Protein Science, Vol 3, Issue 10 1847-1857, Copyright © 1994 by Cold Spring Harbor Laboratory Press

ARTICLE

Discovering structural correlations in {alpha}-helices

T. M. KLINGLER and D. L. BRUTLAG
Department of Biochemistry and Section on Medical Informatics, Stanford University School of Medicine, Stanford, California 94305-5307

We have developed a new representation for structural and functional motifs in protein sequences based on correlations between pairs of amino acids and applied it to {alpha}-helical and {beta}-sheet sequences. Existing probabilistic methods for representing and analyzing protein sequences have traditionally assumed conditional independence of evidence. In other words, amino acids are assumed to have no effect on each other. However, analyses of protein structures have repeatedly demonstrated the importance of interactions between amino acids in conferring both structure and function. Using Bayesian networks, we are able to model the relationships between amino acids at distinct positions in a protein sequence in addition to the amino acid distributions at each position. We have also developed an automated program for discovering sequence correlations using standard statistical tests and validation techniques. In this paper, we test this program on sequences from secondary structure motifs, namely {alpha}-helices and {beta}-sheets. In each case, the correlations our program discovers correspond well with known physical and chemical interactions between amino acids in structures. Furthermore, we show that, using different chemical alphabets for the amino acids, we discover structural relationships based on the same chemical principle used in constructing the alphabet. This new representation of 3-dimensional features in protein motifs, such as those arising from structural or functional constraints on the sequence, can be used to improve sequence analysis tools including pattern analysis and database search.
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