Probing protein structural dynamics using simplified models

Structure and dynamics play crucial roles in many aspects of protein function. The detailed characterization of structure and dynamics of a protein is therefore critical for elucidation of its function. Despite the rapid advances in experimental methods, we are still much limited in our ability to characterize the structure and dynamics of a protein due to the resolution capability at length and time scales of the current methods. As complimentary approaches to the experimental methods, coarse-grained simulations based on simplified models offer unparallel opportunities for studying structure and dynamics that are hardly subject to direct experimental characterization. In this dissertation, we first develop a new methodology that enables the study of the meta-stable states of protein by incorporating hydrogen-exchange data derived from NMR experiments into coarse-grained simulations, and applied this method to characterize the folding intermediate of FAT domain. Second, we study large-scale conformational dynamics of vinculin and reveal new insights into allosteric control of its function. Third, we study the fidelity of protein structure reconstruction using inter-residue proximity constraints and rational strategies for constraint selection for protein structure determination