Scoring Matrices Scoring matrices Scoring matrices Different types ...

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Different types of matricesChemical similarity scoring (for proteins) -this matrix gives greater weight to aminoacids with similar chemical properties (e.gsize, shape or charge of the aa).Observed matrices for proteins - mostcommonly used by all programs. Thesematrices are constructed by analyzing thesubstitution frequencies seen in thealignments of known families of proteins.Different types of matricesThe most frequently observed matrices usedare PAM and BLOSUM matrices.PAM MatricesDeveloped by Margaret Dayhoff andco-workers.Derived from global alignments of verysimilar sequences (at least 85% identity), sothat there would be little likelihood of anobserved change being the result of severalsuccessive mutations, but it should reflectone mutation only.PAM - Point Accepted Mutations. An accepted point mutation in a protein is areplacement of one amino acid by another,accepted by natural selection. It is the result of twodistinct processes: the first is the occurrence of a mutation in theportion of the gene template producing one aminoacid of a protein the second is the acceptance of the mutation by thespecies as the new predominant form. To beaccepted, the new amino acid usually mustfunction in a way similar to the old one: chemicaland physical similarities are found between theamino acids that are observed to interchangefrequently.
Dayhoff estimated mutation rates fromsubstitutions observed in closely relatedproteins and extrapolated those rates tomodel distant relationships.PAM gives the probability that a givenamino acid will be replaced by any otherparticular amino acid after a givenevolutionary interval, in this case 1 acceptedpoint mutation per 100 amino acids.When used for protein comparison, themutation probability (odds) matrix isnormalized and the logarithm is taken. (thislets us add the scores along a protein insteadof multiplying the probabilities)The resulting matrix is the “log-odds”matrix, known as the PAM matrix.PAM#=Point Accepted Mutations / 100 basesThe number with the matrix (PAM120,PAM90), refers to the evolutionarydistance. Greater numbers are greaterdistances.To derive PAM250 you multiply PAM1250 times itselfPAM250 is the matrix derived of sequenceswith 250 PAMs.PAM250 At this evolutionary distance, only one amino acid infive remains unchanged. However, the amino acids vary greatly in theirmutability; 55% of the tryptophans. 52% of thecysteines and 27% of the glycines would still beunchanged, but only 6% of the highly mutableasparagines would remain. Several other aminoacids, particularly alanine, aspartic acid, glutamicacid, glycine, lysine, and serine are more likely tooccur in place of an original asparagine thanasparagine itself at this evolutionary distance!
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Scoring Matrices Scoring matrices Scoring matrices Different types ...

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