Simplifying amino acid alphabets by means of a branch and bound algorithm and substitution matrices

MOTIVATION Protein and DNA are generally represented by sequences of letters. In a number of circumstances simplified alphabets (where one or more letters would be represented by the same symbol) have proved their potential utility in several fields of bioinformatics including searching for patterns occurring at an unexpected rate, studying protein folding and finding consensus sequences in multiple alignments. The main issue addressed in this paper is the possibility of finding a general approach that would allow an exhaustive analysis of all the possible simplified alphabets, using substitution matrices like PAM and BLOSUM as a measure for scoring. RESULTS The computational approach presented in this paper has led to a computer program called AlphaSimp (Alphabet Simplifier) that can perform an exhaustive analysis of the possible simplified amino acid alphabets, using a branch and bound algorithm together with standard or user-defined substitution matrices. The program returns a ranked list of the highest-scoring simplified alphabets. When the extent of the simplification is limited and the simplified alphabets are maintained above ten symbols the program is able to complete the analysis in minutes or even seconds on a personal computer. However, the performance becomes worse, taking up to several hours, for highly simplified alphabets. AVAILABILITY AlphaSimp and other accessory programs are available at http://bioinformatics.cribi.unipd.it/alphasimp

[1]  S Karlin,et al.  Multiple-alphabet amino acid sequence comparisons of the immunoglobulin kappa-chain constant domain. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[2]  David R. Gilbert,et al.  Approaches to the Automatic Discovery of Patterns in Biosequences , 1998, J. Comput. Biol..

[3]  E. Balas,et al.  Set Partitioning: A survey , 1976 .

[4]  R. Levy,et al.  Simplified amino acid alphabets for protein fold recognition and implications for folding. , 2000, Protein engineering.

[5]  L. H. Bradley,et al.  Protein design by binary patterning of polar and nonpolar amino acids. , 1993, Methods in molecular biology.

[6]  Jun Wang,et al.  A computational approach to simplifying the protein folding alphabet , 1999, Nature Structural Biology.

[7]  D. Baker,et al.  Functional rapidly folding proteins from simplified amino acid sequences , 1997, Nature Structural Biology.

[8]  K. Dill.  Theory for the folding and stability of globular proteins. , 1985, Biochemistry.

[9]  S. Henikoff,et al.  Amino acid substitution matrices from protein blocks. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[10]  J. C. Shepherd.  Method to determine the reading frame of a protein from the purine/pyrimidine genome sequence and its possible evolutionary justification. , 1981, Proceedings of the National Academy of Sciences of the United States of America.