Reference:
Ioerger, T. (1997). The context-dependence of amino acid properties. Proceedings of the Fifth International Conference on Intelligent Systems for Molecular Biology, 157-166.
Abstract:
One of the current limitations of using sequence alignments to identify
proteins with similar structures is that some proteins with similar structures
do not have significant sequence similarity by identity. One way to address
this ``hidden-homology'' problem is to match amino acids based on their
chemical and physical properties. However, the amino acid properties overlap,
creating orthogonal dimensions of similarity, the relative strengths of which
are ambiguous. It has been observed that the role an amino acid plays (and
hence the property that is important) at a site in a protein depends on its
secondary and tertiary environment. To approximate and take advantage of this
dependence on context for improving the sensitivity of alignments of proteins
whose structures are unknown, we propose a surrogate definition of context
based on the pattern of hydropathy in a small window of contiguous neighbors
surrounding each amino acid. We present the results of an experiment in which
a search-based program iteratively tests and selects various properties in
independent contexts, and incrementally increases the ability of sequence
alignments to detect relationships among distantly-related proteins. The
method is shown to perform better than using the MDM78 substitution table for
partial match scores.