UC San Diego

Proteins dance; the atoms of a protein move through time in our cellular aqueous environment, and each atom is important in this process. The dance of a protein is unique to that protein, and alone controls how that protein functions. In this way, our cells are a world unto their own, and as the proteins of a cell dance along, they orchestrate life. In this thesis, I discuss the dance, or dynamics, of five different proteins: the ankyrin repeat and SOCS box protein 9 (ASB9), creatine kinase (CK), the L99A mutant of T4 lysozyme, the Inhibitor of κB kinase 2 (IKK2), and the NFκB essential modulator (NEMO). Each of these proteins have unique sizes, shapes, dynamics, and roles in the cell. To study these proteins, I chose to use the computational microscope, performing molecular dynamics simulations at the atomic level. Through the solving of theoretical models of the bonds between atoms, iterated over and over again through time, a dance unfolded for each of these proteins, illuminating how these proteins perform their duties in our cells and in our test tubes. I demonstrate that ASB9 and CK interact through a highly disordered interface, uncover the dynamics which guide both excited state transitioning and benzene release in the L99A mutant of T4 lysozyme, and present a hypothesis for how NEMO appends itself to the IKK2 hexamer.