Thermodynamic Properties Of DNA Research Articles

Unveiled electric profiles within hydrogen bonds suggest DNA base pairs with similar bond strengths.

Electrical forces are the background of all the interactions occurring in biochemical systems. From here and by using a combination of ab-initio and ad-hoc models, we introduce the first description of electric field profiles with intrabond resolution to support a characterization of single bond forces attending to its electrical origin. This fundamental issue has eluded a physical description so far. Our method is applied to describe hydrogen bonds (HB) in DNA base pairs. Numerical results reveal that base pairs in DNA could be equivalent considering HB strength contributions, which challenges previous interpretations of thermodynamic properties of DNA based on the assumption that Adenine/Thymine pairs are weaker than Guanine/Cytosine pairs due to the sole difference in the number of HB. Thus, our methodology provides solid foundations to support the development of extended models intended to go deeper into the molecular mechanisms of DNA functioning.

Editorial: Recent Advances of Epigenetics in Crop Biotechnology.

Editorial: Recent Advances of Epigenetics in Crop Biotechnology.

Crop epigenetics and the molecular hardware of genotype × environment interactions.

Crop plants encounter thermal environments which fluctuate on a diurnal and seasonal basis. Future climate resilient cultivars will need to respond to thermal profiles reflecting more variable conditions, and harness plasticity that involves regulation of epigenetic processes and complex genomic regulatory networks. Compartmentalization within plant cells insulates the genomic central processing unit within the interphase nucleus. This review addresses the properties of the chromatin hardware in which the genome is embedded, focusing on the biophysical and thermodynamic properties of DNA, histones and nucleosomes. It explores the consequences of thermal and ionic variation on the biophysical behavior of epigenetic marks such as DNA cytosine methylation (5mC), and histone variants such as H2A.Z, and how these contribute to maintenance of chromatin integrity in the nucleus, while enabling specific subsets of genes to be regulated. Information is drawn from theoretical molecular in vitro studies as well as model and crop plants and incorporates recent insights into the role epigenetic processes play in mediating between environmental signals and genomic regulation. A preliminary speculative framework is outlined, based on the evidence of what appears to be a cohesive set of interactions at molecular, biophysical and electrostatic level between the various components contributing to chromatin conformation and dynamics. It proposes that within plant nuclei, general and localized ionic homeostasis plays an important role in maintaining chromatin conformation, whilst maintaining complex genomic regulation that involves specific patterns of epigenetic marks. More generally, reversible changes in DNA methylation appear to be consistent with the ability of nuclear chromatin to manage variation in external ionic and temperature environment. Whilst tentative, this framework provides scope to develop experimental approaches to understand in greater detail the internal environment of plant nuclei. It is hoped that this will generate a deeper understanding of the molecular mechanisms underlying genotype × environment interactions that may be beneficial for long-term improvement of crop performance in less predictable climates.

Monte Carlo Simulation of Transcriptional Control in 6kbp DNA

Eukaryotic genes are regulated by gene-control regions such as enhancers and insulators. Enhancers are regulatory DNA sequences that can activate transcription of genes located at large distance. Insulators are regulatory DNA sequences that can inhibit transcription when they are located between an enhancer and a promoter. Recently, it has been reported that the enhancer is in physical proximity to the active genes in vivo with the intervening DNA looping out [1]. It has also been indicated that insulators may modulate the enhancer-promoter interactions by interacting with each other and facilitating the formation of chromatin or the DNA loop domains [2, 3]. In this way, importance of the DNA or chromatin conformation at transcriptional control has begun to be recognized. However, by only using molecular biological techniques, we can hardly see the relationship between the atomic level information of DNA and the transcriptional control. Thus, in order to investigate effects of atomistic and thermodynamic properties of DNA on the enhancer-blocking activity, we performed Monte Carlo simulation with the wormlike chain model of DNA. Results are consistent with the experimental data of Ameres et al. [3], showing that the amount of gene expression is proportional to the relative proximity probability between an enhancer and a promoter. Furthermore, our results suggest that the proximity probability between these two elements is reduced because the stretching and bending energies increase when the formation of DNA loop domains modulates the enhancer-promoter interactions.[1] B. Tolhuis et al.,Mol. Cell, 10, 1453 (2002).[2] H.N. Cai and P. Shen, Science, 291, 493 (2001).[3] S.L. Ameres et al.,EMBO J. 24, 358 (2005).

Solving traveling salesman problems with DNA molecules encoding numerical values

We introduce a DNA encoding method to represent numerical values and a biased molecular algorithm based on the thermodynamic properties of DNA. DNA strands are designed to encode real values by variation of their melting temperatures. The thermodynamic properties of DNA are used for effective local search of optimal solutions using biochemical techniques, such as denaturation temperature gradient polymerase chain reaction and temperature gradient gel electrophoresis. The proposed method was successfully applied to the traveling salesman problem, an instance of optimization problems on weighted graphs. This work extends the capability of DNA computing to solving numerical optimization problems, which is contrasted with other DNA computing methods focusing on logical problem solving.

NMR structure of a gemcitabine-substituted model Okazaki fragment.

Gemcitabine (2'-deoxy-2',2'-difluorodeoxycytidine; dFdC) is a potent anticancer drug that exerts cytotoxic activity, in part, through incorporation of the nucleoside triphosphate dFdCTP into DNA and perturbations to DNA-mediated processes. The structure of a model Okazaki fragment containing a single dFdC substitution, [GEM], was determined using NMR spectroscopy and restrained molecular dynamics to understand structural distortions that may be induced in replicating DNA resulting from dFdC substitution. The electrostatic surface of [GEM] was also computed to determine how the geminal difluoro group of dFdC perturbs DNA electrostatics. The stability of [GEM] was investigated using temperature-dependent UV spectroscopy. dFdC adopted a C3'-endo conformation in [GEM] and decreased the melting temperature of the duplex by 4.3 degrees C. dFdC substitution did not decrease helical stacking among adjacent purines in the DNA duplex region. dFdC substitution substantially altered the electrostatic properties of the model Okazaki fragment, with increased electron density in the vicinity of the geminal difluoro group. The results are consistent with dFdC substitution altering the structural, electrostatic, and thermodynamic properties of DNA and interfering in DNA-mediated processes. Interference in DNA-mediated processes due to dFdC substitution likely contributes to the anticancer activity of dFdC.

Structural and thermodynamic properties of DNA uncover different evolutionary histories.

We propose an index of DNA homogeneity (IDH) based on a binary distribution model that quantifies structural and thermodynamic aggregates present in DNA primary structures. Extensive analysis of sequence databases with the IDH uncovers significant constraints on DNA sequence other than those derived from codon usage or protein function. This index clearly distinguishes between organisms of different evolutive origins and places them in disjoint domains of DNA sequence space.

The role of metals in the initiation and the development of malignant transformation

The concentration of metal ions in DNA molecules of a malignant growth is higher than in the norm. The genetic consequences appearing in the DNA molecule as a result of mutations of certain type and of the penetration of metal ions into its structure are considered. The present state of investigation of metal influence upon the structural and thermodynamic properties of DNA, histones and chromatin in the norm and in the malignant transformation is considered. Metals endogen-bound with DNA leave the latter susceptible to the influence of X-rays and certain antitumor preparations. The change in the physical properties (electronic density distribution, thermostability) of DNA, histones and their complexes in the case of cancer are interpreted from the view-point of the influence of endogen-bound metal ions on the structure and cooperative properties of these molecules. The change of dipole moments of DNA sites after the incorporation of certain bivalent metal ions has been established using computation methods. The change in histone structure under the influence of metals has been demonstrated experimentally using X-ray diffraction and spectral methods. The predicted changes in chromatin structure and thermodynamic properties under the influence of metal ions have been confirmed by direct calorimetric and spectral investigations. A general analysis of the available data is given. The program of investigations required in this field is laid out.