It is difficult to answer a general question like this because I am not sure how much you already know about this subject.

First, there are 4 vs. 20 residues in nucleic acids and proteins, respectively. That already is a big difference. Second, nucleotide substitution scoring tends to be black and white: it is either a match or a mismatch. See a nucleotide substitution matrix here that will illustrate the concept. Substitutions of amino acids are not always black and white, as there are many conservative substitutions that are acceptable to various degrees. See here for an example.