Homology graphing

Next, we explain evolutional and structural bases for searching for sequence-function relationships in proteins. Then, we describe homology graphing, a method for sequence analysis to Identify which regions In a sequence are those of functionally Importance,... 

Figure 4 shows two homology graphs of the amino acid sequence of human GR obtained against the two different sets of reference sequences. One (- - -) Is a graph the reference sequences of which are the sequences of NAD(P)/FAD-related enzymes. In the other graph... 

Figure 4. Homology graphs of human glutathione reductase.

Asp-331, Hls-467, and Glu-472 are assigned as the residues that are In contact with a bound FAD molecule or that catalyze the reaction of human GR (47). Except for Asp-331, all of these Important residues are around the peak maxima In the homology graph. 

In the above analysis of the sequence of human GR by homology graphing, four sequence segments are assigned as those which have affinity with or make recognition of the chemical structures (or substructures) of FAD and NADPH. 

Since the number of amino acid residues defined In consensus sequences are usually less than 10 residues, consensus sequences are too small as a unit of function and molecular evolution of proteins. Therefore sequence segments found In homology graphs are favored for sequence-function relationships over consensus sequences. 

Application of Homology Graphing to Finding Lead Structures. 

Figure 5, Flow chart of finding lead structures using homology graph of a target protein.

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