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At the nucleotide level, the scoring landscape is much simpler. More often than not, the matrices used here simply count matches and mismatches. These matrices also assume that each of the possible four nucleotide bases occurs with equal frequency (25% of the time). In some cases, ambiguities or chemical similarities between the bases are also considered; this type of matrix is shown in Figure 3.2. The basic differences in the construction of nucleotide and protein scoring matrices should make obvious the fact that protein-based searches are always more powerful than nucleotide-based searches of coding DNA sequences in determining similarity and inferring homology, given the inherently higher information content of the 20-letter amino acid alphabet versus the four-letter nucleotide alphabet.