SEMINAR ON PAM AND BLOSUM

PRESENTED BY: GAJENDRA SINGH VISHWAKARMA MSc II Yr

Contents
 Introduction  What

is PAM  PAM properties and method  PAM250  What is BLOSUM  BLOSUM property and method  Comparison Between PAM and BLOSUM

Introduction
 The

aim of a sequence alignment is to match "the most similar elements" of two sequences.  In sequence alignment scoring matrics system is used.
WHAT IS SCRIONG MATRICS SYSTEM:
In bioinformatics, scoring matrices for computing alignment scores are often based on observed substitution rates, derived from the substitution frequencies seen in multiple alignments of sequences.

SCORING MATRICES FOR AMINO ACID
 PAM

(Point Accepted Mutation )  BLOSUM (Blocks Substitution Matrix)

The Dayhoff Matrix (PAM)
 Developed

1978.  Counted likelihood of all possible substitutions in closely related proteins.  PAM – Point Accepted Mutation /Percent Accepted Mutation  Point accepted mutation – mutation of one residue accepted by evolution.

by Margaret Dayhoff,

PAM METHOD
Examine the kinds mutation that occur in closely related protein sequence, i.e. at short evolutionary times.  Extrapolate these differences to greater mutational distance/longer times.  Accepted point mutations tabulate actual mutations by looking at proteins that are sufficiently closely related than 15% different so that changes can be thought of as a single evolutionary step.  Consider a tree to correctly count changes.

TWO TYPE OF PAM MATRICES CAN BE CONSTUCTED
 MUTATIONALPROBABILITY

MATRIX: probability that residue in column j will replaced by residue in row i after some amount of evolution.  RELATIONAL ODD MATRIX : log odds from of the mutation probability matrix.

PAM 250

PROBLEMS WITH PAM
Not

all position are same. Evolutionary rates very greatly with in a sequence. Environment changes over evolutionary time.

BLOSUM
This is the series of blocks Amino acid substitution matrices (BLOSUM), all of which are derived based on direct on direct observation for every possible amino acid substitution in multiple sequence alignments.  These were constructed based on more than 2,000 conserved amino acid patterns representing 500 groups of protein sequences, the sequences patterns, also called blocks, are ungapped of amino acid substitutions of the residues in these blocks are calculated to produce a numerical table called block substitution matrix (BLOSAM).

BLOSUM METHOD
Data base Data Base of blocks

Deriving a frequency tables from a data base of blocks .. w 1 ..
1 A .. .. .. .. .. .. .. .. S .. .. .. ..

Computing a logarithm of odds matrix
1.2 7.5 6.3 1.9 5.5 3.1 6.5 2.0 8.1 4.3 3.7 5.8 2.9 7.7 3.2

PAM vs BLOSUM
 Dayhoff

estimated mutation rates from substitutions observed in closely related proteins and extrapolated those rates to models distant relationships.  In BLOSUM approach, frequencies were obtained directly from relationships represented in the block, regardless of evolutionary distance.  The Dayhoff frequency table included 36 pairs in which no accepted point mutations.

PAM vs BLOSUM
 In

contrast, the pairs counted with BLOSUM, included no fewer than 2369 occurrences of any particular substitution. • The BLOSUM matrices depend only on the identity and composition of groups protein in Prosite. • Therefore, there is no expectation that these substitution matrices will change significantly in the future.

PAM Versus BLOSUM
 PAM

is based on an evolutionary model.  BLOSUM is based on protein families.  PAM is based on global alignment.  BLOSUM is based on local alignment.

Referances
 ESSENTIAL • • • •

OF BIOINFORMATCES BY- JIN XIONG BIOINFORMATICS BY RASTOGY www.bioinformatics.cs.vt.edu www.cshprotocals.org www.biotechnica.org

THANX FOR U R PATIENCE

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