Abstract:The underlying physical causes of SOD1---related ALS are still not well---understood. We address this problem here by computationally designing two de novo mutants, A89R and K128N, which were predicted theoretically to be either significantly destabilizing or stabilizing respectively. We subjected these in silico designed mutants to a series of experimental tests, including in vitro measures of thermodynamic stability, cell---based aggregation and toxicity assays, and an in vivo developmental model of zebrafis… Show more
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