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Title: A computational exploration of green tea catechins and their interaction with cardiac proteins
Author: Botten, Dominic Frith
ISNI:       0000 0004 5917 8874
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2015
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Green tea catechins have been in use for some time as a curative for a number of disorders and illnesses, however their direct benefits are still disputed. In this thesis several computational techniques have been applied to systems involving green tea catechins in order to study their properties and better ascertain their supposed health benefits. Based on first principles data, classical force fields of four selected green tea catechins (-)-Epigallocatechin 3-Gallate (EGCg), (-)-Epicatechin 3- Gallate (ECg), (-)-Epigallocatechin-3-O-(3-O-Methyl)-Gallate (EGCmg) and (-)-Epigallocatechin (EGC) have been parametrised in order to examine their behaviour under different conditions. Classical Molecular Dynamics coupled with Metadynamics has been used to explore the potential energy surface of these molecules as a function of selected torsions deemed crucial to the conformation of the system. In depth analysis of their interactions under classical conditions has been carried out in gas phase, water and chloroform. The catechins EGCg and EGC were further examined using Density Functional Theory (DFT) to determine their radical properties which are closely linked to their antioxidant activity. By calculating their ionisation potentials, bond dissociation enthalpies and acidity in gas phase, water and benzene solution we find little difference in their energies, despite large structural differences, and we investigate the limit of DFT in accurately describing these systems. Classical simulations of the cardiac protein Troponin C (a protein known to be crucial to the process of heart contraction), in complex with EGCg, were carried out from the basis of previous experimental work and it was found that EGCg exerts a stabilising effect on the calcium ion mobility present in the system and may help regulate calcium signalling in the cardiac sarcomere. Using sparse experimental data as a guide, alternative proteinligand binding possibilities were uncovered and used to help validate and expand the current experimental knowledge on the troponin C - troponin I system, giving rise to two low affinity, non-specific binding sites for EGCg which also affect calcium mobility.
Supervisor: Molteni, Carla ; Fraternali, Franca Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available