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Title: Calculating free energy profiles for enzyme catalysed reactions
Author: Chudyk, Ewa Iwona
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2013
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Hydrolysis of biologically active compounds by enzymes is one of the most important processes in living organisms. This thesis describes the use of molecular dynamics (MD) simulations and free energy calculations to investigate two types of enzymes that catalyse hydrolysis reactions: fatty acid amide hydrolase, a target for antidepressant drugs, and class A B-lactamases, responsible for emerging antibiotic resistance in bacteria. Fatty acid amide hydrolase (FAAH) is an enzyme that deactivates neurotransmitters involved in inducing sleep, anxiety, inflammatory and pain states. To investigate catalysis in FAAH, an empirical valence bond approach was used to study the first step of acylation with oleamide. Results from this approach were compared with previous quantum mechanics/molecular mechanics (QM/MM) potential energy simulations and with experimental data. Further analysis of the FAAH active site indicated residues important for catalysis, which may provide insight for inhibitor design.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available