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Investigation of I the Stability of B-DNA Molecule: A Molecular Dynamics Simulation

Izanloo, Cobra | 2011

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  1. Type of Document: Ph.D. Dissertation
  2. Language: Farsi
  3. Document No: 42086 (03)
  4. University: Sharif University of Technology
  5. Department: Chemistry
  6. Advisor(s): Parsafar, Gholam Abbas
  7. Abstract:
  8. In this thesis, the molecular dynamics simulation is used to investigate the melting transition of B-DNA molecule, via of configurational entropy, the fraction of broken hydrogen bonds (f-curve) and hydrogen bonding energy.We have performed molecular dynamics simulation on Drew-Dickerson oligomer with sequence of (CGCGAATTGCGC) at different temperatures, within the range of 280-400 K with the 20 K intervals. The simulation was done in two different mediums (pure water and 1 M NaCl), to see influences of water and salt in stabilizing the DNA molecule. At each temperature, configurational entropy is calculated by the Schlitter’s formula, using the Cartesian coordinate of all atoms. So, in each medium, we have calculated the transition curve based on the configurational entropy which is similar to experimental one. At each temperature, on the basis of the criteria for stability of hydrogen bonding (the distance between donor-acceptor must be less than 3 Å and the angle of donor-H-acceptor must be more than 160°), we have calculated the fraction of broken hydrogen bonds and hydrogen bonding energy. Then these quantities have been used to obtain the transition curve in the two mediums. By comparison of these curves to experimental transition curve, we noticed that the curves are some what broader than its experimental counterpart, particularly in the shoulder regions. By comparison of experimental melting temperature (Tm) of Drew-Dickerson oligomer (is 341 K in 1M NaCl) with that obtained from the configurational entropy curve (329.7 K in pure water medium and 349 K in 1M NaCl) and the f-curve and hydrogen bonding energy (330.9 K in pure water medium and 340 K in 1M NaCl), we have concluded that: (1) a significant portion of phosphate charge neutralization is done by the water molecules hydrating the DNA. (2) The columbic interactions displace the melting temperature. (3) The nonbonded stacking interactions influence on the sharpness of the transition curve. (4) In high salt concentration, the stability of DNA increases and perhaps that might be a reason for surviving of a live tissue in a salt medium for a long time. (5) The Tm obtained from the hydrogen bond breaking is closer to experimental value.
    Noticing the increase in configurational entropy in medium with the high salt concentration, we have concluded that the transition state of melting process involves the peeling. We have calculated the configurational entropy of different base pairs of the DNA sequence at different temperatures in the salt medium, from which we have concluded that the bridge of phosphate oxygen-cation-phosphate oxygen in the minor groove, is destroyed when temperature increases. Finally, we have investigated the arrangement of water molecules and ions around the oxygen atoms of the phosphate groups and some atoms of aromatic bases of DNA at different temperatures. We have found that by increasing temperature, the water molecules are moved away from these atoms and the competition between hydration and direct cation coupling proceed is in the favor of the of cations.

  9. Keywords:
  10. Molecular Dynamic Simulation ; Melting Temperature ; B-DNA Molecule ; Configurational Entropy ; Hydrogen Bonding Energy

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