Molecular dynamics simulation of a single-stranded DNA with heterogeneous distribution of nucleobases in aqueous medium

Abstract

The DNA metabolic processes often involve single-stranded DNA (ss-DNA) molecules as important intermediates. In the absence of base complementarity, ss-DNAs are more flexible and interact strongly with water in aqueous media. Ss-DNA-water interactions are expected to control the conformational flexibility of the DNA strand, which in turn should influence the properties of the surrounding water molecules. We have performed room temperature molecular dynamics simulation of an aqueous solution containing the ss-DNA dodecamer, 5'-CGCGAATTCGCG-3'. The conformational flexibility of the DNA strand and the microscopic structure and ordering of water molecules around it have been explored. The simulation reveals transformation of the initial base-stacked form of the ss-DNA to a fluctuating collapsed coil-like conformation with the formation of a few non-sequentially stacked base pairs. A preliminary analysis shows further collapse of the DNA conformation in presence of additional salt (NaCl) due to screening of negative charges along the backbone by excess cations. Additionally, higher packing of water molecules within a short distance from the DNA strand is found to be associated with realignment of water molecules by breaking their regular tetrahedral ordering.

Ion assisted structural collapse of a single stranded DNA: A molecular dynamics approach

“…Interestingly, no definite trend in the time evolutions of distance /interaction energy parameters is observed due to significant overcharging induced DNA chain reswelling at 0.3 and 1 M concentrations of Mg 2+ . The findings of this work are contrary to that of Chakraborty and coworkers [16] where it has been shown that an ss-DNA molecule exhibits reduced end-to-end distance, followed by higher lifetime of the stacked base pairs on increasing NaCl concentration up to 500 mM. These qualitatively different results in the case of ss-DNA in the presence of the similar concentrations of Na + and Mg 2+ ions, agree reasonably well with the experimental findings by Pollack et al that almost 20-40 times lower ionic strength of MgCl 2 than that of NaCl is sufficient to achieve the same chain compaction of ss-DNA and ss-RNA [55].…”

“…For our study we take a single stranded Dickerson Drew dodecamer [23] with base sequence 5 0 -CGCGAATTCGCG-3 0 and all the simulations are carried out at 300 K. A trajectory of the DNA structure is obtained after a 50 ns simulation and the calculations of different parameters reveal the discrete patterns of structural collapse of ss-DNA when different counterion concentrations are involved under otherwise similar MD simulation conditions. MD simulations of the same ss-DNA at different Mg 2+ concentrations (0.01, 0.05, 0.1, 0.3 and 1 M) reveal a trend in structural changes, qualitatively different to that observed in the case of a monovalent species such as Na + [16]. A combined analysis of the data reported in this paper, may be helpful in comparing the patterns encountered in the structural collapse of the DNA at different concentrations of a divalent counterion such as Mg 2+ .…”

Determination of pKa values for deprotonable nucleobases in short model oligonucleotides

“…We use a B-form geometry for the model single-stranded oligonucleotide. The positive charge in the system is depicted as an hydronium ion formed by the binding of a water molecule to the departing proton, which is 2 Å apart from its original position on guanine-N1 to avoid unfavorable contacts [43,44], as is shown in point A of Fig. 6.…”

Exploring ion induced folding of a single-stranded DNA oligomer from molecular simulation studies

“…In this particular arrangement, the central Na + counterion is surrounded by five non-hydrogen DNA atoms, three of which are from residue A6 (O4 0 , O1P and N3) and the remaining two are from residue C9 (O5 0 and O4 0 ). 24 Thus, it is clear that formation of a few such ion-induced inner-sphere complexes plays an important role in the formation of the folded configuration of ss-DNA. To analyze further how such Na + ion binding takes place, we have monitored the time evolutions of the distances (R) between the bound DNA atoms and the central Na + ion, as shown in Fig.…”

“…[8][9][10][11] In the absence of cations, nucleic acids become relatively rigid macromolecules with longer persistence lengths. 24 In an important study, Murphy et al 25 reported single molecule fluorescence resonance energy transfer (FRET) measurements of a series of labeled oligodeoxythymidylates, (dT) N (10 r N r 70), over a wide range of NaCl concentrations. During folding both diffused and specifically bound ions are believed to play important roles.…”