Two-state model of conformational fluctuation in a DNA hairpin-loop

Ying, Liming; Wallace, Mark I.; Klenerman, David

doi:10.1016/s0009-2614(00)01425-1

Cited by 42 publications

(72 citation statements)

References 30 publications

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“…ii) Folding structures for all the DNA sticky ends must be minimized. Secondary structures, such as loops and hairpins, reduce the number of active ends, and hence the binding free energy and melting temperature (26,(28)(29)(30)(31).…”

Section: Polygamous Particlesmentioning

confidence: 99%

Polygamous particles

Feng

Sha

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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DNA is increasingly used as an important tool in programming the self-assembly of micrometer-and nanometer-scale particles. This is largely due to the highly specific thermoreversible interaction of cDNA strands, which, when placed on different particles, have been used to bind precise pairs in aggregates and crystals. However, DNA functionalized particles will only reach their true potential for particle assembly when each particle can address and bind to many different kinds of particles. Indeed, specifying all bonds can force a particular designed structure. In this paper, we present the design rules for multiflavored particles and show that a single particle, DNA functionalized with many different "flavors," can recognize and bind specifically to many different partners. We investigate the cost of increasing the number of flavors in terms of the reduction in binding energy and melting temperature. We find that a single 2-μm colloidal particle can bind to 40 different types of particles in an easily accessible time and temperature regime. The practical limit of ∼100 is set by entropic costs for particles to align complementary pairs and, surprisingly, by the limited number of distinct "useful" DNA sequences that prohibit subunits with nonspecific binding. For our 11 base "sticky ends," the limit is 73 distinct sequences with no unwanted overlaps of 5 bp or more. As an example of phenomena enabled by polygamous particles, we demonstrate a three-particle system that forms a fluid of isolated clusters when cooled slowly and an elastic gel network when quenched. multifunctional | thermodynamicsA defining feature of DNA nanotechnology is the ability of DNA single strands to bind selectively only with complementary strands (1-8). Identical particles coated with identical DNA strands can be joined together by adding to the suspension a linker strand that attaches to the two coatings (9, 10). Such structures have been used for immunoassays (11), particle aggregation, and formation of crystalline structures, typically Face Centered Cubic (FCC) (12). Use has also been made of different particles, A and B, functionalized with cDNA strands (13). This configuration, where A-A and B-B bonds do not occur but A-B bonds do (14-16), has been exploited to form more complex crystals, such as BCC or CsCl structures (12,17). Over the past several years, there has been a great deal of progress in modeling the DNA-mediated interparticle interaction and making quantitative comparisons with experiments (16,(18)(19)(20)(21)(22)(23). Although nanoscale particles are typically coated with tens to hundreds of DNA molecules, and micrometer-scale colloids can be coated with 10 4 -10 5 DNA strands, there has been little work on coating particles with more than one type of DNA sequence on the same particle. Allowing these particles to be "polygamous," to specifically bind to a particular set of other particles, enables not only the fabrication of more complex crystals but the design of more general programmed structures. For rigid structures,...

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Section: Polygamous Particlesmentioning

confidence: 99%

Polygamous particles

Feng

Sha

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…A range of classical physical studies led to the assumption that the unfolding of short DNA fragments is reversible and follows a two-state mechanism, starting at d(A·T) pairs. [1][2][3] Nevertheless, this traditional view has been recently challenged [4][5][6][7][8][9] by ultrafast techniques, which suggested a more complex scenario where compact intermediates are detected during the microsecond-long unfolding process.[4] Unfortunately, these experiments were not able to provide atomistic-detailed information on the process, thus making necessary the use of simulation techniques (mainly molecular dynamics, MD) as complementary tools. For computational reasons MD simulations of unfolding have typically followed indirect approaches, such as the use of multiple short trajectories, [10,11] replica exchange, [12,13] or moderately large (100 ns) simulations under nonphysical denaturing conditions (T = 400 K).…”

mentioning

confidence: 99%

Real‐Time Atomistic Description of DNA Unfolding

Pérez

Orozco

2010

Angew Chem Int Ed

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Despite recent efforts, the folding/unfolding of DNA (understood as a dramatic conformational change from the native conformation in a significantly large portion of the duplex) is still poorly described. A range of classical physical studies led to the assumption that the unfolding of short DNA fragments is reversible and follows a two-state mechanism, starting at d(A·T) pairs. [1][2][3] Nevertheless, this traditional view has been recently challenged [4][5][6][7][8][9] by ultrafast techniques, which suggested a more complex scenario where compact intermediates are detected during the microsecond-long unfolding process.[4] Unfortunately, these experiments were not able to provide atomistic-detailed information on the process, thus making necessary the use of simulation techniques (mainly molecular dynamics, MD) as complementary tools. For computational reasons MD simulations of unfolding have typically followed indirect approaches, such as the use of multiple short trajectories, [10,11] replica exchange, [12,13] or moderately large (100 ns) simulations under nonphysical denaturing conditions (T = 400 K). [14,15] These simulations provided clear evidence of the complexity of DNA unfolding but were unable to define a mechanistic view, which would require multiple very large unbiased trajectories. Herein, we present a full atomistic description [16] of the unfolding of a full turn of DNA under realistic denaturing conditions. The study, a real "tour de force" for MD, provides for the first time a detailed atomistic picture of DNA unfolding in the microsecond timescale.All simulations were performed using Dickersons dodecamer [17] (DDD; Protein Data Bank (PDB) code 1BNA), a well-studied model of a short nonhairpin duplex. To guarantee unfolding on the microsecond timescale, [10,11] we simulated strong (but realistic) denaturing conditions by adding a high concentration of a chemical denaturant (pyridine; Pyr) and increasing the temperature to nearly the boiling point of water (these simulations are coded as PHT). Control simulations were performed that considered: 1) water at low temperature (WLT), where we expected no signal of unfolding on the microsecond timescale; 2) a mixture of water and Pyr at low temperature (PLT), where we expected the beginning of unfolding; and 3) simulations in water at high temperature (WHT), where we expected partial unfolding. WLT and PLT microsecond simulations were performed at T = 300 K considering pure water (5000 water molecules) and a 1:1 (by mass) Pyr/water mixture (3923 water and 760 Pyr molecules), respectively. Simulations in hot solvent (WHT and PHT) were performed at T = 368 K using the same simulation boxes as before (for simulation details, see the Supporting Information). To gain better statistics, ten replicas were performed under PHT conditions for at least 1 ms. Simulations were performed using state-of-the-art simulation conditions (see the Supporting Information), the parmbsc0/parm99 [18] force field for DNA, TIP3P [16] for water, and a new force field for Pyr deri...

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“…A range of classical physical studies led to the assumption that the unfolding of short DNA fragments is reversible and follows a two-state mechanism, starting at d(A·T) pairs. [1][2][3] Nevertheless, this traditional view has been recently challenged [4][5][6][7][8][9] by ultrafast techniques, which suggested a more complex scenario where compact intermediates are detected during the microsecond-long unfolding process. [4] Unfortunately, these experiments were not able to provide atomistic-detailed information on the process, thus making necessary the use of simulation techniques (mainly molecular dynamics, MD) as complementary tools.…”

mentioning

confidence: 99%

Real‐Time Atomistic Description of DNA Unfolding

Pérez

Orozco

2010

Angewandte Chemie

View full text Add to dashboard Cite

Despite recent efforts, the folding/unfolding of DNA (understood as a dramatic conformational change from the native conformation in a significantly large portion of the duplex) is still poorly described. A range of classical physical studies led to the assumption that the unfolding of short DNA fragments is reversible and follows a two-state mechanism, starting at d(A·T) pairs. [1][2][3] Nevertheless, this traditional view has been recently challenged [4][5][6][7][8][9] by ultrafast techniques, which suggested a more complex scenario where compact intermediates are detected during the microsecond-long unfolding process. [4] Unfortunately, these experiments were not able to provide atomistic-detailed information on the process, thus making necessary the use of simulation techniques (mainly molecular dynamics, MD) as complementary tools. For computational reasons MD simulations of unfolding have typically followed indirect approaches, such as the use of multiple short trajectories, [10,11] replica exchange, [12,13] or moderately large (100 ns) simulations under nonphysical denaturing conditions (T = 400 K). [14,15] These simulations provided clear evidence of the complexity of DNA unfolding but were unable to define a mechanistic view, which would require multiple very large unbiased trajectories. Herein, we present a full atomistic description [16] of the unfolding of a full turn of DNA under realistic denaturing conditions. The study, a real "tour de force" for MD, provides for the first time a detailed atomistic picture of DNA unfolding in the microsecond timescale.All simulations were performed using Dickersons dodecamer [17] (DDD; Protein Data Bank (PDB) code 1BNA), a well-studied model of a short nonhairpin duplex. To guarantee unfolding on the microsecond timescale, [10,11] we simulated strong (but realistic) denaturing conditions by adding a high concentration of a chemical denaturant (pyridine; Pyr) and increasing the temperature to nearly the boiling point of water (these simulations are coded as PHT). Control simulations were performed that considered: 1) water at low temperature (WLT), where we expected no signal of unfolding on the microsecond timescale; 2) a mixture of water and Pyr at low temperature (PLT), where we expected the beginning of unfolding; and 3) simulations in water at high temperature (WHT), where we expected partial unfolding. WLT and PLT microsecond simulations were performed at T = 300 K considering pure water (5000 water molecules) and a 1:1 (by mass) Pyr/water mixture (3923 water and 760 Pyr molecules), respectively. Simulations in hot solvent (WHT and PHT) were performed at T = 368 K using the same simulation boxes as before (for simulation details, see the Supporting Information). To gain better statistics, ten replicas were performed under PHT conditions for at least 1 ms. Simulations were performed using state-of-the-art simulation conditions (see the Supporting Information), the parmbsc0/parm99 [18] force field for DNA, TIP3P [16] for water, and a new force field for Pyr der...

show abstract

Two-state model of conformational fluctuation in a DNA hairpin-loop

Cited by 42 publications

References 30 publications

Polygamous particles

Polygamous particles

Real‐Time Atomistic Description of DNA Unfolding

Real‐Time Atomistic Description of DNA Unfolding

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