Ideal amino acid exchange forms for approximating substitution matrices

Abstract

We have analyzed 29 published substitution matrices (SMs) and five statistical protein contact potentials (CPs) for comparison. We find that popular, 'classical' SMs obtained mainly from sequence alignments of globular proteins are mostly correlated by at least a value of 0.9. The BLOSUM62 is the central element of this group. A second group includes SMs derived from alignments of remote homologs or transmembrane proteins. These matrices correlate better with classical SMs (0.8) than among themselves (0.7). A third group consists of intermediate links between SMs and CPs - matrices and potentials that exhibit mutual correlations of at least 0.8. Next, we show that SMs can be approximated with a correlation of 0.9 by expressions c(0) + x(i)x(j) + y(i)y(j) + z(i)z(j), 1<or= i, j <or= 20, where c(0) is a constant and the vectors (x(i)), (y(i)), (z(i)) correlate highly with hydrophobicity, molecular volume and coil preferences of amino acids, respectively. The present paper is the continuation of our work (Pokarowski et al., Proteins 2005;59:49-57), where similar approximation were used to derive ideal amino acid interaction forms from CPs. Both approximations allow us to understand general trends in amino acid similarity and can help improve multiple sequence alignments using the fast Fourier transform (MAFFT), fast threading or another methods based on alignments of physicochemical profiles of protein sequences. The use of this approximation in sequence alignments instead of a classical SM yields results that differ by less than 5%. Intermediate links between SMs and CPs, new formulas for approximating these matrices, and the highly significant dependence of classical SMs on coil preferences are new findings.

Nature of Protein Family Signatures: Insights from Singular Value Analysis of Position-Specific Scoring Matrices

“…In addition to these two properties, Pokarowski et al[10] also noted the importance of the coil propensity. Wrabl and Grishin[50] also found similar preferences in the study of properties extracted from multiple sequence alignments.…”

“…There have been many kinds of AASMs developed to date among which the most popular ones include the PAM [5] and the BLOSUM series [6]. General properties of AASMs are now well clarified[7], [8], [9], [10]. Tomii and Kanehisa found that the PAM matrices can be well approximated by the volume and hydrophobicity of amino acid residues[8].…”

Amino acid interaction networks provide a new lens for therapeutic antibody discovery and anti-viral drug optimization

“…Finally, the nature of the mutations that do occur in regions of high SIN were investigated. Whereas mutations that occur elsewhere in the protein do not cluster based on their BLOSUM62 score [15,16] (a measure of relatedness of two differing amino acids), only positive BLOSUM-scored mutations (viz., conserved) occur within high SIN networks. Taken together these results demonstrate that amino acids found on the surface of viral proteins that have high SIN scores tend to cluster and that these regions are highly limited in the frequency and extent of mutation.…”

The Ancient Operational Code is Embedded in the Amino Acid Substitution Matrix and aaRS Phylogenies

“…Pokarowski et al [35] used a parametric approach to compare a large number of diverse amino acid substitution matrices and establish correlations between them. It was found that three almost completely independent factors are the major determinants of amino acid substitutability: whether or not pairs of amino acids are (i) hydrophobic or polar, (ii) large or small, or (iii) occurring in or absent from peptide backbone loops.…”