Amino acid substitution scoring matrices specific to

[lindahollander]

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.

[Autumnrennie]

A stable three - dimensional native structure has been considered to be the obligatory prerequisite condition for a protein to perform its biological function1. However, 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). In many cases, instead of the whole protein, only some segments in the protein are disordered, and such peptide segments have been referred to as intrinsically disordered regions (IDRs)2. Interestingly, intrinsically disordered regions have been known to endow proteins with functional promiscuity3.

[lindahollander]

Structural disorder is not an uncommon feature among proteins, and the proportion of disorder increases as the complexity of genomes increases from bacteria, archaea to eukaryotes with a sharp increase at the prokaryote/eukaryote boundary4,5,6. About 33% of eukaryotic proteins contain at least one functionally relevant long (>30 residues) intrinsically disordered region in comparison to 2.0% in archaean and 4.2% in eubacterial proteins7. It is interesting to note that IDRs often harbour short linear motifs (3–10 amino acid residues) which anchor with their cognate structural domains of other proteins thereby enabling protein-protein physical interactions8,9.

[Jeanine Devon]

Matrix algebra is doubtlessly being among the most powerful mathematical tools that are available for the analysis of linear networks. The advantages of matrices for our present purpose are that in a couple of linear differential equations, all the variables of 1 kind can be represented by an individual symbol therefore also all the parameters of each kind.