Role of electrostatic interactions in determining the G-quadruplex structures

Chemical Physics Letters xxx (2017) xxx–xxx

Contents lists available at ScienceDirect

Chemical Physics Letters journal homepage: www.elsevier.com/locate/cplett

Frontiers article

Role of electrostatic interactions in determining the G-quadruplex structures Jinkeong Lee 1, Haeri Im 1, Song-Ho Chong, Sihyun Ham ⇑ Department of Chemistry, Sookmyung Women’s University, Cheongpa-ro 47-gil 100, Yongsan-Ku, Seoul 04310, Republic of Korea

a r t i c l e

i n f o

Article history: Received 15 October 2017 In final form 24 November 2017 Available online xxxx Keywords: DNA Conformational energy Solvation free energy Molecular dynamics simulation Integral-equation theory

a b s t r a c t We investigate the energetics of the antiparallel, hybrid and parallel type G-quadruplex structures of the human telomere DNA sequence. We find that both the conformational energy and solvation free energy of these structures are roughly inversely proportional to their radii of gyration. We rationalize this finding in terms of the dominance of the electrostatic contributions. We also show that the solvation free energy is more significant than the conformational energy in determining the G-quadruplex structures, which is in contrast to the canonical B-DNA structures. Our work will contribute to an understanding of the molecular mechanisms dictating various G-quadruplex topologies. Ó 2017 Elsevier B.V. All rights reserved.

1. Introduction Guanine-rich DNA sequences identified in the telomere and promotor regions can fold into non-B-form structures called Gquadruplexes [1]. Such non-canonical DNA structures are of recent biological interest because of their regulatory roles and potential relevance as therapeutic targets [2–4]. G-quadruplexes take fourstranded structures in which G-tetrads, each consisting of four guanine bases arranged in a planar configuration, are stacked successively on top of each other with stabilizing central cations. A number of G-quadruplex structures exhibiting varying topologies have been reported [5–13], which are characterized by different orientation of the four strands. These diverse structures are formed depending on both the internal (e.g., sequence contexts and central cation types) and external factors (temperature, ionic strength, and concentration of co-solutes) [14–17]. The thermodynamic stability of differing G-quadruplex structures has been one of the central issues since it impacts the transcription, translation and replication efficiencies [18–22]. Predicting the particular topology under a given solution condition is also critical for the structure-based drug design. However, the thermodynamic driving forces determining the stability of differing topologies remain poorly understood because of the complexity of analysis in which a multitude of factors need to be simultaneously taken into account.

Herein, we investigate the energetics of the antiparallel, hybrid and parallel type G-quadruplexes, focusing on the consequences that solely stem from the topological differences. For this purpose, we study the G-quadruplexes of the identical human telomere sequence 50 -AGGG-(TTAGGG)3-30 (Tel22), containing two K+ central cations, under the simplest solution condition, i.e., pure water at an ambient condition (300 K and 1 bar). We carried out molecular dynamics simulations for each type of those G-quadruplexes to sample solution-phase conformations. For those simulated conformations, we computed the intrasolute conformational energy and the solvation free energy. We observe that both the conformational energy and solvation free energy are roughly inversely proportional to the radii of gyration of the G-quadruplex structures. By decomposing those energies into the contributions arising from the bond, Lennard-Jones, and electrostatic interactions, we argue that this observation reflects the electrostatic dominance in the energetics of the G-quadruplexes. We also show that the solvation free energy is the more important thermodynamic driving factor than the conformational energy in determining the G-quadruplex structures. Thereby, we would like to provide a basis toward a comprehensive understanding of the thermodynamic stability of various G-quadruplex topologies. 2. Materials and methods 2.1. Molecular dynamics simulations

⇑ Corresponding author. 1

E-mail address: [email protected] (S. Ham). These authors contributed equally to this work.

The initial G-quadruplex structures for our simulations were taken from the Protein Data Bank (PDB): PDB entry 143D (obtained

https://doi.org/10.1016/j.cplett.2017.11.053 0009-2614/Ó 2017 Elsevier B.V. All rights reserved.

Please cite this article in press as: J. Lee et al., Chem. Phys. Lett. (2017), https://doi.org/10.1016/j.cplett.2017.11.053

2

J. Lee et al. / Chemical Physics Letters xxx (2017) xxx–xxx

by NMR) [5] was used for the antiparallel; 2E4I (NMR) [6] for the hybrid; and 1KF1 (X-ray) [7] for the parallel. All of these structures are formed from the identical human telomere fragment 50 -AGGG(TTAGGG)3-30 (Tel22). We used K+ ions for the antiparallel though its structure was determined in Na+ solution [5], so that the Gquadruplexes studied here consist of the same central cations. We conducted all-atom, explicit-water molecular dynamics simulations at T ¼ 300 K and P ¼ 1 bar using the AMBER16 simulation suite [23]. We adopted the Parmbsc1 force field for DNA [24], the TIP4P-Ew model for water [25], and the renewed parameters for K+ [26]. Each initial structure was solvated by water molecules and neutralizing counter K+ ions in a cubic box with a minimum distance of 10 Å between the G-quadruplex and the box edge. (Neutralizing counter ions were added here since they are necessary for handling the long-range electrostatic interactions with the particle mesh Ewald method [27], but they are to be removed in the analysis as we will mention below.) After the standard minimization and equilibration procedures, the production run was carried out for 100 ns with a 2 fs time step. The system temperature and pressure were controlled with the Berendsen’s method [28]. Two independent simulations were conducted for each system, from which we computed averages and standard errors.

2.2. Energetics analysis From each 100 ns trajectory, we took 20,000 G-quadruplex conformations with a 5 ps time interval, along with the two central K+ ions but removing all the surrounding waters and neutralizing counter ions. For these simulated conformations, the intrasolute conformational energy Eu and the solvation free energy Gsolv were computed. The computation of Eu was done using the force field adopted, whereas Gsolv was calculated by combining the threedimensional reference interaction site model (3D-RISM) theory [29,30] and the Kirkwood charging formula [31]. Briefly, the 3DRISM theory computes the distribution function g i ðrÞ for the solvent site i (oxygen or hydrogen for pure water) surrounding a solute by solving the generalized Ornstein-Zernike equation and an approximate closure relation based on the knowledge of the solute-solvent interaction potential ui ðrÞ and the solvent susceptibility function vij ðr; r0 Þ. The function vij ðr; r0 Þ is determined by specifying the solution condition, and in the present work we used the one for pure water. The solvation free energy can be computed from

XZ Gsolv ¼ q i

0

Z

1

dk

dr

@ui ðr; kÞ g i ðr; kÞ @k

ð1Þ

Fig. 1. (a–c) Schematic representation of the antiparallel (a), hybrid (b), and parallel (c) type G-quadruplex structures formed from the sequence 50 -AGGG-(TTAGGG)3-30 . (d) Corresponding simulated structures (taken from the last snapshots of the respective trajectories). (e) Illustration of the radii of gyration for the respective structures.

Please cite this article in press as: J. Lee et al., Chem. Phys. Lett. (2017), https://doi.org/10.1016/j.cplett.2017.11.053

3

J. Lee et al. / Chemical Physics Letters xxx (2017) xxx–xxx Table 1 Structural characteristics.a

Antiparallel Hybrid Parallel a b c d

RMSD [Å]b

Rg [Å]c

RP [Å]d

Rg =RP

2.2  0.0 2.2  0.0 3.0  0.0

10.1  0.0 10.6  0.0 11.9  0.1

12.3  0.0 12.9  0.0 13.7  0.0

0.82 0.82 0.87

Average  standard error. RMSD (all heavy atoms) to the respective PDB structure. Radius of gyration. Radius defined by phosphorous atoms (see text for details).

Here q is the average solvent number density; k is the parameter that gradually turns on the interaction potential from ui ðr; k ¼ 0Þ ¼ 0 to ui ðr; k ¼ 1Þ ¼ ui ðrÞ; and g i ðr; kÞ is the distribution function when the interaction potential is ui ðr; kÞ. We adopted the numerical procedures detailed in [32] to solve the 3D-RISM equation and to obtain Gsolv . The intrasolute conformational energy Eu comprises the bond term (denoted as Eu; bond ; a sum of bond, angle, and dihedralangle potentials) and nonbonded Lennard-Jones (Eu; LJ ) and electrostatic (Eu; elec ) terms:

Eu ¼ Eu; bond þ Eu; LJ þ Eu; elec

Gsolv  Gsolv; elec . Thus, the Rg -dependence of Eu and Gsolv originates from that of Eu; elec and Gsolv; elec . G-quadruplexes are highly negatively charged because of the presence of the phosphate groups along the DNA backbone. There-

ð2Þ

Similarly, since the solute-solvent interaction potential consists of the Lennard-Jones and electrostatic terms, the solvation free energy Gsolv can also be decomposed into these contributions [32]

Gsolv ¼ Gsolv; LJ þ Gsolv; elec

ð3Þ

3. Results and discussion We carried out molecular dynamics simulations for the antiparallel, hybrid and parallel type G-quadruplexes. These are formed from the same Tel22 DNA sequence, but possess different topologies characterized by the directions of the four strands, or equivalently, by the loops connecting them (see Fig. 1(a)–(c)): the antiparallel type has one diagonal and two lateral loops located at the top and bottom of the G-tetrad stem; the parallel type bears three propeller loops located at the sides of the stem; and the hybrid type exhibits a mixed character and contains two diagonal loops at the top and bottom and one propeller loop at the side. These topological structures were stable during the simulations (see Fig. 1(d)). Indeed, the average root mean square deviation (RMSD) of all heavy atoms relative to the respective PDB structure remained within 2–3 Å (see Table 1). The topological differences in the G-quadruplex structures are also reflected in their radii of gyration (Rg ): the parallel type has the largest Rg since it has three propeller loops positioned horizontally, the hybrid type comes to the next since it also bears one propeller loop, and the antiparallel type is the smallest since there is no such loop (see Fig. 1(e) for the illustration and Table 1 for the numerical values of Rg ). For these simulated G-quadruplex structures, we computed the intrasolute conformational energy (Eu ) and the solvation free energy (Gsolv ). These quantities are plotted in Fig. 2(a) and (b) as a function of the radius of gyration (Rg ); their numerical values and statistics are summarized in Table 2. We observe that both Eu and Gsolv are correlated with Rg , and their magnitudes are roughly inversely proportional to Rg (i.e., jEu j and jGsolv j become smaller for larger Rg ). To explore the molecular origin of this behavior, we decomposed Eu and Gsolv into the individual potential energy terms (see (2) and (3)). The results of the decomposition for Eu are shown in Fig. 3, and those for Gsolv in Fig. 4. It is clear from these figures that the behaviors of Eu and Gsolv are primarily determined by their electrostatic components, i.e., Eu  Eu; elec and

Fig. 2. (a–c) Conformational energy Eu (a), solvation free energy Gsolv (b), and effective energy f ¼ Eu þ Gsolv (c) versus the radius of gyration (Rg ) of the antiparallel, hybrid and parallel type G-quadruplexes.

Please cite this article in press as: J. Lee et al., Chem. Phys. Lett. (2017), https://doi.org/10.1016/j.cplett.2017.11.053

4

J. Lee et al. / Chemical Physics Letters xxx (2017) xxx–xxx

Table 2 Energetic characteristics.a

Antiparallel Hybrid Parallel a b

Eu [kcal/mol]

Gsolv [kcal/mol]

f [kcal/mol]b

881.5  4.5 810.8  6.9 767.1  6.2

4569:9  4.2 4488:9  8.3 4419:2  3.3

3688:4  0.3 3678:1  1.4 3652:1  2.9

Average  standard error. f ¼ Eu þ Gsolv .

fore, Eu; elec is mainly contributed by the Coulomb repulsion between the phosphate groups. Let us assume for our qualitative discussion here that the negative charge of the phosphate group is localized at the phosphorous atom. It is then reasonable to approximate Eu; elec to be inversely proportional to the average distance between phosphorous atoms. Let us introduce here the ‘‘radius of phosphorous atoms” RP , which is defined similarly to the radius of gyration Rg but only with phosphorous atoms. It is well-known that Rg can be expressed as the root mean square distance between constituent atoms, and hence, RP provides the corresponding average distance between phosphorous atoms. We therefore expect Eu; elec / 1=RP to hold at the qualitative level. Based on the numerical values of Rg ; RP , and their ratio Rg =RP listed in Table 1, we also note that RP is roughly proportional to Rg . Taken together, we obtain Eu  Eu; elec / 1=Rg , and this qualitatively explains our observation in Fig. 2(a). This is physically quite reasonable since the smaller overall size (Rg ) implies the smaller average distance between the phosphate groups (RP ), and hence, the larger electrostatic repulsion between them (Eu; elec ) which dominates the conformational energy (Eu ). A qualitative understanding of the Rg -dependence of Gsolv  Gsolv; elec is obtained by resorting to the Born model of solvation [33]. This model deals with a spherical solute immersed in a continuum dielectric solvent, and provides an analytic expression for the electrostatic part of the solvation free energy (Gsolv; elec ).

According to this model, Gsolv; elec is proportional to the square of the solute’s charge and is inversely proportional to its radius. By approximating each G-quadruplex structure as a sphere of the radius Rg as illustrated in Fig. 1(e), we obtain Gsolv  Gsolv; elec / 1=Rg since all the G-quadruplexes investigated here have the same total charge. Of course, this is just a rough estimation since the Born model is quite a primitive one, but it does provide a qualitative explanation of our observation made in Fig. 2(b). To summarize our discussion so far, the topological effects on the conformational energy and solvation free energy of the Gquadruplex can be roughly understood in terms of the overall size (Rg ) of the molecule, which in turn reflects the arrangement of the loops connecting the four strands. Of course, characterizing the complex G-quadruplex structure just by a single quantity (Rg ) is too much simplified, and introducing more parameters that more precisely describe the shapes of different G-quadruplex structures would be necessary to quantitatively elucidate the trend observed for Eu and Gsolv . However, we believe that our argument serves as a good zeroth-order approximation that may provide a novel clue for understanding and further studying various G-quadruplex topologies. Finally, let us examine the implications on the thermodynamic stability that follow from Eu and Gsolv . For this purpose, we introduce f ¼ Eu þ Gsolv , which is the solvent-averaged effective energy for a solute [34]. This quantity agrees with the Gibbs free energy up to the solute configurational entropy (i.e., entropy arising from the solute’s internal degrees of freedom), and hence, is relevant to the thermodynamic stability [34]. The effective energy f for the Gquadruplexes we studied is shown in Fig. 2(c). There are two points worthy of note from a comparison of Fig. 2(c) with Fig. 2(a) and (b). First, the solvation free energy (Gsolv ) is more significant than the conformational energy (Eu ) in dictating the stability (f) of the Gquadruplex structure. This is in contrast to the canonical B-DNA conformation that is mainly determined by the electrostatic com-

Fig. 3. (a–d) Conformational energy Eu (a) and its bond component Eu; bond (b), Lennard-Jones component Eu; LJ (c), and electrostatic component Eu; LJ (d) versus the radius of gyration (Rg ) of the antiparallel, hybrid and parallel type G-quadruplexes.

Please cite this article in press as: J. Lee et al., Chem. Phys. Lett. (2017), https://doi.org/10.1016/j.cplett.2017.11.053

J. Lee et al. / Chemical Physics Letters xxx (2017) xxx–xxx

5

Fig. 4. (a–c) Solvation free energy Gsolv (a) and its Lennard-Jones component Gsolv; LJ (b) and electrostatic component Gsolv; elec (c) versus the radius of gyration (Rg ) of the antiparallel, hybrid and parallel type G-quadruplexes.

ponent in Eu : Coulomb repulsion between the backbone phosphates leads to such a structure in which the backbones in two strands are separated as far away as possible, and this is realized by adopting the B-DNA structure [35]. Second, in terms of f, the antiparallel type G-quadruplex is most stable, followed by the hybrid type, and the parallel type is most unstable. This stability order is in accord with the previous computational studies [36,37]. However, some reservation is necessary in this result for the stability order since, as we noted above, the stability analysis in terms of f does not incorporate the solute configurational entropy. In fact, a recent experimental analysis for the G-quadruplexes formed from the same Tel22 sequence indicates that the hybrid type is most stable, followed by the antiparallel type, and the parallel type is most unstable (i.e., the stability order of the antiparallel and hybrid types is reversed compared to our result) and that the entropy contribution is significant in dictating the stability of the hybrid type [38]. The presence of large conformational fluctuations has also been reported for the hybrid-type structures [11]. Indeed, it was necessary to stabilize the particular hybrid structure by substituting guanosines with 8-bromoguanosines at proper positions in the its structure determination [6]. Thus, a more detailed analysis that takes into account the configurational entropy is necessary for a more comprehensive understanding of the thermodynamic stability of various G-quadruplex structures. To this end, much longer simulations are needed since the convergence of the configurational entropy is known to be quite slow (e.g., simulations of 1000 ns length were necessary to reliably estimate this quantity even for a small protein [34]).

4. Conclusions Here, we investigate the energetics associated with the formation of the antiparallel, hybrid and parallel type G-quadruplex structures. We find that the electrostatic interactions dominate

both the intrasolute conformational energy (Eu ) and the solvation free energy (Gsolv ) of the G-quadruplexes. For this reason, Eu and Gsolv exhibit a significant correlation with the radius of gyration, which in turn reflects the particular topology, i.e., the arrangement of the loops connecting the four strands, of the G-quadruplex. We also show that the solvation free energy provides the more important thermodynamic driving force than the conformational energy in dictating the G-quadruplex structure, which is in contrast to the case for the canonical B-DNA structure. Our work will serve as a basis for a more complete comprehension of the thermodynamic stability of various G-quadruplex structures.

Acknowledgement This research was supported by the Sookmyung Women’s University Research Grants (1-1403-0228).

References [1] S. Burge, G.N. Parkinson, P. Hazel, A.K. Todd, S. Neidle, Quadruplex DNA: sequence, topology and structure, Nucl. Acids Res. 34 (2006) 5402. [2] M.L. Bochman, K. Paeschke, V.A. Zakian, DNA secondary structures: stability and function of G-quadruplex structures, Nat. Rev. Genet. 13 (2012) 770. [3] D. Rhodes, H.J. Lipps, G-quadruplexes and their regulatory roles in biology, Nucl. Acids Res. 43 (2015) 8627. [4] R. Hänsel-Hertsch, M. Di Antonio, S. Balasubramanian, DNA G-quadruplexes in the human genome: detection, functions and therapeutic potential, Nat. Rev. Mol. Cell Biol. 18 (2017) 279. [5] Y. Wang, D.J. Patel, Solution structure of the human telomeric repeat d [AG3(T2AG3)3] G-tetraplex, Structure 1 (1993) 263. [6] A. Matsugami, Y. Xu, Y. Noguchi, H. Sugiyama, M. Katahira, Structure of a human telomeric DNA sequence stabilized by 8-bromoguanosine substitutions, as determined by NMR in a K+ solution, FEBS J. 274 (2007) 3545. [7] G.N. Parkinson, M.P.H. Lee, S. Neidle, Crystal structure of parallel quadruplexes from human telomeric DNA, Nature 417 (2002) 876. [8] K.N. Luu, A.T. Phan, V. Kuryavyi, L. Lacroix, D.J. Patel, Structure of the human telomere in K+ solution: an intramolecular (3 + 1) G-quadruplex scaffold, J. Am. Chem. Soc. 128 (2006) 9963.

Please cite this article in press as: J. Lee et al., Chem. Phys. Lett. (2017), https://doi.org/10.1016/j.cplett.2017.11.053

6

J. Lee et al. / Chemical Physics Letters xxx (2017) xxx–xxx

[9] A.T. Phan, V. Kuryavyi, K.N. Luu, D.J. Patel, Structure of two intramolecular Gquadruplexes formed by natural human telomere sequences in K+ solution, Nucl. Acids Res. 35 (2007) 6517. [10] J. Dai, C. Punchihewa, A. Ambrus, D. Chen, R.A. Jones, D. Yang, Structure of the intramolecular human telomeric G-quadruplex in potassium solution: a novel adenine triple formation, Nucl. Acids Res. 35 (2007) 2440. [11] J. Dai, M. Carver, C. Punchihewa, R.A. Jones, D. Yang, Structure of the hybrid-2 type intramolecular human telomeric G-quadruplex in K+ solution: insights into structure polymorphism of the human telomeric sequence, Nucl. Acids Res. 35 (2007) 4927. [12] K.W. Lim, S. Amrane, S. Bouaziz, W. Xu, Y. Mu, D.J. Patel, K.N. Luu, A.T. Phan, Structure of the human telomere in K+ solution: a stable basket-type Gquadruplex with only two G-tetrad layers, J. Am. Chem. Soc. 131 (2009) 4301. [13] B. Heddi, A.T. Phan, Structure of human telomeric DNA in crowded solution, J. Am. Chem. Soc. 133 (2011) 9824. [14] J. Dai, M. Carver, D. Yang, Polymorphism of human telomeric quadruplex structures, Biochimie 90 (2008) 1172. [15] A.T. Phan, Human telomeric G-quadruplex: structures of DNA and RNA sequences, FEBS J. 277 (2010) 1107. [16] S. Dhakal, Y. Cui, D. Koirala, C. Ghimire, S. Kushwaha, Z. Yu, P.M. Yangyuoru, H. Mao, Structural and mechanical properties of individual human telomeric Gquadruplexes in molecularly crowded solutions, Nucl. Acids Res. 41 (2013) 3915. [17] T. Fujii, P. Podbevšek, J. Plavec, N. Sugimoto, Effects of metal ions and cosolutes on G-quadruplex topology, J. Inorg. Biochem. 166 (2017) 190. [18] F. Boán, M.G. Blanco, P. Barros, A.I. González, J.G. Gómez-Márquez, Inhibition of DNA synthesis by K+-stabilised G-quadruplex promotes allelic preferential amplification, FEBS Lett. 571 (2004) 112. [19] K. Paeschke, J.A. Capra, V.A. Zakian, DNA replication through G-quadruplex motifs is promoted by the Saccharomyces cerevisiae Pif1 DNA helicase, Cell 145 (2011) 678. [20] T. Endoh, Y. Kawasaki, N. Sugimoto, Suppression of gene expression by Gquadruplexes in open reading frames depends on G-quadruplex stability, Angew. Chem. Int. Ed. 52 (2013) 5522. [21] C.T. Murphy, A. Gupta, B.A. Armitage, P.L. Opresko, Hybridization of Gquadruplex-forming peptide nucleic acids to guanine-rich DNA templates inhibits DNA polymerase g extension, Biochemistry 53 (2014) 5315. [22] H. Tateishi-Karimata, N. Isono, N. Sugimoto, New insights into transcription fidelity: thermal stability of non-canonical structures in template DNA

[23] [24] [25]

[26]

[27] [28]

[29]

[30] [31] [32]

[33] [34] [35] [36] [37]

[38]

regulates transcriptional arrest, pause, and slippage, PLoS One 9 (2014) e90580. D.A. Case et al., AMBER 16, University of California, San Francisco, 2016. I. Ivani et al., Parmbsc1: a refined force field for DNA simulations, Nat. Methods 13 (2016) 55. H.W. Horn, W.C. Swope, J.W. Pitera, J.D. Madura, T.J. Dick, G.L. Hura, T. HeadGordon, Development of an improved four-site water model for biomolecular simulations: TIP4P-Ew, J. Chem. Phys. 120 (2004) 9665. I.S. Joung, T.E. Cheatham III, Determination of alkali and halide monovalent ion parameters for use in explicitly solvated biomolecular simulations, J. Phys. Chem. B 112 (2008) 9020. T. Darden, D. York, L. Pedersen, Particle mesh Ewald: an N-logðNÞ method for Ewald sums in large systems, J. Chem. Phys. 98 (1993) 10089. H.J.C. Berendsen, J.P.M. Postma, W.F. van Gunsteren, A. DiNola, J.R. Haak, Molecular dynamics with coupling to an external bath, J. Chem. Phys. 81 (1984) 3684. A. Kovalenko, Three-dimensional RISM theory for molecular liquids and solidsolid interfaces, in: F. Hirata (Ed.), Molecular Theory of Solvation, Kluwer Academic, Dordrecht, 2003, p. 169. T. Imai, Y. Harano, M. Kinoshita, A. Kovalenko, F. Hirata, A theoretical analysis on hydration thermodynamics of proteins, J. Chem. Phys. 125 (2006) 024911. A. Ben-Naim, Molecular Theory of Solutions, Oxford University Press, New York, 2006. S.-H. Chong, S. Ham, Atomic decomposition of the protein solvation free energy and its application to amyloid-beta protein in water, J. Chem. Phys. 135 (2011) 034506. P. Atkins, J. de Paula, Physical Chemistry, eighth ed., Oxford University Press, Oxford, 2006. S.-H. Chong, S. Ham, Protein folding thermodynamics: a new computational approach, J. Phys. Chem. B 118 (2014) 5017. S.A. Benner, Unusual hydrogen bonding patterns and the role of the backbone in nucleic acid information transfer, ACS Cent. Sci. 2 (2016) 882. Y. Maruyama, T. Matsushita, R. Ueoka, F. Hirata, Solvent and salt effects on structural stability of human telomere, J. Phys. Chem. B 115 (2011) 2408. A.E. Bergues-Pupo, J.R. Arias-Gonzalez, M.C. Morón, A. Fiasconaro, F. Falo, Role of the central cations in the mechanical unfolding of DNA and RNA Gquadruplexes, Nucl. Acids Res. 43 (2015) 7638. M. Boncˇina, G. Vesnaver, J.B. Chaires, J. Lah, Unraveling the thermodynamics of the folding and interconversion of human telomere G-quadruplexes, Angew. Chem. Int. Ed. 55 (2016) 10340.

Please cite this article in press as: J. Lee et al., Chem. Phys. Lett. (2017), https://doi.org/10.1016/j.cplett.2017.11.053