Abstract
An amino acid substitution scoring matrix encapsulates the rates at which various amino acid residues in proteins are substituted by other amino acid residues, over time. Database search methods make use of substitution scoring matrices to identify sequences with homologous relationships. However, widely used substitution scoring matrices, such as BLOSUM series, have been developed using aligned blocks that are mostly devoid of disordered regions in proteins. Hence, these substitution-scoring matrices are mostly inappropriate for homology searches involving proteins enriched with disordered regions as the disordered regions have distinct amino acid compositional bias, and therefore expected to have undergone amino acid substitutions that are distinct from those in the ordered regions. We, therefore, developed a novel series of substitution scoring matrices referred to as EDSSMat by exclusively considering the substitution frequencies of amino acids in the disordered regions of the eukaryotic proteins. The newly developed matrices were tested for their ability to detect homologs of proteins enriched with disordered regions by means of SSEARCH tool. The results unequivocally demonstrate that EDSSMat matrices detect more number of homologs than the widely used BLOSUM, PAM and other standard matrices, indicating their utility value for homology searches of intrinsically disordered proteins.
Highlights
An amino acid substitution scoring matrix encapsulates the rates at which various amino acid residues in proteins are substituted by other amino acid residues, over time
We have developed substitution matrices appropriate for homology searches involving eukaryotic proteins enriched with intrinsically disordered regions (IDRs)
It is clearly evident from coverage values and Z-scores that Eukaryotic Disorder Substitution Scoring Matrix (EDSSMat)[90] performance is significantly better than VTML120 on all three Less Disordered (LD), Moderately Disordered (MD) and Highly Disordered (HD) test datasets
Summary
An amino acid substitution scoring matrix encapsulates the rates at which various amino acid residues in proteins are substituted by other amino acid residues, over time. Widely used substitution scoring matrices, such as BLOSUM series, have been developed using aligned blocks that are mostly devoid of disordered regions in proteins. These substitution-scoring matrices are mostly inappropriate for homology searches involving proteins enriched with disordered regions as the disordered regions have distinct amino acid compositional bias, and expected to have undergone amino acid substitutions that are distinct from those in the ordered regions. We developed a novel series of substitution scoring matrices referred to as EDSSMat by exclusively considering the substitution frequencies of amino acids in the disordered regions of the eukaryotic proteins. There are many naturally occurring functional proteins that do not attain stable three - dimensional structures and appear unfolded Such proteins have been referred to as intrinsically disordered proteins (IDPs). The use of scoring matrices developed from ordered regions of proteins for Matrix Parameters Matrix Average Expected Score (E) Relative Entropy (H)
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