Application of landscape theory and the dehydron hypothesis to a crystal structure of a G85R mutant superoxide dismutase (SOD1) tetrameric complex allows for the description of a prion-like hypothesis that serves to explain propagated SOD1 misfolding. We have developed two conformational-change scenarios, one local to the ESL at the complex interface, and a second displacement at the ESL of the otherdimeric subunit. When taken together these provide for a prion-like mechanism that can serve to explain the observed conversion of wtSOD1 to a misfolded form by the G85R mutant. (C) 2016 Elsevier Inc. All rights reserved.