The Role of Loop Stacking in the Dynamics of DNA Hairpin Formation

Mosayebi, Majid; Romano, Flavio; Ouldridge, Thomas E.; Louis, Ard A.; Doye, Jonathan P. K.

doi:10.1021/jp510061f

Cited by 34 publications

(36 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The model has been shown to reproduce important aspects of basic processes such as hybridization, 42 toehold mediated strand displacement 52 and hairpin formation. 56 It has also been successfully applied to explore stress-induced transitions. [57][58][59] In this paper we use a sequence-averaged parameterization of oxDNA, 49,50 which is ideal for identifying generic trends.…”

Section: Methodsmentioning

confidence: 99%

Force-Induced Rupture of a DNA Duplex: From Fundamentals to Force Sensors

et al. 2015

Self Cite

View full text Add to dashboard Cite

The rupture of double-stranded DNA under stress is a key process in biophysics and nanotechnology. In this article, we consider the shear-induced rupture of short DNA duplexes, a system that has been given new importance by recently designed force sensors and nanotechnological devices. We argue that rupture must be understood as an activated process, where the duplex state is metastable and the strands will separate in a finite time that depends on the duplex length and the force applied. Thus, the critical shearing force required to rupture a duplex depends strongly on the time scale of observation. We use simple models of DNA to show that this approach naturally captures the observed dependence of the force required to rupture a duplex within a given time on duplex length. In particular, this critical force is zero for the shortest duplexes, before rising sharply and then plateauing in the long length limit. The prevailing approach, based on identifying when the presence of each additional base pair within the duplex is thermodynamically unfavorable rather than allowing for metastability, does not predict a time-scale-dependent critical force and does not naturally incorporate a critical force of zero for the shortest duplexes. We demonstrate that our findings have important consequences for the behavior of a new force-sensing nanodevice, which operates in a mixed mode that interpolates between shearing and unzipping. At a fixed time scale and duplex length, the critical force exhibits a sigmoidal dependence on the fraction of the duplex that is subject to shearing.

show abstract

Section: Methodsmentioning

confidence: 99%

Force-Induced Rupture of a DNA Duplex: From Fundamentals to Force Sensors

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…For longer loops, the difference in predicted melting temperatures between oxDNA2 and SantaLucia widens further. This difference is unsurprising, as in oxDNA2 (and physical DNA), ssDNA becomes stiffer at lower salt concentrations, making the formation of a hairpin less favorable, 44 whereas in the SantaLucia model, the loops' contribution to hairpin stability is salt-independent. 49 It seems plausible that oxDNA2's performance is better than implied by the salt-independent loop contribution in the SantaLucia model.…”

Section: Physical Properties Of Oxdna2mentioning

confidence: 99%

“…This treatment is sufficient to obtain good agreement with experimental data on the structural, mechanical, and especially the thermodynamic properties of single-and double-stranded DNA. Consequently, the model has provided key insights into many different processes relevant to DNA nanotechnology [32][33][34][35][36][37][38][39][40] and biophysics [41][42][43][44][45] and importantly has also been shown to provide direct agreement with experimentally measured properties on a range of systems including DNA overstretching, 45 a two-footed DNA walker, 35 and toehold-mediated strand displacement. 39,46 Despite these achievements, there are some areas where oxDNA can be improved.…”

Section: Introductionmentioning

confidence: 99%

Introducing improved structural properties and salt dependence into a coarse-grained model of DNA

Snodin

Randisi

Mosayebi

et al. 2015

The Journal of Chemical Physics

Self Cite

317

444

View full text Add to dashboard Cite

We introduce an extended version of oxDNA, a coarse-grained model of deoxyribonucleic acid (DNA) designed to capture the thermodynamic, structural, and mechanical properties of single-and double-stranded DNA. By including explicit major and minor grooves and by slightly modifying the coaxial stacking and backbone-backbone interactions, we improve the ability of the model to treat large (kilobase-pair) structures, such as DNA origami, which are sensitive to these geometric features. Further, we extend the model, which was previously parameterised to just one salt concentration ([Na + ] = 0.5M), so that it can be used for a range of salt concentrations including those corresponding to physiological conditions. Finally, we use new experimental data to parameterise the oxDNA potential so that consecutive adenine bases stack with a different strength to consecutive thymine bases, a feature which allows a more accurate treatment of systems where the flexibility of single-stranded regions is important. We illustrate the new possibilities opened up by the updated model, oxDNA2, by presenting results from simulations of the structure of large DNA objects and by using the model to investigate some salt-dependent properties of DNA. C 2015 AIP Publishing LLC. [http://dx

show abstract

“…However, there are cases where chemically-specific CG models for biomolecules are capable of generating rates and pathways of structure formation that are consistent with experimental measurements. For example, the OxDNA model [171]-a two-site per nucleotide model for DNA parametrized to reproduce the melting temperatures of short duplexesgenerates relative rates of duplex hybridization [172,173], strand displacement [174], and hairpin formation [175] that appear directly comparable to experiments. Apparently, the melting-curvebased parametrization probes the dominant energetic driving forces (i.e., base pairing interactions) for a whole range of larger-scale structure formation.…”

Section: Outstanding Challenges Through Representative Examplesmentioning

confidence: 99%

Recent Progress towards Chemically-Specific Coarse-Grained Simulation Models with Consistent Dynamical Properties

Rudzinski

2019

Computation

View full text Add to dashboard Cite

Coarse-grained (CG) models can provide computationally efficient and conceptually simple characterizations of soft matter systems. While generic models probe the underlying physics governing an entire family of free-energy landscapes, bottom-up CG models are systematically constructed from a higher-resolution model to retain a high level of chemical specificity. The removal of degrees of freedom from the system modifies the relationship between the relative time scales of distinct dynamical processes through both a loss of friction and a "smoothing" of the free-energy landscape. While these effects typically result in faster dynamics, decreasing the computational expense of the model, they also obscure the connection to the true dynamics of the system. The lack of consistent dynamics is a serious limitation for CG models, which not only prevents quantitatively accurate predictions of dynamical observables but can also lead to qualitatively incorrect descriptions of the characteristic dynamical processes. With many methods available for optimizing the structural and thermodynamic properties of chemically-specific CG models, recent years have seen a stark increase in investigations addressing the accurate description of dynamical properties generated from CG simulations. In this review, we present an overview of these efforts, ranging from bottom-up parametrizations of generalized Langevin equations to refinements of the CG force field based on a Markov state modeling framework. We aim to make connections between seemingly disparate approaches, while laying out some of the major challenges as well as potential directions for future efforts.

show abstract

The Role of Loop Stacking in the Dynamics of DNA Hairpin Formation

Cited by 34 publications

References 49 publications

Force-Induced Rupture of a DNA Duplex: From Fundamentals to Force Sensors

Force-Induced Rupture of a DNA Duplex: From Fundamentals to Force Sensors

Introducing improved structural properties and salt dependence into a coarse-grained model of DNA

Recent Progress towards Chemically-Specific Coarse-Grained Simulation Models with Consistent Dynamical Properties

Contact Info

Product

Resources

About