This question might be silly but I need some clarification.
I'm slightly confused about if there are multiple PAM and BLOSUM matrices? Is there a different matrix for each sequence?
My understanding is that PAM and BLOSUM are substitution matrices that are used to demonstrate how similar a sequence is to other sequences by seeing how many iterations of the matrix multiplication are needed before being able to achieve a "similar primary composition". Is this correct?
As I've understood it this means that if I want to compare 2 sequences together I can just this iterative calculation until the relationship between my target sequence and my initial sequence is maximized and then see if that similarity is enough that I can say they are closely related.
This is all assuming there is one standard PAM250 and BLOSUM62 matrix which I'm assuming are calculated from information derived from all information collected on protein sequences.
So when using PSIBLAST to search for similar sequences using BLOSUM matrices does it calculate similarity scores using BLOSUM matrices and then if this score is above a certain threshold it returns that sequence. If you do this for multiple iterations then what is the next input that it uses?
EDIT: I think some of the reason for my misunderstanding is that I'm not sure why there would be one single matrix which can be used to determine the "resilience" of a particular amino acid in general. Isn't the "usefulness" or that amino acid dependent on the function of the protein? In that case shouldn't there be different substitution matrices for different proteins? Is this why PAM matrices have difficulty and is this semi-solved by using BLOSUM matrices which use blocks and so can capture when certain "blocks" of amino acids correspond to particular functions and are therefore seen together a lot and are resilient to change in that way? It still seems a bit strange to lump them together in this case.