Date of Completion
2021
Document Type
Honors College Thesis
Department
Biology Department, Physics Department
Thesis Type
Honors College, College of Arts and Science Honors
First Advisor
Brent Lockwood
Second Advisor
Juan Vanegas
Keywords
Computational Biology, Biology, Physics, Molecular Dynamics
Abstract
Anthropogenic climate change and its impact on ecosystems is one of the major concerns of the century. Temperature influences the rates of reactions in biochemical pathways, thus temperature adaptation among species is likely to occur in the face of this threat. The objective of this project was to analyze the ethanol metabolism pathway and the two allelic variants of the enzyme alcohol dehydrogenase (ADH) through the lens of temperature-driven evolutionary adaptations. One isozyme is found at lower latitude regions with higher temperature (ADH-S), while the fast allele is found at higher latitudes with lower temperature (ADH-F). The experimental and computational data suggest a disproportionate decrease in the stability of the two dimer forms of ADH with an increase in temperature (with the ADH-S version being more stable and thus more temperature resistant). The computational analyses of the monomer of the protein indicate no significant difference in response to the increase of temperature in the two variants. The results have led us to conclude that the structural stability of the quaternary structure of the ADH protein in the dimeric and monomeric state is altered via the mutation, with the mutation resulting in increased stability in the dimeric state and decreased stability in the monomeric state. Moreover, atomistic simulations show that there is a major difference in the Root Mean Square Fluctuations (RMSF) value of the two isozymes at the location of the mutation. This opens the possibility for future research endeavors focused on the impact of the mutation on the connection between the monomers. Such research could shed light on the biochemical basis of the temperature adaptation of ADH.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
Recommended Citation
Razavi, Ali; Razavi, Ali (Shervin); and Razavi, Shervin (Ali), "A computational and experimental analysis of the temperature stability of the enzyme Drosophila Alcohol Dehydrogenase" (2021). UVM Honors College Senior Theses. 427.
https://scholarworks.uvm.edu/hcoltheses/427