Finding the good vibes of life, man: Identifying catalytic vibrations in enzyme catalysis
Schipper, D.-A. (2020). Finding the good vibes of life, man: Identifying catalytic vibrations in enzyme catalysis (Thesis, Master of Science (MSc)). The University of Waikato, Hamilton, New Zealand. Retrieved from https://hdl.handle.net/10289/13645
Permanent Research Commons link: https://hdl.handle.net/10289/13645
Enzyme catalysis is one of the most vital components of life. As such the elucidation of the exact mechanics of this kind of catalysis is important. The aim of this work is to look into enzyme catalysis though the lens of macromolecular rate theory (MMRT). MMRT is an idea focused around the heat capacity of an enzyme changing over the course of a reaction. Our hypothesis is that this change in heat capacity is strongly tied to the nature of enzyme catalysis. As such, the focus of this thesis is to determine what a large change in heat capacity at the transition state on the reaction pathway means and why it happens. From previous work I know that there is a difference in heat capacity when an enzyme is bound to a reaction state compared to a transition state analog. One of the components of this project is to investigate the causes of this difference using all-atom molecular dynamics (MD) and calculations based on the MD trajectories. In the harmonic case, it was found that there was no significant difference between our chosen enzyme in the reaction state and it in a transition state analog; which was possibly either due to insufficient simulation time or higher order anharmonic behavior driving the change in heat capacity. I computed the vibrational frequencies used to test this from the trajectories of a molecular dynamics simulation. In addition, the patterns of how the change in heat capacity evolves with temperature acts similarly to how changes in heat capacity act during phase transitions. These transitions are characterized by long range fluctuations, which I aimed to detect; however, no change in the distance of fluctuations was detected in the harmonic case in the simulations. Finally, I looked into computing heat capacities for a large system using the variance in energies. Previous attempts at doing this found reasonable values for the change in heat capacity when looking at an enzyme bound to a transition state analog vs bound to the reactant state. However, the absolute values of the heat capacities were an order of magnitude too high for each state. I investigated why this was the case and concluded that it was almost entirely due to not including quantum effects and the fact that interaction energies between the system and the solvent are dynamic.
The University of Waikato
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- Masters Degree Theses