EVIDENCE FOR NONRANDOM HYDROPHOBICITY STRUCTURES IN PROTEIN CHAINS

The question of whether proteins originate from random sequences of am ino acids is addressed, A statistical analysis is performed in terms o f blocked and random walk values formed by binary hydrophobic assignme nts of the amino acids along the protein chains, Theoretical expectati ons of these variables from random distributions of hydrophobicities a re compared with those obtained from functional proteins, The results, which are based upon proteins in the SWISS-PROT data base, convincing ly show that the amino acid sequences in proteins differ from what is expected from random sequences in a statistically significant way, By performing Fourier transforms on the random walks, one obtains additio nal evidence for nonrandomness of the distributions, We have also anal yzed results from a synthetic model containing only two amino acid typ es, hydrophobic and hydrophilic. With reasonable criteria on good fold ing properties in terms of thermodynamical and kinetic behavior, seque nces that fold well are isolated. Performing the same statistical anal ysis on the sequences that fold well indicates similar deviations from randomness as for the functional proteins, The deviations from random ness can be interpreted as originating from anticorrelations in terms of an Ising spin model for the hydrophobicities. Our results, which di ffer from some previous investigations using other methods, might have impact on how permissive with respect to sequence specificity the pro tein folding process is-only sequences with nonrandom hydrophobicity d istributions fold well, Other distributions give rise to energy landsc apes with poor folding properties and hence did not survive the evolut ion.