Improving protein alignment algorithms using amino-acid hydrophobicities - Applications of TMATCH, A new algorithms

Abstract

MotivationSequence database search and matching algorithms are an important tool when trying to understand the structure (and so the function) of proteins.Proteins with similar structure and function often have very similar primary structure. There are however many cases where proteins with similar structure have very different primary structures. Substitution matrices (PAM, BLOSUM, Gonnett) can be used to identify proteins of similar structure, but they fail when the sequence similarity falls below about 25%. ResultsWe have described a new algorithm for examining the the primary structure of proteins against a database of known proteins with a new hydrophobicity index. In this paper, we examine the ability of TMATCH to identify proteins of similar structure using sequence matching with the hydrophobicity index. We compare results from TMATCH with those obtained using FASTA and PSI-BLAST.We show that by using similarity patterns spread across the entire length of two proteins we get a more robust indicator of remote relatedness than relying upon high similarity scoring pair regions.

F1000ResearchTMATCH: A New Algorithm for Protein Alignments using amino-acid hydrophobicities

“…The average P (parameter) value is the assumed maximum percent threshold at which two random sequences should be deemed to be unrelated as the significance function F(Zb') (or Bn(Zb)) will result in a value above the alpha value of 0.1. The hyperbolic significance function calibration results we report above, was essentially replicated with datasets representing multiple protein families: DNA Polymerase B enzymes, G proteins, Glutathione proteins and Rhodopisin/GPCR proteins [6].…”

“…Figure 1 shows the modified fHst according to the defining equations above with a threshold value of 0.69 for the average score Sa. The linearity with a 469 member DNA polymerase B dataset (see the companion applications paper [6]) is excellent, with the regression line possessing an obvious 45 degree angle and passing through zero. The modified % Hst calculation eliminated fHst values above 100 % resulting from Sa values above 1.…”

“…Similarly, we see in table 5 that these two Serine protease enzymes also span the E() transition from marginally significant to nonsignificance. These F(Zb') values have been reported in a table in the companion application paper [6] where we have applied the TMATCH algorithm to the set of Tryptophan like Serine Proteases characterized by Pearson [4]. The Bn(Z) function is fitted with a 5 parameter hyperbolic significance function F(Zb') (see below).…”