Prediction of Contact Residue Sites Based on 
Concurrent and Compensatory Substitutions Between Sites in Protein Evolution

			Sanzo Miyazawa

		    sanzo.miyazawa@gmail.com
		Graduate School of Engineering
		Gunma University, Japan


Structural and functional constraints originating in
residue-residue interactions act on each amino acid in a
protein, because a protein must fold into a unique
three-dimensional structure and play a specific function.
Selective constrains on amino acids in proteins are recorded
in amino acid orders in homologous protein sequences and
also in the evolutionary trace of amino acid substitutions.
Thus, statistical analyses of amino acid orders and of the
evolutionary trace of amino acid substitutions can provide
information on residue pair couplings.  A challenge is to
extract direct dependencies between residue sites by
excluding indirect correlations that originate from indirect
interactions through other residues within a protein or even
through other molecules.  Recent attempts of disentangling
direct from indirect dependencies of amino acid types
between residue positions in multiple sequence alignments of
proteins have revealed that the strength of inferred residue
couplings is an excellent predictor of residue-residue
proximity in folded structures.  Here, we report an
alternative attempt of inferring site couplings from
concurrent and compensatory substitutions between sites at
each branch of a phylogenetic tree.  Accuracy of contact
prediction based on the present method is comparable to that
of the maximum entropy method.