Minor Groove Binding between Norfloxacin and DNA Duplexes in Solution: A Molecular Dynamics Study

Molecular dynamics were used to investigate the interaction between norfloxacin and DNA duplex. The results showed that norfloxacin was situated in the minor groove of DNA, binding to the TCGA region of d [ATATCGATAT] 2- Specific hydrogen bonds were formed between norfloxacin and guanine base of DNA during the 2 ns MD, which may be the reason for the preferentiality of quinolone antibacterial towards the guanine base of DNA duplex.

Adsorption dynamics of double-stranded DNA on a graphene oxide surface with both large unoxidized and oxidized regions

The adsorption dynamics of double-stranded DNA(dsDNA)molecules on a graphene oxide(GO)surface are important for applications of DNA/GO functional structures in biosensors,biomedicine and materials science.In this work,molecular dynamics simulations were used to examine the adsorption of different length dsDNA molecules(from 4 bp to24 bp)on the GO surface.The dsDNA molecules could be adsorbed on the GO surface through the terminal bases and stand on the GO surface.For short dsDNA(4 bp)molecules,the double-helix structure was partially or totally broken and the adsorption dynamics was affected by the structural fluctuation of short dsDNA and the distribution of the oxidized groups on the GO surface.For long dsDNA molecules(from 8 bp to 24 bp)adsorption is stable.By nonlinear fitting of the contact angle between the axis of the dsDNA molecule and the GO surface,we found that a dsDNA molecule adsorbed on a GO surface has the chance of orienting parallel to the GO surface if the length of the dsDNA molecule is longer than 54 bp.We attributed this behavior to the flexibility of dsDNA molecules.With increasing length,the flexibility of dsDNA molecules also increases,and this increasing flexibility gives an adsorbed dsDNA molecule more chance of reaching the GO surface with the free terminal.This work provides a whole picture of adsorption of dsDNA molecules on the GO surface and should be of benefit for the design of DNA/GO based biosensors.

Molecular dynamics simulation of peeling a DNA molecule on substrate

Molecular dynamics （MD） simulations are performed to study adhesion and peeling of a short fragment of single strand DNA （ssDNA） molecule from a graphite surface. The critical peel-off force is found to depend on both the peeling angle and the elasticity of ssDNA. For the short ssDNA strand under investigation, we show that the simulation results can be explained by a continuum model of an adhesive elastic band on substrate. The analysis suggests that it is often the peak value, rather than the mean value, of adhesion energy which determines the peeling of a nanoscale material.

Processes of DNA condensation induced by multivalent cations: Approximate annealing experiments and molecular dynamics simulations

The condensation of DNA induced by spermine is studied by atomic force microscopy （AFM） and molecular dynamics （MD） simulation in this paper. In our experiments, an equivalent amount of multivalent cations is added to the DNA solutions in different numbers of steps, and we find that the process of DNA condensation strongly depends on the speed of adding cations. That is, the slower the spermine cations are added, the slower the DNA aggregates. The MD and steered molecular dynamics （SMD） simulation results agree well with the experimental results, and the simulation data also show that the more steps of adding multivalent cations there are, the more compact the condensed DNA structure will be. This investigation can help us to control DNA condensation and understand the complicated structures of DNA--cation complexes.

Decondensation behavior of DNA chains induced by multivalent cations at high salt concentrations:Molecular dynamics simulations and experiments

Using molecular dynamics simulations and atomic force microscopy （AFM）, we study the decondensation process of DNA chains induced by multivalent cations at high salt concentrations in the presence of short cationic chains in solutions. The typical simulation conformations of DNA chains with varying salt concentrations for multivalent cations imply that the concentration of salt cations and the valence of multivalent cations have a strong influence on the process of DNA decondensation. The DNA chains are condensed in the absence of salt or at low salt concentrations, and the compacted conformations of DNA chains become loose when a number of cations and anions are added into the solution. It is explicitly demonstrated that cations can overcompensate the bare charge of the DNA chains and weaken the attraction interactions between the DNA chains and short cationic chains at high salt concentrations. The condensation-decondensation transi- tions of DNA are also experimentally observed in mixing spermidine with X-phage DNA at different concentrations of NaCl/MgCl2 solutions.

Molecular dynamics simulations of a DNA photolyase protein: High-mobility and conformational changes of the FAD molecule at low temperatures

A molecular dynamics (MD) simulation is performed on a DNA photolyase to study the conformational behavior of the photoactive cofactor flavin adenine dinucleotide (FAD) inside the enzyme pocket. A DNA photolyase is a highly efficient light-driven enzyme that repairs the UV-induced cyclobutane pyrimidine dimer in damaged DNA. In this work, the FAD conformational and dynamic changes were studied within the total complex structure of a DNA photolyase protein (containing FADH–, MTHF, and DNA molecules) embedded in a water solvent. We aimed to compare the conformational changes of the FAD cofactor and other constituent fragments of the molecular system under consideration. The obtained results were discussed to gain insight into the light-driven mechanism of DNA repair by a DNA photolyase enzyme—based on the enzyme structure, the FAD mobility, and conformation shape.

Molecular Dynamics Simulations of the DNA-CNT Interaction Process: Hybrid Quantum Chemistry Potential and Classical Trajectory Approach

In this work the quantum chemistry Tersoff potential in combination with classical trajectory calculations was used to investigate the interaction of the DNA molecule with a carbon nanotube (CNT). The so-called hybrid approach—the classical and quantum-chemical modeling, where the force fields and interaction between particles are based on a definite (but not unique) description method, has been outlined in some detail. In such approach the molecules are described as a set of spheres and springs, thereby the spheres imitate classical particles and the spring the interaction force fields provided by quantum chemistry laws. The Tersoff potential in hybrid molecular dynamics (MD) simulations correctly describes the nature of covalent bonding. The aim of the present work was to estimate the dynamical and structural behavior of the DNA-CNT system at ambient temperature conditions. The dynamical configurations were built up for the DNA molecule interacting with the CNT. The analysis of generated МD configurations for the DNA-CNT complex was carried out. For the DNA-CNT system the observations reveal an encapsulation-like behavior of the DNA chain inside the CNT chain. The discussions were made on possible use of the DNA-CNT complex as a candidate material in drug delivery and related systems.

Molecular dynamics simulations exploring the interaction between DNA and metalated bleomycin

Bleomycin (Blm) is a natural antibiotic with antitumour activity, used as a combination drug in treatment of various types of cancers. Blm intercalates with DNA and will in the presence of a redox metal ion and molecular oxygen form an activated bleomycin complex capable of releasing free radicals and subsequently leading to DNA cleavage. The present theoretical work was carried out to better understand the interaction between DNA and Blm using different metal co-factors (Co and Fe). Binding energies and structural properties were analysed for both the complexes. The results show that Blm binds stronger to DNA when complexed with Fe, and provides a better structural orientation compared to the CoBlm complex in order to abstract the H4' hydrogen of deoxyribose that initiates the DNA strand cleavage process. The short distance between the iron-bound peroxide and the deoxyribose H4' furthermore supports the previously proposed direct abstraction mechanism.

石墨烯与抑癌基因p53 DNA片段相互作用的分子模拟与光谱学验证

石墨烯(graphene,G)及其衍生物由于具有独特的理化性质,被广泛应用于能源、生物医学等领域,但尚缺乏其对生物体和环境潜在危害的研究。采用分子动力学模拟并结合光谱学方法(紫外可见吸收光谱、紫外变温实验及荧光光谱),分析了石墨烯与抑癌基因p53启动子区DNA片段(p53-DNA)间的相互作用,并探讨了相关作用机制。石墨烯的部分芳香环与p53-DNA碱基的芳香环之间存在π-π堆积作用,两者可以通过嵌插作用进行结合,同时还通过沟槽作用进一步结合。光谱实验进一步证实,在石墨烯作用下,p53-DNA的熔点(Tm)值升高,EB-DNA体系发生静态荧光淬灭,说明石墨烯能与p53-DNA结合;同时,p53-DNA与石墨烯结合后在260 nm处的吸光度升高,说明石墨烯对p53-DNA的双螺旋结构具有一定的破坏作用。上述研究结果从分子水平上分析了石墨烯与p53-DNA间的相互作用机制,有助于进一步阐明石墨烯的毒性作用机理。

Normal Mode Analysis on Three Different Structures of a Duplex DNA d(CGCGAATTCGCG)

Normal mode analysis in dihedral angle space was carried out on two X ray crystal structures and one model structure responded to the same sequence of duplex DNA: d(CGCGAATTCGCG). Comparing these results indicates that it is reliable and meaningful to carry out normal mode analysis on model structures. The reliability is greater except for the ends of helix.

Molecular dynamics simulations on the interactions between nucleic acids and a phospholipid bilayer

Recently,lipid nanoparticles(LNPs)have been extensively investigated as non-viral carriers of nucleic acid vaccines due to their high transport efficiency,safety,and straightforward production and scalability.However,the molecular mechanism underlying the interactions between nucleic acids and phospholipid bilayers within LNPs remains elusive.In this study,we employed the all-atom molecular dynamics simulation to investigate the interactions between single-stranded nucleic acids and a phospholipid bilayer.Our findings revealed that hydrophilic bases,specifically G in single-stranded RNA(ssRNA)and single-stranded DNA(ssDNA),displayed a higher propensity to form hydrogen bonds with phospholipid head groups.Notably,ssRNA exhibited stronger binding energy than ssDNA.Furthermore,divalent ions,particularly Ca2+,facilitated the binding of ssRNA to phospholipids due to their higher binding energy and lower dissociation rate from phospholipids.Overall,our study provides valuable insights into the molecular mechanisms underlying nucleic acidphospholipid interactions,with potential implications for the nucleic acids in biotherapies,particularly in the context of lipid carriers.

Mechanism studies of the activation of DNA methyltransferase DNMT1 triggered by histone H3 ubiquitination,revealed by multi-scale molecular dynamics simulations

DNMT1 is a DNA methyltransferase that catalyzes and maintains methylation in CpG dinucleotides.It blocks the entrance of DNA into the catalytic pocket via the replication foci targeting sequence(RFTS)domain.Recent studies have shown that an H3-tail-conjugated two-mono-ubiquitin mark(H3Ub2)activates DNMT1 by binding to the RFTS domain.However,the activation mechanism of DNMT1 remains unclear.In this work,we combine various sampling methods of extensive simulations,including conventional molecular dynamics,Gaussian-accelerated molecular dynamics,and coarse-grained molecular dynamics,to elucidate the activation mechanism of DNMT1.Geometric and energy analyses show that binding of H3Ub2 to the RFTS domain of DNMT1 results in the bending of theα4-helix in the RFTS domain at approximately 30°–35°,and the RFTS domain rotates~20°anti-clockwise and moves~3?away from the target recognition domain(TRD).The hydrogen-bonding network at the RFTSTRD interface is significantly disrupted,implying that the RFTS domain is dissociated from the catalytic core,which contributes to activating the auto-inhibited conformation of DNMT1.These results provide structural and dynamic evidence for the role of H3Ub2 in regulating the catalytic activity of DNMT1.

Molecular dynamics simulation reveals DNA-specific recognition mechanism via c-Myb in pseudo-palindromic consensus of mim-1 promoter

This study aims to gain insight into the DNA-specific recognition mechanism of c-Myb transcription factor during the regulation of cell early differentiation and proliferation.Therefore,we chose the chicken myeloid gene,mitochondrial import protein 1(mim-1),as a target to study the binding specificity between potential dual-Myb-binding sites.The c-Myb-binding site in mim-1 is a pseudo-palindromic sequence AACGGTT,which contains two AACNG consensuses.Simulation studies in different biological scenarios revealed that c-Myb binding with mim-1 in the forward strand(complex F)is more stable than that in the reverse strand(complex R).The principal component analysis(PCA)dynamics trajectory analyses suggested an opening motion of the recognition helices of R2 and R3(R2R3),resulting in the dissociation of DNA from c-Myb in complex R at 330 K,triggered by the reduced electrostatic potential on the surface of R2R3.Furthermore,the DNA confirmation and hydrogen-bond interaction analyses indicated that the major groove width of DNA increased in complex R,which affected on the hydrogenbond formation ability between R2R3 and DNA,and directly resulted in the dissociation of DNA from R2R3.The steered molecular dynamics(SMD)simulation studies also suggested that the electrostatic potential,major groove width,and hydrogen bonds made major contribution to the DNA-specific recognition.In vitro trials confirmed the simulation results that c-Myb specifically bound to mim-1 in the forward strand.This study indicates that the three-dimensional(3D)structure features play an important role in the DNA-specific recognition mechanism by c-Myb besides the AACNG consensuses,which is beneficial to understanding the cell early differentiation and proliferation regulated by c-Myb,as well as the prediction of novel c-Myb-binding motifs in tumorigenesis.

Ethylene glycol solution-induced DNA conformational transitions

We study the properties of the ethylene glycol solutions and the conformational transitions of DNA segment in the ethylene glycol solutions by molecular dynamics simulations based on GROMACS. The hydrogen network structures of water–water and ethylene glycol–water are reinforced by ethylene glycol molecules when the concentrations of the solutions increase from 0% to 80%. As illustrated by the results, conformation of the double-stranded DNA in ethylene glycol solutions, although more compact, is similar to the structure of DNA in the aqueous solutions. In contrast, the DNA structure is an A–B hybrid state in the ethanol/water mixed solution. A fraying of terminal base-pairs is observed for the terminal cytosine. The ethylene glycol molecules preferentially form a ring structure around the phosphate groups to influence DNA conformation by hydrogen interactions, while water molecules tend to reside in the grooves. The repulsion between the negatively charged phosphate groups is screened by ethylene glycol molecules, preventing the repulsion from unwinding and extending the helix and thus making the conformation of DNA more compact.

MD Simulations of the P53 oncoprotein structure: the effect of the Arg273→His mutation on the DNA binding domain

A comparative molecular dynamics (MD) simulation study was performed on the p53 oncoprotein to investigate the effect of the Arg273His (R273H) mutation on the p53→DNA Binding Domain (DBD). The two p53 dimer structures of the wild-type and mutant Arg273His (R273H) were simulated with the same thermodynamic and environmental parameters. The obtained results demonstrate that the induced Arg273His mutation has a considerable effect on the p53→DNA close contact interaction and changes the picture of hydrogen formation. The Arg273His mutation, in some cases, destroys the existing native hydrogen bond, but, in other cases, forms a strong p53→DNA hydrogen bond, which is not proper for the native protein. The MD simulation results illustrate some molecular mechanism of the conformational changes of the Arg273His key amino acid residue in the p53→DNA binding domain, which might be important for the understanding of the physiological functioning of the p53 protein and the origin of cancer.

Thymidine Glycol: The Effect on DNA Structure and DNA Binding by Site-Specific Proteins

Thymidine glycol (5,6-dihydroxy-5,6-dihydrothymidine, Tg) is a major type of oxidative damage in DNA. During chemical oligonucleotide synthesis, Tg residue was incorporated in the different positions of 17 b.p. DNA duplexes, which differ in one base pair in the internal part. According to UV-melting curves, Tg destabilizes the double helix in a sequence independent manner. In contrast, the localized alterations in duplex structure were shown by CD spectroscopy to depend on the type of base pairs flanking the Tg lesion. Molecular dynamics simulations demonstrate that Tg is partially out of the double helix. For the first time, Tg impact on several site-specific DNA-binding proteins is studied, namely p50 and p65 subunits of nuclear factor kappa-B (NF-κB) and DNA methyltransferase SsoII (M.SsoII). Our results show that p50/p50 and p65/p65 homodimers of NF-κB can tolerate a single Tg residue in the binding site quite well. Nevertheless the homodimers have different affinities to the oxidized κB site depending on the Tg position. M.SsoII can act as a transcription repressor when bound to the regulatory site. M.SsoII demonstrates decreased affinity and lowered methylation efficiency when its methylation site contains Tg in the central position. Single Tg in one half of the regulatory site decreases M.SsoII affinity to the oxidized DNA, whereas Tg presence in both half-sites prevents M.SsoII binding to such ligand.

Nature of DNA-graphene Interaction System: An Theoretic Account

The nature of DNA-graphene interaction system was investigated by using molecular dynamic simulations and density functional theory calculations. The detailed adsorption behaviors of single-stranded DNA( ssDNA) and double-stranded DNA( dsDNA) on the surface of graphene were discussed. The π-π stacking would contribute to the maximum average loading of ssDNA( 167 segments) with the adsorption potential distribution at the range of-6. 0 eV to-2. 1 eV,higher than that of dsDNA( 30 segments) with the adsorption energy distribution ranging from-3. 0 eV to- 0. 2 eV. Gradually shielding the base of ssDNA using hydrogen atom and gradually changing ssDNA into dsDNA through base-pairing were performed to further detect the detailed interaction between DNA and graphene. E B for * CGC,G* GC,GC* C,and GCG* is-15. 130,-15. 276,-15. 137,and- 15. 271 eV,respectively. E B for GCGC-CGCG / graphene,GCGC-CGC / graphene,GCGC-CG / graphene,GCGC-C / graphene,and GCGC / graphene is-14. 941,-14. 700,-14. 204,-15. 561,and- 15. 810 eV,respectively. DOS of the adsorbed ssDNA down shifted 1. 885 eV,which becomes more stable and less reactive than the other cases. Further,oxidation reaction shows that graphene protects ssDNA from breaking by active oxide. And stable adsorption,protection from destroying,and undamaged desorption insure the possibility of graphene to deliver or hybrid DNA for novel and creative use.

Modified "DMC" technique for stretching DNA molecules

A modified "dynamic molecular combing"(DMC) technique used for stretching double-stranded DNA is reported. DNA molecules were stretched on the silanized mica surface by this technique, its speed being precisely controlled with a computer. This approach combined the precise DNA stretching method with high resolution AFM imaging at nanometer scale, thus making it useful for DNA alignment manipulation and subsequent gene research.

Molecular dynamics simulations of A-DNA in bivalent metal ions salt solution

A-form DNA is one of the biologically active double helical structure.The study of A-DNA structure has an extensive application for developing the field of DNA packaging in biotechnology.In aqueous solution,the A-DNA structure will have a free transformation,the A-DNA structure will be translated into B-form structure with the evolution of time,and eventually stabilized in the B-DNA structure.To explore the stability function of the bivalent metal ions on the A-DNA structure,a series of molecular dynamics simulations have been performed on the A-DNA of sequence(CCCGGCCGGG).The results show that bivalent metal ions(Mg^(2+),Zn^(2+),Ca^(2+))generate a great effect on the structural stability of A-DNA in the environment of high concentration.As the interaction between metal ions and electronegative DNA chains,the stability of A-DNA in solution is gradually improved with the increasing solution concentration of ions.In metal salt solution with high concentration,metal ions can be easily distributed in the solvation shells around the phosphate groups and further lead to the formation of shorter and more compact DNA structure.Also,under the condition of the same concentration and valency of the metal ions,the stability of A-DNA structure is different.The calculations indicate that the structure of A-DNA in CaCl_(2)solution is less stable than in MgCl_(2)and ZnCl_(2)solution.

Molecular dynamics simulation on DNA translocating through MoS_(2) nanopores with various structures

The emergence of MoS_(2) nanopores has provided a new avenue for high performance DNA sequencing,which is critical for modem chemical/biological research and applications.Herein,molecular dynamics simulations were performed to design a conceptual device to sequence DNA with MoS_(2) nanopores of different structures(e.g.,pore rim contained Mo atoms only,S atoms only,or both Mo and S atoms),where various unfolded single-stranded DNAs(ssDNAs)translocated through the nanopores driven by transmembrane bias;the sequence content was identified by the associating ionic current.All ssDNAs adsorbed onto the MoS_(2) surface and translocated through the nanopores by transmembrane electric field in a stepwise manner,where the pause between two permeation events was long enough for the DNA fragments in the nanopore to produce well-defined ionic blockage current to deduce the DNA’s base sequence.The transmembrane bias and DNA-MoS_(2) interaction could regulate the speed of the translocation process.Furthermore,the structure(atom constitution of the nanopore rim)of the nanopore considerably regulated both the translocate process and the ionic current.Thus,MoS_(2) nanopores could be employed to sequence DNA with the flexibility to regulate the translocation process and ionic current to yield the optimal sequencing performance.