Similarity graphing and enzyme-reaction database: methods to detect sequence regions of importance for recognition of chemical structures

We developed a new method which searches sequence segments responsiblefor the recognition of a given chemical structure. These segmentsare detected as those locally conserved among a sequence tobe analyzed (target sequence) and a set of sequences (referencesequences). Reference sequences are the sequences of functionallyrelated proteins, ligands of which contain a common chemicalsubstructure in their molecular structures. ‘Similaritygraphing’ cuts target sequences into segments, alignsthem with reference sequence pairwise, calculates the degreeof similarity for each alignment, and shows graphically cumulativesimilarity values on target sequence. Any locally conservedregions, short or long in length and weak or strong in similarity,are detected at their optimal conditions by adjusting threeparameters. The ‘enzyme-reaction database’ containschemical structures and their related enzymes. When a chemicalsubstructure is input into the database, sequences of the enzymesrelated to the input substructure are systematically searchedfrom the NBRF sequence database and output as reference sequences.Examples of analysis using similarity graphing in combinationwith the enzyme-reaction database showed a great potentialityin the systematic analysis of the relationships between sequencesand molecular recognitions for protein engineering.