bioinformatics in PAM AND BLOSUM

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 by Margaret Dayhoff, 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.

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 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 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 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 of blocks

Data base

Deriving a frequency tables from a data base of blocks 1 .. .. w 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, Therefore, there there is is no no expectation 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