Biophysical Journal 71: 148-155 (1996)
© 1996 the Biophysical Society

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Strait, B J Articles by Dewey, T G Search for Related Content PubMed PubMed Citation Articles by Strait, B J Articles by Dewey, T G

The Shannon information entropy of protein sequences.

Department of Chemistry, University of Denver, Colorado 80208, USA.

ABSTRACT

A comprehensive data base is analyzed to determine the Shannon information content of a protein sequence. This information entropy is estimated by three methods: a k-tuplet analysis, a generalized Zipf analysis, and a "Chou-Fasman gambler." The k-tuplet analysis is a "letter" analysis, based on conditional sequence probabilities. The generalized Zipf analysis demonstrates the statistical linguistic qualities of protein sequences and uses the "word" frequency to determine the Shannon entropy. The Zipf analysis and k-tuplet analysis give Shannon entropies of approximately 2.5 bits/amino acid. This entropy is much smaller than the value of 4.18 bits/amino acid obtained from the nonuniform composition of amino acids in proteins. The "Chou-Fasman" gambler is an algorithm based on the Chou-Fasman rules for protein structure. It uses both sequence and secondary structure information to guess at the number of possible amino acids that could appropriately substitute into a sequence. As in the case for the English language, the gambler algorithm gives significantly lower entropies than the k-tuplet analysis. Using these entropies, the number of most probable protein sequences can be calculated. The number of most probable protein sequences is much less than the number of possible sequences but is still much larger than the number of sequences thought to have existed throughout evolution. Implications of these results for mutagenesis experiments are discussed.

This article has been cited by other articles:

				P. W. Hildebrand, S. Gunther, A. Goede, L. Forrest, C. Frommel, and R. Preissner Hydrogen-Bonding and Packing Features of Membrane Proteins: Functional Implications Biophys. J., March 15, 2008; 94(6): 1945 - 1953. [Abstract] [Full Text] [PDF]

				Y. Sawada and S. Honda Structural Diversity of Protein Segments Follows a Power-Law Distribution Biophys. J., August 15, 2006; 91(4): 1213 - 1223. [Abstract] [Full Text] [PDF]

				T. Aynechi and I. D. Kuntz An Information Theoretic Approach to Macromolecular Modeling: I. Sequence Alignments Biophys. J., November 1, 2005; 89(5): 2998 - 3007. [Abstract] [Full Text] [PDF]

				B. Shen and M. Vihinen Conservation and covariance in PH domain sequences: physicochemical profile and information theoretical analysis of XLA-causing mutations in the Btk PH domain Protein Eng. Des. Sel., March 1, 2004; 17(3): 267 - 276. [Abstract] [Full Text] [PDF]

				J. P. Zbilut, A. Colosimo, F. Conti, M. Colafranceschi, C. Manetti, M. Valerio, C. L. Webber Jr., and A. Giuliani Protein Aggregation/Folding: The Role of Deterministic Singularities of Sequence Hydrophobicity as Determined by Nonlinear Signal Analysis of Acylphosphatase and A{beta}(1-40) Biophys. J., December 1, 2003; 85(6): 3544 - 3557. [Abstract] [Full Text] [PDF]

				E. A. Szell, G. T. Somogyi, W. C. de Groat, and G. P. Szigeti Developmental changes in spontaneous smooth muscle activity in the neonatal rat urinary bladder Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2003; 285(4): R809 - R816. [Abstract] [Full Text] [PDF]

				R. Schwartz, S. Istrail, and J. King Frequencies of amino acid strings in globular protein sequences indicate suppression of blocks of consecutive hydrophobic residues Protein Sci., May 1, 2001; 10(5): 1023 - 1031. [Abstract] [Full Text]

				A. Giuliani, P. Sirabella, R. Benigni, and A. Colosimo Mapping protein sequence spaces by recurrence quantification analysis: a case study on chimeric structures Protein Eng. Des. Sel., October 1, 2000; 13(10): 671 - 678. [Abstract] [Full Text] [PDF]

				W. R. Atchley, K. R. Wollenberg, W. M. Fitch, W. Terhalle, and A. W. Dress Correlations Among Amino Acid Sites in bHLH Protein Domains: An Information Theoretic Analysis Mol. Biol. Evol., January 1, 2000; 17(1): 164 - 178. [Abstract] [Full Text] [PDF]