Many neurodegenerative diseases,including the Prion diseases and familial amyotrophic lateral sclerosis,have a molecular basis in the misfolding and aggregation of normally healthy proteins.In this talk I will present results of recent calculations analyzing the stability of local regions of both wild type and mutant PrPc,as well as holo and Zn-deficient SOD1.Analysis of the propensity of different regions for fluctuation-induced misfolding leads to candidate scenarios for conversion as a template-directed aggregation process.