Double Helix Research Articles

Atomistic simulations of polysaccharide materials for insights into their crystal structure, nanostructure, and dissolution mechanism

AbstractCrystalline polysaccharides are abundant in nature and can be transformed into highly functional materials. However, the molecular basis for the formation of higher-order structures remains unclear. Computer simulation is an advanced tool for modeling macromolecular structures, and the atomistic simulations provide valuable information on the crystalline polysaccharides. Fiber deformation, crystalline transition, and novel nanostructures of cellulose were characterized through molecular dynamics simulations and density functional theory calculations of models of molecular chain sheets extracted from the crystal structure of the cellulose polymorphs. Extended ensemble molecular dynamics simulations were applied to analyze the artificial crystal structure of non-natural amylose analog polysaccharides, revealing the hexagonal packing of double helices through the self-assembly of molecular chains dispersed in aqueous solution. Dissolution simulations of the cellulose and chitin crystalline fibers revealed that the anions of ionic liquids, with their solvation power, played a key role in the cleavage of intermolecular hydrogen bonds in the crystal structure, whereas the cations contributed to irreversible molecular chain dispersion. The good correlation between the actual solubility of polysaccharides and the predicted number of intermolecular hydrogen bonds prompted the development of a platform that combined simulations and machine learning for high-throughput screening of solvents for cellulose and chitin.

First Principle Studies of Electronic Properties, Global Reactivity Descriptors, and Molecular Docking of Olivacine Drug

AbstractOlivacine, a semisynthetic isomer of ellipticine, belongs to the family of natural alkaloids; which possess analgesic, antibacterial, and antipyretic properties. It is a model anticancer drug acting as topoisomerase II inhibitor. The mechanism of action and antineoplastic properties of olivacine are ascribed to its intercalative binding into DNA helices. The present paper reports DFT investigation of the molecular structure, electronic properties, and global reactivity descriptors of the drug. Frontier orbitals (HOMO and LUMO) and MEP surface of the olivacine molecule have been examined. Furthermore, inhibition activity and binding sites of olivacine with kinase protein (PDB Id: 3OG7) have been explored by molecular docking technique. Results have been used to elucidate physico‐chemical aspects and preferred binding patterns of the olivacine drug.

Experimental research on the heat balance of independent heat extraction-release double helix energy pile

The use of spiral buried pipe of ground source heat pump in civil defense engineering shows great potential, exploring its complex heat transfer features and thermal balance through experimental approaches is essential. This paper utilizes an independent heat extraction-release double helix energy pile to manage condensation heat discharge in underground projects. An experimental platform was established to compare three scenarios: pure heat release, centralized heat extraction, and uniform heat extraction. The pure heat release mode resulted in substantial soil heat accumulation, whereas the centralized heat extraction and uniform heat extraction demonstrated significant reductions in average temperature rise, with decreases of 24.7 % and 31.3 % near the buried pipes, and 27.3 % and 46.3 % in the central regions. The heat-extracting pipe under centralized heat extraction and uniform heat extraction conditions remove 18.7 MJ and 20.3 MJ of accumulated heat, amounting to 10.3 % and 11.2 % of the total heat dissipation, respectively, effectively mitigating the thermal accumulation in the soil during operation. Besides, the outlet temperature of the heat-extracting pipe is predominantly influenced by the highest temperature in the heat exchange zone, lowering the inlet temperature effectively increases the temperature difference between the inlet and outlet, enhancing the amount of heat removed. The accumulation of underground heat can enhance the heat extraction performance of the pipes, and increasing the water flow rate of the heat-releasing pipe positively impacts the heat extraction capacity. After soil temperatures rise, running the heat-extracting pipe with cooler inlet water and a moderately higher flow rate is advised for extracting the accumulated heat.

Structural insights into the recognition of purine-pyrimidine dinucleotide repeats by zinc finger protein ZBTB43.

Purine-pyrimidine repeats (PPRs) can form left-handed Z-form DNA and induce DNA double-strand breaks (DSBs), posing a risk for genomic rearrangements and cancer. The zinc finger (ZF) and BTB domain-containing protein 43 (ZBTB43) is a transcription factor containing two Cys2-His2 (C2H2) and one C3H1 zinc fingers and plays a crucial role in maintaining genomic and epigenomic integrity by converting mutagenic Z-form PPRs to the B-form in prospermatogonia. Despite its importance, the molecular mechanism underlying the recognition of PPRs by ZBTB43 remains elusive. In this study, we determined the X-ray crystal structure of the ZBTB43 ZF1-3 in complex with the B-form DNA containing the CA repeats sequence. The structure reveals that ZF1 and ZF2 primarily recognize the CACA sequence through specific hydrogen-bonding and van der Waals contacts via a quadruple center involving Arg389, Met411, His413, and His414. These interactions were further validated by fluorescence-based DNA-binding assays using mutated ZBTB43 variants. Our structural investigation provides valuable insights into the recognition mechanism of PPRs by ZBTB43 and suggests a potential role for ZBTB43 in the transformation of Z-DNA to B-DNA, contributing to the maintenance of genomic stability.

Cross-linking Arenga pinnata starch and chitosan by citric acid: Structure and properties

In order to improve the processing and digestibility of the Arenga pinnata (Wurmb.) Merr. starch (APS), low concentration citric acid (CA) and chitosan (CS) were used for dual modification. The purpose of this study was to prepare APS and CS complexes with CA, the complexes (CA-CS-APS) physicochemical properties were investigated. The short-range ordered structure (DO), double helix structure (DO) and relative crystallinity (RC) were decreased; CA-CS resulted in the surface roughness of APS, but the particle integrity was preserved; the particle size of CA-CS-APS was increased. Compared with APS, the peak viscosity of CA-CS-APS was decreased from 2534 cP to 27 cP; CA-CS reduced the swelling power of APS, CA3%-CS-APS decreased from 19.00 g/g to 8.17 g/g. The gelatinization enthalpy was decreased after CA-CS modification from 3.25 J/g to 0.55 J/g. CA-CS-APS exhibits higher storage modulus and loss modulus (2067 Pa and 80 Pa). CA-CS significantly improved the anti-digestibility of APS, and the resistant starch (RS) content was increased from 32 % to 39 %. This study provided a simple and effective way to prepare modified starch, which had the potential as food additives or used as a base material for film preparation.

Pd(II)/1,10-phenanthroline complexes bearing arene ligands: On the role of N- vs O-coordination to tune their cellular activity and binding ability towards DNA and RNA

Three Pd(II)-based complexes of 1,10-phenanthroline and N- or O-coordinating ligands have been synthesised and tested with different relevant biosubstrates like double-stranded DNA, double and triple helix of RNA, DNA G-quadruplexes of different conformations and bovine serum albumin. Here a correlation between N- vs O-coordinating elements and binding mechanism emerged, where the N-coordinating ligands proved to be the most promising. These outcomes were confirmed also in the cellular experiments. The Pd(II) complex with naphthalene-1,8-diamine is the one that is able to be carried by BSA, to strongly bind nucleic acids, to produce reactive oxygen species (ROS) and to show the best cellular performances (poorly toxic towards healthy cells and highly toxic against the cisplatin-resistant cancer cell line). On the opposite, the complex with benzene-1,2-diolate may be sequestered by BSA, weakly binds nucleic acids, does not produce ROS and shows poor cellular activity. The complex with benzene-1,2-diamine stays in between. Other mechanistic details are discussed which show that the biophysical behaviour is the sum of the contribution of aromaticity, charge and N- or O-coordination.

Comparative molecular dynamics calculations of duplexation of chemically modified analogs of DNA used for antisense applications.

We have subjected several analogs of DNA that have been widely used as antisense oligonucleotide (ASO) inhibitors of gene expression to comparative molecular dynamics (MD) calculations of their ability to form duplexes with DNA and RNA. The analogs included in this study are the phosphorothioate (PS), peptide nucleic acid (PNA), locked nucleic acid (LNA), morpholino nucleic acid (PMO), the 2'-OMe, 2'-F, 2'-methoxyethyl (2'-MOE) and the constrained cET analogs, as well as the natural phosphodiester (PO) as control, for a total of nine structures, in both XNA-DNA and XNA-RNA duplexes. This is intended as an objective criterion for their relative ability to duplex with an RNA complement and their comparative potential for antisense applications. We have found that the constrained furanose ring analogs show increased stability when considering this study's structural and energetic parameters. The 2'-MOE modification, even though energetically stable, has an elevated dynamic range and breathing properties due to the bulkier moiety in the C2' position of the furanose. The smaller modifications in the C2' position, 2'-F, 2'-OMe and PS also form stable and energetically favored duplexes with both DNA and RNA. The morpholino moiety allows for increased tolerance in accommodating either DNA or RNA and the PNA, with the PNA being the most energetically stable, although with a preference for the B-form DNA. In summary, we can rank the overall preference of hybrid strand formations as PNA>cET/LNA>PS/2'-F/2'-OMe>morpholino>2'-MOE for the efficacy of duplex formation.

Enantioselectively generating imidazolone dIz by the chiral DNA intercalating and “light-switching” Ru(II) polypyridyl complex via a novel flash-quench method

The 2-aminoimidazolone is a major and ubiquitous in vitro product of guanine oxidation. The flash-quench method, combining spectroscopy and product analysis, offers a novel and tunable approach to study guanine oxidation on double helical DNA. Herein we found that imidazolone dIz (2-amino-5-[(2-deoxy-β-D-erythro-pentofuranosyl)amino]-4H-imidazole-4-one) and dZ (2,2-diamino-5-[2-deoxy-β-D-erythro-pentofuranosyl)amino]-5(2H)-oxazolone) were the major oxidation products of double-strand DNA from the visible-light irradiation of the well-known DNA intercalating and light-switching Ru(OP)2dppz2+ (OP = 1,10-phenanthroline, dppz = dipyrido [3,2-a:2′,3′-c]phenazine) in the presence of a typical quencher methyl viologen (MV2+). Using ESR spin-trapping method, the radical intermediate MV•+ with typical hyperfine pattern was detected which indicated the successful formation of the corresponding Ru3+ intercalated oxidant. The formation of dIz and dZ decreased markedly with the addition of nitrotetrazolium blue chloride (NBT), a typical O2•- reactant. With a more specific and highly sensitive O2•- probe CT02-H, its ESR signal decayed rapidly in the presence of Ru(OP)2dppz2+ and MV2+, suggesting that O2•- was indeed produced. More interestingly, enantio-selective generation of oxidation products from dsDNA was observed with the two chiral forms of Ru(OP)2dppz2+. This represents the first report that the flash-quench technique with MV2+ as the quencher can oxidize dsDNA effectively to form dIz and dZ via the Ru3+/O2•- mediated mechanism. Our new findings provide a novel method to generate two radicals simultaneously, G (-H)• and O2•-, in close proximity to one another in dsDNA.

A Comprehensive Review of the Antitumor Properties and Mechanistic Insights of Duocarmycin Analogs.

The duocarmycin family is a group of potent cytotoxic agents originally isolated from the bacterium Streptomyces. This discovery has spurred significant interest due to duocarmycins' unique chemical structures and powerful mechanism of action. This review comprehensively details the history of the duocarmycin family, the current understanding of their therapeutic potential, and the major clinical trials that have been conducted. Chemically, the duocarmycin family is characterized by a DNA-binding unit that confers specificity, a subunit-linking amide that positions the molecule within the DNA helix, and an alkylating unit that interacts with the DNA. This configuration allows them to bind selectively to the minor groove of DNA and alkylate adenine bases, a notable deviation from the more common guanine targeting performed by other alkylating agents. Duocarmycin's mechanism of action involves the formation of covalent adducts with DNA, leading to the disruption of the DNA architecture and subsequent inhibition of replication and transcription. Recent advancements in drug delivery systems, such as antibody-drug conjugates (ADCs), have further elevated the therapeutic prospects of duocarmycin analogs by providing a promising mechanism for enhancing intracellular concentrations and selective tumor delivery. Preclinical studies have highlighted the efficacy of duocarmycin derivatives in various in vitro models, providing a strong foundation for translational research. However, further biological research is required to fully understand the toxicology of duocarmycin family members before it can be clinically relevant. The major focus of this review is to cache the major biologically relevant findings of different duocarmycin analogs as well as their biological shortcomings to propose next steps in the field of cancer therapy with these potent therapeutics.

Single-Molecule Real-Time Visualization of DNA Unwinding by CMG Helicase.

Faithful genome duplication is essential for preserving the genetic stability of dividing cells. DNA replication is carried out during the S phase by a dynamic complex of proteins termed the replisome. At the heart of the replisome is theCDC45-MCM2-7-GINS (CMG) helicase, which separates the two strands of the DNA double helix such that DNA polymerases can copy each strand. During genome duplication, replisomes must overcome a plethora of obstacles and challenges. Each of these threatens genome stability, as failure to replicate DNA completely and accurately can lead to mutations, diseases, or cell death. Therefore, it is of great interest to understand how CMG functions in the replisome during both normal replication and replication stress. Here, we describe a total internal reflection fluorescence (TIRF) microscopy assay using recombinant purified proteins, which allows for real-time visualization of surface-tethered stretched DNA molecules by individual CMG complexes. This assay provides a powerful platform to investigate CMG behavior at the single-molecule level, allowing helicase dynamics to be directly observed with real-time control over reaction conditions.

Temperature switchable linkers suitable for triggered drug release in cancer thermo-chemotherapy

In drug delivery systems, a stimuli-responsive linker that attaches a targeting carrier and a cytotoxic payload can be dissociated to release the payload on the target over the action of a stimuli, thereby it would harden the selectivity, specificity and potency of the cytotoxic agent against targeted tissues whilst sparing the drug-induced toxicity on normal cells. Oligonucleotide duplexes can unwind and be separated into single-stranded random coils under a defined temperature, and this property makes the oligonucleotide an appealing thermo-responsive linker. In this work, we studied the melting temperatures of different DNA linkers with various lengths and mismatches inserted in the double helix with either different numbers or positions. We further chose the DNA linkers that can unwind at the hyperthermia temperature and used them in the construction of four different drug delivery systems both in vitro and in vivo. Results showed that the chosen DNA linkers in all of the constructed delivery systems can successfully unwind and release cargos or drugs after application of heat compared to control groups. This research demonstrated the potential applications of DNA duplexes as temperature-sensitive linkers of drug delivery systems for cancer therapy.

Reflections on the history of the double helix and the motivations, methods and history of scientific work

Not available.

Hunting the Cell Cycle Snark.

In this very personal hunt for the meaning of the bacterial cell cycle, the snark, I briefly revisit and update some of the mechanisms we and many others have proposed to regulate the bacterial cell cycle. These mechanisms, which include the dynamics of calcium, membranes, hyperstructures, and networks, are based on physical and physico-chemical concepts such as ion condensation, phase transition, crowding, liquid crystal immiscibility, collective vibrational modes, reptation, and water availability. I draw on ideas from subjects such as the 'prebiotic ecology' and phenotypic diversity to help with the hunt. Given the fundamental nature of the snark, I would expect that its capture would make sense of other parts of biology. The route, therefore, followed by the hunt has involved trying to answer questions like "why do cells replicate their DNA?", "why is DNA replication semi-conservative?", "why is DNA a double helix?", "why do cells divide?", "is cell division a spandrel?", and "how are catabolism and anabolism balanced?". Here, I propose some relatively unexplored, experimental approaches to testing snark-related hypotheses and, finally, I propose some possibly original ideas about DNA packing, about phase separations, and about computing with populations of virtual bacteria.

Integrated OPECT and Smartphone Colorimetry Dual‐Mode Detection of Okadaic Acid Based on Ce‐MOF Modified MXene@SnO2 Z‐Scheme Heterostructure

AbstractThe organic photoelectrochemical transistor (OPECT) biosensing relies solely on a singular signal readout inherently, which restrains the precision and dependability nestled within pertinent biological measurements. Herein, a high‐precision magnetic assisted OPECT and smartphone colorimetric (SCL) dual‐mode biosensing platform is first established for detecting harmful algal toxin okadaic acid (OA) by biocatalytic reaction. MXene@SnO2‐Ce‐MOF (MXSnO/Ce‐MOF) Z‐scheme heterojunctions with abundant oxygen vacancies are prepared as photoactive materials. Initially, in the presence of OA, the coupling of trigger DNA (tDNA) to magnetic beads (MBs) via anchor DNA (aDNA) is released through the interaction of the target analyte with the aptamer. Subsequently, the carried tDNA triggers HCR between the two hairpin sequences, producing long double helix chains to capture glucose oxidase (GOx). The obtained GOx supernatant catalyzes glucose to produce H2O2, which can oxidize Ce‐MOF, leading to the alteration of electrode color and a significant decrease in the overall photocurrent of MXSnO/Ce‐MOF. Crucially, the novel OPECT‐SCL biosensor exhibits excellent sensitivity and precision, boasting detection thresholds as low as 42.9 pM and 1.2 nM, respectively, and accomplishes the automated detection of OA within real samples. The proposed OPECT‐SCL dual‐signal measurement model constitutes a sensitive, portable, and precise platform for the quantification of marine toxins.

Research on the thermal balance of a novel independent heat extraction-release double helix energy pile in long-term operation

Ground source heat pump buried pipes offer potential in civil defense due to their concealment and reliability, yet face thermal imbalance issues. This paper adopts a double helix energy pile with independent heat extraction-release capacity and develops an experiment to compare the performance of independent operation versus joint operation. Furthermore, a verified 2D model facilitated extensive simulations for long-term thermal balance, integrating refrigeration load, principles of water use in an underground engineering, and heat pump model. Comparative experiments show that joint operation can effectively alleviate soil heat accumulation by more than 20%. Extended simulations reveal that as accumulated heat is removed, the unit's performance is improved, and soil heat accumulation can boost heat extraction. However, under domestic water heat extraction, the heat-extracting pipe shows low flow rates, leading to thermal accumulation, necessitating the use of water for equipment or additional feed water to improve heat extraction. Compared to uniform enhancement heat extraction, centralized enhanced heat extraction boosts overall heat extraction capacity by 35.1%, which can more effectively mitigate thermal imbalances and improve unit performance, and achieving thermal balance in the geotechnical area requires an enhanced extraction flow rate above 10.5 L/h, with over 56 m3 of water passing through the heat-extracting pipe.

Developing flame retardant, smoke suppression and self-healing polyvinyl alcohol composites by dynamic reversible cross-linked chitosan-based macromolecule

With the increasing threat of white pollution to the public health and ecosystem, functional materials driven by green and sustainable biological macromolecule are attracting considerable attention. Inspired by the double-helix structure of DNA, a P–B–N ternary synergistic chitosan-based macromolecule (PBCS) was constructed to prepare flame retardant, smoke suppression and self-healing polyvinyl alcohol composite (PVA@PBCS) via dynamic reversible interactions. The limiting oxygen index value of PVA@PBCS increased from 19.6 % to 28.7 %, whereas the peak heat release rate and total heat release decreased by 47.04 % and 43.37 %, respectively. Besides, the peak smoke production rate and total smoke production of PVA@PBCS also decreased by 45.31 % and 54.98 %. With the presence of borate ester-based covalent and multiple hydrogen bonds, the tensile strength and elongation at break of PVA@PBCS increased by 19.50 % and 16.85 % compared to the control sample, and the healing efficiency for tensile strength and elongation at break was as high as 93.86 % and 90.57 %, respectively. This work developed an eco-friendly and effective scenario for fabricating flame retardant and smoke suppression PVA materials, stimulating the substantial potential of chitosan-based biomacromolecule and dynamic reversible cross-linked tactics in self-healing field.

Metal-Based Drug-DNA Interactions and Analytical Determination Methods.

DNA structure has many potential places where endogenous compounds and xenobiotics can bind. Therefore, xenobiotics bind along the sites of the nucleic acid with the aim of changing its structure, its genetic message, and, implicitly, its functions. Currently, there are several mechanisms known to be involved in DNA binding. These mechanisms are covalent and non-covalent interactions. The covalent interaction or metal base coordination is an irreversible binding and it is represented by an intra-/interstrand cross-link. The non-covalent interaction is generally a reversible binding and it is represented by intercalation between DNA base pairs, insertion, major and/or minor groove binding, and electrostatic interactions with the sugar phosphate DNA backbone. In the present review, we focus on the types of DNA-metal complex interactions (including some representative examples) and on presenting the methods currently used to study them.

Nucleotide excision repair of aflatoxin-induced DNA damage within the 3D human genome organization.

Aflatoxin B1 (AFB1), a potent mycotoxin, is one of the environmental risk factors that cause liver cancer. In the liver, the bioactivated AFB1 intercalates into the DNA double helix to form a bulky DNA adduct which will lead to mutation if left unrepaired. Here, we adapted the tXR-seq method to measure the nucleotide excision repair of AFB1-induced DNA adducts at single-nucleotide resolution on a genome-wide scale, and compared it with repair data obtained from conventional UV-damage XR-seq. Our results showed that transcription-coupled repair plays a major role in the damage removal process. We further analyzed the distribution of nucleotide excision repair sites for AFB1-induced DNA adducts within the 3D human genome organization. Our analysis revealed a heterogeneous AFB1-dG repair across four different organization levels, including chromosome territories, A/B compartments, TADs, and chromatin loops. We found that chromosomes positioned closer to the nuclear center and regions within A compartments have higher levels of nucleotide excision repair. Notably, we observed high repair activity around both TAD boundaries and loop anchors. These findings provide insights into the complex interplay between AFB1-induced DNA damage repair, transcription, and 3D genome organization, shedding light on the mechanisms underlying AFB1-induced mutagenesis.

Conversion of oxidative combustion into powerful thermal and light energy

The phenomenon of transformation of the oxidative combustion of natural coolants - coal, methane, propane, etc. - into the production of powerful light and thermal energy when their combustion zone is exposed to supersonic spiral-twisted jets of dusty plasma from a dynamic emitter has been experimentally discovered. The phenomenon occurs without emissions of harmful substances from chemical combustion that contribute to the greenhouse effect. The structure of dusty plasma jet is a self-compressing double helix with collective resonant oscillations. The phenomenon opens up a new type of energy production, connected with a conversion of coal into aluminosilicate minerals, etc.

Autoclaved Starch: Structure and Functionality Relationship in a Matrix With the Same Contribution ofAmylose and Amylopectin.

The rational use of autoclaved starches in food applications is difficult because there is a lack of information on their structure-functionality relationship. The novelty of this research relies on disclosing such an association. Hylon V starch was autoclaved at 105, 120, and 135°C to investigate its crystalline and double-helical features and its relationship with functionality. In autoclaved Hylon V starch, interactions of amylopectin and amylose improved while the crystalline regions decreased. The degree of double helices (DD) decreased after autoclaving at 105°C and the degree of order (DO) increased after treatment at 120 and 135°C. The water solubility index (WSI) (4.63-6.38%) and swelling power (SP) (4.39-7.1 g/g) increased when the temperature increased. On the other hand, water (103.49-225.01%) and oil (61.91-94.53%) holding capacity (WHC and OHC, respectively) increased after autoclaving treatment, although the values decreased with the treatment intensity. The functional properties were affected when the structure changed as a function of the treatment temperatures. PCA analysis showed that WSI and SP of autoclaved Hylon V starch were associated with a high DD, with better compaction, and with stronger amylopectin-amylose interactions. WHC and OHC were associated with better crystallinity, stronger interactions of amylopectin and amylose, and heterogeneous double-helical crystallites. These findings are useful for understanding the structure-functionality relationship of autoclaved Hylon V starch and pave the way for future research regarding the effects of its incorporation on the properties of food matrices such as bread, yogurt, cakes, and pudding.