Roles of residues in the interface of transient protein-protein complexes before complexation

Transient protein-protein interactions play crucial roles in all facets of cellular physiology. Here, using an analysis on known 3-D structures of transient protein-protein complexes, their corresponding uncomplexed forms and energy calculations we seek to understand the roles of protein-protein interfacial residues in the unbound forms. We show that there are conformationally near invariant and evolutionarily conserved interfacial residues which are rigid and they account for similar to 65% of the core interface. Interestingly, some of these residues contribute significantly to the stabilization of the interface structure in the uncomplexed form. Such residues have strong energetic basis to perform dual roles of stabilizing the structure of the uncomplexed form as well as the complex once formed while they maintain their rigid nature throughout. This feature is evolutionarily well conserved at both the structural and sequence levels. We believe this analysis has general bearing in the prediction of interfaces and understanding molecular recognition.

Relaxation and jump dynamics of water at the mica interface

The orientational relaxation dynamics of water confined between mica surfaces is investigated using molecular dynamics simulations. The study illustrates the wide heterogeneity that exists in the dynamics of water adjacent to a strongly hydrophilic surface such as mica. Analysis of the survival probabilities in different layers is carried out by normalizing the corresponding relaxation times with bulk water layers of similar thickness. A 10-fold increase in the survival times is observed for water directly in contact with the mica surface and a non-monotonic variation in the survival times is observed moving away from the mica surface to the bulk-like interior. The orientational relaxation time is highest for water in the contact layer, decreasing monotonically away from the surface. In all cases the ratio of the relaxation times of the 1st and 2nd rank Legendre polynomials of the HH bond vector is found to lie between 1.5 and 1.9 indicating that the reorientational relaxation in the different water layers is governed by jump dynamics. The orientational dynamics of water in the contact layer is particularly novel and is found to undergo distinct two-dimensional hydrogen bond jump reorientational dynamics with an average waiting time of 4.97 ps. The waiting time distribution is found to possess a long tail extending beyond 15 ps. Unlike previously observed jump dynamics in bulk water and other surfaces, jump events in the mica contact layer occur between hydrogen bonds formed by the water molecule and acceptor oxygens on the mica surface. Despite slowing down of the water orientational relaxation near the surface, life-times of water in the hydration shell of the K ion are comparable to that observed in bulk salt solutions. (C) 2012 American Institute of Physics. http://dx.doi.org/10.1063/1.4717710]

In Situ Electrochemical Polymerization at Air-Water Interface: Surface-Pressure-Induced, Graphene-Oxide-Assisted Preferential Orientation of Polyaniline

In situ electrochemical polymerization of aniline in a Langmuir trough under applied surface pressure assists in the preferential orientation of polyaniline (PANI) in planar polaronic structure. Exfoliated graphene oxide (EGO) spread on water surface is used to bring anilinium cations present in the subphase to air-water interface through electrostatic interactions. Subsequent electrochemical polymerization of aniline under applied surface pressure in the Schaefer mode results in EGO/PANT composite with PANT in planar polaronic form. The orientation of PANI is confirmed by electrochemical and Raman spectroscopic studies. This technique opens up possibilities of 2-D polymerization at the air-water interface. Electrochemical sensing of hydrogen peroxide is used to differentiate the activity of planar and coiled forms of PANI toward electrocatalytic reactions.

Structural and mechanistic investigations on Salmonella typhimurium acetate kinase (AckA): identification of a putative ligand binding pocket at the dimeric interface

Background: Bacteria such as Escherichia coli and Salmonella typhimurium can utilize acetate as the sole source of carbon and energy. Acetate kinase (AckA) and phosphotransacetylase (Pta), key enzymes of acetate utilization pathway, regulate flux of metabolites in glycolysis, gluconeogenesis, TCA cycle, glyoxylate bypass and fatty acid metabolism. Results: Here we report kinetic characterization of S. typhimurium AckA (StAckA) and structures of its unliganded (Form-I, 2.70 angstrom resolution) and citrate-bound (Form-II, 1.90 angstrom resolution) forms. The enzyme showed broad substrate specificity with k(cat)/K-m in the order of acetate > propionate > formate. Further, the K-m for acetyl-phosphate was significantly lower than for acetate and the enzyme could catalyze the reverse reaction (i.e. ATP synthesis) more efficiently. ATP and Mg2+ could be substituted by other nucleoside 5'-triphosphates (GTP, UTP and CTP) and divalent cations (Mn2+ and Co2+), respectively. Form-I StAckA represents the first structural report of an unliganded AckA. StAckA protomer consists of two domains with characteristic beta beta beta alpha beta alpha beta alpha topology of ASKHA superfamily of proteins. These domains adopt an intermediate conformation compared to that of open and closed forms of ligand-bound Methanosarcina thermophila AckA (MtAckA). Spectroscopic and structural analyses of StAckA further suggested occurrence of inter-domain motion upon ligand-binding. Unexpectedly, Form-II StAckA structure showed a drastic change in the conformation of residues 230-300 compared to that of Form-I. Further investigation revealed electron density corresponding to a citrate molecule in a pocket located at the dimeric interface of Form-II StAckA. Interestingly, a similar dimeric interface pocket lined with largely conserved residues could be identified in Form-I StAckA as well as in other enzymes homologous to AckA suggesting that ligand binding at this pocket may influence the function of these enzymes. Conclusions: The biochemical and structural characterization of StAckA reported here provides insights into the biochemical specificity, overall fold, thermal stability, molecular basis of ligand binding and inter-domain motion in AckA family of enzymes. Dramatic conformational differences observed between unliganded and citrate-bound forms of StAckA led to identification of a putative ligand-binding pocket at the dimeric interface of StAckA with implications for enzymatic function.

Relation between the work function and Young's modulus of RhSi and estimate of Schottky-barrier height at RhSi/Si interface: An ab-initio study

Density-functional calculations are performed to explore the relationship between the work function and Young's modulus of RhSi, and to estimate the p-Schottky-barrier height (SBH) at the Si/RhSi(010) interface. It is shown that the Young's modulus and the workfunction of RhSi satisfy the generic sextic relation, proposed recently for elemental metals. The calculated p-SBH at the Si/RhSi interface is found to differ only by 0.04 eV in opposite limits, viz., no-pinning and strong pinning. We find that the p-SBH is reduced as much as by 0.28 eV due to vacancies at the interface. (C) 2012 American Institute of Physics. http://dx.doi.org/10.1063/1.4761994]

Smart Network Interface Selection for E-DTNs

We implement two energy models that accurately and comprehensively estimates the system energy cost and communication energy cost for using Bluetooth and Wi-Fi interfaces. The energy models running on a system is used to smartly pick the most energy optimal network interface so that data transfer between two end points is maximized.

On the dynamic contact angle in simulation of impinging droplets with sharp interface methods

Effects of dynamic contact angle models on the flow dynamics of an impinging droplet in sharp interface simulations are presented in this article. In the considered finite element scheme, the free surface is tracked using the arbitrary Lagrangian-Eulerian approach. The contact angle is incorporated into the model by replacing the curvature with the Laplace-Beltrami operator and integration by parts. Further, the Navier-slip with friction boundary condition is used to avoid stress singularities at the contact line. Our study demonstrates that the contact angle models have almost no influence on the flow dynamics of the non-wetting droplets. In computations of the wetting and partially wetting droplets, different contact angle models induce different flow dynamics, especially during recoiling. It is shown that a large value for the slip number has to be used in computations of the wetting and partially wetting droplets in order to reduce the effects of the contact angle models. Among all models, the equilibrium model is simple and easy to implement. Further, the equilibrium model also incorporates the contact angle hysteresis. Thus, the equilibrium contact angle model is preferred in sharp interface numerical schemes.

An approach toward the synthesis of PPAP natural product garsubellin A: construction of the tricyclic core

In a study directed toward the bioactive natural product garsubellin A, an expedient route to the bicyclo 3.3.1]nonan-9-one bearing tricyclic core, with a bridgehead anchored tetrahydrofuran ring, is delineated. The approach emanating from commercially available dimedone involved a DIBAL-H mediated retro aldol/re-aldol cyclization cascade and a PCC mediated oxidative cyclization as the key steps. (C) 2013 Elsevier Ltd. All rights reserved.

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.

Combining product information and process information to build virtual assembly situations for knowledge acquisition

Assembly is an important part of the product development process. To avoid potential issues during assembly in specialized domains such as aircraft assembly, expert knowledge to predict such issues is helpful. Knowledge based systems can act as virtual experts to provide assistance. Knowledge acquisition for such systems however, is a challenge, and this paper describes one part of an ongoing research to acquire knowledge through a dialog between an expert and a knowledge acquisition system. In particular this paper discusses the use of a situation model for assemblies to present experts with a virtual assembly and help them locate the specific context of the knowledge they provide to the system.

Geometry of static balancing during posture transition

The interaction between the digital human model (DHM) and environment typically occurs in two distinct modes; one, when the DHM maintains contacts with the environment using its self weight, wherein associated reaction forces at the interface due to gravity are unidirectional; two, when the DHM applies both tension and compression on the environment through anchoring. For static balancing in first mode of interaction, it is sufficient to maintain the projection of the centre of mass (COM) inside the convex region induced by the weight supporting segments of the body on a horizontal plane. In DHM, static balancing is required while performing specified tasks such as reach, manipulation and locomotion; otherwise the simulations would not be realistic. This paper establishes the geometric relationships that must be satisfied for maintaining static balance while altering the support configurations for a given posture and altering the posture for a given support condition. For a given location of the COM for a system supported by multiple point contacts, the conditions for simultaneous withdrawal of a specified set of contacts have been determined in terms of the convex hulls of the subsets of the points of contact. When the projection of COM must move beyond the existing support for performing some task, new supports must be enabled for maintaining static balance. This support seeking behavior could also manifest while planning for reduction of support stresses. Feasibility of such a support depends upon the availability of necessary features in the environment. Geometric conditions necessary for selection of new support on horizontal,inclined and vertical surfaces within the workspace of the DHM for such dynamic scenario have been derived. The concepts developed are demonstrated using the cases of sit-to-stand posture transition for manipulation of COM within the convex supporting polygon, and statically stable walking gaits for support seeking within the kinematic capabilities of the DHM. The theory developed helps in making the DHM realize appropriate behaviors in diverse scenarios autonomously.

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.

Total synthesis and determination of the absolute configuration of 5,6-Dihydro-alpha-pyrone natural product synargentolide B

Enantiospecific total synthesis and determination of the absolute stereochemistry of the alpha-pyrone-containing natural product synargentolide B were accomplished. The absolute stereochemistry of the natural product was established by synthesizing the possible diastereomers and comparison of the data with those reported for the natural product. During the process, total synthesis of the putative structure of related natural product 6R-1S,2R,SR,6S-(tetraacetyloxy)-3E-heptenyl]-5,6-dihydro-2H-pyran-2-o ne was also accomplished and confirmed by X-ray crystal structure analysis. Wittig-Horner reaction of a chiral phosphonate derived from (S)-lactic acid and ring-closing metathesis were the key reactions during the course of the total synthesis.

Effect of Stress and Interface defects on Photo Luminescence of Si nano-crystals embedded in SiO2

Effect of stress and interface defects on photo luminescence property of a silicon nano-crystal (Si-nc) embedded in amorphous silicon dioxide (a-SiO2) are studied in this paper using a self-consistent quantum-continuum based modeling framework. Si-ncs or quantum dots show photoluminescence at room temperature. Whether its origin is due to Si-nc/a-SiO2 interface defects or quantum confinement of carriers in Si-nc is still an outstanding question. Earlier reports have shown that stresses greater than 12 GPa change the indirect energy band gap structure of bulk Si to a direct energy band gap structure. Such stresses are observed very often in nanostructures and these stresses influence the carrier confinement energy significantly. Hence, it is important to determine the effect of stress in addition to the structure of interface defects on photoluminescence property of Si-nc. In the present work, first a Si-nc embedded in a-SiO2 is constructed using molecular dynamics simulation framework considering the actual conditions they are grown so that the interface and residual stress in the structure evolves naturally during formation. We observe that the structure thus created has an interface of about 1 nm thick consisting of 41.95% of defective states mostly Sin+ (n = 0 to 3) coordination states. Further, both the Si-nc core and the embedding matrix are observed to be under a compressive strain. This residual strain field is applied in an effective mass k.p Hamiltonian formulation to determine the energy states of the carriers. The photo luminescence property computed based on the carrier confinement energy and interface energy states associated with defects will be analysed in details in the paper.