Abstract: The dynamical properties of proteins are critical for their function and are often perturbed in disease. Despite this knowledge, developing chemical probes that explicitly target protein dynamics is challenging, and therapeutic molecules that alter protein dynamics are often discovered serendipitously. However, all living organisms contain a dedicated class of proteins, termed molecular chaperones, that specifically regulate protein folding and dynamics to prevent pathological outcomes. Can understanding the function of these molecular chaperone proteins inspire development of novel “pharmacological chaperones”? By combining biochemistry, biophysics, and chemical biology approaches with human genetics and emerging technologies, my research aims to answer this question. Specifically, my goal is to use these molecules to study and correct altered protein dynamics in neurodegenerative and neuromuscular diseases.
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