The defect sequence for contractive tuples

We introduce the defect sequence for a contractive tuple of Hilbert space operators and investigate its properties. The defect sequence is a sequence of numbers, called defect dimensions associated with a contractive tuple. We show that there are upper bounds for the defect dimensions. The tuples for which these upper bounds are obtained, are called maximal contractive tuples. The upper bounds are different in the non-commutative and in the commutative case. We show that the creation operators on the full Fock space and the coordinate multipliers on the Drury-Arveson space are maximal. We also study pure tuples and see how the defect dimensions play a role in their irreducibility. (C) 2012 Elsevier Inc. All rights reserved.

Efficient post-processing techniques for speech enhancement

We address the problem of speech enhancement in real-world noisy scenarios. We propose to solve the problem in two stages, the first comprising a generalized spectral subtraction technique, followed by a sequence of perceptually-motivated post-processing algorithms. The role of the post-processing algorithms is to compensate for the effects of noise as well as to suppress any artifacts created by the first-stage processing. The key post-processing mechanisms are aimed at suppressing musical noise and to enhance the formant structure of voiced speech as well as to denoise the linear-prediction residual. The parameter values in the techniques are fixed optimally by experimentally evaluating the enhancement performance as a function of the parameters. We used the Carnegie-Mellon university Arctic database for our experiments. We considered three real-world noise types: fan noise, car noise, and motorbike noise. The enhancement performance was evaluated by conducting listening experiments on 12 subjects. The listeners reported a clear improvement (MOS improvement of 0.5 on an average) over the noisy signal in the perceived quality (increase in the mean-opinion score (MOS)) for positive signal-to-noise-ratios (SNRs). For negative SNRs, however, the improvement was found to be marginal.

DoSA: Database of Structural Alignments

Protein structure alignment is a crucial step in protein structure-function analysis. Despite the advances in protein structure alignment algorithms, some of the local conformationally similar regions are mislabeled as structurally variable regions (SVRs). These regions are not well superimposed because of differences in their spatial orientations. The Database of Structural Alignments (DoSA) addresses this gap in identification of local structural similarities obscured in global protein structural alignments by realigning SVRs using an algorithm based on protein blocks. A set of protein blocks is a structural alphabet that abstracts protein structures into 16 unique local structural motifs. DoSA provides unique information about 159 780 conformationally similar and 56 140 conformationally dissimilar SVRs in 74 705 pairwise structural alignments of homologous proteins. The information provided on conformationally similar and dissimilar SVRs can be helpful to model loop regions. It is also conceivable that conformationally similar SVRs with conserved residues could potentially contribute toward functional integrity of homologues, and hence identifying such SVRs could be helpful in understanding the structural basis of protein function.

The sequence and structure of snake gourd (Trichosanthes anguina) seed lectin, a three-chain nontoxic homologue of type II RIPs

The sequence and structure of snake gourd seed lectin (SGSL), a nontoxic homologue of type II ribosome-inactivating proteins (RIPs), have been determined by mass spectrometry and X-ray crystallography, respectively. As in type II RIPs, the molecule consists of a lectin chain made up of two beta-trefoil domains. The catalytic chain, which is connected through a disulfide bridge to the lectin chain in type II RIPs, is cleaved into two in SGSL. However, the integrity of the three-dimensional structure of the catalytic component of the molecule is preserved. This is the first time that a three-chain RIP or RIP homologue has been observed. A thorough examination of the sequence and structure of the protein and of its interactions with the bound methyl-alpha-galactose indicate that the nontoxicity of SGSL results from a combination of changes in the catalytic and the carbohydrate-binding sites. Detailed analyses of the sequences of type II RIPs of known structure and their homologues with unknown structure provide valuable insights into the evolution of this class of proteins. They also indicate some variability in carbohydrate-binding sites, which appears to contribute to the different levels of toxicity exhibited by lectins from various sources.

Common recognition principles across diverse sequence and structural families of sialic acid binding proteins

Sialic acids form a large family of 9-carbon monosaccharides and are integral components of glycoconjugates. They are known to bind to a wide range of receptors belonging to diverse sequence families and fold classes and are key mediators in a plethora of cellular processes. Thus, it is of great interest to understand the features that give rise to such a recognition capability. Structural analyses using a non-redundant data set of known sialic acid binding proteins was carried out, which included exhaustive binding site comparisons and site alignments using in-house algorithms, followed by clustering and tree computation, which has led to derivation of sialic acid recognition principles. Although the proteins in the data set belong to several sequence and structure families, their binding sites could be grouped into only six types. Structural comparison of the binding sites indicates that all sites contain one or more different combinations of key structural features over a common scaffold. The six binding site types thus serve as structural motifs for recognizing sialic acid. Scanning the motifs against a non-redundant set of binding sites from PDB indicated the motifs to be specific for sialic acid recognition. Knowledge of determinants obtained from this study will be useful for detecting function in unknown proteins. As an example analysis, a genome-wide scan for the motifs in structures of Mycobacterium tuberculosis proteome identified 17 hits that contain combinations of the features, suggesting a possible function of sialic acid binding by these proteins.

Specific Sequence of a Beta Turn in Human La Protein May Contribute to Species Specificity of Hepatitis C Virus

Human La protein is known to be an essential host factor for translation and replication of hepatitis C virus (HCV) RNA. Previously, we have demonstrated that residues responsible for interaction of human La protein with the HCV internal ribosomal entry site (IRES) around the initiator AUG within stem-loop IV form a beta-turn in the RNA recognition motif (RRM) structure. In this study, sequence alignment and mutagenesis suggest that the HCV RNA-interacting beta-turn is conserved only in humans and chimpanzees, the species primarily known to be infected by HCV. A 7-mer peptide corresponding to the HCV RNA-interacting region of human La inhibits HCV translation, whereas another peptide corresponding to the mouse La sequence was unable to do so. Furthermore, IRES-mediated translation was found to be significantly high in the presence of recombinant human La protein in vitro in rabbit reticulocyte lysate. We observed enhanced replication with HCV subgenomic and full-length replicons upon overexpression of either human La protein or a chimeric mouse La protein harboring a human La beta-turn sequence in mouse cells. Taken together, our results raise the possibility of creating an immunocompetent HCV mouse model using human-specific cell entry factors and a humanized form of La protein.

PLIC: protein-ligand interaction clusters

Most of the biological processes are governed through specific protein-ligand interactions. Discerning different components that contribute toward a favorable protein-ligand interaction could contribute significantly toward better understanding protein function, rationalizing drug design and obtaining design principles for protein engineering. The Protein Data Bank (PDB) currently hosts the structure of similar to 68 000 protein-ligand complexes. Although several databases exist that classify proteins according to sequence and structure, a mere handful of them annotate and classify protein-ligand interactions and provide information on different attributes of molecular recognition. In this study, an exhaustive comparison of all the biologically relevant ligand-binding sites (84 846 sites) has been conducted using PocketMatch: a rapid, parallel, in-house algorithm. PocketMatch quantifies the similarity between binding sites based on structural descriptors and residue attributes. A similarity network was constructed using binding sites whose PocketMatch scores exceeded a high similarity threshold (0.80). The binding site similarity network was clustered into discrete sets of similar sites using the Markov clustering (MCL) algorithm. Furthermore, various computational tools have been used to study different attributes of interactions within the individual clusters. The attributes can be roughly divided into (i) binding site characteristics including pocket shape, nature of residues and interaction profiles with different kinds of atomic probes, (ii) atomic contacts consisting of various types of polar, hydrophobic and aromatic contacts along with binding site water molecules that could play crucial roles in protein-ligand interactions and (iii) binding energetics involved in interactions derived from scoring functions developed for docking. For each ligand-binding site in each protein in the PDB, site similarity information, clusters they belong to and description of site attributes are provided as a relational database-protein-ligand interaction clusters (PLIC).

Comparative Study of Protein Unfolding in Aqueous Urea and Dimethyl Sulfoxide Solutions: Surface Polarity, Solvent Specificity, and Sequence of Secondary Structure Melting

Elucidation of possible pathways between folded (native) and unfolded states of a protein is a challenging task, as the intermediates are often hard to detect. Here, we alter the solvent environment in a controlled manner by choosing two different cosolvents of water, urea, and dimethyl sulfoxide (DMSO) and study unfolding of four different proteins to understand the respective sequence of melting by computer simulation methods. We indeed find interesting differences in the sequence of melting of alpha helices and beta sheets in these two solvents. For example, in 8 M urea solution, beta-sheet parts of a protein are found to unfold preferentially, followed by the unfolding of alpha helices. In contrast, 8 M DMSO solution unfolds alpha helices first, followed by the separation of beta sheets for the majority of proteins. Sequence of unfolding events in four different alpha/beta proteins and also in chicken villin head piece (HP-36) both in urea and DMSO solutions demonstrate that the unfolding pathways are determined jointly by relative exposure of polar and nonpolar residues of a protein and the mode of molecular action of a solvent on that protein.

Role of DNA sequence based structural features of promoters in transcription initiation and gene expression

D Regulatory information for transcription initiation is present in a stretch of genomic DNA, called the promoter region that is located upstream of the transcription start site (TSS) of the gene. The promoter region interacts with different transcription factors and RNA polymerase to initiate transcription and contains short stretches of transcription factor binding sites (TFBSs), as well as structurally unique elements. Recent experimental and computational analyses of promoter sequences show that they often have non-B-DNA structural motifs, as well as some conserved structural properties, such as stability, bendability, nucleosome positioning preference and curvature, across a class of organisms. Here, we briefly describe these structural features, the differences observed in various organisms and their possible role in regulation of gene expression.

Real-time magnetic resonance imaging and electromagnetic articulography database for speech production research (TC)

USC-TIMIT is an extensive database of multimodal speech production data, developed to complement existing resources available to the speech research community and with the intention of being continuously refined and augmented. The database currently includes real-time magnetic resonance imaging data from five male and five female speakers of American English. Electromagnetic articulography data have also been presently collected from four of these speakers. The two modalities were recorded in two independent sessions while the subjects produced the same 460 sentence corpus used previously in the MOCHA-TIMIT database. In both cases the audio signal was recorded and synchronized with the articulatory data. The database and companion software are freely available to the research community. (C) 2014 Acoustical Society of America.

An extended Shine-Dalgarno sequence in mRNA functionally bypasses a vital defect in initiator tRNA

Initiator tRNAs are special in their direct binding to the ribosomal P-site due to the hallmark occurrence of the three consecutive G-C base pairs (3GC pairs) in their anticodon stems. How the 3GC pairs function in this role, has remained unsolved. We show that mutations in either the mRNA or 16S rRNA leading to extended interaction between the Shine-Dalgarno (SD) and anti-SD sequences compensate for the vital need of the 3GC pairs in tRNA(fMet) for its function in Escherichia coli. In vivo, the 3GC mutant tRNA(fMet) occurred less abundantly in 70S ribosomes but normally on 30S subunits. However, the extended SD:anti-SD interaction increased its occurrence in 70S ribosomes. We propose that the 3GC pairs play a critical role in tRNA(fMet) retention in ribosome during the conformational changes that mark the transition of 30S preinitiation complex into elongation competent 70S complex. Furthermore, treating cells with kasugamycin, decreasing ribosome recycling factor (RRF) activity or increasing initiation factor 2 (IF2) levels enhanced initiation with the 3GC mutant tRNA(fMet), suggesting that the 70S mode of initiation is less dependent on the 3GC pairs in tRNA(fMet).

An Unusual Ring-Contraction/Rearrangement Sequence for Making Functionalized Di- and Triquinanes

A novel ring contraction/rearrangement sequence leading to functionalized 2,8-oxymethano-bridged di- and triquinane compounds is observed in the reaction of various substituted 1-methyl-4-isopropenyl-6-oxabicylo3.2.1]octan-8-ones with Lewis acids. The reaction is novel and is unprecedented for the synthesis of di- and triquinane frameworks.

An Unusual Ring-Contraction/Rearrangement Sequence for Making Functionalized Di- and Triquinanes

A novel ring contraction/rearrangement sequence leading to functionalized 2,8-oxymethano-bridged di- and triquinane compounds is observed in the reaction of various substituted 1-methyl-4-isopropenyl-6-oxabicylo3.2.1]octan-8-ones with Lewis acids. The reaction is novel and is unprecedented for the synthesis of di- and triquinane frameworks.

An Unusual Ring-Contraction/Rearrangement Sequence for Making Functionalized Di- and Triquinanes

A novel ring contraction/rearrangement sequence leading to functionalized 2,8-oxymethano-bridged di- and triquinane compounds is observed in the reaction of various substituted 1-methyl-4-isopropenyl-6-oxabicylo3.2.1]octan-8-ones with Lewis acids. The reaction is novel and is unprecedented for the synthesis of di- and triquinane frameworks.