Amino acid substitution matrices scoring

For fold recognition, the amino acid substitution matrix can be replaced by a 3D-ID substitution matrix (scoring table) computed from a database of known structures and sets of sequence-structure alignments (Bowie et al., 1991). Recently, the matrix has been further extended to include predicted secondary structure of the sequence using a H3P2 matrix (Rice Eisenberg, 1997). The 3D-ID substitution matrix allows one to match the amino acid residues (and/or their secondary structure prediction) with structural (environmental) classes. 

PAM matrix PAM (percent accepted mutation) and BLOSUM (blocks substitution matrix) are matrices that define scores for each of the 210 possible amino acid substitutions. The scores are based on empirical substitution frequencies observed in alignments of database sequences and in general reflect similar physicochemical properties (e.g., a substitiution of leucine for isoleucine, two amino acids of similar hydrophobicity and size, will score higher than a substitution of leucine for glutamate.)... 

Fig. 4. Substitution matrix based on disordered protein families. Below the diagonal are the scores for each amino acid substitution. Above the diagonal are the differences between BLOSUM 62 and the disorder matrix. On the diagonal are the scores/differences. (From Radivojac et al., 2002, PSB 2002 7, 589-600, with permission of World Scientific Publishing Co. Pte Ltd.)...

From the examination of appropriately aligned sequences, substitution matrices can be deduced. In these matrices, a large positive score corresponds to a substitution that occurs relatively frequently, whereas a large negative score corresponds to a substitution that occurs only rarely. The Blosum-62 substitution matrix illustrated in Figure 7 9 is an example. The highest scores in this substitution matrix indicate that amino acids such as cysteine (C) and tryptophan (W) tend to be conserved more than those such as serine (S) and alanine (A). Furthermore, structurally conservative... 

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