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Bioinformatics in PAM AND BLOSUM

This document summarizes a seminar on the PAM and BLOSUM scoring matrices used for sequence alignment. PAM matrices are based on observed mutation rates between closely related proteins, extrapolated over evolutionary time. BLOSUM matrices are based directly on observed substitution frequencies within conserved blocks of multiple sequence alignments, regardless of evolutionary distance. Key differences are that PAM is based on an evolutionary model and global alignment, while BLOSUM is based on observed protein families and local alignment. Both aim to match the most similar elements between sequences but use different methodologies to derive scoring values.

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16K views17 pages

Bioinformatics in PAM AND BLOSUM

This document summarizes a seminar on the PAM and BLOSUM scoring matrices used for sequence alignment. PAM matrices are based on observed mutation rates between closely related proteins, extrapolated over evolutionary time. BLOSUM matrices are based directly on observed substitution frequencies within conserved blocks of multiple sequence alignments, regardless of evolutionary distance. Key differences are that PAM is based on an evolutionary model and global alignment, while BLOSUM is based on observed protein families and local alignment. Both aim to match the most similar elements between sequences but use different methodologies to derive scoring values.

Uploaded by

gladson
Copyright
© Attribution Non-Commercial (BY-NC)
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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
 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
Computing a logarithm of
tables from a data base
odds matrix
of blocks
1 .. .. w 1.2
1 A .. .. ..
7.5 6.3
.. .. .. .. .. 1.9 5.5 3.1
S .. .. .. .. 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
 Incontrast, 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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