DNA hybridization kinetics: zippering, internal displacement and sequence dependence
TLDR
This work explores DNA oligomer hybridization kinetics using a coarse-grained model and explains why experimentally observed association rates of GC-rich oligomers are higher than rates of AT- rich equivalents, and how association rates can be modulated by sequence choice.Abstract:
Although the thermodynamics of DNA hybridization is generally well established, the kinetics of this classic transition is less well understood. Providing such understanding has new urgency because DNA nanotechnology often depends critically on binding rates. Here, we explore DNA oligomer hybridization kinetics using a coarse-grained model. Strand association proceeds through a complex set of intermediate states, with successful binding events initiated by a few metastable base-pairing interactions, followed by zippering of the remaining bonds. But despite reasonably strong interstrand interactions, initial contacts frequently dissociate because typical configurations in which they form differ from typical states of similar enthalpy in the double-stranded equilibrium ensemble. Initial contacts must be stabilized by two or three base pairs before full zippering is likely, resulting in negative effective activation enthalpies. Non-Arrhenius behavior arises because the number of base pairs required for nucleation increases with temperature. In addition, we observe two alternative pathways-pseudoknot and inchworm internal displacement-through which misaligned duplexes can rearrange to form duplexes. These pathways accelerate hybridization. Our results explain why experimentally observed association rates of GC-rich oligomers are higher than rates of AT- rich equivalents, and more generally demonstrate how association rates can be modulated by sequence choice.read more
Citations
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疟原虫var基因转换速率变化导致抗原变异[英]/Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Journal ArticleDOI
On the biophysics and kinetics of toehold-mediated DNA strand displacement
Niranjan Srinivas,Thomas E. Ouldridge,Petr Šulc,Joseph M. Schaeffer,Bernard Yurke,Ard A. Louis,Jonathan P. K. Doye,Erik Winfree +7 more
TL;DR: This work study strand displacement at multiple levels of detail, using an intuitive model of a random walk on a 1D energy landscape, a secondary structure kinetics model with single base-pair steps and a coarse-grained molecular model that incorporates 3D geometric and steric effects to provide a biophysical explanation of strand displacement kinetics.
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Beware of density dependent pair potentials
TL;DR: In this paper, it was shown that the pair potential that correctly reproduces the pair structure will not generate the right virial pressure, which can lead to an apparent dependence of thermodynamic properties on the ensemble within which they are calculated.
Journal ArticleDOI
Enzyme-free nucleic acid dynamical systems.
TL;DR: The creation of a biochemical oscillator that requires no enzymes or evolved components, but rather is implemented through DNA molecules designed to function in strand displacement cascades is described.
Journal ArticleDOI
Introducing improved structural properties and salt dependence into a coarse-grained model of DNA
Benedict E. K. Snodin,Ferdinando Randisi,Majid Mosayebi,Petr Šulc,John S. Schreck,Flavio Romano,Thomas E. Ouldridge,Roman Tsukanov,Eyal Nir,Ard A. Louis,Jonathan P. K. Doye +10 more
TL;DR: In this paper, an extended version of oxDNA, called oxDNA2, was proposed to capture the thermodynamic, structural, and mechanical properties of single and double-stranded DNA.
References
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疟原虫var基因转换速率变化导致抗原变异[英]/Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Journal ArticleDOI
A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules
Wendy D. Cornell,Piotr Cieplak,Piotr Cieplak,Christopher I. Bayly,Christopher I. Bayly,Ian R. Gould,Ian R. Gould,Kenneth M. Merz,Kenneth M. Merz,David M. Ferguson,David M. Ferguson,David C. Spellmeyer,David C. Spellmeyer,Thomas R. Fox,James W. Caldwell,Peter A. Kollman +15 more
TL;DR: Weiner et al. as mentioned in this paper derived a new molecular mechanical force field for simulating the structures, conformational energies, and interaction energies of proteins, nucleic acids, and many related organic molecules in condensed phases.
Journal ArticleDOI
Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid
James D. Watson,Francis Crick +1 more
TL;DR: The determination in 1953 of the structure of deoxyribonucleic acid (DNA), with its two entwined helices and paired organic bases, was a tour de force in X-ray crystallography and opened the way for a deeper understanding of perhaps the most important biological process.
Book
Principles of Nucleic Acid Structure
TL;DR: The goal of this series is to pinpoint areas of chemistry where recent progress has outpaced what is covered in any available textbooks, and then seek out and persuade experts in these fields to produce relatively concise but instructive introductions to their fields.