Date of Award

10-19-2015

Publication Type

Master Thesis

Degree Name

M.Sc.

Department

Chemistry and Biochemistry

Keywords

Computational enzymology, Phosphate cleavage, Quantum mechanics/molecular mechanics, Sulfur intermediates, β-lactamases

Supervisor

Gauld, James

Rights

info:eu-repo/semantics/openAccess

Abstract

Enzymes are the bimolecular “workhorses” of the cell due to their range of functions and their requirement for cellular success. The atomistic details of how they function can provide key insights into the fundamentals of catalysis and in turn, provide a blueprint for biotechnological advances. A wide range of contemporary computational techniques has been applied with the aim to characterize recently discovered intermediates or to provide insights into enzymatic mechanisms and inhibition. More specifically, an assessment of methods was conducted to evaluate the presence of the growing number 3– and 4–coordinated sulfur intermediates in proteins/enzymes. Furthermore, two mechanisms have been investigated, the μ-OH mechanism of the hydrolysis of dimethylphosphate in Glycerophosphodiesterase (GpdQ) using five different homonuclear metal combinations Zn(II)/Zn(II), Co(II)/Co(II), Mn(II)/Mn(II), Cd(II)/Cd(II) and Ca(II)/Ca(II) as well as a preliminary study into the effectivness of boron as an inhibitor in the serine protease reaction of class A TEM-1 β-lactamases.

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