Coarse-Grained Model DNA: Structure, Sequences, Stems, Circles, Hairpins

Abstract

A coarse-grained model for DNA that is intended to function realistically at the level of individual bases is reported. The model is composed of residues with up to eight coarse-grained beads each, which is sufficient for DNA-like base stacking and base-base recognition by hydrogen bonding. The beads interact by means of short-ranged pair potentials and a simple implicit solvent model. Movement is simulated by Brownian dynamics without hydrodynamic coupling. The main stabilizing forces are base stacking and hydrogen bonding, as modified by the effects of solvation. Complementary double-stranded chains of such residues form stable double helices over long runs (~10 μs) at or near room temperature, with structural parameters close to those of B-form DNA. Most mismatched chains or mismatched regions within a complementary molecule melt and become disordered. Long-range fluctuations and elastic properties, as measured by bending and twisting persistence lengths, are close to experimental values. Single-stranded chains are flexible, with transient stretches of free bases in equilibrium with globules stabilized by intrastrand stacking and hydrogen bonding. Model DNAs in covalently closed loops form right- or left-handed supercoils, depending on the sign of overtwist or undertwist. Short stem-loop structures melt at elevated temperatures and reanneal when the temperature is carefully lowered. Overall, most qualitative properties of real DNA arise naturally in the model from local interactions at the base-pair level.

Sequence-Dependent Three Interaction Site Model for Single- and Double-Stranded DNA

“…Subsequently, several CG models of higher resolution have been proposed. 10,25,31,37,38 Notably, the model of Scheraga and co-workers 25 has been used to study the assembly of the DNA double helix, from two single strands. However, the mechanical properties of both single-stranded and double-stranded DNA were not correctly reproduced.…”

An experimentally-informed coarse-grained 3-site-per-nucleotide model of DNA: Structure, thermodynamics, and dynamics of hybridization

“…Beginning with an n = 2 representation, coarse-grained models of increasing complexity have been introduced. [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] By increasing n, it has become possible to reproduce more a) Electronic mail: depablo@uchicago.edu of the structural features of DNA, such as the major and minor grooves, as well as thermodynamic properties such as the melting temperature. 9,14,17,18,22 Here we focus on the so-called 3-Site-Per-Nucleotide (3SPN) model, originally introduced by Knotts et al 9 Note that n = 3 is the minimum number of sites that enable resolution of major and minor grooves using isotropic potentials, thereby providing a reasonable compromise between structural fidelity and computational efficiency.…”

“…Edens et al 21 developed a coarse-grained model with a rigid nucleotide consisting of 7 or 8 sites designed to create a lockand-key relationship with the complementary nucleotide. By creating a close-packed representation of the excluded volume core, it reproduces the major and minor grooves while utilizing short-ranged isotropic potentials.…”

Coarse-grained modeling of DNA curvature

“…Most CG models include sequence-dependence to some degree, usually in the CG topology and the energy parameters of the base stacking and base pairing interactions. Some models have demonstrated consistency with local base-step properties such as rise and twist 4,6 . However, no CG model to date has been demonstrated to capture the intrinsic curvature and global flexibility of DNA.…”