With the rapid development of industrialization, human beings have caused many negative effects on the environment that have endangered the survival and development of human beings, such as the greenhouse effect, water pollution, energy depletion, etc [...]

A new classical nonpolarizable force field, KBFF20, for the simulation of peptides and proteins is presented. The force field relies heavily on the use of Kirkwood-Buff theory to provide a comparison of simulated and experimental Kirkwood-Buff integrals for solutes containing the functional groups common in proteins, thus ensuring intermolecular interactions that provide a good balance between the peptide-peptide, peptide-solvent, and solvent-solvent distributions observed in solution mixtures. In this way, it differs significantly from other biomolecular force fields. Further development and testing of the intermolecular potentials are presented here. Subsequently, rotational potentials for the ϕ/ψ and χ dihedral degrees of freedom are obtained by analysis of the Protein Data Bank, followed by small modifications to provide a reasonable balance between simulated and observed α and β percentages for small peptides. This, the first of two articles, describes in detail the philosophy and development behind KBFF20.

Viscoelasticity of corn zein is associated with the formation of β-sheet secondary structures; however, studies of the fundamentals of this conformational change are limited due to zein insolubility and poor analytical resolution. Here, changes in soluble zein conformation were evaluated as the protein self-assembles in increasingly hydrophilic solvents to the concentration just before aggregation and precipitation. Circular dichroism spectra of zein showed that α-helix structures decrease in favor of random coil and β-sheets with increases in water content in an ethanol-water system, similar to observations of zein when it becomes viscoelastic in dough systems. This was further supported by changes in Thioflavin T fluorescence emission spectra and intrinsic viscosity measurements. Two widely recognized molecular models for α-zein (hairpin and superhelical conformations) were tested at 75 and 45% ethanol concentration using molecular dynamics simulation for agreement with experimental results. Increase in solvent hydrophilicity increased β-sheets and reduced distance between backbone anomeric carbons only for hairpin model, suggesting it to be the more valid of the two. These findings emphasize the importance of transformation to β-sheets during zein self-assembly and provide further insight into the mechanisms by which the protein is functionalized into viscoelastic systems.

Ternary complex system of amylose/whey protein/free fatty acid has attracted significant interest in food nutraceuticals or functional compounds in food delivery systems due to the well-known low toxicity,excellent biocompatibility,and solubility.Maize amylose,β-lactoglobulin,α-linoleic acid were self-assembled and characterized by the TEM.Then,in order to understand the mechanism of the self-assembling actions of such a ternary system (interaction among amylose,β-lactoglobulin and α-linoleic acid) deeply,all-atom molecular dynamics simulations were performed to analyze the self-assembling of the 3 components by the Gromacs software.An amylose segment of 55 glucose residues was used to form a 6-fold left-handed helix with 55 nm inner diameter and 135 nm outer diameter approximately and a length of 738 nm.A β-lactoglobulin peptide segment was used on the basis of the three-dimensional (3D) structure determined from an NMR (nuclear magnetic resonance) analysis.The PDB (protein data bank) file for α-linoleic acid was obtained from the Heterocompound Information Centre in Uppsala,Sweden.The glucose force field was chosen and all simulations for the amylose-like molecule were carried out using the glucose force field.The Gromacs 4.6.1 MD package (ScalaLife Competence Center,European Research Council) was used for the simulation.The MD simulations were performed using the leapfrog motion routine with a 2× 10-15 s time step.A total of 250 000 000 simulation steps (for a total of 500 ns simulation time) were performed to assess the progression of the self-assembly process.The LINCS algorithm was used to constrain all bond lengths.In the simulation,the temperature was set at 100 ℃,necessary for the initial formation of the nanoparticle.This was performed using the modified Berendsen thermocouple between the different groups with a relaxation time of 0.1 ps,and the pressure was maintained at 1.0× 105 Pa using the Parrinello-Rahman coupling to a pressure bath via an isotropic coordinate scaling with a relaxation time of 2× 10-12 s.Non-chemical bond interactions were handled using a neighboring grid cell cutoff scheme.Within a neighboring molecules list's cutoff distance of 0.9 nm in a short range,the interactions were evaluated at every time step based on a pair list.A short-range electrostatic cutoff radius of 0.9 nm and a long-range Van der Waals' cutoff radius of 1.4 nm were evaluated simultaneously with each list updating.The binding order of the 3 components could be obtained through the self-assembly snapshot diagram of ternary nanoparticles within 500 ns.The TEM images showed that ternary nanoparticles had a rod-like conformation,which could be confirmed by the snapshot at 500 ns of ternary system from molecular dynamic simulation.Further analyses of their gyration radius and solvent accessible surface area showed that the ternary nanoparticles were highly hydrosoluble,which indicated that the nanoparticles could significantly enhance the aqueous solubility of some hydrophobic nutraceuticals or functional compounds.It also indicated that the formation of the ternary nanoparticles was a thermodynamically spontaneous process among amylose,β-lactoglobulin and α-linoleic acid interaction through the free energy curved-surface map of the ternary nanoparticle.The present work provides insights into the mechanism of the atomic structures of aqueous soluble self-assembled nanoparticles and presents new perspective for the design of nutraceuticals delivery systems with desirable properties.

It is commonly the case that a small number of widely used applications make up a large fraction of the workload of HPC centers. Predicting the performance of important applications running on specific processors enables HPC centers to design best performing system configurations and to insure good performance for the most popular applications on new systems. In the analyses presented in this paper we use applications that are widely used on current open science HPC systems. We characterize the performance of these applications across a spectrum of modern processors and then create a mathematical model to predict their behavior on possible future processors. The hardware sensitivity studies required to build the predictive model are carried out in an HPC cloud resource with bare metal access, and we describe the process and advantages of this approach in detail. We define and discuss the mathematical model that we have designed and compare the predicted performance of these codes with the empirical results obtained in different chips. Finally, we also use the model to estimate the efficiency of future chips. The results indicate that the model is able to estimate the performance of these codes with a relatively small error across a fairly wide spectrum of chips.

We present direct performance measurements for six popular HPC applications in the Knights Landing (KNL) platform. Performance numbers for Sandy Bridge and Haswell processors are provided for contrast. The applications (NAMD, Gromacs, FLASH4, WRF, Quantum Espresso and NCBI BLAST) were selected from among the ten most used in the Stampede supercomputer at the Texas Advanced Computing Center as well as good representative of workloads used by large number of users and, given their diversity, should be representative of typical HPC workloads. All runs were performed with publicly available codes without modification – except a single line added to FLASH4 to enable threading in a given code section – and so results should be expected to improve as developers gain access to KNL. Current results are promising, with execution on a single KNL processor showing speedups up to 2.7X with respect to a dual socket Sandy Bridge and up to 1.7x with respect to a dual socket Haswell.

α-亚油酸和直链淀粉可以形成热力学稳定复合物.为了研究α-亚油酸影响直链淀粉构象的机理、复合物的构象趋势及复合作用过程中氢键的变化情况,在373 K条件下进行了长时间(500 ns)的全原子分子动力学模拟.模拟发现在有/无α-亚油酸存在的情况下,在500 ns内都可以观察到大量有序到无序的构象转变,这表明直链淀粉和α-亚油酸之间结合作用微弱.原子均方根偏差(RMSD)、α-亚油酸与直链淀粉轴心间距、氢键增加都证明直链淀粉-α-亚油酸复合物的形成是热力学自发行为.

Kα radiative transitions of C-like to F-like Al ions are studied using the multiconfiguration Dirac–Fock (MCDF) method. The fully relativistic MCDF approach was specifically designed to calculate atomic structures and radiative transition rates, and hence it ensures a reasonable description of the emission effects and spectral intensities. The energies and wavefunctions, corresponding mixing coefficients, the influence of electron correlation effects on energy levels, and radiative transition rates for C-like to F-like Al ions are investigated in detail. Good agreement is found between the calculated Kα emission spectra in this work and the spectra from experimental measurements.

A previously reported nanoparticle formed through the self-assembly of common food constituents (amylose, protein, and fatty acids) was shown to have the capacity to carry a sparingly soluble small molecule (1-naphthol) in a dispersed system. Potentiometric titration showed that 1-naphthol locates in the lumen of the amylose helix of the nanoparticle. This finding was further supported by calorimetric measurements, showing higher enthalpies of dissociation and reassociation in the presence of 1-naphthol. Visually, the 1-naphthol-loaded nanoparticle appeared to be well-dispersed in aqueous solution. Molecular dynamics simulation showed that the self-assembly was favorable, and at 500 ns, the 1-naphthol molecule resided in the helix of the amylose lumen in proximity to the hydrophobic tail of the fatty acid. Thus, sparingly soluble small molecules, such as some nutraceuticals or drugs, could be incorporated and delivered by this soft nanoparticle carrier.

We also propose a website to host such a DBMS that can facilitate researchers to upload their data and perform analysis efficiently. Users can analyze their data using efficient functions implemented to access the data. Index structures are generated to store all results of analysis that may be interesting to other users, so that the results of analysis are readily available without the need to duplicate the analysis. The data upload feature can be made available through application program interfaces (APIs). Users can upload their data using the APIs. The DBMS takes care of generating indexes, storing results of analysis and retrieving efficiently, whenever users run analysis query or request information.

Molecular dynamics (MD) simulation has become one of the key tools to obtain deeper insights into biological systems using various levels of descriptions such as all‐atom, united‐atom, and coarse‐grained models. Recent advances in computing resources and MD programs have significantly accelerated the simulation time and thus increased the amount of trajectory data. Although many laboratories routinely perform MD simulations, analyzing MD trajectories is still time consuming and often a difficult task. ST‐analyzer, http://im.bioinformatics.ku.edu/st‐analyzer, is a standalone graphical user interface (GUI) toolset to perform various trajectory analyses. ST‐analyzer has several outstanding features compared to other existing analysis tools: (i) handling various formats of trajectory files from MD programs, such as CHARMM, NAMD, GROMACS, and Amber, (ii) intuitive web‐based GUI environment—minimizing administrative load and reducing burdens on the user from adapting new software environments, (iii) platform independent design—working with any existing operating system, (iv) easy integration into job queuing systems—providing options of batch processing either on the cluster or in an interactive mode, and (v) providing independence between foreground GUI and background modules—making it easier to add personal modules or to recycle/integrate pre‐existing scripts utilizing other analysis tools. The current ST‐analyzer contains nine main analysis modules that together contain 18 options, including density profile, lipid deuterium order parameters, surface area per lipid, and membrane hydrophobic thickness. This article introduces ST‐analyzer with its design, implementation, and features, and also illustrates practical analysis of lipid bilayer simulations. © 2014 Wiley Periodicals, Inc.

The Rayleigh–Ritz variation method using a multiconfiguration interaction wavefunction is carried out on the high-lying core-excited states 6Se,o(n) and 6Pe,o(n) (n=1–5) for the boron isoelectronic sequence (Z=6–10), including mass polarization and relativistic corrections. Energy levels, fine structure, transition rates, and transition wavelengths for this system are calculated. Some energy levels of the high-n states are reported for the first time. Wavelengths of the electric-dipole transitions from these core-excited sextet states with quantum electro-dynamical effects and higher-order relativistic corrections are included. The lifetimes of the 1s2s2p23p6So,1s2p33s6So,1s2s2p23s6P, 1s2s2p23d6P, and 1s2p33p6P states for the boron isoelectronic sequence are also reported. Our calculated results agree well in most cases with available theoretical and experimental data in the literature.

ABSTRACT The gH/gL heterodimer represents two of the four herpes simplex virus glycoproteins necessary and sufficient for membrane fusion. We generated deletions and point mutations covering gL residues 24 to 43 to investigate that region's role in gH/gL intracellular trafficking and in membrane fusion. Multiple mutants displayed a 40 to 60% reduction in cell fusion with no effect on gH/gL trafficking. The amino terminus of gL plays an important role in the gH/gL contribution to membrane fusion.

Energy levels, radiative rates, Auger branching ratios of the 1s vacancyresonances 1s2s 22p 2 and1s2s2p 3   2,4L (L  =  S,P, D) of the boron isoelectronic sequence including O3+, Ne5+, Mg7+, Si9+ ions are calculated by the saddle-point variation andsaddle-point complex-rotation methods. Large-scale wavefunctions are used to obtain reliable results. Relativistic corrections and mass polarisation effects are taken intoaccount to get precise energy levels. Calculated X-ray wavelengths, radiative rates, Auger electron energies, and Auger rates for these core-excited states are compared withavailable theoretical and experimental results. Furthermore, calculated reliable X-ray wavelengths are used to give possible identifications for satellite lines in the X-rayspectrum of foil-excited magnesium and silicon ions. Calculated Auger electron energies and Auger branching ratios are used to identify oxygen and neon Auger electron spectrallines in previous collision experiments. Three unidentified experimental spectral lines in neon KLL Auger electron spectrum are identified in the present work. The total radiativerates and the total Auger rates for the 1s2s 22p 2 and1s2s2p 3 resonances of B-like ions are also discussed, as a function of atomic number Z. It isfound that the total Auger rates of these resonances are several orders of magnitude larger than the total radiative rates for these low-Z(Z = 6–14) ions.

Tyrosyl-DNA phosphodiesterase I (Tdp1) is a cellular enzyme that repairs the irreversible topoisomerase I (Top1)-DNA complexes and confers chemotherapeutic resistance to Top1 inhibitors. Inhibiting Tdp1 provides an attractive approach to potentiating clinically used Top1 inhibitors. However, despite recent efforts in studying Tdp1 as a therapeutic target, its inhibition remains poorly understood and largely underexplored. We describe herein the discovery of arylidene thioxothiazolidinone as a scaffold for potent Tdp1 inhibitors based on an initial tyrphostin lead compound 8. Through structure-activity relationship (SAR) studies we demonstrated that arylidene thioxothiazolidinones inhibit Tdp1 and identified compound 50 as a submicromolar inhibitor of Tdp1 (IC₅₀ = 0.87 μM). Molecular modeling provided insight into key interactions essential for observed activities. Some derivatives were also active against endogenous Tdp1 in whole cell extracts. These findings contribute to advancing the understanding on Tdp1 inhibition.

Energies for the multiexcited states 1s(2)2s(2)pnl and 1s(2)2p(2)nl 4Pe,o (n = 2) of B-like oxygen are calculated using RayleighRitz variation method with configuration interaction. The mass polarization and relativistic corrections are obtained with first-order perturbation theory. Configuration structures of the high-lying multiexcited series are identified by energies and contribution to normalization of angular-spin components. These structures are further checked by calculations of relativistic corrections and fine structure splittings. Hyperfine parameters and hyperfine coupling constants are calculated for the first time. Wavelengths including quantum electrodynamic effect and higher-order relativistic corrections and lifetimes are also calculated. These results are compared with available results in the literature. (C) 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2012

Energy levels, Auger branching ratios, and radiative rates of the core-excited states of B-like carbon are calculated by the saddle-point variation and saddle-point complex-rotation methods. Relativistic and mass polarization corrections are included using first-order perturbation theory. Calculated Auger channel energies and branching ratios are used to identify high-resolution Auger spectrum in the 300-keV C(+) → CH(4) collision experiment. It is found that Auger decay of these five-electron core-excited states gives significant contributions to Auger spectrum in the range of 238-280 eV.