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.

Effect of temperature on the plastic zone size and the shear band density in a bulk metallic glass

High temperature bonded interface indentation experiments are carried out on a Zr based bulk metallic glass (BMG) to examine the plastic deformation characteristics in subsurface deformation zone under a Vickers indenter. The results show that the shear bands are semi-circular in shape and propagate in radial direction. At all temperatures the inter-band spacing along the indentation axis is found to increase with increasing distance from the indenter tip. The average shear band spacing monotonically increases with temperature whereas the shear band induced plastic deformation zone is invariant with temperature. These observations are able to explain the increase in pressure sensitive plastic flow of BMGs with temperature. (C) 2011 Elsevier B.V. All rights reserved.

Deorphanization of Malonyl CoA:ACP Transacylase Drug Target in Plasmodium falciparum (PfFabD) Using Bacterial Antagonists: A Piggyback' Approach for Antimalarial Drug Discovery

Quest for new drug targets in Plasmodium sp. has underscored malonyl CoA:ACP transacylase (PfFabD) of fatty acid biosynthetic pathway in apicoplast. In this study, a piggyback approach was employed for the receptor deorphanization using inhibitors of bacterial FabD enzymes. Due to the lack of crystal structure, theoretical model was constructed using the structural details of homologous enzymes. Sequence and structure analysis has localized the presence of two conserved pentapeptide motifs: GQGXG and GXSXG and five key invariant residues viz., Gln109, Ser193, Arg218, His305 and Gln354 characteristic of FabD enzyme. Active site mapping of PfFabD using substrate molecules has disclosed the spatial arrangement of key residues in the cavity. As structurally similar molecules exhibit similar biological activities, signature pharmacophore fingerprints of FabD antagonists were generated using 0D-3D descriptors for molecular similarity-based cluster analysis and to correlate with their binding profiles. It was observed that antagonists showing good geometrical fitness score were grouped in cluster-1, whereas those exhibiting high binding affinities in cluster-2. This study proves important to shed light on the active site environment to reveal the hotspot for binding with higher affinity and to narrow down the virtual screening process by searching for close neighbors of the active compounds.

Junction between surfaces of two topological insulators

We study the properties of a line junction which separates the surfaces of two three-dimensional topological insulators. The velocities of the Dirac electrons on the two surfaces may be unequal and may even have opposite signs. For a time-reversal invariant system, we show that the line junction is characterized by an arbitrary parameter alpha which determines the scattering from the junction. If the surface velocities have the same sign, we show that there can be edge states which propagate along the line junction with a velocity and spin orientation which depend on alpha and the ratio of the velocities. Next, we study what happens if the two surfaces are at an angle phi with respect to each other. We study the scattering and differential conductance through the line junction as functions of phi and alpha. We also find that there are edge states which propagate along the line junction with a velocity and spin orientation which depend on phi. Finally, if the surface velocities have opposite signs, we find that the electrons must transmit into the two-dimensional interface separating the two topological insulators.

Nucleation-Growth Mode of Cubic-Tetragonal Transition with Coexistence of Phases over a Wide Temperature Interval in the High Temperature Ferroelectric Systems PbTiO3-BiMeO3:Me = Sc , and Zn1/2Ti1/2

Temperature dependent X-ray powder diffraction and dielectric studies have been carried out on tetragonal compositions of (1-x) PbTiO 3(x) BiMeO 3; Me similar to Sc and Zn 1/2 Ti 1/2. The cubic and the tetragonal phases coexist over more than 100 degrees C for 0.70 PbTiO 30.3 Bi ( Zn 1/2 Ti 1/2) O 3 and 0.66 PbTiO 30.34 BiScO 3. The wide temperature range of phase coexistence is shown to be an intrinsic feature of the system, and is attributed to the increase in the degree of the covalent character of the ( Pb +Bi ) O bond with increasing concentration of Bi at the Pb -site. The d-values of the {111} planes of the coexisting phases are nearly identical, suggesting this plane to be the invariant plane for the martensitic type cubic-tetragonal transformation occurring in these systems.

Continuum theory of edge states of topological insulators: variational principle and boundary conditions

We develop a continuum theory to model low energy excitations of a generic four-band time reversal invariant electronic system with boundaries. We propose a variational energy functional for the wavefunctions which allows us to derive natural boundary conditions valid for such systems. Our formulation is particularly suited for developing a continuum theory of the protected edge/surface excitations of topological insulators both in two and three dimensions. By a detailed comparison of our analytical formulation with tight binding calculations of ribbons of topological insulators modelled by the Bernevig-Hughes-Zhang (BHZ) Hamiltonian, we show that the continuum theory with a natural boundary condition provides an appropriate description of the low energy physics.

A Bifunctional Enzyme That Has Both Monoacylglycerol Acyltransferase and Acyl Hydrolase Activities

Monoacylglycerol acyltransferase (MGAT) catalyzes the synthesis of diacylglycerol, the precursor of triacylglycerol biosynthesis and an important signaling molecule. Here, we describe the isolation and characterization of the peanut (Arachis hypogaea) MGAT gene. The soluble enzyme utilizes invariant histidine-62 and aspartate-67 residues of the acyltransferase motif for its MGAT activity. A sequence analysis revealed the presence of a hydrolase (GXSXG) motif, and enzyme assays revealed the presence of monoacylglycerol (MAG) and lysophosphatidylcholine (LPC) hydrolytic activities, indicating the bifunctional nature of the enzyme. The overexpression of the MGAT gene in yeast (Saccharomyces cerevisiae) caused an increase in triacylglycerol accumulation. Similar to the peanut MGAT, the Arabidopsis (Arabidopsis thaliana) homolog (At1g52760) also exhibited both acyltransferase and hydrolase activities. Interestingly, the yeast homolog lacks the conserved HX4D motif, and it is deficient in the acyltransferase function but exhibits MAG and LPC hydrolase activities. This study demonstrates the presence of a soluble MGAT/hydrolase in plants. The predicted three-dimensional homology modeling and substrate docking suggested the presence of two separate substrate (MAG and LPC)-binding sites in a single polypeptide. Our study describes a soluble bifunctional enzyme that has both MGAT and hydrolase functions.

Ca2+ Binding to the ExDxD Motif Regulates the DNA Cleavage Specificity of a Promiscuous Endonuclease

Most of the restriction endonucleases (REases) are dependent on Mg2+ for DNA cleavage, and in general, Ca2+ inhibits their activity. RKpnI, an HNH active site containing beta beta alpha-Me finger nuclease, is an exception. In presence of Ca2+, the enzyme exhibits high-fidelity DNA cleavage and complete suppression of Mg2+-induced promiscuous activity. To elucidate the mechanism of unusual Ca2+-mediated activity, we generated alanine variants in the putative Ca-2+ binding motif, E(132)xD(134)xD(136), of the enzyme. Mutants showed decreased levels of DNA cleavage in the presence of Ca2+. We demonstrate that ExDxD residues are involved in Ca2+ coordination; however, the invariant His of the catalytic HNH motif acts as a general base for nucleophile activation, and the other two active site residues, D148 and Q175, also participate in Ca2+-mediated cleavage. Insertion of a 10-amino acid linker to disrupt the spatial organization of the ExDxD and HNH motifs impairs Ca2+ binding and affects DNA cleavage by the enzyme. Although ExDxD mutant enzymes retained efficient cleavage at the canonical sites in the presence of Mg2+, the promiscuous activity was greatly reduced, indicating that the carboxyl residues of the acidic triad play an important role in sequence recognition by the enzyme. Thus, the distinct Ca2+ binding motif that confers site specific cleavage upon Ca2+ binding is also critical for the promiscuous activity of the Mg2+-bound enzyme, revealing its role in metal ion-mediated modulation of DNA cleavage.

c-theorems in arbitrary dimensions

The dilaton action in 3 + 1 dimensions plays a crucial role in the proof of the a-theorem. This action arises using Wess-Zumino consistency conditions and crucially relies on the existence of the trace anomaly. Since there are no anomalies in odd dimensions, it is interesting to ask how such an action could arise otherwise. Motivated by this we use the AdS/CFT correspondence to examine both even and odd dimensional conformal field theories. We find that in even dimensions, by promoting the cutoff to a field, one can get an action for this field which coincides with the Wess-Zumino action in flat space. In three dimensions, we observe that by finding an exact Hamilton-Jacobi counterterm, one can find a non-polynomial action which is invariant under global Weyl rescalings. We comment on how this finding is tied up with the F-theorem conjectures.

Turning visual search time on its head

Our everyday visual experience frequently involves searching for objects in clutter. Why are some searches easy and others hard? It is generally believed that the time taken to find a target increases as it becomes similar to its surrounding distractors. Here, I show that while this is qualitatively true, the exact relationship is in fact not linear. In a simple search experiment, when subjects searched for a bar differing in orientation from its distractors, search time was inversely proportional to the angular difference in orientation. Thus, rather than taking search reaction time (RT) to be a measure of target-distractor similarity, we can literally turn search time on its head (i.e. take its reciprocal 1/RT) to obtain a measure of search dissimilarity that varies linearly over a large range of target-distractor differences. I show that this dissimilarity measure has the properties of a distance metric, and report two interesting insights come from this measure: First, for a large number of searches, search asymmetries are relatively rare and when they do occur, differ by a fixed distance. Second, search distances can be used to elucidate object representations that underlie search - for example, these representations are roughly invariant to three-dimensional view. Finally, search distance has a straightforward interpretation in the context of accumulator models of search, where it is proportional to the discriminative signal that is integrated to produce a response. This is consistent with recent studies that have linked this distance to neuronal discriminability in visual cortex. Thus, while search time remains the more direct measure of visual search, its reciprocal also has the potential for interesting and novel insights. (C) 2012 Elsevier Ltd. All rights reserved.

From Molecular to Supramolecular: An Exploration into the Modes of Self-assembly in Conformationally Locked Polycyclitols

This brief account highlights the notable findings of our investigation into the supramolecular chemistry of conformationally locked polycyclitols in the solid state. The study was aimed at analyzing the crystal packing and unraveling the modalities of non-covalent interactions (particularly, intramolecular vis-a-vis intermolecular OH center dot center dot center dot O hydrogen bonds) in polyols. The know-how obtained thereof, was successfully utilized to engineer self-assemblies of designer polycyclitols, having hydrogen bond donors and acceptors fettered onto a trans-decalin scaffold. The results seek to draw particular attention to the intrinsic attribute of this rigid carbocyclic framework to lock functional groups into spatially invariant positions and bring potential intramolecular hydrogen bonding partners into favorable interaction geometry to engender predictability in the self-assembly patterns.

Field extension code based dispersion matrices for coherently detected space-time shift keying

Motivated by the recent Coherent Space-Time Shift Keying (CSTSK) philosophy, we construct new dispersion matrices for rotationally invariant PSK signaling sets. Given a specific PSK signal constellation, the dispersion matrices of the existing CSTSK scheme were chosen by maximizing the mutual information over randomly generated sets of dispersion matrices. In this contribution we propose a general method for constructing a set of structured dispersion matrices for arbitrary PSK signaling sets using Field Extension (FE) codes and then study the attainable Symbol Error Rate (SER) performance of some example constructions. We demonstrate that the proposed dispersion scheme is capable of outperforming the existing dispersion arrangement at medium to high SNRs.

Quadrature approximation properties of the spiral-phase quadrature transform

The notion of the 1-D analytic signal is well understood and has found many applications. At the heart of the analytic signal concept is the Hilbert transform. The problem in extending the concept of analytic signal to higher dimensions is that there is no unique multidimensional definition of the Hilbert transform. Also, the notion of analyticity is not so well under stood in higher dimensions. Of the several 2-D extensions of the Hilbert transform, the spiral-phase quadrature transform or the Riesz transform seems to be the natural extension and has attracted a lot of attention mainly due to its isotropic properties. From the Riesz transform, Larkin et al. constructed a vortex operator, which approximates the quadratures based on asymptotic stationary-phase analysis. In this paper, we show an alternative proof for the quadrature approximation property by invoking the quasi-eigenfunction property of linear, shift-invariant systems. We show that the vortex operator comes up as a natural consequence of applying this property. We also characterize the quadrature approximation error in terms of its energy as well as the peak spatial-domain error. Such results are available for 1-D signals, but their counter part for 2-D signals have not been provided. We also provide simulation results to supplement the analytical calculations.

Renormalization of noncommutative quantum field theories

We report on a comprehensive analysis of the renormalization of noncommutative phi(4) scalar field theories on the Groenewold-Moyal plane. These scalar field theories are twisted Poincare invariant. Our main results are that these scalar field theories are renormalizable, free of UV/IR mixing, possess the same fixed points and beta-functions for the couplings as their commutative counterparts. We also argue that similar results hold true for any generic noncommutative field theory with polynomial interactions and involving only pure matter fields. A secondary aim of this work is to provide a comprehensive review of different approaches for the computation of the noncommutative S-matrix: noncommutative interaction picture and noncommutative Lehmann-Symanzik-Zimmermann formalism. DOI: 10.1103/PhysRevD.87.064014

Supersymmetry of classical solutions in Chern-Simons higher spin supergravity

We construct and study classical solutions in Chern-Simons supergravity based on the superalgebra sl(N vertical bar N = 1). The algebra for the N = 3 case is written down explicitly using the fact that it arises as the global part of the super conformal W-3 superalgebra. For this case we construct new classical solutions and study their supersymmetry. Using the algebra we write down the Killing spinor equations and explicitly construct the Killing spinor for conical defects and black holes in this theory. We show that for the general sl(N|N - 1) theory the condition for the periodicity of the Killing spinor can be written in terms of the products of the odd roots of the super algebra and the eigenvalues of the holonomy matrix of the background. Thus the supersymmetry of a given background can be stated in terms of gauge invariant and well defined physical observables of the Chern-Simons theory. We then show that for N >= 4, the sl(N|N - 1) theory admits smooth supersymmetric conical defects.