Calculation of Free Energy Barrier for Base Flipping of Thymine Dimer Outward the DNA Double Strand Using Molecular Dynamics

Please enable javascript in your browser.

Arab Bagheri, Amin | 2011

884 Viewed

Type of Document: M.Sc. Thesis
Language: Farsi
Document No: 41948 (03)
University: Sharif University of Technology
Department: Chemistry
Advisor(s): Parsafar, Golam Abbas
Abstract:
Formation of Cyclobutane Pyrimidine Dimer (CPD), one of the most abundant types of damages in DNA double helices, is caused by UV radiation and plays a major role in causing skin cancer. DNA photolyase is an efficient enzyme that repairs this UV-induced damaged DNA-base. Previous studies have shown that the enzyme flips the dimer out of the DNA double helix into its binding pocket.
In this project, several nanoseconds of molecular dynamics simulations was performed to investigate the process of base flipping energetically. These simulations are consist of equilibration of repaired and damaged double strands for 3 and 8 nanoseconds respectively. All these simulations ran over NVT ensembles for repaired and NPT ensembles for damaged cases. The energy barrier of flipping for damaged case was estimated about 6.4 kcal per mole which shows the non-spontaneous nature of the flipping process. The same energy barrier calculations have reported the value of 13 kcal per mole which proves that the flipping is much more easier in the case of non-damaged DNA double strand helix
Keywords:
Molecular Dynamic Simulation ; Free Energy ; Thymine Dimer ; DNA Double Strand ; Photolyase

No TOC