DNA Hybridization And DNA Stretching Process Studied By Molecular Dynamics Simulations

DNA molecules are the hereditary material of every living organism; they take along all the hereditary information of the organism. DNA can copy the information by replicating themselves; DNA could transcribe the hereditary information to RNA then the information can be used to produce proteins. Nowadays, DNA molecules have been wildly studied as a new material. Taking the advantage of that the single-stranded DNA uniquely recognizes its complementary strand, scientists have made new DNA sensors, new self-assembly materials guided by DNA molecules and DNA nano-machines. Hybridization of DNA molecules is the key in both biology process and the new nano-techniques.The hybridization process is the conformational variations of the DNA molecule in atomic scale and there is no electronic transport, so the molecular dynamics (MD) simulation is the best method to investigate this process. Since 2003, the dehybridization of one base pair has been studied by the MD simulation. Recently, the DNA/RNA hairpin folding, which involved hybridization process, has been extensively studied with the help of the MD simulations, the transition stats and hydrophobic collapse has been found in the hairpin folding process. In experiments, it has been found that the DNA hybridization shown non-Arrhenius behavior and there are temperature dependent meta-stable states in DNA/RNA hairpin folding. Despite the efforts mentioned above, the mechanism of DNA hybridization is still far from fully understanding.In this thesis, we performed molecular dynamics simulations to investigate the base-to-base hybridization of a DNA segment and the DNA structure changes induced by gradually increasing the distance between the opposing 3'-termini (03',03') and the opposing 5'-termini (05',05') of a 22mer DNA (22 base pairs) molecule by MD simulations. In the base-to-base hybridization process, we have found that the probability of successful hybridization decreased as the solvent accessible surface area (SASA) of two successive base pairs increased. We note that the SASA describes the surface area of the unpaired base pair and its adjacent paired base pair accessible to water. Decreasing SASA indicates a fewer number of water molecules on the solvent accessible surface. This leads to a reduction in the enthalpy of the whole system due to more water molecules entering the bulk water. Importantly, two metastable structures were discovered by the analysis of the free energy landscape of an A-T base pair. Both structures involved the addition of a water molecule to the linkage between the two nucleobases in one base pair. We noted that to our knowledge, this is the first report to describe Metal. Although Meta2 has been previously predicted by ab initio calculations at zero temperature, our simulation results reveal the remarkable observation that this structure still exists at room temperature. We have also found a metastable structure in the DNA segment for G-C sequences. The simulations of DNA stretching show that the two stretching methods caused different variations in the DNA conformation. Stretching the both 3'-termini by 3.5 run required 142 KJ/mol and the force plateau was at?80 pN, whereas stretching the both 5'-termini by the same length required 190 KJ/mol and the force plateau was at?100 pN. Stretching 3'-termini led to a larger untwisting of the double helix and the successive base pairs rolled to the side of DNA minor groove. In contrast, stretching 5'-termini resulted in the base pairs rolling to major groove side and reduction of the diameter of the DNA molecule. The most important difference between stretching both 3'-termini and both 5'-termini was that at the force plateau region stretching 5'-termini resulted in breakage of the base pairs, which considerably disturbed the structure of the DNA double helix. All of the variations of base rotation and translation for both stretching methods took place when the relative length 1 of the DNA molecule was longer than 1.2, which was the point the force plateau appeared.The base-to-base hybridization simulations contribute an important step towards our understanding of the mechanism and the physics involved in DNA hybridization and hybridization-related process, such as the polymerase chain reaction, DNA sensor, self-assembly materials guided by DNA molecules and DNA nano-machines. These studies may be also helpful to the facilitation of the experimental designs for fast hybridization, a process that is believed to be very important in bio-/nano-technology. The conformational changes of DNA molecules give us an insight into DNA melting transitions occurring during the stretching process. These findings of different stretching methods caused different structural variations may also help to further understand the DNA-protein interaction.