Dose calculation validation of a convolution algorithm in a solid water phantom

PurposeThe dose calculated using a convolution algorithm should be validated in a simple homogeneous water-equivalent phantom before clinical use. The dose calculation accuracy within a solid water phantom was investigated.MethodsThe specific Gamma knife design requires a dose rate calibration within a spherical solid water phantom. The TMR10 algorithm, which approximates the phantom material as liquid water, correctly computes the absolute dose in water. The convolution algorithm, which considers electron density miscalculates the dose in water as the phantom Hounsfield units were converted into higher electron density when the original CT calibration curve was used. To address this issue, the electron density of liquid water was affected by modifying the CT calibration curve. The absolute dose calculated using the convolution algorithm was compared with that computed by the TMR10. The measured depth dose profiles were also compared to those computed by the convolution and TMR10 algorithms. A patient treatment was recalculated in the solid-water phantom and the delivery quality assurance was checked.ResultsThe convolution algorithm and the TMR10 calculate an absolute dose within 1% when using the modified CT calibration curve. The dose depth profile calculated using the convolution algorithms was superimposed on the TMR10 and measured dose profiles when the modified CT calibration curve was applied. The Gamma index was better than 93%.ConclusionsDose calculation algorithms, which consider electron density, require a CT calibration curve adapted to the phantom material to correctly compute the dose in water.     

Molecular Dynamics Simulation of Model Lipid Membranes: Structural Effects of Impurities

Abstract

The gel to fluid phase transition or ordered to disordered phase transition observed in biological membranes are simulated by using constant energy Molecular Dynamics. The surface part of the membrane is modelled as a two-dimensional matrix formed by the head groups of the phospholipid molecules. Head molecules which are modelled as three spheres fused with three force centers, interact with each other via van der Waals and Coulomb type interactions. The -so called- impurity or foreign molecule embedded in the surface represents the protein type molecule which is present in biological membranes and control its activity. It is modelled as a pentagon having one force centers in each corner. It also interacts with the surface molecules again via van der Waals and Coulomb type interactions. The surface density is kept constant in the simulations of the systems with or without impurity. Structural and orientational changes due to impurity were observed and proved by monitoring two-dimensional order parameter. It has been shown that melting of the surface or breakage of the ordering of the surface molecules becomes easier and ordered to disordered phase transition temperature was lowered by 100 K if the impurity is present.     

Non Equilibrium Molecular Dynamics Simulation of Coupled Heat- and Mass Transport Across a Liquid/Vapor Interface

Abstract

The transport properties of bulk liquid, gas and at the gas/liquid interface were studied for two binary Lennard-Jones/spline mixtures by use of nonequilibrium molecular dynamics. One of the mixtures was an ideal isotope mixture, the other a non-ideal mixture. The simulations gave the thermal conductivity, mutual diffusion coefficient, heat flux, mass flux, and the changes in these quantities across the interface. The local entropy production was expressed in terms of fluxes and thermodynamic forces, and numercial estimates are given. It was shown that the largest contribution to the total entropy production occurs in the vapor phase under the chosen conditions. We expect, however that if the mass flux were larger, the major contribution to the entropy production would come from the liquid phase.     

The nature of the helix-random coil transition of biological macromolecules attached to a surface

The effect of the presence of a surface on the helix–random coil transition is investigated. It is found that a grand canonical ensemble formation used previously to solve exactly the problem of a polymer between two plates can be used to solve approximately the problem of DNA near a plane surface. The formalism is applied to the homogeneous perfect-matching model of infinite molecular weight. A crucial part of the calculation for double-stranded molecules involves the evaluation of the entropy of the loops connecting the helical portions of the double-stranded chains. One obtains as a measure of the configurational freedom of a loop Asⁱ/j^c where c has the following values: for a loop connecting two helical regions both off the surface c = 3/2; for a loop connecting a helical region on the surface to a helical region off the surface c = 5/2; for a loop connecting helixes both on the surface c = 4. Corresponding values for an n-stranded molecule are c = (3n ? 3)/2, c = (4n ? 3)/2, c = (5n ? 2)/2. In all cases, the effect of the surface is to sharpen the transition. In the case of double-stranded molecules, the transition becomes first order. We take the view that self-assembly of biological macromolecules can be considered as a sharp thermodynamic phase transition. Thus, the above systems become models of self-assembling systems. They are also relevant to the problem of surface-induced enzymatic activity.     

Study on properties of liquid ammonia via molecular dynamics simulation based on ABEEMσπ polarisable force field

Abstract

The molecular dynamics simulation has been performed to investigate the charge distribution, structural and dynamical properties of liquid ammonia at 273 K using a polarisable force field of the atom-bond electronegativity equalisation method (ABEEMσπ). One ammonia molecule in this model has eight charge sites, one N atomic site, three H atomic sites, three N–H bond sites and one lone-pair electron site. ABEEMσπ model can present the quantitative site charges of molecular ammonias in liquid and their changing in response to their surroundings. The radial distribution functions and dynamical properties are in fair agreement with the available experimental data. The first peak of g_NN(r) appears at N–N distance of ~3.50 ± 0.05 Å where most hydrogen bonds are formed. The average coordination number of the first shell is 13.0 ± 0.1 among which a central ammonia molecule intimately connects 3 ~ 4 ammonia molecules by hydrogen bonds. The power spectrum shows the vibrations of hydrogen bonds. For a reference, a simple estimation of the average hydrogen bonding energy in liquid ammonia is 6.5 ± 0.1 kcal/mol larger than 3.8 ± 0.3 kcal/mol in dimer ammonia. Our simulation results provide more detailed information about liquid ammonia.     

硝酸盐对牛粪梭菌甲酸脱氢酶缺失型Wood-Ljungdahl途径固碳的影响

【背景】异于同型产乙酸菌通常利用Wood-Ljungdahl途径将2分子CO₂还原为1分子乙酰辅酶A,Clostridium bovifaecis缺失Wood-Ljungdahl途径甲基支路第1步将CO₂还原为甲酸的甲酸脱氢酶,需甲酸存在时将1分子甲酸和1分子CO₂还原为乙酰辅酶A发生葡萄糖的同型产乙酸型发酵。已有报道显示,硝酸盐也可作为同型产乙酸菌的电子受体,而且对不同同型产乙酸菌的代谢影响有所不同,然而硝酸盐对这种独特的甲酸脱氢酶缺失型Wood-Ljungdahl途径固碳的影响尚不清楚。【目的】探究硝酸盐对C.bovifaecis甲酸脱氢酶缺失型Wood-Ljungdahl途径固碳的影响。【方法】硝酸盐浓度分别为10 mmol/L和30 mmol/L时,以未添加硝酸盐为对照实验,研究C.bovifaecis在葡萄糖+甲酸+CO₂为基质条件下的细菌生长、底物消耗和产物生成情况。【结果】10 mmol/L和30 mmol/L硝酸盐存在时,主要产物乙醇浓度分别为5.80 mmol/L和1.66 mmo...     

Effect of Cosmological Neutrinos on Discrimination Between the Two Enantiomers of a Chiral Molecule

In the framework of an extraterrestrial origin of biological homochirality, universal mechanisms are of particular interest. In this sense we consider the weak parity-violating neutrino-electron interaction through weak charged currents W ^± between the relic flux of cosmological neutrinos and the electrons of a chiral molecule. We use the known theoretical result of the split in energy of the two helicity sates of an electron in the cosmic neutrino bath, due to weak charged currents. In the case that electrons of a chiral molecule are submitted to a helicoidal potential due to the nuclear conformation, these electrons have opposite helicities for the two enantiomers of the molecule and consequently the mentioned neutrino-electron interaction would produce a splitting in energy between the two enantiomers. An estimation of this energy for the case of a single electron yields a small value of the order of 10⁻²⁶ eV. This value results amplified by the contribution of all the molecular electrons having helicity and other possible mechanisms.     

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 structure of Escherichia coli membranes studied by fluorescence measurements of lipid phase transitions

Lipid phase transitions in Escherichia coli membranes and in dispersions of the extracted lipids were studied using the negatively charged fluorescence probe 1-anilinonaphthalene-8-sulfonate (ANS⁻) and the hydrophobic fluorescence probe N-phenyl-1-naphthylamine (NPN). The fluorescence change, ΔI, at the phase transition approaches a limiting value (ΔI)_lim with increasing dye concentration. A comparison of the limiting values (Δ)_lim^NPN obtained for membranes and the lipid standard allows us to estimate the lipid fraction, ρ, in the membrane that takes part in the phase transition (ρ = 80%). The same procedure carried out with ANS⁻ yields a value of 42.5% for the lipid fraction that is accessible from the aqueous phase. These values, combined with published freeze-etching data for the particle density within the fracture plane of membranes are used to quantify the Davson-Danielli-Robertson-Benson-Singer membrane model which assumes a fluid lipid bilayer with “integral” proteins embedded in the lipid matrix and surface proteins attached to the lipid head groups. It appears that on the average one “integral” membrane protein is surrounded by about 600 lipid molecules and that about 130 of these molecules are closely coupled to the protein molecule, forming an halo in which the chain-chain interaction between the lipids is disturbed. About half of the bilayer surface is covered with proteins; part of these seem to be stacked.     

The extent to which ATP demand controls the glycolytic flux depends strongly on the organism and conditions for growth

Using molecular genetics we have introduced uncoupled ATPase activity in two different bacterial species, Escherichia coli and Lactococcus lactis, and determined the elasticities of the growth rate and glycolytic flux towards the intracellular [ATP]/[ADP] ratio. During balanced growth in batch cultures of E. coli the ATP demand was found to have almost full control on the glycolytic flux (FCC=0.96) and the flux could be stimulated by 70%. In contrast to this, in L. lactis the control by ATP demand on the glycolytic flux was close to zero. However, when we used non-growing cells of L. lactis (which have a low glycolytic flux) the ATP demand had a high flux control and the flux could be stimulated more than two fold. We suggest that the extent to which ATP demand controls the glycolytic flux depends on how much excess capacity of glycolysis is present in the cells.     

Structural and Chemical Characterization of a Natural Fracture Surface from 2.8 Kilometers Below Land Surface: Biofilms in the Deep Subsurface

A freshly intersected water-bearing fracture zone from the Mponeng Au mine located in the Witwatersrand Basin, Republic of South Africa was sampled, providing an opportunity to examine the natural, deep subsurface biosphere. The fracture, intersected by an advancing tunnel 2.8 kilometers below land surface, possessed a millimeter thick layer of chlorite group minerals, i.e., chamosite, at the water-mineral interface. Water flowing out from the fracture zone had a temperature of 52°C, pH of 9.16 and Eh of ?263 mV. Using scanning electron microscopy, the water-mineral interface was generally found to be clean, i.e., it did not possess any secondary mineral or dominant organic coatings. Irregular patches (10's of μm ² ) of organic material, however, resembling bacterial exopolysaccharides, occurred in the presence or absence of bacteria. The surface was colonized by highly dispersed individual bacteria or by microcolonies containing up to 5 cells, with an overall cell density of 5 × 10⁴ bacteria cm ^?2 . This biofilm population, although low, was 2 orders of magnitude greater than the bacteria present within the aqueous phase and provides the first direct observation of the sessile population from the terrestrial deep subsurface. Time of Flight-Secondary Ion Mass spectrometry revealed that the fracture surface was actually coated with a thin, i.e., molecular, organic conditioning film over much of its surface that was separate from the exopolysaccharide layers associated with the mineral water interface and with some of the attached cells.     

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     

Comparative analysis of plastocyanin–cytochrome f complex formation in higher plants,green algae and cyanobacteria

Mechanisms of the complex formation between plastocyanin and cytochrome f in higher plants (Spinacia oleracea and Brassica rapa), green microalgae Chlamydomonas reinhardtii and two species of cyanobacteria (Phormidium laminosum and Nostoc sp.) were investigated using combined Brownian and molecular dynamics simulations and hierarchical cluster analysis. In higher plants and green algae, electrostatic interactions force plastocyanin molecule close to the heme of cytochrome f. In the subsequent rotation of plastocyanin molecule around the point of electrostatic contact in the vicinity of cytochrome f, copper (Cu) atom approaches cytochrome heme forming a stable configuration where cytochrome f molecule behaves as a rather rigid body without conformational changes. In Nostoc plastocyanin molecule approaches cytochrome f in a different orientation (head‐on) where the stabilization of the plastocyanin–cytochrome f complex is accompanied by the conformational changes of the G188E189D190 loop that stabilizes the whole complex. In cyanobacterium P. laminosum, electrostatic preorientation of the approaching molecules was not detected, thus indicating that random motions rather than long‐range electrostatic interactions are responsible for the proper mutual orientation. We demonstrated that despite the structural similarity of the investigated electron transport proteins in different photosynthetic organisms, the complexity of molecular mechanisms of the complex formation increases in the following sequence: non‐heterocystous cyanobacteria – heterocystous cyanobacteria – green algae – flowering plants.     

A Two-Ellipsoid Model Based Upon A Gaussian Overlap Potential

Abstract

The two-ellipsoid model (TEM) is proposed as a versatile single-site model which can be used in the study of liquid crystal phases. This TEM uses two ellipsoids to describe a molecule, one ellipsoid for the geometry and the other for the interaction strengths of the molecule. The present TEM can mimic asymmetric interactions of a liquid crystal molecule by separating the center of the interaction ellipsoid from that of the geometry ellipsoid. The potential energy surfaces of the present TEMs compare favorably with those of the corresponding Gay-Berne and the site–site models.

Monte Carlo simulations with 320 particles are performed for a symmetric interaction TEM and an asymmetric interaction TEM. The asymmetric interaction TEM displays a slightly higher transition temperature than the symmetric interaction TEM indicating that asymmetric interactions can be a driving force in a phase transition. Radial and cylindrical distribution functions of two models in the isotropic phase are similar, but those in the nematic phase are quite different.     

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).     

Removal of toluene in waste gases using a biological trickling filter

The removal of toluene from waste gas was studied in a trickling biofilter. A high level of water recirculation (4.7 m h^–1) was maintained in order to keep the liquid phase concentration constant and to achieve a high degree of wetting. For loads in the range from 6 to 150 g m^–3 h^–1 the maximum volumetric removal rate (elimination capacity) was 35±10 g m^–3 h^–1, corresponding to a zero order removal rate of 0.11±0.03 g m^–2 h^–1 per unit of nominal surface area. The surface removal was zero order above the liquid phase concentrations of approximately 1.0 g m^–3, corresponding to inlet gas concentrations above 0.7–0.8 g m^–3. Below this concentration the surface removal was roughly of first order. The magnitude of the first order surface removal rate constant, k_1A , was estimated to be 0.08–0.27 m h^–1 (k_1A a=24–86 h^–1). Near-equilibrium conditions existed in the gas effluent, so mass transfer from gas to liquid was obviously relatively fast compared to the biological degradation. An analytical model based on a constant liquid phase concentration through the trickling filter column predicts the effluent gas concentration and the liquid phase concentration for a first and a zero order surface removal. The experimental results were in reasonable agreement with a very simple model valid for conditions with an overall removal governed by the biological degradation and independent of the gas/liquid mass transfer. The overall liquid mass transfer coefficient, K_La, was found to be a factor 6 higher in the system with biofilm compared to the system without. The difference may be explained by: 1. Difference in the wetting of the packing material, 2. Mass transfer occurring directly from the gas phase to the biofilm, and 3. Enlarged contact area between the gas phase and the biofilm due to a rough biofilm surface.     

A Study of Conformational Equilibria in Chain Molecules. I. Liquid n-Butane

Abstract

We have performed molecular dynamics simulations for liquid n-butane in order to understand liquid structures in terms of both inter- and intra-molecular interactions. Each n-butane molecule consists of four sites interacting with LJ potential and only a dihedral angle is taken into account as the internal degree of freedom. The population of gauche conformations with respect to the ideal gas state is found to increase in the liquid state. To investigate how the intermolecular interaction affects the dihedral angle distribution, we also adopt the repulsive LJ potential (RLJ) model. It is found that the nearest neighbor packing of the methyl and/or methylene groups can be approximately represented by using only the repulsive interaction. From the dihedral angle distribution, however, the rate of the shift of RLJ model to gauche is larger than that of LJ model and the attractive force also plays a significant role in the conformational equilibrium.     

Proton Transfer in Liquid Water II; A Semiempirical Method to Describe Chemical Reactions

Abstract

A new semiempirical method is developed to deal with the proton transfer in liquid water. In the previous work, we have shown that two- and three-body charge transfer interactions and electrostatic interactions are the most important factors to describe the potential energy surfaces (PES) of the proton transfer in liquid water [Chemical Physics 180, 239–269, 1994], In order to take account of these factors, we develop a semiempirical method imposing the principle of electronegativity equalization to the Atoms in Molecule (AIM) method. The method is free from the well-known discrepancy of the traditional AIM methods, that is, the fractional molecular charges at large molecular separation, and thus can be applied to the charge transfer reactions. Intra- and intermolecular physical quantities, such as total energies, force vectors, dipole moment vectors and intermolecular charge transfer, obtained by the present method are found to be in good agreement with those by ab initio calculation.     

Exploring the nature of the H-bonds between the human class II MHC protein,HLA-DR1 (DRB*0101) and the influenza virus hemagglutinin peptide,HA306-318, using the quantum theory of atoms in molecules

The nature of the H-bonds between the human protein HLA-DR1 (DRB*0101) and the hemagglutinin peptide HA306-318 has been studied using the Quantum Theory of Atoms in Molecules for the first time. We have found four H-bond groups: one conventional CO··HN bond group and three nonconventional CO··HC, π··HC involving aromatic rings and HN··HC_aliphatic groups. The calculated electron density at the determined H-bond critical points suggests the follow protein pocket binding trend: P1 (2,311) >> P9 (1.109) > P4 (0.950) > P6 (0.553) > P7 (0.213) which agrees and reveal the nature of experimental findings, showing that P1 produces by a long way the strongest binding of the HLA-DR1 human protein molecule with the peptide backbone as consequence of the vast number of H-bonds in the P1 area and at the same time the largest specific binding of the peptide Tyr308 residue with aromatic residues located at the binding groove floor. The present results suggest the topological analysis of the electronic density as a valuable tool that allows a non-arbitrary partition of the pockets binding energy via the calculated electron density at the determined critical points.