AbstractThe Entropic Landscape Analysis was applied to the prion protein sequences of various mammals in order to detect potential sites of variants that would be responsible for the susceptibility of prion disease infection. Among familiar mammals, canines including dogs have been demonstrating strong resistance to prion diseases. Among the canine specifc substitutions the entropic landscape analysis pinpoints the substitutions Asn104Gly and Ser107Asn having the biggest impact to the conformational transition and stability. Although they must be further corroborated by experiments in vivo et vitro, the results are demonstrating that the entropic landscape analysis is useful enough to screen substitutions and polymorphisms potentially relevant to conformational stability and transition because the calculation time for the analysis is as long as a few seconds, and the analysis can be done without knowing the 3D structures.