钠离子浓度对核小体纤维结构影响的Monte Carlo模拟

通过核小体纤维模型的构建，利用Monto Carlo方法模拟其在各种钠离子浓度的溶液中结构变化的过程.模拟结果显示当溶液的钠离子浓度增大时，核小体由锯齿状结构转变为螺旋状结构.在常温所得到的核小体结构参数与实验结果接近，较好地解释了溶液中的钠离子浓度对核小体纤维结构的影响. 关键词： 核小体纤维 超螺旋结构 Monte Carlo方法 钠离子浓度     

Finite-Size Conformational Transitions：A Unifying Concept Underlying Chromosome Dynamics

Investigating average thermodynamic quantities is not sufficient to understand conformational transitions of a finite-size polymer. We propose that such transitions are better described in terms of the probability distribution of some finite-size order parameter, and the evolution of this distribution as a control parameter varies. We demonstrate this claim for the coil-globule transition of a linear polymer and its mapping onto a two-state model. In a biological context, polymer models delineate the physical constraints experienced by the genome at different levels of organization, from DNA to chromatin to chromosome. We apply our finite-size approach to the formation of plectonemes in a DNA segment submitted to an applied torque and the ensuing helix-coil transition that can be numerically observed, with a coexistence of the helix and coil states in a range of parameters. Polymer models are also essential to analyze recent in vivo experiments providing the frequency of pairwise contacts between genomic loci. The probability distribution of these contacts yields quantitative information on the conformational fluctuations of chromosome regions. The changes observed in the shape of the distribution when the cell type or the physiological conditions vary may reveal an epigenetic modulation of the conformational constraints experienced by the chromosomes.     

Supercooled superfluids in Monte Carlo simulations

We perform path integral Monte Carlo simulations to study the imaginary time dynamics of metastable supercooled superfluid states and nearly superglassy states of a one component fluid of spinless bosons square wells. Our study shows that the identity of the particles and the exchange symmetry is crucial for the frustration necessary to obtain metastable states in the quantum regime. Whereas the simulation time has to be chosen to determine whether we are in a metastable state or not, the imaginary time dynamics tells us if we are or not close to an arrested glassy state.     

Universal behavior of nearly free electron states in carbon nanotubes

The nearly free electron state of a carbon nanotube drops rapidly in energy relative to the other conduction bands under alkali doping. A natural (and previously proposed) explanation for this rapid downshift is hybridization with the potassium states. However, we show that the downshift occurs even when the extra electrons are compensated by a uniform positive background, wherein there can be no hybridization, since there are no alkali atoms. Instead, the motion of the nearly free band arises from a universal electrostatic mechanism, which applies for any type of positive countercharge independent of tube diaf/meter and helicity. The nearly free electron state, being weakly bound to the tube wall, is extraordinarily labile and deforms onto the countercharge, whereas the remaining pi* conduction band states are held to the surface of the carbon sheet by the strong carbon potential.     

Overstretching of a 30 bp DNA duplex studied with steered molecular dynamics simulation: Effects of structural defects on structure and force-extension relation

Single-molecule experiments on polymeric DNA show that the molecule can be overstretched at nearly constant force by about 70% beyond its relaxed contour length. In this publication we use steered molecular dynamics (MD) simulation to study the effect of structural defects on force-extension curves and structures at high elongation in a 30 base pair duplex pulled by its torsionally unconstrained 5' -5' ends. The defect-free duplex shows a plateau in the force-extension curve at 120pN in which large segments with inclined and paired bases (“S-DNA”) near both ends of the duplex coexist with a central B-type segment separated from the former by small denaturation bubbles. In the presence of a base mismatch or a nick, force-extension curves are very similar to the ones of the defect-free duplex. For the duplex with a base mismatch, S-type segments with highly inclined base pairs are not observed; rather, the overstretched duplex consists of B-type segments separated by denaturation bubbles. The nicked duplex evolves, via a two-step transition, into a two-domain structure characterized by a large S-type segment coexisting with several short S-type segments which are separated by short denaturation bubbles. Our results suggest that in the presence of nicks the force-extension curve of highly elongated duplex DNA might reflect locally highly inhomogeneous stretching.     

Nucleosome Dynamics as Studied by Single-pair Fluorescence Resonance Energy Transfer: A Reevaluation

Accessibility of nucleosomal DNA to protein factor binding is ensured by at least three mechanisms: post-synthetic modifications to the histones, chromatin remodeling, and spontaneous unwrapping of the DNA from the histone core. We have previously used single-pair fluorescence resonance energy transfer (spFRET) experiments to investigate long-range conformational fluctuations in nucleosomal DNA (Tomschik M, Zheng H, van Holde K, Zlatanova J, Leuba SH in Proc Natl Acad Sci USA 102(9):3278–3283, 2005). Recent work has drawn attention to a major artifact in such studies due to photoblinking of the acceptor fluorophore. We have now used formaldehyde-crosslinked nucleosomes and imaging in the presence of Trolox, an efficient triplet-state quencher that suppresses photoblinking, to reevaluate our previous conclusions. Careful analysis of the data indicates that most of the events previously characterized as nucleosome ‘opening’ must have corresponded to photoblinking. There is, nevertheless, evidence for the existence of infrequent, rapid opening events.     

Allosteric Mechanism of Calmodulin Revealed by Targeted Molecular Dynamics Simulation

Calmodulin(CaM) is involved in the regulation of a variety of cellular signaling pathways. To accomplish its physiological functions, CaM binds with Ca~(2+) at its EF-hand Ca~(2+) binding sites which induce the conformational switching of CaM. However, the molecular mechanism by which Ca~(2+) binds with CaM and induces conformational switching is still obscure. Here we combine molecular dynamics with targeted molecular dynamics simulation and achieve the state-transition pathway of CaM. Our data show that Ca~(2+) binding speeds up the conformational transition of CaM by weakening the interactions which stabilize the closed state. It spends about 6.5 ns and 5.25 ns for transition from closed state to open state for apo and holo CaM, respectively. Regarding the contribution of two EF-hands, our data indicate that the first EF-hand triggers the conformational transition and is followed by the second one. We determine that there are two interaction networks which contribute to stabilize the closed and open states, respectively.     

5-Aza-2′-deoxycytidine reactivates the CDH1 gene without influencing methylation of the entire CpG island or histone modification in a human cancer cell line

It is well-recognized that DNA methylation and histone modifications play critical roles in epigenetic regulation of gene activity through the alteration of chromatin structure. Recent studies have shown that in a subset of cancer cells, the silencing of the human E-cadherin (CDH1) gene is associated with hypermethylation of the CpG island. However, the associated molecular mechanism remains unclear. To understand the mechanism, we have investigated the alteration of CpG island methylation and histone modifications during the reactivation of the CDH1 gene by treatment with 5-aza-2′-deoxycytidine (5-aza-dC). Although the CDH1 gene expression was recovered by treatment with 5-aza-dC in a liver cancer cell line Li21, the methylation status of the entire CpG island and acetylation and methylation status of associated histones were not significantly altered. These results demonstrate that the silenced CDH1 gene can be reactivated without apparent alteration of histone modification or CpG island methylation.     

A morphological study of the effect of chlorambucil during the S and G2 phases of the cell cycle of synchronized HEp-2 cancer cell populations using computerized morphometry

Chlorambucil, a bisalkylating agent, used extensively in the treatment of autoimmune and neoplastic diseases, is known to affect DNA synthesis. However recent studies have revealed that it also affects the synthesis of other nuclear protein constituents, especially histones. Since histones play a major role in both the structural and functional integrity of chromatin, we have analyzed the morphological effects of this agent, using low dose conditions and synchronized populations of HEp-2 cancer cells in the S and G2 phases of the cell cycle. Analyses at the light and electron microscopy levels were undertaken using synchronous image analysis techniques. Computerized morphometry was used so as to evaluate various nuclear and cytological morphological parameters. It was found that chlorambucil affects the organization of chromatin, as well as other cellular parameters in a manner characteristic of decreased tumor aggressiveness. A finding of significance in this study was that chlorambucil exerted its influence on all these morphological parameters only when treatment was initiated at the beginning of the S phase and not during the second half of the S phase or the G2 phase.     

Effects of Ionic Dependence of DNA Persistence Length on the DNA Condensation at Room Temperature

DNA persistence length is a key parameter for quantitative interpretation of the conformational properties of DNA and related to the bending rigidity of DNA.A series of experiments pointed out that,in the DNA condensation process by multivalent cations,the condensed DNA takes elongated coil or compact globule states and the population of the compact globule states increases with an increase in ionic concentration.At the same time,single molecule experiments carried out in solution with multivalent cations(such as spermidine,spermine)indicated that DNA persistence length strongly depends on the ionic concentration.In order to revolve the effects of ionic concentration dependence of persistence length on DNA condensation,a model including the ionic concentration dependence of persistence length and strong correlation of multivalent cation on DNA is provided.The autocorrelation function of the tangent vectors is found as an effective way to detect the ionic concentration dependence of toroidal conformations.With an increase in ion concentration,the first periodic oscillation contained in the autocorrelation function shifts,the number of segment contained in the first periodic oscillation decreases gradually.According to the experiments,the average long-axis length is defined to estimate the ionic concentration dependence of condensation process further.The relation between long-axis length and ionic concentration matches the experimental results qualitatively.     

Fourier Transform Infrared Spectroscopic Investigation of the Binary and Ternary Cyanide Adducts of the Oxidized Horseradish Peroxidase: Identification of a Second Stretching Mode for the Carbon-Nitrogen Bond of the Bound Cyanide Ion

The binary and ternary cyanide adducts of the ferric horseradish peroxidase were investigated by Fourier transform infrared spectroscopy. The carbon-nitrogen bond of the bound cyanide ion in the binary ferric cyanohorseradish peroxidase exhibits two stretching vibrations at 2130 cm^?1 and 2127 cm^?1 with the latter mode being observed in this work for the first time. This finding supports the results of the resonance Raman study of cyanohorseradish peroxidase, which identified two iron-carbon-nitrogen bending vibrations and two iron-carbon stretching vibrations, proving the existence of two conformational states. The identification of the latter carbon-nitrogen stretching frequency allowed the assignment of all of the vibrational modes of the iron-carbon-nitrogen groups of the two conformational states of the ferric cyanohorseradish peroxidase. The first conformer is characterized by a carbon-nitrogen stretch at 2130 cm^?1, an iron-carbon stretch at 453 cm^?1, and an iron-carbon-nitrogen bending mode at 405 cm^?1. The second state has a carbon-nitrogen stretch at 2127 cm^?1, an iron-carbon stretch at 360 cm^?1, and an iron-carbon-nitrogen bending mode at 422 cm^?1. The iron-carbon stretching band is weakly sensitive to pH changes, but it is sensitive to H₂O/D₂O substitution, indicating that the bound cyanide ion in cyanohorseradish peroxidase is hydrogen bonded to the surrounding protein. The two states were attributed to variation in the extent of hydrogen bonding of the iron-carbon-nitrogen groups in the two states. The carbon-nitrogen stretching vibrations of the ternary complexes of cyanohorseradish peroxidase with ferulic acid, benzamide, and benzhydroxamic acid have been investigated for the first time. The binding of the substrate to cyanohorseradish peroxidase does not always lead to the vanishing of one of the conformational states as in the carbon monoxide adducts of the ferrous horseradish peroxidase, but can cause shifts in the νC-N frequency and in the relative population of both conformational states.     

The amplitudes of s and d bosons in deformed nuclei

It is shown that the ground state of deformed nuclei can be considered as a condensate of bosons that do not have a well defined angular momentum. The projection on well defined angular momentum states shows that the s and d bosons take care of nearly 90% of the boson wave function.     

Low-frequency dynamics of DNA in Brillouin light scattering spectra

Brillouin light scattering studies of deoxyribonucleic acid (DNA) in the temperature interval 297–375 K are presented. The DNA fragment (119 bp) from the first intron of D melanogaster limk1 gene with AT-rich insertion (28 bp, mutant agn ^ts3) was used as an experimental sample. The temperature dependence of the hypersonic velocity was found to exhibit anomalies in the vicinity of 347 and 335 K. Computer modeling of possible conformational states which might be attained by the DNA fragment under study has shown the existence of local structures that evolve with varying temperature. Combined analysis of experimental data and results of the modeling reveals a close relation between the anomalous behavior of Brillouin light scattering spectra and conformational DNA dynamics. The results are discussed in the framework of modern models of conformational DNA transformations.     

Micromechanics of base pair unzipping in the DNA duplex

All-atom molecular dynamics (MD) simulations of DNA duplex unzipping in a water environment were performed. The investigated DNA double helix consists of a Drew-Dickerson dodecamer sequence and a hairpin (AAG) attached to the end of the double-helix chain. The considered system is used to examine the process of DNA strand separation under the action of an external force. This process occurs in vivo and now is being intensively investigated in experiments with single molecules. The DNA dodecamer duplex is consequently unzipped pair by pair by means of the steered MD. The unzipping trajectories turn out to be similar for the duplex parts with G·C content and rather distinct for the parts with A·T content. It is shown that during the unzipping each pair experiences two types of motion: relatively quick rotation together with all the duplex and slower motion in the frame of the unzipping fork. In the course of opening, the complementary pair passes through several distinct states: (i) the closed state in the double helix, (ii) the metastable preopened state in the unzipping fork and (iii) the unbound state. The performed simulations show that water molecules participate in the stabilization of the metastable states of the preopened base pairs in the DNA unzipping fork.     

Conductance switching mechanism of Rose Bengal organic thin films in ambient conditions

The molecular thin films of Rose Bengal (RB) embedded in polymethyl methacrylate matrix are fabricated by using the spin-coating technique. The macroscopic current--voltage (I--V) characterization of the film shows that the RB molecule has two conductance switching states with a high ON/OFF ratio in ambient conditions. The infrared spectra indicate that intermolecular hydrogen bonds can form in the RB thin films after their hydrolysis in air. With the first-principles calculations, we demonstrate that the hydrogen bonds will be destroyed in concomitance with the conformational change when the RB molecule switches to its high-conductance state after applying a voltage.     

Quantum theory and time asymmetry

The relation between quantum measurement and thermodynamically irreversible processes is investigated. The reduction of the state vector is fundamentally asymmetric in time and shows an observer-relatedness which may explain the double interpretation of the state vector as a representation of physical states as well as ofinformation about physical states. The concept of relevance being used in all statistical theories of irreversible thermodynamics is demonstrated to be based on the same observer-relatedness. Quantum theories of irreversible processes implicitly use an objectivized process of state vector reduction. The conditions for the reduction are discussed, and it is concluded that the final (subjective) observer system may be carried by a space point.     

Fault tolerant channel-encrypting quantum dialogue against collective noise

In this paper,two fault tolerant channel-encrypting quantum dialogue(QD)protocols against collective noise are presented.One is against collective-dephasing noise,while the other is against collective-rotation noise.The decoherent-free states,each of which is composed of two physical qubits,act as traveling states combating collective noise.Einstein-Podolsky-Rosen pairs,which play the role of private quantum key,are securely shared between two participants over a collective-noise channel in advance.Through encryption and decryption with private quantum key,the initial state of each traveling two-photon logical qubit is privately shared between two participants.Due to quantum encryption sharing of the initial state of each traveling logical qubit,the issue of information leakage is overcome.The private quantum key can be repeatedly used after rotation as long as the rotation angle is properly chosen,making quantum resource economized.As a result,their information-theoretical efficiency is nearly up to 66.7%.The proposed QD protocols only need single-photon measurements rather than two-photon joint measurements for quantum measurements.Security analysis shows that an eavesdropper cannot obtain anything useful about secret messages during the dialogue process without being discovered.Furthermore,the proposed QD protocols can be implemented with current techniques in experiment.     

New estimates of single photon parameters for satellite-based QKD

A new decoy state method has been presented to tighten the lower bound of the key generation rate for BB84 using one decoy state and one signal state. It can give us different lower and upper bounds of the fraction of single-photon counts and single-photon QBER, respectively, for one decoy state protocol. We have also analyzed the feasibility of performing quantum key distribution (QKD), with different exiting protocols, in earth-satellite and intersatellite links. Our simulation shows the choice of intensity of signal state and the effect of choosing the number of decoy states on key generation rate. The final key rate over transmission distance has been simulated, which shows that security proofs give a zero key generation rate at long distances (larger than 16,000 km). It has been shown that the practical QKD can be established with low earth orbit and medium earth orbit satellites.