Stable Local Structures Research Articles

CFD-DEM numerical study on air impacted packing densification of equiaxed cylindrical particles

A CFD-DEM model was developed to reproduce the packing densification process of mono-sized equiaxed cylindrical particles under air impact. The effects of operating parameters on packing density were firstly studied. Then various microscopic properties of packing structures such as coordination number (CN), contact types, particle orientations, pore features were characterized and compared. And corresponding densification mechanisms were analysed based on particle motion behaviour, local structure evolution, and forces. Results indicate that the air impact can realize the packing densification of cylindrical particles under appropriate conditions. The pore size distribution in the packing of cylindrical particles shows a tail at larger pore sizes compared with that in the packing of equal spheres. Both the size and the sphericity of the pores decrease in the final dense packing; also, more surface-surface and less surface-edge contacts between two particles therein can be formed. More cylindrical particles tend to be in parallel or perpendicular contact with each other to form more stable local structures during air impact. Most particles at higher position move down (direction of gravity/air impact) with about one particle length during the densification process and most particles exhibit translational motion to realize the local rearrangement for pore filling through air impact induced inter-particle forces.

First-principles calculations of stable local structures and electronic structures of magnesium secondary battery cathode materials, MgCo2−xMnxO4 (x = 0, 0.5), in second charged state after first discharge

First-principles calculations of stable local structures and electronic structures of magnesium secondary battery cathode materials, MgCo2−xMnxO4 (x = 0, 0.5), in second charged state after first discharge

Dynamics of 5R-Tg Base Flipping in DNA Duplexes Based on Simulations─Agreement with Experiments and Beyond.

Damaged or mismatched DNA bases are normally thought to be able to flip out of the helical stack, providing enzymes with access to the faulty genetic information otherwise hidden inside the helix. Thymine glycol (Tg) is one of the most common products of nucleic acid damage. However, the static and dynamic structures of DNA duplexes affected by 5R-Tg epimers are still not clearly understood, including the ability of these to undergo spontaneous base flipping. Structural effects of the 5R-Tg epimers on the duplex DNA are herein studied using molecular dynamics together with reliable DFT based calculations. In comparison with the corresponding intact DNA, the cis-5R,6S-Tg epimer base causes little perturbation to the duplex DNA, and a barrier of 4.9 kcal mol–1 is obtained by meta-eABF for cis-5R,6S-Tg base flipping out of the duplex DNA, comparable to the 5.4 kcal mol–1 obtained for the corresponding thymine flipping in intact DNA. For the trans-5R,6R-Tg epimer, three stable local structures were identified, of which the most stable disrupts the Watson–Crick hydrogen-bonded G5/C20 base pair, leading to conformational distortion of the duplex. Interestingly, the relative barrier height of the 5R-Tg flipping is only 1.0 kcal mol–1 for one of these trans-5R,6R-Tg epimers. Water bridge interactions were identified to be essential for 5R-Tg flipping. The study clearly demonstrates the occurrence of partial trans-5R,6R-Tg epimer flipping in solution.

Utilizing Time-Resolved Protein-Induced Fluorescence Enhancement to Identify Stable Local Conformations One α-Synuclein Monomer at a Time.

Using spectroscopic rulers to track multiple conformations of single biomolecules and their dynamics have revolutionized the understanding of structural dynamics and its contributions to biology. While the FRET-based ruler reports on inter-dye distances in the 3-10 nm range, other spectroscopic techniques, such as protein-induced fluorescence enhancement (PIFE), report on the proximity between a dye and a protein surface in the shorter 0-3 nm range. Regardless of the method of choice, its use in measuring freely-diffusing biomolecules one at a time retrieves histograms of the experimental parameter yielding separate centrally-distributed sub-populations of biomolecules, where each sub-population represents either a single conformation that stayed unchanged within milliseconds, or multiple conformations that interconvert much faster than milliseconds, and hence an averaged-out sub-population. In single-molecule FRET, where the reported parameter in histograms is the inter-dye FRET efficiency, an intrinsically disordered protein, such as the α-Synuclein monomer in buffer, was previously reported as exhibiting a single averaged-out sub-population of multiple conformations interconverting rapidly. While these past findings depend on the 3-10 nm range of the FRET-based ruler, we sought to put this protein to the test using single-molecule PIFE, where we track the fluorescence lifetime of site-specific sCy3-labeled α-Synuclein proteins one at a time. Interestingly, using this shorter range spectroscopic proximity sensor, sCy3-labeled α-Synuclein exhibits several lifetime sub-populations with distinctly different mean lifetimes that interconvert in 10-100 ms. These results show that while α-Synuclein might be disordered globally, it nonetheless attains stable local structures. In summary, in this work we highlight the advantage of using different spectroscopic proximity sensors that track local or global structural changes one biomolecule at a time.

2D-LCoLBP: A Learning Two-Dimensional Co-Occurrence Local Binary Pattern for Image Recognition.

The rotation, scale and translation invariance of extracted features have a high significance in image recognition. Local binary pattern (LBP) and LBP-based descriptors have been widely used in image recognition due to feature discrimination and computational efficiency. However, most of the existing LBP-based descriptors have been designed to achieve rotation invariance while fail to achieve scale invariance. Moreover, it is usually difficult to achieve a good trade-off between the feature discrimination and the feature dimension. In this work, a learning 2D co-occurrence LBP termed 2D-LCoLBP is proposed to address these issues. Firstly, a weighted joint histogram is constructed in different neighborhoods and scales of an image to represent the multi-neighborhood and multi-scale LBP (2D-MLBP) and achieve the rotation invariance. A feature learning strategy is then designed to learn the compact and robust descriptor (2D-LCoLBP) from LBP pattern pairs across different scales in the extracted 2D-MLBP to characterize the most stable local structures and achieve the scale invariance, as well as decrease the feature dimension and improve the noise robustness. Finally, a linear SVM classifier is employed for recognition. We applied the proposed 2D-LCoLBP on four image recognition tasks-texture, object, face and food recognition with ten image databases. Experimental results show that 2D-LCoLBP has obviously low feature dimension but outperforms the state-of-the-art LBP-based descriptors in terms of recognition accuracy under noise-free, Gaussian noise and JPEG compression conditions.

Structural and electronic properties of Mo6S3I6 nanowires by newly proposed theoretical compositional ordering

The structural, electronic, and magnetic properties of molybdenum-based nanowires have been actively investigated for their potential applications in nanodevices; however, further advancement is hindered by incomplete knowledge of the electronic and atomic structures of Mo6S3I6. To facilitate further development of Mo6S3I6 nanowire devices, we propose possible atomic structures and corresponding electronic properties of Mo6S3I6 nanowires based on density functional theory. We explored various combinations of atomic structures by changing the positions of sulfur and iodine atoms linked to the two Mo6 octahedra in the Mo6S3I6 unit cell. We found two stable local energy minima structures characterized by elongation of the wire length, and therefore propose 28 possible atomic configurations. We calculated band structures of the newly proposed atomic models and found three structures that behaved as conductors. According to our compositional ordering structural analysis, we concluded that (i) periodic distortion of the bond lengths influences the behavior of the electrons in the system, (ii) the role of sulfur atoms in the bridging plane is important for intramolecular charge transport due to delocalized charge differences, and (iii) the electronic band gap energy is proportional to the integrated Mo-S bonding orbital energy.

Compressive Binary Patterns: Designing a Robust Binary Face Descriptor with Random-Field Eigenfilters.

A binary descriptor typically consists of three stages: image filtering, binarization, and spatial histogram. This paper first demonstrates that the binary code of the maximum-variance filtering responses leads to the lowest bit error rate under Gaussian noise. Then, an optimal eigenfilter bank is derived from a universal assumption on the local stationary random field. Finally, compressive binary patterns (CBP) is designed by replacing the local derivative filters of local binary patterns (LBP) with these novel random-field eigenfilters, which leads to a compact and robust binary descriptor that characterizes the most stable local structures that are resistant to image noise and degradation. A scattering-like operator is subsequently applied to enhance the distinctiveness of the descriptor. Surprisingly, the results obtained from experiments on the FERET, LFW, and PaSC databases show that the scattering CBP (SCBP) descriptor, which is handcrafted by only 6 optimal eigenfilters under restrictive assumptions, outperforms the state-of-the-art learning-based face descriptors in terms of both matching accuracy and robustness. In particular, on probe images degraded with noise, blur, JPEG compression, and reduced resolution, SCBP outperforms other descriptors by a greater than 10 percent accuracy margin.

Folding in Pieces

Circulating inhibitory serpins regulate important physiological processes including inflammation. Misfolding and polymerization of serpins in the endoplasmic reticulum (ER) can lead to both loss-of-function and gain-of-function diseases. The topology of the two-domain, non-sequential serpin fold is complicated with both the αβ and mainly β domains containing regions from near the N- and the C-termini. Despite these complications recent molecular dynamics simulations of serpin folding suggest that significant amounts of local secondary structure forms and rearranges for long-range contact formation resulting in the folded, active serpin. This folding pathway requires a balance between local structural stability and the flexibility/dynamics needed for long-range contact formation. To help test this proposed mechanism, we expressed and characterized N- to C-terminal fragments of the canonical, 394 residue serpin α1-antitrypsin (Alpha1). Even the shortest, 150 residue long, fragment showed cooperative unfolding and surprising stability with a denaturation midpoint of 1.9 M guanidinium hydrochloride. Nonetheless, the far-UV circular dichroism (CD) spectra differ from the spectra predicted for the full-length, native protein. Similarly, fluorescence emission of the longest fragment, 1-323, exhibited the hyper-fluorescent signature of the unfolding/folding intermediate observed during equilibrium denaturation or refolding of full-length Alpha1. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) was used to better define the structure of the fragments. After 10 seconds of deuteration, significant protection is observed in parts of the N-terminal region of the αβ domain, and for longer fragments in some of the β strands that form the core of the β domain. These results suggest that surprisingly stable local structures can be formed by fragments of the serpin Alpha1 and are consistent with models for serpin folding derived from molecular dynamics simulations. The results also suggest that significant amounts of serpin structure might form co-translationally.

Finding consensus stable local optimal structures for aligned RNA sequences and its application to discovering riboswitch elements.

Many non-coding RNAs (ncRNAs) can fold into alternate native structures and perform different biological functions. The computational prediction of an ncRNA's alternate native structures can be conducted by analysing the ncRNA's energy landscape. Previously, we have developed a computational approach, RNASLOpt, to predict alternate native structures for a single RNA. In this paper, in order to improve the accuracy of the prediction, we incorporate structural conservation information among a family of related ncRNA sequences to the prediction. We propose a comparative approach, RNAConSLOpt, to produce all possible consensus SLOpt stack configurations that are conserved on the consensus energy landscape of a family of related ncRNAs. Benchmarking tests show that RNAConSLOpt can reduce the number of candidate structures compared with RNASLOpt, and can predict ncRNAs' alternate native structures accurately. Moreover, an application of the proposed pipeline to bacteria in Bacillus genus has discovered several novel riboswitch candidates.

Local Structures and Chemical Properties of Deprotonated Arginine

The potential energy surface of gaseous deprotonated arginine has been systematically investigated by first principles calculations. At the B3LYP/6-31G(d) level, apart from the identification of several stable local structures, a new global minimum is located which is about 6.56 kJ/mol more stable than what has been reported. The deprotonated arginine molecule has two distinct forms with the deprotonation at the carboxylate group (COO−). These two forms are bridged by a very high energy barrier and possess very different IR spectral profiles. Our calculated proton dissociation energy and gas-phase acidity of arginine molecule are found to be in good agreement with the corresponding experimental results. The predicted geometries, dipole moments, rotational constants, vertical ionization energies and IR spectra of low energy conformers will be useful for future experimental measurements.

Molecular dynamics simulations and statistical coupling analysis reveal functional coevolution network of oncogenic mutations in the CDKN2A–CDK6 complex

Coevolution between proteins is crucial for understanding protein–protein interaction. Simultaneous changes allow a protein complex to maintain its overall structural–functional integrity. In this study, we combined statistical coupling analysis (SCA) and molecular dynamics simulations on the CDK6–CDKN2A protein complex to evaluate coevolution between proteins. We reconstructed an inter-protein residue coevolution network, consisting of 37 residues and 37 interactions. It shows that most of the coevolved residue pairs are spatially proximal. When the mutations happened, the stable local structures were broken up and thus the protein interaction was decreased or inhibited, with a following increased risk of melanoma. The identification of inter-protein coevolved residues in the CDK6–CDKN2A complex can be helpful for designing protein engineering experiments.

Finding stable local optimal RNA secondary structures

Many RNAs, such as riboswitches, can fold into multiple alternate structures and perform different biological functions. These biologically functional structures usually have low free energies in their local energy landscapes and are very stable such that they cannot easily jump out of the current states and fold into other stable conformations. The conformational space of feasible RNA secondary structures is prohibitively large, and accurate prediction of functional structure conformations is challenging. Because the stability of an RNA secondary structure is determined predominantly by energetically favorable helical regions (stacks), we propose to use configurations of putative stacks to represent RNA secondary structures. By considering a reduced conformational space of local optimal stack configurations instead of all feasible RNA structures, we first present an algorithm for enumerating all possible local optimal stack configurations. In addition, we present a fast heuristic algorithm for approximating energy barriers encountered during folding pathways between each pair of local optimal stack configurations and finding all the stable local optimal structures. Benchmark tests have been conducted on several RNA riboswitches, whose alternate secondary structures have been experimentally verified. The benchmark results show that our method can successfully predict the native 'on' and 'off' secondary structures, and better rank them compared with other state-of-art approaches. The software is freely available and can be downloaded at http://genome.ucf.edu/RNASLOpt. shzhang@eecs.ucf.edu. Supplementary data are available at Bioinformatics online.

Simulation of NMR Data Reveals That Proteins’ Local Structures Are Stabilized by Electronic Polarization

Molecular dynamics simulations of NMR backbone relaxation order parameters have been carried out to investigate the polarization effect on the protein's local structure and dynamics for five benchmark proteins (bovine pancreatic trypsin inhibitor, immunoglobulin-binding domain (B1) of streptococcal protein G, bovine apo-calbindin D9K, human interleukin-4 R88Q mutant, and hen egg white lysozyme). In order to isolate the polarization effect from other interaction effects, our study employed both the standard AMBER force field (AMBER03) and polarized protein-specific charges (PPCs) in the MD simulations. The simulated order parameters, employing both the standard nonpolarizable and polarized force fields, are directly compared with experimental data. Our results show that residue-specific order parameters at some specific loop and turn regions are significantly underestimated by the MD simulations using the standard AMBER force field, indicating hyperflexibility of these local structures. Detailed analysis of the structures and dynamic motions of individual residues reveals that the hyperflexibility of these local structures is largely related to the breaking or weakening of relevant hydrogen bonds. In contrast, the agreement with the experimental results is significantly improved and more stable local structures are observed in the MD simulations using the polarized force field. The comparison between theory and experiment provides convincing evidence that intraprotein hydrogen bonds in these regions are stabilized by electronic polarization, which is critical to the dynamical stability of these local structures in proteins.

Size dependence of energy gaps in small carbon clusters: the origin of broadband luminescence

Abstract The visible broadband luminescence from carbon-related films has recently been attributed to the band-tail states caused by the variations in the energy gap of individual sp 2 carbon clusters due to their difference in size and/or shape. In this paper, these band-tail states are classified into two parts: localized and confined. The localized states result from the structural deviation from graphite-like configuration, and the associated luminescence may be described by using the conventional theory for amorphous materials. The confined states are generated due to the existence of stable graphite-like local structures with various sizes and are the main factor for giving efficient, room-temperature luminescence. Our calculations of a series of small hexagonal carbon clusters with first-principle and semi-empirical methods demonstrate that the energy-gap distribution, due to the difference in size, is considerably broad, which may explain the broadband feature of luminescence. Calculations for some tetrahedral clusters were also made for comparison.

Initial studies of the equilibrium folding pathway of staphylococcal nuclease

Spectroscopic methods were used to examine the sequential build up of structure in the denatured state of staphylococcal nuclease. The 'free energy distance' between the native and denatured states was manipulated by altering conditions in solution (for example altering urea or glycerol concentration) and by changing the amino acid sequences. Initial studies employed a fragment of nuclease, referred to as delta 131 delta, which lacks six structural residues from the amino terminus and one structural residue from the carboxy-terminus. Nuclear magnetic resonance analysis of this fragment in solution revealed a modest quantity of dynamic structure which is native-like in character. With the addition of urea, 12 new HN peaks appeared in the 1H-15N correlation spectrum, presumably as a result of the breakdown of residual structure involving the first three beta strands. With the addition of glycerol, there was a rapid increase in the quantity of beta sheet structure detected by circular dichroism spectroscopy. At very high glycerol concentrations, an increase in helical structure became apparent. These data in addition to previously published results suggest that: (i) a beta-meander (strands beta 1-beta 2-beta 3) and the second alpha helix (alpha 2) are among the most stable local structures; (ii) the five-strand beta-barrel forms in a reaction which does not require the presence of several other native substructures; and (iii) the last step on the equilibrium folding pathway may be the formation and packing of the carboxy terminal alpha helix (alpha 3) to give the native state.

Effect of local secondary structure of mRNA on expression of recombinant human lymphotoxin inEscherichia coli

We substituted a few alternative codons close to the N-terminal coding region of human lymphotoxin (LT) gene for natural ones to avoid stable local secondary structures of mRNA, predicted in the 5′-terminal 130 nucleotides of mRNA. With this modification, we have overexpressed a recombinant lymphotoxin (rLT) inEscherichia coli under the control of trc promoter. Most of the produced rLT was a soluble and active form.

Topological Properties of Legendrian Singularities

AbstractA wavefront set is defined to be an image of Legendrian mapping. In this note we prove that generic wavefront sets have stable local topological structures by using Mather's stratification theory.

Gene expression in the polycistronic operons of Escherichia coli heat-labile toxin and cholera toxin: a new model of translational control

A new model is proposed based on the suggestion that stable local secondary structures of mRNA interfere with ribosome movement on mRNA and consequently reduce the translation rate. This model accounts for a different level of translation for each cistron in the polycistronic mRNA of Escherichia coli heat-labile toxin (LT) and cholera toxin. We also conclude that the mRNA secondary structures have been conserved during the evolution of the toxin genes for its functional importance.