AbstractAlthough the rules which describes the atomic basis of structure–function relationships of proteins have yet to be deciphered, they are nevertheless coded within the framework of the amino acid and nucleotide sequence. The objectives of the present investigations were to document a composite, new approach for the evaluation of the structure–function dependencies of proteins based on the analysis of the informational content of the primary amino acid sequence as well as the topological and functional regions of a protein. This approach is validated with the example of the p21 Ha‐ras oncogene family of proteins. Using this approach is validated with the example of the p21 Ha‐ras oncogene family of proteins. Using this approach, amino acids crucial for p21 transforming activity have been identified and these amino acid residue assignments compared with experiment