Influence of glycosidic linkage on the nature of carbohydrate binding in beta-prism I fold lectins: An X-ray and molecular dynamics investigation on banana lectin-carbohydrate complexes

The three crystal structures reported here provide details of the interactions of mannose and the mannosyl-alpha-1,3-mannose component of a pentamannose with banana lectin and evidence for the binding of glucosyl-alpha-1,2-glucose to the lectin. The known structures involving the lectin include a complex with glucosyl-beta-1,3-glucose. Modeling studies on the three disaccharide complexes with the reducing end and the nonreducing end at the primary binding site are also provided here. The results of the Xray and modeling studies show that the disaccharides with an alpha-1,3 linkage prefer to have the nonreducing end at the primary binding site, whereas the reducing end is preferred at the site when the linkage is beta-1,3 in mannose/glucose-specific beta-prism I fold lectins. In the corresponding galactose-specific lectins, however, alpha-1,3-linked disaccharides cannot bind the lectin with the nonreducing end at the primary binding site on account of steric clashes with an aromatic residue that occurs only when the lectin is galactose-specific. Molecular dynamics simulations based on the known structures involving banana lectin enrich the information on lectin-carbohydrate interactions obtained from crystal structures. They demonstrate that conformational selection as well as induced fit operate when carbohydrates bind to banana lectin.

Crystal structures, dynamics and functional implications of molybdenum-cofactor biosynthesis protein MogA from two thermophilic organisms

Molybdenum-cofactor (Moco) biosynthesis is an evolutionarily conserved pathway in almost all kingdoms of life, including humans. Two proteins, MogA and MoeA, catalyze the last step of this pathway in bacteria, whereas a single two-domain protein carries out catalysis in eukaryotes. Here, three crystal structures of the Moco-biosynthesis protein MogA from the two thermophilic organisms Thermus thermophilus (TtMogA; 1.64 angstrom resolution, space group P2(1)) and Aquifex aeolicus (AaMogA; 1.70 angstrom resolution, space group P2(1) and 1.90 angstrom resolution, space group P1) have been determined. The functional roles and the residues involved in oligomerization of the protein molecules have been identified based on a comparative analysis of these structures with those of homologous proteins. Furthermore, functional roles have been proposed for the N- and C-terminal residues. In addition, a possible protein-protein complex of MogA and MoeA has been proposed and the residues involved in protein-protein interactions are discussed. Several invariant water molecules and those present at the subunit interfaces have been identified and their possible structural and/or functional roles are described in brief. In addition, molecular-dynamics and docking studies with several small molecules (including the substrate and the product) have been carried out in order to estimate their binding affinities towards AaMogA and TtMogA. The results obtained are further compared with those obtained for homologous eukaryotic proteins.

Molecular-dynamics studies of systems of confined dumbbell molecules

We present the results of molecular-dynamics simulations of systems of dumbbell molecules confined by parallel molecular walls. We have carried out systematic studies of three cases: freezing, steady flows, and stick-slip friction. We find that the molecular orientational degrees of freedom cause the surface layers to deviate from a planar configuration. Nevertheless, steady flows, in a channel as narrow as 15 molecular sizes, display continuum behavior. A range of mechanisms in the dynamics of the freezing of a confined fluid is found, as a function of the wall-fluid interactions and the bond length of the dumbbell molecules. The simple order-disorder transition associated with stick-slip motion in the presence of a layer of monoatomic lubricant molecules is supplanted by more complex behavior due to rotational degrees of freedom of the diatomic molecules.

Modeling of angiogenin-3 '-NMP complex

Angiogenin belongs to the Ribonuclease superfamily and has a weak enzymatic activity that is crucial for its biological function of stimulating blood vessel growth. Structural studies on ligand bound Angiogenin will go a long way in understanding the mechanism of the protein as well as help in designing drugs against it. In this study we present the first available structure of nucleotide ligand bound Angiogenin obtained by computer modeling. The importance of this study in itself notwithstanding, is a precursor to modeling a full dinucleotide substrate onto Angiogenin. Bovine Angiogenin, the structure of which has been solved at a high resolution, was earlier subjected to Molecular Dynamics simulations for a nanosecond. The MD structures offer better starting points for docking as they offer lesser obstruction than the crystal structure to ligand binding. The MD structure with the least serious short contacts was modeled to obtain a steric free Angiogenin - 3' mononucleotide complex structure. The structures were energetically minimized and subjected to a brief spell of Molecular Dynamics. The results of the simulation show that all the li,ligand-Angiogenin interactions and hydrogen bonds are retained, redeeming the structure and docking procedure. Further, following ligand - protein interactions in the case of the ligands 3'-CMP and 3'-UMP we were able to speculate on how Angiogenin, a predominantly prymidine specific ribonuclease prefers Cytosine to Uracil in the first base position.

A homobimetallic complex of chromium(0) with a sigma-borane component

The synthesis, characterization, and reactivity of a chromium(0) complex bearing an amine-borane moiety (eta(6)-C(6)H(5)CH(2)NMe(2)center dot BH(3))Cr(CO)(3) (2) is reported. Photolysis of complex 2 results in the elimination of a CO ligand followed by the formation of an intramolecular sigma-borane complex (eta(1)-(eta(6)- C(6)H(5)CH(2)NMe(2)center dot BH(2)-H))Cr(CO)(2) (3). This species was characterized in solution by NMR spectroscopy. Reaction of complex 2 with photochemically generated (OC)(5)Cr(THF) affords a novel homobimetallic sigma-borane complex (OC)(3)Cr(eta(6)-C(6)H(5)CH(2)NMe(2)center dot BH(2)-H-Cr(CO)(5)) (4), wherein one of the BH moieties is bound to the chromium center in an eta(1)-fashion. The sigma-borane complex 4 was isolated in moderate to good yield (72%). The BH(3) fragment in the complexes 3 and 4 are highly dynamic involving exchange of the BH hydrogen bound to the metal with the terminal BH hydrogen atoms. The dynamics has been studied using variable-temperature NMR spectroscopy. Complexes 2 and 4 have been characterized by X-ray crystallography.

Spectral Finite Element Modeling of Complex Structures for Applications in Real-time Structural Health Monitoring

In this paper we discuss the recent progresses in spectral finite element modeling of complex structures and its application in real-time structural health monitoring system based on sensor-actuator network and near real-time computation of Damage Force Indicator (DFI) vector. A waveguide network formalism is developed by mapping the original variational problem into the variational problem involving product spaces of 1D waveguides. Numerical convergence is studied using a h()-refinement scheme, where is the wavelength of interest. Computational issues towards successful implementation of this method with SHM system are discussed.

Development of novel multiple quantummethodologies for the analyses of complex protonNMR spectra of scalar coupled spins

One of the significant advancements in Nuclear Magnetic Resonance spectroscopy (NMR) in combating the problem of spectral complexity for deriving the structure and conformational information is the incorporation of additional dimension and to spread the information content in a two dimensional space. This approach together with the manipulation of the dynamics of nuclear spins permitted the designing of appropriate pulse sequences leading to the evolution of diverse multidimensional NMR experiments. The desired spectral information can now be extracted in a simplified and an orchestrated manner. The indirect detection of multiple quantum (MQ) NMR frequencies is a step in this direction. The MQ technique has been extensively used in the study of molecules aligned in liquid crystalline media to reduce spectral complexity and to determine molecular geometries. Unlike in dipolar coupled systems, the size of the network of scalar coupled spins is not big in isotropic solutions and the MQ 1H detection is not routinely employed,although there are specific examples of spin topology filtering. In this brief review, we discuss our recent studies on the development and application of multiple quantum correlation and resolved techniques for the analyses of proton NMR spectra of scalar coupled spins.

The Structure of the Thioredoxin-Triosephosphate Isomerase Complex Provides Insights into the Reversible Glutathione-Mediated Regulation of Triosephosphate Isomerase

Protein-protein interactions are crucial for many biological functions. The redox interactome encompasses numerous weak transient interactions in which thioredoxin plays a central role. Proteomic studies have shown that thioredoxin binds to numerous proteins belonging to various cellular processes, including energy metabolism. Thioredoxin has cross talk with other redox mechanisms involving glutathionylation and has functional overlap with glutaredoxin in deglutathionylation reactions. In this study, we have explored the structural and biochemical interactions of thioredoxin with the glycolytic enzyme, triosephosphate isomerase. Nuclear magnetic resonance chemical shift mapping methods and molecular dynamics-based docking have been applied in deriving a structural model of the thioredoxin-triosephosphate isomerase complex. The spatial proximity of active site cysteine residues of thioredoxin to reactive thiol groups on triosephosphate isomerase provides a direct link to the observed deglutathionylation of cysteine 217 in triosephosphate isomerase, thereby reversing the inhibitory effect of S-glutathionylation of triosephosphate isomerase.

The Structure of the Thioredoxin−Triosephosphate Isomerase Complex Provides Insights into the Reversible Glutathione-Mediate Regulation of Triosephosphate Isomerase

Protein−protein interactions are crucial for many biological functions. The redox interactome encompasses numerous weak transient interactions in which thioredoxin plays a central role. Proteomic studies have shown that thioredoxin binds to numerous proteins belonging to various cellular processes, including energy metabolism. Thioredoxin has cross talk with other redox mechanisms involving glutathionylation and has functional overlap with glutaredoxin in deglutathionylation reactions. In this study, we have explored the structural and biochemical interactions of thioredoxin with the glycolytic enzyme, triosephosphate isomerase. Nuclear magnetic resonance chemical shift mapping methods and molecular dynamics-based docking have been applied in deriving a structural model of the thioredoxin−triosephosphate isomerase complex. The spatial proximity of active site cysteine residues of thioredoxin to reactive thiol groups on triosephosphate isomerase provides a direct link to the observed deglutathionylation of cysteine 217 in triosephosphate isomerase, thereby reversing the inhibitory effect of S-glutathionylation of triosephosphate isomerase.

Insights to urban dynamics through landscape spatial pattern analysis

Urbanisation is a dynamic complex phenomenon involving large scale changes in the land uses at local levels. Analyses of changes in land uses in urban environments provide a historical perspective of land use and give an opportunity to assess the spatial patterns, correlation, trends, rate and impacts of the change, which would help in better regional planning and good governance of the region. Main objective of this research is to quantify the urban dynamics using temporal remote sensing data with the help of well-established landscape metrics. Bangalore being one of the rapidly urbanising landscapes in India has been chosen for this investigation. Complex process of urban sprawl was modelled using spatio temporal analysis. Land use analyses show 584% growth in built-up area during the last four decades with the decline of vegetation by 66% and water bodies by 74%. Analyses of the temporal data reveals an increase in urban built up area of 342.83% (during 1973-1992), 129.56% (during 1992-1999), 106.7% (1999-2002), 114.51% (2002-2006) and 126.19% from 2006 to 2010. The Study area was divided into four zones and each zone is further divided into 17 concentric circles of 1 km incrementing radius to understand the patterns and extent of the urbanisation at local levels. The urban density gradient illustrates radial pattern of urbanisation for the period 1973-2010. Bangalore grew radially from 1973 to 2010 indicating that the urbanisation is intensifying from the central core and has reached the periphery of the Greater Bangalore. Shannon's entropy, alpha and beta population densities were computed to understand the level of urbanisation at local levels. Shannon's entropy values of recent time confirms dispersed haphazard urban growth in the city, particularly in the outskirts of the city. This also illustrates the extent of influence of drivers of urbanisation in various directions. Landscape metrics provided in depth knowledge about the sprawl. Principal component analysis helped in prioritizing the metrics for detailed analyses. The results clearly indicates that whole landscape is aggregating to a large patch in 2010 as compared to earlier years which was dominated by several small patches. The large scale conversion of small patches to large single patch can be seen from 2006 to 2010. In the year 2010 patches are maximally aggregated indicating that the city is becoming more compact and more urbanised in recent years. Bangalore was the most sought after destination for its climatic condition and the availability of various facilities (land availability, economy, political factors) compared to other cities. The growth into a single urban patch can be attributed to rapid urbanisation coupled with the industrialisation. Monitoring of growth through landscape metrics helps to maintain and manage the natural resources. (C) 2012 Elsevier B.V. All rights reserved.

Probing ultrafast carrier dynamics, nonlinear absorption and refraction in core-shell silicon nanowires

We investigate the relaxation dynamics of photogenerated carriers in silicon nanowires consisting of a crystalline core and a surrounding amorphous shell, using femtosecond time-resolved differential reflectivity and transmission spectroscopy at 3.15 eV and 1.57 eV photon energies. The complex behaviour of the differential transmission and reflectivity transients is the mixed contributions from the crystalline core and the amorphous silicon on the nanowire surface and the substrate where competing effects of state-filling and photoinduced absorption govern the carrier dynamics. Faster relaxation rates are observed on increasing the photogenerated carrier density. Independent experimental results on crystalline silicon-on-sapphire (SOS) help us in separating the contributions from the carrier dynamics in crystalline core and the amorphous regions in the nanowire samples. Further, single-beam z-scan nonlinear transmission experiments at 1.57 eV in both open- and close-aperture configurations yield two-photon absorption coefficient beta (similar to 3 cm/GW) and nonlinear refraction coefficient gamma (-2.5 x 10 (-aEuro parts per thousand 4) cm(2)/GW).

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]

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.

Solvation dynamics of tryptophan in water-dimethyl sulfoxide binary mixture: In search of molecular origin of composition dependent multiple anomalies

Experimental and simulation studies have uncovered at least two anomalous concentration regimes in water-dimethyl sulfoxide (DMSO) binary mixture whose precise origin has remained a subject of debate. In order to facilitate time domain experimental investigation of the dynamics of such binary mixtures, we explore strength or extent of influence of these anomalies in dipolar solvation dynamics by carrying out long molecular dynamics simulations over a wide range of DMSO concentration. The solvation time correlation function so calculated indeed displays strong composition dependent anomalies, reflected in pronounced non-exponential kinetics and non-monotonous composition dependence of the average solvation time constant. In particular, we find remarkable slow-down in the solvation dynamics around 10%-20% and 35%-50% mole percentage. We investigate microscopic origin of these two anomalies. The population distribution analyses of different structural morphology elucidate that these two slowing down are reflections of intriguing structural transformations in water-DMSO mixture. The structural transformations themselves can be explained in terms of a change in the relative coordination number of DMSO and water molecules, from 1DMSO:2H(2)O to 1H(2)O:1DMSO and 1H(2)O:2DMSO complex formation. Thus, while the emergence of first slow down (at 15% DMSO mole percentage) is due to the percolation among DMSO molecules supported by the water molecules (whose percolating network remains largely unaffected), the 2nd anomaly (centered on 40%-50%) is due to the formation of the network structure where the unit of 1DMSO:1H(2)O and 2DMSO:1H(2)O dominates to give rise to rich dynamical features. Through an analysis of partial solvation dynamics an interesting negative cross-correlation between water and DMSO is observed that makes an important contribution to relaxation at intermediate to longer times.

Simulations reveal that the HIV-1 gp120-CD4 complex dissociates via complex pathways and is a potential target of the polyamidoamine (PAMAM) dendrimer

The polyamidoamine (PAMAM) dendrimer prevents HIV-1 entry into target cells in vitro. Its mechanism of action, however, remains unclear and precludes the design of potent dendrimers targeting HIV-1 entry. We employed steered molecular dynamics simulations to examine whether the HIV-1 gp120-CD4 complex is a target of PAMAM. Our simulations mimicked single molecule force spectroscopy studies of the unbinding of the gp120-CD4 complex under the influence of a controlled external force. We found that the complex dissociates via complex pathways and defies the standard classification of adhesion molecules as catch and slip bonds. When the force loading rate was large, the complex behaved as a slip bond, weakening gradually. When the loading rate was small, the complex initially strengthened, akin to a catch bond, but eventually dissociated over shorter separations than with large loading rates. PAMAM docked to gp120 and destabilized the gp120-CD4 complex. The rupture force of the complex was lowered by PAMAM. PAMAM disrupted salt bridges and hydrogen bonds across the gp120-CD4 interface and altered the hydration pattern of the hydrophobic cavity in the interface. In addition, intriguingly, PAMAM suppressed the distinction in the dissociation pathways of the complex between the small and large loading rate regimes. Taken together, our simulations reveal that PAMAM targets the gp120-CD4 complex at two levels: it weakens the complex and also alters its dissociation pathway, potentially inhibiting HIV-1 entry.