As we know, when we generate multiple sequence alignments, we usually set a E value cutoff as a threshold. Here is the E value calculation for BLAST. https://www.ncbi.nlm.nih.gov/BLAST/tutorial/Altschul-1.html#head2
Now, the problem is if we have another input with a library with different size, and different alphabets size. How to calculate the corresponding E value for the second input to make sure the effects of two inputs are same.