Abstract: The present disclosure includes predicting a three-dimensional structure of one residue mutant of a membrane protein where respective amino acid residues have been substituted by all amino acids, calculating a solvation entropy change in formation of a tertiary structure from a primary structure or formation of the tertiary structure from secondary-structure units within a transmembrane segment, and extracting a candidate of an amino acid mutant to be thermostabilized based on a difference between a solvation entropy change in the membrane protein and a solvation entropy change in the amino acid mutant.