Origin of DNA helical structure and its sequence dependence

Sarai, Akinori; Mazur, J.; Nussinov, Ruth; Jernigan, Robert L.

doi:10.1021/bi00422a030

Cited by 92 publications

(56 citation statements)

References 19 publications

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“…Subsequently, Zhurkin et al 24 applied Monte Carlo simulation on DNA to the problem, elaborated the idea, noted the possibility of context effects, and made the distinction between static and statistical bending, and issue of curvature vs. flexibility. Subsequent Monte Carlo simulations were reported by Maroun and Olson 99 (in the context of polymer statistics), and by Shore and Baldwin 108,109 and Jernigan and coworkers 25,110 , all of which are discussed in more detail by Olson and Zhurkin. 26 A promising alternative approach to the study of DNA curvature and bending based on MD simulations is being pursued independently by Lankas et al 111 The vehicle for this analysis is the sequencedependent elastic rod model of DNA developed in terms of parameters that can be identified with a Young's modulus tensor with respect to any welldefined subunit and define a flexible anisotropic rod model 112 for the DNA representative of the MD results.…”

Section: Figurementioning

confidence: 96%

“…A:T base pairs exhibit a higher intra-base pair propeller deformation than C:G, a simple consequence of two Watson-Crick hydrogen bonds between base pairs, rather than three. Experimental data based on crystal structures 113 and theoretical energy calculations 17,24,110,114 indicate that ApA steps show little tendency for deformation or deformability with respect to B-DNA. An explanation has been offered in terms of steric clashes due to the large propeller ("a stack of carpenter's sawhorses is more difficult to push over than a stack of flat wooden planks" 115 ) and particularly favorable base pair stacking.…”

Section: Figurementioning

confidence: 99%

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Molecular dynamics simulations of DNA curvature and flexibility: Helix phasing and premelting

et al. 2004

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Recent studies of DNA axis curvature and flexibility based on molecular dynamics (MD) simulations on DNA are reviewed. The MD simulations are on DNA sequences up to 25 base pairs in length, including explicit consideration of counterions and waters in the computational model. MD studies are described for ApA steps, A-tracts, for sequences of A-tracts with helix phasing. In MD modeling, ApA steps and A-tracts in aqueous solution are essentially straight, relatively rigid, and exhibit the characteristic features associated with the B'-form of DNA. The results of MD modeling of A-tract oligonucleotides are validated by close accord with corresponding crystal structure results and nuclear magnetic resonance (NMR) nuclear Overhauser effect (NOE) and residual dipolar coupling (RDC) structures of d(CGCGAATTCGCG) and d(GGCAAAAAACGG). MD simulation successfully accounts for enhanced axis curvature in a set of three sequences with phased A-tracts studied to date. The primary origin of the axis curvature in the MD model is found at those pyrimidine/purine YpR "flexible hinge points" in a high roll, open hinge conformational substate. In the MD model of axis curvature in a DNA sequence with both phased A-tracts and YpR steps, the A-tracts appear to act as positioning elements that make the helix phasing more precise, and key YpR steps in the open hinge state serve as curvature elements. Our simulations on a phased A-tract sequence as a function of temperature show that the MD simulations exhibit a premelting transition in close accord with experiment, and predict that the mechanism involves a B'-to-B transition within A-tracts coupled with the prediction of a transition in key YpR steps from the high roll, open hinge, to a low roll, closed hinge substate. Diverse experimental observations on DNA curvature phenomena are examined in light of the MD model with no serious discrepancies. The collected MD results provide independent support for the "non-A-tract model" of DNA curvature. The "junction model" is indicated to be a special case of the non-A-tract model when there is a Y base at the 5' end of an A-tract. In accord with crystallography, the "ApA wedge model" is not supported by MD.

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Section: Figurementioning

confidence: 96%

Section: Figurementioning

confidence: 99%

Molecular dynamics simulations of DNA curvature and flexibility: Helix phasing and premelting

et al. 2004

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“…However, modeling the interactions between the charge distributions has been less developed It is usual practice to use a dielectric constant that is either a constant,6 or some simple function of distance .9,28, 3 1-35 Such models do not take into account the effect on the electrostatic energy of the irregular boundary between the low dielectric solute and the high dielectric solvent that may contain Our laboratory has developed a method of calculat-145 ro1e. 6,[9][10][11][12][14][15][16][17][18][19][20][21][22][23][24][25] M ing electrostatic energies using the finite difference Poisson-Boltzmann ( FDPB ) equation that takes these effects into account.36 This method, which is rigorous at the level of continuum electrostatics, has proven successful in predicting the pKas3' and redox potentials of proteins, 3 7~3 9 and the solvation energies of ions4' and small molecule^.^^^^^ We have recently applied the method to DNA, focusing on phosphatephosphate interaction^.^^ The present paper extends this work to base-stacking interaction^.^^ Our goals are to test simple dielectric models, and to assess the relative role of electrostatic and Lennard-Jones ( L J ) interactions in determining the sequence and conformational dependence of stacking energies in DNA. The present paper is limited to consideration of base-base and phosphate-phosphate interactions.…”

Section: Introductionmentioning

confidence: 99%

The electrostatic contribution to DNA base‐stacking interactions

Friedman

Honig

1992

Biopolymers

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Base-stacking and phosphate-phosphate interactions in B-DNA are studied using the finite difference Poisson-Boltzmann equation. Interaction energies and dielectric constants are calculated and compared to the predictions of simple dielectric models. No extant simple dielectric model adequately describes phosphate-phosphate interactions. Electrostatic effects contribute negligibly to the sequence and conformational dependence of base-stacking interactions. Electrostatic base-stacking interactions can be adequately modeled using the Hingerty screening function. The repulsive and dispersive Lennard-Jones interactions dominate the dependence of the stacking interactions on roll, tilt, twist, and propellor. The Lennard-Jones stacking energy in ideal B-DNA is found to be essentially independent of sequence.

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“…The most prominent, the A, B, and Z helixes are deduced from crystals, and thus reflect average conformations. Beyond this, each DNA sequence shows an individual bending, which has been investigated extensively by other techniques (16)(17)(18). These studies resulted in different models providing sets of bending parameters for any triplet or quartet of consecutive bases, and, thus, can be used to describe the bending of any longer DNA sequence.…”

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confidence: 99%

Single-molecule FRET measures bends and kinks in DNA

Woźniak

Schröder

Grubmüller

et al. 2008

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

188

212

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We present advances in the use of single-molecule FRET measurements with flexibly linked dyes to derive full 3D structures of DNA constructs based on absolute distances. The resolution obtained by this single-molecule approach harbours the potential to study in detail also protein-or damage-induced DNA bending. If one is to generate a geometric structural model, distances between fixed positions are needed. These are usually not experimentally accessible because of unknown fluorophore-linker mobility effects that lead to a distribution of FRET efficiencies and distances. To solve this problem, we performed studies on DNA double-helices by systematically varying donor acceptor distances from 2 to 10 nm. Analysis of dye-dye quenching and fluorescence anisotropy measurements reveal slow positional and fast orientational fluorophore dynamics, that results in an isotropic average of the FRET efficiency. We use a nonlinear conversion function based on MD simulations that allows us to include this effect in the calculation of absolute FRET distances. To obtain unique structures, we performed a quantitative statistical analysis for the conformational search in full space based on triangulation, which uses the known helical nucleic acid features. Our higher accuracy allowed the detection of sequence-dependent DNA bending by 16°. For DNA with bulged adenosines, we also quantified the kink angles introduced by the insertion of 1, 3 and 5 bases to be 32°؎ 6°, 56°؎ 4°a nd 73 ؎ 2°, respectively. Moreover, the rotation angles and shifts of the helices were calculated to describe the relative orientation of the two arms in detail.absolute distance measurements ͉ fluorescence energy transfer ͉ multiparameter fluorescence detection ͉ nucleic acid structures I n recent years, fluorescence energy transfer experiments (FRET) have shown great potential for subnanometer analysis of biomolecular structures and their dynamics that can even be applied to single molecules (1-5). Calculation of absolute FRET distances between a donor and acceptor fluorophore is complicated because of several ''calibration'' factors such as detection efficiencies, spectral cross-talk and fluorescence quantum yields (6) that are difficult to determine accurately. Multiparameter Fluorescence Detection (MFD) (7) avoids most pitfalls (5) by simultaneously collecting all fluorescence parameters (intensity, lifetime and anisotropy in both spectral ranges) at the singlemolecule level.However, determination of absolute distances remains a major challenge because of the uncertainty in the fluorophore positions. This uncertainty is due to the use of the long linkers through which the fluorophores are attached to the biomolecules. Orientational freedom is a prerequisite to safely assume an orientation factor ( 2 ) of 2/3 (8); however, this prevents a defined fluorophore position, which is needed for fitting data to a geometric model. Here, we present a new conversion function for experimental FRET efficiencies that considers the dynamics of the movement of the fluorop...

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Origin of DNA helical structure and its sequence dependence

Cited by 92 publications

References 19 publications

Molecular dynamics simulations of DNA curvature and flexibility: Helix phasing and premelting

Molecular dynamics simulations of DNA curvature and flexibility: Helix phasing and premelting

The electrostatic contribution to DNA base‐stacking interactions

Single-molecule FRET measures bends and kinks in DNA

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