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Computing
Mutability Probability Between Amino Acid Pairs
Normalizing
Mutability Probability, X to Y
For each Y among all amino acids,
compute mutability probability of X to Y
as described above
Get a total of these 20 probabilities.
Divide them by a normalizing factor such
that the probability that X will NOT
change is 99% and the sum of
probabilities that it will change to any
other amino acid is 1%
Converting
Mutability Probabilities to
Log Odds Score for X to Y
x = -1.01
Disadvantages of PAM
Matrices
A
phylogenetic
tree
must
be
constructed
first,
implying
some
circularity in the analysis
Disadvantage:
The original PAM-1
matrix was based on a limited number
of
families,
not
necessarily
representative of all protein families
The Markov model does not take into
account that multi-step mutations
should be treated differently from
single-step ones