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.

Molecular probe dynamics reveals suppression of ice-like regions in strongly confined supercooled water

The structure of the hydrogen bond network is a key element for understanding water's thermodynamic and kinetic anomalies. While ambient water is strongly believed to be a uniform, continuous hydrogen-bonded liquid, there is growing consensus that supercooled water is better described in terms of distinct domains with either a low-density ice-like structure or a high-density disordered one. We evidenced two distinct rotational mobilities of probe molecules in interstitial supercooled water of polycrystalline ice Banerjee D, et al. (2009) ESR evidence for 2 coexisting liquid phases in deeply supercooled bulk water. Proc Natl Acad Sci USA 106: 11448-11453]. Here we show that, by increasing the confinement of interstitial water, the mobility of probe molecules, surprisingly, increases. We argue that loose confinement allows the presence of ice-like regions in supercooled water, whereas a tighter confinement yields the suppression of this ordered fraction and leads to higher fluidity. Compelling evidence of the presence of ice-like regions is provided by the probe orientational entropy barrier which is set, through hydrogen bonding, by the configuration of the surrounding water molecules and yields a direct measure of the configurational entropy of the same. We find that, under loose confinement of supercooled water, the entropy barrier surmounted by the slower probe fraction exceeds that of equilibrium water by the melting entropy of ice, whereas no increase of the barrier is observed under stronger confinement. The lower limit of metastability of supercooled water is discussed.

Projecting low-dimensional chaos from spatiotemporal dynamics in a model for plastic instability

We investigate the possibility of projecting low-dimensional chaos from spatiotemporal dynamics of a model for a kind of plastic instability observed under constant strain rate deformation conditions. We first discuss the relationship between the spatiotemporal patterns of the model reflected in the nature of dislocation bands and the nature of stress serrations. We show that at low applied strain rates, there is a one-to-one correspondence with the randomly nucleated isolated bursts of mobile dislocation density and the stress drops. We then show that the model equations are spatiotemporally chaotic by demonstrating the number of positive Lyapunov exponents and Lyapunov dimension scale with the system size at low and high strain rates. Using a modified algorithm for calculating correlation dimension density, we show that the stress-strain signals at low applied strain rates corresponding to spatially uncorrelated dislocation bands exhibit features of low-dimensional chaos. This is made quantitative by demonstrating that the model equations can be approximately reduced to space-independent model equations for the average dislocation densities, which is known to be low-dimensionally chaotic. However, the scaling regime for the correlation dimension shrinks with increasing applied strain rate due to increasing propensity for propagation of the dislocation bands.

Subdiffusion in hair bundle dynamics: The role of protein conformational fluctuations

The detection of sound signals in vertebrates involves a complex network of different mechano-sensory elements in the inner ear. An especially important element in this network is the hair bundle, an antenna-like array of stereocilia containing gated ion channels that operate under the control of one or more adaptation motors. Deflections of the hair bundle by sound vibrations or thermal fluctuations transiently open the ion channels, allowing the flow of ions through them, and producing an electrical signal in the process, eventually causing the sensation of hearing. Recent high frequency (0.1-10 kHz) measurements by Kozlov et al. Proc. Natl. Acad. Sci. U. S. A. 109, 2896 (2012)] of the power spectrum and the mean square displacement of the thermal fluctuations of the hair bundle suggest that in this regime the dynamics of the hair bundle are subdiffusive. This finding has been explained in terms of the simple Brownian motion of a filament connecting neighboring stereocilia (the tip link), which is modeled as a viscoelastic spring. In the present paper, the diffusive anomalies of the hair bundle are ascribed to tip link fluctuations that evolve by fractional Brownian motion, which originates in fractional Gaussian noise and is characterized by a power law memory. The predictions of this model for the power spectrum of the hair bundle and its mean square displacement are consistent with the experimental data and the known properties of the tip link. (C) 2012 American Institute of Physics. http://dx.doi.org/10.1063/1.4768902]

Acoustic and optical phonon dynamics from femtosecond time-resolved optical spectroscopy of the superconducting iron pnictide Ca(Fe0.944Co0.056)(2)As-2

We report the temperature evolution of coherently excited acoustic and optical phonon dynamics in the superconducting iron pnictide single crystal Ca(Fe0.944Co0.056)(2)As-2 across the spin density wave transition at T-SDW similar to 85 K and the superconducting transition at T-SC similar to 20 K. The strain pulse propagation model applied to the generation of the acoustic phonons yields the temperature dependence of the optical constants, and longitudinal and transverse sound velocities in the temperature range from 3.1 K to 300 K. The frequency and dephasing times of the phonons show anomalous temperature dependence below T-SC indicating a coupling of these low-energy excitations with the Cooper-pair quasiparticles. A maximum in the amplitude of the acoustic modes at T similar to 170 is seen, attributed to spin fluctuations and strong spin-lattice coupling before T-SDW. Copyright (c) EPLA, 2012

Simulation of Influence of Bilayer Melting on Dynamics and Thermodynamics of Interfacial Water

We investigate the effect of bilayer melting transition on thermodynamics and dynamics of interfacial water using molecular dynamics simulation with the two-phase thermodynamic model. We show that the diffusivity of interface water depicts a dynamic crossover at the chain melting transition following an Arrhenius behavior until the transition temperature. The corresponding change in the diffusion coefficient from the bulk to the interface water is comparable with experimental observations found recently for water near 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) vesicles Phys. Chem. Chem. Phys. 13, 7732 (2011)]. The entropy and potential energy of interfacial water show distinct changes at the bilayer melting transition, indicating a strong correlation in the thermodynamic state of water and the accompanying first-order phase transition of the bilayer membrane. DOI: 10.1103/PhysRevLett.110.018303

Vaporization dynamics of functional droplets in a hot laminar air jet

The vaporization characteristics of pendant droplets of various chemical compositions (like conventional fuels, alternative fuels and nanosuspensions) subjected to convective heating in a laminar air jet have been analyzed. Different heating conditions were achieved by controlling the air temperature and velocity fields around the droplet. A hybrid timescale has been proposed which incorporates the effects of latent heat of vaporization, saturation vapor pressure and thermal diffusivity. This timescale in essence encapsulates the different parameters that influence the droplet vaporization rate. The analysis further permits the evaluation of the effect of various parameters such as surrounding temperature, Reynolds number, far-field vapor presence, impurity content and agglomeration dynamics (nanosuspensions) in the droplet. Flow visualization has been carried out to understand the role of internal recirculation on the vaporization rate. The visualization indicates the presence of a single vortex cell within the droplet on account of the rotation and oscillation of the droplet due to aerodynamic load. External heating induced agglomeration in nanofluids leads to morphological changes during the vaporization process. These morphological changes and alteration in vaporization behavior have been assessed using high speed imaging of the diameter regression and Scanning Electron Microscopy images of the resultant precipitate. (C) 2012 Elsevier Ltd. All rights reserved.

Advanced multifunctional inorganic nanostructured oxides for controlled release and sensing

ADVANCED MULTIFUNCTIONAL INORGANIC NANOSTRUCTURED OXIDES FOR CONTROLLED RELEASE AND SENSING. We demonstrate here certain examples of multifunctional nanostructured oxidematerials for biotechnological and environmental applications.Various in-house synthesized homogeneous nanostructured viz.mesoporous and nanotubes silica and titania have been employed for controlled drug delivery and electrochemical biosensing applications. Confinement of macromolecules such as proteins studied via electrochemical, thermal and spectroscopic methods showed no detrimental effect on native protein structure and function, thus suggesting effective utility of oxide nanostructures as bio-encapsulators. Multi-functionalitywas demonstrated via employing similar nanostructures for sensing organic water pollutants e.g. textile dyes.

Force Biased Molecular Dynamics Simulation Study of Effect of Dendrimer Generation on Interaction with DNA

We have studied the effect of dendrimer generation on the interaction between dsDNA and the PAMAM dendrimer using force biased simulation of dsDNA with three generations of dendrimer: G3, G4, and G5. Our results for the potential of mean force (PMF) and the dendrimer asphericity along the binding pathway, combined with visualization of the simulations, demonstrate that dendrimer generation has a pronounced impact on the interaction. The PMF increases linearly with increasing generation of the dendrimer. While, in agreement with previous results, we see an increase in the extent to which the dendrimer bends the dsDNA with increasing dendrimer generation, we also see that the deformation of the dendrimer is greater with smaller generation of the dendrimer. The larger dendrimer forces the dsDNA to conform to its structure, while the smaller dendrimer is forced to conform to the structure of the dsDNA. Monitoring the number of bound cations at different values of force bias distance shows the expected effect of ions being expelled when the dendrimer binds dsDNA.

A computational study of flame dynamics on soot production and transport for an acetylene-air laminar diffusion flame in the field of a convecting line vortex

The present work involves a computational study of soot formation and transport in case of a laminar acetylene diffusion flame perturbed by a convecting line vortex. The topology of the soot contours (as in an earlier experimental work [4]) have been investigated. More soot was produced when vortex was introduced from the air side in comparison to a fuel side vortex. Also the soot topography was more diffused in case of the air side vortex. The computational model was found to be in good agreement with the experimental work [4]. The computational simulation enabled a study of the various parameters affecting soot transport. Temperatures were found to be higher in case of air side vortex as compared to a fuel side vortex. In case of the fuel side vortex, abundance of fuel in the vort ex core resulted in stoichiometrically rich combustion in the vortex core, and more discrete soot topography. Overall soot production too was low. In case of the air side vortex abundance of air in the core resulted in higher temperatures and more soot yield. Statistical techniques like probability density function, correlation coefficient and conditional probability function were introduced to explain the transient dependence of soot yield and transport on various parameters like temperature, a cetylene concentration.

Interface capturing simulations of acoustically driven bubble dynamics in and near tissue

Tissue injury during therapeutic ultrasound or lithotripsy is thought, in cases, to be due to the action of cavitation bubbles. Assessing this and mitigating it is challenging since bubble dynamics in the complex confinement of tissues or in small blood vessels are challenging to predict. Simulations tools require specialized algorithms to simultaneously represent strong acoustic waves and shocks, topologically complex liquid‐vapor phase boundaries, and the complex viscoelastic material dynamics of tissue. We discuss advances in a simulation tool for such situations. A single‐mesh Eulerian solver is used to solve the governing equations. Special sharpening terms maintain the liquid‐vapor interface in face of the finite numerical dissipation included in the scheme to accurately capture shocks. A recent enhancement to this formulation has significantly improved this interface capturing procedure, which is demonstrated for simulation of the Rayleigh collapse of a bubble. The solver also transports elastic stresses and can thus be used to assess the effects of elastic properties on bubble dynamics. A shock‐induced bubble collapse adjacent to a model elastic tissue is used to demonstrate this and draw some conclusions regarding the injury suppressing role that tissue elasticity might play.

Water treatment potential in relation to phytoplankton dynamics in tropical sewage-fed urban water bodies

Urban water bodies frequently receive untreated sewage and water levels in such water bodies are maintained by daily inputs of sewage. They function as “variable-zone” anaerobic-aerobic lagoons suffering several macrophyte, biotic and abiotic stresses. We have studied two such lakes in Bangalore (Bellandur-360 ha and Varthur-220 ha) to understand whether such an occurrence could be made beneficial (maintaining water levels as well as treatment). Such hypertrophic water body receives sewage at 180-250mg/L and is discharged at 25-80mg/L COD/BOD in different seasons. In an earlier study we reported macrophyte altering the purification function of the water body. In this paper we studied the impact of phytoplankton dynamics and macrophyte cover on the functions such as organic load removal. Algal community analysis, algal biomass, macrophyte cover, water quality, nutrient status was studied seasonally during 2009-2010. Oxygen deficiency and sometimes anoxia, recorded from surface samples resulted in high quantities of NH4+-N (30-40mg/L) and phosphate (0.5-4mg/L)-characteristics of anoxic hypertrophic urban lakes. The productiveness favoured high phytoplanktonic community characterized by small cells (<10μm; Chlorella sp. - highest numbers). The lake could be clearly demarcated into an initial anaerobic zone (40% area), a facultative zone (20%) and an aerobic zone (40%) based on redox values and GIS/bathymetry. During summer the lake is covered by floating macrophytes converting the lake into an anoxic/anaerobic water pool subduing the water purification function as well as aesthetics. When macrophytes are controlled such sewage fed water bodies can be used for treating urban wastewater while also maintaining water sustainability in these semi-arid ecosystems. This paper reports the community dynamics of phytoplankton, their function and competition with macrophytes.

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.

Microscopic dynamics of nanoparticle monolayers at air-water interface

We present results of surface mechanical and particle tracking measurements of nanoparticles trapped at the air-water interface as a function of their areal density. We monitor both the surface pressure (II) and isothermal compression modulus (epsilon) as well as the dynamics of nanoparticle clusters, using fluorescence confocal microscopy while they are compressed to very high density near the two dimensional close packing density Phi similar to 0.82. We observe non-monotonic variation in both epsilon and the dynamic heterogeneity, characterized by the dynamical susceptibility chi(4) with Phi, in such high density monolayers. We provide insight into the underlying nature of such transitions in close packed high density nanoparticle monolayers in terms of the morphology and flexibility of these soft colloidal particles.. We discuss the significance our results in the context of related studies on two dimensional granular or colloidal systems. (C) 2013 Elsevier Inc. All rights reserved.

Gap-Dependent Quasiparticle Dynamics and Coherent Acoustic Phonons in CaFe2As2 across Spin Density Wave Phase Transition

We report ultrafast quasiparticle (QP) dynamics and coherent acoustic phonons in undoped CaFe2As2 iron pnictide single crystals exhibiting spin-density wave (SDW) and concurrent structural phase transition at temperature T-SDW similar to 165K using femtosecond time-resolved pump-probe spectroscopy. The contributions in transient differential reflectivity arising from exponentially decaying QP relaxation and oscillatory coherent acoustic phonon mode show large variations in the vicinity of T-SDW. From the temperature-dependence of the QP recombination dynamics in the SDW phase, we evaluate a BCS-like temperature dependent charge gap with its zero-temperature value of similar to(1.6 perpendicular to 0.2)k(B)T(SDW), whereas, much above T-SDW, an electron-phonon coupling constant of similar to 0.13 has been estimated from the linear temperature-dependence of the QP relaxation time. The long-wavelength coherent acoustic phonons with typical time-period of similar to 100 ps have been analyzed in the light of propagating strain pulse model providing important results for the optical constants, sounds velocity and the elastic modulus of the crystal in the whole temperature range of 3 to 300 K.