Coarse grained modeling of self assembled DNA 3D structure using pragmatic soft ellipsoid contact potential

In this paper, we present a coarse-grained model of DNA based on the soft ellipsoid contact potential (ECP) to evaluate the base pairing interaction properly. We extend the ellipsoid contact like potential model (ECP), suitably modified and used previously by our group to model lipid bilayer phases with considerable success. This potential is used for base-base interactions, along with other potentials to capture bending, dihedral and solvent effects. The model shows a phase transition during hybridization and is able to reproduce the experimental melting curves with sufficient adequacy. Thermodynamical, along with conformational characteristics and structural properties of our model are studied in detail.

💡 Research Summary

The manuscript introduces a novel coarse‑grained (CG) model of double‑stranded DNA that builds upon a soft ellipsoid contact potential (ECP) originally developed for lipid bilayer self‑assembly. The authors adapt the ECP to capture base‑pairing interactions by representing each nucleotide base as a uniaxial ellipsoid with orientation‑dependent energy depth (ε) and contact distance (σ). These quantities are functions of the rotation matrices of the interacting particles and the unit vector connecting their centers, following a modified Gay‑Berne formulation with ν = 2 and μ = 1. By separating the interaction into a “pairing” part (long‑range attraction between complementary bases) and a “stacking” part (short‑range repulsion/attraction between neighboring bases on the same strand), the model reproduces the planar geometry of nucleobases and the anisotropic nature of hydrogen bonding versus π‑stacking.

The total potential energy comprises six contributions: (i) a harmonic bending term V_bend that penalizes deviations of the sugar‑sugar‑sugar angle, (ii) a cosine dihedral term V_dihedral that controls the torsional flexibility of the backbone, (iii) an excluded‑volume repulsion V_exc implemented as a Weeks‑Chandler‑Andersen (WCA) potential for all non‑base‑base pairs, (iv) a Debye‑Hückel electrostatic term V_el to mimic screened Coulomb interactions at physiological ionic strength (100 mM Na⁺, Debye length ≈ 1 nm), (v) an implicit solvent Morse‑type term V_solv that provides an attractive “hydrophobic” interaction between sugar beads (well depth ε_s = 1 k_BT, equilibrium distance 20 Å, width α = 5.33 Å⁻¹), and (vi) the orientation‑dependent ECP V_ECP for base‑base contacts. Bond lengths (sugar‑sugar and sugar‑base) are constrained at 6.4 Å using the RATTLE algorithm, effectively freezing high‑frequency bond vibrations and allowing the slower bending/dihedral motions to dominate the dynamics.

Simulation details: two 20‑base strands are initialized on a lattice, each base modeled as an ellipsoid with semi‑axes (σ_x,σ_y,σ_z) = (2.0, 2.0, 1.0) × 3.4 Å and energy anisotropy (ε_x,ε_y,ε_z) = (1.0, 1.0, 2.0) × ε_0. The system is heated to reduced temperature T* = 0.9, then annealed in steps of ΔT* = 0.02, equilibrating for 10⁶ Langevin‑thermostatted steps at each temperature (time step 0.005, damping coefficient 1.0). A flat‑bottom harmonic confinement of radius 50 Å keeps the two strands from drifting apart during heating; this confinement is gradually removed during cooling to allow free duplex formation. Translational motion is integrated with a velocity‑Verlet scheme, while rotational dynamics use quaternion‑based integration following Rozmanov et al.

Results: As temperature decreases, the fraction of correctly paired bases (Φ) remains high until a critical reduced temperature T* ≈ 0.48, where Φ drops sharply, indicating duplex melting. Correspondingly, the specific heat capacity derived from energy fluctuations exhibits a pronounced peak at the same temperature, confirming a first‑order-like phase transition. The simulated melting curve, obtained by fitting a sigmoid function to Φ(T), aligns closely with experimental melting data taken from the literature (Ref