The overriding goal of thsi course is the transfer of information from
well-studied proteins to your protein of interest. To do that we would
like to superpose their structures, but as that normally isn't possible,
we will have to do with sequence alignments. CLUSTAL (or any other sequence
alignment program) can do that for you, but CLUSTAL is just software, it
cannot think, and thus cannot cope with exceptions. Humans can, at least, when
they understand the amino acids well enough to see the relation between
amino acid characteristics and alignment characteristics.
The most important characteristic of amino acids is their hydrophobicity. Hydrophobicity is underlying the entropy of water, and the entropy of water, in turn, is underlying everything else (protein folding, drug binding, membrane formation, etc., eveything).