Study of non-local wave properties of nanotubes with surface effects

In macroscopic and even microscopic structural elements, surface effects can be neglected and classical theories are sufficient. As the structural size decreases towards the nanoscale regime, the surface-to-bulk energy ratio increases and surface effects must be taken into account. In the present work, the terahertz wave dispersion characteristics of a nanotube are studied with consideration of the surface effects as well as the non-local small scale effects. Non-local elasticity theory is used to derive the general governing differential equation based on equilibrium approach to include those scale effects. Scale and surface property dependent wave characteristic equations are obtained via spectral analysis. For the present study the material properties of an anodic alumina nanotube with crystallographic of < 111 > direction are considered. The present analysis shows that the effect of surface properties (surface integrated residual stress and surface integrated modulus) on the flexural wave characteristics of anodic nanotubes are more significant. It has been found that the flexural wavenumbers with surface effects are high as compared to that without surface effects. It has also been shown that, with consideration of surface effects the flexural wavenumbers are under compressive nature. The effect of the small scale and the size of the nanotube on wave dispersion properties are also captured in the present work. (C) 2012 Elsevier B.V. All rights reserved.

Targeting ribosome assembly on the HCV RNA using a small RNA molecule

Translation initiation of hepatitis C virus (HCV) RNA is the initial obligatory step of the viral life cycle, mediated through the internal ribosome entry site (IRES) present in the 5'-untranslated region (UTR). Initiation on the HCV IRES is mediated by multiple structure-specific interactions between IRES RNA and host 40S ribosomal subunit. In the present study we demonstrate that the SLIIIef domain, in isolation from other structural elements of HCV IRES, retain the ability to interact with 40S ribosome subunit. A small RNA SLRef, mimicking the SLIIIef domain was found to interact specifically with human La protein and the ribosomal protein S5 and selectively inhibit HCV RNA translation. More importantly, SLRef RNA showed significant suppression of replication in HCV monocistronic replicon and decrease of negative strand synthesis in HCV cell culture system. Finally, using Sendai virus based virosome, the targeted delivery of SLRef RNA into mice liver succeeded in selectively inhibiting HCV IRES mediated translation in vivo.

H-1, C-13, N-15 assignment and secondary structure determination of glutamine amido transferase subunit of gaunosine monophosphate synthetase from Methanocaldococcus jannaschii

Sequence specific resonance assignments have been obtained for H-1, C-13 and N-15 nuclei of the 21 kDa (188 residues long) glutamine amido transferase subunit of guanosine monophosphate synthetase from Methanocaldococcus jannaschii. From an analysis of H-1 and C-13(alpha), C-13(beta) secondary chemical shifts, (3) JH(N)H(alpha) scalar coupling constants and sequential, short and medium range H-1-H-1 NOEs, it was deduced that the glutamine amido transferase subunit has eleven strands and five helices as the major secondary structural elements in its tertiary structure.

Study of terahertz wave propagation properties in nanoplates with surface and small-scale effects

In macroscopic and even microscopic structural elements, surface effects can be neglected and classical theories are sufficient. As the structural size decreases towards the nanoscale regime, the surface-to-bulk energy ratio increases and surface effects must be taken into account. In the present work, the terahertz wave dispersion characteristics of a nanoplate are studied with consideration of the surface effects as well as the nonlocal small-scale effects. Nonlocal elasticity theory of plate is used to derive the general differential equation based on equilibrium approach to include those scale effects. Scale and surface property dependent wave characteristic equations are obtained via spectral analysis. For the present study the material properties of an anodic alumina with crystallographic of < 111 > direction are considered. The present analysis shows that the effect of surface properties on the flexural waves of nanoplates is more significant. It can be found that the flexural wavenumbers with surface effects are high as compared to that without surface effects. The scale effects show that the wavenumbers of the flexural wave become highly non-linear and tend to infinite at certain frequency. After that frequency the wave will not propagate and the corresponding wave velocities tend to zero at that frequency (escape frequency). The effects of surface stresses on the wave propagation properties of nanoplate are also captured in the present work. (C) 2012 Elsevier Ltd. All rights reserved.

Correlation between enhanced lattice polarizability and high piezoelectric response in BiScO3-PbTiO3

Piezoelectric and ex situ electric-field induced structural studies were carried out on closely spaced compositions in the morphotropic phase boundary region of (1 - x) PbTiO3-(x)BiScO3. While the common approach of zero field structural analysis failed to provide a unique relationship between the anomalous piezoresponse of x = 0.3725 and structural factor(s), ex situ study of electric-field induced structural changes revealed that the composition exhibiting the highest piezoelectric response is the one which also exhibits significantly enhanced polarizability of the lattices of both coexisting (monoclinic and tetragonal) phases. The enhanced lattice polarizability manifests as a significant fraction of the monoclinic phase transforming irreversibly to the tetragonal phase after electric poling. DOI: 10.1103/PhysRevB.87.064106

DEFINING alpha-HELIX GEOMETRY BY C-alpha ATOM TRACE vs (phi-psi) TORSION ANGLES: A COMPARATIVE ANALYSIS

A regular secondary structure is described by a well defined set of values for the backbone dihedral angles (phi,psi and omega) in a polypeptide chain. However in real protein structures small local variations give rise to distortions from the ideal structures, which can lead to considerable variation in higher order organization. Protein structure analysis and accurate assignment of various structural elements, especially their terminii, are important first step in protein structure prediction and design. Various algorithms are available for assigning secondary structure elements in proteins but some lacunae still exist. In this study, results of a recently developed in-house program ASSP have been compared with those from STRIDE, in identification of alpha-helical regions in both globular and membrane proteins. It is found that, while a combination of hydrogen bond patterns and backbone torsional angles (phi-psi) are generally used to define secondary structure elements, the geometry of the C-alpha atom trace by itself is sufficient to define the parameters of helical structures in proteins. It is also possible to differentiate the various helical structures by their C-alpha trace and identify the deviations occurring both at mid-positions as well as at the terminii of alpha-helices, which often lead to occurrence of 3(10) and pi-helical fragments in both globular and membrane proteins.

The Non-catalytic ``Cap Domain'' of a Mycobacterial Metallophosphoesterase Regulates Its Expression and Localization in the Cell

Despite highly conserved core catalytic domains, members of the metallophosphoesterase (MPE) superfamily perform diverse and crucial functions ranging from nucleotide and nucleic acid metabolism to phospholipid hydrolysis. Unique structural elements outside of the catalytic core called ``cap domains'' are thought to provide specialization to these enzymes; however, no directed study has been performed to substantiate this. The cap domain of Rv0805, an MPE from Mycobacterium tuberculosis, is located C-terminal to its catalytic domain and is dispensable for the catalytic activity of this enzyme in vitro. We show here that this C-terminal extension (CTE) mediates in vivo localization of the protein to the cell membrane and cell wall as well as modulates expression levels of Rv0805 in mycobacteria. We also demonstrate that Rv0805 interacts with the cell wall of mycobacteria, possibly with the mycolyl-arabinogalactan-peptidoglycan complex, by virtue of its C terminus, a hitherto unknown property of this MPE. Using a panel of mutant proteins, we identify interactions between active site residues of Rv0805 and the CTE that determine its association with the cell wall. Finally, we show that Rv0805 and a truncated mutant devoid of the CTE produce different phenotypic effects when expressed in mycobacteria. Our study thus provides a detailed dissection of the functions of the cap domain of an MPE and suggests that the repertoire of cellular functions of MPEs cannot be understood without exploring the modulatory effects of these subdomains.

Sequence and conformational preferences at termini of alpha-helices in membrane proteins: Role of the helix environment

-helices are amongst the most common secondary structural elements seen in membrane proteins and are packed in the form of helix bundles. These -helices encounter varying external environments (hydrophobic, hydrophilic) that may influence the sequence preferences at their N and C-termini. The role of the external environment in stabilization of the helix termini in membrane proteins is still unknown. Here we analyze -helices in a high-resolution dataset of integral -helical membrane proteins and establish that their sequence and conformational preferences differ from those in globular proteins. We specifically examine these preferences at the N and C-termini in helices initiating/terminating inside the membrane core as well as in linkers connecting these transmembrane helices. We find that the sequence preferences and structural motifs at capping (Ncap and Ccap) and near-helical (N' and C') positions are influenced by a combination of features including the membrane environment and the innate helix initiation and termination property of residues forming structural motifs. We also find that a large number of helix termini which do not form any particular capping motif are stabilized by formation of hydrogen bonds and hydrophobic interactions contributed from the neighboring helices in the membrane protein. We further validate the sequence preferences obtained from our analysis with data from an ultradeep sequencing study that identifies evolutionarily conserved amino acids in the rat neurotensin receptor. The results from our analysis provide insights for the secondary structure prediction, modeling and design of membrane proteins. Proteins 2014; 82:3420-3436. (c) 2014 Wiley Periodicals, Inc.

Design of symmetric TIM barrel proteins from first principles

Background: Computational protein design is a rapidly maturing field within structural biology, with the goal of designing proteins with custom structures and functions. Such proteins could find widespread medical and industrial applications. Here, we have adapted algorithms from the Rosetta software suite to design much larger proteins, based on ideal geometric and topological criteria. Furthermore, we have developed techniques to incorporate symmetry into designed structures. For our first design attempt, we targeted the (alpha/beta)(8) TIM barrel scaffold. We gained novel insights into TIM barrel folding mechanisms from studying natural TIM barrel structures, and from analyzing previous TIM barrel design attempts. Methods: Computational protein design and analysis was performed using the Rosetta software suite and custom scripts. Genes encoding all designed proteins were synthesized and cloned on the pET20-b vector. Standard circular dichroism and gel chromatographic experiments were performed to determine protein biophysical characteristics. 1D NMR and 2D HSQC experiments were performed to determine protein structural characteristics. Results: Extensive protein design simulations coupled with ab initio modeling yielded several all-atom models of ideal, 4-fold symmetric TIM barrels. Four such models were experimentally characterized. The best designed structure (Symmetrin-1) contained a polar, histidine-rich pore, forming an extensive hydrogen bonding network. Symmetrin-1 was easily expressed and readily soluble. It showed circular dichroism spectra characteristic of well-folded alpha/beta proteins. Temperature melting experiments revealed cooperative and reversible unfolding, with a T-m of 44 degrees C and a Gibbs free energy of unfolding (Delta G degrees) of 8.0 kJ/mol. Urea denaturing experiments confirmed these observations, revealing a C-m of 1.6 M and a Delta G degrees of 8.3 kJ/mol. Symmetrin-1 adopted a monomeric conformation, with an apparent molecular weight of 32.12 kDa, and displayed well resolved 1D-NMR spectra. However, the HSQC spectrum revealed somewhat molten characteristics. Conclusions: Despite the detection of molten characteristics, the creation of a soluble, cooperatively folding protein represents an advancement over previous attempts at TIM barrel design. Strategies to further improve Symmetrin-1 are elaborated. Our techniques may be used to create other large, internally symmetric proteins.

Dissecting Ubiquitin Folding Using the Self-Organized Polymer Model

Folding of Ubiquitin (Ub), a functionally important protein found in eukaryotic organisms, is investigated at low and neutral pH at different temperatures using simulations of the coarse-grained self-organized-polymer model with side chains (SOP-SC). The melting temperatures (T-m's), identified with the peaks in the heat capacity curves, decrease as pH decreases, in qualitative agreement with experiments. The calculated radius of gyration, showing dramatic variations with pH, is in excellent agreement with scattering experiments. At T-m Ub folds in a two-state manner at low and neutral pH. Clustering analysis of the conformations sampled in equilibrium folding trajectories at T-m with multiple transitions between the folded and unfolded states, shows a network of metastable states connecting the native and unfolded states. At low and neutral pH, Ub folds with high probability through a preferred set of conformations resulting in a pH-dependent dominant folding pathway. Folding kinetics reveal that Ub assembly at low pH occurs by multiple pathways involving a combination of nucleation-collapse and diffusion collision mechanism. The mechanism by which Ub folds is dictated by the stability of the key secondary structural elements responsible for establishing long-range contacts and collapse of Ub. Nucleation collapse mechanism holds if the stability of these elements are marginal, as would be the case at elevated temperatures. If the lifetimes associated with these structured microdomains are on the order of hundreds of microseconds, then Ub folding follows the diffusion collision mechanism with intermediates, many of which coincide with those found in equilibrium. Folding at neutral pH is a sequential process with a populated intermediate resembling that sampled at equilibrium. The transition state structures, obtained using a P-fold analysis, are homogeneous and globular with most of the secondary and tertiary structures being native-like. Many of our findings for both the thermodynamics and kinetics of folding are not only in agreement with experiments but also provide missing details not resolvable in standard experiments. The key prediction that folding mechanism varies dramatically with pH is amenable to experimental tests.

The putative role of some conserved water molecules in the structure and function of human transthyretin

Human transthyretin (hTTR) is a multifunctional protein that is involved in several neurodegenerative diseases. Besides the transportation of thyroxin and vitamin A, it is also involved in the proteolysis of apolipoprotein A1 and A beta peptide. Extensive analyses of 32 high-resolution X-ray and neutron diffraction structures of hTTR followed by molecular-dynamics simulation studies using a set of 15 selected structures affirmed the presence of 44 conserved water molecules in its dimeric structure. They are found to play several important roles in the structure and function of the protein. Eight water molecules stabilize the dimeric structure through an extensive hydrogen-bonding network. The absence of some of these water molecules in highly acidic conditions (pH <= 4.0) severely affects the interfacial hydrogen-bond network, which may destabilize the native tetrameric structure, leading to its dissociation. Three pairs of conserved water molecules contribute to maintaining the geometry of the ligand-binding cavities. Some other water molecules control the orientation and dynamics of different structural elements of hTTR. This systematic study of the location, absence, networking and interactions of the conserved water molecules may shed some light on various structural and functional aspects of the protein. The present study may also provide some rational clues about the conserved water-mediated architecture and stability of hTTR.

Anomalous reduction in domain wall displacement at the morphotropic phase boundary of the piezoelectric alloy system PbTiO3-BiScO3

A comparative study of field-induced domain switching and lattice strain was carried out by in situ electric-field-dependent high-energy synchrotron x-ray diffraction on a morphotropic phase boundary (MPB) and a near-MPB rhombohedral/pseudomonoclinic composition of a high-performance piezoelectric alloy (1-x) PbTiO3-(x)BiScO3. It is demonstrated that the MPB composition showing large d(33) similar to 425 pC/N exhibits significantly reduced propensity of field-induced domain switching as compared to the non-MPB rhombohedral composition (d(33) similar to 260 pC/N). These experimental observations contradict the basic premise of the martensitic-theory-based explanation which emphasizes on enhanced domain wall motion as the primary factor for the anomalous piezoelectric response in MPB piezoelectrics. Our results favor field-induced structural transformation to be the primary mechanism contributing to the large piezoresponse of the critical MPB composition of this system.

Structural variations in aromatic 2 pi-electron three-membered rings of the main group elements

Structural variations of different Z pi-aromatic three-membered ring systems of main group elements, especially group 14 and 13 elements as compared to the classical description of cyclopropenyl cation has been reviewed in this article. The structures of heavier analogues as well as group 13 analogues of cyclopropenyl cation showed an emergence of dramatic structural patterns which do not conform, to the general norms of carbon chemistry. Isolobal analogies between the main group fragments have been efficiently used to explain the peculiarities observed in these three-membered ring systems.

New main group ligands for complexation with transition and inner transition elements

Symmetrical and unsymmetrical diphosphinoamines of the type X(2)PN(R)PX(2) and X(2)PN(R)YY' offer vast scope for the synthesis of a variety of transition metal organometallic complexes. Diphosphinoamines can be converted into their dioxides which are also accessible from appropriate (chloro)phosphane oxide precursors. The diphosphazane dioxides form an interesting series of complexes with lanthanide and actinide elements. Structural and spectroscopic studies have been carried out on a wide range of transition metal complexes incorporating linear P-N-P ligands and judiciously functionalized cyclophosphazanes and cyclo-phosphazenes.

NMR Spectroscopic and X-Ray Structural Studies of Two Diazadiphosphetidines

The crystal structures of the two diazadiphosphetidines, [PhNP(OCH2CF3)]2 (1) and [MeNP(NMe2)(O2C6H4)]2 (2) have been determined. The trifluoroethoxy groups in (1) have a trans orientation. The phosphorus chemical shift for (1) is at 189.8 δ. On standing in solution, (1) transforms slowly (∼ 10 days) and almost completely into its 'high-field' (cis) isomer (142.2δ).