Study On Structural Stability Of DNA In Methanol/water Mixed Solvent

Deoxyribonucleic acid（DNA）is the most important substance in human life activities,and its most prominent feature is that it has a stable double helix structure.The water environment of DNA plays a very important role in maintaining the double helix structure and realizing its function.Compared with the water environment,methanol is an organic solvent whose molecular structure and polarity are very close to water and can be infinitely miscible.Therefore,it is of great significance to explore the structural stability of DNA in methanol and methanol / water mixed solvents for the study of environmental adaptability of DNA,and can further reveal the important influence of the polarity of solvent environment on the structural stability of DNA.In this thesis,molecular simulation was used as the main research tool to systematically study the conformational tra nsition,structural stability and te nsile behavior of DNA in methanol/water mixed solvents.The effect of solvent polarity on the structural stability of DNA was revealed in detail at the single molecular level.The specific work includes the following aspects:（1）Through molecular dynamics simulation,it is found that the double helix structure of DNA in 50% methanol/water mixed solvent is more compact due to the formation of methanol-hydrate complex so that there are almost no free water and methanol molecules in the solvent.In 70%,75% and 80% methanol / water mixed solvents,the structure of DNA showed varying degrees of i nstability.With the increase of solvent polarity,due to the gradual increase of free methanol molecules in the solvent,the double helix structure at both ends of the chain gradually uncoiled,but the middle part can still be maintained.（2）The precise stretching of DNA molecules was carried out by steered molecular dynamics simulation.It was found that the typical "B-S" conformational tra nsition occurred when DNA molecules were stretched in water,but not in pure methanol.When stretching in methanol/water mixed solvent,the phenomenon of B-DNA to S-DNA also appeared,and the typical "B-S" conformational tra nsition platform also appeared in the force-tension distance curve,but its platform length was obviously smaller than that in water,which was closely related to the volume ratio of methanol in the mixed solvent.The mechanical stability of DNA in 70% methanol / water mixed solvent was the best.（3）The results of molecular simulation experiments were verified by UV-vis absorption spectra and circular dichroism spectra.It can be found that when DNA is in 50%methanol/water mixed solvent,the solvent environment becomes non-polar due to the formation of complexes between methanol and water molecules,which leads to the compact structure of DNA and the enhancement of base accumulation.In the polar environment of mixed solvents from 70% methanol to 80% methanol,the unwinding degree of DNA increases gradually,which confirms the previous molecular dynamics simulation results.