Base-pair Steps Research Articles

Computational Study of Nucleosome Positioning and Stability

Nucleosomes are a highly conserved molecular mechanism for packing genetic material into the cell nucleus. Biologic functionality requires that the histone core be able to fold virtually any sequence of DNA into a nucleosome. However all nucleosomes are not created equal. In vitro histones occupy preferred locations on lengths of DNA greater than 147bp (i.e. positioning) and exhibit preferential binding in mixtures containing different 147bp long oligomers (i.e. affinity). In vivo nucleosome positioning is also observed. But the physical basis for stability and relationships between positioning and affinity remain unclear. For this purpose we have simulated over 300 nucleosomes using all atom molecular dynamics (MD) to investigate nucleosome energetics, structure and dynamics as a function of DNA sequence. The 336 nuclesomes modeled represent 16 segments of DNA, one from each chromosome of Saccharomyces Cerevisiae. Each segment contains the highest occupied and least variable nucleosome positioning sequence for the parent chromosome. Each segment is 167bp long and includes: the observed 147bp positioning sequence and 10bp on each side. Every 147bp subsequence of each segment is threaded onto the octamer core as observed in xray structure 1kx5 and solvated, yielding 21 mononucleosomes for each of the 16 segments. Each mononucleosome is subjected to MD simulation. Here we report how the simulations are accomplished and focus attention on the segments for which all 21 mononucleosomes have been simulated for at least 20ns. Helical parameter analysis is used to investigate variations in structure and dynamics of nucleosomal DNA as a function of sequence. Results are compared to values obtained from a systematic MD study of nearest-neighbor effects on base pair step conformations and fluctuations of free DNA. The goal is to quantify variations in structure, dynamics and energetics of nucleosomal DNA as a function of sequence.

Testing the Use of Implicit Solvent in the Molecular Dynamics Modelling of DNA Flexibility

DNA flexibility controls packaging, looping and in some cases sequence specific protein binding. Molecular dynamics simulations carried out with a computationally efficient implicit solvent model are potentially a powerful tool for studying larger DNA molecules than can be currently simulated when water and counterions are represented explicitly. In this work we compare DNA flexibility at the base pair step level modelled using an implicit solvent model to that previously determined from explicit solvent simulations and database analysis. Although much of the sequence dependent behaviour is preserved in implicit solvent, the DNA is considerably more flexible when the approximate model is used. In addition we test the ability of the implicit solvent to model stress induced DNA disruptions by simulating a series of DNA minicircle topoisomers which vary in size and superhelical density. When compared with previously run explicit solvent simulations, we find that while the levels of DNA denaturation are similar using both computational methodologies, the specific structural form of the disruptions is different.

Nucleic‐acid structural deformability deduced from anisotropic displacement parameters

The growing numbers of very well resolved nucleic-acid crystal structures with anisotropic displacement parameters provide an unprecedented opportunity to learn about the natural motions of DNA and RNA. Here we report a new Monte-Carlo approach that takes direct account of this information to extract the distortions of covalent structure, base pairing, and dinucleotide geometry intrinsic to regularly organized double-helical molecules. We present new methods to test the validity of the anisotropic parameters and examine the apparent deformability of a variety of structures, including several A, B, and Z DNA duplexes, an AB helical intermediate, an RNA, a ligand-DNA complex, and an enzyme-bound DNA. The rigid-body parameters characterizing the positions of the bases in the structures mirror the mean parameters found when atomic motion is taken into account. The base-pair fluctuations intrinsic to a single structure, however, differ from those extracted from collections of nucleic-acid structures, although selected base-pair steps undergo conformational excursions along routes suggested by the ensembles. The computations reveal surprising new molecular insights, such as the stiffening of DNA and concomitant separation of motions of contacted nucleotides on opposite strands by the binding of Escherichia coli endonuclease VIII, which suggest how the protein may direct enzymatic action.

Structural Stability of Tandemly Occurring Noncanonical Basepairs within Double Helical Fragments: Molecular Dynamics Studies of Functional RNA

Noncanonical basepairs have gained importance over the past few years because of their various functions in RNA biochemistry. These basepairs appear quite frequently in different double helical stems also, but whether they are stabilized by contextual pressure or act as seeds of folding is not yet clear. We have used all-atom molecular dynamics simulations to characterize the stability and functional features of a few noncanonical basepairs within two RNA double helical fragments obtained from ribosome crystal structures. It is anticipated that the noncanonical basepairs would open up spontaneously if they had appeared due to contextual pressure. However, we have found from MD simulations that the noncanonical basepairs occurring in tandem at the central regions of double helical stretches are quite stable. Analysis of basepairing parameters carried out in terms of H-bonding edge-specific axis system indicates that dynamics of the noncanonical basepairs are very similar to those of the canonical ones. The stacking parameters for dinucleotide steps consisting of noncanonical basepairs are rather unusual, but the variability patterns indicate their significant stability. The stacking free-energy values as presumed from the distributions of structural parameters also appear to be similar for both canonical and noncanonical basepair steps.

Mechanism of DNA Recognition by the Restriction Enzyme EcoRV

EcoRV, a restriction enzyme in Escherichia coli, destroys invading foreign DNA by cleaving it at the center step of a GATATC sequence. In the EcoRV–cognate DNA crystallographic complex, a sharp kink of 50° has been found at the center base-pair step (TA). Here, we examine the interplay between the intrinsic propensity of the cognate sequence to kink and the induction by the enzyme by performing all-atom molecular dynamics simulations of EcoRV unbound and interacting with three DNA sequences: the cognate sequence, GATATC (TA); the non-cognate sequence, GAATTC (AT); and with the cognate sequence methylated on the first adenine GACH3TATC (TA-CH3). In the unbound EcoRV, the cleft between the two C-terminal subdomains is found to be open. Binding to AT narrows the cleft and forms a partially bound state. However, the intrinsic bending propensity of AT is insufficient to allow tight binding. In contrast, the cognate TA sequence is easier to bend, allowing specific, high-occupancy hydrogen bonds to form in the complex. The absence of cleavage for this methylated sequence is found to arise from the loss of specific hydrogen bonds between the first adenine of the recognition sequence and Asn185. On the basis of the results, we suggest a three-step recognition mechanism. In the first step, EcoRV, in an open conformation, binds to the DNA at a random sequence and slides along it. In the second step, when the two outer base pairs, GAxxTC, are recognized, the R loops of the protein become more ordered, forming strong hydrogen-bonding interactions, resulting in a partially bound EcoRV–DNA complex. In the third step, the flexibility of the center base pair is probed, and in the case of the full cognate sequence the DNA bends, the complex strengthens and the protein and DNA interact more closely, allowing cleavage.

Corrections and Clarifications

News of the Week: “Appearances can deceive, even with standard reagents” by H. Xin (22 May, p. [997][1]). The reference to a survey conducted with the biweekly magazine Science News should have made clear that the magazine is a Chinese publication unrelated to the U.S. magazine of the same name. Reports: “Remeasuring the double helix” by R. S. Mathew-Fenn et al. (17 October 2008, p. [446][1]). In Fig. 3B and fig. S4, a bending-derived variance estimate was added to the observed variances; it should have been subtracted from the observed variances. The corrected figures show the raw, experimentally observed variances. A corrected version of Fig. 3B and one sentence in the text are provided here. In the supporting online material, similar corrections have been made to fig. S4 and its caption. We thank N. Becker for pointing out these mistakes. ![Figure][1] (B) Observed variance in nanocrystal-nanocrystal separation distance of end-labeled duplexes (circles) and internally labeled duplexes (triangles), plotted with respect to the number of intervening DNA base-pair steps. The variance predictions for an ideal elastic rod with a stretching modulus of 1000 pN (the value measured in single-molecule stretching experiments) are shown (dashed black line) and deviate grossly from the data. A linear relationship between variance and base-pair steps (dashed cyan line, two variables, R 2 = 0.868) is expected if the stretching of base-pair steps is uncorrelated along the DNA duplex (24) . Alternatively, a quadratic relationship (solid black line, two variables, R 2 = 0.989) should hold if the DNA stretches cooperatively. The quadratic fit indicates that each base-pair step contributes 0.21 A of standard deviation to the end-to-end length of a duplex. The y intercept of 5.8 A2 corresponds to variance arising from experimental factors. The variance data points derive from the Gaussian curves in Fig. 2B. The uncertainties in the variance values are estimated to be ±6.6%, based on the standard deviation of repeated measurements for the 25-bp duplex at independent beamlines and with independently prepared samples (fig. S3). The fifth sentence of the third paragraph on page 448 should read, “The data fit a quadratic dependence to within this measurement error (black line; χ2 = 9.95 with 7 degrees of freedom; P = 0.19), but not to a linear dependence (cyan dashed line; χ2 = 62.5 with 7 degrees of freedom; P = 4.8 × 10−11).” [1]: pending:yes

Origins of Specificity in Protein-DNA Recognition

Specific interactions between proteins and DNA are fundamental to many biological processes. In this review, we provide a revised view of protein-DNA interactions that emphasizes the importance of the three-dimensional structures of both macromolecules. We divide protein-DNA interactions into two categories: those when the protein recognizes the unique chemical signatures of the DNA bases (base readout) and those when the protein recognizes a sequence-dependent DNA shape (shape readout). We further divide base readout into those interactions that occur in the major groove from those that occur in the minor groove. Analogously, the readout of the DNA shape is subdivided into global shape recognition (for example, when the DNA helix exhibits an overall bend) and local shape recognition (for example, when a base pair step is kinked or a region of the minor groove is narrow). Based on the >1500 structures of protein-DNA complexes now available in the Protein Data Bank, we argue that individual DNA-binding proteins combine multiple readout mechanisms to achieve DNA-binding specificity. Specificity that distinguishes between families frequently involves base readout in the major groove, whereas shape readout is often exploited for higher resolution specificity, to distinguish between members within the same DNA-binding protein family.

55 Association of mammographic density with selected nutrients in Norwegian women

XPD-like helicases constitute a prominent DNA helicase family critical for many aspects of genome maintenance. These enzymes share a unique structural feature, an auxiliary domain stabilized by an iron-sulphur (FeS) cluster, and a 5′–3′ polarity of DNA translocation and duplex unwinding. Biochemical analyses alongside two single-molecule approaches, total internal reflection fluorescence microscopy and high-resolution optical tweezers, have shown how the unique structural features of XPD helicase and its specific patterns of substrate interactions tune the helicase for its specific cellular function and shape its molecular mechanism. The FeS domain forms a duplex separation wedge and contributes to an extended DNA binding site. Interactions within this site position the helicase in an orientation to unwind the duplex, control the helicase rate, and verify the integrity of the translocating strand. Consistent with its cellular role, processivity of XPD is limited and is defined by an idiosyncratic stepping kinetics. DNA duplex separation occurs in single base pair steps punctuated by frequent backward steps and conformational rearrangements of the protein–DNA complex. As such, the helicase in isolation mainly stabilizes spontaneous base pair opening and exhibits a limited ability to unwind stable DNA duplexes. The presence of a cognate ssDNA binding protein converts XPD into a vigorous helicase by destabilizing the upstream dsDNA as well as by trapping the unwound strands. Remarkably, the two proteins can co-exist on the same DNA strand without competing for binding. The current model of the XPD unwinding mechanism will be discussed along with possible modifications to this mechanism by the helicase interacting partners and unique features of such bio-medically important XPD-like helicases as FANCJ (BACH1), RTEL1 and CHLR1 (DDX11).

DNA Architecture, Deformability, and Nucleosome Positioning

The positioning of DNA on nucleosomes is critical to both the organization and expression of the genetic message. Here we focus on DNA conformational signals found in the growing library of known high-resolution core-particle structures and the ways in which these features may contribute to the positioning of nucleosomes on specific DNA sequences. We survey the chemical composition of the protein-DNA assemblies and extract features along the DNA superhelical pathway—the minor-groove width and the deformations of successive base pairs—determined with reasonable accuracy in the structures. We also examine the extent to which the various nucleosome core-particle structures accommodate the observed settings of the crystallized sequences and the known positioning of the high-affinity synthetic ‘601’ sequence on DNA. We ‘thread’ these sequences on the different structural templates and estimate the cost of each setting with knowledge-based potentials that reflect the conformational properties of the DNA base-pair steps in other high-resolution protein-bound complexes.

Evaluation of Elastic Rod Models with Long Range Interactions for Predicting Nucleosome Stability

The ability of a dinucleotide-step based elastic-rod model of DNA to predict nucleosome binding free energies is investigated using four available sets of elastic parameters. We compare the predicted free energies to experimental values derived from nucleosome reconstitution experiments for 84 DNA sequences. Elastic parameters (conformation and stiffnessess) obtained from MD simulations are shown to be the most reliable predictors, as compared to those obtained from analysis of base-pair step melting temperatures, or from analysis of x-ray structures. We have also studied the effect of varying the folded conformation of nucleosomal DNA by means of our Fourier filtering knock-out and knock-in procedure. This study confirmed the above ranking of elastic parameters, and helped to reveal problems inherent in models using only a local elastic energy function. Long-range interactions were added to the elastic-rod model in an effort to improve its predictive ability. For this purpose a Debye-Huckel energy term with a single, homogenous point charge per base- pair was introduced. This term contains only three parameters,—its weight relative to the elastic energy, the Debye screening length, and a minimum sequence distance for including pairwise interactions between charges. After optimization of these parameters, our Debye-Huckel term is attractive, and yields the same level of correlation with experiment (R = 0.75) as was achieved merely by varying the nucleosomal shape in the elastic-rod model. We suggest this result indicates a linker DNA—histone attraction or, possibly, entropic effects, that lead to a stabilization of a nucleosome away from the ends of DNA segments longer than 147 bp. Such effects are not accounted for by a localized elastic energy model.

The 5-Methyl Group in Thymine Dynamically Influences the Structure of A-Tracts in DNA at the Local and Global Level

DNA sequences containing a stretch of several A:T basepairs without a 5'-TA-3' step are known as A-tracts and have been the subject of extensive investigation because of their unique structural features such as a narrow minor groove and their crucial role in several biological processes. One of the aspects under investigation has been the influence of the 5-methyl group of thymine on the properties of A-tracts. Detailed molecular dynamics simulation studies of the sequences d(CGCAAAUUUGCG) and d(CGCAAATTTGCG) indicate that the presence of the 5-methyl group in thymine increases the frequency of a narrow minor groove conformation, which could facilitate its specific recognition by proteins, and reduce its susceptibility to cleavage by DNase I. The bias toward a wider minor groove in the absence of the thymine 5-methyl group is a static structural feature. Our results also indicate that the presence of the thymine 5-methyl group is necessary for calibrating the backbone conformation and the basepair and dinucleotide step geometry of the core A-tract as well as the flanking CA/TG and the neighboring GC/GC steps, as observed in free and protein-bound DNA. As a consequence, it also fine-tunes the curvature of the longer DNA fragment in which the A-tract is embedded.

Changes in Thermodynamic Properties of DNA Base Pairs in Protein-DNA Recognition

The mechanism of protein-DNA recognition, particularly the induced fit mechanism, is poorly understood due to ineffective analysis of the protein-DNA complex crystal structures. It is expected that upon protein binding the DNA becomes structurally more rigid. However, a previous analysis (W.K. Olson, A. A. Gorin, X. Lu, L. M. Hock and V. Zhurkin, Proc. Natl. Acad. Sci. USA, 95, 11163 (1998)) indicates increase in the flexibility of the DNA segment complexed with protein. We have considered an ensemble of configurations from crystallographic data of the TBP-TATA box complex structures under a given thermodynamic condition. Analysis of the ensemble of structures of this complex indicates that the DNA deforms significantly to form specific hydrogen bonds and as a consequence, its structure attains more rigidity. We calculate the free energy profiles in term of the DNA base pair (bp) step parameters via the binding patterns in the ensemble of the given complex, and for free DNA bp steps as well. The rigidities estimated from these free energies for small deformations around the minimum indicate enhanced structural rigidities of DNA upon complexation with protein. Further, the changes in the thermodynamic properties of the bp steps upon complex formation have been estimated from the two sets of free energy profiles. These results indicate differential role played by different bp steps in the thermodynamic stabilization of the complex.

The mechanism of the translocation step in DNA replication by DNA polymerase I: a computer simulation analysis.

High-fidelity DNA polymerases copy DNA rapidly and accurately by adding correct deoxynucleotide triphosphates to a growing primer strand of DNA. Following nucleotide incorporation, a series of conformational changes translocate the DNA substrate by one base pair step, readying the polymerase for the next round of incorporation. Molecular dynamics simulations indicate that the translocation consists globally of a polymerase fingers-opening transition, followed by the DNA displacement and the insertion of the template base into the preinsertion site. They also show that the pyrophosphate release facilitates the opening transition and that the universally conserved Y714 plays a key role in coupling polymerase opening to DNA translocation. The transition involves several metastable intermediates in one of which the O helix is bent in the vicinity of G711. Completion of the translocation appears to require a gating motion of the O1 helix, perhaps facilitated by the presence of G715. These roles are consistent with the high level of conservation of Y714 and the two glycine residues at these positions. It is likely that a corresponding mechanism is applicable to other polymerases.

Insights from the structure of a smallpox virus topoisomerase-DNA transition state mimic.

Poxviruses encode their own type IB topoisomerases (TopIBs), which release superhelical tension generated by replication and transcription of their genomes. To investigate the reaction catalyzed by viral TopIBs, we have determined the structure of a variola virus topoisomerase-DNA complex trapped as a vanadate transition state mimic. The structure reveals how the viral TopIB enzymes are likely to position the DNA duplex for ligation following relaxation of supercoils and identifies the sources of friction observed in single-molecule experiments that argue against free rotation. The structure also identifies a conformational change in the leaving group sugar that must occur prior to cleavage and reveals a mechanism for promoting ligation following relaxation of supercoils that involves an Asp-minor groove interaction. Overall, the new structural data support a common catalytic mechanism for the TopIB superfamily but indicate distinct methods for controlling duplex rotation in the small versus large enzyme subfamilies.

Applications of VDNA from Basic Geometry to Chromatin Folding

We recently introduced VDNA(1), a plugin for VMD, that allows users to construct arbitrarily complex models of double stranded DNA. VDNA is preinstalled in VMD 1.8.7 and has a number of predefined mathematical expressions that allow for investigation of the complex relations between the DNA base pair step parameters (Tilt, Roll, Twist, Shift, Slide, Rise) and spatial conformation. VDNA is capable of producing static images, ensembles and trajectories. Using VDNA we demonstrate some of the geometric relations between the DNA step parameters and Cartesian coordinates that do not readily yield to intuition. We also consider a number of biologically motivated models including: a model of thermal fluctuations in linear DNA, comparison of a Torsion Helix and a Shear Helix model of the nucleosome(2), and models for regular and irregularly folded chromatin. Finally we demonstrate how VDNA can be used to convert nucleosome footprints from a chromatin map into a three dimensional chromatin fold. Such folding provides an immediate answer as to whether or not the footprints yield a conformation that is sterically allowed or if extra-nucleosomal proteins, non-canonical nucleosome conformations or thermal effects should also be considered. The most up to date version of VDNA is available from http://dna.ccs.tulane.edu/vdna. Acknowledgement: This work supported in part by NIH R01-GM076356. (1) T. C. Bishop. VDNA: The Virtual DNA plug-in for VMD, Bioinformatics (2009). (2) T. C. Bishop. Geometry of the nucleosomal DNA superhelix, Biophys. J. 95, 1007-1017 (2008).

NMR structural studies on the covalent DNA binding of a pyrrolobenzodiazepine–naphthalimide conjugate

The DNA binding of a naphthalimide drug conjugated through a piperazine containing linker with a pyrrolo[2,1-c][1,4]benzodiazepine (PBD) to d(AACAATTGTT)(2) was studied by a combination of high-resolution (1)H and (31)P 2D NMR spectroscopy and restrained molecular dynamics calculations in explicit solvent. The bifunctional hybrid binds with its PBD moiety covalently linked within the minor groove to a guanine with an S stereochemistry at its covalent linkage site at C11 and a 5'-orientation of its A-ring carrying the linker with the naphthalimide ligand. The latter inserts from the minor groove between an A-A.T-T base pair step resulting in an opposite buckling of the base pairs at the intercalation site and duplex unwinding at adjacent internucleotide steps. There is NMR spectroscopic evidence that the naphthalimide undergoes a ring-flip motion with exchange rates slow to intermediate on the chemical shift time scale at ambient temperatures.

How stiff is DNA?

The natural stiffness of DNA, which contributes to the interactions of the many proteins involved in its biological processing and packaging, also plays an important role in modern nanotechnology. Here we report new Monte-Carlo simulations of deformable DNA molecules of potential utility in understanding the behavior of the long, double-helical polymer in the tight confines of a cell and in the design of novel nanomaterials and molecular devices. We directly determine the fluctuations in end-to-end extension associated with the conventional elastic-rod representation of DNA and with more realistic models that take account of the precise deformability of the constituent base-pair steps. Notably, the variance of end-to-end distance shows a quadratic increase with chain length in short chains of both types. We also consider the contributions to chain extension from the chemical linkages used to attach small molecular probes to DNA. The distribution of computed distances is sensitive to the intrinsic structure and allowed deformations of the tether. Surprisingly, the enhancement in end-to-end variance associated with the presence of the probe depends upon chain length, even when the probe is rigidly connected to DNA. We find that the elastic rod model of DNA in combination with a slightly fluctuating tether accounts satisfactorily for the distributions of end-to-end distances extracted from the small-angle X-ray scattering of gold nanocrystals covalently linked to the ends of short DNAs. There is no need to introduce additional structural fluctuations to reproduce the measured uptake in end-to-end fluctuations with chain length.

Two perspectives on the twist of DNA.

Because of the double-helical structure of DNA, in which two strands of complementary nucleotides intertwine around each other, a covalently closed DNA molecule with no interruptions in either strand can be viewed as two interlocked single-stranded rings. Two closed space curves have long been known by mathematicians to exhibit a property called the linking number, a topologically invariant integer, expressible as the sum of two other quantities, the twist of one of the curves about the other, and the writhing number, or writhe, a measure of the chiral distortion from planarity of one of the two closed curves. We here derive expressions for the twist of supercoiled DNA and the writhe of a closed molecule consistent with the modern view of DNA as a sequence of base-pair steps. Structural biologists commonly characterize the spatial disposition of each step in terms of six rigid-body parameters, one of which, coincidentally, is also called the twist. Of interest is the difference in the mathematical properties between this step-parameter twist and the twist of supercoiling associated with a given base-pair step. For example, it turns out that the latter twist, unlike the former, is sensitive to certain translational shearing distortions of the molecule that are chiral in nature. Thus, by comparing the values for the two twists for each step of a high-resolution structure of a protein-DNA complex, we may be able to determine how the binding of various proteins contributes to chiral structural changes of the DNA.

Comparison of Intrinsic Stacking Energies of Ten Unique Dinucleotide Steps in A-RNA and B-DNA Duplexes. Can We Determine Correct Order of Stability by Quantum-Chemical Calculations?

High level ab initio methods have been used to study stacking interactions in ten unique base pair steps both in A-RNA and in B-DNA duplexes. The protocol for selection of geometries based on molecular dynamics (MD) simulations is proposed, and its suitability is demonstrated by comparison with stacking in steps at fiber diffraction geometries. It is shown that fiber diffraction geometries are not sufficiently accurate for interaction energy calculations. In addition, the protocol for selection of geometries based on MD simulations allows for the evaluation of the variability of the intrinsic stacking energies along the MD trajectories. The uncertainty in stacking energies (difference between the most and least stable geometry) due to the dynamical nature of systems can be, in some cases, as large as 3.0 kcal x mol(-1), which is almost 50% of the actual sequence dependence of base stacking energies (the energy difference between the most and least stable sequences). Thus, assessing the relative magnitude of the gas phase stacking energy using a single geometry for each sequence is insufficient to obtain an unambiguous order of gas phase stacking energies in canonical double helices. Though the ordering of ten unique dinucleotide steps cannot be definitive, some general conclusions were drawn. The stacking energies of base pair steps in A-RNA are more evenly separated compared to B-DNA, and their ordering is less sensitive to the dynamics of the system compared to be B-DNA. The most stable step both in B-DNA and A-RNA is the GC/GC [corrected] step that is well separated from the second most stable step CG/CG. [corrected] Also the least stable step (the CC/GG step) is well separated from the rest of the structures. The calculations further show that B-DNA stacking is favorable only marginally (on average by 1.14 kcal x mol(-1) per base pair step) over A-RNA stacking, and this difference vanishes after subtracting the stabilizing van der Waals effect of the thymine 5-methyl group that is absent in RNA. Basically, no correlation between the sequence dependence of gas phase stacking energies and the sequence dependence of DeltaG degrees(37) free energies used in nearest-neighbor models was found either for B-DNA or for A-RNA. This reflects the complexity of the balance of forces that are responsible for the sequence dependence of thermodynamics stability of nucleic acids, which masks the effect of the intrinsic interactions between the stacked base pairs.

3DNALandscapes: a database for exploring the conformational features of DNA

3DNALandscapes, located at: http://3DNAscapes.rutgers.edu, is a new database for exploring the conformational features of DNA. In contrast to most structural databases, which archive the Cartesian coordinates and/or derived parameters and images for individual structures, 3DNALandscapes enables searches of conformational information across multiple structures. The database contains a wide variety of structural parameters and molecular images, computed with the 3DNA software package and known to be useful for characterizing and understanding the sequence-dependent spatial arrangements of the DNA sugar-phosphate backbone, sugar-base side groups, base pairs, base-pair steps, groove structure, etc. The data comprise all DNA-containing structures—both free and bound to proteins, drugs and other ligands—currently available in the Protein Data Bank. The web interface allows the user to link, report, plot and analyze this information from numerous perspectives and thereby gain insight into DNA conformation, deformability and interactions in different sequence and structural contexts. The data accumulated from known, well-resolved DNA structures can serve as useful benchmarks for the analysis and simulation of new structures. The collective data can also help to understand how DNA deforms in response to proteins and other molecules and undergoes conformational rearrangements.