Characterizing cell cycle Cdk mechanisms and the influence of Cdk inhibitors on cyclin assembly.

The study of the cell cycle, specifically, understanding mechanistic regulation is fundamental for the development of therapeutic treatment in the event of disease. Limitless cell proliferation is a hallmark of cancer and often tied to cell cycle control. My research studied Cyclin- dependent kinases (Cdks) and their role in cell proliferation at the G1-S phase restriction point. I was able to shed insight on cyclin binding kinetics using Biolayer Interferometry (BLI) and the influence different types of inhibitors have on association of Cdks and cyclins. I reveal that Type I inhibitors increase binding affinity of CycA for Cdk2, whereas Type II inhibitors decrease affinity but differ in how they alter the CycA kinetic profile. Moreover, I explore an allosteric binding site of Cdk4-CycD that may be responsible for structural rearrangement to an active kinase configuration. My research as a whole gives insight into the development of a Cdk2 specific inhibitor and highlight the use of allosteric sites to understand mechanistic control of the cell cycle for Cdk inhibitor treatment therapy