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Sequence analysis is the primary and simplest approach to discover structural, functional and evolutionary details of related proteins. All the alignment based approaches of sequence analysis make use of amino acid substitution matrices, and the accuracy of the results largely depends on the type of scoring matrices used to perform alignment tasks. An amino acid substitution matrix is a 20 × 20 matrix in which the individual elements encapsulate the rates at which each of the 20 amino acid residues in proteins are substituted by other amino acid residues over time. In contrast to most globular/ordered proteins whose amino acids composition is considered as standard, there are several classes of proteins (e.g., transmembrane proteins) in which certain types of amino acid (e.g., hydrophobic residues) are enriched. These compositional differences among various classes of proteins are manifested in their …