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. 2021 May 26;6(22):14371–14378. doi: 10.1021/acsomega.1c01228

Spectroscopic and Simulation Studies of the Sequence-Dependent DNA Destabilization by a Fungicide

Sunipa Sarkar 1, Prashant Chandra Singh 1,*
PMCID: PMC8190899  PMID: 34124459

Abstract

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The understanding of the structural change of DNA induced by fungicides is essential as the non-targeted action of fungicides causes genotoxicity, leading to several serious diseases such as cancer, behavioral change, and nausea. In this study, the binding of an important fungicide, namely, n-dodecylguanidine acetate (dodine), with B-DNA having different sequences of nucleobases and its effect on the structure of B-DNA has been investigated using spectroscopic and simulation methods. In general, the addition of dodine destabilizes DNA; however, the binding of dodine causing the destabilization of DNA is highly sequence dependent. In the case of adenine(A)–thymine(T)-based DNA, dodine intrudes into the minor groove of DNA and interacts with the A–T bases mainly through its hydrocarbon tail, which destabilizes the stacking interaction of the flanking bases. In contrast, the polar group of dodine interacts with guanine(G)–cytosine(C)-rich DNA, and the interaction is dynamic as it shuttles between the minor groove and terminal regions. The binding of dodine with G–C-rich DNA affects the stacking interaction of the terminal base regions specifically. This study reveals the base-specific binding mode of dodine, which causes destabilization of the duplex DNA.

Introduction

Fungi are one of the most responsible organisms for the damage of crops worldwide.1−3 However, the development of fungicides has improved the situation substantially as it kills or reduces the action of fungi in a targeted manner.4,5 The application of fungicides is also associated with the non-targeted action, which causes genotoxicity in living organisms.6−9 The genotoxic material interacts with DNA and thereby perturbs, ruptures, or modifies its structure, which adversely affects the replication and transcription process, leading to several gene-related diseases.10,11 Indeed, it has been shown that the non-targeted action of fungicides causes nausea, cancer, fetus malformations, movement dysfunction, and behavioral changes in human and animals.6,12,13

Dodine (n-dodecylguanidine acetate, structure is shown in Figure 1a) is one of the important fungicides which has been used extensively to control the foliar and black spot diseases on several fruit plants such as peach, apple, strawberry, and pear.14,15 However, the genetic assay experiments suggest that the non-targeted genotoxic effect of dodine is serious and it should be used in a controlled manner.8,10,16 The genotoxic substances induce damage to the genetic material in the cells through interactions with DNA sequences. These substances have some preferential binding tendency to a particular DNA sequence depending on the nucleobases.17−20 Hence, it is essential to understand the mechanism of DNA structural change in the presence of dodine as well as the binding of dodine toward different nucleobases. Recently, we have studied the interaction of dodine with a polymeric DNA (calf thymus DNA) and found that dodine interacts specifically with A–T bases in the minor groove of B-DNA and perturbs the helicity as well as base stacking, which leads to the structural change of the canonical form of DNA.11 However, this study lacks the information about the specificity of dodine binding with nucleobases present in the particular sequence of DNA and its effect on the structure of the duplex DNA as the earlier study was performed on polymeric DNA, which does not contain the well-defined sequence of nucleobases.

Figure 1.

Figure 1

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Structure of dodine molecule (a). The central carbon atom of the polar head group and the terminal carbon atom of the hydrocarbon tail have been denoted as CH and CT, respectively. Different DNA-sequences used for this study (b).

In this manuscript, spectroscopic and simulation studies of dodine with different base sequences of B-DNA (Figure 1b) were performed to understand the specificity of the binding of dodine with different sequences of DNA and its effect on the structure of DNA. The experimental and simulation data suggest that dodine perturbs the structure of DNA, irrespective of the nature of nucleobases present in that particular sequence of DNA. However, the binding of dodine with DNA, which causes the structural change of DNA, is highly specific to the nucleobases present in that sequence. In the case of A–T-based DNA (seq1), dodine intrudes into the minor groove and interacts with the A–T bases mainly through its hydrocarbon tail. The interaction of dodine with the A–T bases present in the minor groove of seq1 causes destabilization in the base stacking of the flanking bases. On the other hand, the preferable binding of dodine with DNA containing less A–T bases (seq2) or no A–T bases (seq3) takes place via its polar guanidinium head group in the minor groove of DNA. It is noteworthy that dodine binding is not restricted to the central region of minor groove for DNA containing only G–C nucleobases (seq3); rather, it shuttles between the central base region of the minor groove to the terminal bases and thereby destabilizes the stacking of the bases present in the terminal region.

Materials and Methods

High-pressure liquid chromatography grade dodecamer DNA of the sequences, seq1: 5′-(CGCGAATTCGCG)-3′, seq2: 5′-(CGCGACGTCGCG)-3′, and seq3: 5′-(CGCGCGCGCGCG)-3′, were purchased from Integrated DNA Technology and used without any further purification. DNA samples were dissolved in tris–HCl buffer of pH 7.4 and then the solutions were annealed at 92 °C, followed by slow cooling to room temperature. The solutions were kept in a refrigerator at 4 °C overnight before the measurement to stabilize the duplex form of DNA. The concentration of the stock solutions was measured from the absorption value at ∼260 nm by using molar extinction coefficients of each DNA, εseq1 = 110,700 M–1 cm–1, εseq2 = 108,100 M–1 cm–1, and εseq3 = 101,500 M–1 cm–1. 4′,6-Diamino-2-phenylindole (DAPI, ≥98%, molecular biology grade) and dodine (molecular biology grade) were purchased from Sigma-Aldrich. The concentration of DAPI was measured using εDAPI = 23,000 M–1 cm–1 at 342 nm.21 The absorbance of samples was measured using Evolution 201 (Thermo Fisher), whereas Fluoromax 4 (HORIBA Scientific) instrument was used for the steady-state emission measurements. The slit widths of UV and fluorescence experiments were 1 and 2 nm, respectively. The B form of the duplex DNA sequences in buffer was confirmed from the CD spectra recorded using the JASCO (J1500) instrument. The concentration of DNA used for CD measurement was ∼10 μM. All the measurements were done at 25 ± 2 °C. The UV-melting study was performed by recording the temperature-dependent UV spectra of DNA in the presence of buffer as well as dodine. The melting profile was obtained from the temperature-dependent (20–65 °C) absorption spectra of the sample.

The molecular dynamics (MD) simulations with the B form of the 3 dodecamer sequences in water as well as in dodine medium were performed. The structure of seq1 was taken from the Protein data bank (PDB ID: 1BNA),11,22 whereas seq2 and seq3 were prepared using the fiber utility program included in 3DNA software.23 First, DNA was placed at the center of a cubic box of the length 70 Å and the rest of the volume was filled with water (TIP3P24 water model). For DNA in dodine systems, six dodinium cations along with six acetate anions were randomly inserted into the box, followed by solvation with water. Twenty-two sodium ions were inserted to neutralize the system. AMBER99sb-ildn25 force field was used to describe DNA, whereas generalized AMBER force field26 (GAFF) has been used for dodine as it is well known that GAFF is suitable for the description of small molecules.11 GROMACS (version 2016.3) software27 was used to perform MD simulation and visual MDs software28 (VMD 1.9.3) for visualization purpose.

At the beginning, energy minimization of each system with 10,000 steps was performed to obtain a stabilized system. In order to mix the randomly placed molecules around DNA, 2 ns position restrain equilibration was done by fixing the DNA position. Further, the equilibration process was taken forward using the canonical ensemble (NVT) for 2 ns, followed by the 5 ns isobaric–isothermal (NPT) ensemble. The LINCS algorithm was used to constrain the bond length between heavy atoms and hydrogen.29 The final production run was performed for 450 ns with a 2 fs time interval. The temperature and pressure were controlled by applying the velocity rescaling (V-rescale) thermostat30 (τ = 0.1 ps) and Parrinello–Rahman pressure coupling31 (τ = 2 ps), respectively. The cutoff radius for neighbor searching and nonbonded interactions was 10 Å. The effect of long-range electrostatic interaction was implemented by applying the particle Mesh-Ewald method with a grid spacing of 1.6 Å with fourth order interpolation.32 Structure change was monitored by calculating the root-mean-square deviation (rmsd) of the whole DNA in both water and dodine medium, whereas the root-mean-square fluctuation (RMSF) value was determined to observe basewise fluctuation compare to the native form in water. The structural parameters of the base pairs of DNA were calculated using the 3DNA and do_x3dna softwares.23,33

Results and Discussion

Figure 2a–c shows the CD spectra of all the sequences of DNA in buffer medium, which shows the maximum positive ellipticity at ∼280 nm and negative ellipticity at ∼250 nm, confirming their B nature in aqueous medium.34,35 The positive feature in the CD spectrum represents the base pair stacking, whereas the negative feature corresponds to the helicity of B-DNA.36,37 With the addition of dodine, the ellipticity of the positive as well as negative features of all the sequences of DNA decreases. In earlier studies, it has been suggested that the decrease in the ellipticity of both the peaks indicates the unwinding of nucleobases, leading to the structural perturbation of DNA.38 The CD study suggests that the addition of dodine perturbs the structure of DNA probably by unwinding its bases and the perturbation of DNA is independent of its sequences.

Figure 2.

Figure 2

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CD spectra of seq1 (a), seq2 (b), and seq3 (c) in buffer (0 μM, black line) as well as in the presence of increasing concentrations of dodine (up to 1 mM). Melting curve of seq1 (d), seq2 (e), and seq3 (f) in buffer (black color), 500 μM (red color), and 1 mM (blue color) of dodine.

Further, to get an idea about the stability of DNA sequences in dodine, the melting temperature of B-DNAs was measured in buffer and different concentrations of dodine as shown in Figure 2d–f. It is apparent from the data that the addition of dodine decreases the melting temperature of B-DNAs as compared to the buffer (melting points are shown in Figure S1). The melting study suggests that dodine can unwind the DNA bases, which cause its destabilization compared to buffer. The CD and melting temperature studies indicate that dodine can unwind the B-DNA structure and thereby destabilize it, regardless of the base sequence.

The effect of dodine binding on the different base sequences of DNA has been investigated by measuring the UV–vis spectra as shown in Figures S2 and 3a. The UV–vis spectrum of DNA shows characteristic peak maxima at ∼260 nm. The UV–vis spectra of all the three B-DNA show hyperchromicity (Figure S2) along with the bathochromic shift (Figure 3a) on the addition of dodine. The hyperchromicity along with the bathochromic shift of the UV–vis spectra for all the sequences of DNA suggest that the addition of dodine unwinds the base pair regardless of the base pair sequence.11 However, the bathochromic shift is significantly high for the DNA with A-T bases (seq1 and seq2, ∼20 nm) as compared to the G–C-rich DNA (seq3, 2 nm), suggesting that the probable mode of interaction of G–C-rich DNA with dodine is different from the A–T bases containing DNAs. The UV–vis study of DNA in the presence of dodine suggests that the unwinding process of G–C-rich DNA by dodine is different from the DNA with A–T bases.

Figure 3.

Figure 3

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Shift in the characteristic UV–vis peak of DNAs on the addition of dodine (a). Fluorescence spectra of free DAPI (cyan color) along with the DAPI–DNA complex (red color) and its change on the addition of dodine for seq1 (b), seq2 (c), and seq3 (d).

To get more idea about the binding of dodine with the different sequences of DNA, dye displacement assay experiment has been performed in which the fluorescence spectra of DAPI-bound DNA have been monitored in the presence of different concentrations of DNA. DAPI is weakly fluorescent in aqueous medium due to the intramolecular proton transfer from its amidino to indoline group.21 However, the binding of DAPI with the A and T bases in the minor groove of DNA hinders the possibility of the proton transfer to enhance the fluorescence intensity of the DAPI–DNA complex significantly than the aqueous medium.21,39,40 The fluorescence intensity of DAPI-bound DNA will decrease if the molecules of interest also compete for the binding in the minor groove of DNA along with DAPI as it can replace from DAPI from the minor groove of DNA.

It is apparent that the binding of DAPI with seq1 DNA increases its fluorescence intensity significantly as discussed above (Figure 3b).41 The dye displacement study for seq1 DNA shows that the addition of dodine decreases the fluorescence intensity of DAPI significantly, which suggests that dodine intrudes into the minor groove of seq1 DNA and interacts with the A–T bases (Figure 3b). The increase in the fluorescence intensity of DAPI on binding with seq2 DNA is significantly less compared to the seq1 DNA (Figure 3c), which is expected as the number of A–T bases is significantly less in the minor groove of seq2 DNA than seq1.21 The addition of dodine in seq2 DNA decreases the fluorescence of DAPI; however, the decrease in the fluorescence intensity of seq2-DAPI complex is less than the case of the seq1-DAPI complex (Figure 3c). The dye displacement experiment of seq2 DNA suggests that dodine interacts in the minor groove of DNA of seq2. However, the efficacy of the interaction of dodine in the seq2 DNA is less than seq1 due to the presence of less number of A–T bases in the minor groove of DNA than seq1.

In contrast to DNAs with A–T bases (seq1 and seq2), the fluorescence intensity of DAPI on binding with G–C-rich DNA (seq3) decreases compared to the aqueous medium, which is in agreement with earlier studies (Figure 3d).42 The decrease in the fluorescence intensity of DAPI on binding with G–C-rich DNA has been assigned to the intercalation mode of interaction of DAPI with G–C bases, which probably facilitate the charge transfer from DAPI causing to decrease in the fluorescence intensity.21,42,43 With the addition of dodine in G–C-rich DNA, the fluorescence intensity of DAPI increases again, which shows that dodine displaces DAPI from the surface of DNA and behaves like free DAPI in dodine medium.11 It is apparent from the dye displacement data that dodine has propensity to influence minor groove along with the base stacking region. The different binding mode of dodine for A–T and G–C DNA bases obtained from the dye displacement experiments are in line with the UV–vis data mentioned above. The CD, melting temperature, UV–vis and dye displacement fluorescence data together suggest that the interaction of dodine unwinds the B-DNA bases; however, the mechanism of the unwinding is different for DNA-containing A–T bases compared to only G–C-rich DNA.

In order to understand the difference in the interaction of dodine with DNAs containing A–T and G–C bases and its effect on the structure of DNAs, MD simulation of all the three sequences of DNA in the aqueous as well as dodine has been performed. The rmsd of all the sequences of DNA in the aqueous medium has been found to oscillate ∼2 Å, which is in agreement with the earlier reports of the rmsd of B-DNA.44,45 The rmsd of DNAs with A–T bases (seq1and seq2) increases with the addition of dodine, whereas the change is not so prominent in the case of G–C-rich DNA (seq3). The rmsd data suggest that the effect of dodine is more prominent in the B-DNAs, which have the higher content of A–T nucleobases. Further, basewise RMSF has been calculated for all the sequences of DNA in aqueous as well as dodine and the results are depicted in Figure S3. It is evident that the prominent change in the RMSF is in the central region (base pair number 5–8) of all the sequences of DNA, suggesting that the effect of dodine in the minor groove region of B-DNA is pronounced. Noticeably, the change in the RMSF is less in the case of seq3 than seq1 and seq2, suggesting that the minor groove binding of dodine in the G–C-rich DNA is less than the DNA-containing A–T bases.

To understand the binding of dodine in the phosphate, minor and major groove regions of DNA, the g(r) calculation of the polar head group carbon (CH) of dodine with the mentioned regions of DNA has been calculated as shown in Figure S4. The g(r) data suggests that dodine interacts mainly with the phosphate (Figure S4) and the minor groove (Figure 4) of all the sequences of DNA, and the possibility of the interaction of dodine with the major groove bases of DNA is extremely weak as the peak for g(r) appears after 5 Å (Figure S4).11 This observation is evident from the snapshot of all the DNAs bound in the minor groove at the last frame of the simulation as shown in Figure 4e. Dodine contains the polar head group comprising the guanidinium moiety as well as long hydrocarbon chain and both can interact with the nucleobases through the minor groove region of DNA (Figure 4b–d). In order to distinguish the mode of dodine binding between its polar head or long hydrocarbon tail with the nucleobases in the minor groove region of DNA, the g(r) for the terminal carbon of long hydrophobic tail (CT) and polar head group (CH) of dodine with the minor groove of all the sequences of DNA have been calculated as shown in Figure 4b–d. It is apparent from the g(r) data that the polar mode of the interaction of dodine (dod-CH) is higher in the seq2 and seq3 than seq1, whereas the trend of the terminal hydrocarbon chain interaction (dod-CT) is opposite and maximum for seq1 and almost absent for seq3 (Figure 4b,c). The g(r) data suggests that both polar and hydrophobic groups of dodine may interact with the minor groove of seq1 DNA; however, the interaction of dodine through its hydrocarbon chain is more preferable (Figure S5).11 However, the polar interaction of dodine increases at the cost of hydrophobic interaction with the decrease of the A–T content in the DNA sequences. In the case of G–C-rich DNA, the possibility of the hydrophobic interaction of dodine with the minor groove of DNA is extremely sparse and the polar group of dodine is mainly interacting with the minor groove bases of DNA (Figures 4e and S5). Time-dependent g(r) data for CH of dodine in the minor groove suggests that the presence of dodine in the minor groove of seq3 is higher than seq1 for 200–300 ns (Figure 4c), whereas the trend is reversed for the 300–400 ns time frame (Figure 4d), which indicates that the interaction of dodine in the minor groove of seq3 is dynamic as compared to the cases of seq1 and seq2.

Figure 4.

Figure 4

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Time evolution of the rmsd values for seq1, seq2, and seq3 (top to bottom) in the presence of water and dodine (a). Radial distribution function, g(r) of the terminal carbon atom of the hydrocarbon tail (dod-CT) around the minor groove (b), and the g(r) for polar head group of dodinium cation (dod-CH) around the minor groove for 200–300 (c) and 350–450 ns (d) time range, respectively. The C atom of the polar head group of dodinium cation and electronegative atoms of the minor groove (N3, N2, and O2) were selected for the calculation. The snapshot of DNA structures bound with dodinium cations at the end of the 450 ns simulation time (e). All the three sequences are shown in surface style and the bases (A, T, G, and C) are represented in different colors as mentioned in the figure. Dodinium cations are represented in licorice style, where C, N, and H atoms are shown in cyan, blue, and white colors, respectively.

The major difference between all the three sequences of DNA is the presence of different bases in the base pair region 5–8 as it contains 5′-AATT-3′ for seq1, 5′-ACGT-3′ for seq2, and 5′-CGCG-3′ for seq3. Hence, to understand the binding of dodine in the base pair region 5–8, we have calculated the time-dependent distance of dodine with the base pair region 5–8 of all the three sequences of DNA as shown in Figure 5a. It is apparent from the data that dodine stays longer in the base pair region 5–8 of seq1 and seq2. However, for seq3, the distance of dodine from its base pair region 5–8 increases after 300 ns, which suggests that the dodine interaction with the G–C base pairs is dynamic. We have also analyzed the distance dependence for all the dodine molecules with all the three sequences, which suggests that the distance of dodine from the base pair region 5–8 is maximum for G–C-based DNA than A–T, reconfirming the dynamic binding of dodine in the central region of G–C-based DNA. In order to get more insights into the dynamical binding of dodine with G–C DNA, we have calculated the time-dependent change of dodine from the terminal bases (base pair 1–3 which is the same for all the sequences) of all the three sequences of DNA as shown in Figure 5b. It is apparent from the data that the distance of dodine for G–C-containing DNA is less than the A–T-containing DNAs, suggesting that dodine gets closer to the terminal bases of G–C DNA. From the distance data, it is evident that dodine binding with the G–C DNA is dynamical compared to A–T-containing DNA, and it shuttles between the central bases of minor groove to terminal bases of G–C. Apart from the average distance of all the dodinium cations, we have calculated the minimum distance of individual cations from the minor groove (base pair 5–8) and found that the distance increases with the increase in the G–C bases of DNA (Figure S6). From the rmsd, g(r), and distance data, it is apparent that dodine binds mainly in the central region of the minor groove of A–T DNA via its hydrophobic and polar groups, whereas for G–C DNA, the polar group of dodine interacts with the minor groove of G–C-rich DNA, and the interaction of dodine with G–C is dynamical as dodine shuttles from the central to the terminal regions of the minor groove of G–C-rich DNA. The simulation data is in agreement with the UV–vis and fluorescence data, which suggests that the mode of interaction of A–T DNA is different from the G–C-rich DNA.

Figure 5.

Figure 5

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Distance of dodinium (dod) cations from the minor groove region of the base pair 5–8 (a) and base pair 1–3 (b) for the entire simulation time. Electronegative atoms toward the minor groove of the selected bases and terminal C of the hydrocarbon tail of the dodinium cation were chosen for distance calculation.

The simulation study clearly indicates that the binding of dodine with the A–T- and G–C-containing DNAs are different as dodine binds in the central region of the minor groove, whereas the terminal regions of G–C DNA are preferential binding sites. Hence, we have investigated the structural change of A–T and G–C DNAs induced by the binding of dodine. The structural change of DNAs was obtained by the calculation of the change in base pair step parameters (helical twist and slide) for A–T and G–C DNAs in the aqueous as well as in the presence of dodine as shown in Figure S7 using 3DNA and do_x3dna software. It is apparent from the structural change parameters (Figure S7) that the helical twist and the slide of the central region of A–T-containing DNAs change significantly compared to aqueous medium. It is known that the helical twist and slide of the base pairs are correlated with the helicity and base pair stacking of DNA.46 The change observed in the simulation data (Figure S7a,b) for the A–T DNAs suggests that the binding of dodine affects the helicity and base pair stacking of DNA, which is well correlated with the CD results also. For the G–C-containing DNA, no significant change was observed in the central region; however, the helical twist and the slide of the terminal region of the bases change in the presence of dodine compared to the aqueous medium (Figure S7c). It is apparent from the simulation that the binding of dodine perturbs the structure of DNA; however, the structural change for A–T and G–C DNAs is being initiated in the different regions.

Furthermore, to understand the impact of this structural change on base stacking energy, the interaction energy between the rings of the flanking nucleobases in the buffer as well as dodine has been calculated as base stacking plays a major role in DNA stabilization.47Table 1 shows some representative interaction energy of flanking bases of all the three base sequences of DNA in the presence of water and dodine. In the case of seq1, the interaction energy of the flanking bases becomes positive, suggesting that the stacking between the bases of DNA is reduced probably due to the unwinding of the bases. The interaction of dodine with seq2 also shows the decrease in the interaction energy between the bases present in the minor groove; however, the extent of destabilization is less than seq1. The less destabilization of seq2 than seq1 is due to the less number of A–T bases, which reduces the interaction of dodine with seq2 compared to seq1. The effect on the interaction energy of the terminal bases was also calculated for both sequences in the presence of dodine and found that the minor groove binding of dodine does not affect much to the interaction energy of the terminal bases of seq1 and seq2 DNA. In contrast, the interaction energy of the terminal bases decreases, and almost no change in the interaction energy of the central bases of the minor groove was observed for the interaction of seq3 DNA with dodine. The change in the interaction energy of the terminal bases of G–C-rich DNA is due to preferable interaction of dodine in the terminal region in contrast to A–T DNA where dodine interacts preferably in the central bases of the minor groove region of DNA. It is apparent from the data that the unwinding of A–T bases containing DNA probably takes place from the central bases of the minor groove region, whereas terminal bases are the hot spot for the G–C-rich DNA. The experimental and simulation data together suggest that the fungicide, dodine, disrupts the structure of B-DNA irrespective of the nature of the bases present in the sequence. However, the mode of the interaction of dodine with DNA causing the structural change of DNA is different for A–T- and G–C-containing DNAs.

Table 1. Average Interaction Energy of the Flanking Stacked Nucleobases for All the Sequences of DNAa.

  stacked bases native dodine
seq1 T7-T8 –5.0 ± 0.2 4.3 ± 0.1
  T8-C9 –4.9 ± 0.2 2.0 ± 0.1
seq2 C6-G7 –13.6 ± 1 –8.1 ± 0.5
  T8-C9 –5.2 ± 0.3 –2.9 ± 0.2
seq3 G2-C3 –13.2 ± 0.3 –11.4 ± 0.1
  G8-C9 –11.6 ± 0.2 –11.0 ± 0.1
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a

Energies are in kcal/mol unit.

Conclusions

In this study, the binding of dodine with DNAs having different A–T- and G–C-containing sequences resulting to its structural change was probed using the spectroscopic and simulation studies. Spectroscopic studies suggest that the binding of dodine perturbs the structure of DNA irrespective of the nature of bases, although the mode of interaction of dodine with DNA-containing A–T bases is different from the G–C bases. The hydrocarbon chain of dodine prefers to bind in the central A–T bases of A–T-containing DNA. In the case of G–C-rich DNA, dodine prefers to bind through its polar head group with the terminal bases of the minor groove. In contrast to DNA-containing A–T bases, the binding of dodine with G–C-rich DNA is highly dynamical and shuttles between the minor groove to the terminal region. The binding of dodine with DNA having A–T bases destabilizes the stacking between the bases present in the minor groove, whereas in the case of G–C-rich DNA, the stacking of the terminal bases decreases, although the extent is less than A–T DNA.

Acknowledgments

We acknowledge the funding from DST-SERB (CRG/2019/001389). S.S. acknowledges DST-inspire for the fellowship and CRAY supercomputer for the simulation.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.1c01228.

  • UV–vis spectra of DNA sequences in the presence of dodine, average RMSF, RDF of dodinium with phosphate and major groove, preferable binding mode of dodine with different sequences of DNA, distance of each dodinium cations from central region of minor groove, and structural parameters of all the sequences (PDF)

The authors declare no competing financial interest.

Supplementary Material

ao1c01228_si_001.pdf (688.3KB, pdf)

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