Single-molecule derivation of salt dependent base-pair free energies in DNA

Abstract

Accurate knowledge of the thermodynamic properties of nucleic acids is crucial to predicting their structure and stability. To date most measurements of base-pair free energies in DNA are obtained in thermal denaturation experiments, which depend on several assumptions. Here we report measurements of the DNA base-pair free energies based on a simplified system, the mechanical unzipping of single DNA molecules. By combining experimental data with a physical model and an optimization algorithm for analysis, we measure the 10 unique nearest-neighbor base-pair free energies with 0.1 kcal mol-1 precision over two orders of magnitude of monovalent salt concentration. We find an improved set of standard energy values compared with Unified Oligonucleotide energies and a unique set of 10 base-pair-specific salt-correction values. The latter are found to be strongest for AA/TT and weakest for CC/GG. Our new energy values and salt corrections improve predictions of DNA unzipping forces and are fully compatible with melting temperatures for oligos. The method should make it possible to obtain free energies, enthalpies and entropies in conditions not accessible by bulk methodologies.

Main text: 27 pages, 4 figures, 2 tables. Supporting Information: 51 pages, 19 figures, 4 tables

Cited by in corpus (30)

• Sequence-dependent thermodynamics of a coarse-grained DNA model
• Large work extraction and the Landauer limit in a continuous Maxwell demon
• Experimental free energy measurements of kinetic molecular states using fluctuation theorems
• Improving signal-to-noise resolution in single molecule experiments using molecular constructs with short handles
• A primer on the oxDNA model of DNA: When to use it, how to simulate it and how to interpret the results
• Experimental measurement of binding energy, selectivity and allostery using fluctuation theorems
• Stem-loop formation drives RNA folding in mechanical unzipping experiments
• Single-molecule stochastic resonance
• Electrostatic Binding and Hydrophobic Collapse of Peptide-Nucleic Acid Aggregates Quantified Using Force Spectroscopy
• Entropy involved in fidelity of DNA replication
• Phase diagram of mechanically stretched DNA: The salt effect
• Cooperativity-Dependent Folding of Single-Stranded DNA
• Force Feedback Effects on Single Molecule Hopping and Pulling Experiments
• The role of non-conservative scattering forces and damping on Brownian particles in optical traps
• Folding and unfolding of a triple-branch DNA molecule with four conformational states
• Force-Dependent Folding Kinetics of Single Molecules with Multiple Intermediates and Pathways
• Efficient methods for determining folding free energies in single-molecule pulling experiments
• Dissipation reduction and information-to-measurement conversion in DNA pulling experiments with feedback protocols
• Single-molecule pulling: phenomenology and interpretation
• Experimental test of Sinai's model in DNA unzipping
• Stacking correlation length in single-stranded DNA
• Sugar-Pucker Force-Induced Transition in Single-Stranded~DNA
• Nonequilibrium thermodynamics of DNA nanopore unzipping
• Force Dependence of Proteins' Transition State Position and the Bell-Evans Model
• A polymer model of bacterial supercoiled DNA including structural transitions of the double helix
• Breathing dynamics based parameter sensitivity analysis of hetero-polymeric DNA
• Information-to-work conversion in single molecule experiments: from discrete to continuous feedback
• Detecting molecular folding from noise measurements
• Possible scenarios of DNA double helix unzipping process
• Steady state of overdamped particles in the non-conservative force field of a simple non-linear model of optical trap