Evaluating viewpoint entropy for ribbon representation of protein structure

While many measures of viewpoint goodness have been proposed in computer graphics, none have been evaluated for ribbon representations of protein secondary structure. To fill this gap, we conducted a user study on Amazon’s Mechanical Turk platform, collecting human viewpoint preferences from 65 participants for 4 representative su- perfamilies of protein domains. In particular, we evaluated viewpoint entropy, which was previously shown to be a good predictor for human viewpoint preference of other, mostly non-abstract objects. In a second study, we asked 7 molecular biology experts to find the best viewpoint of the same protein domains and compared their choices with viewpoint entropy. Our results show that viewpoint entropy overall is a significant predictor of human viewpoint preference for ribbon representations of protein secondary structure. However, the accuracy is highly dependent on the complexity of the structure: while most participants agree on good viewpoints for small, non-globular structures with few secondary structure elements, viewpoint preference varies considerably for complex structures. Finally, experts tend to choose viewpoints of both low and high viewpoint entropy to emphasize different aspects of the respective structure.

Simple repetitive sequences in the genome: structure and functional significance

The current explosion of DNA sequence information has generated increasing evidence for the claim that noncoding repetitive DNA sequences present within and around different genes could play an important role in genetic control processes, although the precise role and mechanism by which these sequences function are poorly understood. Several of the simple repetitive sequences which occur in a large number of loci throughout the human and other eukaryotic genomes satisfy the sequence criteria for forming non-B DNA structures in vitro. We have summarized some of the features of three different types of simple repeats that highlight the importance of repetitive DNA in the control of gene expression and chromatin organization. (i) (TG/CA)n repeats are widespread and conserved in many loci. These sequences are associated with nucleosomes of varying linker length and may play a role in chromatin organization. These Z-potential sequences can help absorb superhelical stress during transcription and aid in recombination. (ii) Human telomeric repeat (TTAGGG)n adopts a novel quadruplex structure and exhibits unusual chromatin organization. This unusual structural motif could explain chromosome pairing and stability. (iii) Intragenic amplification of (CTG)n/(CAG)n trinucleotide repeat, which is now known to be associated with several genetic disorders, could down-regulate gene expression in vivo. The overall implications of these findings vis-à-vis repetitive sequences in the genome are summarized.

Synthesis, Structure, and Transformation Studies in a Family of Inorganic-Organic Hybrid Framework Structures Based on Indium

Eight new open-framework inorganic-organic hybrid compounds based on indium have been synthesized employing hydrothermal methods. All of the compounds have InO6, C2O4, and HPO3/HPO4/SO4 units connected to form structures of different dimensionality Thus, the compounds have zero- (I), two- (II, III, IV, V, VII, and VIII), and three-dimensionally (VI) extended networks. The formation of the first zero-dimensional hybrid compound is noteworthy In addition, concomitant polymorphic structures have been observed in the present study. The molecular compound, I, was found to be reactive, and the transformation studies in the presence of a base (pyridine) give rise to the polymorphic structures of II and III, while the addition of an acid (H3PO3) gives rise to a new indium phosphite with a pillared layer structure (T1). Preliminary density functional theory calculations suggest that the stabilities of the polymorphs are different, with one of the forms (II) being preferred over the other, which is consistent with the observed experimental behavior. The oxalate units perform more than one role in the present structures. Thus, the oxalate units connect two In centers to satisfy the coordination requirements as well as to achieve charge balance in compounds II, IV, and VI. The terminal oxalate units observed in compounds I, IV, and V suggest the possibility of intermediate structures. Both in-plane and out-of-plane connectivity of the oxalate units were observed in compound VI. The 31 compounds have been characterized by powder X-ray diffraction, IR spectroscopy, thermogravimetric analysis, and P-31 NMR studies.

On the Structure of Contractible Edges in k-connected Partial k-trees

Contraction of an edge e merges its end points into a new single vertex, and each neighbor of one of the end points of e is a neighbor of the new vertex. An edge in a k-connected graph is contractible if its contraction does not result in a graph with lesser connectivity; otherwise the edge is called non-contractible. In this paper, we present results on the structure of contractible edges in k-trees and k-connected partial k-trees. Firstly, we show that an edge e in a k-tree is contractible if and only if e belongs to exactly one (k + 1) clique. We use this characterization to show that the graph formed by contractible edges is a 2-connected graph. We also show that there are at least |V(G)| + k - 2 contractible edges in a k-tree. Secondly, we show that if an edge e in a partial k-tree is contractible then e is contractible in any k-tree which contains the partial k-tree as an edge subgraph. We also construct a class of contraction critical 2k-connected partial 2k-trees.

Structure-Based Phylogeny as a Diagnostic for Functional Characterization of Proteins with a Cupin Fold

Background: The members of cupin superfamily exhibit large variations in their sequences, functions, organization of domains, quaternary associations and the nature of bound metal ion, despite having a conserved beta-barrel structural scaffold. Here, an attempt has been made to understand structure-function relationships among the members of this diverse superfamily and identify the principles governing functional diversity. The cupin superfamily also contains proteins for which the structures are available through world-wide structural genomics initiatives but characterized as ``hypothetical''. We have explored the feasibility of obtaining clues to functions of such proteins by means of comparative analysis with cupins of known structure and function. Methodology/Principal Findings: A 3-D structure-based phylogenetic approach was undertaken. Interestingly, a dendrogram generated solely on the basis of structural dissimilarity measure at the level of domain folds was found to cluster functionally similar members. This clustering also reflects an independent evolution of the two domains in bicupins. Close examination of structural superposition of members across various functional clusters reveals structural variations in regions that not only form the active site pocket but are also involved in interaction with another domain in the same polypeptide or in the oligomer. Conclusions/Significance: Structure-based phylogeny of cupins can influence identification of functions of proteins of yet unknown function with cupin fold. This approach can be extended to other proteins with a common fold that show high evolutionary divergence. This approach is expected to have an influence on the function annotation in structural genomics initiatives.

Synthesis, Structure, and Properties of Boron- and Nitrogen-Doped Graphene

Boron- and nitrogen-doped graphenes are are prepared by the arc discharge between carbon electrodes or by the transformation of nanodiamond under appropriate atmospheres. Using a combination of experiment and theories based on first principles, systematic changes in the carrier-concentration and electronic structure of the doped graphenes are demonstrated. Stiffening of the G-band mode and intensification of the defect-related D-band in the Raman spectra are also observed.

Mycobacterial Stress Regulation: The Dps ``Twin Sister'' Defense Mechanism and Structure-Function Relationship

In this work, we have tried to emphasize the connection between mycobacterial growth and regulation of gene expression. Utilization of multiple carbon sources and diauxic growth helps bacteria to regulate gene expression at an optimum level so that the inhospitable conditions encountered during nutrient depletion can be circumvented. These aspects will be discussed with respect to mycobacterial growth in subsequent sections. Identification and characterization of genes induced under such conditions is helpful to understand the physiology of the bacterium. Although it is necessary to compare the total expression profile of proteins as they transit from vegetative growth to stationary phase, at times a lot of insights can be deciphered from the expression pattern of one or two proteins. We have compared the protein expression and sigma factor selectivity of two such proteins in M. smegmatis to understand the differential regulation of genes playing diverse function in the same species. Some newer insights on the structure and function of one of the Dps proteins are also explained.

Allostery and conformational free energy changes in human tryptophanyl-tRNA synthetase from essential dynamics and structure networks

The interdependence of the concept of allostery and enzymatic catalysis, and they being guided by conformational mobility is gaining increased prominence. However, to gain a molecular level understanding of llostery and hence of enzymatic catalysis, it is of utter importance that the networks of amino acids participating in allostery be deciphered. Our lab has been exploring the methods of network analysis combined with molecular dynamics simulations to understand allostery at molecular level. Earlier we had outlined methods to obtain communication paths and then to map the rigid/flexible regions of proteins through network parameters like the shortest correlated paths, cliques, and communities. In this article, we advance the methodology to estimate the conformational populations in terms of cliques/communities formed by interactions including the side-chains and then to compute the ligand-induced population shift. Finally, we obtain the free-energy landscape of the protein in equilibrium, characterizing the free-energy minima accessed by the protein complexes. We have chosen human tryptophanyl-tRNA synthetase (hTrpRS), a protein esponsible for charging tryptophan to its cognate tRNA during protein biosynthesis for this investigation. This is a multidomain protein exhibiting excellent allosteric communication. Our approach has provided valuable structural as well as functional insights into the protein. The methodology adopted here is highly generalized to illuminate the linkage between protein structure networks and conformational mobility involved in the allosteric mechanism in any protein with known structure.

The influence of impurities on calcium phosphate floc structure and size in sugar solutions

Settling, dewatering and filtration of flocs are important steps in industry to remove solids and improve subsequent processing. The influence of non-sucrose impurities (Ca2+, Mg2+, phosphate and aconitic acid) on calcium phosphate floc structure (scattering exponent, Sf), size and shape were examined in synthetic and authentic sugar juices using X-ray diffraction techniques. In synthetic juices, Sf decreases with increasing phosphate concentration to values where loosely bound and branched flocs are formed for effective trapping and removal of impurities. Although, Sf did not change with increasing aconitic acid concentration, the floc size significantly decreased reducing the ability of the flocs to remove impurities. In authentic juices, the flocs structures were marginally affected by increasing proportions of non-sucrose impurities. However, optical microscopy indicated the formation of well-formed macro-floc network structures in sugar cane juices containing lower proportions of non-sucrose impurities. These structures are better placed to remove suspended colloidal solids.

Vertex-Fused Metallaborane Clusters: Synthesis, Characterization and Electronic Structure of [(eta(5)-C5Me5Mo)(3)MoB9H18]

The reaction of the [(eta(5)-C5Me5)MoCl4] complex with [LiBH4 - TH F] in toluene at - 70 degrees C, followed by pyrolysis at 110 degrees C, afforded dark brown [(eta(5)-C5Me5Mo)(3)MoB9H18], 2, in parallel with the known [(eta(5)-C5Me5Mo)(2)B5H9], 1. Compound 2 has been characterized in solution by H-1, B-11, and C-13 NMR spectroscopy and elemental analysis, and the structural types were unequivocally established by crystallographic studies. The title compound represents a novel class of vertex-fused clusters in which a Mo atom has been fused in a perpendicular fashion between two molybdaborane clusters. Electronic structure calculations employing density functional theory yield geometries in agreement with the structure determinations, and on grounds of density functional theory calculations, we have analyzed the bonding patterns in the structure,

Understanding solvent effects on structure and reactivity of organic intermediates: a Raman study

The effect of solvent on chemical reactivity has generally been explained on the basis of the dielectric constant and viscosity. However a number of spectroscopic studies, including UV-VIS, IR and Raman, has led to numerous empirical parameters to define solvent effect based on either solvating ability or polarity scale. These parameters include solvent polarizability, dipolarity, Lewis acidity and Lewis basicity, E-T(30), pi*, alpha, beta etc. However, from a structural point of view, we can separate solvation as static and dynamic processes. The static solvation basically relates to stabilization of the molecular structure by the solvent to attain the equilibrium structure, both in the intermediate and ground state. Dynamic solvation relates to solvent reorganization-induced dynamics prior to the structural reorganization to reach the equilibrium state. In this paper, we present (a) structural distortions induced by the solvent due to preferential solvation of the triplet excited state, and (b) the importance of dynamic solvation induced by vibronic coupling (pseudo-Jahn-Teller coupling). The examples include the effect of solvent on structure and reactivity of excited states of 2,2,2-trifluoroacetophenone (TFA). Based on the comparison of time resolved resonance Raman (TR3) data of TFA and other substituted acetophenone systems, it was found that change in solvent polarity indeed results in electronic state switching and structural changes in the excited state, which explains the trend in reactivity. Further, a TR3 study of fluoranil (FA) in the triplet excited state in solvents of varying polarities indicates that the structure of FA in the triplet excited state is determined by vibronic coupling effects and thus distorted structure. These experimental results have been well supported by density functional theoretical computational studies.

Structure of Mycobacterium tuberculosis RuvA, a protein involved in recombination

The process of recombinational repair is crucial for maintaining genomic integrity and generating biological diversity. In association with RuvB and RuvC, RuvA plays a central role in processing and resolving Holliday junctions, which are a critical intermediate in homologous recombination. Here, the cloning, purification and structure determination of the RuvA protein from Mycobacterium tuberculosis (MtRuvA) are reported. Analysis of the structure and comparison with other known RuvA proteins reveal an octameric state with conserved subunit-subunit interaction surfaces, indicating the requirement of octamer formation for biological activity. A detailed analysis of plasticity in the RuvA molecules has led to insights into the invariant and variable regions, thus providing a framework for understanding regional flexibility in various aspects of RuvA function.

Formation of a novel surface structure encoded by Salmonella Pathogenicity Island 2.

The type III secretion system (T3SS) encoded by Salmonella Pathogenicity Island 2 (SPI2) is essential for virulence and intracellular proliferation of Salmonella enterica. We have previously identified SPI2-encoded proteins that are secreted and function as a translocon for the injection of effector proteins. Here, we describe the formation of a novel SPI2-dependent appendage structure in vitro as well as on the surface of bacteria that reside inside a vacuole of infected host cells. In contrast to the T3SS of other pathogens, the translocon encoded by SPI2 is only present singly or in few copies at one pole of the bacterial cell. Under in vitro conditions, appendages are composed of a filamentous needle-like structure with a diameter of 10 nm that was sheathed with secreted protein. The formation of the appendage in vitro is dependent on acidic media conditions. We analyzed SPI2-encoded appendages in infected cells and observed that acidic vacuolar pH was not required for induction of SPI2 gene expression, but was essential for the assembly of these structures and their function as translocon for delivery of effector proteins.