Molecular simulation study of assembly of DNA-grafted nanoparticles: effect of bidispersity in DNA strand length

In this paper, we use molecular dynamics simulations to study the assembly of DNA-grafted nanoparticles to demonstrate specifically the effect of bidispersity in grafted DNA strand length on the thermodynamics and structure of nanoparticle assembly at varying number of grafted single-stranded DNA (ssDNA) strands and number of guanine/cytosine (G/C) bases per strand. At constant number of grafted ssDNA strands and G/C nucleotides per strand, as bidispersity in strand lengths increases, the number of nanoparticles that assemble as well as the number of neighbours per particle in the assembled cluster increases. When the number of G/C nucleotides per strand in short and long strands is equal, the long strands hybridise with the other long strands with higher frequency than the short strands hybridise with short/long strands. This dominance of the long strands leads to bidisperse systems having similar thermodynamics to that in corresponding systems with monodisperse long strands. Structurally, however, as a result of long–long, long–short and short–short strand hybridisation, bidispersity in DNA strand length leads to a broader inter-particle distance distribution within the assembled cluster than seen in systems with monodisperse short or monodisperse long strands. The effect of increasing the number of G/C bases per strand or increasing the number of grafted DNA strands on the thermodynamics of assembly is similar for bidisperse and monodisperse systems. The effect of increasing the number of grafted ssDNA strands on the structure of the assembled cluster is dependent on the extent of strand bidispersity because the presence of significantly shorter ssDNA strands among long ssDNA strands reduces the crowding among the strands at high grafting density. This relief in crowding leads to larger number of strands hybridised and as a result larger coordination number in the assembled cluster in systems with high bidispersity in strands than in corresponding monodisperse or low bidispersity systems.     

Molecular dynamics simulation of formation and growth of CdS nanoparticles

Monodispersed semiconducting nanoparticles are usually synthesised in a liquid medium using injection of an appropriate solution. A key factor in attaining a narrow particle size distribution (PSD) is the temporal separation of the nucleation and growth stages, where the former takes place during the injection. Faster injection produces a larger number of nuclei and a narrower PSD. The injection speed is expected to affect the diffusion of the ions in the solution and to create uniformly high supersaturation for a short period of time. In this paper, we study the growth of CdS nanoparticles during the injection by molecular dynamics simulation. A solution of Cd ions is injected into the simulation cell that contains sulphure ions; the variation of the PSD and its mean and variance are studied as functions of the injection velocity. Higher injection velocities produce narrower PSDs and smaller particles, hence providing a precise method for controlling both.     

Molecular dynamics simulation of the size-dependent morphological stability of cubic shape silver nanoparticles

The morphological stability of sharp-edged silver nanoparticles is examined by the classical molecular dynamics (MD) simulations. The crystalline structure and the perfect fcc atom packing of a series of silver nanocubes (AgNC) of different sizes varying from 63 up to 1099 atoms are compared against quasi-spherical nanoparticles of the same sizes at temperature 303 K. Our MD simulations demonstrate that starting from the preformed perfect crystalline structures the cubic shape is preserved for AgNCs composed of 365–1099 atoms. Surprisingly, the rapid loss of the cubic shape morphology and transformation into the non-fcc-structure are found for smaller AgNCs composed of less than ~256 atoms. No such loss of the preformed crystalline structure is seen for quasi-spherical nanoparticles composed of 38–1007 atoms. The analysis of the temperature dependence and the binding energy of outermost Ag surface atoms suggests that the loss of the perfect cubic shape, rounding and smoothing of sharp edges and corners are driven by the tendency towards the increase in their coordination number. In addition, we revealed that AgNC₁₀₉₉ partially loses its sharp edges and corners in the aqueous environment; however, the polymer coating with poly(vinyl alcohol) (PVA) was able to preserve the well-defined cubic morphology. Finally, these results help improve the understanding of the role of surface capping agents in solution phase synthesis of Ag nanocubes.     

Effect of gold nanoparticle on stability of the DNA molecule: A study of molecular dynamics simulation

An understanding of the mechanism of DNA interactions with gold nanoparticles is useful in today medicine applications. We have performed a molecular dynamics simulation on a B-DNA duplex (CCTCAGGCCTCC) in the vicinity of a gold nanoparticle with a truncated octahedron structure composed of 201 gold atoms (diameter ～1.8 nm) to investigate gold nanoparticle (GNP) effects on the stability of DNA. During simulation, the nanoparticle is closed to DNA and phosphate groups direct the particles into the major grooves of the DNA molecule. Because of peeling and untwisting states that are occur at end of DNA, the nucleotide base lies flat on the surface of GNP. The configuration entropy is estimated using the covariance matrix of atom-positional fluctuations for different bases. The results show that when a gold nanoparticle has interaction with DNA, entropy increases. The results of conformational energy and the hydrogen bond numbers for DNA indicated that DNA becomes unstable in the vicinity of a gold nanoparticle. The radial distribution function was calculated for water hydrogen–phosphate oxygen pairs. Almost for all nucleotide, the presence of a nanoparticle around DNA caused water molecules to be released from the DNA duplex and cations were close to the DNA.     

Molecular dynamics simulation studies for DNA sequence recognition by reactive metabolites of anticancer compounds

The discovery of novel anticancer molecules 5F‐203 (NSC703786) and 5‐aminoflavone (5‐AMF, NSC686288) has addressed the issues of toxicity and reduced efficacy by targeting over expressed Cytochrome P450 1A1 (CYP1A1) in cancer cells. CYP1A1 metabolizes these compounds into their reactive metabolites, which are proven to mediate their anticancer effect through DNA adduct formation. However, the drug metabolite–DNA binding has not been explored so far. Hence, understanding the binding characteristics and molecular recognition for drug metabolites with DNA is of practical and fundamental interest. The present study is aimed to model binding preference shown by reactive metabolites of 5F‐203 and 5‐AMF with DNA in forming DNA adducts. To perform this, three different DNA crystal structures covering sequence diversity were selected, and 12 DNA‐reactive metabolite complexes were generated. Molecular dynamics simulations for all complexes were performed using AMBER 11 software after development of protocol for DNA‐reactive metabolite system. Furthermore, the MM‐PBSA/GBSA energy calculation, per‐nucleotide energy decomposition, and Molecular Electrostatic Surface Potential analysis were performed. The results obtained from present study clearly indicate that minor groove in DNA is preferable for binding of reactive metabolites of anticancer compounds. The binding preferences shown by reactive metabolites were also governed by specific nucleotide sequence and distribution of electrostatic charges in major and minor groove of DNA structure. Overall, our study provides useful insights into the initial step of mechanism of reactive metabolite binding to the DNA and the guidelines for designing of sequence specific DNA interacting anticancer agents. Copyright © 2014 John Wiley & Sons, Ltd.     

Probing the role of sequence in the assembly of three‐dimensional DNA crystals

DNA is a widely used biopolymer for the construction of nanometer‐scale objects due to its programmability and structural predictability. One long‐standing goal of the DNA nanotechnology field has been the construction of three‐dimensional DNA crystals. We previously determined the X‐ray crystal structure of a DNA 13‐mer that forms a continuously hydrogen bonded three‐dimensional lattice through Watson‐Crick and non‐canonical base pairs. Our current study sets out to understand how the sequence of the Watson‐Crick duplex region influences crystallization of this 13‐mer. We screened all possible self‐complementary sequences in the hexameric duplex region and found 21 oligonucleotides that crystallized. Sequence analysis showed that one specific Watson‐Crick pair influenced the crystallization propensity and the speed of crystal self‐assembly. We determined X‐ray crystal structures for 13 of these oligonucleotides and found sequence‐specific structural changes that suggests that this base pair may serve as a structural anchor during crystal assembly. Finally, we explored the crystal self‐assembly and nucleation process. Solution studies indicated that these oligonucleotides do not form base pairs in the absence of cations, but that the addition of divalent cations leads to rapid self‐assembly to higher molecular weight complexes. We further demonstrate that crystals grown from mixtures of two different oligonucleotide sequences contain both oligonucleotides. These results suggest that crystal self‐assembly is nucleated by the formation of the Watson‐Crick duplexes initiated by a simple chemical trigger. This study provides new insight into the role of sequence for the assembly of periodic DNA structures. © 2015 Wiley Periodicals, Inc. Biopolymers 103: 618–626, 2015.     

分子模拟方法及其在分子生物学中的应用

常用的分子模拟方法有 :量子力学法、分子力学方法、蒙特卡洛法和分子动力学法。四种方法各有优势 ,共同成为分子模拟的组成部分。综述了分子模拟法在分子生物学中的应用 ,最后介绍了分子模拟的发展方向 ,并预测了其未来的发展趋势。常用的分子模拟方法有 :量子力学法、分子力学方法、蒙特卡洛法和分子动力学法。四种方法各有优势 ,共同成为分子模拟的组成部分。综述了分子模拟法在分子生物学中的应用 ,最后介绍了分子模拟的发展方向 ,并预测了其未来的发展趋势。     

Molecular simulation study of the quantum effects of hydrogen adsorption in metal-organic frameworks: influences of pore size and temperature

In this work a systematic molecular simulation study was performed to investigate the influence of pore size and temperature on the quantum effects of hydrogen adsorption in metal-organic frameworks (MOFs) with temperature varied from 40 to 120 K. To do this, three isoreticular MOFs (IRMOFs) with different pore sizes were adopted, and quadratic Feynman–Hibbs (FH) effective potential was introduced to consider the quantum effect. The results show that quantum effects diminish with increasing pore size of IRMOFs at lower pressure (loading), while the opposite trend appears at higher pressure (loading). Through the simulations it is also found that the quantum effects may be dominantly determined by the adsorbate–adsorbate or adsorbate–MOFs interactions with the varying of pressure (loading). In addition, the results also indicate how the temperature influences the quantum effects of H₂ adsorption in MOFs within the pressure range considered.     

Molecular dynamics simulation study of oriented polyamine- and Na-DNA: sequence specific interactions and effects on DNA structure

Molecular dynamics (MD) computer simulations have been carried out on four systems that correspond to an infinite array of parallel ordered B-DNA, mimicking the state in oriented DNA fibers and also being relevant for crystals of B-DNA oligonucleotides. The systems were all comprised of a periodical hexagonal cell with three identical DNA decamers, 15 water molecules per nucleotide, and counterions balancing the DNA charges. The sequence of the double helical DNA decamer was d(5'-ATGCAGTCAG)xd(5'-TGACTGCATC). The counterions were the two natural polyamines spermidine(3+) (Spd(3+)) and putrescine(2+) (Put(2+)), the synthetic polyamine diaminopropane(2+) (DAP(2+)), and the simple monovalent cation Na(+). This work compares the specific structures of the polyamine- and Na-DNA systems and how they are affected by counterion interactions. It also describes sequence-specific hydration and interaction of the cations with DNA. The local DNA structure is dependent on the nature of the counterion. Even the very similar polyamines, Put(2+) and DAP(2+), show clear differences in binding to DNA and in effect on hydration and local structure. Generally, the polyamines disorder the hydration of the DNA around their binding sites whereas Na(+) being bound to DNA attracts and organizes water in its vicinity. Cation binding at the selected sites in the minor and in the major groove is compared for the different polyamines and Na(+). We conclude that the synthetic polyamine (DAP(2+)) binds specifically to several structural and sequence-specific motifs on B-DNA, unlike the natural polyamines, Spd(3+) and Put(2+). This specificity of DAP(2+) compared to the more dynamic behavior of Spd(3+) and Put(2+) may explain why the latter polyamines are naturally occurring in cells.     

Effect of the surface charge density of nanoparticles on their translocation across pulmonary surfactant monolayer: a molecular dynamics simulation

Interaction between nanoparticles (NPs) and pulmonary surfactant monolayer plays a very significant role in nanoparticle-based pulmonary drug delivery system. Previous researches have indicated that different properties of nanoparticles can affect their translocation across pulmonary surfactant monolayer. Here we performed coarse-grained molecular dynamics simulation aimed at nanoparticles’ surface charge density effect on their penetration behaviours. Several hydrophilic nanoparticles with different surface charge densities were modelled in the simulations. The results show that NPs’ surface charge density affects their translocation capability: the higher the surface charge densities of NPs are, the worse their translocation capability is. It will cause the structural changes of pulmonary surfactant monolayer, and inhibit the normal phase transition of the monolayer during the compression process. Besides, charged NPs can be adsorbed on the surface of the monolayer after translocation as a stable state, and the adsorption capability of NPs increases generally with the increase of surface charge densities. Our simulation results suggest that the study of nanoparticle-based pulmonary drug delivery system should consider the nanoparticles’ surface charge density effect in order to avoid biological toxicity and improve efficacy.     

Effect of nanostructure on heat transfer between fluid and copper plate: a molecular dynamics simulation study

A molecular simulation is developed to study the effect of surface nanostructures on nanoscale flows. Based on this method, particles equation of motion is solved through the Verlet algorithm. Meanwhile, a physically sound method is applied to control the momentum and temperature of the simulation box. By adding an external force on the top copper plate according to the velocity difference between on-the-fly and desired velocities, simulations on convection of argon flows between two solid walls are performed. The top wall, which holds a higher temperature, moves at a constant velocity relative to bottom one along with the streamwise direction. These simulation results show that the nanostructures particularly affect fluid density oscillations adjacent to solid wall and nanostructures. In addition, these nanostructures also have significant effects on temperature and velocity distributions in simulation system.     

A comparative study of the adsorption of water and methanol in zeolite BEA: a molecular simulation study

Grand canonical Monte Carlo simulations were carried out to study the equilibrium adsorption concentration of methanol and water in all-silica BEA zeolite and HBEA zeolites with different Si/Al ratios over a wide range of temperatures and loadings. These zeolites have oval-shaped channels with one side longer than the other. Water sorption into the hydrophobic BEA zeolite had a sharp transition with its sorption going from zero to near full capacity over a very small pressure range. Methanol sorption was much more gradual with respect to pressure. With the addition of hydrophilic sites for the HBEA zeolites by decreasing the Si/Al ratio, adsorption at lower pressures increased significantly for water and methanol. At higher loadings, water and methanol adsorption were found to behave in fundamentally different ways. Water structures in the zeolite channels formed hydrogen-bonded chains while maximising contact with the surfaces on the longer edges of the zeolite channels. Methanol molecules, in contrast, formed very few hydrogen bonds between themselves, with their hydroxyl groups primarily binding with surface of the shorter edge of the zeolite channels and their methyl groups located near the middle of the zeolite channels. The addition of hydrophilic groups in the HBEA zeolites strongly influenced positions of the methanol hydroxyl groups at high loadings, but did not have a significant effect on water structure.     

A computer simulation study of the hierarchical assembly behaviour of triblock patchy particles

We study the hierarchical self-assembly behaviour of ACB triblock patchy particles via Brownian dynamics (BD) simulations, where the product of the first stage is set as the initial structure for the second stage. We offer a promising design rule to investigate the assembly mechanism of ACB triblock patchy particles in selective solvent conditions by two-stage optimisation. At the first stage, the attractive hydrophobic interactions only exist between patches A at low concentration in order to generate subunits. At the second stage, the attractions also exist between patches B for studying the assembly process from subunits to target structures by heating/cooling method. By regulating the interactions between patches B as well as the concentrations of patchy particles, the ordered structures that determined by various influence factors are studied. Via properly designing the assembly models and routes, we can observe the formation process of simple cubic lattice and kagome lattice structures, respectively. The results reveal that the concentration and attractive strength play the critical roles in the whole process of hierarchical self-assembly.     

Molecular dynamics simulation of thread break-up and formation of droplets in nanoejection system

This study investigated nanojet processes by a non-equilibrium molecular dynamics simulation. The phenomena of liquid thread break-up and droplet formation were simulated by compressing liquid propane molecules with various compressing velocities. Properties' distributions show that, at the nanoscale, density and pressure were neither uniform nor continuous during the ejection process. Shear heating phenomena were found in the contact area of the nozzle channel. A linear relationship between the length of liquid threads and the compressing velocity was also found in this study. The results from different trials using various compressing velocities show that higher compressing velocities in nanojet processes result in longer liquid thread lengths and liquid molecules with higher energy levels. Therefore, the ejection process is more unstable, resulting in an increase in the number of evaporating molecules and satellite droplets. Results that illustrate various features are presented to aid in the comprehension of the nanojet processes.     

Molecular dynamics simulation of formation and control of nanodroplets in piezoelectric nanoejection systems

In this paper, the formation of nanodroplets in piezoelectric nanoejection processes is investigated by non-equilibrium molecular dynamics simulation. By compressing liquid propane molecules with various specific pushing periods of oscillation, the phenomena of liquid thread breakup and droplet formation are simulated. The simulation results revealed that various features aid the piezoelectric nanoejection system. Two breakup shapes including double-cone and long tail structures were found in this process. To analyse the ejection process in detail, 2D contour plots and thermal properties for various pushing periods are shown and discussed in this paper. The results show that the sizes of nanodroplets are linear depending on the pushing periods. The findings show a new control factor and mechanism for nanodroplet formation through piezoelectric nanoejection processes.     

Prediction,docking study and molecular simulation of 3D DNA aptamers to their targets of endocrine disrupting chemicals

Abstract

Typical endocrine disrupting chemicals, including BPA (Bisphenol A), E₂ (17-β-Estradiol) and PCB 72 (polychlorinated biphenyl 72), are commonly and widely present in the environment with good chemical stability that are difficult to decompose in vitro and in vivo. Most of the high-qualified antibodies are required as the key biomaterials to fabricate the immunosensor for capturing and detecting. As an ideal alternative, the short-chain oligonucleotides (aptamer) are essentially and effectively employed with the advantages of small size, chemical stability and high effectiveness for monitoring these environmental contaminants. However, the molecular interaction, acting site and mode are still not well understood. In this work, we explored the binding features of the aptamers with their targeting ligands. The molecular dynamics simulations were performed on the aptamer–ligand complex systems. The stability of each simulation system was evaluated based on its root-mean-square deviation. The affinities of these proposed ligands and the predicted binding sites are analyzed. According to the binding energy analysis, the affinities between ligands and aptamers and the stability of the systems are BPA?>?PCB 72 >E₂. Trajectory analysis for these three complexes indicated that these three ligands were able to steadily bind with aptamers at docking site from 0 to 50?ns and contributed to alteration of conformation of aptamers.     

Molecular simulation for separation of ethylene and ethane by functionalised graphene membrane

ABSTRACT

Graphene is an excellent adsorbent and a membrane material for separation which has attracted wide attention in recent years. Moreover, compared with typical polymer materials, porous graphene has exhibited superior performance. In this paper, molecular dynamics and quantum mechanics were used to explore the appropriate pore size and separation mechanism of graphene. The 2N-Pore-13 (modified by N and H atom) membrane can prevent the penetration of ethane while maintaining high ethylene flux. The permeation rate of ethylene reached 3.7×10⁶ GPU in 5N-Pore-13 membrane, while the one of ethane was only 227 GPU. The mechanism is based on the fact that molecular structure of ethylene is two-dimensional, so that ethylene can get closer to membrane surface when it is adsorbed. When passing through the pores, ethylene has lower enthalpy and entropy barrier.     

The selectivity of protein‐imprinted gels and its relation to protein properties: A computer simulation study

Polymer‐based protein recognition systems have enormous potential within clinical and diagnostic fields due to their reusability, biocompatibility, ease of manufacturing, and potential specificity. Imprinted polymer matrices have been extensively studied and applied as a simple technique for creating artificial polymer‐based recognition gels for a target molecule. Although this technique has been proven effective when targeting small molecules (such as drugs), imprinting of proteins have so far resulted in materials with limited selectivity due to the large molecular size of the protein and aqueous environment. Using coarse‐grained molecular simulation, we investigate the relation between protein makeup, polymer properties, and the selectivity of imprinted gels. Nonspecific binding that results in poor selectivity is shown to be strongly dependent on surface chemistry of the template and competitor proteins as well as on polymer chemistry. Residence time distributions of proteins diffusing within the gels provide a transparent picture of the relation between polymer constitution, protein properties, and the nonspecific interactions with the imprinted gel. The pronounced effect of protein surface chemistry on imprinted gel specificity is demonstrated.