Conformational dynamics of HIV-1 protease: a comparative molecular dynamics simulation study with multiple amber force fields

Flap dynamics of HIV-1 protease (HIV-pr) controls the entry of inhibitors and substrates to the active site. Dynamical models from previous simulations are not all consistent with each other and not all are supported by the NMR results. In the present work, the er effect of force field on the dynamics of HIV-pr is investigated by MD simulations using three AMBER force fields ff99, ff99SB, and ff03. The generalized order parameters for amide backbone are calculated from the three force fields and compared with the NMR S2 values. We found that the ff99SB and ff03 force field calculated order parameters agree reasonably well with the NMR S2 values, whereas ff99 calculated values deviate most from the NMR order parameters. Stereochemical geometry of protein models from each force field also agrees well with the remarks from NMR S2 values. However, between ff99SB and ff03, there are several differences, most notably in the loop regions. It is found that these loops are, in general, more flexible in the ff03 force field. This results in a larger active site cavity in the simulation with the ff03 force field. The effect of this difference in computer-aided drug design against flexible receptors is discussed.

Nonlocal continuum mechanics based ultrasonic flexural wave dispersion characteristics of a monolayer graphene embedded in polymer matrix

Wave propagation in graphene sheet embedded in elastic medium (polymer matrix) has been a topic of great interest in nanomechanics of graphene sheets, where the equivalent continuum models are widely used. In this manuscript, we examined this issue by incorporating the nonlocal theory into the classical plate model. The influence of the nonlocal scale effects has been investigated in detail. The results are qualitatively different from those obtained based on the local/classical plate theory and thus, are important for the development of monolayer graphene-based nanodevices. In the present work, the graphene sheet is modeled as an isotropic plate of one-atom thick. The chemical bonds are assumed to be formed between the graphene sheet and the elastic medium. The polymer matrix is described by a Pasternak foundation model, which accounts for both normal pressure and the transverse shear deformation of the surrounding elastic medium. When the shear effects are neglected, the model reduces to Winkler foundation model. The normal pressure or Winkler elastic foundation parameter is approximated as a series of closely spaced, mutually independent, vertical linear elastic springs where the foundation modulus is assumed equivalent to stiffness of the springs. For this model, the nonlocal governing differential equations of motion are derived from the minimization of the total potential energy of the entire system. An ultrasonic type of flexural wave propagation model is also derived and the results of the wave dispersion analysis are shown for both local and nonlocal elasticity calculations. From this analysis we show that the elastic matrix highly affects the flexural wave mode and it rapidly increases the frequency band gap of flexural mode. The flexural wavenumbers obtained from nonlocal elasticity calculations are higher than the local elasticity calculations. The corresponding wave group speeds are smaller in nonlocal calculation as compared to local elasticity calculation. The effect of y-directional wavenumber (eta(q)) on the spectrum and dispersion relations of the graphene embedded in polymer matrix is also observed. We also show that the cut-off frequencies of flexural wave mode depends not only on the y-direction wavenumber but also on nonlocal scaling parameter (e(0)a). The effect of eta(q) and e(0)a on the cut-off frequency variation is also captured for the cases of with and without elastic matrix effect. For a given nanostructure, nonlocal small scale coefficient can be obtained by matching the results from molecular dynamics (MD) simulations and the nonlocal elasticity calculations. At that value of the nonlocal scale coefficient, the waves will propagate in the nanostructure at that cut-off frequency. In the present paper, different values of e(0)a are used. One can get the exact e(0)a for a given graphene sheet by matching the MD simulation results of graphene with the results presented in this article. (c) 2012 Elsevier Ltd. All rights reserved.

Structure of a carbon nanotube-dendrimer composite

Using all atomistic molecular dynamics (MD) simulations we report a microscopic picture of the carbon nanotube (6,5)-dendrimer complex for PAMAM dendrimers of generations 2 to 4. We study the compact wrapping conformations of the dendrimer onto the nanotube surface for all the three generations of PAMAM dendrimer. A high degree of wrapping for the non-protonated dendrimer is observed as compared to the protonated dendrimer. For comparison, we also study the interaction of another dendrimer, poly(propyl ether imine) (PETIM), with the nanotube. The results of the distance of closest approach as well as the number of close contacts between the nanotube and the dendrimer reveal that the PAMAM dendrimer interacts strongly as compared to the PETIM dendrimer. We also calculate the binding energy between the nanotube and the dendrimer using MM/PBSA methods and attribute the strong binding to the charge transfer between them. Dendrimer wrapping on the CNT will make it soluble and the dendrimer can act as an efficient dispersing agent for the nanotubes.

Coupled polynomial field approach for elimination of flexure and torsion locking phenomena in the Timoshenko and Euler-Bernoulli curved beam elements

The curvature related locking phenomena in the out-of-plane deformation of Timoshenko and Euler-Bernoulli curved beam elements are demonstrated and a novel approach is proposed to circumvent them. Both flexure and Torsion locking phenomena are noticed in Timoshenko beam and torsion locking phenomenon alone in Euler-Bernoulli beam. Two locking-free curved beam finite element models are developed using coupled polynomial displacement field interpolations to eliminate these locking effects. The coupled polynomial interpolation fields are derived independently for Timoshenko and Euler-Bernoulli beam elements using the governing equations. The presented of penalty terms in the couple displacement fields incorporates the flexure-torsion coupling and flexure-shear coupling effects in an approximate manner and produce no spurious constraints in the extreme geometric limits of flexure, torsion and shear stiffness. the proposed couple polynomial finite element models, as special cases, reduce to the conventional Timoshenko beam element and Euler-Bernoulli beam element, respectively. These models are shown to perform consistently over a wide range of flexure-to-shear (EI/GA) and flexure-to-torsion (EI/GJ) stiffness ratios and are inherently devoid of flexure, torsion and shear locking phenomena. The efficacy, accuracy and reliability of the proposed models to straight and curved beam applications are demonstrated through numerical examples. (C) 2012 Elsevier B.V. All rights reserved.

SEU Tolerant Robust Memory Cell Design

The implementation of semiconductor circuits and systems in nano-technology makes it possible to achieve high speed, lower voltage level and smaller area. The unintended and undesirable result of this scaling is that it makes integrated circuits susceptible to soft errors normally caused by alpha particle or neutron hits. These events of radiation strike resulting into bit upsets referred to as single event upsets(SEU), become increasingly of concern for the reliable circuit operation in the field. Storage elements are worst hit by this phenomenon. As we further scale down, there is greater interest in reliability of the circuits and systems, apart from the performance, power and area aspects. In this paper we propose an improved 12T SEU tolerant SRAM cell design. The proposed SRAM cell is economical in terms of area overhead. It is easy to fabricate as compared to earlier designs. Simulation results show that the proposed cell is highly robust, as it does not flip even for a transient pulse with 62 times the Q(crit) of a standard 6T SRAM cell.

Detection of glycated hemoglobin using 3-Aminophenylboronic acid modified graphene oxide

This paper presents the chemical synthesis of 3-Aminophenylboronic acid (APBA) modified graphene oxide (GO) and its application to the electrochemical detection of glycated hemoglobin (GHb). The compound (GO-APBA) was synthesized by forming an amide linkage between the amino group (-NH2) of APBA and the carboxylic group (-COOH) of GO. The compound was characterized using IR spectroscopy. Detection of GHb was carried out using Electrochemical Impedance Spectroscopic (EIS) measurements with GO-APBA modified glassy carbon electrode as the working electrode.

Multiuser detection in large-dimension multicode MIMO-CDMA systems with higher-order modulation

In this paper, we are interested in high spectral efficiency multicode CDMA systems with large number of users employing single/multiple transmit antennas and higher-order modulation. In particular, we consider a local neighborhood search based multiuser detection algorithm which offers very good performance and complexity, suited for systems with large number of users employing M-QAM/M-PSK. We apply the algorithm on the chip matched filter output vector. We demonstrate near-single user (SU) performance of the algorithm in CDMA systems with large number of users using 4-QAM/16-QAM/64-QAM/8-PSK on AWGN, frequency-flat, and frequency-selective fading channels. We further show that the algorithm performs very well in multicode multiple-input multiple-output (MIMO) CDMA systems as well, outperforming other linear detectors and interference cancelers reported in the literature for such systems. The per-symbol complexity of the search algorithm is O(K2n2tn2cM), K: number of users, nt: number of transmit antennas at each user, nc: number of spreading codes multiplexed on each transmit antenna, M: modulation alphabet size, making the algorithm attractive for multiuser detection in large-dimension multicode MIMO-CDMA systems with M-QAM.

Tensile behavior of a free-standing Pt-aluminide (PtAl) bond coat

The tensile behavior of a high activity stand-alone Pt-aluminide (PtAl) bond coat was evaluated by the micro-tensile test method at various temperatures (room temperature to 1100 degrees C) and strain rates (10(-5) s(-1)-10(-1) s(-1).) At all strain rates, the stress strain behavior of the stand-alone coating was significantly affected by the variation in temperature. The stress strain response was linear, indicating brittle behavior, at temperatures below the brittle ductile transition temperature (BDTT). The coating exhibited appreciable ductility (up to 2%) above the BDTT. The strength (both yield stress and ultimate tensile strength) of the coating decreased and its ductility increased with increasing temperature above the BDTT. The tensile behavior of the coating was sensitive to strain rate in the ductile regime, with its strength increasing with increasing strain rate at any given temperature. The BDTT of the coating was found to increase with increasing with increasing strain rate. The coating exhibited two distinct mechanisms of deformation above the BDTT. The transition temperature for the change of deformation mechanism also increased with increasing strain rate. (C) 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Diffusion of pentane isomers in faujasite-type zeolites : NMR and molecular dynamics study

Diffusion of pentane isomers in zeolites NaX has been investigated using pulsed field gradient nuclear magnetic resonance (PFG-NMR) and molecular dynamics (MD) techniques respectively. Temperature and concentration dependence of diffusivities have been studied. The diffusivities obtained from NMR are roughly an order of magnitude smaller than those obtained from MD. The dependence of diffusivity on loading at high temperatures exhibits a type I behavior according to the classification of Karger and Pfeifer 1]. NMR diffusivities of the isomers exhibit the order D(n-pentane) > D(isopentane) > D(neopentane). The results from MD suggest that the diffusivities of the isomers follow the order D(n-pentane) < D(isopentane) < D(neopentane). The activation energies from NMR show E-a(n-pentane) < E-a(isopentane) < E-a(neopentane) whereas those from MD suggest the order E-a(n-pentane) > (isopentane) > E-a(neopentane). The latter follows the predictions of levitation effect whereas those of NMR appears to be due to the presence of defects in the zeolite crystals. The differences between diffusivities estimated by NMR and MD are attributed to the longer time and length scales sampled by the NMR technique, as compared to MD. (C) 2012 Elsevier Inc. All rights reserved.

Molecular dynamics simulations of PPI dendrimer-drug complexes

Dendrimeric nanoparticles are potential drug delivery devices which can enhance the solubility of hydrophobic drugs, thus increasing their bioavailability and sustained release action. A quantitative understanding of the dendrimer-drug interactions can give valuable insight into the solubility and release profile of hydrophobic drug molecules in various solvent conditions. Fully atomistic molecular dynamics (MD) simulations have been performed to study the interactions of G5 PPIEDA (G5 ethylenediamine cored poly(propylene imine)) dendrimer and two well known drugs (Famotidine and Indomethacin) at different pH conditions. The study suggested that at low pH the dendrimer-drug complexes are thermodynamically unstable as compared to neutral and high pH conditions. Calculated Potential of Mean Force (PMF) by umbrella sampling showed that the release of drugs from the dendrimer at low pH is spontaneous, median release at neutral pH and slow release at high pH. In addition, Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) binding free energy calculations were also performed at each umbrella sampling window to identify the various energy contributions. To understand the effect of dendrimer chemistry and topology on the solubility and release profile of drugs, this study is extended to explore the solubility and release profile of phenylbutazone drug complexed with G3 poly(amidoamine) and G4 diaminobutane cored PPI dendrimers. The results indicate that the pH-induced conformational changes in dendrimer, ionization states, dendrimer type and pK(a) of the guest molecules influence the free energy barrier and stability of complexation, and thus regulate drug loading, solubility and release.

Data assimilation using ensemble transform Kalman filter (ETKF) in ROMS model for Indian Ocean

Study of Oceans dynamics and forecast is crucial as it influences the regional climate and other marine activities. Forecasting oceanographic states like sea surface currents, Sea surface temperature (SST) and mixed layer depth at different time scales is extremely important for these activities. These forecasts are generated by various ocean general circulation models (OGCM). One such model is the Regional Ocean Modelling System (ROMS). Though ROMS can simulate several features of ocean, it cannot reproduce the thermocline of the ocean properly. Solution to this problem is to incorporates data assimilation (DA) in the model. DA system using Ensemble Transform Kalman Filter (ETKF) has been developed for ROMS model to improve the accuracy of the model forecast. To assimilate data temperature and salinity from ARGO data has been used as observation. Assimilated temperature and salinity without localization shows oscillations compared to the model run without assimilation for India Ocean. Same was also found for u and v-velocity fields. With localization we found that the state variables are diverging within the localization scale.

Relation Between the Diffusivity, Viscosity, and Ionic Radius of LiCl in Water, Methanol, and Ethylene Glycol: A Molecular Dynamics Simulation

A molecular dynamics (MD) investigation of LiCl in water, methanol, and ethylene glycol (EG) at 298 K is reported. Several; structural and dynamical properties of the ions as well as the solvent such as self-diffusivity, radial distribution functions, void and neck distributions, velocity autocorrelation functions, and mean residence times of solvent in the first solvation shell have been computed. The results show that the reciprocal relationship between the self-diffusivity of the ions and the viscosity is valid in almost all solvents with the exception of water. From an analysis of radial distribution functions and coordination numbers the nature of hydrogen bonding within the solvent and its influence on the void and neck distribution becomes evident. It is seen that the solvent solvent interaction is important in EG while solute solvent interactions dominate in water and methanol. From Voronoi tessellation, it is seen that the voids and necks within methanol are larger as compared to those within water or EG. On the basis of the void and neck distributions obtained from MD simulations and literature experimental data of limiting ion conductivity for various ions of different sizes we show that there is a relation between the void and neck radius on e one hand and dependence of conductivity on the ionic radius on the other. It is shown that the presence of large diameter voids and necks in methanol is responsible for maximum in limiting ion conductivity (lambda(0)) of TMA(+), while in water in EG, the maximum is seen for Rb+. In the case of monovalent anions, maximum in lambda(0) as a function ionic radius is seen for Br- in water EG but for the larger ClO4- ion in methanol. The relation between the void and neck distribution and the variation in lambda(0) with ionic radius arises via the Levitation effect which is discussed. These studies show the importance of the solvent structure and the associated void structure.

Inference for the Component and System Lifetime Distribution of a k-unit Parallel System Based on System Data

In this paper, we consider the inference for the component and system lifetime distribution of a k-unit parallel system with independent components based on system data. The components are assumed to have identical Weibull distribution. We obtain the maximum likelihood estimates of the unknown parameters based on system data. The Fisher information matrix has been derived. We propose -expectation tolerance interval and -content -level tolerance interval for the life distribution of the system. Performance of the estimators and tolerance intervals is investigated via simulation study. A simulated dataset is analyzed for illustration.

Study on the detection efficiency of gaseous photomultipliers

Efficient photon detection in gaseous photomultipliers require maximum photoelectron yield from the photocathode surface and also detection of them. In this work we have investigated the parameters that affect the photoelectron yield from the photocathode surface and methods to improve them thus ensuring high detection efficiency of the gaseous photomultiplier. The parameters studied are the electric field at the photocathode surface, surface properties of photocathode and pressure of gas mixture inside the gaseous photomultiplier. It was observed that optimized electric field at the photocathode ensures high detection efficiency. Lower pressure of filled gas increases the photoelectron yield from the photocathode surface but reduces the focusing probability of electrons inside the electron multiplier. Also evacuation for longer duration before gas filling increases the photoelectron yield.

Deformation-induced grain growth and twinning in nanocrystalline palladium thin films

The microstructure and mechanical properties of nanocrystalline Pd films prepared by magnetron sputtering have been investigated as a function of strain. The films were deposited onto polyimide substrates and tested in tensile mode. In order to follow the deformation processes in the material, several samples were strained to defined straining states, up to a maximum engineering strain of 10%, and prepared for post-mortem analysis. The nanocrystalline structure was investigated by quantitative automated crystal orientation mapping (ACOM) in a transmission electron microscope (TEM), identifying grain growth and twinning/detwinning resulting from dislocation activity as two of the mechanisms contributing to the macroscopic deformation. Depending on the initial twin density, the samples behaved differently. For low initial twin densities, an increasing twin density was found during straining. On the other hand, starting from a higher twin density, the twins were depleted with increasing strain. The findings from ACOM-TEM were confirmed by results from molecular dynamics (MD) simulations and from conventional and in-situ synchrotron X-ray diffraction (CXRD, SXRD) experiments.