Exploring polymorphisms in B-DNA helical conformations

Dans, Pablo D.; Pérez, Alberto; Faustino, Ignacio; Lavery, Richard; Orozco, Modesto

doi:10.1093/nar/gks884

Cited by 82 publications

(132 citation statements)

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“…In any case, at least in our hands, a simple scaling of van der Waals parameters [46] This result argue the prevalent idea that DNA deformation can be described by means of nearneighbor harmonic models [40•]. An in-depth analysis of non-harmonic deformations in DNA [41,58] characterized the atomistic mechanisms of this movement, the role of ions in DNA polymorphism, and the surprising correlation between apparently disconnected degrees of freedom in the DNA.…”

Section: Atomistic Studiessupporting

confidence: 58%

Multiscale simulation of DNA

Dans¹,

Walther

Gómez

et al. 2016

Current Opinion in Structural Biology

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148

131

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DNA is not only among the most important molecules in life, but a meeting point for biology, physics and chemistry, being studied by numerous techniques. Theoretical methods can help in gaining a detailed understanding of DNA structure and function, but their practical use is hampered by the multiscale nature of this molecule. In this regard, the study of DNA covers a broad range of different topics, from sub-Angstrom details of the electronic distributions of nucleobases, to the mechanical properties of millimeter-long chromatin fibers. Some of the biological processes involving DNA occur in femtoseconds, while others require years. In this review, we describe the most recent theoretical methods that have been considered to study DNA, from the electron to the chromosome, enriching our knowledge on this fascinating molecule.

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Section: Atomistic Studiessupporting

confidence: 58%

Multiscale simulation of DNA

Dans¹,

Walther

Gómez

et al. 2016

Current Opinion in Structural Biology

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148

131

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“…In addition, both experimental sources of BII values suffer from a sequence bias due to the limited number of tetranucleotide represented in the limited set of sequence available 20,22,29 .…”

Section: Resultsmentioning

confidence: 99%

The Role of Unconventional Hydrogen Bonds in Determining BII Propensities in B-DNA

Balaceanu

Pasi

Dans

et al. 2016

J. Phys. Chem. Lett.

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An accurate understanding of DNA backbone transitions is likely to be the key for elucidating the puzzle of the intricate sequence-dependent mechanical properties that govern most of the biologically relevant functions of the double helix. One factor believed to be important in indirect recognition within protein-DNA complexes is the combined effect of two DNA backbone torsions (ε and ζ) which give rise to the well-known BI/BII conformational equilibrium. In this work we explain the sequence dependent BII propensity observed in RpY steps (R = purine; Y = pyrimidine) at the tetranucleotide level with the help of a previously undetected C-H···O contact between atoms belonging to adjacent bases. Our results are supported by extensive multi-microsecond molecular dynamics simulations from the Ascona B-DNA Consortium, high-level quantum mechanical calculations, and data mining of the experimental structures deposited in the Protein Data Bank.

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“…If the distributions of parameters in a large sample of known structures are Gaussian, the mean values will provide a good approximation of the equilibrium rest states and the widths of the distributions will provide an estimate of the elastic constants governing the spatial arrangements of neighboring basepairs. The original estimates of DNA sequence-dependent structural deformability, derived nearly 20 years ago from the few available well-resolved, DNA-containing crystal structures (6), have been supplemented over the years by analyses of larger, better-resolved, nonredundant structural data sets (29) and by massive atomic-level simulations with the capability to examine the influence of sequence content (e.g., nonadjacent nearby residues) on double-helical structure and deformability (30)(31)(32).Until very recently, the predicted effects of sequence on DNA structure failed to account for many key features of the double-helical molecule, including the basepair twist-a parameter that can be reliably measured in solution, gels, and the solid state (33-37). In particular, atomic-level simulations based on some of the most widely used nucleic-acid force fields predicted the twist angle of a generic DNA basepair step (a step generated by averaging the twist angles over all possible combinations of adjacent basepairs) to be~1.2 lower on average than the corresponding values compiled from experiments on mixed-sequence DNA (Fig.…”

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confidence: 99%

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confidence: 99%

“…(A) Average sequence-dependent values of the twist angle between successive basepairs grouped by chemical class (pyrimidine-purine, purine-purine, and purine-pyrimidine). Gold, trends deduced from early biophysical studies of DNA in gels and in solution (35); violet, values accumulated over time in crystal structures of protein-bound DNA (6,29) and a mix of ligand-bound and free DNA (31); green, values predicted with increasingly improved atomic force fields (30)(31)(32). Note that the twist of a generic, sequence-averaged DNA step (MN) found in the most recent data corresponds to a helix with a nucleotide repeat close to the~10.5 bp/turn repeat of mixed-sequence DNA (dashed line) (33,34,36) and that large changes in twist at pyrimidine-purine steps underlie this improvement.…”

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confidence: 99%

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Contributions of Sequence to the Higher-Order Structures of DNA

Todolli

Perez

Clauvelin

et al. 2017

Biophysical Journal

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One of the critical unanswered questions in genome biophysics is how the primary sequence of DNA bases influences the global properties of very-long-chain molecules. The local sequence-dependent features of DNA found in high-resolution structures introduce irregularities in the disposition of adjacent residues that facilitate the specific binding of proteins and modulate the global folding and interactions of double helices with hundreds of basepairs. These features also determine the positions of nucleosomes on DNA and the lengths of the interspersed DNA linkers. Like the patterns of basepair association within DNA, the arrangements of nucleosomes in chromatin modulate the properties of longer polymers. The intrachromosomal loops detected in genomic studies contain hundreds of nucleosomes, and given that the simulated configurations of chromatin depend on the lengths of linker DNA, the formation of these loops may reflect sequence-dependent information encoded within the positioning of the nucleosomes. With knowledge of the positions of nucleosomes on a given genome, methods are now at hand to estimate the looping propensities of chromatin in terms of the spacing of nucleosomes and to make a direct connection between the DNA base sequence and larger-scale chromatin folding.Despite the astonishing amount of information now known about the sequential makeup and spatial organization of genomic DNA, there is much to learn about how the vast numbers of basepairs in these systems contribute to the three-dimensional architectures and workings of long, spatially constrained, double-helical molecules. New biochemical and imaging methodologies, such as proximity-based ligation and fluorescence in situ hybridization (1-3), have shed light on the large-scale organization of genomic DNA, enabling investigators to pinpoint DNA elements in close spatial proximity and follow the course of these associations during cellular processes. The resulting measurements have motivated the study of long genomes in terms of simple polymer models (4,5), which have in turn illuminated the physical nature of the contacted elements and pointed to mechanisms potentially governing genome architecture and dynamics. Although these models are appropriate for the very large scale of the experimental data, they rest on the assumption that the chemical makeup of DNA does not matter, and thus provide no link between the primary sequence of bases and the tertiary structures and interactions of genomic folds.At the other extreme of chain length, the detailed molecular structures of DNA with only tens of basepairs point to various sequence-dependent spatial and energetic codes underlying the three-dimensional organization of the double helix and its susceptibility to interactions with proteins and other molecules (6). The structural data also include more than 100 crystallographic examples of the tight, superhelical wrapping of~150 DNA basepairs (bp) around the core of the histone proteins in the nucleosome core particle, the fundamental packagi...

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Exploring polymorphisms in B-DNA helical conformations

Cited by 82 publications

References 38 publications

Multiscale simulation of DNA

Multiscale simulation of DNA

The Role of Unconventional Hydrogen Bonds in Determining BII Propensities in B-DNA

Contributions of Sequence to the Higher-Order Structures of DNA

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