A New Potential Model for Carbon Dioxide from AB Initio Calculations

Abstract

Ab initio quantum chemical calculations have been carried out for carbon dioxide dimer and the results have been used to establish potential functions usable in molecular simulations. Since the intermolecular interaction in carbon dioxide is fairly weak, careful treatment is required: this study uses 6–31G* basis set and takes electron correlations by the 2nd order Møller-Plesset theory into account. The potential energy surface is elucidated using the four representative relative configurations of the dimer. A new potential function model has been proposed on the basis of these ab initio data. In the super-critical region, this model is used to calculate the PVT relation of carbon dioxide fluid by the Monte Carlo simulations and confirmed to reproduce reasonably well the experimental isotherms.     

Blocking effect of benzene-like fluid transport in nanoscale block-pores

Abstract

The flux through nanoscale pore is one of the key quantities in many processes including membrane applications and fluid separation. Whereas many efforts have been dedicated to the investigation of the fluid flux in nano-channels, the fluid transport behaviours in the block-pores, which contain distinct parts with different geometries or interactions with fluid, are still poorly understood. In this work, by combining both non-equilibrium dynamics simulation and density functional theory, we developed an efficient method for investigating the fluid flux in the block-pores, with which the fluxes of benzene in graphene block slit pores containing a hydrophobic and a hydrophilic region are thereafter investigated. We demonstrate that a region with a stronger interaction with fluid generates a bottleneck for the fluid flow, which greatly suppresses the flux in the pore even though there is no geometrical variation. By tuning the fluid-substrate interaction, the flux inside can be controlled. This study gives clues for the practical application of membrane design.     

Monte Carlo Simulation Study of Adsorption Characteristics in Slit-Like Micropores Under Supercritical Conditions

Abstract

Adsorption characteristics of a solute diluted in supercritical fluids has been investigated by using the Monte Carlo simulation techniques. The Lennard-Jones potential function is used for describing interactions for a model system of CO₂ + benzene in slit-like micropores with infinite graphitic carbon walls. A modified μVT ensemble method with particle exchange proposed by Cracknell, Nicholson and Quirke (1993) is found to be much superior to the conventional μVT ensemble method especially for dense mixtures in a pore. Adsorption isotherms of CO₂ and benzene, in equilibrium with a dilute benzene mixture in CO₂ (mole fraction of benzene = 0.001), are computed by varying pressure, temperature, the benzene–surface interaction potential, and the slitwidth. Adsorption isotherm curve of CO₂ increases with an increase in pressure while that of benzene shows a maximum at a pressure far below the critical pressure of CO₂ and then it decreases with increasing pressure. The decrease in benzene adsorption with increasing pressure is attributable to both the enhanced solubility in supercritical CO₂ and the competitive adsorption of CO₂. The isotherm curves of each component at two temperatures, 313.2 K and 323.2 K, show to cross at a pressure near the critical pressure due to the “density effect” on the chemical potentials of a solute at supercritical fluid conditions. When the interaction between a solute and a surface increases, the adsorption isotherm increases. Narrowing the slitwidth results in the increase in the adsorption of solute since the external potential from two walls becomes deeper.     

Structural and vibrational spectroscopic elucidation of sulpiride in solid state

The study on the conformational and vibrational behaviors of sulpiride molecule which is known as a neuroleptic or antipsychotic drug that is widely used clinically in the treatment of schizophrenic or depressive disorders is an important scientific and practical task. In here, a careful enough study of monomer and dimeric forms of sulpiridine {5-(aminosulfonyl)-N-[(1-ethyl-2-pyrrolidinyl) ethyl]-2-methoxy-benzamide (C₁₅H₂₃N₃O₄S)} is undertaken by density functional theory (DFTB3LYP) method with the B3LYP/6-31G(d,p) basis set. The conformations of free molecule were searched by means of torsion potential energy surfaces scan studies through dihedral angles D₁ (8?N, 18C, 20C, 23?N), D₂ (18C, 20C, 23?N, 25C) and D₃ (28C, 30C, 41S, 44?N) in electronically ground state, employing 6-31G basic set. The final geometrical parameters for the obtained stable conformers were determined by means of geometry optimization, carried out at DFT/B3LYP/6-31G(d,p) theory level. Afterwards, the possible dimer forms of the molecule were formed and their energetically preferred conformations were investigated. Moreover, the effect of basis set superposition error on the structure and energy of the three energetically favourable sulpiride dimers has been determined. The optimized structural parameters of the most stable monomer and three low energy dimer forms were used in the vibrational wavenumber calculations. Raman and IR (4000–400?cm^?1) spectra of sulpiride have been recorded in the solid state. The assignment of the bands was performed based on the potential energy distribution data. The natural bond orbital analysis has been performed on both monomer and dimer geometries in order to elucidate delocalization of electron density within the molecule. The predicted frontier molecular orbital energies at DFT/B3LYP/6-31G(d,p) theory level show that charge transfer occurs within the molecule. The first-order hyperpolarizability (β₀) and related properties (μ and α) of the title molecule were also calculated.     

The Adsorption of Argon and Nitrogen in Silicalite-1 Zeolite: A Grand Canonical Monte-Carlo study

Abstract

Grand Ensemble Monte-Carlo simulations of adsorption of argon and nitrogen in silicalite have been performed using a new adsorbate/zeolite potential function. In both cases, a good agreement with zero coverage data (Henry law constant and isosteric heat of adsorption) has been obtained. For argon, the simulated isotherm at 77 K exhibits the experimentally observed step. This is attributed to an in site/off-site phase transition of the adsorbed phase. The calculated neutron diffraction spectra are in reasonable agreement with those obtained experimentally. Furthermore, we suggest, in light of recent ⁴⁰Ar diffraction experiments of Tosi-Pellenq and Coulomb [18,44], that the shift in pressure between the simulated and the experimental isotherms corresponds to changes in the zeolite structure accompanied with the adsorbate phase transition itself. For nitrogen, only the first of the two experimentally observed steps is reproduced in the simulation. This step corresponds to an ordering of the adsorbed phase. The fact that the second step is missing in the simulated isotherm supports the hypothesis of a distortion of the zeolite framework under the stress of the adsorbed fluid at high loading.     

Entropy versus aromaticity in the conformational dynamics of aromatic rings

Comparison of the results of Car-Parrinello molecular dynamics simulations of isolated benzene, pyrimidine and 1,2,4-triazine molecules reveals that the unusually low population of planar geometry of the benzene ring is caused by entropy effects despite its high aromaticity. The decrease in symmetry of the molecule results in smaller changes in entropy and Gibbs free energy due to out-of-plane deformations of the ring, leading to an increase in the population of planar geometry of the ring. This leads to differences in the topology of potential energy and Gibbs free energy surfaces.

Applications of Genetic Algorithms in Cluster Optimisation

Abstract

Applications of Genetic Algorithms for optimisation of atomic clusters are reported. It is shown that the genetic algorithms are very useful tools for determining the minimum energy structures of clusters of atoms described by interatomic potential functions containing up to a few hundred atoms. The algorithm generally outperforms other optimisation methods for this task. A number of applications are given including covalent carbon and silicon clusters, close-packed structures such as argon and silver and the two-component C—H system.     

A novel dual luciferase based high throughput assay to monitor autophagy in real time in yeast S. cerevisiae

BackgroundMacroautophagy is a cellular response to starvation wherein superfluous and damaged cytoplasmic constituents are degraded to provide energy for survival and to maintain cellular homeostasis. Dysfunctional autophagy is attributed to disease progression in several pathological conditions and therefore, autophagy has appeared as a potential pharmacological target for such conditions.ObjectiveIn search of potential drugs that modulate autophagy, identifying small molecule effectors of autophagy is the primary step. The conventional autophagy assays have a limitation that they cannot be scaled down to a high throughput format, therefore, novel sensitive assays are needed to discover new candidate molecules. Keeping this rationale in mind, a dual luciferase based assay was developed in the yeast S. cerevisiae that could measure both selective and general autophagy in real time.MethodsFirefly and Renilla luciferase reporter genes were cloned under POT-1 promoter. Using fatty acid medium the promoter was induced and the luciferase cargo was allowed to build up. The cells were then transferred to starvation conditions to stimulate autophagy and the degradation of luciferase markers was followed with time.Results and conclusionThe assay was more sensitive than conventional assays and could be scaled down to a 384 well format using an automated system. A good Z-factor score indicated that the assay is highly suitable for High Throughput Screening (HTS) of small molecule libraries. Screening of a small molecule library with our assay identified several known and novel modulators of autophagy.     

The Lennard-Jones Fluid Revisited: Computer Simulation Results

Abstract

Pseudoexperimental data of high accuracy on the pressure and the internal energy of the Lennard-Jones fluid have been generated both by the Monte Carlo and molecular dynamics methods for five subcritical and three supercritical isotherms. Values of the chemical potential of the Lennard-Jones fluid computed by a new version of the gradual insertion particle method for two isotherms up to very high densities are also reported and discussed, and compared with existing data.     

Investigating the effects of wettability and gaseous nanobubbles on roughened wall–fluid interface using molecular dynamics simulation

This paper reports on the use of molecular dynamics (MD) simulation to investigate the coupling effects of wettability, surface roughness and interfacial nanobubbles (INBs) on wall–fluid interfaces. The fluid properties close to the wall–fluid interface, such as potential energy, density, diffusion coefficients of fluid molecules and effective slip length are simulated. In the cases without surface nanobubbles, regions with lower potential energy have a higher probability of hosting water molecules. The local translational and rotational diffusion coefficients of water within the cavities are strongly influenced by wettability but largely unaffected by hydrodynamic effects. In cases where INBs exist, variations in wettability result in distinctly different argon morphologies. Argon nanobubbles form a convex shape on Wenzel-like interfaces but a shallow concave shape on Cassie-like interfaces. The phenomenon of water molecules invading grooves tends to occur on Wenzel-like interfaces; however, this depends largely on the morphology of the grooves. The high mobility and high density of argon molecules indicate that the state of the argon molecules within the grooves may require further investigation. Our results also show that the effective slip length is significantly influenced by wall–fluid wettability as well as the morphology of INBs.     

Structure of Lennard–Jones fluid near large spherical particles: further test of the “universality” of adjustable parameter in perturbation density functional theory

Grand canonical Monte Carlo simulation is used to study the density profiles of Lennard–Jones (LJ) fluid next to a large hard sphere (mimicking a colloidal particle) of various sizes. The LJ fluid in the inhomogeneous system thus maintains equilibrium with the bulk LJ fluid. The chosen density and potential parameters for the bulk fluid correspond to the conditions situated at “dangerous” regions of the phase diagram, i.e. near the critical temperature or close to the gas–liquid coexistence curve. The aim of present extensive simulations is to provide exact data for the broad range of the bulk parameters against which the “universality” of adjustable parameter associated with a perturbation density functional approximation (DFA) can be tested. Here the term “universality” means independence of this parameter on the particular external field responsible for the generation of a non-uniform density profile of the fluid. It is shown that the “universality” of this parameter associated with a third order+second order perturbation DFA holds also in the present case of a large spherical particle as a source of external potential, similarly as established in previous studies dealing with other interaction potential and other external fields [J. Chem. Phys., 122, 064503 (2005); J. Chem. Phys., 123 124708 (2005)]. This DFA can be used as input into a recently proposed framework for the calculation of interparticle potential of mean force (PMF).     

Study of curcumin behavior in two different lipid bilayer models of liposomal curcumin using molecular dynamics simulation

Liposomal formulation of curcumin is an important therapeutic agent for the treatment of various cancers. Despite extensive studies on the biological effects of this formulation in cancer treatment, much remains unknown about curcumin–liposome interactions. Understanding how different lipid bilayers respond to curcumin molecule may help us to design more effective liposomal curcumin. Here, we used molecular dynamics simulation method to investigate the behavior of curcumin in two lipid bilayers commonly used in preparation of liposomal curcumin, namely dipalmitoylphosphatidylcholine (DPPC) and dimyristoylphosphatidylglycerol (DMPG). First, the free energy barriers for translocation of one curcumin molecule from water to the lipid bilayer were determined by using the potential of mean force (PMF). The computed free energy profile exhibits a global minimum at the solvent–headgroup interface (LH region) for both lipid membranes. We also evaluated the free energy difference between the equilibrium position of curcumin in the lipid bilayer and bulk water as the excess chemical potential. Our results show that curcumin has the higher affinity in DMPG compared to DPPC lipid bilayer (?8.39 vs. ?1.69 k_BT) and this is related to more hydrogen bond possibility for curcumin in DMPG lipid membrane. Next, using an unconstrained molecular dynamic simulation with curcumin initially positioned at the center of lipid bilayer, we studied various properties of each lipid bilayer system in the presence of curcumin molecule that was in full agreement with PMF and experimental data. The results of these simulation studies suggest that membrane composition could have a large effect on interaction of curcumin–lipid bilayer.     

On the Implementation of Friedman Boundary Conditions in Liquid Water Simulations

Abstract

We have applied the image approximation to the reaction field as suggested by H.L. Friedman [Mol. Phys., 29, 1533 (1975)] by investigating appropriate cavity sizes and system parameters for use in molecular simulations. The energy of and the structure around a central simple point charge (SPC) water molecule in a dielectric cavity was found to be in good agreement with the properties of a liquid sample. To confine the water molecules within the cavity, we introduced a short-range repulsion between a real charge and its image as the Lennard-Jones repulsive potential between oxygen atoms of the SPC potential. For a system of 65 water molecules a cavity radius of 10.45 Å is appropriate; this radius is altered to 12.00 Å for a cavity surrounding 113 molecules. The effect of the boundary is restricted to the outer-most water layer which is in contact with the dielectric continuum.     

A conformational study of N-phenyl-1-naphthylamine and 1-anilino-8-naphthalene sulfonate by the empirical method

Conformational analysis of N-phenyl-1-naphthylamine and 1-anilinonaphthalene-8-sulfonate (ANS) was carried out using the empirical method. Properties such as conformational energies and dipole moments were considered. Furthermore, the effect of solvent medium was examined through the effective dielectic constant. The N-phenyl-1-naphthylamine molecule showed two energy minima which were independent of dielectic constant. The ANS molecule also showed two energy minima but the minima changed positions when the dielectic constant increased from 1.0 (vacuum) to 80.0 (highly polar medium). Hydrogen bonding appeared to play an important role in stabilizing these conformations. The minimum energy conformations may have relevance to the binding of ANS to lipid bilayers and bimembranes. The dipole moment, in contrast to the energy minimum, was found to depend on orientation of the sulfonate group rather than of the benzene ring with respect to the naphthalene ring. Thus binding and fluorescence enhancement of ANS may be attributed to the orientation of the sulfonate group, which to a large extent may determine the magnitude of the dipole moment and the degree of electrostatic interactions between the probe and binding domains. Various dimensions like intra-atomic distances, volume and area of the ANS molecule were calculated.     

Cation—π and Amino-Acceptor Interactions Between Hydrated Metal Cations and DNA Bases. A Quantum-Chemical View

Abstract

Cation—π interactions between cytosine and hexahydrated cations have been characterized using ab initio method with inclusion of electron correlation effects, assuming idealized and crystal geometries of the interacting species. Hydrated metal cations can interact with nucleobases in a cation—π manner. The stabilization energy of such complexes would be large and comparable to the one for cation—π complex with benzene. Further, polarized water molecules belonging to the hydration shell of the cation are capable to form a strong hydrogen bond interaction with the nitrogen lone electron pair of the amino groups of bases and enforce a pronounced sp³ pyramidalization of the nucleobase amino groups. However, in contrast to the benzene—cation complexes, the cation—π configurations are highly unstable for a nucleobase since the conventional in plane binding of hydrated cations to the acceptor sites on the nucleobase is strongly preferred. Thus, a cation—π interaction with a nucle-obase can occur only if the position of the cation is locked above the nucleobase plane by another strong interaction. This indeed can occur in biopolymers and may have an effect on the local DNA architecture. Nevertheless, nucleobases have no intrinsic propensity to form cation—π interactions.     

Tyrosinase inhibitory effect of benzoic acid derivatives and their structure-activity relationships

A series of benzoic acid derivatives 1–10 have been synthesised by two different methods. Compounds 1–6 were synthesised by a facile procedure for esterification using N,N’-dicyclohexylcarbodiimide (DCC) as a coupling agent, methylene chloride as a solvent system and dimethylaminopyridine (DMAP). While 7–10 were synthesised by converting benzoic acid into benzoyl chloride by treating with thionyl chloride in the presence of benzene and performing a further reaction with amine in dried benzene. The structures of all the synthesised derivatives of benzoic acid (1–10) were assigned on the basis of extensive NMR studies. All of them showed inhibitory potential against tyrosinase. Among them, compound 7 was found to be the most potent (1.09 μM) when compared with the standard tyrosinase inhibitors of kojic acid (16.67 μM) and L-mimosine (3.68 μM). Finally in this paper, we have discussed the structure–activity relationships of the synthesised molecules.     

Discovery of new potential triplet acting inhibitor for Alzheimer’s disease via X-ray crystallography,molecular docking and molecular dynamics

Abstract

The most common brain disorder of late life is Alzheimer’s disease (AD), which is highly complicating dementia. There are several drug targets which are reported to control the severe level of AD; notably, acetylcholinesterase, β-Secretase and glycogen synthase kinase enzymes are approached as a good drug targets for AD. Hence, the present study mainly focused to discover newly synthesized molecule (7-propyl-6H-pyrano[3,2-c:5,6-c']dichromene-6,8(7H)-dione) as a potential triplet acting drug for above said enzymes through the analysis of X-ray crystallography, molecular docking, molecular dynamics and quantum chemical calculation. The target drug molecule was crystallized in the monoclinic crystal structure with P21/n space group. The structure was solved by SHELXS and refined by SHELXL. The crystal packing is stabilized by C???H···O type of interactions. Further, the induced fit docking shows that the molecule has high docking score, glide energy, favorable hydrogen bonding and hydrophobic interactions on the protein targets. The molecular dynamics simulation was performed to understand the stability of the molecule in the presence of active site environment. Finally, quantum chemical calculation has been carried out for the molecule in gas phase and for the corresponding molecule lifted from the active site region. The structural comparison between gas phase and active site helps to understand the conformational modification of the molecule in the active site.

Communicated by Ramaswamy H. Sarma     

基于转录组分析的染色体大片段缺失及其对井冈霉素高产菌株的影响

【目的】测试大片段删减低转录区域对菌体生长和井冈霉素产量的影响。【方法】通过转录组分析,选择染色体上连续的基因低转录区域进行大片段缺失,通过Cre-loxP位点特异性重组得到1.2 Mb片段缺失突变株LCY-4。HPLC检测缺失株井冈霉素产量的变化,并测定干重绘制生长曲线。【结果】通过转录组分析,我们在井冈霉素高产菌株TL01染色体左侧末端发现了1.9 Mb的连续基因低转录区,使用Cre-loxP系统对其中的1.2 Mb区域进行大片段缺失,成功得到了1.2 Mb缺失突变株LCY-4。和出发菌株TL01相比,缺失突变株LCY-4中井冈霉素发酵产量基本保持不变,生物量有显著提高,最高增幅达到44%。【结论】1.2 Mb区域的成功缺失,意味着基于转录组分析寻找连续的基因低转录区域并加以缺失的策略的可行性。1.2 Mb片段缺失对菌体生物量积累具有明显促进作用,为后续将其开发成氨基环醇类药物异源表达的通用高产宿主奠定了基础。     

A stereochemical model for phospholipids: I. Conformational energy refinement and molecular packing of l-α-Dipalmitoyl lecithin (DPL)

The preferred conformations of L-α-dipalmitoyl-lecithin (DPL) have been refined using a steepest descent procedure throughout non-bonded potential energy calculations. The results indicate that energy differences between the conformers is very low and the energy parameters are quite constant around the minimum, suggesting a large degree of flexibility of this molecule.The molecular packing energy calculations have been performed by separating the two hydrocarbon chains from the polar head groups of the molecule. From the energy parameters for the packing of the aliphatic chains it results that for distances between adjacent chains up to 4·4 Å the intermolecular forces allow the maximum degree of freedom. This suggests that hydrocarbon chains do not play the main role in the packing process of DPL molecule. Therefore the energy parameters of the polar segment have been calculated, assuming that the C₂ asymmetric carbon atom represents the points of the hexagonal lattice and the rotation centre for each molecule. For the internal symmetry of this segment of the molecule two non-equivalent conformers have been selected over all sets of allowed conformations (the GGG and GGG¹ for the α₂, α₃ and α₅ torsion angles). The energy packing calculation has been carried out for two independent sets of data, with and without the electrostatic contributions. In the first case a unique topological situation is allowed with the P-N dipole lying parallel to the lattice plane. In the second case different situations including that with the P-N dipole lying orthogonal to the plane are allowed. These data are discussed in relation to different physical conditions.