Position Specific Scoring Matrix
Evolutionary information, one of the most import kinds of information in protein functionality annotation in biological analysis, has been widely used in many studies [21,60-63]. In this study, evolutionary information in forms of PSSM profile of every protein sequence is obtained by running the PSI-BLAST [64] program to search the non-redundant (NR) database through three iteration with 0.001 as the E-value cutoff for multiple sequence alignment. The final PSSM profile is a matrix with dimension of L*20 (excluding dummy residue X), which can depicted as follows:
(2)  PSS  M  = S  1 , 1     S  1 , 2     ⋯   S  1 , 20      S  2 , 1     S  2 , 2     ⋯   S  2 , 20      ⋮  ⋮  ⋮  ⋮   S  L , 1     S  L , 2     ⋯   S  L , 20
where L is the length of protein, the Si,j represents the occurrence probability of amino acid j at position i of the protein sequence, the rows of matrix represent the positions of the sequence and the columns of the matrix represent the 20 types original amino acids. PSSM scores are generally shown as positive or negative integers. Positive scores indicate that the given amino acid occurs more frequently in the alignment than expected by chance, while negative scores indicate that the given amino acid occurs less frequently than expected. Large positive scores often indicate critical functional residues, which may be active site residues or residues required for other intermolecular interactions. Therefore the element of PSSM profile can be used to approximately measure the occurrence probability of the corresponding amino acid at a specific position.