The Effects Of Solution Conditions On Inter-DNAs Interaction And DNA Structure Flexibility

The interaction between nucleic acid segments and the flexibility of nucleic acids play important effects in their biological functions such as folding and transcription.Under physiological conditions,each nucleotide of nucleic acids carries a unit of negative charge.Thus,a nucleic acid has a very high negative charge density on its backbone.During folding process,the cations and proteins are required to overcome the very strong coulombic repulsion.Thus,cations play an important role in the folding of nucleic acid structure and the structure stability.In the thesis,we mainly studied the divalent ion-mediated interaction between DNAs and the effect of alcohol in solution on DNA flexibility.This thesis includes the following two parts:(1)Divalent ion-mediated interaction between DNAs.The ion-mediated interaction between DNAs is essential for DNA assembly and it is generally believed that monovalent and nonspecifically binding divalent cations cannot induce the aggregation of double-stranded(ds)DNA.Interestingly,recent experiments found that alkaline earth metal ions such as Mg2+ can lead to the aggregation of triple-stranded(ts)DNAs,while there is still lack of a deep understanding on the relevant divalent ion-mediated interaction between DNAs at microscopic level.In this work,we have employed all-atom dynamic simulations to directly calculate the potentials of mean force(PMFs)between two tsDNAs,between two dsDNAs and between a tsDNA and a dsDNA in Mg2+ solutions.Our calculations show that the PMF between tsDNAs is apparently attractive and the attractive PMF can become stronger at higher[Mg2+],while the PMF between dsDNAs cannot become apparently attractive even at very high[Mg2+].Our microscopic analyses show that Mg2+ would internally bind into grooves and externally binding to phosphate groups for both tsDNA and dsDNA,while the external binding of Mg2+ is much stronger for tsDNA than for dsDNA.Such strong external binding of Mg2+ for tsDNA favors the ion-bridge between adjacent helices and is responsible for an effective attraction between tsDNAs.Furthermore,our microscopic analyses directly illustrate the tight correlation between inter-DNA force and bridging ions.(2)The flexibility of DNA in solution with alcohol.We used the all-atom molecular dynamics to simulate dsDNA,dsRNA in aqueous solution and dsDNA in a solution with 80%alcohol in volume.The global flexibilities of the three structures were compared by calculating the RMSDs and using principal component analysis method.It was found that the global flexibility of B-DNA is the strongest and that A-DNA is the weakest.However,the stretch modulus of B-DNA is the largest,which is mainly due to the small inclination of B-DNA.For A-RNA and A-DNA,because its inclination and slide are more apparent than B-DNA,their stretch moduli are smaller.For the three helical structures,their torsional moduli are similar.In addition,we calculated the elastic parameters with considering stretch-twist coupling,and the calculated elastic parametes are close to the values that calculated without considering the coupling,indicating that the stretch-twist coupling is relatively weak.Our calculated values are consistent with the experimental results,indicating that B-DNA overwinds when stretched and A-RNA unwinds when stretched.For A-DNA,the stretch-twist coupling constant is small,but the sign is is same as that of B-DNA,in contrary to previous predictions based on coase-grained modeling.