Cooperativity-Dependent Folding of Single-Stranded DNA

Abstract

The folding of biological macromolecules is a fundamental process of which we lack a full comprehension. Mostly studied in proteins and RNA, single-stranded DNA (ssDNA) also folds, at physiological salt conditions, by forming non-specific secondary structures that are difficult to characterize with biophysical techniques. Here we present a helix-coil model for secondary structure formation, where ssDNA bases are organized in two different types of domains (compact and free). The model contains two parameters: the energy gain per base in a compact domain, $\epsilon$, and the cooperativity related to the interfacial energy between different domains, $\gamma$. We tested the ability of the model to quantify the formation of secondary structure in ssDNA molecules mechanically stretched with optical tweezers. The model reproduces the experimental force-extension curves in ssDNA of different molecular lengths and varying sodium and magnesium concentrations. Salt-correction effects for the energy of compact domains and the interfacial energy are found to be compatible with those of DNA hybridization. The model also predicts the folding free energy and the average size of domains at zero force, finding good agreement with secondary structure predictions by Mfold. We envision the model could be further extended to investigate native folding in RNA and proteins.

arXiv commentPublished in PRX

References in corpus (11)

• Why is the DNA Denaturation Transition First Order?
• Single-molecule derivation of salt dependent base-pair free energies in DNA
• Non-specific binding of Na${}^{+}$ and Mg${}^{2+}$ to RNA determined by force spectroscopy methods
• The effects of mismatches on hybridization in DNA microarrays: determination of nearest neighbor parameters
• Improving signal-to-noise resolution in single molecule experiments using molecular constructs with short handles
• Glassy transition in a disordered model for the RNA secondary structure
• The Effects of Stacking on the Configurations and Elasticity of Single Stranded Nucleic Acids
• The secondary structure of RNA under tension
• Inferring the diameter of a biopolymer from its stretching response
• Inferring the effective thickness of polyelectrolytes from stretching measurements at various ionic strengths: applications to DNA and RNA
• Efficient methods for determining folding free energies in single-molecule pulling experiments

Cited by in corpus (4)

• Stem-loop formation drives RNA folding in mechanical unzipping experiments
• OxDNA to study species interactions
• Sugar-Pucker Force-Induced Transition in Single-Stranded~DNA
• Stacking correlation length in single-stranded DNA