Deoxyribonucleic Acid Double Helix Research Articles

Classifying promoters by interpreting the hidden information of DNA sequences for disease prediction in clinical laboratories using Gaussian decision boundary estimation

A promoter is a brief stretch of DNA (100–1,000 bp) where RNA polymerase starts to transcribe a gene. A DNA (Deoxyribonucleic Acid) base pair is a fundamental unit of DNA structure and represents the pairing of two complementary nucleotide bases within the DNA double helix. The four DNA nucleotide bases are adenine (A), thymine (T), cytosine (C), and guanine (G). DNA base pairs are the building blocks of the DNA molecule, and their complementary pairing is central to the storage and transmission of genetic information in all living organisms. Normally, a promoter is found at the 5′ end of the transcription initiation site or immediately upstream. Numerous human disorders, particularly diabetes, cancer, and Huntington’s disease, have been shown to have DNA promoter as their root cause. The scientific community has long been interested in learning crucial information about protein-coding genes. Finding the promoters is therefore the first step in finding genes in DNA sequences. The scientific world has always been attracted by the effort to glean crucial knowledge about protein-coding genes. Consequently, identifying promoters has emerged as an intriguing challenge that has caught the interest of numerous researchers in the field of bioinformatics. We proposed Gaussian Decision Boundary Estimation in machine learning models to detect transcription start sites (promoters) in the DNA sequences of a common bacteria, Escherichia coli. The best features are identified through a score-based function to select relevant nucleotides that are directly responsible for promoter recognition, in order maximise the models’ performance. The Gaussian Decision Boundary Estimation based support-vector-machine model is trained with these features and finds the best hyperplane that separates the data into different classes. Throughout this study, promoter regions could be identified with high accuracy 99.9% which is better compared to other state of art algorithms. The comparison of machine learning classification models is another major emphasis of this paper in order to identify the model that most accurately predicts DNA sequence promoters. It provides analysis for further biological research as well as precision medicine.

A theoretical study on the role of stability of cytosine and its tautomers in DNA (deoxyribonucleic acid), and investigation of interactions of Na+, K+, Mg2+, Ca2+, Zn2+ metal ions and OH radical with cytosine tautomers

In the present study, 21 cytosine tautomers were investigated so that some tautomers were reported for the first time in the gas phase and aqueous solution. C3 tautomer was the most stable tautomer in gas phase but C1 was the most stable structure in aqueous solution. The potential energy surface of all trajectories was determined for 21 tautomers and 22 transition states. Also, interactions of cytosine tautomers with Na+, K+, Mg2+, Ca2+ and Zn2+ metal ions were studied in gas phase and aqueous solution. Three types of interactions among metal ions and (N1 and O10), (N3 and O10) and (N3 and N9) of cytosine tautomers were investigated. The study of interaction energies of all complexes showed the stability of complexes in which interactions among Mg2+ and Zn2+ with tautomers were stronger than interactions among Ca2+, Na+ and K+ with tautomers, respectively. Some interactions of metal ions with cytosine tautomers made the most stable tautomers. So, the stability of rare tutomeric forms had a significant effect on stabilization of anomalous DNA (deoxyribonucleic acid) double helix and spontaneous mutations. Also, one of the most important causes of mutations in DNA (deoxyribonucleic acid) was the reaction of OH radical with nucleotide bases. So, interactions of OH radical with cytosine and its tautomers were investigated in gas phase and aqueous solution. Communicated by Ramaswamy H. Sarma

Understanding biochemistry: structure and function of nucleic acids.

Nucleic acids, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), carry genetic information which is read in cells to make the RNA and proteins by which living things function. The well-known structure of the DNA double helix allows this information to be copied and passed on to the next generation. In this article we summarise the structure and function of nucleic acids. The article includes a historical perspective and summarises some of the early work which led to our understanding of this important molecule and how it functions; many of these pioneering scientists were awarded Nobel Prizes for their work. We explain the structure of the DNA molecule, how it is packaged into chromosomes and how it is replicated prior to cell division. We look at how the concept of the gene has developed since the term was first coined and how DNA is copied into RNA (transcription) and translated into protein (translation).

Molecular Modeling of Indeno [1, 2-b] Quinoline-9, 11-Diones as Cytotoxic Agents.

Deoxyribonucleic acid (DNA) is an important molecular target for anti-cancer agents due to its involvement in gene expression and protein synthesis which are fundamental steps in cell division and growth. A number of antineoplastic agents interfere with DNA and hence disturb the cell cycle. Compounds including planar aromatic rings are privileged scaffolds in binding to DNA. This characteristic is mainly arisen from the fact that such structural feature may be appropriate to insert between the base pairs of the DNA double helix and produce relatively stable non-covalent complexes. Besides π-π stacking interactions, binding to the DNA molecule might be intensified through H-bond interactions of heterocyclic rings. In the present contribution, a series of experimentally validated cytotoxic indeno[1,2-b]quinoline-9,11-diones (1-12) and their aromatized analogues (13-21) developed in our group were subjected to docking and molecular dynamics simulations to elucidate their most probable binding modes with DNA.

Bright luminescence from pure DNA-curcumin-based phosphors for bio hybrid light-emitting diodes.

Recently, significant advances have occurred in the development of phosphors for bio hybrid light-emitting diodes (Bio-HLEDs), which have created brighter, metal-free, rare-earth phosphor-free, eco-friendly, and cost-competitive features for visible light emission. Here, we demonstrate an original approach using bioinspired phosphors in Bio-HLEDs based on natural deoxyribonucleic acid (DNA)-curcumin complexes with cetyltrimethylammonium (CTMA) in bio-crystalline form. The curcumin chromophore was bound to the DNA double helix structure as observed using field emission tunnelling electron microscopy (FE-TEM). Efficient luminescence occurred due to tightly bound curcumin chromophore to DNA duplex. Bio-HLED shows low luminous drop rate of 0.0551 s−1. Moreover, the solid bio-crystals confined the activating bright luminescence with a quantum yield of 62%, thereby overcoming aggregation-induced quenching effect. The results of this study herald the development of commercially viable large-scale hybrid light applications that are environmentally benign.

Interaction of antioxidant flavonoids with calf thymus DNA analyzed by spectroscopic and electrochemical methods

Mechanism of interaction of bioactive flavonoids, hesperitin (HES) and naringenin (NAR) with calf thymus deoxyribonucleic acid (DNA) was studied employing UV absorption, fluorescence, circular dichroism, melting temperature, fluorescence anisotropy and differential pulse voltammetric methods. The observed fluorescence quenching of DNA-ethidium bromide system by the flavonoid indicated the intercalative mode of binding between the flavonoid and DNA. Stern-Volmer plots have revealed the presence of static quenching mechanism. Binding and thermodynamic characteristics of interaction were evaluated. Melting temperature of DNA was found to be increased up to 5 °C in the presence of the flavonoid indicating the stabilization of DNA double helix upon binding. CD and fluorescence anisotropic results have revealed the conformational changes in DNA upon binding to the flavonoid. The observed positive shift in peak potential and decreased peak current of the flavonoid in the presence of DNA further supported the intercalative mode of binding.

Role of Surfactants in the Interaction of Dye Molecules in Natural DNA Polymers

Solutions and powders formed from salmon sperm deoxyribonucleic acid (DNA) reacted with the cationic surfactant cetyltrimethylammonium chloride (CTMA-Cl) incorporated fluorescent rhodamine molecules: anionic sulforhodamine 640 (SRh) or cationic/zwitterionic rhodamine 640 perchlorate (RhP). The role of the cationic surfactant in the interaction between rhodamine dye and DNA-surfactant molecules has been investigated in both solution and solid state using optical spectroscopy and electrophoresis. Unexpectedly, the dye molecules did not interact directly with DNA, rather the DNA double helix acted as a template for the interaction between dye molecules and CTMA in the DNA/CTMA complex. The SRh and RhP molecules yield different fluorescence characteristics with increasing DNA/CTMA amount, indicating different configurations between the CTMA ligands.

The interaction of native DNA with iron(III)- N, N′-ethylene-bis(salicylideneiminato)-chloride

The interaction between native calf thymus deoxyribonucleic acid (DNA) and Fe III- N, N ′-ethylene-bis (salicylideneiminato)-chloride, Fe(Salen)Cl, was investigated in aqueous solutions by UV–visible (UV–vis) absorption, circular dichroism (CD), thermal denaturation and viscosity measurements. The results obtained from CD, UV–vis and viscosity measurements exclude DNA intercalation and can be interpreted in terms of an electrostatic binding between the Fe(Salen) + cation and the phosphate groups of DNA. The trend of the UV–vis absorption band of the Fe(Salen)Cl complex at different ratios [DNA phosphate]/[Fe(Salen)Cl] and the large increase of the melting temperature of DNA in the presence of Fe(Salen)Cl, support the hypothesis of an external electrostatic interaction between the negatively charged DNA double helix and the axially stacked positively charged Fe(Salen) + moieties, analogously to what reported for a number of porphyrazines and metal–porphyrazine complexes interacting with DNA.

On the reaction of mutagenic aflatoxin B 1 oxide and benz[ a]pyrene diol oxide with guanine residue in DNA double helix

Theoretical calculation was performed to study the binding mechanism of intercalators to deoxyribonucleic acid (DNA) base pairs. The structures of intercalating complexes and ligand–DNA adducts of mutagenic aflatoxin B 1 8,9-oxide ( 1) and benz[ a]pyrene diol oxide ( 2) and the reactivity for S N2 type nucleophilic oxirane ring opening for 2 were investigated. Calculation clarified the following points: 1. The atomic contacts between two reaction sites (nucleophilic N2 or N7 nitrogen lone pair of guanine residue in DNA base pairs and electrophilic carbon of three-membered oxirane ring in mutagenic 1 and 2) are considerably short, suggesting that intercalation makes two reaction sites closer and consequently promotes the covalent binding of mutagens to guanine base. 2. In the adducts of 1 and 2 with DNA double helix, large planar coumarin ring of 1 exists in the major groove of double helix and planar aromatic ring system of 2 in minor groove of it. The regularly layered structure of B type DNA double helix is not distorted in the adduct of 1, however, the double helix is considerably distorted in the adduct of 2. 3. Two mutagens probably intercalate into DNA base pairs and make stable complexes which are followed by transition structures (TSs) for covalent binding. Judging from the activation energy (Δ E ≠) estimated to be 47.7 kcal/mol, the reactivity for covalent binding is considerably low, implying that intercalation must play an important role as precedent phenomena to covalent binding between bases and intercalators. Calculation suggests that the reactivity for S N2 type nucleophilic reaction itself (the stability of TS for covalent binding) is not so high, and therefore, the potency for mutagenesis might be attributing to the formation of stable (and consequently) long standing intercalating complex and stable ligand–DNA adduct.

Electronic-structure-based molecular-dynamics method for large biological systems: Application to the 10 basepair poly(dG)⋅poly(dC) DNA double helix

Combining several recently developed theoretical techniques, we have developed an electronic-structure-based method for performing molecular-dynamical simulations of large biological systems. The essence of the method can be summarized in three points: (i) There are two energy scales in the Hamiltonian and each is treated differently---the strong intramolecular interactions are treated within approximate density-functional theory, whereas the weak intermolecular interactions (e.g., hydrogen bonds) are described within a simple theory that accounts for Coulomb, exchange, and hopping interactions between the weakly interacting fragments. (ii) A localized basis of atomic states is used, yielding sparse Hamiltonian and overlap matrices. (iii) The total energies and forces from the sparse Hamiltonian and overlap matrices are solved using a linear scaling technique to avoid the ${\mathrm{N}}^{3}$ scaling problem of standard electronic structure methods. As an initial benchmark and test case of the method, we performed calculations of a deoxyribonucleic acid (DNA) double-helix poly(dG)\ensuremath{\cdot}poly(dC) segment containing ten basepairs, with a total of 644 atoms. By a dynamical simulation, we obtained the minimum-energy geometry and the electronic structure of this DNA dehydrated segment, as well as the full dynamical matrix corresponding to the relaxed structure. The vibrational data and energy band gap obtained compare qualitatively well with previous experimental data and other theoretical results.

Time domain reflectometry techniques used as an analytical tool to investigate water molecules bound to solid-state deoxyribonucleic acid (DNA)

In this study, the dielectric properties of ion-reduced Na- and Mg-DNA have been investigated over a frequency range 105–1010 Hz as a function of hydration and temperature, using time domain reflectometry techniques. Three distinct dispersions have been indentified, centred at frequencies of ca. 107, 108 and 1010 Hz, respectively. The lowest frequency dispersion has been attributed to localised relaxation of counter-ions associated with the phosphate groups of the DNA double helix (G. P. Archer, S. Bone and R. Pethig, J. Mol. Electron., 1990, 6, 199). The highest frequency dispersion is thought to be the result of the rotational relaxation of DNA-bound water molecules. The origin of the dispersion centred in the 108 Hz region is discussed in terms of a number of possible relaxation processes.

Covalent immobilization of DNA onto glassy carbon electrodes

AbstractDenatured calf thymus deoxyribonucleic acid (DNA) and synthetic poly(dG)poly(dC) have been covalently immobilized onto oxidized glassy carbon electrode surfaces using the water‐soluble carbodiimide, 1‐(3‐dimethylaminopropyl)‐3‐ethylcarbodiimide. Immobilized DNA has been detected using the complex Co(bpy) (bpy = 2,2′ ‐bipyridine). This complex has a reversible one‐electron oxidation (Eo′ = 0.33 V versus SHE), binds electrostatically in the minor groove of the DNA double helix, and preconcentrates at the surface of the DNA‐modified electrode prior to a voltammetric scan. Our cyclic voltammetric data indicate that larger Co(bpy) signals are observed at low ionic strength; this is consistent with the larger association constants obtained for the binding of Co(bpy) with calf thymus DNA at low ionic strength. While immobilizations were attempted for four species, poly(dA)poly(dT), native calf thymus DNA, denatured calf thymus DNA, and poly(dG)poly(dC), only the last two species could be successfully immobilized with the carbodiimide procedure; these results show that guanosine and/or cytosine bases will bind covalently to the o‐acylisourea on the glassy carbon surface.

Left-handed deoxyribonucleic acid double helix in solution.

Magnetic shielding constants were calculated for the synthetic deoxyribonucleic acid (DNA) double helix poly(dG-dC).poly(dG-dC) from the x, y, and z coordinates of Z-DNA of Rich and co-workers [Wang, A. H-J., Quigley, G. J., Kolpak, F. J., Crawford, J. L., van Boom, J. H., van der Marel, G., & Rich, A. (1979) Nature (London) 282, 680-686)] and B-DNA of Arnott & Hukins [Arnott, S., & Hukins, D. W. L. (1972) Biochem. Biophys. Res. Commun. 47, 1504-1509], taking into account the contribution to shielding from ring current effects and effects from the diamagnetic and paramagnetic components of the atomic magnetic anisotropy. Comparison of the calculated shielding values with the experimentally observed nuclear magnetic resonance shift data for poly(dG-dC).poly(dG-dC) in high salt solution shows striking agreement for Z-DNA and considerable deviation for B-DNA, indicating that this synthetic DNA double helix is high salt solution can assume the spatial configuration of the left-handed Z-DNA double helix known to occur in crystals.

Optical anisotropy of oriented deoxyribonucleic acid films of different water content

AbstractUltraviolet absorption and dichroism measurements on oriented films of calf thymus deoxyribonucleic acid (DNA) at varying degrees of hydration show a structural hysteresis which occurs within a relative humidity of 0 to 65% RH. This hysteresis is interpreted on the basis of a model which assumes the existence of structure‐stabilizing hydrogen water bridges in the DNA double helix.

Kinetics of ribonucleic acid synthesis on deoxyribonucleic acid template.

THE purpose of this communication is to propose a mechanism, and to establish on its basis a system of equations, for the description of the kinetics of the synthesis of ribonucleic acid (RNA) templated by deoxyribonucleic acid (DNA). The models proposed1 for the kinetics of the DNA synthesis cannot be extended to the RNA synthesis, since they assume that the uncoiling of the DNA double helix is the rate determining step. The time required for the unwinding of a DNA molecule with a length of 104 nucleotide pairs is of the order of about 30 sec (ref. 1). The in vivo synthesis rate for RNA is experimentally found to be much larger. It is therefore reasonable to assume that, in contrast to the replication of the DNA molecule, the RNA synthesis does not require the unwinding of the whole DNA double helix but only of a short part of it.

Deoxyribonucleic acid side-chain model of the chromosomes.

AT the 1954 Oak Ridge Symposium on Genetic Recombination, I proposed a model of the chromosome in which the molecules of deoxyribonucleic acid projected as side-chains from the main protein axis of the chromosome1. The advantages of such a model for explaining the results of cross-over studies involving closely linked markers were briefly discussed at one of the sessions of the 1956 Cold Spring Harbor Symposium on Genetic Mechanism. In this model, the genes (deoxyribonucleic acid) are linearly arranged along the chromosome; however, the linearity within the gene is not continuous with, or a part of, the linearity between genes. Intergenic cross-overs would be of the classical type involving exchanges of whole segments of the chromosome, whereas intragenic cross-overs would not exchange other markers on the chromosome. According to this conception, the chromosome is composed of alternate sections of deoxyribonucleic acid and protein. To satisfy the requirement for chromosomal continuity it was suggested that the two chains of the Watson–Crick deoxyribonucleic acid double helix are tied together at the free end. Taylor2 has published a chromosome model that differs from mine in that the chromosomal elements are tied together at the other end of the deoxyribonucleic acid instead by making the backbone continuous. In this communication I propose to consider three lines of evidence that may serve to distinguish between these two models.