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1.
J Chem Phys ; 151(12): 125101, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31575173

RESUMO

Gene regulation is one of the most important fundamental biological processes in living cells. It involves multiple protein molecules that locate specific sites on DNA and assemble gene initiation or gene repression multimolecular complexes. While the protein search dynamics for DNA targets has been intensively investigated, the role of intermolecular interactions during the genetic activation or repression remains not well quantified. Here, we present a simple one-dimensional model of target search for two interacting molecules that can reversibly form a dimer molecular complex, which also participates in the search process. In addition, the proteins have finite residence times on specific target sites, and the gene is activated or repressed when both proteins are simultaneously present at the target. The model is analyzed using first-passage analytical calculations and Monte Carlo computer simulations. It is shown that the search dynamics exhibit a complex behavior depending on the strength of intermolecular interactions and on the target residence times. We also found that the search time shows a nonmonotonic behavior as a function of the dissociation rate for the molecular complex. Physical-chemical arguments to explain these observations are presented. Our theoretical approach highlights the importance of molecular interactions in the complex process of gene activation/repression by multiple transcription factor proteins.


Assuntos
DNA/química , Modelos Químicos , Simulação por Computador , DNA/genética , DNA/metabolismo , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Cinética , Método de Monte Carlo , Proteína Supressora de Tumor p53/química , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
2.
J Chem Phys ; 151(12): 125102, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31575191

RESUMO

We present an analytical model for the role of hydrogen bonding on the spin-orbit coupling of a model DNA molecule. Here, we analyze in detail the electric fields due to the polarization of the hydrogen bond on the DNA base pairs and derive, within a tight binding analytical band folding approach, an intrinsic Rashba coupling which should dictate the order of the spin active effects in the chiral-induced spin selectivity effect. The coupling found is ten times larger than the intrinsic coupling estimated previously and points out to the predominant role of hydrogen bonding in addition to chirality in the case of biological molecules. We expect similar dominant effects in oligopeptides, where the chiral structure is supported by hydrogen-bonding and bears on orbital carrying transport electrons.


Assuntos
DNA/química , Modelos Químicos , Transporte de Elétrons , Ligações de Hidrogênio , Oligopeptídeos/química
3.
Phys Chem Chem Phys ; 21(36): 20095-20106, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31482894

RESUMO

Rational modification of biomolecules especially DNA base pairs for the theoretical design of molecular magnets has attracted extensive interest. In this work, we report a modification strategy for adenine/thymine-based magnets through introducing a N,N-dioxidized pyrazine ring to either adenine or thymine to form ring-expanded bases (noA/noT) based on their experimentally synthesized derivatives. Further functionalization is conducted by double protonation and pairing with a normal complementary base (nohA-T/nohT-A), respectively. The diversity of protonation sites in noA generates totally six nohA-Ts, together with nohT-A forming seven two-step modified topic base pairs. DFT calculations are performed to characterize the magnetic properties and the diradical character, which indicate three diamagnetic (DM) nohA-Ts and three antiferromagnetic (AFM) nohA-Ts with extremely large magnetic coupling constants J ranging from -1279.7 to -2807.4 cm-1, while a relatively mild AFM nohT-A with a J of -194.6 cm-1. The electron separation effect induced by attraction of positive charges originating from protonation is proposed to explain the diradicalization, which is different from the traditional radical-coupler-radical coupling mode. In addition, atomic natural charges and spin densities, and H-bond and molecular orbital analyses are further discussed for verification and deep understanding of the observed unique phenomena. It should be noted that our designed seven topic base pairs have excellent characters including a good synthetic basis, a large scope of the |J| values, and the AFM-DM magnetic conversion or AFM strength modulation controlled by protonation/deprotonation, prototropic tautomerization, base pairing/dissociation, single proton transfer, and even the applied electric field. All these indicate the promising applications in the field of magnetic information storage or switch control. This work highlights the magnetic modification schemes and possible modulation methods of double positive charge doped DNA base pairs by utilizing their potential spin coupling modes.


Assuntos
Pareamento de Bases , DNA/química , Magnetismo , Pirazinas/química , Timina/química , Prótons
4.
Phys Chem Chem Phys ; 21(37): 20606-20612, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31528919

RESUMO

In this work, the interaction between an Auramine O (AuO) fluorescent molecular rotor and natural DNA, its thermodynamic aspects and the resulting variation of the optical properties upon binding are addressed by a combined spectroscopic (UV-vis and fluorescence) and computational approach. DNA binding causes a shift in the maximum of absorption from 432 nm to 444 nm, a decrease of the extinction coefficient and a dramatic enhancement of fluorescence emission, these results being in agreement with intercalation into the polynucleotide helix. Intercalation is indeed confirmed by the thermodynamic parameters for the binding reaction (in particular, the highly negative ΔH). Theoretical modelling at the TD-DFT level was done on a simplified model system consisting of the AuO molecule intercalated between two DNA base pairs. The evolution of the calculated vertical transitions quantitatively reproduces the experimentally observed hypo- and bathochromic shifts, thus confirming the intercalation hypothesis.


Assuntos
Benzofenoneídio/química , DNA/química , Modelos Químicos , Análise Espectral , Fluorescência , Simulação de Dinâmica Molecular
5.
Chem Commun (Camb) ; 55(66): 9857-9860, 2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31364637

RESUMO

A novel fluorescent sensing platform for telomerase activity assay was developed by coupling a three-dimensional (3D) DNA walker with the MnO2 nanosheet-upconversion nanoparticle (UCNPs) complex-based fluorescence resonance energy-transfer (FRET) system.


Assuntos
Técnicas Biossensoriais/métodos , DNA/química , Transferência Ressonante de Energia de Fluorescência/instrumentação , Compostos de Manganês/química , Nanoestruturas/química , Óxidos/química , Telomerase/metabolismo , Limite de Detecção
6.
Phys Chem Chem Phys ; 21(32): 17971-17977, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31384846

RESUMO

The electron-hole injection from a family of spiropyran photoswitches into A/T-duplex DNA has been investigated at the molecular level for the first time. Multiscale computations coupled with automatized quantitative wavefunction analysis reveal a pronounced directionality and regioselectivity towards the template strand of the duplex DNA. Our findings suggest that this directional and regioselective photoinduced electron-hole transfer could thus be exploited to tailor the charge transport processes in DNA in specific applications.


Assuntos
Benzopiranos/química , DNA/química , Indóis/química , Substâncias Intercalantes/química , Nitrocompostos/química , Transporte de Elétrons , Luz , Modelos Moleculares , Conformação de Ácido Nucleico , Oxirredução , Processos Fotoquímicos , Prótons , Termodinâmica
7.
Chem Commun (Camb) ; 55(67): 9955-9958, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31364619

RESUMO

A silver nanocluster-based ratiometric fluorescent nanosensor was developed for the determination of ATP in the cerebrospinal fluid of a mouse brain. Using this useful tool with good stability and high selectivity as well as a wide linear detection range, it was found that the ATP concentration in a mouse brain with Alzheimer's disease was 2300-fold higher than that in a normal one.


Assuntos
Trifosfato de Adenosina/líquido cefalorraquidiano , Química Encefálica , DNA/química , Corantes Fluorescentes/química , Nanopartículas Metálicas/química , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Encéfalo/citologia , Encéfalo/patologia , Córtex Cerebral/química , Hipocampo/química , Camundongos , Conformação de Ácido Nucleico , Prata/química , Espectrometria de Fluorescência/métodos
8.
Chem Commun (Camb) ; 55(69): 10300-10303, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31397452

RESUMO

Shorter DNA probes provide better specificity for hybridization, but they may not form stable duplexes at room temperature. In this study, we used thiazole orange to follow DNA hybridization upon freezing and achieved stable 5-mer duplex DNA. Using multiple short probes in tandem, long DNA could also be studied. This study provides insights into DNA hybridization in the frozen state and expands the application of freezing for nucleic acid chemistry.


Assuntos
DNA/química , Hibridização de Ácido Nucleico , Oligonucleotídeos/química , Pareamento Incorreto de Bases , Sequência de Bases , Benzotiazóis/análise , DNA/genética , Sondas de DNA/química , Sondas de DNA/genética , Corantes Fluorescentes/análise , Congelamento , Oligonucleotídeos/genética , Quinolinas/análise , Espectrometria de Fluorescência
9.
J Nanobiotechnology ; 17(1): 86, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31387581

RESUMO

BACKGROUND: Controllable and multiple DNA release is critical in modern gene-based therapies. Current approaches require complex assistant molecules for combined release. To overcome the restrictions on the materials and environment, a novel and versatile DNA release method using a nano-electromechanical (NEMS) hypersonic resonator of gigahertz (GHz) frequency is developed. RESULTS: The micro-vortexes excited by ultra-high frequency acoustic wave can generate tunable shear stress at solid-liquid interface, thereby disrupting molecular interactions in immobilized multilayered polyelectrolyte thin films and releasing embedded DNA strands in a controlled fashion. Both finite element model analysis and experiment results verify the feasibility of this method. The release rate and released amount are confirmed to be well tuned. Owing to the different forces generated at different depth of the films, release of two types of DNA molecules with different velocities is achieved, which further explores its application in combined gene therapy. CONCLUSIONS: Our research confirmed that this novel platform based on a nano-electromechanical hypersonic resonator works well for controllable single and multi-DNA release. In addition, the unique features of this resonator such as miniaturization and batch manufacturing open its possibility to be developed into a high-throughput, implantable and site targeting DNA release and delivery system.


Assuntos
DNA/química , Nanoestruturas/química , Polieletrólitos/química , Acústica/instrumentação , Fenômenos Biofísicos , Desenho de Equipamento , Análise de Elementos Finitos , Técnicas de Transferência de Genes , Terapia Genética/métodos , Membranas Artificiais , Propriedades de Superfície
10.
Phys Rev Lett ; 123(3): 038101, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31386470

RESUMO

Synthesis of biopolymers such as DNA, RNA, and proteins are biophysical processes aided by enzymes. The performance of these enzymes is usually characterized in terms of their average error rate and speed. However, because of thermal fluctuations in these single-molecule processes, both error and speed are inherently stochastic quantities. In this Letter, we study fluctuations of error and speed in biopolymer synthesis and show that they are in general correlated. This means that, under equal conditions, polymers that are synthesized faster due to a fluctuation tend to have either better or worse errors than the average. The error-correction mechanism implemented by the enzyme determines which of the two cases holds. For example, discrimination in the forward reaction rates tends to grant smaller errors to polymers with faster synthesis. The opposite occurs for discrimination in monomer rejection rates. Our results provide an experimentally feasible way to identify error-correction mechanisms by measuring the error-speed correlations.


Assuntos
Biopolímeros/biossíntese , Enzimas/química , Enzimas/metabolismo , Biopolímeros/química , DNA/biossíntese , DNA/química , Humanos , Modelos Biológicos , Modelos Químicos , RNA/biossíntese , RNA/química
11.
Chem Commun (Camb) ; 55(72): 10673-10676, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31433407

RESUMO

We used single-molecule FRET experiments to monitor the conformational equilibrium of a DNA hairpin under pressure-stress in the presence of an aqueous two-phase system mimicking intracellular liquid-liquid phase separation (LLPS). Our data demonstrate the important role of LLPS with its immanent strong excluded volume effect in rescuing biological function under harsh environmental conditions.


Assuntos
DNA/química , Transferência Ressonante de Energia de Fluorescência , Conformação de Ácido Nucleico
12.
Chem Commun (Camb) ; 55(71): 10603-10606, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31424058

RESUMO

A truly ratiometric homogeneous electrochemical biosensor has been developed for sensitive miRNA detection based on the unique diffusion/intercalation properties of electroactive dyes without the need for electrode modification or materials preparation.


Assuntos
Técnicas Biossensoriais/métodos , Corantes/química , Técnicas Eletroquímicas/métodos , Substâncias Intercalantes/química , MicroRNAs/análise , DNA/química , Eletrodos , Exodesoxirribonucleases/química , Compostos Ferrosos/química , Limite de Detecção , Metalocenos/química , Azul de Metileno/química , Oxirredução
13.
Arch Virol ; 164(10): 2627-2630, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31363923

RESUMO

A lytic bacteriophage, designated Vibrio phage vB_VpP_BA6, was isolated from sewage collected in Guangzhou, China. The double-stranded DNA genome of phage BA6 is composed of 50,520 bp with a G+C content of 41.77%. It possesses 64 open reading frames relating to phage structure, packaging, host lysis, DNA metabolism, and additional functions. Three tRNAs genes (encoding Pro, Ile and Trp) were detected. Comparison of its genomic features and phylogenetic analysis revealed that phage BA6 is a novel member of the family Podoviridae. This phage may represent a potential therapeutic agent against multidrug-resistant Vibrio parahaemolyticus.


Assuntos
Bacteriófagos/genética , Bacteriófagos/isolamento & purificação , Genoma Viral , Podoviridae/genética , Podoviridae/isolamento & purificação , Vibrio parahaemolyticus/virologia , Bacteriólise , Bacteriófagos/classificação , Bacteriófagos/crescimento & desenvolvimento , Composição de Bases , China , DNA/química , DNA/genética , Fases de Leitura Aberta , Filogenia , Podoviridae/classificação , Podoviridae/crescimento & desenvolvimento , RNA de Transferência/genética , Esgotos/virologia
14.
Chem Commun (Camb) ; 55(67): 9967-9970, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31367705

RESUMO

Herein, a seesaw ratiometric (SR) probe is designed which integrates fluorescence and surface enhanced Raman scattering (SERS) technology. Fluorescence imaging enables tracking of the spatiotemporal dynamic behaviour of telomerase. Meanwhile, SERS reverse ratiometric measurement can enable sensitive detection of telomerase activity in single living cells.


Assuntos
Corantes/química , Imagem Óptica/métodos , Análise de Célula Única/métodos , Análise Espectral Raman/métodos , Telomerase/metabolismo , DNA/química , Transferência Ressonante de Energia de Fluorescência/métodos , Ouro/química , Humanos , Células MCF-7 , Nanopartículas Metálicas/química
15.
Chem Commun (Camb) ; 55(67): 9971-9974, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31367709

RESUMO

Photodynamic therapy (PDT) is a clinically approved cancer treatment that uses light, oxygen and a photosensitizer to produce localized reactive oxygen species (ROS). Due to the short lifetime of ROS, the location of the photosensitizer in the cell is believed to be the key determinant governing the outcome of PDT. To explore the effect of direct association between a photosensitizer and DNA a well know DNA-binding dye, DAPI, was converted into a photosensitizer. Br-DAPI - unlike native DAPI - upon irradiation produces ROS. We demonstrate that the ROS are only effective in inducing dsDNA breaks when Br-DAPI is bound to DNA. In cancer cells (A549) Br-DAPI causes rapid light dependent cell death. This work supports the design of photosensitizers which bind with high affinity to the DNA of target cells for potentially more effective PDT.


Assuntos
Bromo/química , DNA/química , Indóis/química , Fármacos Fotossensibilizantes/química , Células A549 , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Dano ao DNA , Corantes Fluorescentes/química , Humanos , Luz , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Estudo de Prova de Conceito , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/metabolismo
16.
Phys Rev Lett ; 122(21): 218101, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31283336

RESUMO

Base-pair mismatch can relieve mechanical stress in highly strained DNA molecules, but how it affects their kinetic stability is not known. Using single-molecule fluorescence resonance energy transfer, we measured the lifetimes of tightly bent DNA loops with and without base-pair mismatch. Surprisingly, for loops captured by stackable sticky ends which leave single-stranded DNA breaks (or nicks) upon annealing, the mismatch decreased the loop lifetime despite reducing the overall bending stress, and the decrease was largest when the mismatch was placed at the DNA midpoint. These findings suggest that base-pair mismatch increases bending stress at the opposite side of the loop through an allosteric mechanism known as cooperative kinking. Based on this mechanism, we present a three-state model that explains the apparent dichotomy between thermodynamic and kinetic stability.


Assuntos
Pareamento Incorreto de Bases , DNA/química , Transferência Ressonante de Energia de Fluorescência , Cinética , Modelos Químicos , Conformação de Ácido Nucleico , Termodinâmica
17.
J Chem Phys ; 150(24): 244120, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31255081

RESUMO

Recently derived steady-state differential rate laws for the catalytic turnover of molecules containing two substrate sites are reformulated as integrated rate laws. The analysis applies to a broad class of Markovian dynamic models, motivated by the varied and often complex mechanisms associated with DNA modifying enzymes. Analysis of experimental data for the methylation kinetics of DNA by Dam (DNA adenine methyltransferase) is drastically improved through the use of integrated rate laws. Data that are too noisy for fitting to differential predictions are reliably interpreted through the integrated rate laws.


Assuntos
DNA/química , DNA Metiltransferases Sítio Específica (Adenina-Específica)/química , Metilação de DNA , Cinética , Cadeias de Markov , Modelos Químicos
18.
J Chem Theory Comput ; 15(8): 4699-4707, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31314523

RESUMO

We present a fast implementation of the nudged elastic band (NEB) method into the particle mesh Ewald molecular dynamics module of the Amber software package for both central processing units (CPU) and graphics processing units (GPU). The accuracy of the new implementation has been validated for three cases: a conformational change of alanine dipeptide, the α-helix to ß-sheet transition in polyalanine, and a large conformational transition in the human 8-oxoguanine-DNA glycosylase with DNA complex (OGG1-DNA). Timing benchmark tests were performed on the explicitly solvated OGG1-DNA system containing ∼50 000 atoms. The GPU-optimized implementation of NEB achieves a more than two orders of magnitude speedup compared with the previous CPU implementation performed with a two-core CPU processor. The speed and scalable features of this implementation will enable NEB applications on larger and more complex systems.


Assuntos
DNA Glicosilases/química , Dipeptídeos/química , Simulação de Dinâmica Molecular , Peptídeos/química , Gráficos por Computador , DNA/química , Humanos , Conformação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Software , Fatores de Tempo
19.
J Chem Phys ; 151(1): 014901, 2019 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-31272182

RESUMO

The elasticity of dsDNA molecules is investigated by Monte Carlo simulations based on a coarse-grained model of DNA. The force-displacement (f-r) curves are computed under the constraints of the constant force (Gibbs) or the constant length (Helmholtz) ensemble. Particular attention was paid to the compressional (negative) and weak tensile forces. It was confirmed that simulations using the vector Gibbs ensemble fail to represent the compression behavior of polymers. Simulations using the scalar Gibbs protocol resulted in a qualitatively correct compressional response of DNA provided that the quadratic averages of displacements were employed. Furthermore, a well-known shortcoming of the popular Marko-Siggia relation for DNA elasticity at weak tensile forces is elucidated. Conversely, the function f-r from the simulation at the constant length constraint, as well as the new closed-form expressions, provides a realistic depiction of the DNA elasticity over the wide range of negative and positive forces. Merely a qualitative resemblance of the compression functions f-r predicted by the employed approaches supports the notion that the elastic response of DNA molecules may be greatly affected by the specifics of the experimental setups and the kind of averaging of the measured variable.


Assuntos
DNA/química , Microscopia de Força Atômica , Método de Monte Carlo , Pinças Ópticas
20.
Chem Soc Rev ; 48(16): 4347-4360, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31263808

RESUMO

To exert its role of a functional polymer, DNA relies on a molecular self-assembly process that is driven by the interactions of only four units placed in a defined order. Extending the structural diversity of recognition motifs in DNA, to and beyond analogues of the nucleobases, will open doors to self-assembled materials with advanced programmable properties. DNA-inspired systems are becoming useful for numerous applications unachievable by the nucleic acids in their native composition. Potential applications of rationally designed oligo- and polyphosphodiesters reside in the areas of drug delivery, diagnostic signalling and imaging, in systems for efficient energy transfer or the precise ordering on the nanoscale. The field of DNA-inspired phosphodiesters highlights the general value and utility of precision in the composition of oligomers and polymers. In this tutorial review, we will summarize the approaches of directing the self-assembly of DNA-inspired, sequence-specific polyphosphodiesters into soft materials with unique properties. These data expose the so far underexploited potential of DNA-derived systems in solving some of the key issues in various technological areas, such as advanced biomaterials, morphologically defined soft matter or the controlled polymer folding and assembly. Moreover, precise positioning of structurally diverse molecules within a polymer chain creates unmatched opportunities for encoding information on the molecular level and transmitting it further to the microscopic and even macroscopic level via noncovalent interactions.


Assuntos
DNA/química , Polímeros/química , Azidas/química , Lipossomos/química , Compostos Organofosforados/química , Polímeros/síntese química
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