Computational determination of radiation damage effects on DNA structure

Open Physics ◽  
2003 ◽  
Vol 1 (1) ◽  
Author(s):  
Miroslav Pinak
Keyword(s):  
Structural Changes ◽  
Double Helix ◽  
Helical Structure ◽  
Electrostatic Energy ◽  
Necessary Condition ◽  
Enzyme Complex ◽  
Repair Enzyme ◽  
Thymine Dimer ◽  
Thymine Glycol ◽  
Double Helical Structure

AbstractMolecular dynamics (MD) studies of several radiation originated lesions on the DNA molecules are presented. The pyrimidine lesions (cytosinyl radical, thymine dimer, thymine glycol) and purine lesion (8-oxoguanine) were subjected to the MD simulations for several hundred picoseconds using MD simulation code AMBER 5.0 (4.0). The simulations were performed for fully dissolved solute molecules in water. Significant structural changes in the DNA double helical structure were observed in all cases which may be categorized as: a) the breaking of hydrogen bonds network between complementary bases and resulted opening of the double helix (cytosinyl, radical, 8-oxoguanine); b) the sharp bending of the DNA helix centered at the lesion site (thymine dimer, thymine glycol); and c) the flippingout of adenine on the strand complementary to the lesion (8-oxoguanine). These changes related to the overall collapsing of the double helical structure around the lesion, are expected to facilitate the docking of the repair enzyme into the DNA in the formation of DNA-enzyme complex. The stable DNA-enzyme complex is a necessary condition for the onset of the enzymatic repair process. In addition to structural changes, specific values of electrostatic interaction energy were determined at several lesion sites (thymine dimer, thymine glycol and 8-oxoguanine). This lesion-specific electrostatic energy is a factor that enables repair enzyme to discriminate lesion from the native site during the scanning of the DNA surface.

DNA: Not Merely the Secret of Life

2010 ◽  
Author(s):  
Nadrian C. Seeman
Keyword(s):  
Double Helix ◽  
Genetic Material ◽  
Helical Structure ◽  
Prominent Feature ◽  
Base Pairing ◽  
Double Helical Structure ◽  
Reciprocal Exchange ◽  
Sequence Selection ◽  
Living Organisms ◽  
Dna Double Helix

DNA is well-known as the genetic material of living organisms. Its most prominent feature is that it contains information that enables it to replicate itself. This information is contained in the well-known Watson-Crick base pairing interactions, adenine with thymine and guanine with cytosine. The double helical structure that results from this complementarity has become a cultural icon of our era. To produce species more diverse than the DNA double helix, we use the notion of reciprocal exchange, which leads to branched molecules. The topologies of these species are readily programmed through sequence selection; in many cases, it is also possible to program their structures. Branched species can be connected to one another using the same interactions that genetic engineers use to produce their constructs, cohesion by molecules tailed in complementary single-stranded overhangs, known as ‘sticky ends.’ Such sticky-ended cohesion is used to produce N-connected objects and lattices [1]. This notion is shown in the drawing, which shows cohesion between sticky-ended branched species.

scholarly journals The emergence of sequence-dependent structural motifs in stretched, torsionally constrained DNA

2020 ◽  
Vol 48 (4) ◽  
pp. 1748-1763 ◽  
Author(s):  
Jack W Shepherd ◽  
Robert J Greenall ◽  
Matt I J Probert ◽  
Agnes Noy ◽  
Mark C Leake
Keyword(s):  
Structural Changes ◽  
Periodic Structures ◽  
Helical Structure ◽  
Specific Response ◽  
Base Pairs ◽  
Structural Motifs ◽  
Double Helical Structure ◽  
Physiological Relevance ◽  
Stable Periodic ◽  
Dynamics Simulations

Abstract The double-helical structure of DNA results from canonical base pairing and stacking interactions. However, variations from steady-state conformations resulting from mechanical perturbations in cells have physiological relevance but their dependence on sequence remains unclear. Here, we use molecular dynamics simulations showing sequence differences result in markedly different structural motifs upon physiological twisting and stretching. We simulate overextension on different sequences of DNA ((AA)12, (AT)12, (CC)12 and (CG)12) with supercoiling densities at 200 and 50 mM salt concentrations. We find that DNA denatures in the majority of stretching simulations, surprisingly including those with over-twisted DNA. GC-rich sequences are observed to be more stable than AT-rich ones, with the specific response dependent on the base pair order. Furthermore, we find that (AT)12 forms stable periodic structures with non-canonical hydrogen bonds in some regions and non-canonical stacking in others, whereas (CG)12 forms a stacking motif of four base pairs independent of supercoiling density. Our results demonstrate that 20–30% DNA extension is sufficient for breaking B-DNA around and significantly above cellular supercoiling, and that the DNA sequence is crucial for understanding structural changes under mechanical stress. Our findings have important implications for the activities of protein machinery interacting with DNA in all cells.

scholarly journals The emergence of sequence-dependent structural motifs in stretched, torsionally constrained DNA

2019 ◽  
Author(s):  
Jack W Shepherd ◽  
R J Greenall ◽  
M I J Probert ◽  
Agnes Noy ◽  
Mark C. Leake
Keyword(s):  
Structural Changes ◽  
Periodic Structures ◽  
Helical Structure ◽  
Specific Response ◽  
Base Pairs ◽  
Structural Motifs ◽  
Double Helical Structure ◽  
Physiological Relevance ◽  
Stable Periodic ◽  
Dynamics Simulations

ABSTRACTThe double-helical structure of DNA results from canonical base pairing and stacking interactions. However, variations from steady-state conformations result from mechanical perturbations in cells. These different topologies have physiological relevance but their dependence on sequence remains unclear. Here, we use molecular dynamics simulations to show that sequence differences result in markedly different structural motifs upon physiological twisting and stretching. We simulated overextension on four different sequences of DNA ((AA)12, (AT)12, (GG)12and (GC)12) with supercoiling densities within the physiological range. We found that DNA denatures in the majority of stretching simulations, surprisingly including those with overtwisted DNA. GC-rich sequences were observed to be more stable than AT-rich, with the specific response dependent on base pair ordering. Furthermore, we found that (AT)12forms stable periodic structures with non-canonical hydrogen bonds in some regions and non-canonical stacking in others, whereas (GC)12forms a stacking motif of four base pairs independent of supercoiling density. Our results demonstrate that 20-30% DNA extension is sufficient for breaking B-DNA around and significantly above cellular supercoiling, and that the DNA sequence is crucial for understanding structural changes under mechanical stress. Our findings have important implications for the activities of protein machinery interacting with DNA in all cells.

An infrared study of the influence of growth media and myo-inositol on structural changes in DNA induced by dehydration and ultraviolet light

1968 ◽  
Vol 14 (8) ◽  
pp. 841-852 ◽  
Author(s):  
S. J. Webb ◽  
M. D. Dumasia
Keyword(s):  
Structural Changes ◽  
Bound Water ◽  
Helical Structure ◽  
Growth Media ◽  
Minimal Salt Medium ◽  
Infrared Study ◽  
Bacterial Dna ◽  
Double Helical Structure ◽  
Spectral Shifts ◽  
Absorption Frequencies

The infrared spectra of films of deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and synthetic polynucleotides have been studied under varying degrees of relative humidity (R.H.) in the presence and absence of myo-inositol. In addition the effect of 2537 Å light (ultraviolet) on the hydration of DNA has been investigated. As other researchers have shown, when the R.H. is lowered shifts in the P=O and C=O absorption frequencies occur. These shifts seem to be associated with the removal of approximately 12 molecules of water/nucleotide and all are prevented by the presence of 2 molecules of inositol/nucleotide during desiccation. The irradiation of DNA at 75% R.H. with ultraviolet also produces spectral shifts which appear to arise as a result of bound water molecules moving from P=O and C=O groups.The response of bacterial DNA to desiccation appears to depend on the medium in which the cells are grown. The DNA from cells grown in a minimal salts medium is less hydrated at a given R.H. level than the DNA from cells grown in an enriched medium. This loss of water-adsorbing sites is considered to be due to a physiological replacement of water on the DNA of cells grown on minimal salt medium by amino acids or proteins. RNA and polynucleotides are less hydrated than DNA, which is assumed to be due to their lack of an ordered double helical structure. Of the synthetic polynucleotides poly-I was found to most closely resemble the behavior of DNA. The ability of inositol to prevent spectral shifts in DNA caused by desiccation and irradiation tends to substantiate the suggestion that it preserves the biological integrity of cells and viruses during stress by combining with DNA.

scholarly journals The many lives of type IA topoisomerases

2020 ◽  
Vol 295 (20) ◽  
pp. 7138-7153 ◽  
Author(s):  
Anna H. Bizard ◽  
Ian D. Hickson
Keyword(s):  
Double Helix ◽  
Helical Structure ◽  
Dna Topoisomerases ◽  
Double Helical Structure ◽  
Processing Enzymes ◽  
Type Ia ◽  
Cellular Machinery ◽  
The Many ◽  
Dna Double Helix ◽  
Dna Topoisomerase Iii

The double-helical structure of genomic DNA is both elegant and functional in that it serves both to protect vulnerable DNA bases and to facilitate DNA replication and compaction. However, these design advantages come at the cost of having to evolve and maintain a cellular machinery that can manipulate a long polymeric molecule that readily becomes topologically entangled whenever it has to be opened for translation, replication, or repair. If such a machinery fails to eliminate detrimental topological entanglements, utilization of the information stored in the DNA double helix is compromised. As a consequence, the use of B-form DNA as the carrier of genetic information must have co-evolved with a means to manipulate its complex topology. This duty is performed by DNA topoisomerases, which therefore are, unsurprisingly, ubiquitous in all kingdoms of life. In this review, we focus on how DNA topoisomerases catalyze their impressive range of DNA-conjuring tricks, with a particular emphasis on DNA topoisomerase III (TOP3). Once thought to be the most unremarkable of topoisomerases, the many lives of these type IA topoisomerases are now being progressively revealed. This research interest is driven by a realization that their substrate versatility and their ability to engage in intimate collaborations with translocases and other DNA-processing enzymes are far more extensive and impressive than was thought hitherto. This, coupled with the recent associations of TOP3s with developmental and neurological pathologies in humans, is clearly making us reconsider their undeserved reputation as being unexceptional enzymes.

Long-term efficacy of a new medical device containing Fernblock® and DNA repair enzyme complex in the treatment and prevention of cancerization field in patients with actinic keratosis.

2019 ◽  
Vol 2 (02) ◽  
pp. 80-89
Author(s):  
Blanca De Unamuno Bustos ◽  
Natalia Chaparr´´o Aguilera ◽  
Inmaculada Azorín García ◽  
Anaid Calle Andrino ◽  
Margarita Llavador Ros ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Medical Device ◽  
Actinic Keratosis ◽  
Statistical Significance ◽  
Dna Lesions ◽  
Enzyme Complex ◽  
Repair Enzyme ◽  
P53 Expression ◽  
Cancerization Field

Actinic keratosis (AKs) are part of the cancerization field, a region adjacent to AKs containing subclinical and histologically abnormal epidermal tissue due to Ultraviolet (UV)-induced DNA damage. The photoproducts as consequence of DNA damage induced by UV are mainly cyclobutane pyrimidine dimers (CPDs). Fernblock® demonstrated in previous studies significant reduction of the number of CPDs induced by UV radiation. Photolyases are a specific group of enzymes that remove the major UV-induced DNA lesions by a mechanism called photo-reactivation. A monocentric, prospective, controlled, and double blind interventional study was performed to evaluate the effect of a new medical device (NMD) containing a DNA-repair enzyme complex (photolyases, endonucleases and glycosilases), a combination of UV-filters, and Fernblock® in the treatment of the cancerization field in 30 AK patients after photodynamic therapy. Patients were randomized into two groups: patients receiving a standard sunscreen (SS) andpatients receiving the NMD. Clinical, dermoscopic, reflectance confocal microscopy (RCM) and histological evaluations were performed. An increase of AKs was noted in all groups after three months of PDT without significant differences between them (p=0.476). A significant increase in the number of AKs was observed in SS group after six (p=0.026) and twelve months of PDT (p=0.038); however, this increase did not reach statistical significance in the NMD group. Regarding RCM evaluation, honeycomb pattern assessment after twelve months of PDT showed significant differences in the extension and grade of the atypia in the NMD group compared to SS group (p=0.030 and p=0.026, respectively). Concerning histopathological evaluation, keratinocyte atypia grade improved from baseline to six months after PDT in all the groups, with no statistically significant differences between the groups. Twelve months after PDT, p53 expression was significantly lower in the NMD group compared to SS group (p=0.028). The product was well-tolerated, with no serious adverse events reported. Our results provide evidence of the utility of this NMD in the improvement of the cancerization field and in the prevention of the development of new AKs.  

scholarly journals Molecular Dynamics Simulation on the Interaction between Palygorskite Coating and Linear Chain Alkane Base Lubricant

Coatings ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 286
Author(s):  
Jin Zhang ◽  
Lv Yang ◽  
Yue Wang ◽  
Huaichao Wu ◽  
Jiabin Cai ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Structural Changes ◽  
Molecular Diffusion ◽  
Linear Chain ◽  
Interfacial Interaction ◽  
Dynamics Simulation ◽  
Electrostatic Energy ◽  
Experimental Development ◽  
Practical Applications ◽  
Self Diffusion

Molecular dynamics (MD) simulations were conducted to investigate the interactions between a palygorskite coating and linear chain alkanes (dodecane C12, tetradecane C14, hexadecane C16, and octadecane C18), representing base oils in this study. The simulation models were built by placing the alkane molecules on the surface of the palygorskite coating. These systems were annealed and geometrically optimized to obtain the corresponding stable configurations, followed by the analysis of the structural changes occurring during the MD process. The interfacial interaction energies, mean square displacements, and self-diffusion coefficients of the systems were evaluated to characterize the interactions between base lubricant molecules and palygorskite coating. It was found that the alkanes exhibited self-arrangement ability after equilibrium. The interfacial interaction was attractive, and the electrostatic energy was the main component of the binding energy. The chain length of the linear alkanes had a significant impact on the intensity of the interfacial interactions and the molecular diffusion behavior. Moreover, the C12 molecule exhibited higher self-diffusion coefficient values than C14, C16 and C18. Therefore, it could be the best candidate to form an orderliness and stable lubricant film on the surface of the palygorskite coating. The present work provides new insight into the optimization of the structure and composition of coatings and lubricants, which will guide the experimental development of these systems for practical applications.

scholarly journals Both DNA global deformation and repair enzyme contacts mediate flipping of thymine dimer damage

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Alexander Knips ◽  
Martin Zacharias
Keyword(s):  
Repair Enzyme ◽  
Thymine Dimer ◽  
Global Deformation

Hyaluronic acid: a double-helical structure in the presence of potassium at low pH and found also with the cations ammonium, rubidium and caesium

1977 ◽  
Vol 117 (1) ◽  
pp. 113-135 ◽  
Author(s):  
J.K. Sheehan ◽  
K.H. Gardner ◽  
E.D.T. Atkins
Keyword(s):  
Hyaluronic Acid ◽  
Helical Structure ◽  
Low Ph ◽  
Double Helical Structure

scholarly journals Living supramolecular polymerization of fluorinated cyclohexanes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Oleksandr Shyshov ◽  
Shyamkumar Vadakket Haridas ◽  
Luca Pesce ◽  
Haoyuan Qi ◽  
Andrea Gardin ◽  
...  
Keyword(s):  
Dipole Moment ◽  
Self Assembly ◽  
Materials Science ◽  
Helical Structure ◽  
The Self ◽  
Supramolecular Polymers ◽  
Aliphatic Compound ◽  
Double Helical Structure ◽  
Key Driver ◽  
Supramolecular Polymerization

AbstractThe development of powerful methods for living covalent polymerization has been a key driver of progress in organic materials science. While there have been remarkable reports on living supramolecular polymerization recently, the scope of monomers is still narrow and a simple solution to the problem is elusive. Here we report a minimalistic molecular platform for living supramolecular polymerization that is based on the unique structure of all-cis 1,2,3,4,5,6-hexafluorocyclohexane, the most polar aliphatic compound reported to date. We use this large dipole moment (6.2 Debye) not only to thermodynamically drive the self-assembly of supramolecular polymers, but also to generate kinetically trapped monomeric states. Upon addition of well-defined seeds, we observed that the dormant monomers engage in a kinetically controlled supramolecular polymerization. The obtained nanofibers have an unusual double helical structure and their length can be controlled by the ratio between seeds and monomers. The successful preparation of supramolecular block copolymers demonstrates the versatility of the approach.

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