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In this thesis computational methodologies are employed to examine the nature of the interactions between nucleotides and proteins. Programs were developed to enable the examination of the conformations of protein-bound nucleotides. When compared to the conformations of small molecule crystal structures, few differences were found, suggesting the bound nucleotides adopt a low energy conformation when bound to protein. However, protein bound nucleotide did tend to adopt a more extended conformation than unbound. To enable the identification and analysis of ligands within the Protein Databank, a program called DSSA was developed. This searches for ligands on the basis of their chemical connectivity, and can then be used in the analysis of the ligands it finds during its search. Using this program, a dataset of proteins bound to adenylate-containing nucleotides were studied to determine the features of an adenylate binding site. The following features were identified: 1) The nucleotides are exceptionally buried within protein - so much so that these proteins must undergo significant conformational change in order to bind them. 2) The amino acids in the binding site about adenine tend to be hydrophobic, around phosphate predominantly hydrophilic, with no clear preference about ribose. 3) Protein-adenylate hydrogen bonding is not maximised, but rather the protein hydrogen bonds to atoms important in the recognition of adenylate. 4) The hydrophobic effect would appear to be the main stabilising force in protein-adenylate complexes, with hydrogen bonding mainly contributing to the specificity of their interaction. Finally, the implications of this study on the current perception of protein-ligand complexes is discussed, and future work suggested.