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Title: Theoretical studies of steroid hormones and related compounds
Author: Charlton, Michael Hugh
Awarding Body: University of St Andrews
Current Institution: University of St Andrews
Date of Award: 1992
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A theoretical study of steroidal inhibitors of the enzymes Glucose-6-Phosphate Dehydrogenase and Aromatase is presented. Both enzyme systems are of interest in the study of cancer, the latter being the final step in the biosynthesis of oestrogens which are involved in certain types of breast cancer. Two levels of theory are employed in the study, namely, Ab Initio and Semi Empirical methods. Structures and charges have been calculated using the MOPAC and GAUSSIAN programs and these have been used to model the efficacy of various inhibitors. The major tool in comparing these steroids has been the molecular electrostatic potential (MEP). Maps of the MEP and an analysis of the similarity between the MEP s of different molecules have led both to a method of assessing the activities of steroids as enzyme inhibitors and requirements for the electronic structure of the steroid binding sites within these enzymes. A molecular graphics display program has been developed to facilitate this work. It has been designed to make full use of the facilities available. The quality of the resulting display has improved greatly on what was previously available and has been of value in studies of large molecular systems. The program is written in VAX FORTRAN and uses the Graphics Kernel System (GKS) to produce graphical output and should be reasonably easy to transfer to other systems. Finally, to determine whether PM3 really is a significant advance on AM1, a comparison of the two semi empirical methods is presented. The calculated properties of steroid hormones are compared to those of both Ab Initio calculations and experimental determinations, allowing the quality of the semi empirical predictions to be assessed.
Supervisor: Thomson, Colin Sponsor: Biotechnology and Biological Sciences Research Council (BBSRC)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QP572.S7C2 ; Steroid hormones