Role of Hoogsteen interaction in the stability of different phases of triplex DNA

Tanmoy Pal, Keerti Chauhan, and Sanjay Kumar

Phys. Rev. E 105, 044407 – Published 21 April 2022

Abstract

A simple coarse-grained model of DNA which includes both Watson-Crick and Hoogsteen base pairing has been used to study the melting and unzipping of triplex DNA. Using Langevin dynamics simulations, we reproduce the qualitative features of one-step and two-step thermal melting of triplex as seen in experiments. The thermal melting phase diagram shows the existence of a stable interchain three-strand complex (bubble-bound state). Our studies based on the mechanical unzipping of a triplex revealed that it is mechanically more stable compared to an isolated duplex-DNA.

Received 24 October 2021
Accepted 5 April 2022

DOI:https://doi.org/10.1103/PhysRevE.105.044407

Physics Subject Headings (PhySH)

Biomolecular processes

Biomolecules

Physics of Living SystemsStatistical Physics & ThermodynamicsPolymers & Soft MatterInterdisciplinary Physics

Authors & Affiliations

Tanmoy Pal ^*, Keerti Chauhan, and Sanjay Kumar

Banaras Hindu University, Varanasi 221005, India

^*tanmoy.pal@utoronto.ca; Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.

Article Text (Subscription Required)

Click to Expand

Supplemental Material (Subscription Required)

Click to Expand

References (Subscription Required)

Click to Expand

Issue

Vol. 105, Iss. 4 — April 2022

Reuse & Permissions

Access Options

Author publication services for translation and copyediting assistance advertisement

Images

Figure 1
(a) The bead-spring description of triplex DNA used in this study. The starting monomers of each of the strands are anchored at the vertices of an equilateral triangle. Solid and dashed black lines represent Watson-Crick and Hoogsteen bonds, respectively. Unzipping force is applied at the end monomers. The force is applied in the $X − Y$ plane in such a manner that the two pairs of strands (strand-1, strand-2) and (strand-2, strand-3) always feel the same magnitude of unzipping force. (b) Representative snapshots obtained from our simulations showing TRIPLEX (at $T \approx 312 K, g = 0, ɛ_{H} = 1$ ), three single strands (TSS, at $T \approx 390 K, g = 0, ɛ_{H} = 0.6$ ), bubble-bound state (BBS, $T \approx 335 K, g = 0, ɛ_{H} = 0.6$ ), and duplex $+$ single-strand (DSS, $T \approx 312 K, g \approx 56 pN, ɛ_{H} = 0.6$ ). The color convention is of panel (a).
Reuse & Permissions
Figure 2
Zero force melting and forced unzipping of an isolated duplex. (a) Fraction of intact base pairs vs temperature plot with the corresponding specific heat shown in the inset. (b) Separation between the end monomers of the two strands vs unzipping force plot with the corresponding fluctuation in extension shown in the inset. Lines through the data points are guide for the eye.
Reuse & Permissions
Figure 3
Zero force melting of a triplex DNA for different $ɛ_{H}$ . Panels (a–c) show the variation of fraction of bound base-pairs (BP) as a function of temperature. Here, WC-12 represents WC bonds between strand-1 and strand-2 and WC-23 represents WC bonds between strand-2 and strand-3. HO represents HO bonds. End-to-end distances are shown in panels (d–f). Panels (g–i) show the specific heat ( $C$ ) as a function of temperature for different $ɛ_{H}$ . Panels (j, k) are same as panels (b, e) but for nonequilibrated case for $ɛ_{H} = 0.6$ . (l) Comparative plot of UV absorption and $2 - (WC-12 + WC-23 + HO)$ vs temperature. Lines through the data points are guides for the eye.
Reuse & Permissions
Figure 4
(a) Zero force melting phase diagram. Here, $T_{H}$ is the temperature above which no HO-bonds remain intact and above $T_{WC}$ all the WC-bonds break. (b) Force vs temperature phase diagram for $ɛ_{H} = 0.6$ . The filled blue triangles ( $g_{H}$ ) and red diamonds ( $g_{B}$ ) separate the triplex bound state phase and the bubble-bound state (BBS) from the single-strand + duplex phase, respectively. The filled maroon circles ( $g_{T}$ ) act as the phase boundary between the single-strand + duplex phase and the phase where all three strands are completely separated from each other. The maroon stars ( $g_{ID}$ ) represent the critical unzipping forces for an isolated duplex.
Reuse & Permissions
Figure 5
(a, b) Force-Extension plots for triplex DNA for different temperatures at $ɛ_{H} = 0.6$ . Here $Y_{12}$ represents extension between chain-1 and chain-2, etc. Panels (c, d) show the corresponding fluctuation ( $χ$ ) curves of the extension [Eq. (3)]. In panels (c, d), corresponding data for an isolated duplex is also shown (filled orange diamonds). Lines through the data points are guide for the eye.
Reuse & Permissions
Figure 6
Same as described in the caption of Fig. 5 but at $T = 304$ K and at $ɛ_{H} =$ 0 and 1.
Reuse & Permissions

Physical Review E

covering statistical, nonlinear, biological, and soft matter physics