In this study, the computer-based techniques of conformational analysis and molecular docking were used to identify a structure activity relationship (SAR) for the AspXaa hydrolysing enzyme, aspartyl dipeptidase E and also to predict bioactive conformations of the different classes of substrates of N-succinyl-L,L-diaminopimelate desuccinylase. The results of this work indicate that the substrate specificities of these enzymes have evolved due to the selection pressure represented by the conformational profiles adopted by their substrates in solution. In obtaining these results, the applicability of these approaches for conceivably all proteins interacting with small flexible substrates is endorsed. The results provide information that can aid the rational design of inhibitors targeted to these and similar enzymes. Similar computer-based techniques were also used to investigate the substrate specificity and molecular recognition parameters of the periplasmic binding-protein, MppA, which in association with the membrane components of the oligopeptide permease (Opp), is involved in the recycling of the cell wall murein tripeptide and possibly the regulation of the multiple antibiotic resistant phenotype in Escherichia coli. Using homology modelling, a model structure of MppA was constructed based on the protein's sequence identity with the oligopeptide binding-protein, OppA. Comparisons between the conformations adopted by the murein tripeptide and the di-and tripeptide ligands of OppA, combined with studies on docking of the ligand conformations with the MppA model allowed insights into the molecular recognition of substrates by MppA and led to a prediction of the bioactive conformation of the murein tripeptide. The results of these studies were used to direct isoelectric focussing analysis of ligand binding and competition filter binding assays, the results of which indicated that MppA binds only the murein tripeptide with high affinity. A surface-located region of OppA has been previously shown to be intimately involved in the liganded binding-proteins interaction with the membrane components of Opp. Specific residues in this region were changed using site directed mutagenesis: Asp298Glu, Asp300GJu, Ile301Phe and Ile301Thr. Using homology modelling and CD-spectroscopy it was found that the changes introduced by the mutations did not result in gross structural change in the proteins. The effects of these specific changes on the characteristics of the binding-protein were determined with purified mutated proteins in vitro. The Asp300GJu and Ile301Thr mutations affected the ligand binding ability of the binding-protein. Through comparison with results produced by previous workers in this laboratory it is concluded that this region plays an essential role in transport during interaction with the membrane protein complex. OppA-mutant strains of E. coli, to be used as hosts for mutated and wild type oppA-encoding plasmid in these studies were characterised with regards to their OppK phenotype and the mutations causing the phenotype. It was concluded that ideally an alternative strain was required for further studies.