**Definition 1.4**
A 1-

__PAM__ unit is the amount of evolution which will change,
on average,

of the amino acids. In mathematical terms, this
is expressed as a matrix

*M* such that

,
where

*f*_{i} is the frequency of the

*i*^{th}
amino acid and

*M*_{ij} is the probability that an amino acid

*i* mutates into an amino acid

*j*
at one PAM distance [

5]. The function

__
__*PAM*(*s*1,
*s*2) is the PAM distance of two sequences

*s*_{i},

*s*_{2} that
maximizes the OPA score.