Bioinformatics Advance Access originally published online on April 7, 2009
Bioinformatics 2009 25(11):1356-1362; doi:10.1093/bioinformatics/btp164
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Reduced amino acid alphabets exhibit an improved sensitivity and selectivity in fold assignment
1Department of Physics, California Institute of Technology, Pasadena, CA 91125, 2Department of Physics, Brandeis University, Waltham, MA 02454, 3Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305 and 4Department of Applied Physics, California Institute of Technology, Pasadena, CA 91125, USA
*To whom correspondence should be addressed.
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Abstract |
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Motivation: Many proteins with vastly dissimilar sequences are found to share a common fold, as evidenced in the wealth of structures now available in the Protein Data Bank. One idea that has found success in various applications is the concept of a reduced amino acid alphabet, wherein similar amino acids are clustered together. Given the structural similarity exhibited by many apparently dissimilar sequences, we undertook this study looking for improvements in fold recognition by comparing protein sequences written in a reduced alphabet.
Results: We tested over 150 of the amino acid clustering schemes proposed in the literature with all-versus-all pairwise sequence alignments of sequences in the Distance mAtrix aLIgnment database. We combined several metrics from information retrieval popular in the literature: mean precision, area under the Receiver Operating Characteristic curve and recall at a fixed error rate and found that, in contrast to previous work, reduced alphabets in many cases outperform full alphabets. We find that reduced alphabets can perform at a level comparable to full alphabets in correct pairwise alignment of sequences and can show increased sensitivity to pairs of sequences with structural similarity but low-sequence identity. Based on these results, we hypothesize that reduced alphabets may also show performance gains with more sophisticated methods such as profile and pattern searches.
Availability: A table of results as well as the substitution matrices and residue groupings from this study can be downloaded from http://www.rpgroup.caltech.edu/publications/supplements/alphabets.
Contact: phillips{at}pboc.caltech.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Associate Editor: Dmitrij Frishman
Received on September 16, 2008; revised on March 10, 2009; accepted on March 11, 2009
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