennifer Hines (Advisor)
82 p.
Neurosciences
GSK3; computer aided drug design; bipolar disorder

Recommended Citations

Citations

  • Boesger, H. (2022). Computer Aided Drug Design from a Series of GSK3b Inhibitors: Advancements Towards the Treatment of Bipolar Disorder [Undergraduate thesis, Ohio University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1650802882861802

    APA Style (7th edition)

  • Boesger, Hannah. Computer Aided Drug Design from a Series of GSK3b Inhibitors: Advancements Towards the Treatment of Bipolar Disorder . 2022. Ohio University, Undergraduate thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1650802882861802.

    MLA Style (8th edition)

  • Boesger, Hannah. "Computer Aided Drug Design from a Series of GSK3b Inhibitors: Advancements Towards the Treatment of Bipolar Disorder ." Undergraduate thesis, Ohio University, 2022. http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1650802882861802

    Chicago Manual of Style (17th edition)

ouhonors1650802882861802
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© 2022, some rights reserved.Creative Commons License Computer Aided Drug Design from a Series of GSK3b Inhibitors: Advancements Towards the Treatment of Bipolar Disorder by Hannah Boesger is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by Ohio University Honors Tutorial College and OhioLINK.