Cheung, MargaretNde Kengne, Jules Berlin2024-04-262024-04-262024-04-262024NdeKengne_washington_0250E_26617.pdfhttp://hdl.handle.net/1773/51399Thesis (Ph.D.)--University of Washington, 2024Proteins are dynamic entities that constantly undergo conformational changes, influenced by factors such as temperature and ligand binding. Therefore, understanding protein dynamics, protein-protein interactions, and protein complex formation is essential for unraveling the intricate mechanisms behind biological functions. This thesis delves into the dynamic realm of the calcium-binding protein calmodulin (CaM), investigating the nuanced interplay between the structural flexibility and functional specificity of calmodulin as it interacts with the CaM-dependent protein kinase II (CaMKII) peptide. Employing an experimentally guided computational technique, the thesis aims to unravel the dynamic behaviors of CaM, the reciprocal relationship between calcium, CaM, and CaMKII peptide, which is a finely tuned signaling cascade essential for cellular function such as synaptic plasticity, learning and memory. Furthermore, protein-protein interactions are key determinants of cellular processes, enabling the formation of functional complexes and signaling pathways, and advancements in experimental and computational methods have facilitated the study of these interactions on a large scale. However, due to the transient nature of the interactions and the high flexibility of the protein complexes and their components, using a single technique to investigate the three-dimensional structure of the protein complexes, which is paramount for deciphering the function of the complexes, becomes an enormous challenge. The thesis also describes an integrative modeling technique, which uses a combined experiment, computational, and machine learning approaches to determine the three-dimensional structure of macromolecular complexes, while using the INO80 chromatin remodeling complex as an example.application/pdfen-USCC BYcalcium-induced conformational changes on calmodulinCaM/CaMKII interactionsIntegrative modelingModeling protein conformational changesprotein dynamicsprotein protein interactionsBiophysicsPhysicsBiologyPhysicsThesis