Base Pairs Of Deoxyribonucleic Acid Research Articles

Theoretical Study on The Effect of Metal Ions on The Structural Properties of Base

Metal ions play an important role in living organisms, for example Mg2+ is a cofactor for many biological enzymes (including DNA and RNA synthesis), Ca2+ is an important component of bone composition, and metal ions such as Fe, Co, Zn, Ni and Cu also play an important role in the normal functioning of living organisms. One of the main targets of metal ions in living organisms is deoxyribonucleic acid (DNA), which is an important carrier of information stored and transmitted by organisms. The direct interaction between DNA base pairs and metal ions have a significant impact on the structure and function of DNA base pairs, which is demonstrated as following: the binding of metals to bases usually breaks the hydrogen bonds of the base pairs. The N7 atom of a purine residue or the N3 atom of a pyrimidine residue, as well as the outer ring O atom and the phosphate oxygen atom, are the preferred sites for metal binding. The binding of metals to DNA and RNA also indirectly affects the conformation of the sugar ring. REDOX active metal ions have the ability to bind to DNA and can mediate oxidative DNA damage by reacting with endogenous oxidants. According to studies of antioxidants in the field of metal-mediated oxidative DNA damage, metal ion coordination also plays a key role in the mechanism of some antioxidants. Also, metal-DNA interactions are the basis for many anti-cancer drugs, anti-viral drugs and anti-bacterial agents. Metal-mediated oxidative DNA damage is associated with a variety of diseases and conditions, and understanding the binding interactions and subsequent reactivity can facilitate the management or prevention of oxidative damage. It can be seen that the study of the effect of metal ions on the structural properties of DNA bases has far-reaching implications, providing a theoretical basis for the development of novel anticancer drugs, DNA-based metal nanodevice technologies and the fabrication of spectroscopic and reactive probes.

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.

Changes in molecular conformation and electronic structure of DNA under 12C ions based on first-principles calculations

Fundamental studies on the interaction between ionizing radiation and deoxyribonucleic acid (DNA) can contribute to understanding the biological effects of radiation protection and radiotherapy. The transitional process from ionized and excited DNA to DNA lesions, such as strand breaks and base lesions, remains uncertain. In this study, we focused in particular on the direct effects of radiation on DNA and calculated the number of ionizations induced within 10 base pairs of DNA using the Particle and Heavy Ion Transport code System, a general-purpose Monte Carlo code for radiation transport. The electronic structure of the ionized DNA is subsequently calculated using the first-principles calculation software OpenMX. Through these calculations, we successfully identified the redox site of DNA and quantitatively evaluated the amount of molecular bond cleavage. The scientific findings of this study will elucidate the cleavage mechanism of DNA in the high-density radiation field realized by ion beam irradiation by determining the redox sites.

Structure and Dynamics of dsDNA in Cell-like Environments.

Deoxyribonucleic acid (DNA) is a fundamental biomolecule for correct cellular functioning and regulation of biological processes. DNA's structure is dynamic and has the ability to adopt a variety of structural conformations in addition to its most widely known double-stranded DNA (dsDNA) helix structure. Stability and structural dynamics of dsDNA play an important role in molecular biology. In vivo, DNA molecules are folded in a tightly confined space, such as a cell chamber or a channel, and are highly dense in solution; their conformational properties are restricted, which affects their thermodynamics and mechanical properties. There are also many technical medical purposes for which DNA is placed in a confined space, such as gene therapy, DNA encapsulation, DNA mapping, etc. Physiological conditions and the nature of confined spaces have a significant influence on the opening or denaturation of DNA base pairs. In this review, we summarize the progress of research on the stability and dynamics of dsDNA in cell-like environments and discuss current challenges and future directions. We include studies on various thermal and mechanical properties of dsDNA in ionic solutions, molecular crowded environments, and confined spaces. By providing a better understanding of melting and unzipping of dsDNA in different environments, this review provides valuable guidelines for predicting DNA thermodynamic quantities and for designing DNA/RNA nanostructures.

A computational study of intercalation of streptozotocin (STZ) into DNA base pairs.

Deoxyribonucleic acid (DNA) drug intercalation is a well-known phenomenon for the treatment of cancer. Streptozotocin (STZ) is a drug agent containing toxic properties that make it good in the pancreatic cancer. The main objective of this study is the intercalation of the anticancer drug into the stacked base pair of DNA sequence with ATGC using a density functional theory (DFT) code named as ADF-Molecule. ADF code implements DFT using the Slater-type orbitals (STO) for computational analysis of atomic and molecular structures. All the calculations were carried out with the GGA and hybrid exchange correlation functional with TZ2P basis sets. It was captivatingly studied that during the intercalation process, the bonds between the DNA base pairs broken. Moreover, during the process of intercalation, the free radicals are considered responsible for disturbance in the base configurations. It was determined that the disturbances that occurred in the base pairs lead to discontinuity in the replication of that particular sequence in the DNA strand.

Effects of Mg2+ on the binding of the CREB/CRE complex: Full-atom molecular dynamics simulations**Project supported by the National Natural Science Foundation of China (Grant Nos. 11705064, 11675060, and 91730301), the Fundamental Research Funds for the Central Universities, China (Grant Nos. 2662016QD005 and 26622018JC017), and the Huazhong Agricultural University Scientific and Technological Self-Innovation Foundation Program, China (Grant No. 2015RC021).

Metal ions play critical roles in the interaction between deoxyribonucleic acid (DNA) and protein. The experimental research has demonstrated that the Mg2+ ion can affect the binding between transcription factor and DNA. In our work, by full-atom molecular dynamic simulation, the effects of the Mg2+ ion on the cyclic adenosine monophosphate (cAMP) response element binding protein (CREB)/cAMP response elements (CRE) complex are investigated. It is illustrated that the number of hydrogen bonds formed at the interface between protein and DNA is significantly increased when the Mg2+ ion is added. Hence, an obvious change in the structure of the DNA is observed. Then the DNA base groove and base pair parameters are analyzed. We find that, due to the introduction of the Mg2+ ion, the DNA base major groove becomes narrower. A potential mechanism for this observation is proposed. It is confirmed that the Mg2+ ion can enhance the stability of the DNA–protein complex.

Envisaging quantum transport phenomenon in a muddled base pair of DNA

The effect of muddled base pair on electron transfer through a deoxyribonucleic acid (DNA) molecule connected to the gold electrodes has been elucidated using tight binding model. The effect of hydrogen and nitrogen bonds on the resistance of the base pair has been minutely observed. Using the semiempirical extended Huckel approach within NEGF regime, we have determined the current and conductance vs. bias voltage for disordered base pairs of DNA made of thymine (T) and adenine (A). The asymmetrical behaviour amid five times depreciation in the current characteristics has been observed for deviated Au–AT base pair–Au devices. An interesting revelation is that the conductance of the intrinsic AT base pair configuration attains dramatically high values with the symmetrical zig-zag pattern of current, which clearly indicates the transformation of the bond length within the strands of base pair when compared with other samples. A thorough investigation of the transmission coefficients T(E) and HOMO–LUMO gap reveals the misalignment of the strands in base pairs of DNA. The observed results present an insight to extend this work to build biosensing devices to predict the abnormality with the DNA.

Anticlastogenic effects of organically grown moringa (Moringa oleifera), lemongrass (Cymbopogon citratus), and sweet sorghum (Sorghum bicolor) using micronucleus test

This study was conducted to determine the anticlastogenic effects of expressed juice of moringa (Moringa oleifera Lam.), lemongrass (Cymbopogon citratus), and sweet sorghum (Sorghum bicolor) on rats (Rattus norvegicus). Twenty five female albino rats aged two months were equally allotted in five treatments. The five treatments were: tetracycline as the positive control, distilled water as the negative control, moringa, lemongrass, and sorghum. Initial body weight and vital signs namely: heart rate, respiratory rate and body temperature were recorded prior to the application of the treatment. During the treatment period of four weeks, R. norvegicus rats were provided extracts of moringa, sweet sorghum and lemongrass at a dosage rate of 0.5 mL 20 g-1 of body weight (bw). The test animals were sacrificed 6 h following the last oral administration of tetracycline and were subjected to micronucleus test. Results revealed that moringa, lemongrass, and sweet sorghum have the potential to significantly reduce the number of micronucleated polychromatic erythrocytes (MPCEs) in clastogen-induced rats. Moringa exhibited the least mean number of MPCEs (3.8), followed by sweet sorghum (5.8) and lemongrass (7.8). The positive control showed the highest mean number of MPCEs (37.2). In terms of body weight, vital signs, feed intake and water intake, statistical analysis revealed that moringa, lemongrass, and sorghum at the level of treatment (0.5 20 g-1 bw) did not elicit any adverse effects such as tachycardia, arrhythmia and hyperpnea after a period of four weeks of treatment. The findings of this study suggest that moringa, sweet sorghum and lemongrass have anticlastogenic activities as shown by their ability to shield the interaction of tetracycline with the base pairs of deoxyribonucleic acid, thereby preventing the chromosomal breaking activity of tetracycline. However, further studies on the chemical constituents present in these medicinal plants need to be further investigated. Moreover, the use of mitomycin as clastogenic drug is considered for future studies.

Somatic Mutation Theory/Tissue Organization Field Theory: Has the Premise been Wrong All along?

ABSTRACT How to cite this article Sarode SC, Anand R, Sarode GS, Patil S. Somatic Mutation Theory/Tissue Organization Field Theory: Has the Premise been Wrong All along? World J Dent 2016;7(4):167-168.

Human Genome - Underlying Scientific Mysteries

A gene refers to the functional unit of heredity. Genes are made up of DNA (deoxyribonucleic acid). In humans, the size of genes varies from a few hundred DNA bases to more than 2 million bases. The genes in human beings (Homo sapiens) are referred as human genome. It is made up of 23 chromosome pairs with a total of about 3 billion DNA base pairs. The gene sequences to make a protein occupy only about 1.1% of the chromosomes. The rest is well known as junk DNA; that is useful in genetic fingerprinting

The Acidic C-terminal Tail of the GyrA Subunit Moderates the DNA Supercoiling Activity of Bacillus subtilis Gyrase

Gyrase is a type II DNA topoisomerase that introduces negative supercoils into DNA in an ATP-dependent reaction. It consists of a topoisomerase core, formed by the N-terminal domains of the two GyrA subunits and by the two GyrB subunits, that catalyzes double-stranded DNA cleavage and passage of a second double-stranded DNA through the gap in the first. The C-terminal domains (CTDs) of the GyrA subunits form a β-pinwheel and bind DNA around their positively charged perimeter. As a result, DNA is bound as a positive supercoil that is converted into a negative supercoil by strand passage. The CTDs contain a conserved 7-amino acid motif that connects blades 1 and 6 of the β-pinwheel and is a hallmark feature of gyrases. Deletion of this so-called GyrA-box abrogates DNA bending by the CTDs and DNA-induced narrowing of the N-gate, affects T-segment presentation, reduces the coupling of DNA binding to ATP hydrolysis, and leads to supercoiling deficiency. Recently, a severe loss of supercoiling activity of Escherichia coli gyrase upon deletion of the non-conserved acidic C-terminal tail (C-tail) of the CTDs has been reported. We show here that, in contrast to E. coli gyrase, the C-tail is a very moderate negative regulator of Bacillus subtilis gyrase activity. The C-tail reduces the degree of DNA bending by the CTDs but has no effect on DNA-induced conformational changes of gyrase that precede strand passage and reduces DNA-stimulated ATPase and DNA supercoiling activities only 2-fold. Our results are in agreement with species-specific, differential regulatory effects of the C-tail in gyrases from different organisms.

Human Consciousness: A Theoretical Prospective on Repetitive DNA Base Pairs Relation to Psychological Behavior

In this paper an attempt has been made to bridge the gap between the repetitive Deoxyribonucleic acid (DNA) base pair sequences and psychological human behavior. Assuming the brain as a perfect fluid, the DNA coefficient between the biological and non-biological forms of the brain is calculated. These calculations are based on the Friedman density equations that describe the expansion or contraction of the universe in homogeneous and isotropic way in physical cosmology (only time independent equation is considered). We have tested this DNA coefficient with a sample size of eighty persons with belief constructs on consciousness behavior. The Pearson’s coefficient thus obtained is then compared with DNA coefficient. A logical justification is made for the comparison of these two values. The coefficient values are found to tally but with an error margin of thirteen percent. The major result of this research study is in finding a relation between the experimental DNA values with that of psychology of consciousness behavior in terms of coefficient values. NeuroQuantology | December 2013 | Volume 11 | Issue4 |Page 618-626

Probing radiation damage by alternated current conductivity as a method to characterize electron hopping conduction in DNA molecules

Analysis of AC electrical conductivity of deoxyribonucleic acid (DNA) thin films, irradiated with ultraviolet (UV) light, revealed that electrical conduction arises from DNA chain electron hopping between base-pairs and phosphate groups. The hopping distance calculated from correlated barrier hopping model equals the distance between DNA base-pairs, which is consistent with the loss of conductivity with irradiation time arising from a decrease in phosphates groups. In the high frequency regime, at a given frequency, real part of conductivity strongly depends on irradiation time particularly for low dose levels suggesting the use of DNA based films for UV radiation sensors.

Binding of bisphenol A and acrylamide to BSA and DNA: Insights into the comparative interactions of harmful chemicals with functional biomacromolecules

The interactions between bisphenol A (BPA)/acrylamide (AA) and bovine serum albumin (BSA)/deoxyribonucleic acid (DNA) was investigated by the equilibrium dialysis, fluorophotometry, isothermal titration calorimetry (ITC) and circular dichroism (CD). The bindings of BPA and AA to BSA and DNA responded to the partition law and Langmuir isothermal model, respectively. The saturation mole number of AA was calculated to be 24 per mol BSA and 0.26 per mol DNA-P. All the reactions were spontaneous driven by entropy change. BPA stacked into the aromatic hydrocarbon groups of BSA and between adjacent basepairs of DNA via the hydrophobic effect. The interactions of AA with BSA and DNA induced the formation of hydrogen bond and caused changes of their secondary structures. At normal physiological condition, 0.100 mmol/l BPA reduced the binding of vitamin B 2 to BSA by more than 70%, and 2.8 mmol/l AA by almost one half. This work provides an insight into non-covalent intermolecular interaction between organic contaminant and biomolecule, helping to elucidate the toxic mechanism of harmful chemicals.

Nanopore Sequencing: Electrical Measurements of the Code of Life

Sequencing a single molecule of deoxyribonucleic acid (DNA) using a nanopore is a revolutionary concept because it combines the potential for long read lengths (>5 kbp) with high speed (1 bp/10 ns), while obviating the need for costly amplification procedures due to the exquisite single molecule sensitivity. The prospects for implementing this concept seem bright. The cost savings from the removal of required reagents, coupled with the speed of nanopore sequencing places the $1000 genome within grasp. However, challenges remain: high fidelity reads demand stringent control over both the molecular configuration in the pore and the translocation kinetics. The molecular configuration determines how the ions passing through the pore come into contact with the nucleotides, while the translocation kinetics affect the time interval in which the same nucleotides are held in the constriction as the data is acquired. Proteins like α-hemolysin and its mutants offer exquisitely precise self-assembled nanopores and have demonstrated the facility for discriminating individual nucleotides, but it is currently difficult to design protein structure ab initio, which frustrates tailoring a pore for sequencing genomic DNA. Nanopores in solid-state membranes have been proposed as an alternative because of the flexibility in fabrication and ease of integration into a sequencing platform. Preliminary results have shown that with careful control of the dimensions of the pore and the shape of the electric field, control of DNA translocation through the pore is possible. Furthermore, discrimination between different base pairs of DNA may be feasible. Thus, a nanopore promises inexpensive, reliable, high-throughput sequencing, which could thrust genomic science into personal medicine.

Hydrogen-Bonding Strengths in Pyrrolidinyl Peptide Nucleic Acid and DNA Base Pairs: A Density Functional Theory (DFT) Study

The H-bond strengths of the single base pair formed from Pyrrolidinyl Peptide Nucleic Acid (PNA) and charged as well as neutral Deoxyribonucleic Acid (DNA) were studied using the density functional theory. The B3LYP/6-31+G(d,p) level of theory was employed for evaluating the binding energies and structural parameters of heterogeneous and homogeneous base pairs. The strongest H-bond strengths were obtained from the heterogeneous base pairs, yielding the binding energies of −29.9 and −18.9 kcal/mol for the PNA-GC-DNA and PNA-AT-DNA base pairs, respectively. In contrast, a dramatic change on the H-bond strengths was observed from the charged homogenous base pairs with the binding energies of −6.2 and +10.2 kcal/mol for the DNA-GC-DNA and DNA-AT-DNA base pairs, respectively. With the neutralization of negative charges in the DNA backbone, the corresponding values of −29.1 and −11.7 kcal/mol were elucidated from the Na-DNA-GC-DNA-Na and Na-DNA-AT-DNA-Na base pairs, respectively, proving that the repulsion between two negative charges in the phosphate backbone plays a significant role to the H-bond interactions in base pairs. In addition, a high specificity and preferential binding between the pyrrolidinyl PNA and DNA base pairs were also observed.

Pyrimido[4,5-b]quinoline-2-thiol/ol: microwave-induced one-pot synthesis, DNA binding and cleavage studies

This article describes the synthesis of pyrimido[4,5-b]quinoline-2-thiol/ol (3a/3b) by microwave irradiation technique. The dynamic interaction of compounds with deoxyribonucleic acid (DNA) was investigated by absorption spectra, viscosity measurements, and thermal denaturation studies. Intrinsic binding constants (K b ) had values 3.1×106 for 3a and 2.3×105 for 3b. The proposed DNA binding mode supports the large enhancement in the relative viscosity of calf thymus (CT-DNA) on binding to compounds. Results suggest that 3a/3b can bind to CT-DNA by intercalation via the aromatic ring into the base pairs of DNA. Moreover, efficient DNA damage was observed on oxidative cleavage in the presence of 3a/3b.

Photoluminescence and lasing from deoxyribonucleic acid (DNA) thin films doped with sulforhodamine

Thin solid films of salmon deoxyribonucleic acid (DNA) have been fabricated by treatment with a surfactant and used as host for the laser dye sulforhodamine (SRh). The DNA films have an absorption peak at approximately 260 nm owing to absorption by the nitrogenous aromatic bases. The SRh molecules in the DNA films have absorption and emission peaks at 578 and 602 nm, respectively. The maximum emission was obtained at approximately 1 wt. % SRh in DNA, equivalent to approximately 100 DNA base pairs per SRh molecule. A distributed feedback grating structure was fabricated on a SiO(2)-Si substrate using interference lithography. The grating period of 437 nm was selected, corresponding to second-order emission at the amplified spontaneous emission wavelength of 650 nm. Lasing was obtained by pumping with a doubled Nd:YAG laser at 532 nm. The lasing threshold was 3 microJ, corresponding to approximately 30 microJ/cm(2) or 4 kW/cm(2). The emission linewidth decreased from approximately 30 nm in the amplified spontaneous emission mode to <0.4 nm (instrument limited) in the lasing mode. The slope efficiency of the lasing was approximately 1.2%.

Estimation of minimum electron dose necessary to resolve molecular structure of deoxyribonucleic acid by phase transmission electron microscopy

The minimum electron dose that is necessary to resolve the molecular structure of deoxyribonucleic acid (DNA) was estimated based on experimental measurements of information limits and simulated DNA images, considering conditions of a low electron dose. From these results, a dose of ∼400e∕Å2 was found to be necessary to achieve observation of DNA on a molecular scale under the present experimental setup. A DNA molecule was observed by a phase reconstruction method using through-focus images under the limited electron dose. In the reconstructed images, the helical structure and the intervals of the base pairs of DNA were partially resolved.

Molecular-scale imaging of unstained deoxyribonucleic acid fibers by phase transmission electron microscopy

The molecular structure of deoxyribonucleic acid (DNA) fibers was observed by a phase reconstruction method called three-dimensional Fourier filtering using a 200kV transmission electron microscope. The characteristic helical structure and the spacing of adjacent base pairs of DNA were partially resolved due to an improved signal-to-noise ratio and resolution enhancement by the phase reconstruction although the molecular structure was damaged by the electron beam irradiation. In the spherical aberration-free phase images, the arrangements of single atom-sized spots forming sinusoidal curves were sometimes observed, which seem to be the contrast originating in the sulfur atoms along the main chains.