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Sample records for folding model analysis

  1. The influence of modeling assumptions on the modal analysis of vocal fold structures

    NASA Astrophysics Data System (ADS)

    Cook, Douglas D.; Mongeau, Luc

    2005-09-01

    Finite-element modal analysis studies of several vocal fold structural models were performed in vacuo under a variety of assumptions. The sensitivity of the vocal folds to changes in geometry and tissue properties was investigated. The Ritz method and the finite-element code ADINA were used to perform linear modal analysis of two-dimensional and three-dimensional models of the human vocal folds. The results allow for comparison and evaluation of various modeling approaches. In particular, the influence of geometrical constraints was shown to introduce errors of varying magnitude depending on the degree of anisotropy of the vocal fold tissue. [Research supported by the National Institute for Deafness and Other Communication Disorders.

  2. Comprehensive, Population-Based Sensitivity Analysis of a Two-Mass Vocal Fold Model

    PubMed Central

    Robertson, Daniel; Zañartu, Matías; Cook, Douglas

    2016-01-01

    Previous vocal fold modeling studies have generally focused on generating detailed data regarding a narrow subset of possible model configurations. These studies can be interpreted to be the investigation of a single subject under one or more vocal conditions. In this study, a broad population-based sensitivity analysis is employed to examine the behavior of a virtual population of subjects and to identify trends between virtual individuals as opposed to investigating a single subject or model instance. Four different sensitivity analysis techniques were used in accomplishing this task. Influential relationships between model input parameters and model outputs were identified, and an exploration of the model’s parameter space was conducted. Results indicate that the behavior of the selected two-mass model is largely dominated by complex interactions, and that few input-output pairs have a consistent effect on the model. Results from the analysis can be used to increase the efficiency of optimization routines of reduced-order models used to investigate voice abnormalities. Results also demonstrate the types of challenges and difficulties to be expected when applying sensitivity analyses to more complex vocal fold models. Such challenges are discussed and recommendations are made for future studies. PMID:26845452

  3. Statistical analysis of native contact formation in the folding of designed model proteins

    NASA Astrophysics Data System (ADS)

    Tiana, Guido; Broglia, Ricardo A.

    2001-02-01

    The time evolution of the formation probability of native bonds has been studied for designed sequences which fold fast into the native conformation. From this analysis a clear hierarchy of bonds emerge: (a) local, fast forming highly stable native bonds built by some of the most strongly interacting amino acids of the protein; (b) nonlocal bonds formed late in the folding process, in coincidence with the folding nucleus, and involving essentially the same strongly interacting amino acids already participating in the fast bonds; (c) the rest of the native bonds whose behavior is subordinated, to a large extent, to that of the strong local and nonlocal native contacts.

  4. Folding of a model three-helix bundle protein: a thermodynamic and kinetic analysis.

    PubMed

    Zhou, Y; Karplus, M

    1999-11-05

    The kinetics and thermodynamics of an off-lattice model for a three-helix bundle protein are investigated as a function of a bias gap parameter that determines the energy difference between native and non-native contacts. A simple dihedral potential is used to introduce the tendency to form right-handed helices. For each value of the bias parameter, 100 trajectories of up to one microsecond are performed. Such statistically valid sampling of the kinetics is made possible by the use of the discrete molecular dynamics method with square-well interactions. This permits much faster simulations for off-lattice models than do continuous potentials. It is found that major folding pathways can be defined, although ensembles with considerable structural variation are involved. The large gap models generally fold faster than those with a smaller gap. For the large gap models, the kinetic intermediates are non-obligatory, while both obligatory and non-obligatory intermediates are present for small gap models. Certain large gap intermediates have a two-helix microdomain with one helix extended outward (as in domain-swapped dimers); the small gap intermediates have more diverse structures. The importance of studying the kinetic, as well as the thermodynamics, of folding for an understanding of the mechanism is discussed and the relation between kinetic and equilibrium intermediates is examined. It is found that the behavior of this model system has aspects that encompass both the "new" view and the "old" view of protein folding.

  5. Cerebral Cortical Folding Analysis with Multivariate Modeling and Testing: Studies on Gender Differences and Neonatal Development

    PubMed Central

    Awate, Suyash P.; Yushkevich, Paul A.; Song, Zhuang; Licht, Daniel J.; Gee, James C.

    2010-01-01

    This paper presents a novel statistical framework for human cortical folding pattern analysis that relies on a rich multivariate descriptor of folding patterns in a region of interest (ROI). The ROI-based approach avoids problems faced by spatial-normalization-based approaches stemming from the deficiency of homologous features between typical human cerebral cortices. Unlike typical ROI-based methods that summarize folding by a single number, the proposed descriptor unifies multiple characteristics of surface geometry in a high-dimensional space (hundreds/thousands of dimensions). In this way, the proposed framework couples the reliability of ROI-based analysis with the richness of the novel cortical folding pattern descriptor. This paper presents new mathematical insights into the relationship of cortical complexity with intra-cranial volume (ICV). It shows that conventional complexity descriptors implicitly handle ICV Differences in Different ways, thereby lending Different meanings to “complexity”. The paper proposes a new application of a non-parametric permutation-based approach for rigorous statistical hypothesis testing with multivariate cortical descriptors. The paper presents two cross-sectional studies applying the proposed framework to study folding Differences between genders and in neonates with complex congenital heart disease. Both studies lead to novel interesting results. PMID:20630489

  6. Moho topography, ranges and folds of Tibet by analysis of global gravity models and GOCE data

    PubMed Central

    Shin, Young Hong; Shum, C.K.; Braitenberg, Carla; Lee, Sang Mook; Na, Sung -Ho; Choi, Kwang Sun; Hsu, Houtse; Park, Young-Sue; Lim, Mutaek

    2015-01-01

    The determination of the crustal structure is essential in geophysics, as it gives insight into the geohistory, tectonic environment, geohazard mitigation, etc. Here we present the latest advance on three-dimensional modeling representing the Tibetan Mohorovičić discontinuity (topography and ranges) and its deformation (fold), revealed by analyzing gravity data from GOCE mission. Our study shows noticeable advances in estimated Tibetan Moho model which is superior to the results using the earlier gravity models prior to GOCE. The higher quality gravity field of GOCE is reflected in the Moho solution: we find that the Moho is deeper than 65 km, which is twice the normal continental crust beneath most of the Qinghai-Tibetan plateau, while the deepest Moho, up to 82 km, is located in western Tibet. The amplitude of the Moho fold is estimated to be ranging from −9 km to 9 km with a standard deviation of ~2 km. The improved GOCE gravity derived Moho signals reveal a clear directionality of the Moho ranges and Moho fold structure, orthogonal to deformation rates observed by GPS. This geophysical feature, clearly more evident than the ones estimated using earlier gravity models, reveals that it is the result of the large compressional tectonic process. PMID:26114224

  7. Elastic {sup 16}O+{sup 20}Ne scattering from a folding model analysis

    SciTech Connect

    Yang Yongxu; Li Qingrun

    2011-07-15

    A folding potential for elastic {sup 16}O+{sup 20}Ne scattering is constructed based on the four-{alpha}-particle model for the {sup 16}O nucleus and the {alpha}+{sup 16}O model for the {sup 20}Ne nucleus. The elastic scattering angular distributions of the {sup 16}O+{sup 20}Ne system in the energy range of E{sub c.m.}=24.5-35.5 MeV are calculated by use of the {alpha}-folding potential obtained. The calculations show that the experimental data can be reasonably well described. The surface term in the imaginary potential has a significant effect on the calculations of the cross section at large angles for the energies considered.

  8. Mesoscale Modeling of Chromatin Folding

    NASA Astrophysics Data System (ADS)

    Schlick, Tamar

    2009-03-01

    Eukaryotic chromatin is the fundamental protein/nucleic acid unit that stores the genetic material. Understanding how chromatin fibers fold and unfold in physiological conditions is important for interpreting fundamental biological processes like DNA replication and transcription regulation. Using a mesoscopic model of oligonucleosome chains and tailored sampling protocols, we elucidate the energetics of oligonucleosome folding/unfolding and the role of each histone tail, linker histones, and divalent ions in regulating chromatin structure. The resulting compact topologies reconcile features of the zigzag model with straight linker DNAs with the solenoid model with bent linker DNAs for optimal fiber organization and reveal dynamic and energetic aspects involved.

  9. Modelling of lateral fold growth and fold linkage: Applications to fold-and-thrust belt tectonics

    NASA Astrophysics Data System (ADS)

    Grasemann, Bernhard; Schmalholz, Stefan

    2013-04-01

    We use a finite element model to investigate the three-dimensional fold growth and interference of two initially isolated fold segments. The most critical parameter, which controls the fold linkage mode, is the phase difference between the laterally growing fold hinge lines: 1) "Linear-linkage" yields a sub-cylindrical fold with a saddle at the location where the two initial folds linked. 2) "Oblique-linkage" produces a curved fold resembling a Type II refold structure. 3) "Oblique-no-linkage" results in two curved folds with fold axes plunging in opposite directions. 4) "Linear-no-linkage" yields a fold train of two separate sub-cylindrical folds with fold axes plunging in opposite directions. The transition from linkage to no-linkage occurs when the fold separation between the initially isolated folds is slightly larger than one half of the low-amplitude fold wavelength. The model results compare well with previously published plasticine analogue models and can be directly applied to the investigation of fold growth history in fold-and-thust belts. An excellent natural example of lateral fold linkage is described from the Zagros fold-and-thrust belt in the Kurdistan Region of Iraq. The fold growth in this region is not controlled by major thrust faults but the shortening of the Paleozoic to Cenozoic passive margin sediments of the Arabian plate occurred mainly by detachment folding. The sub-cylindrical anticlines with hinge-parallel lengths of more than 50 km have not developed from single sub-cylindrical embryonic folds but they have merged from different fold segments that joined laterally during fold amplification and lateral fold growth. Linkage points are marked by geomorphological saddle points which are structurally the lowermost points of antiforms and points of principal curvatures with opposite sign. Linkage points can significantly influence the migration of mineral-rich fluids and hydrocarbons and are therefore of great economic importance.

  10. Cluster folding model analysis of 3He elastic and inelastic scattering from 12C

    NASA Astrophysics Data System (ADS)

    Khallaf, S. A. E.; Nossair, A. M. A.; Ebrahim, A. A.; Ebraheem, Awad A.

    2003-02-01

    Angular distributions of differential cross sections for the 12C( 3He, 3He) 12C, 12C( 3He, 3He) 12C ∗ reactions at E=72 MeV have been analyzed with a double folding cluster model DFC based on five sets of the effective N-N interaction of Gaussian form with different parameters. The transition to the (2 +; 4.44 MeV) state in 12C is studied and the deformation length δ2 is extracted. It is found that the extracted deformation length is sensitive to the nuclear model used and it is similar to the corresponding value found in the literature.

  11. Folding Model Analysis of Elastic Scattering of 11B from Light, Medium, and Heavy Nuclei

    NASA Astrophysics Data System (ADS)

    Aygun, M.

    2016-11-01

    The elastic scattering angular distributions of 11B projectile on light, medium, and heavy target nuclei including 7Li, 9Be, 12C, 16O, 24,25,26Mg, 27Al, 28Si, 40Ca, 58Ni, 59Co, 60Ni, 197Au, 208Pb, and 209Bi have been analyzed at various incident energies. The theoretical results have been obtained by using two different nuclear potentials within the framework of the optical model (OM). Firstly, the double folding potential for real part and the Wood—Saxon (WS) potential for imaginary part have been applied. Secondly, the calculations with double folding potential for both real and imaginary part have been performed and compared with the experimental data. It has been seen that the results are in very good agreement with the experimental data. Also, the volume integrals and cross-sections for each reaction have been obtained. Finally, a new and simple formula for the imaginary potential depth has been derived to clarify the nuclear interactions of 11B nucleus at low energy reactions.

  12. Polyphase tertiary fold-and-thrust tectonics in the Belluno Dolomites: new mapping, kinematic analysis, and 3D modelling

    NASA Astrophysics Data System (ADS)

    Chistolini, Filippo; Bistacchi, Andrea; Massironi, Matteo; Consonni, Davide; Cortinovis, Silvia

    2014-05-01

    performed a dip-domain analysis that allowed to categorize the different fold limbs and reduce the uncertainty in the reconstruction of the fault network topology in map view. This enabled us to reconstruct a high-quality, low-uncertainty 3D structural and geological model, which unambiguously proves that deformations with a top-to-WSW Dinaric transport direction propagate farther to the west than previously supposed in this part of the Southern Alps. Our new structural reconstruction of the Vajont valley have also clarified the structural control on the 1963 catastrophic landslide (which caused over 2000 losses). Besides being a challenging natural laboratory for testing analysis and modelling methodologies to be used when reconstructing in 3D this kind of complex interference structures, the Vajont area also provides useful clues on the still-enigmatic structures in the frontal part of the Friuli-Venetian Southern Alps, buried in the Venetian Plain foredeep. These include active seismogenic thrust-faults and, at the same time, represent a growing interest for the oil industry.

  13. Strain modelling of extensional fault-propagation folds based on an improved non-linear trishear model: A numerical simulation analysis

    NASA Astrophysics Data System (ADS)

    Zhao, Haonan; Guo, Zhaojie; Yu, Xiangjiang

    2017-02-01

    This paper focuses on the strain modelling of extensional fault-propagation folds to reveal the effects of key factors on the strain accumulation and the relationship between the geometry and strain distribution of fault-related folds. A velocity-geometry-strain method is proposed for the analysis of the total strain and its accumulation process within the trishear zone of an extensional fault-propagation fold. This paper improves the non-linear trishear model proposed by Jin and Groshong (2006). Based on the improved model, the distribution of the strain rate within the trishear zone and the total strain are obtained. The numerical simulations of different parameters performed in this study indicate that the shape factor R, the total apical angle, and the P/S ratio control the final geometry and strain distribution of extensional fault-propagation folds. A small P/S ratio, a small apical angle, and an R value far greater or far smaller than 1 produce an asymmetric, narrow, and strongly deformed trishear zone. The velocity-geometry-strain analysis method is applied to two natural examples from Big Brushy Canyon in Texas and the northwestern Red Sea in Egypt. The strain distribution within the trishear zone is closely related to the geometry of the folds.

  14. Implicit modeling of folds and overprinting deformation

    NASA Astrophysics Data System (ADS)

    Laurent, Gautier; Ailleres, Laurent; Grose, Lachlan; Caumon, Guillaume; Jessell, Mark; Armit, Robin

    2016-12-01

    Three-dimensional structural modeling is gaining importance for a broad range of quantitative geoscientific applications. However, existing approaches are still limited by the type of structural data they are able to use and by their lack of structural meaning. Most techniques heavily rely on spatial data for modeling folded layers, but are unable to completely use cleavage and lineation information for constraining the shape of modeled folds. This lack of structural control is generally compensated by expert knowledge introduced in the form of additional interpretive data such as cross-sections and maps. With this approach, folds are explicitly designed by the user instead of being derived from data. This makes the resulting structures subjective and deterministic. This paper introduces a numerical framework for modeling folds and associated foliations from typical field data. In this framework, a parametric description of fold geometry is incorporated into the interpolation algorithm. This way the folded geometry is implicitly derived from observed data, while being controlled through structural parameters such as fold wavelength, amplitude and tightness. A fold coordinate system is used to support the numerical description of fold geometry and to modify the behavior of classical structural interpolators. This fold frame is constructed from fold-related structural elements such as axial foliations, intersection lineations, and vergence. Poly-deformed terranes are progressively modeled by successively modeling each folding event going backward through time. The proposed framework introduces a new modeling paradigm, which enables the building of three-dimensional geological models of complex poly-deformed terranes. It follows a process based on the structural geologist approach and is able to produce geomodels that honor both structural data and geological knowledge.

  15. Analysis of folded pulse forming line operation.

    PubMed

    Domonkos, M T; Watrous, J; Parker, J V; Cavazos, T; Slenes, K; Heidger, S; Brown, D; Wilson, D

    2014-09-01

    A compact pulse forming line (CPFL) concept based on a folded transmission line and high-breakdown strength dielectric was explored through an effort combining proof-of-principle experiments with electromagnetic modeling. A small-scale folded CPFL was fabricated using surface-mount ceramic multilayer capacitors. The line consisted of 150 capacitors close-packed in parallel and delivered a 300 ns flat-top pulse. The concept was carried to a 10 kV class device using a polymer-ceramic nanocomposite dielectric with a permittivity of 37.6. The line was designed for a 161 ns FWHM length pulse into a matched load. The line delivered a 110 ns FWHM pulse, and the pulse peak amplitude exceeded the matched load ideal. Transient electromagnetic analysis using the particle-in-cell code ICEPIC was conducted to examine the nature of the unexpected pulse shortening and distortion. Two-dimensional analysis failed to capture the anomalous behavior. Three-dimensional analysis replicated the pulse shape and revealed that the bends were largely responsible for the pulse shortening. The bends not only create the expected reflection of the incident TEM wave but also produce a non-zero component of the Poynting vector perpendicular to the propagation direction of the dominant electromagnetic wave, resulting in power flow largely external to the PFL. This analysis explains both the pulse shortening and the amplitude of the pulse.

  16. A Computational Model of Cerebral Cortex Folding

    PubMed Central

    Nie, Jingxin; Guo, Lei; Li, Gang; Faraco, Carlos; Miller, L Stephen; Liu, Tianming

    2010-01-01

    The geometric complexity and variability of the human cerebral cortex has long intrigued the scientific community. As a result, quantitative description of cortical folding patterns and the understanding of underlying folding mechanisms have emerged as important research goals. This paper presents a computational 3-dimensional geometric model of cerebral cortex folding initialized by MRI data of a human fetal brain and deformed under the governance of a partial differential equation modeling cortical growth. By applying different simulation parameters, our model is able to generate folding convolutions and shape dynamics of the cerebral cortex. The simulations of this 3D geometric model provide computational experimental support to the following hypotheses: 1) Mechanical constraints of the skull regulate the cortical folding process. 2) The cortical folding pattern is dependent on the global cell growth rate of the whole cortex. 3) The cortical folding pattern is dependent on relative rates of cell growth in different cortical areas. 4) The cortical folding pattern is dependent on the initial geometry of the cortex. PMID:20167224

  17. Mechanical Models of Fault-Related Folding

    SciTech Connect

    Johnson, A. M.

    2003-01-09

    The subject of the proposed research is fault-related folding and ground deformation. The results are relevant to oil-producing structures throughout the world, to understanding of damage that has been observed along and near earthquake ruptures, and to earthquake-producing structures in California and other tectonically-active areas. The objectives of the proposed research were to provide both a unified, mechanical infrastructure for studies of fault-related foldings and to present the results in computer programs that have graphical users interfaces (GUIs) so that structural geologists and geophysicists can model a wide variety of fault-related folds (FaRFs).

  18. The Numba ductile deformation zone (northwest Cameroon): A geometric analysis of folds based on the Fold Profiler method

    NASA Astrophysics Data System (ADS)

    Njanko, T.; Chatué, C. Njiki; Kwékam, M.; Nké, B. E. Bella; Sandjo, A. F. Yakeu; Fozing, E. M.

    2017-03-01

    The Numba ductile deformation zone (NDDZ) is characterised by folds recorded during the three deformation phases that affected the banded amphibole gneiss. Fold-shape analyses using the program Fold Profiler with the aim to show the importance of folding events in the structural analysis of the NDDZ and its contribution to the Pan-African orogeny in central Africa have been made. Classical field method, conic sections method and Ramsay's fold classification method were applied to (i) have the general orientation of folds, (ii) analyze the fold shapes and (iii) classify the geometry of the folded bands. Fold axes in banded amphibole gneiss plunge moderately (<15°) towards the NNE or SSW. The morphology of F1, F2 and F3 folds in the study area clearly points to (i) Z-shape folds with SE vergence and (ii) a dextral sense of shear motion. Conic section method reveals two dominant families: F1 and F3 folds belong to parabolic shape folds, while F2 folds belong to parabolic shape and hyperbolic shape folds. Ramsay's scheme emphasizes class 1C (for F1, F2 and F3 folds) and class 3 (for F2 folds) as main fold classes. The co-existence of the various fold shapes can be explained by (i) the structuration of the banded gneiss, (ii) the folding mechanisms that associate shear with a non-least compressive or flattening component in a ductile shear zone and (iii) the change in rheological properties of the band during the period of fold formation. These data allow us to conclude that the Numba region underwent ductile dextral shear and can be integrated (i) in a correlation model with the Central Cameroon Shear Zone (CCSZ) and associated syn-kinematic intrusions and (ii) into the tectonic model of Pan-African belt of central Africa in Cameroon.

  19. Regional structural analysis and velocity model (Vp) of the Chittagong-Myanmar Fold and Thrust Belt, Bangladesh

    NASA Astrophysics Data System (ADS)

    Burgi, P.; Hubbard, J.; Peterson, D. E.; Akhter, S. H.

    2015-12-01

    Bangladesh sits on the seismically active Chittagong-Myanmar Fold and Thrust Belt (CMFB), a partially exposed accretionary prism associated with the India-Eurasia collision. Ground shaking due to local and regional earthquakes presents a potential hazard to Bangladesh, one of the most populated areas in the world. In order to constrain this hazard, we first investigate potential seismic sources (active faults), and second we analyze the material through which seismic energy propagates. To address potential earthquake sources, we focus on the Comilla Anticline, which is the frontal-most exposed structure of the CMFB as well as the most proximal to the capital city of Dhaka. We present several industry-acquired and depth-converted seismic reflection profiles, which exhibit an asymmetric detachment fold rising from a relatively deep décollement (5-6 km). Because there is no strong evidence for an associated emergent thrust, this actively growing fold may have low seismic potential. We place this work into a regional context by integrating previous research of CMFB structures to create a regional structural model, which reveals laterally varying wedge geometry. To address ground shaking, the second component of this work, we assess stacking velocities from our seismic reflection data in conjunction with sonic log velocities from several locations in Bangladesh. These data show varying velocity versus depth trends by region. Following similar, data-rich studies performed in the Los Angeles and adjacent basins, we use data and theory-driven fitting techniques to analyze depth-velocity trends for these different regions, and interpolate to create a laterally varying regional seismic velocity model. Velocities generally slow from east to west, consistent with the younging trend as we move from older, exhumed CMFB formations to recent and undeformed deposits.

  20. Predictive Computational Modeling of Chromatin Folding

    NASA Astrophysics Data System (ADS)

    di Pierro, Miichele; Zhang, Bin; Wolynes, Peter J.; Onuchic, Jose N.

    In vivo, the human genome folds into well-determined and conserved three-dimensional structures. The mechanism driving the folding process remains unknown. We report a theoretical model (MiChroM) for chromatin derived by using the maximum entropy principle. The proposed model allows Molecular Dynamics simulations of the genome using as input the classification of loci into chromatin types and the presence of binding sites of loop forming protein CTCF. The model was trained to reproduce the Hi-C map of chromosome 10 of human lymphoblastoid cells. With no additional tuning the model was able to predict accurately the Hi-C maps of chromosomes 1-22 for the same cell line. Simulations show unknotted chromosomes, phase separation of chromatin types and a preference of chromatin of type A to sit at the periphery of the chromosomes.

  1. Observation of a tropopause fold by MARA VHF wind-profiler radar and ozonesonde at Wasa, Antarctica: comparison with ECMWF analysis and a WRF model simulation

    NASA Astrophysics Data System (ADS)

    Mihalikova, M.; Kirkwood, S.; Arnault, J.; Mikhaylova, D.

    2012-09-01

    Tropopause folds are one of the mechanisms of stratosphere-troposphere exchange, which can bring ozone rich stratospheric air to low altitudes in the extra-tropical regions. They have been widely studied at northern mid- or high latitudes, but so far almost no studies have been made at mid- or high southern latitudes. The Moveable Atmospheric Radar for Antarctica (MARA), a 54.5 MHz wind-profiler radar, has operated at the Swedish summer station Wasa, Antarctica (73° S, 13.5° W) during austral summer seasons from 2007 to 2011 and has observed on several occasions signatures similar to those caused by tropopause folds at comparable Arctic latitudes. Here a case study is presented of one of these events when an ozonesonde successfully sampled the fold. Analysis from European Center for Medium Range Weather Forecasting (ECMWF) is used to study the circumstances surrounding the event, and as boundary conditions for a mesoscale simulation using the Weather Research and Forecasting (WRF) model. The fold is well resolved by the WRF simulation, and occurs on the poleward side of the polar jet stream. However, MARA resolves fine-scale layering associated with the fold better than the WRF simulation.

  2. Modelling RNA folding under mechanical tension

    PubMed Central

    VIEREGG, JEFFREY R.; TINOCO, IGNACIO

    2006-01-01

    We investigate the thermodynamics and kinetics of RNA unfolding and refolding under mechanical tension. The hierarchical nature of RNA structure and the existence of thermodynamic parameters for base pair formation based on nearest-neighbour interactions allows modelling of sequence-dependent folding dynamics for any secondary structure. We calculate experimental observables such as the transition force for unfolding, the end-to-end distribution function and its variance, as well as kinetic information, for a representative RNA sequence and for a sequence containing two homopolymer segments: A.U and G.C. PMID:16969426

  3. A Canonical Biomechanical Vocal Fold Model

    PubMed Central

    Bhattacharya, Pinaki; Siegmund, Thomas H.

    2012-01-01

    Summary The present article aimed at constructing a canonical geometry of the human vocal fold (VF) from subject-specific image slice data. A computer-aided design approach automated the model construction. A subject-specific geometry available in literature, three abstractions (which successively diminished in geometric detail) derived from it, and a widely used quasi two-dimensional VF model geometry were used to create computational models. The first three natural frequencies of the models were used to characterize their mechanical response. These frequencies were determined for a representative range of tissue biomechanical properties, accounting for underlying VF histology. Compared with the subject-specific geometry model (baseline), a higher degree of abstraction was found to always correspond to a larger deviation in model frequency (up to 50% in the relevant range of tissue biomechanical properties). The model we deemed canonical was optimally abstracted, in that it significantly simplified the VF geometry compared with the baseline geometry but can be recalibrated in a consistent manner to match the baseline response. Models providing only a marginally higher degree of abstraction were found to have significant deviation in predicted frequency response. The quasi two-dimensional model presented an extreme situation: it could not be recalibrated for its frequency response to match the subject-specific model. This deficiency was attributed to complex support conditions at anterior-posterior extremities of the VFs, accentuated by further issues introduced through the tissue biomechanical properties. In creating canonical models by leveraging advances in clinical imaging techniques, the automated design procedure makes VF modeling based on subject-specific geometry more realizable. PMID:22209063

  4. Dissecting Ubiquitin Folding Using the Self-Organized Polymer Model.

    PubMed

    Reddy, Govardhan; Thirumalai, D

    2015-08-27

    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 (Tm'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 Tm, Ub folds in a two-state manner at low and neutral pH. Clustering analysis of the conformations sampled in equilibrium folding trajectories at Tm, 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 Pfold analysis, are homogeneous and globular with most of the secondary and tertiary structures being native-like. Many of our findings for

  5. Fold assessment for comparative protein structure modeling

    PubMed Central

    Melo, Francisco; Sali, Andrej

    2007-01-01

    Accurate and automated assessment of both geometrical errors and incompleteness of comparative protein structure models is necessary for an adequate use of the models. Here, we describe a composite score for discriminating between models with the correct and incorrect fold. To find an accurate composite score, we designed and applied a genetic algorithm method that searched for a most informative subset of 21 input model features as well as their optimized nonlinear transformation into the composite score. The 21 input features included various statistical potential scores, stereochemistry quality descriptors, sequence alignment scores, geometrical descriptors, and measures of protein packing. The optimized composite score was found to depend on (1) a statistical potential z-score for residue accessibilities and distances, (2) model compactness, and (3) percentage sequence identity of the alignment used to build the model. The accuracy of the composite score was compared with the accuracy of assessment by single and combined features as well as by other commonly used assessment methods. The testing set was representative of models produced by automated comparative modeling on a genomic scale. The composite score performed better than any other tested score in terms of the maximum correct classification rate (i.e., 3.3% false positives and 2.5% false negatives) as well as the sensitivity and specificity across the whole range of thresholds. The composite score was implemented in our program MODELLER-8 and was used to assess models in the MODBASE database that contains comparative models for domains in approximately 1.3 million protein sequences. PMID:17905832

  6. Fold assessment for comparative protein structure modeling.

    PubMed

    Melo, Francisco; Sali, Andrej

    2007-11-01

    Accurate and automated assessment of both geometrical errors and incompleteness of comparative protein structure models is necessary for an adequate use of the models. Here, we describe a composite score for discriminating between models with the correct and incorrect fold. To find an accurate composite score, we designed and applied a genetic algorithm method that searched for a most informative subset of 21 input model features as well as their optimized nonlinear transformation into the composite score. The 21 input features included various statistical potential scores, stereochemistry quality descriptors, sequence alignment scores, geometrical descriptors, and measures of protein packing. The optimized composite score was found to depend on (1) a statistical potential z-score for residue accessibilities and distances, (2) model compactness, and (3) percentage sequence identity of the alignment used to build the model. The accuracy of the composite score was compared with the accuracy of assessment by single and combined features as well as by other commonly used assessment methods. The testing set was representative of models produced by automated comparative modeling on a genomic scale. The composite score performed better than any other tested score in terms of the maximum correct classification rate (i.e., 3.3% false positives and 2.5% false negatives) as well as the sensitivity and specificity across the whole range of thresholds. The composite score was implemented in our program MODELLER-8 and was used to assess models in the MODBASE database that contains comparative models for domains in approximately 1.3 million protein sequences.

  7. Kinematic Analysis of Fold-Thrust-Belt Using Integrated Analogue Sandbox Modeling and 3D Palinspatic Reconstructions in Babar-Selaru Area, Banda Sea Region, Indonesia

    NASA Astrophysics Data System (ADS)

    Sapiie, Benyamin; Hadiana, Meli; Kurniawan, Ade; Daniel, Dicky; Danio, Harya; Fujimoto, Masamichi; Ohara, Michio; Alam Perdana, Lisnanda; Saputra, Afif

    2016-04-01

    Kinematic analysis of Babar-Selaru fold-thrust-belt is challenging and often difficult particularly in conducting seismic interpretation due to complex structural geometries. Resolving such as issue, in this study we proposed to use integrated seismic interpretation, analogue sandbox modeling and 3D palinspatic reconstructions. This paper is presented results of detail kinematic analysis for understanding tectonic evolution as well as mechanism of fold-thrust-belt in relation to their hydrocarbon prospect. Babar-Selaru Area is located within the collisional boundary between Australian continental margin and Banda Arc region of Indonesia. The area is characterized by complex deformation zone of fold-thrust-belt, involving Mesozoic and Tertiary sedimentary sequences of Australian continental margin. The age of deformation is ranging from 8-5 Ma. Seismic interpretations show two styles of faults developed in the area, which are thrust and normal faults system. The last deformation observed in the Babar Selaru area is controlled by south verging imbricated thin-skinned thrust fault system, with the staircase style of fault detachment. Although, both structural styles occurred in separated locations, they are formed not only in the same time but also related in time and space. Total extension is ranging from 1-3 % where average shortening is in the order of 35-38%. Sandbox modeling is an effective way to study and understand the style, pattern and geometry of the deformed sedimentary sequences in the study area. Based on comparison of five settings experiments (mainly different geological boundary condition) with more than 50 different modeling; deformation is particularly controlled by types and thickness of lithology package and detachment geometry. These two parameters were quite sensitive in generating different deformation style and pattern in Babar-Selaru fold-thrust-belt. Therefore, choosing the right combination of stratigraphy model and material setting are

  8. A Rat Excised Larynx Model of Vocal Fold Scar

    ERIC Educational Resources Information Center

    Welham, Nathan V.; Montequin, Douglas W.; Tateya, Ichiro; Tateya, Tomoko; Choi, Seong Hee; Bless, Diane M.

    2009-01-01

    Purpose: To develop and evaluate a rat excised larynx model for the measurement of acoustic, aerodynamic, and vocal fold vibratory changes resulting from vocal fold scar. Method: Twenty-four 4-month-old male Sprague-Dawley rats were assigned to 1 of 4 experimental groups: chronic vocal fold scar, chronic vocal fold scar treated with 100-ng basic…

  9. Visualization of Protein Folding Funnels in Lattice Models

    PubMed Central

    Oliveira, Antonio B.; Fatore, Francisco M.; Paulovich, Fernando V.; Oliveira, Osvaldo N.; Leite, Vitor B. P.

    2014-01-01

    Protein folding occurs in a very high dimensional phase space with an exponentially large number of states, and according to the energy landscape theory it exhibits a topology resembling a funnel. In this statistical approach, the folding mechanism is unveiled by describing the local minima in an effective one-dimensional representation. Other approaches based on potential energy landscapes address the hierarchical structure of local energy minima through disconnectivity graphs. In this paper, we introduce a metric to describe the distance between any two conformations, which also allows us to go beyond the one-dimensional representation and visualize the folding funnel in 2D and 3D. In this way it is possible to assess the folding process in detail, e.g., by identifying the connectivity between conformations and establishing the paths to reach the native state, in addition to regions where trapping may occur. Unlike the disconnectivity maps method, which is based on the kinetic connections between states, our methodology is based on structural similarities inferred from the new metric. The method was developed in a 27-mer protein lattice model, folded into a 3×3×3 cube. Five sequences were studied and distinct funnels were generated in an analysis restricted to conformations from the transition-state to the native configuration. Consistent with the expected results from the energy landscape theory, folding routes can be visualized to probe different regions of the phase space, as well as determine the difficulty in folding of the distinct sequences. Changes in the landscape due to mutations were visualized, with the comparison between wild and mutated local minima in a single map, which serves to identify different trapping regions. The extension of this approach to more realistic models and its use in combination with other approaches are discussed. PMID:25010343

  10. Tectonic analysis of folds in the Colorado plateau of Arizona

    NASA Technical Reports Server (NTRS)

    Davis, G. H.

    1975-01-01

    Structural mapping and analysis of folds in Phanerozoic rocks in northern Arizona, using LANDSAT-1 imagery, yielded information for a tectonic model useful in identifying regional fracture zones within the Colorado Plateau tectonic province. Since the monoclines within the province developed as a response to differential movements of basement blocks along high-angle faults, the monoclinal fold pattern records the position and trend of many elements of the regional fracture system. The Plateau is divided into a mosaic of complex, polyhedral crustal blocks whose steeply dipping faces correspond to major fracture zones. Zones of convergence and changes in the trend of the monoclinal traces reveal the corners of the blocks. Igneous (and salt) diapirs have been emplaced into many of the designated zones of crustal weakness. As loci of major fracturing, folding, and probably facies changes, the fractures exert control on the entrapment of oil and gas.

  11. Learning generative models for protein fold families.

    PubMed

    Balakrishnan, Sivaraman; Kamisetty, Hetunandan; Carbonell, Jaime G; Lee, Su-In; Langmead, Christopher James

    2011-04-01

    We introduce a new approach to learning statistical models from multiple sequence alignments (MSA) of proteins. Our method, called GREMLIN (Generative REgularized ModeLs of proteINs), learns an undirected probabilistic graphical model of the amino acid composition within the MSA. The resulting model encodes both the position-specific conservation statistics and the correlated mutation statistics between sequential and long-range pairs of residues. Existing techniques for learning graphical models from MSA either make strong, and often inappropriate assumptions about the conditional independencies within the MSA (e.g., Hidden Markov Models), or else use suboptimal algorithms to learn the parameters of the model. In contrast, GREMLIN makes no a priori assumptions about the conditional independencies within the MSA. We formulate and solve a convex optimization problem, thus guaranteeing that we find a globally optimal model at convergence. The resulting model is also generative, allowing for the design of new protein sequences that have the same statistical properties as those in the MSA. We perform a detailed analysis of covariation statistics on the extensively studied WW and PDZ domains and show that our method out-performs an existing algorithm for learning undirected probabilistic graphical models from MSA. We then apply our approach to 71 additional families from the PFAM database and demonstrate that the resulting models significantly out-perform Hidden Markov Models in terms of predictive accuracy.

  12. Palaeomagnetic analysis of plunging fold structures: Errors and a simple fold test

    NASA Astrophysics Data System (ADS)

    Stewart, Simon A.

    1995-02-01

    The conventional corrections for bedding dip in palaeomagnetic studies involve either untilting about strike or about some inclined axis—the choice is usually governed by the perceived fold hinge orientation. While it has been recognised that untilting bedding about strike can be erroneous if the beds lie within plunging fold structures, there are several types of fold which have plunging hinges, but whose limbs have rotated about horizontal axes. Examples are interference structures and forced folds; restoration about inclined axes may be incorrect in these cases. The angular errors imposed upon palaeomagnetic lineation data via the wrong choice of rotation axis during unfolding are calculated here and presented for lineations in any orientation which could be associated with an upright, symmetrical fold. This extends to palaeomagnetic data previous analyses which were relevant to bedding-parallel lineations. This numerical analysis highlights the influence of various parameters which describe fold geometry and relative lineation orientation upon the angular error imparted to lineation data by the wrong unfolding method. The effect of each parameter is described, and the interaction of the parameters in producing the final error is discussed. Structural and palaeomagnetic data are cited from two field examples of fold structures which illustrate the alternative kinematic histories. Both are from thin-skinned thrust belts, but the data show that one is a true plunging fold, formed by rotation about its inclined hinge, whereas the other is an interference structure produced by rotation of the limbs about non-parallel horizontal axes. Since the angle between the palaeomagnetic lineations and the inclined fold hinge is equal on both limbs in the former type of structure, but varies from limb to limb in the latter, a simple test can be defined which uses palaeomagnetic lineation data to identify rotation axes and hence fold type. This test can use pre- or syn-folding

  13. Analysis of 12C+12C Elastic and Inelastic Scatterings in the Framework of the Cluster Double Folding Model and Coupled-Channels Mechanism

    NASA Astrophysics Data System (ADS)

    Hassanain, M. A.

    2011-08-01

    A double folding cluster (DFC) model is proposed for the analysis of (12) C+(12) C elastic and inelastic scatterings. The DFC procedure is performed using the alpha-clusters structure of (12) C nucleus. Angular distributions of the (12) C+(12) C elastic and inelastic scatterings in the energy range 70.7-126 MeV were analyzed using the derived DFC potentials in the framework of the coupled-channels (CC) mechanism. Successful descriptions of the data are obtained over the full measured angular range without the need to normalize the DFC potentials. Furthermore, the deduced deformation length and the quadrupole deformation parameter are quite consistent with the corresponding electromagnetic measurements.

  14. Folding model analysis of pion elastic and inelastic scattering from {sup 6}Li and {sup 12}C

    SciTech Connect

    Ebrahim, A. A.

    2013-04-15

    {pi}{sup {+-}}-Nucleus scattering cross sections are calculated applying the Watanabe superposition model with a phenomenological Woods-Saxon potential. The phenomenological potential parameters are searched for {pi}{sup {+-}} scattering from {sup 6}Li and {sup 12}C to reproduce not only differential elastic cross sections but also inelastic and total and reaction cross sections at pion kinetic energies from 50 to 672 MeV. The optical potentials of {sup 6}Li and {sup 12}C are calculated in terms of the alpha particle and deuteron optical potentials. Inelastic scattering has been analyzed using the distorted waves from elastic-scattering data. The values of deformation lengths thus obtained compare very well with the ones reported earlier.

  15. Computational analysis of hydrogenated graphyne folding

    NASA Astrophysics Data System (ADS)

    Lenear, Christopher; Becton, Matthew; Wang, Xianqiao

    2016-02-01

    This letter employs molecular mechanics simulations to analyze the geometric changes of foreign-atom-doped graphyne. Simulation results show that higher the density of dopant and the greater area covered by the dopant correlates to a greater folding angle of the graphyne sheet. Compared to graphene, graphyne folding could prove to be more effective for various nanodevices based on its unique band gap, especially when doped, and its tunable interactions with and absorption of foreign molecules. Therefore, our findings may offer unique perspectives into the development of novel graphyne-based nanodevices and stimulate the community's research interest in graphene-related origami.

  16. Folded-path optical analysis gas cell

    DOEpatents

    Carangelo, R.M.; Wright, D.D.

    1995-08-08

    A folded-path gas cell employs an elliptical concave mirror in confronting relationship to two substantially spherical concave mirrors. At least one of the spherical mirrors, and usually both, are formed with an added cylindrical component to increase orthogonal foci coincidence and thereby to increase the radiation energy throughput characteristic of the cell. 10 figs.

  17. Folded-path optical analysis gas cell

    DOEpatents

    Carangelo, Robert M.; Wright, David D.

    1995-01-01

    A folded-path gas cell employs an elliptical concave mirror in confronting relationship to two substantially spherical concave mirrors. At least one of the spherical mirrors, and usually both, are formed with an added cylindrical component to increase orthogonal focii coincidence and thereby to increase the radiation energy throughput characteristic of the cell.

  18. Vocal fold and ventricular fold vibration in period-doubling phonation: physiological description and aerodynamic modeling.

    PubMed

    Bailly, Lucie; Henrich, Nathalie; Pelorson, Xavier

    2010-05-01

    Occurrences of period-doubling are found in human phonation, in particular for pathological and some singing phonations such as Sardinian A Tenore Bassu vocal performance. The combined vibration of the vocal folds and the ventricular folds has been observed during the production of such low pitch bass-type sound. The present study aims to characterize the physiological correlates of this acoustical production and to provide a better understanding of the physical interaction between ventricular fold vibration and vocal fold self-sustained oscillation. The vibratory properties of the vocal folds and the ventricular folds during phonation produced by a professional singer are analyzed by means of acoustical and electroglottographic signals and by synchronized glottal images obtained by high-speed cinematography. The periodic variation in glottal cycle duration and the effect of ventricular fold closing on glottal closing time are demonstrated. Using the detected glottal and ventricular areas, the aerodynamic behavior of the laryngeal system is simulated using a simplified physical modeling previously validated in vitro using a larynx replica. An estimate of the ventricular aperture extracted from the in vivo data allows a theoretical prediction of the glottal aperture. The in vivo measurements of the glottal aperture are then compared to the simulated estimations.

  19. ON THE SINGLE-MASS MODEL OF THE VOCAL FOLDS

    PubMed Central

    Howe, M. S.; McGowan, R. S.

    2010-01-01

    SUMMARY An analysis is made of the fluid-structure interactions necessary to support self-sustained oscillations of a single-mass mechanical model of the vocal folds subject to a nominally steady subglottal overpressure. The single-mass model of Fant and Flanagan is re-examined and an analytical representation of vortex shedding during ‘voiced speech’ is proposed that promotes cooperative, periodic excitation of the folds by the glottal flow. Positive feedback that sustains glottal oscillations is shown to occur during glottal contraction, when the flow separates from the ‘trailing edge’ of the glottis producing a low pressure ‘suction’ force that tends to pull the folds together. Details are worked out for flow that can be regarded as locally two-dimensional in the glottal region. Predictions of free-streamline theory are used to model the effects of quasi-static variations in the separation point on the glottal wall. Numerical predictions are presented to illustrate the waveform of the sound radiated towards the mouth from the glottis. The theory is easily modified to include feedback on the glottal flow of standing acoustic waves, both in the vocal tract beyond the glottis and in the subglottal region. PMID:20419082

  20. Numerical modeling of fold-and-thrust belts: Applications to Kuqa foreland fold belt, China

    NASA Astrophysics Data System (ADS)

    Yin, H.; Morgan, J. K.; Zhang, J.; Wang, Z.

    2009-12-01

    We constructed discrete element models to simulate the evolution of fold-and-thrust belts. The impact of rock competence and decollement strength on the geometric pattern and deformation mechanics of fold-and-thrust belts has been investigated. The models reproduced some characteristic features of fold-and-thrust belts, such as faulted detachment folds, pop-ups, far-traveled thrust sheets, passive-roof duplexes, and back thrusts. In general, deformation propagates farther above a weak decollement than above a strong decollement. Our model results confirm that fold-and-thrust belts with strong frictional decollements develop relatively steep and narrow wedges formed by closely spaced imbricate thrust slices, whereas fold belts with weak decollements form wide low-taper wedges composed of faulted detachment folds, pop-ups, and back thrusts. Far-traveled thrust sheets and passive-roof duplexes are observed in the model with a strong lower decollement and a weak upper detachment. Model results also indicate that the thickness of the weak layer is critical. If it is thick enough, it acts as a ductile layer that is able to flow under differential stress, which helps to partition deformation above and below it. The discrete element modeling results were used to interpret the evolution of Kuqa Cenozoic fold-and-thrust belt along northern Tarim basin, China. Seismic and well data show that the widely distributed Paleogene rock salt has a significant impact on the deformation in this area. Structures beneath salt are closely spaced imbricate thrust and passive-roof duplex systems. Deformation above salt propagates much farther than below the salt. Faults above salt are relatively wide spaced. A huge controversy over the Kuqa fold-and-thrust belt is whether it is thin-skinned or thick-skinned. With the insights from DEM results, we suggest that Kuqa structures are mostly thin-skinned with Paleogene salt as decollement, except for the rear part near the backstop, where the

  1. Ranking vocal fold model parameters by their influence on modal frequencies

    PubMed Central

    Cook, Douglas D.; Nauman, Eric; Mongeau, Luc

    2009-01-01

    The purpose of this study was to identify, using computational models, the vocal fold parameters which are most influential in determining the vibratory characteristics of the vocal folds. The sensitivities of vocal folds modal frequencies to variations model parameters were used to determine the most influential parameters. A detailed finite element model of the human vocal fold was created. The model was defined by eight geometric and six material parameters. The model included transitional boundary regions to idealize the complex physiological structure of real human subjects. Parameters were simultaneously varied over ranges representative of actual human vocal folds. Three separate statistical analysis techniques were used to identify the most and least sensitive model parameters with respect to modal frequency. The results from all three methods consistently suggest that a set of five parameters are most influential in determining the vibratory characteristics of the vocal folds. PMID:19813811

  2. Lattice model for rapidly folding protein-like heteropolymers.

    PubMed Central

    Shrivastava, I; Vishveshwara, S; Cieplak, M; Maritan, A; Banavar, J R

    1995-01-01

    Protein folding is a relatively fast process considering the astronomical number of conformations in which a protein could find itself. Within the framework of a lattice model, we show that one can design rapidly folding sequences by assigning the strongest attractive couplings to the contacts present in a target native state. Our protein design can be extended to situations with both attractive and repulsive contacts. Frustration is minimized by ensuring that all the native contacts are again strongly attractive. Strikingly, this ensures the inevitability of folding and accelerates the folding process by an order of magnitude. The evolutionary implications of our findings are discussed. PMID:7568102

  3. Thermodynamics of downhill folding: multi-probe analysis of PDD, a protein that folds over a marginal free energy barrier.

    PubMed

    Naganathan, Athi N; Muñoz, Victor

    2014-07-31

    Downhill folding proteins fold in microseconds by crossing a very low or no free energy barrier (<3 RT), and exhibit a complex unfolding behavior in equilibrium. Such unfolding complexity is due to the weak thermodynamic coupling that exists between the various structural segments of these proteins, and it is manifested in unfolding curves that differ depending on the structural probe employed to monitor the process. Probe-dependent unfolding has important practical implications because it permits one to investigate the folding energy landscape in detail using multiprobe thermodynamic experiments. This type of thermodynamic behavior has been investigated in depth on the protein BBL, an example of extreme (one-state) downhill folding in which there is no free energy barrier at any condition, including the denaturation midpoint. However, an open question is, to what extent is such thermodynamic behavior observed on less extreme downhill folders? Here we perform a multiprobe spectroscopic characterization of the microsecond folder PDD, a structural and functional homologue of BBL that folds within the downhill regime, but is not an example of one-state downhill folding; rather at the denaturation midpoint PDD folds by crossing an incipient free energy barrier. Model-free analysis of the unfolding curves from four different spectroscopic probes together with differential scanning calorimetry reveals a dispersion of ∼9 K in the apparent melting temperature and also marked differences in unfolding broadness (from ∼50 to ∼130 kJ mol(-1) when analyzed with a two-state model), confirming that such properties are also observed on less extreme downhill folders. We subsequently perform a global quantitative analysis of the unfolding data of PDD using the same ME statistical mechanical model that was used before for the BBL domain. The analysis shows that this simple model captures all of the features observed on the unfolding of PDD (i.e., the intensity and temperature

  4. Persistent homology analysis of protein structure, flexibility and folding

    PubMed Central

    Xia, Kelin; Wei, Guo-Wei

    2014-01-01

    Proteins are the most important biomolecules for living organisms. The understanding of protein structure, function, dynamics and transport is one of most challenging tasks in biological science. In the present work, persistent homology is, for the first time, introduced for extracting molecular topological fingerprints (MTFs) based on the persistence of molecular topological invariants. MTFs are utilized for protein characterization, identification and classification. The method of slicing is proposed to track the geometric origin of protein topological invariants. Both all-atom and coarse-grained representations of MTFs are constructed. A new cutoff-like filtration is proposed to shed light on the optimal cutoff distance in elastic network models. Based on the correlation between protein compactness, rigidity and connectivity, we propose an accumulated bar length generated from persistent topological invariants for the quantitative modeling of protein flexibility. To this end, a correlation matrix based filtration is developed. This approach gives rise to an accurate prediction of the optimal characteristic distance used in protein B-factor analysis. Finally, MTFs are employed to characterize protein topological evolution during protein folding and quantitatively predict the protein folding stability. An excellent consistence between our persistent homology prediction and molecular dynamics simulation is found. This work reveals the topology-function relationship of proteins. PMID:24902720

  5. Effects of confinement and crowding on folding of model proteins.

    PubMed

    Wojciechowski, M; Cieplak, Marek

    2008-12-01

    We perform molecular dynamics simulations for a simple coarse-grained model of crambin placed inside of a softly repulsive sphere of radius R. The confinement makes folding at the optimal temperature slower and affects the folding scenarios, but both effects are not dramatic. The influence of crowding on folding are studied by placing several identical proteins within the sphere, denaturing them, and then by monitoring refolding. If the interactions between the proteins are dominated by the excluded volume effects, the net folding times are essentially like for a single protein. An introduction of inter-proteinic attractive contacts hinders folding when the strength of the attraction exceeds about a half of the value of the strength of the single protein contacts. The bigger the strength of the attraction, the more likely is the occurrence of aggregation and misfolding.

  6. Analysis and implementation of an improved recycling folded cascode amplifier

    NASA Astrophysics Data System (ADS)

    Yilei, Li; Kefeng, Han; Na, Yan; Xi, Tan; Hao, Min

    2012-02-01

    A generally improved recycling folded cascode (IRFC) is analyzed and implemented. Analysis and comparisons among the IRFC, the original recycling folded cascode (RFC) and the conventional folded cascode (FC) are made, and it is shown that with the flexible structure of IRFC, significant enhancement in transconductance, slew rate and noise can be achieved. Prototype amplifiers were fabricated in 0.13 μm technology. Measurement shows that IRFC has 3× enhancement in gain-bandwidth and slew rate over conventional FC, and the enhancement is 1.5× when compared with the RFC.

  7. $\\cN$-FOLD SUPERSYMMETRY IN QUANTUM MECHANICAL MATRIX MODELS

    NASA Astrophysics Data System (ADS)

    Tanaka, Toshiaki

    2012-03-01

    We formulate Ņ-fold supersymmetry in quantum mechanical matrix models. As an example, we construct general two-by-two Hermitian matrix two-fold supersymmetric quantum mechanical systems. We find that there are two inequivalent such systems, both of which are characterized by two arbitrary scalar functions, and one of which does not reduce to the scalar system. The obtained systems are all weakly quasi-solvable.

  8. Velocity field measurements in oblique static divergent vocal fold models

    NASA Astrophysics Data System (ADS)

    Erath, Byron

    2005-11-01

    During normal phonation, the vocal fold cycle is characterized by the glottal opening transitioning from a convergent to a divergent passage and then closing before the cycle is repeated. Under ordinary phonatory conditions, both vocal folds, which form the glottal passage, move in phase with each other, creating a time-varying symmetric opening. However, abnormal pathological conditions, such as unilateral paralysis, and polyps, can result in geometrical asymmetries between the vocal folds throughout the phonatory cycle. This study investigates pulsatile flow fields through 7.5 times life-size vocal fold models with included divergence angles of 5 to 30 degrees, and obliquities between the vocal folds of up to 15 degrees. Flow conditions were scaled to match physiological parameters. Data were taken at the anterior posterior mid-plane using phase-averaged Particle Image Velocimetry (PIV). Viscous flow phenomena including the Coanda effect, flow separation points, and jet "flapping" were investigated. The results are compared to previously reported work of flow through symmetric divergent vocal fold models.

  9. Dynamically Scaled Glottal Flow Through Symmetrically Oscillating Vocal Fold Models

    NASA Astrophysics Data System (ADS)

    Halvorson, Lori; Baitinger, Andrew; Sherman, Erica; Krane, Michael; Zhang, Lucy; Wei, Timothy

    2011-11-01

    Experimental results derived from DPIV measurements in a scaled up dynamic human vocal fold model are presented. The 10x scale vocal fold model is a new design that incorporates key features of vocal fold oscillatory motion. This includes coupling of down/upstream rocking as well as the oscillatory open/close motions. Experiments were dynamically scaled to examine a range of frequencies, 100 - 200 Hz, corresponding to the male and female voice. By using water as the working fluid, very high resolution, both spatial and temporal resolution, was achieved. Time resolved movies of flow through symmetrically oscillating vocal folds will be presented. Both individual realizations as well as phase-averaged data will be shown. Key features, such as randomness and development time of the Coanda effect, vortex shedding, and volume flow rate data will be shown. In this talk, effects associated with paralysis of one vocal fold will be discussed. This talk provides the baseline fluid dynamics for the vocal fold paralysis study presented in Sherman, et al. Supported by the NIH.

  10. Microscopic folding model analysis of the radiative (n ,γ ) reactions near the Z =28 shell closure and the weak s process

    NASA Astrophysics Data System (ADS)

    Dutta, Saumi; Gangopadhyay, G.; Bhattacharyya, Abhijit

    2016-11-01

    Radiative thermal neutron capture cross sections over the range of thermal energies from 1 keV to 1 MeV are studied in the statistical Hauser-Feshbach formalism. The optical model potential is constructed by folding the density-dependent M3Y nucleon-nucleon interaction with radial matter densities of target nuclei obtained from relativistic-mean-field (RMF) theory. The standard nuclear reaction code talys1.8 is used for calculation of cross sections. The nuclei studied in the present work reside near the Z =28 proton shell closure and are of astrophysical interest, taking part in p ,s , and r processes of nucleosynthesis. The Maxwellian-averaged cross-section (MACS) values for energies important for astrophysical applications are presented.

  11. A theoretical model of sheath fold morphology in simple shear

    NASA Astrophysics Data System (ADS)

    Reber, Jacqueline E.; Dabrowski, Marcin; Galland, Olivier; Schmid, Daniel W.

    2013-04-01

    Sheath folds are highly non-cylindrical structures often associated with shear zones. The geometry of sheath folds, especially cross-sections perpendicular to the stretching direction that display eye-patterns, have been used in the field to deduce kinematic information such as shear sense and bulk strain type. However, how sheath folds form and how they evolve with increasing strain is still a matter of debate. We investigate the formation of sheath folds around a weak inclusion acting as a slip surface in simple shear by means of an analytical model. We systematically vary the slip surface orientation and shape and evaluate the impact on the evolving eye-pattern. In addition we compare our results to existing classifications. Based on field observations it has been suggested that the shear sense of a shear zone can be determined by knowing the position of the center of an eye-pattern and the closing direction of the corresponding sheath fold. In our modeled sheath folds we can observe for a given strain that the center of the eye-structure is subject to change in height with respect to the upper edge of the outermost closed contour for different cross-sections perpendicular to the shear direction. This results in a large variability in layer thickness, questioning the usefulness of sheath folds as shear sense indicators. The location of the center of the eye structure, however, is largely invariant to the initial configurations of the slip surface as well as to strain. It has been suggested that the ratio of the aspect ratio of the innermost and outermost closed contour in eye-patterns could be linked to the bulk strain type based on filed observations. We apply this classification to our modeled sheath folds and we observe that the values of the aspect ratios of the closed contours within the eye-pattern are dependent on the strain and the cross-section location. The ratio (R') of the aspect ratios of the outermost closed contour (Ryz) and the innermost closed

  12. Characterization of protein folding by a Φ-value calculation with a statistical-mechanical model

    PubMed Central

    Wako, Hiroshi; Abe, Haruo

    2016-01-01

    The Φ-value analysis approach provides information about transition-state structures along the folding pathway of a protein by measuring the effects of an amino acid mutation on folding kinetics. Here we compared the theoretically calculated Φ values of 27 proteins with their experimentally observed Φ values; the theoretical values were calculated using a simple statistical-mechanical model of protein folding. The theoretically calculated Φ values reflected the corresponding experimentally observed Φ values with reasonable accuracy for many of the proteins, but not for all. The correlation between the theoretically calculated and experimentally observed Φ values strongly depends on whether the protein-folding mechanism assumed in the model holds true in real proteins. In other words, the correlation coefficient can be expected to illuminate the folding mechanisms of proteins, providing the answer to the question of which model more accurately describes protein folding: the framework model or the nucleation-condensation model. In addition, we tried to characterize protein folding with respect to various properties of each protein apart from the size and fold class, such as the free-energy profile, contact-order profile, and sensitivity to the parameters used in the Φ-value calculation. The results showed that any one of these properties alone was not enough to explain protein folding, although each one played a significant role in it. We have confirmed the importance of characterizing protein folding from various perspectives. Our findings have also highlighted that protein folding is highly variable and unique across different proteins, and this should be considered while pursuing a unified theory of protein folding.

  13. Detachment folds versus thrust-folds: numerical modelling and applications to the Swiss Jura Mountains and the Canadian Foothills

    NASA Astrophysics Data System (ADS)

    Humair, Florian; Bauville, Arthur; Epard, Jean-Luc; Schmalholz, Stefan

    2016-04-01

    The Jura Mountains and the Foothills of the Canadian Rockies fold-and-thrust belts are classical examples of thin-skinned belts where folds develop over weak detachment horizons. They offer the possibility to observe and measure strain in folds. In these two belts, a large spectrum of fold geometries is expressed, from symmetric box-fold or pop-up structures to asymmetric thrust-related folds. In this study, we focus on the quantification and prediction of the brittle strain distribution in folds as a function of the fold geometry. Fold geometry is considered as a continuum between two end-member structural styles: symmetric detachment folds and asymmetric foreland-vergent thrust-folds. We performed two-dimensional numerical simulations of visco-plastic detachment folding. The models are used (1) to systematically examine the influence of different initial parameters on the resulting geometry and style of folding and (2) to quantify the local strain pattern through time. The different parameters tested are the following: presence and size of initial geometrical perturbation at the detachment-sediment interface, rheology of the detachment (frictional vs. viscous), additional detachment layer within the series and overbunden thickness. Results of single detachment layer models show that the asymmetry of folds is primarily controlled by the height of the initial geometrical perturbation, regardless to the rheology of the detachment (frictional vs. viscous). Additional detachment interlayer within the series decreases the brittle strain within the stiff layers and favours more rounded anticlines geometry. The models were then adapted to the Swiss Jura and the Canadian Foothills settings. Compared to field observations and cross-sections of existing fault-related anticlines, the proposed simulations agree with the first order geometry and the development of associated localized zones of brittle deformation.

  14. Collective aspects of protein folding illustrated by a toy model

    SciTech Connect

    Stillinger, F.H.; Head-Gordon, T.

    1995-09-01

    A simple toy model for polypeptides serves as a testbed to illuminate some nonlocal, or collective, aspects of protein folding phenomena. The model is two dimensional and has only two amino acids, but involves a continuous range of backbone bend angles. Global potential energy minima and their folding structures have been determined for leading members of two special and contrasting polypeptide sequences, center doped and Fibonacci, named descriptively for their primary structures. The results display the presence of spontaneous symmetry breaking, elastic strain, and substantial conformational variation for specific embedded amino acid strings. We conclude that collective variables generated by the primary amino acid structure may be required for fully effective protein folding predictors, including those based on neural networks.

  15. Influence of Asymmetric Stiffness on the Structural and Aerodynamic Response of Synthetic Vocal Fold Models

    PubMed Central

    Pickup, B.A.; Thomson, S.L.

    2012-01-01

    The influence of asymmetric vocal fold stiffness on voice production was evaluated using life-sized, self-oscillating vocal fold models with an idealized geometry based on the human vocal folds. The models were fabricated using flexible, materially-linear silicone compounds with Young’s modulus values comparable to that of vocal fold tissue. The models included a two-layer design to simulate the vocal fold layered structure. The respective Young’s moduli of elasticity of the “left” and “right” vocal fold models were varied to create asymmetric conditions. High-speed videokymography was used to measure maximum vocal fold excursion, vibration frequency, and left-right phase shift, all of which were significantly influenced by asymmetry. Onset pressure, a measure of vocal effort, increased with asymmetry. Particle image velocimetry (PIV) analysis showed significantly greater skewing of the glottal jet in the direction of the stiffer vocal fold model. Potential applications to various clinical conditions are mentioned, and suggestions for future related studies are presented. PMID:19664777

  16. Aeroelastic and Flight Dynamics Analysis of Folding Wing Systems

    NASA Astrophysics Data System (ADS)

    Wang, Ivan

    This dissertation explores the aeroelastic stability of a folding wing using both theoretical and experimental methods. The theoretical model is based on the existing clamped-wing aeroelastic model that uses beam theory structural dynamics and strip theory aerodynamics. A higher-fidelity theoretical model was created by adding several improvements to the existing model, namely a structural model that uses ANSYS for individual wing segment modes and an unsteady vortex lattice aerodynamic model. The comparison with the lower-fidelity model shows that the higher-fidelity model typical provides better agreement between theory and experiment, but the predicted system behavior in general does not change, reinforcing the effectiveness of the low-fidelity model for preliminary design of folding wings. The present work also conducted more detailed aeroelastic analyses of three-segment folding wings, and in particular considers the Lockheed-type configurations to understand the existence of sudden changes in predicted aeroelastic behavior with varying fold angle for certain configurations. These phenomena were observed in carefully conducted experiments, and nonlinearities---structural and geometry---were shown to suppress the phenomena. Next, new experimental models with better manufacturing tolerances are designed to be tested in the Duke University Wind Tunnel. The testing focused on various configurations of three-segment folding wings in order to obtain higher quality data. Next, the theoretical model was further improved by adding aircraft longitudinal degrees of freedom such that the aeroelastic model may predict the instabilities for the entire aircraft and not just a clamped wing. The theoretical results show that the flutter instabilities typically occur at a higher air speed due to greater frequency separation between modes for the aircraft system than a clamped wing system, but the divergence instabilities occur at a lower air speed. Lastly, additional

  17. Statistical mechanics of simple models of protein folding and design.

    PubMed Central

    Pande, V S; Grosberg, A Y; Tanaka, T

    1997-01-01

    It is now believed that the primary equilibrium aspects of simple models of protein folding are understood theoretically. However, current theories often resort to rather heavy mathematics to overcome some technical difficulties inherent in the problem or start from a phenomenological model. To this end, we take a new approach in this pedagogical review of the statistical mechanics of protein folding. The benefit of our approach is a drastic mathematical simplification of the theory, without resort to any new approximations or phenomenological prescriptions. Indeed, the results we obtain agree precisely with previous calculations. Because of this simplification, we are able to present here a thorough and self contained treatment of the problem. Topics discussed include the statistical mechanics of the random energy model (REM), tests of the validity of REM as a model for heteropolymer freezing, freezing transition of random sequences, phase diagram of designed ("minimally frustrated") sequences, and the degree to which errors in the interactions employed in simulations of either folding and design can still lead to correct folding behavior. Images FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 6 PMID:9414231

  18. Mechanical Modeling and Computer Simulation of Protein Folding

    ERIC Educational Resources Information Center

    Prigozhin, Maxim B.; Scott, Gregory E.; Denos, Sharlene

    2014-01-01

    In this activity, science education and modern technology are bridged to teach students at the high school and undergraduate levels about protein folding and to strengthen their model building skills. Students are guided from a textbook picture of a protein as a rigid crystal structure to a more realistic view: proteins are highly dynamic…

  19. Modeling fibrosis using fibroblasts isolated from scarred rat vocal folds

    PubMed Central

    Kishimoto, Yo; Kishimoto, Ayami Ohno; Ye, Shuyun; Kendziorski, Christina; Welham, Nathan V.

    2016-01-01

    Following injury, pathologically activated vocal fold fibroblasts (VFFs) can engage in disordered extracellular matrix (ECM) remodeling, leading to VF fibrosis and impaired voice function. Given the importance of scar VFFs to phenotypically appropriate in vitro modeling of VF fibrosis, we pursued detailed characterization of scar VFFs obtained from surgically injured rat VF mucosae, compared to those obtained from experimentally naïve, age-matched tissue. Scar VFFs initially exhibited a myofibroblast phenotype characterized by increased proliferation, increased Col1a1 transcription and collagen, type I synthesis, increased Acta2 transcription and α-smooth muscle actin synthesis, and enhanced contractile function. These features were most distinct at passage 1 (P1); we observed a coalescence of the scar and naïve VFF phenotypes at later passages. An empirical Bayes statistical analysis of the P1 cell transcriptome identified 421 genes that were differentially expressed by scar, compared to naïve, VFFs. These genes were primarily associated with the wound response, ECM regulation, and cell proliferation. Follow-up comparison of P1 scar VFFs and their in vivo tissue source showed substantial transcriptomic differences. Finally, P1 scar VFFs responded to treatment with hepatocyte growth factor and transforming growth factor-β3, two biologics with reported therapeutic value. Despite the practical limitations inherent to working with early passage cells, this experimental model is easily implemented in any suitably equipped laboratory and has the potential to improve the applicability of preclinical VF fibrosis research. PMID:27111284

  20. A numerical strategy for finite element modeling of frictionless asymmetric vocal fold collision.

    PubMed

    Granados, Alba; Misztal, Marek Krzysztof; Brunskog, Jonas; Visseq, Vincent; Erleben, Kenny

    2017-02-01

    Analysis of voice pathologies may require vocal fold models that include relevant features such as vocal fold asymmetric collision. The present study numerically addresses the problem of frictionless asymmetric collision in a self-sustained three-dimensional continuum model of the vocal folds. Theoretical background and numerical analysis of the finite-element position-based contact model are presented, along with validation. A novel contact detection mechanism capable to detect collision in asymmetric oscillations is developed. The effect of inexact contact constraint enforcement on vocal fold dynamics is examined by different variational methods for inequality constrained minimization problems, namely, the Lagrange multiplier method and the penalty method. In contrast to the penalty solution, which is related to classical spring-like contact forces, numerical examples show that the parameter-independent Lagrange multiplier solution is more robust and accurate in the estimation of dynamical and mechanical features at vocal fold contact. Furthermore, special attention is paid to the temporal integration schemes in relation to the contact problem, the results suggesting an advantage of highly diffusive schemes. Finally, vocal fold contact enforcement is shown to affect asymmetric oscillations. The present model may be adapted to existing vocal fold models, which may contribute to a better understanding of the effect of the nonlinear contact phenomenon on phonation. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Curvature of the energy landscape and folding of model proteins.

    PubMed

    Mazzoni, Lorenzo N; Casetti, Lapo

    2006-11-24

    We study the geometric properties of the energy landscape of coarse-grained, off-lattice models of polymers by endowing the configuration space with a suitable metric, depending on the potential energy function, such that the dynamical trajectories are the geodesics of the metric. Using numerical simulations, we show that the fluctuations of the curvature clearly mark the folding transition, and that this quantity allows to distinguish between polymers having a proteinlike behavior (i.e., that fold to a unique configuration) and polymers which undergo a hydrophobic collapse but do not have a folding transition. These geometrical properties are defined by the potential energy without requiring any prior knowledge of the native configuration.

  2. Thermodynamics of folding and association of lattice-model proteins

    NASA Astrophysics Data System (ADS)

    Cellmer, Troy; Bratko, Dusan; Prausnitz, John M.; Blanch, Harvey

    2005-05-01

    Closely related to the "protein folding problem" is the issue of protein misfolding and aggregation. Protein aggregation has been associated with the pathologies of nearly 20 human diseases and presents serious difficulties during the manufacture of pharmaceutical proteins. Computational studies of multiprotein systems have recently emerged as a powerful complement to experimental efforts aimed at understanding the mechanisms of protein aggregation. We describe the thermodynamics of systems containing two lattice-model 64-mers. A parallel tempering algorithm abates problems associated with glassy systems and the weighted histogram analysis method improves statistical quality. The presence of a second chain has a substantial effect on single-chain conformational preferences. The melting temperature is substantially reduced, and the increase in the population of unfolded states is correlated with an increase in interactions between chains. The transition from two native chains to a non-native aggregate is entropically favorable. Non-native aggregates receive ˜25% of their stabilizing energy from intraprotein contacts not found in the lowest-energy structure. Contact maps show that for non-native dimers, nearly 50% of the most probable interprotein contacts involve pairs of residues that form native contacts, suggesting that a domain-swapping mechanism is involved in self-association.

  3. Saddles of the energy landscape and folding of model proteins

    NASA Astrophysics Data System (ADS)

    Angelani, L.; Ruocco, G.

    2009-07-01

    We numerically investigate the Potential Energy Landscape of an off-lattice β-sheet model protein, looking at saddles and minima probed by the system during the folding process. G {\\bar o} - like (with native-state-dependent force field and funnel-like landscape) and non-G {\\bar o} -like models are considered. In the G {\\bar o} -like case, on varying the temperature, we observe: i) a pronounced peak at the collapse/folding temperature T θsimeTf in the energy elevation of visited saddles from underlying minima, ii) a crossover at the same point of the saddle order. Saddles-based quantities seem then to be good candidates as indicators of the funneled shape of the landscape in protein models.

  4. Multiple-probe analysis of folding and unfolding pathways of human serum albumin. Evidence for a framework mechanism of folding.

    PubMed

    Santra, Manas Kumar; Banerjee, Abhijit; Krishnakumar, Shyam Sundar; Rahaman, Obaidur; Panda, Dulal

    2004-05-01

    The changes in the far-UV CD signal, intrinsic tryptophan fluorescence and bilirubin absorbance showed that the guanidine hydrochloride (GdnHCl)-induced unfolding of a multidomain protein, human serum albumin (HSA), followed a two-state process. However, using environment sensitive Nile red fluorescence, the unfolding and folding pathways of HSA were found to follow a three-state process and an intermediate was detected in the range 0.25-1.5 m GdnHCl. The intermediate state displayed 45% higher fluorescence intensity than that of the native state. The increase in the Nile red fluorescence was found to be due to an increase in the quantum yield of the HSA-bound Nile red. Low concentrations of GdnHCl neither altered the binding affinity of Nile red to HSA nor induced the aggregation of HSA. In addition, the secondary structure of HSA was not perturbed during the first unfolding transition (<1.5 m GdnHCl); however, the secondary structure was completely lost during the second transition. The data together showed that the half maximal loss of the tertiary structure occurred at a lower GdnHCl concentration than the loss of the secondary structure. Further kinetic studies of the refolding process of HSA using multiple spectroscopic techniques showed that the folding occurred in two phases, a burst phase followed by a slow phase. An intermediate with native-like secondary structure but only a partial tertiary structure was found to form in the burst phase of refolding. Then, the intermediate slowly folded into the native state. An analysis of the refolding data suggested that the folding of HSA could be best explained by the framework model.

  5. α-α folding cluster model for α-radioactivity

    NASA Astrophysics Data System (ADS)

    Soylu, A.; Bayrak, O.

    2015-04-01

    The -decay half-lives are calculated for heavy and superheavy nuclei for and from the ground state to ground state transitions within the framework of the Wentzel-Kramers-Brillouin (WKB) method and the Bohr-Sommerfeld quantization. In the calculations, the - single folding cluster potential obtained with the folded integral of the - potential with the -cluster density distributions is used in order to model the nuclear interaction between the -particle and core nucleus. While the results show very good agreement with the experimental ones in the heavy-nuclei region, especially for even-even nuclei, smaller values than the experimental ones are obtained for superheavy nuclei. As both the density of the core and the interaction term in the folding integral include the -clustering effects and, in this way, all cluster effects are taken into account in the model, the results of calculations are more physical and reasonable than the calculations done in the other models. The present method could be applied to light nuclei with different types of nuclear densities.

  6. Performance of a reduced-order FSI model for flow-induced vocal fold vibration

    NASA Astrophysics Data System (ADS)

    Chang, Siyuan; Luo, Haoxiang; Luo's lab Team

    2016-11-01

    Vocal fold vibration during speech production involves a three-dimensional unsteady glottal jet flow and three-dimensional nonlinear tissue mechanics. A full 3D fluid-structure interaction (FSI) model is computationally expensive even though it provides most accurate information about the system. On the other hand, an efficient reduced-order FSI model is useful for fast simulation and analysis of the vocal fold dynamics, which is often needed in procedures such as optimization and parameter estimation. In this work, we study the performance of a reduced-order model as compared with the corresponding full 3D model in terms of its accuracy in predicting the vibration frequency and deformation mode. In the reduced-order model, we use a 1D flow model coupled with a 3D tissue model. Two different hyperelastic tissue behaviors are assumed. In addition, the vocal fold thickness and subglottal pressure are varied for systematic comparison. The result shows that the reduced-order model provides consistent predictions as the full 3D model across different tissue material assumptions and subglottal pressures. However, the vocal fold thickness has most effect on the model accuracy, especially when the vocal fold is thin. Supported by the NSF.

  7. Browsing gene banks for Fe2S2 ferredoxins and structural modeling of 88 plant-type sequences: an analysis of fold and function.

    PubMed

    Bertini, Ivano; Luchinat, Claudio; Provenzani, Alessandro; Rosato, Antonio; Vasos, Paul R

    2002-01-01

    One-hundred-and-seventy-nine sequences of Fe2S2 ferredoxins and ferredoxin precursors were identified in and retrieved from currently available protein and cDNA databases. On the basis of their cluster-binding patterns, these sequences were divided into three groups: those containing the CX4CX2CXnC pattern (plant-type ferredoxins), those with the CX5CX2CXnC pattern (adrenodoxins), and those with a different pattern. These three groups contain, respectively, 139, 36, and 4 sequences. After excluding ferredoxin precursors in the first group, two subgroups were identified, again based on their cluster-binding patterns: 88 sequences had the CX4CX2CX29C pattern, and 29 had the CX4CX2CXmC (m not equal 29) pattern. The structures of the 88 ferredoxins with the CX4CX2CX29C pattern were modeled based on the available experimental structures of nine proteins within this same group. The modeling procedure was tested by building structural models for the ferredoxins with known structures. The models resulted, on average, in being within 1 A of the backbone root-mean-square deviation from the corresponding experimental structures. In addition, these structural models were shown to be of high quality by using assessment procedures based on energetic and stereochemical parameters. Thus, these models formed a reliable structural database for this group of ferredoxins, which is meaningful within the framework of current structural genomics efforts. From the analysis of the structural database generated it was observed that the secondary structural elements and the overall three-dimensional structures are maintained throughout the superfamily. In particular, the residues in the hydrophobic core of the protein were found to be either absolutely conserved or conservatively substituted. In addition, certain solvent-accessible charged groups, as well as hydrophobic groups, were found to be conserved to the same degree as the core residues. The patterns of conservation of exposed

  8. Dynamic Folding Pathway Models of the Trp-Cage Protein

    PubMed Central

    Kim, Seung-Yeon

    2013-01-01

    Using action-derived molecular dynamics (ADMD), we study the dynamic folding pathway models of the Trp-cage protein by providing its sequential conformational changes from its initial disordered structure to the final native structure at atomic details. We find that the numbers of native contacts and native hydrogen bonds are highly correlated, implying that the native structure of Trp-cage is achieved through the concurrent formations of native contacts and native hydrogen bonds. In early stage, an unfolded state appears with partially formed native contacts (~40%) and native hydrogen bonds (~30%). Afterward, the folding is initiated by the contact of the side chain of Tyr3 with that of Trp6, together with the formation of the N-terminal α-helix. Then, the C-terminal polyproline structure docks onto the Trp6 and Tyr3 rings, resulting in the formations of the hydrophobic core of Trp-cage and its near-native state. Finally, the slow adjustment processes of the near-native states into the native structure are dominant in later stage. The ADMD results are in agreement with those of the experimental folding studies on Trp-cage and consistent with most of other computational studies. PMID:23865078

  9. Structural evolution of fold-thrust structures in analog models deformed in a large geotechnical centrifuge

    NASA Astrophysics Data System (ADS)

    Noble, Todd E.; Dixon, John M.

    2011-02-01

    We investigate the structural evolution of fault-propagation folds and fold-thrust systems with scaled analog modeling carried out using the 5.5 m radius geotechnical centrifuge at C-CORE, St. John's NL. The experiments presented here are the first of their kind, scaled ten times larger than predecessors and deformed using a custom rig with load monitoring and displacement control. Plane-layered models approximately 1 m long and representing 50 km sections are shortened horizontally under an enhanced gravity field of 160 g. The large model scale allows for a proportionally large number of bedding laminations that act as strain markers. This allows detailed analysis of strain partitioning and interplay, both at the scale of a fold-thrust system and the individual fold-thrust structure. Layer-parallel shortening ("LPS") and rotation of fault-bounded blocks are revealed by mapping contraction fault populations and bedding-contraction fault intersection angles. Low-angle contraction faulting and LPS are found to be dominant at early stages of development and rotation of fault-bounded blocks occurs during progressive folding of the hanging-wall panel during fault-propagation folding. Displacement-distance data obtained from major thrusts in the model show relative stretch values, and consequently fault slip/propagation ratios, that are similar to natural structures.

  10. Coarse-grained models of protein folding: toy models or predictive tools?

    PubMed

    Clementi, Cecilia

    2008-02-01

    Coarse-grained models are emerging as a practical alternative to all-atom simulations for the characterization of protein folding mechanisms over long time scales. While a decade ago minimalist toy models were mainly designed to test general hypotheses on the principles regulating protein folding, the latest coarse-grained models are increasingly realistic and can be used to characterize quantitatively the detailed folding mechanism of specific proteins. The ability of such models to reproduce the essential features of folding dynamics suggests that each single atomic degree of freedom is not by itself particularly relevant to folding and supports a statistical mechanical approach to characterize folding transitions. When combined with more refined models and with experimental studies, the systematic investigation of protein systems and complexes using coarse-grained models can advance our theoretical understanding of the actual organizing principles that emerge from the complex network of interactions among protein atomic constituents.

  11. A workflow for 3D model building in fold-thrust belts

    NASA Astrophysics Data System (ADS)

    Watkins, Hannah; Bond, Clare; Butler, Rob

    2016-04-01

    3D geological models can be used in fold-thrust belts for many purposes such as analysing geometric variation in folds, kinematic modelling to restore fold surfaces, generating strain distribution maps and predicting fracture network distribution. We present a workflow for 3D model building using outcrop bedding data, geological maps, Digital Terrain Models (DTM's), air photos and field photographs. We discuss the challenges of software limitations for 3D kinematic restoration and forward modelling in fold-thrust belt settings. We then discuss the sensitivity of model building approaches to the application of 3D geological models in fold-thrust belts for further analysis e.g. changes in along strike fold geometry, restoration using kinematic and geomechanical modelling, strain prediction and Discrete Fracture Network (DFN) modelling. To create 3D models geological maps and bedding data are digitised using Move software; digitised maps and data are then draped onto DTM's. A series of closely spaced cross section lines are selected; the orientation of these is calculated by determining the average orientation of bedding dip direction. Fault and horizon line intersections, along with bedding data from within a narrow margin of the section lines are projected onto each cross section. Field photographs and sketches are integrated into the cross sections to determine thrust angles at the surface. Horizon lines are then constructed using bedding data. Displacement profiles for thrusts are plotted to ensure thrust displacements are valid with respect to neighbouring cross section interpretations; any discrepancies are alleviated by making minor adjustments to horizon and thrust lines, while ensuring that resultant cross section geometries still adhere to bedding data and other field observations. Once the cross sections have been finalised, 3D surfaces are created using the horizon and thrust line interpretations on each cross section. The simple curvature of 3D surfaces

  12. Folding model calculations for 6He+12C elastic scattering

    NASA Astrophysics Data System (ADS)

    Awad, A. Ibraheem

    2016-03-01

    In the framework of the double folding model, we used the α+2n and di-triton configurations for the nuclear matter density of the 6He nucleus to generate the real part of the optical potential for the system 6He+12C. As an alternative, we also use the high energy approximation to generate the optical potential for the same system. The derived potentials are employed to analyze the elastic scattering differential cross section at energies of 38.3, 41.6 and 82.3 MeV/u. For the imaginary part of the potential we adopt the squared Woods-Saxon form. The obtained results are compared with the corresponding measured data as well as with available results in the literature. The calculated total reaction cross sections are investigated and compared with the optical limit Glauber model description.

  13. Parameter Optimization for the Gaussian Model of Folded Proteins

    NASA Astrophysics Data System (ADS)

    Erman, Burak; Erkip, Albert

    2000-03-01

    Recently, we proposed an analytical model of protein folding (B. Erman, K. A. Dill, J. Chem. Phys, 112, 000, 2000) and showed that this model successfully approximates the known minimum energy configurations of two dimensional HP chains. All attractions (covalent and non-covalent) as well as repulsions were treated as if the monomer units interacted with each other through linear spring forces. Since the governing potential of the linear springs are derived from a Gaussian potential, the model is called the ''Gaussian Model''. The predicted conformations from the model for the hexamer and various 9mer sequences all lie on the square lattice, although the model does not contain information about the lattice structure. Results of predictions for chains with 20 or more monomers also agreed well with corresponding known minimum energy lattice structures. However, these predicted conformations did not lie exactly on the square lattice. In the present work, we treat the specific problem of optimizing the potentials (the strengths of the spring constants) so that the predictions are in better agreement with the known minimum energy structures.

  14. Geomechanical Modeling in Fold-and-Thrust Belts Systems

    NASA Astrophysics Data System (ADS)

    Gao, B.; Flemings, P. B.

    2015-12-01

    We present a large-strain poro-mechanical model to investigate the evolution of stress and strain in fold and thrust belt systems. We impose horizontal shortening in the model and observe that a tapered wedge develops. Inside the accretionary wedge, the horizontal effective stress increases to about 2.3 times the vertical effective stress. The maximum principle stress direction rotates gradually from the initial vertical direction to the horizontal direction as the sediment gets closer to the backstop. We use stress paths to illustrate how the stresses evolve during the thrust loading. We find the sediment stress path starts from uniaxial condition and moves towards critical state condition. We categorize the thrust belt into 3 zones according to their stress conditions from the backstop to the farfield: critical state region, transition region, and uniaxial region. We show that the sediments within the accretionary wedge are at critical state, which indicate they lost their strength to resist deformation. The sediment porosity decreases dramatically within the wedge due to high mean effective and differential stress. We built the model in finite element program Elfen. The sediments are modeled as poro-elastoplastic materials with a critical state soil model. Overall, our results provide insights of stress and porosity evolution in compressional regimes and can assist field stress and pressure predictions.

  15. Emergent protein folding modeled with evolved neural cellular automata using the 3D HP model.

    PubMed

    Santos, José; Villot, Pablo; Diéguez, Martin

    2014-11-01

    We used cellular automata (CA) for the modeling of the temporal folding of proteins. Unlike the focus of the vast research already done on the direct prediction of the final folded conformations, we will model the temporal and dynamic folding process. To reduce the complexity of the interactions and the nature of the amino acid elements, lattice models like HP were used, a model that categorizes the amino acids regarding their hydrophobicity. Taking into account the restrictions of the lattice model, the CA model defines how the amino acids interact through time to obtain a folded conformation. We extended the classical CA models using artificial neural networks for their implementation (neural CA), and we used evolutionary computing to automatically obtain the models by means of Differential Evolution. As the iterative folding also provides the final folded conformation, we can compare the results with those from direct prediction methods of the final protein conformation. Finally, as the neural CA that provides the iterative folding process can be evolved using several protein sequences and used as operators in the folding of another protein with different length, this represents an advantage over the NP-hard complexity of the original problem of the direct prediction.

  16. Modeling chain folding in protein-constrained circular DNA.

    PubMed Central

    Martino, J A; Olson, W K

    1998-01-01

    An efficient method for sampling equilibrium configurations of DNA chains binding one or more DNA-bending proteins is presented. The technique is applied to obtain the tertiary structures of minimal bending energy for a selection of dinucleosomal minichromosomes that differ in degree of protein-DNA interaction, protein spacing along the DNA chain contour, and ring size. The protein-bound portions of the DNA chains are represented by tight, left-handed supercoils of fixed geometry. The protein-free regions are modeled individually as elastic rods. For each random spatial arrangement of the two nucleosomes assumed during a stochastic search for the global minimum, the paths of the flexible connecting DNA segments are determined through a numerical solution of the equations of equilibrium for torsionally relaxed elastic rods. The minimal energy forms reveal how protein binding and spacing and plasmid size differentially affect folding and offer new insights into experimental minichromosome systems. PMID:9591675

  17. Modulation of folding energy landscape by charge-charge interactions: linking experiments with computational modeling.

    PubMed

    Tzul, Franco O; Schweiker, Katrina L; Makhatadze, George I

    2015-01-20

    The kinetics of folding-unfolding of a structurally diverse set of four proteins optimized for thermodynamic stability by rational redesign of surface charge-charge interactions is characterized experimentally. The folding rates are faster for designed variants compared with their wild-type proteins, whereas the unfolding rates are largely unaffected. A simple structure-based computational model, which incorporates the Debye-Hückel formalism for the electrostatics, was used and found to qualitatively recapitulate the experimental results. Analysis of the energy landscapes of the designed versus wild-type proteins indicates the differences in refolding rates may be correlated with the degree of frustration of their respective energy landscapes. Our simulations indicate that naturally occurring wild-type proteins have frustrated folding landscapes due to the surface electrostatics. Optimization of the surface electrostatics seems to remove some of that frustration, leading to enhanced formation of native-like contacts in the transition-state ensembles (TSE) and providing a less frustrated energy landscape between the unfolded and TS ensembles. Macroscopically, this results in faster folding rates. Furthermore, analyses of pairwise distances and radii of gyration suggest that the less frustrated energy landscapes for optimized variants are a result of more compact unfolded and TS ensembles. These findings from our modeling demonstrates that this simple model may be used to: (i) gain a detailed understanding of charge-charge interactions and their effects on modulating the energy landscape of protein folding and (ii) qualitatively predict the kinetic behavior of protein surface electrostatic interactions.

  18. Thermal stability and folding kinetics analysis of intrinsically disordered protein, securin

    NASA Astrophysics Data System (ADS)

    Chang, Chia-Ching; Chu, Hsueh-Liang; Ho, Li-Ping

    2014-03-01

    Lacking a stable tertiary structure, intrinsically disordered proteins (IDPs) possess particular functions in cell regulation, signaling, and controlling pathways. The study of their unique structure features, thermal stabilities, and folding kinetics is intriguing. In this study, an identified IDP, securin, was used as a model protein. By using a quasi-static five-step (on-path) folding process, the function of securin was restored and analyzed by isothermal titration calorimetry. Fluorescence spectroscopy and particle size analysis indicated that securin possessed a compact hydrophobic core and particle size. The glass transition of securin was characterized using differential scanning microcalorimetry. Furthermore, the folding/unfolding rates (kobs) of securin were undetectable, implying that the folding/unfolding rate is very fast and that the conformation of securin is sensitive to solvent environment change. Therefore, securin may fold properly under specific physiological conditions. In summary, the thermal glass transition behavior and undetectable kobs of folding/unfolding reactions may be two of the indices of IDP. This study was supported in part by grants NSC 97-2112-M-009-009-YM3 and NSC 100-2112-M-009-004-MY3, Taiwan, R.O.C.

  19. Natural and forced asymmetries in flow through a vocal fold model

    NASA Astrophysics Data System (ADS)

    Drain, Bethany; Lambert, Lori; Krane, Michael; Wei, Timothy

    2012-11-01

    Much of the complexity and richness of voice production stems from asymmetries in flow through the vocal folds. There are naturally occurring asymmetries, such as the Coanda effect (i . e . deviation of the glottal jet from the centerline as air passes through the nominally symmetric vocal folds). There are also asymmetries which arise from disease or dysfunction of the vocal folds. This study uses DPIV measurements in a dynamically scaled-up human vocal fold model to compare the flow characteristics between symmetric versus asymmetric oscillations. For this study, asymmetries were introduced by running one vocal fold out of phase with the other. Three phase lags, 0 18 and 36, were examined over a range of frequencies corresponding to the physiological frequencies of 50-200 Hz. Control volume analysis was applied and time traces of terms from the conservation of linear momentum equation were generated. This allowed analysis of how differences in the glottal jet flow manifest themselves in the fluid pressure field. In addition, further examination of the Coanda effect in the context of fluid pressure will be discussed. Supported by NIH.

  20. Optimized parameter selection reveals trends in Markov state models for protein folding

    NASA Astrophysics Data System (ADS)

    Husic, Brooke E.; McGibbon, Robert T.; Sultan, Mohammad M.; Pande, Vijay S.

    2016-11-01

    As molecular dynamics simulations access increasingly longer time scales, complementary advances in the analysis of biomolecular time-series data are necessary. Markov state models offer a powerful framework for this analysis by describing a system's states and the transitions between them. A recently established variational theorem for Markov state models now enables modelers to systematically determine the best way to describe a system's dynamics. In the context of the variational theorem, we analyze ultra-long folding simulations for a canonical set of twelve proteins [K. Lindorff-Larsen et al., Science 334, 517 (2011)] by creating and evaluating many types of Markov state models. We present a set of guidelines for constructing Markov state models of protein folding; namely, we recommend the use of cross-validation and a kinetically motivated dimensionality reduction step for improved descriptions of folding dynamics. We also warn that precise kinetics predictions rely on the features chosen to describe the system and pose the description of kinetic uncertainty across ensembles of models as an open issue.

  1. Precursory signatures of protein folding/unfolding: From time series correlation analysis to atomistic mechanisms

    SciTech Connect

    Hsu, P. J.; Lai, S. K.; Cheong, S. A.

    2014-05-28

    Folded conformations of proteins in thermodynamically stable states have long lifetimes. Before it folds into a stable conformation, or after unfolding from a stable conformation, the protein will generally stray from one random conformation to another leading thus to rapid fluctuations. Brief structural changes therefore occur before folding and unfolding events. These short-lived movements are easily overlooked in studies of folding/unfolding for they represent momentary excursions of the protein to explore conformations in the neighborhood of the stable conformation. The present study looks for precursory signatures of protein folding/unfolding within these rapid fluctuations through a combination of three techniques: (1) ultrafast shape recognition, (2) time series segmentation, and (3) time series correlation analysis. The first procedure measures the differences between statistical distance distributions of atoms in different conformations by calculating shape similarity indices from molecular dynamics simulation trajectories. The second procedure is used to discover the times at which the protein makes transitions from one conformation to another. Finally, we employ the third technique to exploit spatial fingerprints of the stable conformations; this procedure is to map out the sequences of changes preceding the actual folding and unfolding events, since strongly correlated atoms in different conformations are different due to bond and steric constraints. The aforementioned high-frequency fluctuations are therefore characterized by distinct correlational and structural changes that are associated with rate-limiting precursors that translate into brief segments. Guided by these technical procedures, we choose a model system, a fragment of the protein transthyretin, for identifying in this system not only the precursory signatures of transitions associated with α helix and β hairpin, but also the important role played by weaker correlations in such protein

  2. FE Modelling of the Fluid-Structure-Acoustic Interaction for the Vocal Folds Self-Oscillation

    NASA Astrophysics Data System (ADS)

    Švancara, Pavel; Horáček, J.; Hrůza, V.

    The flow induced self-oscillation of the human vocal folds in interaction with acoustic processes in the simplified vocal tract model was explored by three-dimensional (3D) finite element (FE) model. Developed FE model includes vocal folds pretension before phonation, large deformations of the vocal fold tissue, vocal folds contact, fluid-structure interaction, morphing the fluid mesh according the vocal folds motion (Arbitrary Lagrangian-Eulerian approach), unsteady viscous compressible airflow described by the Navier-Stokes equations and airflow separation during the glottis closure. Iterative partitioned approach is used for modelling the fluid-structure interaction. Computed results prove that the developed model can be used for simulation of the vocal folds self-oscillation and resulting acoustic waves. The developed model enables to numerically simulate an influence of some pathological changes in the vocal fold tissue on the voice production.

  3. Modeling Fold-And Belts Using Numerical Simulations and Physical Experiments: the Aconcagua and Mexican Fold-And Belts

    NASA Astrophysics Data System (ADS)

    Cruz, L.; Hilley, G. E.; Fitz, E.; Hudleston, P. J.; Malinski, J.; Hernandez, M.; Take, A.

    2010-12-01

    In this contribution we first investigate the impact of erosion on the geometry and kinematics of the central Argentine Aconcagua Fold-and-Thrust Belt (AFTB) using an integrated analog (sandbox) and numerical (Gale) modeling approach in which mass removal from the topographic surface is limited by the rate of fluvial bedrock incision. This method unifies principles of frictional failure used in Critical Coulomb Wedge (CCW) theory with a quasi-mechanistic erosion rule, which allows us to explicitly relate temporal changes in erosional efficiency in this fold-and-thrust belt to its kinematics. We show that theoretical predictions of AFTB geometry, as well as the kinematics predicted by both physical and numerical experiments are both internally consistent and correctly predict the interpreted and measured field geometries. Specifically, the geometric evolution of the AFTB requires relatively high erosion efficiency values (K) during the initial stage of deformation, and relatively low K values during the latter stages, which is consistent with the progressive exposure of different rock types during the different stages of deformation. Model results indicate that the activity of the faults in the hinterland is high when erosion is most efficient during the initial stage of deformation; this activity is facilitated by increased out-of-sequence thrusting. In contrast, the models predict that forward-propagating thrusts dominate the latter stages of deformation when erosion is far less efficient. We next explore the role of the initial configuration of materials with differing constitutive properties using the Gale numerical code, and published and new structural data from the well-documented Mexican Fold-and-Thrust Belt (MFTB). This fold-and-thrust belt is located in central Mexico and its kinematics appear to be influenced by spatially varying material properties within the accreted foreland rocks. Preliminary results from the MFTB simulations show that rheological

  4. Modeling the Biomechanical Influence of Epilaryngeal Stricture on the Vocal Folds: A Low-Dimensional Model of Vocal-Ventricular Fold Coupling

    ERIC Educational Resources Information Center

    Moisik, Scott R.; Esling, John H.

    2014-01-01

    Purpose: Physiological and phonetic studies suggest that, at moderate levels of epilaryngeal stricture, the ventricular folds impinge upon the vocal folds and influence their dynamical behavior, which is thought to be responsible for constricted laryngeal sounds. In this work, the authors examine this hypothesis through biomechanical modeling.…

  5. Folding model description of reactions with exotic nuclei

    SciTech Connect

    Ibraheem, Awad A.; Hassanain, M. A.; Mokhtar, S. R.; Zaki, M. A.; Mahmoud, Zakaria M. M.; Farid, M. El-Azab

    2012-08-15

    Microscopic folding calculations based upon the effective M3Y nucleon-nucleon interaction and the nuclearmatter densities of the interacting nuclei have been carried out to explain recently measured experimental data of the {sup 6}He+{sup 120}Sn elastic scattering cross section at four different laboratory energies near the Coulomb barrier. The extracted reaction cross sections are also considered.

  6. Thermodynamic aspects in a simplified model for the folding of two-stranded coiled-coils

    NASA Astrophysics Data System (ADS)

    Prolongo, Silvia G.; Rubio, Ana M.; Rey, Antonio

    2000-12-01

    We have investigated the thermodynamic properties of a simple model representing the thermal folding/unfolding transition of two-stranded coiled-coils. The transition temperature and the energy change for the process are analyzed in terms of the peptide concentration, using the standard properties and calculations involved in experimental work. The integration of the heat capacity curves provides realistic and correct results for the model, as it does the variation of the transition temperature with concentration. On the other hand, the van't Hoff analysis of the equilibrium constant for the unfolding process produces apparently odd results. They can only be rationalized through a careful analysis of the reaction stoichiometry, according to the reference state defined for the very simple model interactions, and the definition of the unfolded state. This point is extensively discussed, for its possible implications in the correct analysis of this and other simulation models.

  7. The topomer-sampling model of protein folding

    PubMed Central

    Debe, Derek A.; Carlson, Matt J.; Goddard, William A.

    1999-01-01

    Clearly, a protein cannot sample all of its conformations (e.g., ≈3100 ≈ 1048 for a 100 residue protein) on an in vivo folding timescale (<1 s). To investigate how the conformational dynamics of a protein can accommodate subsecond folding time scales, we introduce the concept of the native topomer, which is the set of all structures similar to the native structure (obtainable from the native structure through local backbone coordinate transformations that do not disrupt the covalent bonding of the peptide backbone). We have developed a computational procedure for estimating the number of distinct topomers required to span all conformations (compact and semicompact) for a polypeptide of a given length. For 100 residues, we find ≈3 × 107 distinct topomers. Based on the distance calculated between different topomers, we estimate that a 100-residue polypeptide diffusively samples one topomer every ≈3 ns. Hence, a 100-residue protein can find its native topomer by random sampling in just ≈100 ms. These results suggest that subsecond folding of modest-sized, single-domain proteins can be accomplished by a two-stage process of (i) topomer diffusion: random, diffusive sampling of the 3 × 107 distinct topomers to find the native topomer (≈0.1 s), followed by (ii) intratopomer ordering: nonrandom, local conformational rearrangements within the native topomer to settle into the precise native state. PMID:10077555

  8. Design and analysis of a folded Fresnel Zone Plate antenna

    NASA Astrophysics Data System (ADS)

    Ji, Yu; Fujita, Masaharu

    1994-08-01

    Based on the Kirchhoff-Huygens diffraction theory, a simple analytical method of a planar folded Fresnel zone-plate (FZP), that is the case when a planar reflector is placed behind the zone plates, has been developed. According to the numerical calculation results, the design procedure of the FZP antenna has been presented, and its focusing characteristics and gain-optimized conditions have been discussed. The variations of the focal field distribution with the antenna parameters such as zone numbers, focal length and antenna diameter and the radiation power patterns of the FZP have been simulated numerically. To take a good balance of both receiving and transmitting antennas, at 60GHz operating frequency, the focal length should be designed as a half of the antenna diameter and the zone number should be from 10 to 15. The results in this work show that the folded FZP has good focal characteristics and off-axis performance, and its antenna gain can be optimized by the suitable antenna parameter design. The possibility of applying the folded FZP as a low cost and high gain antenna without strict manufacturing requirement for millimeter-wave communications has been shown.

  9. Predicting the equilibrium protein folding pathway: structure-based analysis of staphylococcal nuclease.

    PubMed

    Hilser, V J; Freire, E

    1997-02-01

    The equilibrium folding pathway of staphylococcal nuclease (SNase) has been approximated using a statistical thermodynamic formalism that utilizes the high-resolution structure of the native state as a template to generate a large ensemble of partially folded states. Close to 400,000 different states ranging from the native to the completely unfolded states were included in the analysis. The probability of each state was estimated using an empirical structural parametrization of the folding energetics. It is shown that this formalism predicts accurately the stability of the protein, the cooperativity of the folding/unfolding transition observed by differential scanning calorimetry (DSC) or urea denaturation and the thermodynamic parameters for unfolding. More importantly, this formalism provides a quantitative account of the experimental hydrogen exchange protection factors measured under native conditions for SNase. These results suggest that the computer-generated distribution of states approximates well the ensemble of conformations existing in solution. Furthermore, this formalism represents the first model capable of quantitatively predicting within a unified framework the probability distribution of states seen under native conditions and its change upon unfolding.

  10. Geometry of the energy landscape and folding transition in a simple model of a protein.

    PubMed

    Mazzoni, Lorenzo N; Casetti, Lapo

    2008-05-01

    A geometric analysis of the global properties of the energy landscape of a minimalistic model of a polypeptide is presented, which is based on the relation between dynamical trajectories and geodesics of a suitable manifold, whose metric is completely determined by the potential energy. We consider different sequences, some with a definite proteinlike behavior, a unique native state and a folding transition, and others undergoing a hydrophobic collapse with no tendency to a unique native state. The global geometry of the energy landscape appears to contain relevant information on the behavior of the various sequences: in particular, the fluctuations of the curvature of the energy landscape, measured by means of numerical simulations, clearly mark the folding transition and allow the proteinlike sequences to be distinguished from the others.

  11. Laryngeal muscular control of vocal fold posturing: Numerical modeling and experimental validation

    PubMed Central

    Yin, Jun; Zhang, Zhaoyan

    2016-01-01

    A three-dimensional continuum model of vocal fold posturing was developed to investigate laryngeal muscular control of vocal fold geometry, stiffness, and tension, which are difficult to measure in live humans or in vivo models. This model was able to qualitatively reproduce in vivo experimental observations of laryngeal control of vocal fold posturing, despite the many simplifications which are necessary due to the lack of accurate data of laryngeal geometry and material properties. The results present a first comprehensive study of the co-variations between glottal width, vocal fold length, stiffness, tension at different conditions of individual, and combined laryngeal muscle activation. PMID:27914396

  12. Web-based toolkits for topology prediction of transmembrane helical proteins, fold recognition, structure and binding scoring, folding-kinetics analysis and comparative analysis of domain combinations.

    PubMed

    Zhou, Hongyi; Zhang, Chi; Liu, Song; Zhou, Yaoqi

    2005-07-01

    We have developed the following web servers for protein structural modeling and analysis at http://theory.med.buffalo.edu: THUMBUP, UMDHMM(TMHP) and TUPS, predictors of transmembrane helical protein topology based on a mean-burial-propensity scale of amino acid residues (THUMBUP), hidden Markov model (UMDHMM(TMHP)) and their combinations (TUPS); SPARKS 2.0 and SP3, two profile-profile alignment methods, that match input query sequence(s) to structural templates by integrating sequence profile with knowledge-based structural score (SPARKS 2.0) and structure-derived profile (SP3); DFIRE, a knowledge-based potential for scoring free energy of monomers (DMONOMER), loop conformations (DLOOP), mutant stability (DMUTANT) and binding affinity of protein-protein/peptide/DNA complexes (DCOMPLEX & DDNA); TCD, a program for protein-folding rate and transition-state analysis of small globular proteins; and DOGMA, a web-server that allows comparative analysis of domain combinations between plant and other 55 organisms. These servers provide tools for prediction and/or analysis of proteins on the secondary structure, tertiary structure and interaction levels, respectively.

  13. Right- and left-handed three-helix proteins. I. Experimental and simulation analysis of differences in folding and structure.

    PubMed

    Glyakina, Anna V; Pereyaslavets, Leonid B; Galzitskaya, Oxana V

    2013-09-01

    Despite the large number of publications on three-helix protein folding, there is no study devoted to the influence of handedness on the rate of three-helix protein folding. From the experimental studies, we make a conclusion that the left-handed three-helix proteins fold faster than the right-handed ones. What may explain this difference? An important question arising in this paper is whether the modeling of protein folding can catch the difference between the protein folding rates of proteins with similar structures but with different folding mechanisms. To answer this question, the folding of eight three-helix proteins (four right-handed and four left-handed), which are similar in size, was modeled using the Monte Carlo and dynamic programming methods. The studies allowed us to determine the orders of folding of the secondary-structure elements in these domains and amino acid residues which are important for the folding. The obtained data are in good correlation with each other and with the experimental data. Structural analysis of these proteins demonstrated that the left-handed domains have a lesser number of contacts per residue and a smaller radius of cross section than the right-handed domains. This may be one of the explanations of the observed fact. The same tendency is observed for the large dataset consisting of 332 three-helix proteins (238 right- and 94 left-handed). From our analysis, we found that the left-handed three-helix proteins have some less-dense packing that should result in faster folding for some proteins as compared to the case of right-handed proteins.

  14. Spatiotemporal analysis of vocal fold vibrations between children and adults

    PubMed Central

    Döllinger, Michael; Dubrovskiy, Denis; Patel, Rita

    2012-01-01

    Objectives/Hypothesis Aim of the study is to quantify differences in spatiotemporal features of vibratory motion in typically developing pre-pubertal children and adults with use of high speed digital imaging. Study Design Prospective case-control study. Methods Vocal fold oscillations of 31 children and 35 adults were analysed. Endoscopic high-speed imaging was performed during sustained phonation at typical pitch and loudness. Quantitative technique of Phonovibrogram was used to compute spatiotemporal features. Spatial features are represented by opening and closing angles along the anterior and posterior parts of the vocal folds, as well as by left-right symmetry ratio. Temporal features are represented by the cycle-to-cycle variability of the spatial features. Group differences (adult females, adult males, and children) were statistically investigated. Results Statistical differences were more pronounced in the temporal behavior compared to the spatial behavior. Children demonstrated greater cycle-to-cycle variability in oscillations compared to adults. Most differences between children and adults were found for temporal characteristics along the anterior parts during closing phase. The spatiotemporal features differed more between children and males than between children and females. Both adults and children showed equally high left-right symmetry. Conclusions Results suggest a more unstable phonation in children than in adults yielding increased perturbation in periodicity. Children demonstrated longer phase delay in the anterior/posterior and medio-lateral parts during the opening phase compared to adults. The data presented may provide the bases for differentiating normal vibratory characteristics from the disordered in the pediatric population and eventually assist in aiding the clinical utility of high speed imaging. PMID:22965771

  15. FRankenstein becomes a cyborg: the automatic recombination and realignment of fold recognition models in CASP6.

    PubMed

    Kosinski, Jan; Gajda, Michal J; Cymerman, Iwona A; Kurowski, Michal A; Pawlowski, Marcin; Boniecki, Michal; Obarska, Agnieszka; Papaj, Grzegorz; Sroczynska-Obuchowicz, Paulina; Tkaczuk, Karolina L; Sniezynska, Paulina; Sasin, Joanna M; Augustyn, Anna; Bujnicki, Janusz M; Feder, Marcin

    2005-01-01

    In the course of CASP6, we generated models for all targets using a new version of the "FRankenstein's monster approach." Previously (in CASP5) we were able to build many very accurate full-atom models by selection and recombination of well-folded fragments obtained from crude fold recognition (FR) results, followed by optimization of the sequence-structure fit and assessment of alternative alignments on the structural level. This procedure was however very arduous, as most of the steps required extensive visual and manual input from the human modeler. Now, we have automated the most tedious steps, such as superposition of alternative models, extraction of best-scoring fragments, and construction of a hybrid "monster" structure, as well as generation of alternative alignments in the regions that remain poorly scored in the refined hybrid model. We have also included the ROSETTA method to construct those parts of the target for which no reasonable structures were generated by FR methods (such as long insertions and terminal extensions). The analysis of successes and failures of the current version of the FRankenstein approach in modeling of CASP6 targets reveals that the considerably streamlined and automated method performs almost as well as the initial, mostly manual version, which suggests that it may be a useful tool for accurate protein structure prediction even in the hands of nonexperts.

  16. Modelling of Folding Patterns in Flat Membranes and Cylinders by Origami

    NASA Astrophysics Data System (ADS)

    Nojima, Taketoshi

    This paper describes folding methods of thin flat sheets as well as cylindrical shells by modelling folding patterns through Japanese traditional Origami technique. New folding patterns have been devised in thin flat squared or circular membrane by modifying so called Miura-Ori in Japan (one node with 4 folding lines). Some folding patterns in cylindrical shells have newly been developed including spiral configurations. Devised foldable cylindrical shells were made by using polymer sheets, and it has been assured that they can be folded quite well. The devised models will make it possible to construct foldable/deployable space structures as well as to manufacture foldable industrial products and living goods, e. g., bottles for soft drinks.

  17. Irregular vocal fold dynamics incited by asymmetric fluid loading in a model of recurrent laryngeal nerve paralysis

    NASA Astrophysics Data System (ADS)

    Sommer, David; Erath, Byron D.; Zanartu, Matias; Peterson, Sean D.

    2011-11-01

    Voiced speech is produced by dynamic fluid-structure interactions in the larynx. Traditionally, reduced order models of speech have relied upon simplified inviscid flow solvers to prescribe the fluid loadings that drive vocal fold motion, neglecting viscous flow effects that occur naturally in voiced speech. Viscous phenomena, such as skewing of the intraglottal jet, have the most pronounced effect on voiced speech in cases of vocal fold paralysis where one vocal fold loses some, or all, muscular control. The impact of asymmetric intraglottal flow in pathological speech is captured in a reduced order two-mass model of speech by coupling a boundary-layer estimation of the asymmetric pressures with asymmetric tissue parameters that are representative of recurrent laryngeal nerve paralysis. Nonlinear analysis identifies the emergence of irregular and chaotic vocal fold dynamics at values representative of pathological speech conditions.

  18. Information from folds: A review

    NASA Astrophysics Data System (ADS)

    Hudleston, Peter J.; Treagus, Susan H.

    2010-12-01

    Folds are spectacular geological structures that are seen in layered rock on many different scales. To mark 30 years of the Journal of Structural Geology, we review the information that can be gained from studies of folds in theory, experiment and nature. We first review theoretical considerations and modeling, from classical approaches to current developments. The subject is dominated by single-layer fold theory, with the assumption of perfect layer-parallel shortening, but we also review multilayer fold theory and modeling, and folding of layers that are oblique to principal stresses and strains. This work demonstrates that viscosity ratio, degree of non-linearity of the flow law, anisotropy, and the thickness and spacing distribution of layers of different competence are all important in determining the nature and strength of the folding instability. Theory and modeling provide the basis for obtaining rheological information from natural folds, through analysis of wavelength/thickness ratios of single layer folds, and fold shapes. They also provide a basis for estimating the bulk strain from folded layers. Information about folding mechanisms can be obtained by analysis of cleavage and fabric patterns in folded rocks, and the history of deformation can be revealed by understanding how asymmetry can develop in folds, by how folds develop in shear zones, and how folds develop in more complex three-dimensional deformations.

  19. Local rules for protein folding on a triangular lattice and generalized hydrophobicity in the HP model

    SciTech Connect

    Agarwala, R.; Batzoglou, S.; Dancik, V.

    1997-06-01

    We consider the problem of determining the three-dimensional folding of a protein given its one-dimensional amino acid sequence. We use the HP model for protein folding proposed by Dill, which models protein as a chain of amino acid residues that are either hydrophobic or polar, and hydrophobic interactions are the dominant initial driving force for the protein folding. Hart and Istrail gave approximation algorithms for folding proteins on the cubic lattice under HP model. In this paper, we examine the choice of a lattice by considering its algorithmic and geometric implications and argue that triangular lattice is a more reasonable choice. We present a set of folding rules for a triangular lattice and analyze the approximation ratio which they achieve. In addition, we introduce a generalization of the HP model to account for residues having different levels of hydrophobicity. After describing the biological foundation for this generalization, we show that in the new model we are able to achieve similar constant factor approximation guarantees on the triangular lattice as were achieved in the standard HP model. While the structures derived from our folding rules are probably still far from biological reality, we hope that having a set of folding rules with different properties will yield more interesting folds when combined.

  20. Comments on single-mass models of vocal fold vibration

    PubMed Central

    McGowan, Richard S.; Howe, Michael S.

    2010-01-01

    Proposed mechanisms for single-mass oscillation in the vocal tract are examined critically. There are two areas that distinguish single-mass models: in the sophistication of the air flow modeling near the oscillator and whether or not oscillation depends on acoustic feedback. Two recent models that do not depend on acoustic feedback are examined in detail. One model that depends on changing flow separation points is extended with approximate calculations. PMID:21117717

  1. The influence of material anisotropy on vibration at onset in a three-dimensional vocal fold model

    PubMed Central

    Zhang, Zhaoyan

    2014-01-01

    Although vocal folds are known to be anisotropic, the influence of material anisotropy on vocal fold vibration remains largely unknown. Using a linear stability analysis, phonation onset characteristics were investigated in a three-dimensional anisotropic vocal fold model. The results showed that isotropic models had a tendency to vibrate in a swing-like motion, with vibration primarily along the superior-inferior direction. Anterior-posterior (AP) out-of-phase motion was also observed and large vocal fold vibration was confined to the middle third region along the AP length. In contrast, increasing anisotropy or increasing AP-transverse stiffness ratio suppressed this swing-like motion and allowed the vocal fold to vibrate in a more wave-like motion with strong medial-lateral motion over the entire medial surface. Increasing anisotropy also suppressed the AP out-of-phase motion, allowing the vocal fold to vibrate in phase along the entire AP length. Results also showed that such improvement in vibration pattern was the most effective with large anisotropy in the cover layer alone. These numerical predictions were consistent with previous experimental observations using self-oscillating physical models. It was further hypothesized that these differences may facilitate complete glottal closure in finite-amplitude vibration of anisotropic models as observed in recent experiments. PMID:24606284

  2. The influence of material anisotropy on vibration at onset in a three-dimensional vocal fold model.

    PubMed

    Zhang, Zhaoyan

    2014-03-01

    Although vocal folds are known to be anisotropic, the influence of material anisotropy on vocal fold vibration remains largely unknown. Using a linear stability analysis, phonation onset characteristics were investigated in a three-dimensional anisotropic vocal fold model. The results showed that isotropic models had a tendency to vibrate in a swing-like motion, with vibration primarily along the superior-inferior direction. Anterior-posterior (AP) out-of-phase motion was also observed and large vocal fold vibration was confined to the middle third region along the AP length. In contrast, increasing anisotropy or increasing AP-transverse stiffness ratio suppressed this swing-like motion and allowed the vocal fold to vibrate in a more wave-like motion with strong medial-lateral motion over the entire medial surface. Increasing anisotropy also suppressed the AP out-of-phase motion, allowing the vocal fold to vibrate in phase along the entire AP length. Results also showed that such improvement in vibration pattern was the most effective with large anisotropy in the cover layer alone. These numerical predictions were consistent with previous experimental observations using self-oscillating physical models. It was further hypothesized that these differences may facilitate complete glottal closure in finite-amplitude vibration of anisotropic models as observed in recent experiments.

  3. Folding model analysis of 240 MeV {sup 6}Li elastic scattering on {sup 116}Sn and inelastic scattering to low-lying states of {sup 116}Sn

    SciTech Connect

    Chen, X.; Lui, Y.-W.; Clark, H. L.; Tokimoto, Y.; Youngblood, D. H.

    2007-11-15

    Elastic scattering of 240 MeV {sup 6}Li ions from {sup 116}Sn was measured from 4 deg.{<=}{theta}{sub c.m.}{<=}32 deg. The data were fitted with a Woods-Saxon phenomenological potential and with double folding models using the M3Y NN effective interaction with and without density dependence. DWBA calculations with the fitted parameters were used to calculate cross sections for inelastic scattering to low-lying 2{sup +}and 3{sup -} states. B(E2) and B(E3) values were extracted and compared with electromagnetic values and those obtained from {alpha} inelastic scattering.

  4. Insights from Coarse-Grained Gō Models for Protein Folding and Dynamics

    PubMed Central

    Hills, Ronald D.; Brooks, Charles L.

    2009-01-01

    Exploring the landscape of large scale conformational changes such as protein folding at atomistic detail poses a considerable computational challenge. Coarse-grained representations of the peptide chain have therefore been developed and over the last decade have proved extremely valuable. These include topology-based Gō models, which constitute a smooth and funnel-like approximation to the folding landscape. We review the many variations of the Gō model that have been employed to yield insight into folding mechanisms. Their success has been interpreted as a consequence of the dominant role of the native topology in folding. The role of local contact density in determining protein dynamics is also discussed and is used to explain the ability of Gō-like models to capture sequence effects in folding and elucidate conformational transitions. PMID:19399227

  5. Mathematics, Thermodynamics, and Modeling to Address Ten Common Misconceptions about Protein Structure, Folding, and Stability

    ERIC Educational Resources Information Center

    Robic, Srebrenka

    2010-01-01

    To fully understand the roles proteins play in cellular processes, students need to grasp complex ideas about protein structure, folding, and stability. Our current understanding of these topics is based on mathematical models and experimental data. However, protein structure, folding, and stability are often introduced as descriptive, qualitative…

  6. Folding in a semi-flexible lattice model for Crambin

    NASA Astrophysics Data System (ADS)

    Shi, Guangjie; Farris, Alfred C. K.; Wüst, Thomas; Landau, David P.

    2016-01-01

    Using the Replica-Exchange Wang-Landau sampling method, we investigated and compared three different coarse-grained lattice protein models for the small, hydrophobic protein Crambin. We show that slight extensions of the HP lattice protein model, including the stiffness of bonds can lead to a significant decrease in ground-state degeneracies (up to 5 orders of magnitudes). Moreover, the ground-state structures begin to bear resemblance to native structures observed in real Crambin.

  7. Using Kinetic Network Models To Probe Non-Native Salt-Bridge Effects on α-Helix Folding.

    PubMed

    Zhou, Guangfeng; Voelz, Vincent A

    2016-02-11

    Salt-bridge interactions play an important role in stabilizing many protein structures, and have been shown to be designable features for protein design. In this work, we study the effects of non-native salt bridges on the folding of a soluble alanine-based peptide (Fs peptide) using extensive all-atom molecular dynamics simulations performed on the Folding@home distributed computing platform. Using Markov State Models, we show how non-native salt-bridges affect the folding kinetics of Fs peptide by perturbing specific conformational states. Furthermore, we present methods for the automatic detection and analysis of such states. These results provide insight into helix folding mechanisms and useful information to guide simulation-based computational protein design.

  8. 100-fold but not 50-fold dystrophin overexpression aggravates electrocardiographic defects in the mdx model of Duchenne muscular dystrophy

    PubMed Central

    Yue, Yongping; Wasala, Nalinda B; Bostick, Brian; Duan, Dongsheng

    2016-01-01

    Dystrophin gene replacement holds the promise of treating Duchenne muscular dystrophy. Supraphysiological expression is a concern for all gene therapy studies. In the case of Duchenne muscular dystrophy, Chamberlain and colleagues found that 50-fold overexpression did not cause deleterious side effect in skeletal muscle. To determine whether excessive dystrophin expression in the heart is safe, we studied two lines of transgenic mdx mice that selectively expressed a therapeutic minidystrophin gene in the heart at 50-fold and 100-fold of the normal levels. In the line with 50-fold overexpression, minidystrophin showed sarcolemmal localization and electrocardiogram abnormalities were corrected. However, in the line with 100-fold overexpression, we not only detected sarcolemmal minidystrophin expression but also observed accumulation of minidystrophin vesicles in the sarcoplasm. Excessive minidystrophin expression did not correct tachycardia, a characteristic feature of Duchenne muscular dystrophy. Importantly, several electrocardiogram parameters (QT interval, QRS duration and the cardiomyopathy index) became worse than that of mdx mice. Our data suggests that the mouse heart can tolerate 50-fold minidystrophin overexpression, but 100-fold overexpression leads to cardiac toxicity. PMID:27419194

  9. Influence of numerical model decisions on the flow-induced vibration of a computational vocal fold model

    PubMed Central

    Shurtz, Timothy E.; Thomson, Scott L.

    2012-01-01

    Computational vocal fold models are often used to study the physics of voice production. In this paper the sensitivity of predicted vocal fold flow-induced vibration and resulting airflow patterns to several modeling selections is explored. The location of contact lines used to prevent mesh collapse and assumptions of symmetry were found to influence airflow patterns. However, these variables had relatively little effect on the vibratory response of the vocal fold model itself. Model motion was very sensitive to Poisson’s ratio. The importance of these parameter sensitivities in the context of vocal fold modeling is discussed. PMID:23794762

  10. Folding style controlled by intermediate decollement thickness change in the Lurestan region (NW of the Zagros fold-and-thrust belt), using analogue models

    NASA Astrophysics Data System (ADS)

    Farzipour Saein, Ali

    2016-07-01

    The basal and intermediate decollements play an important role in structural style of fold-and-thrust belts. The decollement units, or different mechanical stratigraphy within the rock units, are not uniform throughout the ZFTB and show a strong spatial variation. The Lurestan region with varied thickness of the intermediate decollement in its northern and southern parts is one of the most important parts of the Zagros fold-and-thrust belt, regarding its hydrocarbon exploration-extraction projects. Thickness variation of the intermediate decollement in different parts of the Lurestan region allows us to address its role on folding style. Based on scaled analogue modeling, this study outlines the impact of thickness and facies variation of sedimentary rocks in the northern and southern parts of this region on folding style. Two models simulated the mechanical stratigraphy and its consequent different folding styles of the northern and southern parts of the region. In the models, only thickness of the intermediate decollement (thick and thin) for the northern and southern parts of the Lurestan region was varied. Detached minor folds above the intermediate decollement were created in response to the presence of the thicker intermediate decollement, northern part of the study area, which consequently deformed complexly and disharmonically folded, in contrast to polyharmonic folding style in the section, compared to polyharmonic folding style in the southern part, where thin intermediate decollement exists. The model results documented that thickness variation of intermediate decollement levels could explain complex and different folding styles in natural examples which must be taken into account for hydrocarbon exploration throughout these areas.

  11. Lattice and off-lattice side chain models of protein folding: linear time structure prediction better than 86% of optimal.

    PubMed

    Hart, W E; Istrail, S

    1997-01-01

    This paper considers the protein energy minimization problem for lattice and off-lattice protein folding models that explicitly represent side chains. Lattice models of proteins have proven useful tools for reasoning about protein folding in unrestricted continuous space through analogy. This paper provides the first illustration of how rigorous algorithmic analyses of lattice models can lead to rigorous algorithmic analyses of off-lattice models. We consider two side chain models: a lattice model that generalizes the HP model (Dill, 1985) to explicitly represent side chains on the cubic lattice and a new off-lattice model, the HP Tangent Spheres Side Chain model (HP-TSSC), that generalizes this model further by representing the backbone and side chains of proteins with tangent spheres. We describe algorithms with mathematically guaranteed error bounds for both of these models. In particular, we describe a linear time performance guaranteed approximation algorithm for the HP side chain model that constructs conformations whose energy is better than 86% of optimal in a face-centered cubic lattice, and we demonstrate how this provides a better than 70% performance guarantee for the HP-TSSC model. Our analysis provides a mathematical methodology for transferring performance guarantees on lattices to off-lattice models. These results partially answer the open question of Ngo et al. (1994) concerning the complexity of protein folding models that include side chains.

  12. Equilibrium folding and stability of myotrophin: a model ankyrin repeat protein.

    PubMed

    Mosavi, Leila K; Williams, Suzanna; Peng Zy, Zheng-yu

    2002-07-05

    Proteins containing stretches of repeating amino acid sequences are prevalent throughout nature, yet little is known about the general folding and assembly mechanisms of these systems. Here we propose myotrophin as a model system to study the folding of ankyrin repeat proteins. Myotrophin is folded over a large pH range and is soluble at high concentrations. Thermal and urea denaturation studies show that the protein displays cooperative two-state folding properties despite its modular nature. Taken together with previous studies on other ankyrin repeat proteins, our data suggest that the two-state folding pathway may be characteristic of ankyrin repeat proteins and other integrated alpha-helical repeat proteins in general.

  13. Functional analysis of propeptide as an intramolecular chaperone for in vivo folding of subtilisin nattokinase.

    PubMed

    Jia, Yan; Liu, Hui; Bao, Wei; Weng, Meizhi; Chen, Wei; Cai, Yongjun; Zheng, Zhongliang; Zou, Guolin

    2010-12-01

    Here, we show that during in vivo folding of the precursor, the propeptide of subtilisin nattokinase functions as an intramolecular chaperone (IMC) that organises the in vivo folding of the subtilisin domain. Two residues belonging to β-strands formed by conserved regions of the IMC are crucial for the folding of the subtilisin domain through direct interactions. An identical protease can fold into different conformations in vivo due to the action of a mutated IMC, resulting in different kinetic parameters. Some interfacial changes involving conserved regions, even those induced by the subtilisin domain, blocked subtilisin folding and altered its conformation. Insight into the interaction between the subtilisin and IMC domains is provided by a three-dimensional structural model.

  14. Protein folding dynamics: the diffusion-collision model and experimental data.

    PubMed Central

    Karplus, M.; Weaver, D. L.

    1994-01-01

    The diffusion-collision model of protein folding is assessed. A description is given of the qualitative aspects and quantitative results of the diffusion-collision model and their relation to available experimental data. We consider alternative mechanisms for folding and point out their relationship to the diffusion-collision model. We show that the diffusion-collision model is supported by a growing body of experimental and theoretical evidence, and we outline future directions for developing the model and its applications. PMID:8003983

  15. 2-D modelling of the anticlinal structures and structural development of the eastern fold belt of the Bengal Basin, Bangladesh

    NASA Astrophysics Data System (ADS)

    Sikder, Arif Mohiuddin; Alam, M. Mustafa

    2003-02-01

    Structural architecture of the Bengal Basin has been strongly controlled by the collision pattern of the Indian plate with the Burma and Tibetan plates. The eastern fold belt (EFB) of the basin, comprising a series of north-south-trending curvilinear anticlines and synclines, represents a fold-and-thrust belt that constitutes the westward continuation of Arakan-Chin fold system of the Indo-Burman Ranges. The present study is mainly concerned with the 2-D modelling of the anticlinal structures in order to develop an understanding about the process-response relationships between the structural style and tectonic evolution of the eastern fold belt. The dominant fold-generating mechanism is believed to be the east-west-directed compressional force arising from oblique subduction of the Indian plate beneath the Burma plate that resulted in the growth of fault-propagation folds above a detachment or decollement at depth, giving rise to the Neogene accretionary prism complex development. A prominent feature of the region is the major east-dipping thrusts separating successive accretionary wedges. In seismic sections, evidence for several phases of compressional deformation suggests that multiphase stress conditions were responsible for the structural expression of the fold belt. Deep seismic sections reveal that the base of folding is characterized by a low-interval velocity horizon that represents a detachment separating the upper folded zone from the lower, seismically coherent, nearly unfolded zone. This detachment coincides with the undercompacted pressured shale unit, which is thought to have played an important role in the structural development of the eastern fold belt. Clay mineralogical analysis reveals the presence of a low-density shale horizon within the dense and thick shale sequence that is thought to be an undercompacted pressured shale during the geological past, and was responsible for the initiation of decollement and incipient diapirism involving thin

  16. Pipette aspiration applied to the characterization of nonhomogeneous, transversely isotropic materials used for vocal fold modeling

    PubMed Central

    Weiβ, S.; Thomson, S.L.; Lerch, R.; Döllinger, M.; Sutor, A.

    2012-01-01

    The etiology and treatment of voice disorders are still not completely understood. Since the vibratory characteristics of vocal folds are strongly influenced by both anatomy and mechanical material properties, measurement methods to analyze the material behavior of vocal fold tissue are required. Due to the limited life time of real tissue in the laboratory, synthetic models are often used to study vocal fold vibrations. In this paper we focus on two topics related to synthetic and real vocal fold materials. First, because certain tissues within the human vocal folds are transversely isotropic, a fabrication process for introducing this characteristic in commonly-used vocal fold modeling materials is presented. Second, the pipette aspiration technique is applied to the characterization of these materials. By measuring the displacement profiles of stretched specimens that exhibit varying degrees of transverse isotropy, it is shown that local anisotropy can be quantified using a parameter describing the deviation from an axisymmetric profile. The potential for this technique to characterize homogeneous, anisotropic materials, including soft biological tissues such as those found in the human vocal folds, is supplemented by a computational study. PMID:23127628

  17. Structural analysis of sheath folds in the Sylacauga Marble Group, Talladega slate belt, southern Appalachians

    USGS Publications Warehouse

    Mies, J.W.

    1993-01-01

    Remnant blocks of marble from the Moretti-Harrah dimension-stone quarry provide excellent exposure of meter-scale sheath folds. Tubular structures with elliptical cross-sections (4 ???Ryz ??? 5) are the most common expression of the folds. The tubes are elongate subparallel to stretching lineation and are defined by centimeter-scale layers of schist. Eccentrically nested elliptical patterns and opposing asymmetry of folds ('S' and 'Z') are consistent with the sheath-fold interpretation. Sheath folds are locally numerous in the Moretti-Harrah quarry but are not widely distributed in the Sylacauga Marble Group; reconnaissance in neighboring quarries provided no additional observations. The presence of sheath folds in part of the Talladega slate belt indicates a local history of plastic, non-coaxial deformation. Such a history of deformation is substantiated by petrographic study of an extracted hinge from the Moretti-Harrah quarry. The sheath folds are modeled as due to passive amplification of initial structures during simple shear, using both analytic geometry and graphic simulation. As indicated by these models, relatively large shear strains (y ??? 9) and longitudinal initial structures are required. The shear strain presumably relates to NW-directed displacement of overlying crystalline rocks during late Paleozoic orogeny. ?? 1993.

  18. Biomechanical modeling of the three-dimensional aspects of human vocal fold dynamics

    PubMed Central

    Yang, Anxiong; Lohscheller, Jörg; Berry, David A.; Becker, Stefan; Eysholdt, Ulrich; Voigt, Daniel; Döllinger, Michael

    2010-01-01

    Human voice originates from the three-dimensional (3D) oscillations of the vocal folds. In previous studies, biomechanical properties of vocal fold tissues have been predicted by optimizing the parameters of simple two-mass-models to fit its dynamics to the high-speed imaging data from the clinic. However, only lateral and longitudinal displacements of the vocal folds were considered. To extend previous studies, a 3D mass-spring, cover-model is developed, which predicts the 3D vibrations of the entire medial surface of the vocal fold. The model consists of five mass planes arranged in vertical direction. Each plane contains five longitudinal, mass-spring, coupled oscillators. Feasibility of the model is assessed using a large body of dynamical data previously obtained from excised human larynx experiments, in vivo canine larynx experiments, physical models, and numerical models. Typical model output was found to be similar to existing findings. The resulting model enables visualization of the 3D dynamics of the human vocal folds during phonation for both symmetric and asymmetric vibrations. PMID:20136223

  19. Information-Theoretic Uncertainty of SCFG-Modeled Folding Space of The Non-coding RNA

    PubMed Central

    Manzourolajdad, Amirhossein; Wang, Yingfeng; Shaw, Timothy I.; Malmberg, Russell L.

    2012-01-01

    RNA secondary structure ensembles define probability distributions for alternative equilibrium secondary structures of an RNA sequence. Shannon’s Entropy is a measure for the amount of diversity present in any ensemble. In this work, Shannon’s entropy of the SCFG ensemble on an RNA sequence is derived and implemented in polynomial time for both structurally ambiguous and unambiguous grammars. Micro RNA sequences generally have low folding entropy, as previously discovered. Surprisingly, signs of significantly high folding entropy were observed in certain ncRNA families. More effective models coupled with targeted randomization tests can lead to a better insight into folding features of these families. PMID:23160142

  20. Estimating the probability for a protein to have a new fold: A statistical computational model

    PubMed Central

    Portugaly, Elon; Linial, Michal

    2000-01-01

    Structural genomics aims to solve a large number of protein structures that represent the protein space. Currently an exhaustive solution for all structures seems prohibitively expensive, so the challenge is to define a relatively small set of proteins with new, currently unknown folds. This paper presents a method that assigns each protein with a probability of having an unsolved fold. The method makes extensive use of protomap, a sequence-based classification, and scop, a structure-based classification. According to protomap, the protein space encodes the relationship among proteins as a graph whose vertices correspond to 13,354 clusters of proteins. A representative fold for a cluster with at least one solved protein is determined after superposition of all scop (release 1.37) folds onto protomap clusters. Distances within the protomap graph are computed from each representative fold to the neighboring folds. The distribution of these distances is used to create a statistical model for distances among those folds that are already known and those that have yet to be discovered. The distribution of distances for solved/unsolved proteins is significantly different. This difference makes it possible to use Bayes' rule to derive a statistical estimate that any protein has a yet undetermined fold. Proteins that score the highest probability to represent a new fold constitute the target list for structural determination. Our predicted probabilities for unsolved proteins correlate very well with the proportion of new folds among recently solved structures (new scop 1.39 records) that are disjoint from our original training set. PMID:10792051

  1. Modeling of wind gap formation and development of sedimentary basins during fold growth: application to the Zagros Fold Belt, Iran.

    NASA Astrophysics Data System (ADS)

    Collignon, Marine; Yamato, Philippe; Castelltort, Sébastien; Kaus, Boris

    2016-04-01

    Mountain building and landscape evolution are controlled by the interactions between river dynamics and tectonic forces. Such interactions have been largely studied but a quantitative evaluation of tectonic/geomorphic feedbacks remains required for understanding sediments routing within orogens and fold-and-thrust belts. Here, we employ numerical simulations to assess the conditions of uplift and river incision necessary to deflect an antecedent drainage network during the growth of one or several folds. We propose that a partitioning of the river network into internal (endorheic) and longitudinal drainage arises as a result of lithological differences within the deforming crustal sedimentary cover. We show with examples from the Zagros Fold Belt (ZFB) that drainage patterns can be linked to the incision ratio R between successive lithological layers, corresponding to the ratio between their relative erodibilities or incision coefficients. Transverse drainage networks develop for uplift rates smaller than 0.8 mm.yr-1 and -10 < R < 10. Intermediate drainage network are obtained for uplift rates up to 2 mm.yr-1 and incision ratios of 20. Parallel drainage networks and formation of sedimentary basins occur for large values of incision ratio (R >20) and uplift rates between 1 and 2 mm.yr-1. These results have implications for predicting the distribution of sediment depocenters in fold-and-thrust belts, which can be of direct economic interest for hydrocarbon exploration.

  2. Using Innovative Acoustic Analysis to Predict the Postoperative Outcomes of Unilateral Vocal Fold Paralysis

    PubMed Central

    Tsou, Yung-An; Chen, Wei-Chen; Ke, Hsiang-Chun; Lin, Wen-Yang; Yang, Hsing-Rong; Shie, Dung-Yun; Tsai, Ming-Hsui

    2016-01-01

    Objective. Autologous fat injection laryngoplasty is ineffective for some patients with iatrogenic vocal fold paralysis, and additional laryngeal framework surgery is often required. An acoustically measurable outcome predictor for lipoinjection laryngoplasty would assist phonosurgeons in formulating treatment strategies. Methods. Seventeen thyroid surgery patients with unilateral vocal fold paralysis participated in this study. All subjects underwent lipoinjection laryngoplasty to treat postsurgery vocal hoarseness. After treatment, patients were assigned to success and failure groups on the basis of voice improvement. Linear prediction analysis was used to construct a new voice quality indicator, the number of irregular peaks (NIrrP). It compared with the measures used in the Multi-Dimensional Voice Program (MDVP), such as jitter (frequency perturbation) and shimmer (perturbation of amplitude). Results. By comparing the [i] vowel produced by patients before the lipoinjection laryngoplasty (AUC = 0.98, 95% CI = 0.78–0.99), NIrrP was shown to be a more accurate predictor of long-term surgical outcomes than jitter (AUC = 0.73, 95% CI = 0.47–0.91) and shimmer (AUC = 0.63, 95% CI = 0.37–0.85), as identified by the receiver operating characteristic curve. Conclusions. NIrrP measured using the LP model could be a more accurate outcome predictor than the parameters used in the MDVP. PMID:27738634

  3. Theoretical models for designing a 220-GHz folded waveguide backward wave oscillator

    NASA Astrophysics Data System (ADS)

    Cai, Jin-Chi; Hu, Lin-Lin; Ma, Guo-Wu; Chen, Hong-Bin; Jin, Xiao; Chen, Huai-Bi

    2015-06-01

    In this paper, the basic equations of beam-wave interaction for designing the 220 GHz folded waveguide (FW) backward wave oscillator (BWO) are described. On the whole, these equations are mainly classified into small signal model (SSM), large signal model (LSM), and simplified small signal model (SSSM). Using these linear and nonlinear one-dimensional (1D) models, the oscillation characteristics of the FW BWO of a given configuration of slow wave structure (SWS) can be calculated by numerical iteration algorithm, which is more time efficient than three-dimensional (3D) particle-in-cell (PIC) simulation. The SSSM expressed by analytical formulas is innovatively derived for determining the initial values of the FW SWS conveniently. The dispersion characteristics of the FW are obtained by equivalent circuit analysis. The space charge effect, the end reflection effect, the lossy wall effect, and the relativistic effect are all considered in our models to offer more accurate results. The design process of the FW BWO tube with output power of watt scale in a frequency range between 215 GHz and 225 GHz based on these 1D models is demonstrated. The 3D PIC method is adopted to verify the theoretical design results, which shows that they are in good agreement with each other. Project supported by the Innovative Research Foundation of China Academy of Engineering Physics (Grant No. 426050502-2).

  4. Mutational analysis of the BPTI folding pathway: I. Effects of aromatic-->leucine substitutions on the distribution of folding intermediates.

    PubMed Central

    Zhang, J. X.; Goldenberg, D. P.

    1997-01-01

    The roles of aromatic residues in determining the folding pathway of bovine pancreatic trypsin inhibitor (BPTI) were analyzed mutationally by examining the distribution of disulfide-bonded intermediates that accumulated during the refolding of protein variants in which tyrosine or phenylalanine residues were individually replaced with leucine. The eight substitutions examined all caused significant changes in the intermediate distribution. In some cases, the major effect was to decrease the accumulation of intermediates containing two of the three disulfides found in the native protein, without affecting the distribution of earlier intermediates. Other substitutions, however, led to much more random distributions of the intermediates containing only one disulfide. These results indicate that the individual residues making up the hydrophobic core of the native protein make clearly distinguishable contributions to conformation and stability early in folding: The early distribution of intermediates does not appear to be determined by a general hydrophobic collapse. The effects of the substitutions were generally consistent with the structures of the major intermediates determined by NMR studies of analogs, confirming that the distribution of disulfide-bonded species is determined by stabilizing interactions within the ordered regions of the intermediates. The plasticity of the BPTI folding pathway implied by these results can be described using conformational funnels to illustrate the degree to which conformational entropy is lost at different stages in the folding of the wild-type and mutant proteins. PMID:9232656

  5. Asymptotic distribution of motifs in a stochastic context-free grammar model of RNA folding.

    PubMed

    Poznanović, Svetlana; Heitsch, Christine E

    2014-12-01

    We analyze the distribution of RNA secondary structures given by the Knudsen-Hein stochastic context-free grammar used in the prediction program Pfold. Our main theorem gives relations between the expected number of these motifs--independent of the grammar probabilities. These relations are a consequence of proving that the distribution of base pairs, of helices, and of different types of loops is asymptotically Gaussian in this model of RNA folding. Proof techniques use singularity analysis of probability generating functions. We also demonstrate that these asymptotic results capture well the expected number of RNA base pairs in native ribosomal structures, and certain other aspects of their predicted secondary structures. In particular, we find that the predicted structures largely satisfy the expected relations, although the native structures do not.

  6. Capturing the essence of folding and functions of biomolecules using coarse-grained models.

    PubMed

    Hyeon, Changbong; Thirumalai, D

    2011-09-27

    The distances over which biological molecules and their complexes can function range from a few nanometres, in the case of folded structures, to millimetres, for example, during chromosome organization. Describing phenomena that cover such diverse length, and also time, scales requires models that capture the underlying physics for the particular length scale of interest. Theoretical ideas, in particular, concepts from polymer physics, have guided the development of coarse-grained models to study folding of DNA, RNA and proteins. More recently, such models and their variants have been applied to the functions of biological nanomachines. Simulations using coarse-grained models are now poised to address a wide range of problems in biology.

  7. Constructing a folding model for protein S6 guided by native fluctuations deduced from NMR structures

    SciTech Connect

    Lammert, Heiko; Noel, Jeffrey K.; Haglund, Ellinor; Onuchic, José N.; Schug, Alexander

    2015-12-28

    The diversity in a set of protein nuclear magnetic resonance (NMR) structures provides an estimate of native state fluctuations that can be used to refine and enrich structure-based protein models (SBMs). Dynamics are an essential part of a protein’s functional native state. The dynamics in the native state are controlled by the same funneled energy landscape that guides the entire folding process. SBMs apply the principle of minimal frustration, drawn from energy landscape theory, to construct a funneled folding landscape for a given protein using only information from the native structure. On an energy landscape smoothed by evolution towards minimal frustration, geometrical constraints, imposed by the native structure, control the folding mechanism and shape the native dynamics revealed by the model. Native-state fluctuations can alternatively be estimated directly from the diversity in the set of NMR structures for a protein. Based on this information, we identify a highly flexible loop in the ribosomal protein S6 and modify the contact map in a SBM to accommodate the inferred dynamics. By taking into account the probable native state dynamics, the experimental transition state is recovered in the model, and the correct order of folding events is restored. Our study highlights how the shared energy landscape connects folding and function by showing that a better description of the native basin improves the prediction of the folding mechanism.

  8. Investigating the Three-dimensional Flow Separation Induced by a Model Vocal Fold Polyp

    PubMed Central

    Stewart, Kelley C.; Erath, Byron D.; Plesniak, Michael W.

    2014-01-01

    The fluid-structure energy exchange process for normal speech has been studied extensively, but it is not well understood for pathological conditions. Polyps and nodules, which are geometric abnormalities that form on the medial surface of the vocal folds, can disrupt vocal fold dynamics and thus can have devastating consequences on a patient's ability to communicate. Our laboratory has reported particle image velocimetry (PIV) measurements, within an investigation of a model polyp located on the medial surface of an in vitro driven vocal fold model, which show that such a geometric abnormality considerably disrupts the glottal jet behavior. This flow field adjustment is a likely reason for the severe degradation of the vocal quality in patients with polyps. A more complete understanding of the formation and propagation of vortical structures from a geometric protuberance, such as a vocal fold polyp, and the resulting influence on the aerodynamic loadings that drive the vocal fold dynamics, is necessary for advancing the treatment of this pathological condition. The present investigation concerns the three-dimensional flow separation induced by a wall-mounted prolate hemispheroid with a 2:1 aspect ratio in cross flow, i.e. a model vocal fold polyp, using an oil-film visualization technique. Unsteady, three-dimensional flow separation and its impact of the wall pressure loading are examined using skin friction line visualization and wall pressure measurements. PMID:24513707

  9. Monte Carlo simulations of the HP model (the "Ising model" of protein folding)

    NASA Astrophysics Data System (ADS)

    Li, Ying Wai; Wüst, Thomas; Landau, David P.

    2011-09-01

    Using Wang-Landau sampling with suitable Monte Carlo trial moves (pull moves and bond-rebridging moves combined) we have determined the density of states and thermodynamic properties for a short sequence of the HP protein model. For free chains these proteins are known to first undergo a collapse "transition" to a globule state followed by a second "transition" into a native state. When placed in the proximity of an attractive surface, there is a competition between surface adsorption and folding that leads to an intriguing sequence of "transitions". These transitions depend upon the relative interaction strengths and are largely inaccessible to "standard" Monte Carlo methods.

  10. Monte Carlo simulations of the HP model (the "Ising model" of protein folding).

    PubMed

    Li, Ying Wai; Wüst, Thomas; Landau, David P

    2011-09-01

    Using Wang-Landau sampling with suitable Monte Carlo trial moves (pull moves and bond-rebridging moves combined) we have determined the density of states and thermodynamic properties for a short sequence of the HP protein model. For free chains these proteins are known to first undergo a collapse "transition" to a globule state followed by a second "transition" into a native state. When placed in the proximity of an attractive surface, there is a competition between surface adsorption and folding that leads to an intriguing sequence of "transitions". These transitions depend upon the relative interaction strengths and are largely inaccessible to "standard" Monte Carlo methods.

  11. Modeling coupled aerodynamics and vocal fold dynamics using immersed boundary methods.

    PubMed

    Duncan, Comer; Zhai, Guangnian; Scherer, Ronald

    2006-11-01

    The penalty immersed boundary (PIB) method, originally introduced by Peskin (1972) to model the function of the mammalian heart, is tested as a fluid-structure interaction model of the closely coupled dynamics of the vocal folds and aerodynamics in phonation. Two-dimensional vocal folds are simulated with material properties chosen to result in self-oscillation and volume flows in physiological frequency ranges. Properties of the glottal flow field, including vorticity, are studied in conjunction with the dynamic vocal fold motion. The results of using the PIB method to model self-oscillating vocal folds for the case of 8 cm H20 as the transglottal pressure gradient are described. The volume flow at 8 cm H20, the transglottal pressure, and vortex dynamics associated with the self-oscillating model are shown. Volume flow is also given for 2, 4, and 12 cm H2O, illustrating the robustness of the model to a range of transglottal pressures. The results indicate that the PIB method applied to modeling phonation has good potential for the study of the interdependence of aerodynamics and vocal fold motion.

  12. Denatured-state energy landscapes of a protein structural database reveal the energetic determinants of a framework model for folding.

    PubMed

    Wang, Suwei; Gu, Jenny; Larson, Scott A; Whitten, Steven T; Hilser, Vincent J

    2008-09-19

    Position-specific denatured-state thermodynamics were determined for a database of human proteins by use of an ensemble-based model of protein structure. The results of modeling denatured protein in this manner reveal important sequence-dependent thermodynamic properties in the denatured ensembles as well as fundamental differences between the denatured and native ensembles in overall thermodynamic character. The generality and robustness of these results were validated by performing fold-recognition experiments, whereby sequences were matched with their respective folds based on amino acid propensities for the different energetic environments in the protein, as determined through cluster analysis. Correlation analysis between structure and energetic information revealed that sequence segments destined for beta-sheet in the final native fold are energetically more predisposed to a broader repertoire of states than are sequence segments destined for alpha-helix. These results suggest that within the subensemble of mostly unstructured states, the energy landscapes are dominated by states in which parts of helices adopt structure, whereas structure formation for sequences destined for beta-strand is far less probable. These results support a framework model of folding, which suggests that, in general, the denatured state has evolutionarily evolved to avoid low-energy conformations in sequences that ultimately adopt beta-strand. Instead, the denatured state evolved so that sequence segments that ultimately adopt alpha-helix and coil will have a high intrinsic structure formation capability, thus serving as potential nucleation sites.

  13. Critical State Finite Element Models of Contractional Fault-Related Folding: Structural and Mechanical Analyses

    NASA Astrophysics Data System (ADS)

    Albertz, M.; Lingrey, S.; Sanz, P. F.

    2011-12-01

    Geometric/kinematic models of the common fault-related fold types (fault-bend, fault-propagation, detachment folding) typically assume a simplified flexural-slip based bed-parallel simple shear mechanism. The magnitude of local strain is a function of layer dip change irrespective of material properties. Line-lengths parallel to and layer thicknesses orthogonal to the flexural-slip surface remain constant. This study reports on a range of more complicated kinematic and mechanical responses observed in fourteen idealized forward numerical models of contractional fault-related folding. The models test the effects of material properties, initial fault dip, and the presence of weak inter-layer detachment horizons. We employ a Lagrangian finite element method with adaptive remeshing and a constitutive model that is based on critical state mechanics. This approach allows for large, volumetric deformation and realistic evolution of the failure envelope during progressive deformation. We demonstrate that material properties affect the way faults propagate and thus exert a significant control on resultant fold layer geometry. In most cases, these geometries differ from the flexural-slip based kinematic idealizations. For instance, models of uniform sandstone properties exhibit efficient strain localization and clear patterns of fault tip propagation. Uniform shale properties tends to inhibit fault propagation due to distributed plastic deformation. Models with mixed inter-layered sandstone and shale deform in a disharmonic manner, resembling lobate-cuspate arrangements that are common to many outcrop-scale folds. Inter-layer detachments accommodate shortening by bed-parallel slip, resulting in fault-bend fold kinematics, imbrication of sand layers, and a general absence of fault propagation across layers. Constant area based plane strain restoration of the deformed models recovers the first-order contractional deformation (80-90% of true contractional strain). Constant line

  14. Experimental and Numerical Analysis of Composite Folded Sandwich Core Structures Under Compression

    NASA Astrophysics Data System (ADS)

    Heimbs, S.; Middendorf, P.; Kilchert, S.; Johnson, A. F.; Maier, M.

    2007-11-01

    The characterisation of the mechanical behaviour of folded core structures for advanced sandwich composites under flatwise compression load using a virtual testing approach is presented. In this context dynamic compression test simulations with the explicit solvers PAM-CRASH and LS-DYNA are compared to experimental data of two different folded core structures made of aramid paper and carbon fibre-reinforced plastic (CFRP). The focus of the investigations is the constitutive modelling of the cell wall material, the consideration of imperfections and the representation of cell wall buckling, folding or crushing phenomena. The consistency of the numerical results shows that this can be a promising and efficient approach for the determination of the effective mechanical properties and a cell geometry optimisation of folded core structures.

  15. Lattice and off-lattice side chain models of protein folding: Linear time structure prediction better than 86% of optimal

    SciTech Connect

    Hart, W.E.; Istrail, S.

    1996-08-09

    This paper considers the protein structure prediction problem for lattice and off-lattice protein folding models that explicitly represent side chains. Lattice models of proteins have proven extremely useful tools for reasoning about protein folding in unrestricted continuous space through analogy. This paper provides the first illustration of how rigorous algorithmic analyses of lattice models can lead to rigorous algorithmic analyses of off-lattice models. The authors consider two side chain models: a lattice model that generalizes the HP model (Dill 85) to explicitly represent side chains on the cubic lattice, and a new off-lattice model, the HP Tangent Spheres Side Chain model (HP-TSSC), that generalizes this model further by representing the backbone and side chains of proteins with tangent spheres. They describe algorithms for both of these models with mathematically guaranteed error bounds. In particular, the authors describe a linear time performance guaranteed approximation algorithm for the HP side chain model that constructs conformations whose energy is better than 865 of optimal in a face centered cubic lattice, and they demonstrate how this provides a 70% performance guarantee for the HP-TSSC model. This is the first algorithm in the literature for off-lattice protein structure prediction that has a rigorous performance guarantee. The analysis of the HP-TSSC model builds off of the work of Dancik and Hannenhalli who have developed a 16/30 approximation algorithm for the HP model on the hexagonal close packed lattice. Further, the analysis provides a mathematical methodology for transferring performance guarantees on lattices to off-lattice models. These results partially answer the open question of Karplus et al. concerning the complexity of protein folding models that include side chains.

  16. A Turing Reaction-Diffusion Model for Human Cortical Folding Patterns and Cortical Pattern Malformations

    NASA Astrophysics Data System (ADS)

    Hurdal, Monica K.; Striegel, Deborah A.

    2011-11-01

    Modeling and understanding cortical folding pattern formation is important for quantifying cortical development. We present a biomathematical model for cortical folding pattern formation in the human brain and apply this model to study diseases involving cortical pattern malformations associated with neural migration disorders. Polymicrogyria is a cortical malformation disease resulting in an excessive number of small gyri. Our mathematical model uses a Turing reaction-diffusion system to model cortical folding. The lateral ventricle (LV) and ventricular zone (VZ) of the brain are critical components in the formation of cortical patterning. In early cortical development the shape of the LV can be modeled with a prolate spheroid and the VZ with a prolate spheroid surface. We use our model to study how global cortex characteristics, such as size and shape of the LV, affect cortical pattern formation. We demonstrate increasing domain scale can increase the number of gyri and sulci formed. Changes in LV shape can account for sulcus directionality. By incorporating LV size and shape, our model is able to elucidate which parameters can lead to excessive cortical folding.

  17. Frequency Response of Synthetic Vocal Fold Models with Linear and Nonlinear Material Properties

    ERIC Educational Resources Information Center

    Shaw, Stephanie M.; Thomson, Scott L.; Dromey, Christopher; Smith, Simeon

    2012-01-01

    Purpose: The purpose of this study was to create synthetic vocal fold models with nonlinear stress-strain properties and to investigate the effect of linear versus nonlinear material properties on fundamental frequency (F[subscript 0]) during anterior-posterior stretching. Method: Three materially linear and 3 materially nonlinear models were…

  18. A simple quantitative model of macromolecular crowding effects on protein folding: Application to the murine prion protein(121-231)

    NASA Astrophysics Data System (ADS)

    Bergasa-Caceres, Fernando; Rabitz, Herschel A.

    2013-06-01

    A model of protein folding kinetics is applied to study the effects of macromolecular crowding on protein folding rate and stability. Macromolecular crowding is found to promote a decrease of the entropic cost of folding of proteins that produces an increase of both the stability and the folding rate. The acceleration of the folding rate due to macromolecular crowding is shown to be a topology-dependent effect. The model is applied to the folding dynamics of the murine prion protein (121-231). The differential effect of macromolecular crowding as a function of protein topology suffices to make non-native configurations relatively more accessible.

  19. Designability and cooperative folding in a four-letter hydrophobic-polar model of proteins

    NASA Astrophysics Data System (ADS)

    Liu, Hai-Guang; Tang, Lei-Han

    2006-11-01

    The two-letter hydrophobic-polar (HP) model of Lau and Dill [Macromolecules 22, 3986 (1989)] has been widely used in theoretical studies of protein folding due to its conceptual and computational simplicity. Despite its success in elucidating various aspects of the sequence-structure relationship, thermodynamic behavior of the model is not in agreement with a sharp two-state folding transition of many single-domain proteins. To gain a better understanding of this discrepancy, we consider an extension of the HP model by including an “antiferromagnetic” (AF) interaction in the contact potential that favors amino acid residues with complementary attributes. With an enlarged four-letter alphabet, the density of states on the low energy side can be significantly decreased. Computational studies of the four-letter HP model are performed on 36-mer sequences on a square lattice. It is found that the designability of folded structures in the extended model exhibits strong correlation with that of the two-letter HP model, while the AF interaction alone selects a very different class of structures that resembles the Greek key motif for beta sheets. A procedure is introduced to select sequences which have the largest energy gap to the native state. Based on density of states and specific heat calculations in the full configuration space, we show that the optimized sequence is able to fold nearly as cooperatively as a corresponding Gō model.

  20. Characterization of the vocal fold vertical stiffness in a canine model

    PubMed Central

    Oren, Liran; Dembinski, Doug; Gutmark, Ephraim; Khosla, Sid

    2014-01-01

    Objectives/Hypothesis Characterizing the vertical stiffness gradient that exists between the superior and inferior aspects of the medial surface of the vocal fold. Characterization of this stiffness gradient could elucidate the mechanism behind the divergent glottal shape observed during closing. Study Design Basic science. Methods Indentation testing of the folds was done in a canine model. Stress-strain curves are generated using a customized load-cell and the differential Young's modulus is calculated as a function of strain. Results Results from 11 larynges show that stress increases as a function of strain more rapidly in the inferior aspect of the fold. The calculations for local Young's modulus show that at high strain values a stiffness gradient is formed between the superior and inferior aspects of the fold. Conclusions For small strain values, which are observed at low subglottal pressures, the stiffness of the tissue is similar in both the superior and inferior aspects of the vocal fold. Consequently, the lateral force that is applied by the glottal flow at both aspects results in almost identical displacements, yielding no divergence angle. Conversely, at higher strain values, which are measured in high subglottal pressure, the inferior aspect of the vocal fold is much stiffer than the superior edge; thus any lateral force that is applied at both aspects will result in a much greater displacement of the superior edge, yielding a large divergence angle. The increased stiffness observed at the inferior edge could be due to the proximity of the conus elasticus. PMID:24495431

  1. An investigation of jet trajectory in flow through scaled vocal fold models with asymmetric glottal passages

    NASA Astrophysics Data System (ADS)

    Erath, Byron D.; Plesniak, Michael W.

    2006-11-01

    Pulsatile two-dimensional flow through asymmetric static divergent models of the human vocal folds is investigated. Included glottal divergence angles are varied between 10° and 30°, with asymmetry angles between the vocal fold pairs ranging from 5° to 15°. The model glottal configurations represent asymmetries that arise during a phonatory cycle due to voice disorders. The flow is scaled to physiological values of Reynolds, Strouhal, and Euler numbers. Data are acquired in the anterior posterior mid-plane of the vocal fold models using phase-averaged Particle Image Velocimetry (PIV) acquired at ten discrete locations in a phonatory cycle. Glottal jet stability arising from the vocal fold asymmetries is investigated and compared to previously reported work for symmetric vocal fold passages. Jet stability is enhanced with an increase in the included divergence angle, and the glottal asymmetry. Concurrently, the bi-modal jet trajectory and flow unsteadiness diminishes. Consistent with previous findings, the flow attachment due to the Coanda effect occurs when the acceleration of the forcing function is zero.

  2. Steric confinement and enhanced local flexibility assist knotting in simple models of protein folding.

    PubMed

    Soler, Miguel A; Rey, Antonio; Faísca, Patrícia F N

    2016-09-29

    The chaperonin complex GroEL-GroES is able to accelerate the folding process of knotted proteins considerably. However, the folding mechanism inside the chaperonin cage is elusive. Here we use a combination of lattice and off-lattice Monte Carlo simulations of simple Gō models to study the effect of physical confinement and local flexibility on the folding process of protein model systems embedding a trefoil knot in their native structure. This study predicts that steric confinement plays a specific role in the folding of knotted proteins by increasing the knotting probability for very high degrees of confinement. This effect is observed for protein MJ0366 even above the melting temperature for confinement sizes compatible with the size of the GroEL/GroES chaperonin cage. An enhanced local flexibility produces the same qualitative effects on the folding process. In particular, we observe that knotting probability increases up to 40% in the transition state of protein MJ0366 when flexibility is enhanced. This is underlined by a structural change in the transition state, which becomes devoid of helical content. No relation between the knotting mechanism and flexibility was found in the context of the off-lattice model adopted in this work.

  3. Principles of protein folding--a perspective from simple exact models.

    PubMed Central

    Dill, K. A.; Bromberg, S.; Yue, K.; Fiebig, K. M.; Yee, D. P.; Thomas, P. D.; Chan, H. S.

    1995-01-01

    General principles of protein structure, stability, and folding kinetics have recently been explored in computer simulations of simple exact lattice models. These models represent protein chains at a rudimentary level, but they involve few parameters, approximations, or implicit biases, and they allow complete explorations of conformational and sequence spaces. Such simulations have resulted in testable predictions that are sometimes unanticipated: The folding code is mainly binary and delocalized throughout the amino acid sequence. The secondary and tertiary structures of a protein are specified mainly by the sequence of polar and nonpolar monomers. More specific interactions may refine the structure, rather than dominate the folding code. Simple exact models can account for the properties that characterize protein folding: two-state cooperativity, secondary and tertiary structures, and multistage folding kinetics--fast hydrophobic collapse followed by slower annealing. These studies suggest the possibility of creating "foldable" chain molecules other than proteins. The encoding of a unique compact chain conformation may not require amino acids; it may require only the ability to synthesize specific monomer sequences in which at least one monomer type is solvent-averse. PMID:7613459

  4. Mathematics, thermodynamics, and modeling to address ten common misconceptions about protein structure, folding, and stability.

    PubMed

    Robic, Srebrenka

    2010-01-01

    To fully understand the roles proteins play in cellular processes, students need to grasp complex ideas about protein structure, folding, and stability. Our current understanding of these topics is based on mathematical models and experimental data. However, protein structure, folding, and stability are often introduced as descriptive, qualitative phenomena in undergraduate classes. In the process of learning about these topics, students often form incorrect ideas. For example, by learning about protein folding in the context of protein synthesis, students may come to an incorrect conclusion that once synthesized on the ribosome, a protein spends its entire cellular life time in its fully folded native confirmation. This is clearly not true; proteins are dynamic structures that undergo both local fluctuations and global unfolding events. To prevent and address such misconceptions, basic concepts of protein science can be introduced in the context of simple mathematical models and hands-on explorations of publicly available data sets. Ten common misconceptions about proteins are presented, along with suggestions for using equations, models, sequence, structure, and thermodynamic data to help students gain a deeper understanding of basic concepts relating to protein structure, folding, and stability.

  5. Computational Modeling of Ductile Folding in Sedimentary Rocks of the Sheep Mountain Anticline, Wyoming

    NASA Astrophysics Data System (ADS)

    Borja, R. I.; Sanz, P. F.; Fiore, P. E.; Pollard, D. D.

    2005-12-01

    Folding of sedimentary rocks occurs at depths in Earth's crust where some layers respond by brittle deformation while others respond by ductile deformation. Folding results from a number of mechanisms including buckling due to lateral tectonic compression and/or slip on thrust faults in the underlying strata. Movements experienced by folded strata are typically very large (tens to hundreds of meters or more) and may include significant rigid body translation and rotation, in addition to the straining of the folded layers. More specific types of straining could include any one or a combination of the following: plate-like bending, in-plane extension, in-plane contraction, and either in-plane or out-of-plane shearing. The stress state resulting from the overburden load, slip on underlying faults, and the associated folding could induce strain localization even as the layer continues to deform plastically. In this paper we present a mathematical model for capturing isothermal ductile folding processes and the accompanying strain localization in sedimentary rocks using nonlinear continuum mechanics and finite element modeling. We use a fully Lagrangian approach along with multiplicative plasticity theory for finite deformations, considering the effects of all three invariants of the stress tensor in the constitutive description. We also simulate the rigid body translation, finite rotation, and subsequent rupturing of preexisting faults using finite deformation kinematics and stick-slip contact mechanics. We apply the technique to simulate the three-dimensional folding of selected Paleozoic and Mesozoic formations located above the Madison limestone in the Sheep Mountain anticline, formed during the Laramide orogeny in the Bighorn Basin, Wyoming. Supported by U.S. Department of Energy, Grant No. DE-FG02-03ER15454, and U.S. National Science Foundation, Grant No. CMG-0417521.

  6. A Top-Down Approach to Mechanistic Biological Modeling: Application to the Single-Chain Antibody Folding Pathway

    PubMed Central

    Hildebrandt, Scott; Raden, David; Petzold, Linda; Robinson, Anne Skaja; Doyle, Francis J.

    2008-01-01

    A top-down approach to mechanistic modeling of biological systems is presented and exemplified with the development of a hypothesis-driven mathematical model for single-chain antibody fragment (scFv) folding in Saccharomyces cerevisiae by mediators BiP and PDI. In this approach, model development starts with construction of the most basic mathematical model—typically consisting of predetermined or newly-elucidated biological behavior motifs—capable of reproducing desired biological behaviors. From this point, mechanistic detail is added incrementally and systematically, and the effects of each addition are evaluated. This approach follows the typical progression of experimental data availability in that higher-order, lumped measurements are often more prevalent initially than specific, mechanistic ones. It also necessarily provides the modeler with insight into the structural requirements and performance capabilities of the resulting detailed mechanistic model, which facilitates further analysis. The top-down approach to mechanistic modeling identified three such requirements and a branched dependency-degradation competition motif critical for the scFv folding model to reproduce experimentally observed scFv folding dependencies on BiP and PDI and increased production when both species are overexpressed and promoted straightforward prediction of parameter dependencies. It also prescribed modification of the guiding hypothesis to capture BiP and PDI synergy. PMID:18641066

  7. Time-resolved transglottal pressure measurements in a scaled up vocal fold model

    NASA Astrophysics Data System (ADS)

    Ringenberg, Hunter; Krane, Michael; Rogers, Dylan; Misfeldt, Mitchel; Wei, Timothy

    2016-11-01

    Experimental measurements of flow through a scaled up dynamic human vocal fold model are presented. The simplified 10x scale vocal fold model from Krane, et al. (2007) was used to examine fundamental features of vocal fold oscillatory motion. Of particular interest was the temporal variation of transglottal pressure multiplied by the volume flow rate through the glottis throughout an oscillation cycle. Experiments were dynamically scaled to examine a range of frequencies, 100 - 200 Hz, corresponding to the male and female voice. By using water as the working fluid, very high resolution, both spatial and temporal resolution, was achieved. Time resolved movies of flow through symmetrically oscillating vocal folds will be presented. Both individual realizations as well as phase-averaged data will be shown. Key features, such as randomness and development time of the Coanda effect, vortex shedding, and volume flow rate data have been presented in previous APS-DFD meetings. This talk will focus more on the relation between the flow and aeroacoustics associated with vocal fold oscillations. Supported by the NIH.

  8. Simplified Protein Models: Predicting Folding Pathways and Structure Using Amino Acid Sequences

    NASA Astrophysics Data System (ADS)

    Adhikari, Aashish N.; Freed, Karl F.; Sosnick, Tobin R.

    2013-07-01

    We demonstrate the ability of simultaneously determining a protein’s folding pathway and structure using a properly formulated model without prior knowledge of the native structure. Our model employs a natural coordinate system for describing proteins and a search strategy inspired by the observation that real proteins fold in a sequential fashion by incrementally stabilizing nativelike substructures or “foldons.” Comparable folding pathways and structures are obtained for the twelve proteins recently studied using atomistic molecular dynamics simulations [K. Lindorff-Larsen, S. Piana, R. O. Dror, D. E. Shaw, Science 334, 517 (2011)], with our calculations running several orders of magnitude faster. We find that nativelike propensities in the unfolded state do not necessarily determine the order of structure formation, a departure from a major conclusion of the molecular dynamics study. Instead, our results support a more expansive view wherein intrinsic local structural propensities may be enhanced or overridden in the folding process by environmental context. The success of our search strategy validates it as an expedient mechanism for folding both in silico and in vivo.

  9. Modeling epigenome folding: formation and dynamics of topologically associated chromatin domains.

    PubMed

    Jost, Daniel; Carrivain, Pascal; Cavalli, Giacomo; Vaillant, Cédric

    2014-09-01

    Genomes of eukaryotes are partitioned into domains of functionally distinct chromatin states. These domains are stably inherited across many cell generations and can be remodeled in response to developmental and external cues, hence contributing to the robustness and plasticity of expression patterns and cell phenotypes. Remarkably, recent studies indicate that these 1D epigenomic domains tend to fold into 3D topologically associated domains forming specialized nuclear chromatin compartments. However, the general mechanisms behind such compartmentalization including the contribution of epigenetic regulation remain unclear. Here, we address the question of the coupling between chromatin folding and epigenome. Using polymer physics, we analyze the properties of a block copolymer model that accounts for local epigenomic information. Considering copolymers build from the epigenomic landscape of Drosophila, we observe a very good agreement with the folding patterns observed in chromosome conformation capture experiments. Moreover, this model provides a physical basis for the existence of multistability in epigenome folding at sub-chromosomal scale. We show how experiments are fully consistent with multistable conformations where topologically associated domains of the same epigenomic state interact dynamically with each other. Our approach provides a general framework to improve our understanding of chromatin folding during cell cycle and differentiation and its relation to epigenetics.

  10. Influence of subglottic stenosis on the flow-induced vibration of a computational vocal fold model

    PubMed Central

    Smith, Simeon L.; Thomson, Scott L.

    2012-01-01

    The effect of subglottic stenosis on vocal fold vibration is investigated. An idealized stenosis is defined, parameterized, and incorporated into a two-dimensional, fully-coupled finite element model of the vocal folds and laryngeal airway. Flow-induced responses of the vocal fold model to varying severities of stenosis are compared. The model vibration was not appreciably affected by stenosis severities of up to 60% occlusion. Model vibration was altered by stenosis severities of 90% or greater, evidenced by decreased superior model displacement, glottal width amplitude, and flow rate amplitude. Predictions of vibration frequency and maximum flow declination rate were also altered by high stenosis severities. The observed changes became more pronounced with increasing stenosis severity and inlet pressure, and the trends correlated well with flow resistance calculations. Flow visualization was used to characterize subglottal flow patterns in the space between the stenosis and the vocal folds. Underlying mechanisms for the observed changes, possible implications for human voice production, and suggestions for future work are discussed. PMID:23503699

  11. The Fold Analysis Challenge: A virtual globe-based educational resource

    NASA Astrophysics Data System (ADS)

    De Paor, Declan G.; Dordevic, Mladen M.; Karabinos, Paul; Tewksbury, Barbara J.; Whitmeyer, Steven J.

    2016-04-01

    We present an undergraduate structural geology laboratory exercise using the Google Earth virtual globe with COLLADA models, optionally including an interactive stereographic projection and JavaScript controls. The learning resource challenges students to identify bedding traces and estimate bedding orientation at several locations on a fold, to fit the fold axis and axial plane to stereographic projection data, and to fit a doubly-plunging fold model to the large-scale structure. The chosen fold is the Sheep Mountain Anticline, a Laramide uplift in the Big Horn Basin of Wyoming. We take an education research-based approach, guiding students through three levels of difficulty. The exercise aims to counter common student misconceptions and stumbling blocks regarding penetrative structures. It can be used in preparation for an in-person field trip, for post-trip reinforcement, or as a virtual field experience in an online-only course. Our KML scripts can be easily transferred to other fold structures around the globe.

  12. Modeling programmable deformation of self-folding all-polymer structures with temperature-sensitive hydrogels

    NASA Astrophysics Data System (ADS)

    Guo, Wei; Li, Meie; Zhou, Jinxiong

    2013-11-01

    Combination of soft active hydrogels with hard passive polymers gives rise to all-polymer composites. The hydrogel is sensitive to external stimuli while the passive polymer is inert. Utilizing the different behaviors of two materials subject to environmental variation, for example temperature, results in self-folding soft machines. We report our efforts to model the programmable deformation of self-folding structures with temperature-sensitive hydrogels. The self-folding structures are realized either by constructing a bilayer structure or by incorporating hydrogels as hinges. The methodology and the results may aid the design, control and fabrication of 3D complex structures from 2D simple configurations through self-assembly.

  13. Quantitative analysis of vocal fold vibration during register change by high-speed digital imaging system

    NASA Astrophysics Data System (ADS)

    Kumada, Masanobu; Kobayashi, Noriko; Hirose, Hajime; Tayama, Niro; Imagawa, Hiroshi; Sakakibara, Ken-Ichi; Nito, Takaharu; Kakurai, Shin'ichi; Kumada, Chieko; Wada, Mamiko; Niimi, Seiji

    2002-05-01

    The physiological study of prosody is indispensable in terms not only of the physiological interest but also of the evaluation and treatment for pathological cases of prosody. In free talk, the changes of vocal fold vibration are found frequently and these phenomena are very important prosodic events. To analyze quantitatively the vocal fold vibration at the register change as the model of prosodic event, our high-speed digital imaging system was used at a rate of 4500 images of 256-256 pixels per second. Four healthy Japanese adults (2 males and 2 females) were served as subjects. Tasks were sustained phonation containing register changes. Two major categories (Category A and B) were found in the ways of changing of vocal fold vibrations at the register change. In Category A, changes were very smooth in terms of the vocal fold vibration. In Category B, changes were not so smooth with some additional events at the register change, such as the anterior-posterior phase difference of the vibration, the abduction of the vocal folds, or the interruption of the phonation. The number of the subtypes for Category B is thought to increase if more subjects with a wider range of variety are analyzed. For the study of prosody, our high-speed digital imaging system is a very powerful tool by which physiological information can be obtained.

  14. Folding of proteins with an all-atom Go-model.

    PubMed

    Wu, L; Zhang, J; Qin, M; Liu, F; Wang, W

    2008-06-21

    The Go-like potential at a residual level has been successfully applied to the folding of proteins in many previous works. However, taking into consideration more detailed structural information in the atomic level, the definition of contacts used in these traditional Go-models may not be suitable for all-atom simulations. Here, in this work, we develop a rational definition of contacts considering the screening effect in the crowded intramolecular environment. In such a scheme, a large amount of screened atom pairs are excluded and the number of contacts is decreased compared to the case of the traditional definition. These contacts defined by such a new definition are compatible with the all-atom representation of protein structures. To verify the rationality of the new definition of contacts, the folding of proteins CI2 and SH3 is simulated by all-atom molecular dynamics simulations. A high folding cooperativity and good correlation of the simulated Phi-values with those obtained experimentally, especially for CI2, are found. This suggests that the all-atom Go-model is improved compared to the traditional Go-model. Based on the comparison of the Phi-values, the roles of side chains in the folding are discussed, and it is concluded that the side-chain structures are more important for local contacts in determining the transition state structures. Moreover, the relations between side chain and backbone orderings are also discussed.

  15. Complexity of chromatin folding is captured by the strings and binders switch model.

    PubMed

    Barbieri, Mariano; Chotalia, Mita; Fraser, James; Lavitas, Liron-Mark; Dostie, Josée; Pombo, Ana; Nicodemi, Mario

    2012-10-02

    Chromatin has a complex spatial organization in the cell nucleus that serves vital functional purposes. A variety of chromatin folding conformations has been detected by single-cell imaging and chromosome conformation capture-based approaches. However, a unified quantitative framework describing spatial chromatin organization is still lacking. Here, we explore the "strings and binders switch" model to explain the origin and variety of chromatin behaviors that coexist and dynamically change within living cells. This simple polymer model recapitulates the scaling properties of chromatin folding reported experimentally in different cellular systems, the fractal state of chromatin, the processes of domain formation, and looping out. Additionally, the strings and binders switch model reproduces the recently proposed "fractal-globule" model, but only as one of many possible transient conformations.

  16. Generic framework for mining cellular automata models on protein-folding simulations.

    PubMed

    Diaz, N; Tischer, I

    2016-05-13

    Cellular automata model identification is an important way of building simplified simulation models. In this study, we describe a generic architectural framework to ease the development process of new metaheuristic-based algorithms for cellular automata model identification in protein-folding trajectories. Our framework was developed by a methodology based on design patterns that allow an improved experience for new algorithms development. The usefulness of the proposed framework is demonstrated by the implementation of four algorithms, able to obtain extremely precise cellular automata models of the protein-folding process with a protein contact map representation. Dynamic rules obtained by the proposed approach are discussed, and future use for the new tool is outlined.

  17. Folding and association of a homotetrameric protein complex in an all-atom Go model.

    PubMed

    Berhanu, W M; Jiang, P; Hansmann, U H E

    2013-01-01

    The 84-residue homotetrameric BBAT1 is one of the smallest stable protein complexes and therefore is a good test system to study the self-assembly of multimeric proteins. We have researched for this protein the interplay between the folding of monomers and their assembly into tetramers. Replica exchange molecular dynamics simulations relying on a Go model are compared with earlier simulations that use the physics-based coarse-grained UNRES model.

  18. Influence of Embedded Fibers and an Epithelium Layer on the Glottal Closure Pattern in a Physical Vocal Fold Model

    ERIC Educational Resources Information Center

    Xuan, Yue; Zhang, Zhaoyan

    2014-01-01

    Purpose: The purpose of this study was to explore the possible structural and material property features that may facilitate complete glottal closure in an otherwise isotropic physical vocal fold model. Method: Seven vocal fold models with different structural features were used in this study. An isotropic model was used as the baseline model, and…

  19. An in vitro setup to test the relevance and the accuracy of low-order vocal folds models.

    PubMed

    Ruty, Nicolas; Pelorson, Xavier; Van Hirtum, Annemie; Lopez-Arteaga, Ines; Hirschberg, Avraham

    2007-01-01

    An experimental setup and human vocal folds replica able to produce self-sustained oscillations are presented. The aim of the setup is to assess the relevance and the accuracy of theoretical vocal folds models. The applied reduced mechanical models are a variation of the classical two-mass model, and a simplification inspired on the delayed mass model for which the coupling between the masses is expressed as a fixed time delay. The airflow is described as a laminar flow with flow separation. The influence of a downstream resonator is taken into account. The oscillation pressure threshold and fundamental frequency are predicted by applying a stability analysis to the mechanical models. The measured frequency response of the mechanical replica together with the initial (rest) area allows us to determine the model parameters (spring stiffness, damping, geometry, masses). Validation of theoretical model predictions to experimental data shows the relevance of low-order models in gaining a qualitative understanding of phonation. However, quantitative discrepancies remain large due to an inaccurate estimation of the model parameters and the crudeness in either flow or mechanical model description. As an illustration it is shown that significant improvements can be made by accounting for viscous flow effects.

  20. Comparing a simple theoretical model for protein folding with all-atom molecular dynamics simulations.

    PubMed

    Henry, Eric R; Best, Robert B; Eaton, William A

    2013-10-29

    Advances in computing have enabled microsecond all-atom molecular dynamics trajectories of protein folding that can be used to compare with and test critical assumptions of theoretical models. We show that recent simulations by the Shaw group (10, 11, 14, 15) are consistent with a key assumption of an Ising-like theoretical model that native structure grows in only a few regions of the amino acid sequence as folding progresses. The distribution of mechanisms predicted by simulating the master equation of this native-centric model for the benchmark villin subdomain, with only two adjustable thermodynamic parameters and one temperature-dependent kinetic parameter, is remarkably similar to the distribution in the molecular dynamics trajectories.

  1. Note: Network random walk model of two-state protein folding: Test of the theory

    NASA Astrophysics Data System (ADS)

    Berezhkovskii, Alexander M.; Murphy, Ronan D.; Buchete, Nicolae-Viorel

    2013-01-01

    We study two-state protein folding in the framework of a toy model of protein dynamics. This model has an important advantage: it allows for an analytical solution for the sum of folding and unfolding rate constants [A. M. Berezhkovskii, F. Tofoleanu, and N.-V. Buchete, J. Chem. Theory Comput. 7, 2370 (2011), 10.1021/ct200281d] and hence for the reactive flux at equilibrium. We use the model to test the Kramers-type formula for the reactive flux, which was derived assuming that the protein dynamics is described by a Markov random walk on a network of complex connectivity [A. Berezhkovskii, G. Hummer, and A. Szabo, J. Chem. Phys. 130, 205102 (2009), 10.1063/1.3139063]. It is shown that the Kramers-type formula leads to the same result for the reactive flux as the sum of the rate constants.

  2. Studying vocal fold vibrations in Parkinson's disease with a nonlinear model

    NASA Astrophysics Data System (ADS)

    Zhang, Yu; Jiang, Jack; Rahn, Douglas A.

    2005-09-01

    A nonlinear model is applied to study pathologic vocal vibratory characteristics and voice treatments of Parkinson's disease. We find that a number of pathologic vocal characteristics commonly observed in Parkinson's disease, including reduced vibratory intensity, incomplete vocal closure, increased phonation threshold pressure, glottal tremor, subharmonics, and chaotic vocal fold vibrations, can be studied with this nonlinear model. We also find that two kinds of clinical voice treatments for Parkinson's disease, including respiratory effort treatment and Lee Silverman voice treatment can be studied with this computer model. Results suggest that respiratory effort treatment, in which subglottal pressure is increased, might aid in enhancing vibratory intensity, improving glottal closure, and avoiding vibratory irregularity. However, the Lee Silverman voice treatment, in which both subglottal pressure and vocal fold adduction are increased, might be better than respiratory effort treatment. Increasing vocal fold thickness would be further helpful to improve these pathologic characteristics. The model studies show consistencies with clinical observations. Computer models may be of value in understanding the dynamic mechanism of disordered voices and studying voice treatment effects in Parkinson's disease.

  3. Multimodality pH imaging in a mouse dorsal skin fold window chamber model

    NASA Astrophysics Data System (ADS)

    Leung, Hui Min; Schafer, Rachel; Pagel, Mark M.; Robey, Ian F.; Gmitro, Arthur F.

    2013-03-01

    Upregulate levels of expression and activity of membrane H+ ion pumps in cancer cells drives the extracellular pH (pHe,) to values lower than normal. Furthermore, disregulated pH is indicative of the changes in glycolytic metabolism in tumor cells and has been shown to facilitate extracellular tissue remodeling during metastasis Therefore, measurement of pHe could be a useful cancer biomarker for diagnostic and therapy monitoring evaluation. Multimodality in-vivo imaging of pHe in tumorous tissue in a mouse dorsal skin fold window chamber (DSFWC) model is described. A custom-made plastic window chamber structure was developed that is compatible with both imaging optical and MR imaging modalities and provides a model system for continuous study of the same tissue microenvironment on multiple imaging platforms over a 3-week period. For optical imaging of pHe, SNARF-1 carboxylic acid is injected intravenously into a SCID mouse with an implanted tumor. A ratiometric measurement of the fluorescence signal captured on a confocal microscope reveals the pHe of the tissue visible within the window chamber. This imaging method was used in a preliminary study to evaluate sodium bicarbonate as a potential drug treatment to reverse tissue acidosis. For MR imaging of pHe the chemical exchange saturation transfer (CEST) was used as an alternative way of measuring pHe in a DSFWC model. ULTRAVIST®, a FDA approved x-ray/CT contrast agent has been shown to have a CEST effect that is pH dependent. A ratiometric analysis of water saturation at 5.6 and 4.2 ppm chemical shift provides a means to estimate the local pHe.

  4. Dissecting the stability of a beta-hairpin peptide that folds in water: NMR and molecular dynamics analysis of the beta-turn and beta-strand contributions to folding.

    PubMed

    Griffiths-Jones, S R; Maynard, A J; Searle, M S

    1999-10-08

    NMR studies of the folding and conformational properties of a beta-hairpin peptide, several peptide fragments of the hairpin, and sequence-modified analogues, have enabled the various contributions to beta-hairpin stability in water to be dissected. Temperature and pH-induced unfolding studies indicate that the folding-unfolding equilibrium approximates to a two-state model. The hairpin is highly resistant to denaturation and is still significantly folded in 7 M urea at 298 K. Thermodynamic analysis shows the hairpin to fold in water with a significant change in heat capacity, however, DeltaCp degrees in 7 M urea is reduced. V/Y-->A mutations on one strand of the hairpin reduce folding to <10 %, consistent with a hydrophobic stabilisation model. We show that in a truncated peptide (residues 6-16) lacking the hydrophobic residues on one beta-strand, the type I' Asn-Gly turn in the sequence SINGKK is significantly populated in water in the absence of interstrand hydrophobic contacts. Unrestrained molecular dynamics simulations of unfolding, using an explicit solvation model, show that the conformation of the NG turn persists for longer than the AG analogue, which has a much lower propensity for type I' turn formation from a data base analysis of preferred turns. The origin of the high stability of the Asn-Gly turn is not entirely clear; data base analysis of 66 NG turns, together with molecular dynamics simulations, reveals no participation of the Asn side-chain in turn-stabilising interactions with the peptide backbone. However, hydration analysis of the molecular dynamics simulations reveals a pocket of "high density" water bridging between the Asn side-chain and peptide main-chain that suggests solvent-mediated interactions may play an important role in modulating phi,psi propensities in the NG turn region.

  5. Intermediate decollement activation in response to the basal friction variation and its effect on folding style in the Zagros fold-thrust belt, an analogue modeling approach

    NASA Astrophysics Data System (ADS)

    Farzipour-Saein, Ali; Koyi, Hemin

    2016-09-01

    Although the role of various basal and intermediate decollement levels on structural style is well documented individually in many folded terrains, the interaction between basal and intermediate decollements is poorly constrained. This study uses results of two scaled sand-box models shortened from one end to study the variation in structural development in response to varying basal friction and its consequent interaction with intermediate decollement horizons. Two models with similar incompetent intermediate decollement, but with different basal friction (with and without a thick basal decollement), were prepared analogous for the eastern and the western parts of the Razak basement fault in the Fars Region of the eastern part of the Zagros fold thrust belt (ZFTB). Combined results of scaled models with geological observations are used to argue that the basal decollement friction characteristics govern propagation of deformation front. In addition, model results, analogues to north-south direction, show that deformation complexity and disharmonic folding exist in the section where the intermediate decollement has been activated in response to the shortening without the basal decollement (throughout the western part of the Razak basement fault where less thickness of the Hormuz series as the basal decollement has been documented compared to its eastern part). In other words, the complexity in deformation is less portrayed along sections where basal friction beneath the model decreases (e.g. the eastern part of the Razak basement fault). We argue here that, in addition to other parameters (not presented in this study) interaction of intermediate decollement levels with basal decollement friction characteristics could explain decoupling between structures within the sedimentary column of the Fars Region of the eastern part of the Zagros fold thrust belt.

  6. Synergistic Effects of Phase Folding and Wavelet Denoising with Applications in Light Curve Analysis

    DTIC Science & Technology

    2016-09-15

    FOLDING AND WAVELET DENOISING WITH APPLICATIONS IN LIGHT CURVE ANALYSIS I. Introduction Moore’s law, and other exponential growth patterns in technology...that the universe underwent a period of exponential growth shortly after the big bang. The exponential growth of the universe can be accounted for in the...The second section discusses the exponential growth of the solution space which accompanies the linear growth of components. Inherent Error. In

  7. Polymer models of the hierarchical folding of the Hox-B chromosomal locus

    NASA Astrophysics Data System (ADS)

    Annunziatella, Carlo; Chiariello, Andrea M.; Bianco, Simona; Nicodemi, Mario

    2016-10-01

    As revealed by novel technologies, chromosomes in the nucleus of mammalian cells have a complex spatial organization that serves vital functional purposes. Here we use models from polymer physics to identify the mechanisms that control their three-dimensional spatial organization. In particular, we investigate a model of the Hox-B locus, an important genomic region involved in embryo development, to expose the principles regulating chromatin folding and its complex behaviors in mouse embryonic stem cells. We reconstruct with high accuracy the pairwise contact matrix of the Hox-B locus as derived by Hi-C experiments and investigate its hierarchical folding dynamics. We trace back the observed behaviors to general scaling properties of polymer physics.

  8. Differences between the deformed-potential and folding-model descriptions of inelastic nuclear scattering

    SciTech Connect

    Hnizdo, V. )

    1994-08-01

    The differences between the deformed-potential and folding-model descriptions of inelastic nuclear scattering, attention to which has been called recently by Beene, Horen, and Satchler [Phys. Rev. C 48, 3128 (1993)], were pointed out already some time ago by contrasting the rules of equal deformation lengths and equal normalized multipole moments for the optical potential and the underlying nucleon distribution of the excited nucleus.

  9. How to fold a spin chain: Integrable boundaries of the Heisenberg XXX and Inozemtsev hyperbolic models

    NASA Astrophysics Data System (ADS)

    De La Rosa Gomez, Alejandro; MacKay, Niall; Regelskis, Vidas

    2017-04-01

    We present a general method of folding an integrable spin chain, defined on a line, to obtain an integrable open spin chain, defined on a half-line. We illustrate our method through two fundamental models with sl2 Lie algebra symmetry: the Heisenberg XXX and the Inozemtsev hyperbolic spin chains. We obtain new long-range boundary Hamiltonians and demonstrate that they exhibit Yangian symmetries, thus ensuring integrability of the models we obtain. The method presented provides a ;bottom-up; approach for constructing integrable boundaries and can be applied to any spin chain model.

  10. Double Folding Potential of Different Interaction Models for 16O + 12C Elastic Scattering

    NASA Astrophysics Data System (ADS)

    Hamada, Sh.; Bondok, I.; Abdelmoatmed, M.

    2016-12-01

    The elastic scattering angular distributions for 16O + 12C nuclear system have been analyzed using double folding potential of different interaction models: CDM3Y1, CDM3Y6, DDM3Y1 and BDM3Y1. We have extracted the renormalization factor N r for the different concerned interaction models. Potential created by BDM3Y1 model of interaction has the shallowest depth which reflects the necessity to use higher renormalization factor. The experimental angular distributions for 16O + 12C nuclear system in the energy range 115.9-230 MeV exhibited unmistakable refractive features and rainbow phenomenon.

  11. A Self-Folding Hydrogel In Vitro Model for Ductal Carcinoma.

    PubMed

    Kwag, Hye Rin; Serbo, Janna V; Korangath, Preethi; Sukumar, Saraswati; Romer, Lewis H; Gracias, David H

    2016-04-01

    A significant challenge in oncology is the need to develop in vitro models that accurately mimic the complex microenvironment within and around normal and diseased tissues. Here, we describe a self-folding approach to create curved hydrogel microstructures that more accurately mimic the geometry of ducts and acini within the mammary glands, as compared to existing three-dimensional block-like models or flat dishes. The microstructures are composed of photopatterned bilayers of poly (ethylene glycol) diacrylate (PEGDA), a hydrogel widely used in tissue engineering. The PEGDA bilayers of dissimilar molecular weights spontaneously curve when released from the underlying substrate due to differential swelling ratios. The photopatterns can be altered via AutoCAD-designed photomasks so that a variety of ductal and acinar mimetic structures can be mass-produced. In addition, by co-polymerizing methacrylated gelatin (methagel) with PEGDA, microstructures with increased cell adherence are synthesized. Biocompatibility and versatility of our approach is highlighted by culturing either SUM159 cells, which were seeded postfabrication, or MDA-MB-231 cells, which were encapsulated in hydrogels; cell viability is verified over 9 and 15 days, respectively. We believe that self-folding processes and associated tubular, curved, and folded constructs like the ones demonstrated here can facilitate the design of more accurate in vitro models for investigating ductal carcinoma.

  12. Perturbations of the denatured state ensemble: modeling their effects on protein stability and folding kinetics.

    PubMed Central

    Wrabl, J. O.; Shortle, D.

    1996-01-01

    By considering the denatured state of a protein as an ensemble of conformations with varying numbers of sequence-specific interactions, the effects on stability, folding kinetics, and aggregation of perturbing these interactions can be predicted from changes in the molecular partition function. From general considerations, the following conclusions are drawn: (1) A perturbation that enhances a native interaction in denatured state conformations always increases the stability of the native state. (2) A perturbation that promotes a non-native interaction in the denatured state always decreases the stability of the native state. (3) A change in the denatured state ensemble can alter the kinetics of aggregation and folding. (4) The loss (or increase) in stability accompanying two mutations, each of which lowers (or raises) the free energy of the denatured state, will be less than the sum of the effects of the single mutations, except in cases where both mutations affect the same set of partially folded conformations. By modeling the denatured state as the ensemble of all non-native conformations of hydrophobic-polar (HP) chains configured on a square lattice, it can be shown that the stabilization obtained from enhancement of native interactions derives in large measure from the avoidance of non-native interactions in the D state. In addition, the kinetic effects of fixing single native contacts in the denatured state or imposing linear gradients in the HH contact probabilities are found, for some sequences, to significantly enhance the efficiency of folding by a simple hydrophobic zippering algorithm. Again, the dominant mechanism appears to be avoidance of non-native interactions. These results suggest stabilization of native interactions and imposition of gradients in the stability of local structure are two plausible mechanisms involving the denatured state that could play a role in the evolution of protein folding and stability. PMID:8931153

  13. β-hairpin-forming peptides; models of early stages of protein folding

    PubMed Central

    Lewandowska, Agnieszka; Ołdziej, Stanisław; Liwo, Adam; Scheraga, Harold A.

    2010-01-01

    Formation of β-hairpins is considered the initial step of folding of many proteins and, consequently, peptides constituting the β-hairpin sequence of proteins (the β-hairpin-forming peptides) are considered as models of early stages of protein folding. In this article, we discuss the results of experimental studies (circular-dichroism, infrared and nuclear magnetic resonance spectroscopy, and differential scanning calorimetry) of the structure of β-hairpin-forming peptides excised from the B1 domain of protein G, which are known to fold on their own. We demonstrate that local interactions at the turn sequence and hydrophobic interactions between nonpolar residues are the dominant structure-determining factors, while there is no convincing evidence that stable backbone hydrogen bonds are formed in these peptides in aqueous solution. Consequently, the most plausible mechanism for folding of the β-hairpin sequence appears to be the broken-zipper mechanism consisting of the following three steps: (i) bending the chain at the turn sequence owing to favorable local interactions, (ii) formation of loose hydrophobic contacts between nonpolar residues, which occur close to the contacts in the native structure of the protein but not exactly in the same position and, finally, (iii) formation of backbone hydrogen bonds and locking the hydrophobic contacts in the native positions as a hydrophobic core develops, sufficient to dehydrate the backbone peptide groups. This mechanism provides sufficient uniqueness (contacts form between residues that become close together because the chain is bent at the turn position) and robustness (contacts need not occur at once in the native positions) for folding a β-hairpin sequence. PMID:20494507

  14. A geometric model of faulted detachment folding with pure shear and its application in the Tarim Basin, NW China

    NASA Astrophysics Data System (ADS)

    Yao, Zewei; He, Guangyu; Zheng, Xiaoli; Dong, Chuanwan; Cao, Zicheng; Yang, Suju; Gu, Yi

    2016-11-01

    We present an improved geometric model of faulted detachment folding with pure shear that is characterized by core thickening and a ramp-discordant backlimb. The model includes a two-stage evolution: 1) detachment folding involving pure shear with fixed hinges, and 2) faulted detachment folding, in which the core of anticline thrusts above a break-through fault in forelimb by limb rotation. The growth strata patterns of the model are also discussed with respect to factors such as limb rotation, tectonic uplift rate, and sedimentation rate. A thrust-related fold, called a TBE thrust fold, in the Tarim Basin in NW China, is analyzed as an example of the theoretical model. The result indicates that the TBE thrust fold has undergone a two-stage evolution with shortening of a few hundred meters. Both the theoretical model and the actual example indicate that the shortening in the detachment folding stage takes up a large proportion of the total shortening. The structural restoration of the TBE thrust fold also provides new evidence that the formation of a series of thin-skinned structures in the SE Tarim Basin initiated in the Late Ordovician. The model may be applicable to lowamplitude faulted detachment folds.

  15. Structure of the adenovirus E4 Orf6 protein predicted by fold recognition and comparative protein modeling.

    PubMed

    Brown, L M; Gonzalez, R A; Novotny, J; Flint, S J

    2001-08-01

    To facilitate investigation of the molecular and biochemical functions of the adenovirus E4 Orf6 protein, we sought to derive three-dimensional structural information using computational methods, particularly threading and comparative protein modeling. The amino acid sequence of the protein was used for secondary structure and hidden Markov model (HMM) analyses, and for fold recognition by the ProCeryon program. Six alternative models were generated from the top-scoring folds identified by threading. These models were examined by 3D-1D analysis and evaluated in the light of available experimental evidence. The final model of the E4 protein derived from these and additional threading calculations was a chimera, with the tertiary structure of its C-terminal 226 residues derived from a TIM barrel template and a mainly alpha-nonbundle topology for its poorly conserved N-terminal 68 residues. To assess the accuracy of this model, additional threading calculations were performed with E4 Orf6 sequences altered as in previous experimental studies. The proposed structural model is consistent with the reported secondary structure of a functionally important C-terminal sequence and can account for the properties of proteins carrying alterations in functionally important sequences or of those that disrupt an unusual zinc-coordination motif.

  16. A three-dimensional statistical mechanical model of folding double-stranded chain molecules

    NASA Astrophysics Data System (ADS)

    Zhang, Wenbing; Chen, Shi-Jie

    2001-05-01

    Based on a graphical representation of intrachain contacts, we have developed a new three-dimensional model for the statistical mechanics of double-stranded chain molecules. The theory has been tested and validated for the cubic lattice chain conformations. The statistical mechanical model can be applied to the equilibrium folding thermodynamics of a large class of chain molecules, including protein β-hairpin conformations and RNA secondary structures. The application of a previously developed two-dimensional model to RNA secondary structure folding thermodynamics generally overestimates the breadth of the melting curves [S-J. Chen and K. A. Dill, Proc. Natl. Acad. Sci. U.S.A. 97, 646 (2000)], suggesting an underestimation for the sharpness of the conformational transitions. In this work, we show that the new three-dimensional model gives much sharper melting curves than the two-dimensional model. We believe that the new three-dimensional model may give much improved predictions for the thermodynamic properties of RNA conformational changes than the previous two-dimensional model.

  17. A three-dimensional model of vocal fold abduction/adduction

    NASA Astrophysics Data System (ADS)

    Hunter, Eric J.; Titze, Ingo R.; Alipour, Fariborz

    2004-04-01

    A three-dimensional biomechanical model of tissue deformation was developed to simulate dynamic vocal fold abduction and adduction. The model was made of 1721 nearly incompressible finite elements. The cricoarytenoid joint was modeled as a rocking-sliding motion, similar to two concentric cylinders. The vocal ligament and the thyroarytenoid muscle's fiber characteristics were implemented as a fiber-gel composite made of an isotropic ground substance imbedded with fibers. These fibers had contractile and/or passive nonlinear stress-strain characteristics. The verification of the model was made by comparing the range and speed of motion to published vocal fold kinematic data. The model simulated abduction to a maximum glottal angle of about 31°. Using the posterior-cricoarytenoid muscle, the model produced an angular abduction speed of 405° per second. The system mechanics seemed to favor abduction over adduction in both peak speed and response time, even when all intrinsic muscle properties were kept identical. The model also verified the notion that the vocalis and muscularis portions of the thyroarytenoid muscle play significantly different roles in posturing, with the muscularis portion having the larger effect on arytenoid movement. Other insights into the mechanisms of abduction/adduction were given.

  18. Spatio-temporal analysis of irregular vocal fold oscillations: Biphonation due to desynchronization of spatial modes

    NASA Astrophysics Data System (ADS)

    Neubauer, Jürgen; Mergell, Patrick; Eysholdt, Ulrich; Herzel, Hanspeter

    2001-12-01

    This report is on direct observation and modal analysis of irregular spatio-temporal vibration patterns of vocal fold pathologies in vivo. The observed oscillation patterns are described quantitatively with multiline kymograms, spectral analysis, and spatio-temporal plots. The complex spatio-temporal vibration patterns are decomposed by empirical orthogonal functions into independent vibratory modes. It is shown quantitatively that biphonation can be induced either by left-right asymmetry or by desynchronized anterior-posterior vibratory modes, and the term ``AP (anterior-posterior) biphonation'' is introduced. The presented phonation examples show that for normal phonation the first two modes sufficiently explain the glottal dynamics. The spatio-temporal oscillation pattern associated with biphonation due to left-right asymmetry can be explained by the first three modes. Higher-order modes are required to describe the pattern for biphonation induced by anterior-posterior vibrations. Spatial irregularity is quantified by an entropy measure, which is significantly higher for irregular phonation than for normal phonation. Two asymmetry measures are introduced: the left-right asymmetry and the anterior-posterior asymmetry, as the ratios of the fundamental frequencies of left and right vocal fold and of anterior-posterior modes, respectively. These quantities clearly differentiate between left-right biphonation and anterior-posterior biphonation. This paper proposes methods to analyze quantitatively irregular vocal fold contour patterns in vivo and complements previous findings of desynchronization of vibration modes in computer modes and in in vitro experiments.

  19. 3D Fault modeling of the active Chittagong-Myanmar fold belt, Bangladesh

    NASA Astrophysics Data System (ADS)

    Peterson, D. E.; Hubbard, J.; Akhter, S. H.; Shamim, N.

    2013-12-01

    The Chittagong-Myanmar fold belt (CMFB), located in eastern Bangladesh, eastern India and western Myanmar, accommodates east-west shortening at the India-Burma plate boundary. Oblique subduction of the Indian Plate beneath the Burma Plate since the Eocene has led to the development of a large accretionary prism complex, creating a series of north-south trending folds. A continuous sediment record from ~55 Ma to the present has been deposited in the Bengal Basin by the Ganges-Brahmaputra-Meghna rivers, providing an opportunity to learn about the history of tectonic deformation and activity in this fold-and-thrust belt. Surface mapping indicates that the fold-and-thrust belt is characterized by extensive N-S-trending anticlines and synclines in a belt ~150-200 km wide. Seismic reflection profiles from the Chittagong and Chittagong Hill Tracts, Bangladesh, indicate that the anticlines mapped at the surface narrow with depth and extend to ~3.0 seconds TWTT (two-way travel time), or ~6.0 km. The folds of Chittagong and Chittagong Hill Tracts are characterized by doubly plunging box-shaped en-echelon anticlines separated by wide synclines. The seismic data suggest that some of these anticlines are cored by thrust fault ramps that extend to a large-scale décollement that dips gently to the east. Other anticlines may be the result of detachment folding from the same décollement. The décollement likely deepens to the east and intersects with the northerly-trending, oblique-slip Kaladan fault. The CMFB region is bounded to the north by the north-dipping Dauki fault and the Shillong Plateau. The tectonic transition from a wide band of E-W shortening in the south to a narrow zone of N-S shortening along the Dauki fault is poorly understood. We integrate surface and subsurface datasets, including topography, geological maps, seismicity, and industry seismic reflection profiles, into a 3D modeling environment and construct initial 3D surfaces of the major faults in this

  20. Computation of physiological human vocal fold parameters by mathematical optimization of a biomechanical model

    PubMed Central

    Yang, Anxiong; Stingl, Michael; Berry, David A.; Lohscheller, Jörg; Voigt, Daniel; Eysholdt, Ulrich; Döllinger, Michael

    2011-01-01

    With the use of an endoscopic, high-speed camera, vocal fold dynamics may be observed clinically during phonation. However, observation and subjective judgment alone may be insufficient for clinical diagnosis and documentation of improved vocal function, especially when the laryngeal disease lacks any clear morphological presentation. In this study, biomechanical parameters of the vocal folds are computed by adjusting the corresponding parameters of a three-dimensional model until the dynamics of both systems are similar. First, a mathematical optimization method is presented. Next, model parameters (such as pressure, tension and masses) are adjusted to reproduce vocal fold dynamics, and the deduced parameters are physiologically interpreted. Various combinations of global and local optimization techniques are attempted. Evaluation of the optimization procedure is performed using 50 synthetically generated data sets. The results show sufficient reliability, including 0.07 normalized error, 96% correlation, and 91% accuracy. The technique is also demonstrated on data from human hemilarynx experiments, in which a low normalized error (0.16) and high correlation (84%) values were achieved. In the future, this technique may be applied to clinical high-speed images, yielding objective measures with which to document improved vocal function of patients with voice disorders. PMID:21877808

  1. Folding of polyglutamine chains

    NASA Astrophysics Data System (ADS)

    Chopra, Manan; Reddy, Allam S.; Abbott, N. L.; de Pablo, J. J.

    2008-10-01

    Long polyglutamine chains have been associated with a number of neurodegenerative diseases. These include Huntington's disease, where expanded polyglutamine (PolyQ) sequences longer than 36 residues are correlated with the onset of symptoms. In this paper we study the folding pathway of a 54-residue PolyQ chain into a β-helical structure. Transition path sampling Monte Carlo simulations are used to generate unbiased reactive pathways between unfolded configurations and the folded β-helical structure of the polyglutamine chain. The folding process is examined in both explicit water and an implicit solvent. Both models reveal that the formation of a few critical contacts is necessary and sufficient for the molecule to fold. Once the primary contacts are formed, the fate of the protein is sealed and it is largely committed to fold. We find that, consistent with emerging hypotheses about PolyQ aggregation, a stable β-helical structure could serve as the nucleus for subsequent polymerization of amyloid fibrils. Our results indicate that PolyQ sequences shorter than 36 residues cannot form that nucleus, and it is also shown that specific mutations inferred from an analysis of the simulated folding pathway exacerbate its stability.

  2. Influence of supraglottal structures on the glottal jet exiting a two-layer synthetic, self-oscillating vocal fold model

    PubMed Central

    Drechsel, James S.; Thomson, Scott L.

    2008-01-01

    A synthetic two-layer, self-oscillating, life-size vocal fold model was used to study the influence of the vocal tract and false folds on the glottal jet. The model vibrated at frequencies, pressures, flow rates, and amplitudes consistent with human phonation, although some differences in behavior between the model and the human vocal folds are noted. High-speed images of model motion and flow visualization were acquired. Phase-locked ensemble-averaged glottal jet velocity measurements using particle image velocimetry (PIV) were acquired with and without an idealized vocal tract, with and without false folds. PIV data were obtained with varying degrees of lateral asymmetric model positioning. Glottal jet velocity magnitudes were consistent with those measured using excised larynges. A starting vortex was observed in all test cases. The false folds interfered with the starting vortex, and in some cases vortex shedding from the false folds was observed. In asymmetric cases without false folds, the glottal jet tended to skew toward the nearest wall; with the false folds, the opposite trend was observed. rms velocity calculations showed the jet shear layer and laminar core. The rms velocities were higher in the vocal tract cases compared to the open jet and false fold cases. PMID:18537394

  3. Entropy-Driven Folding of an RNA Helical Junction: An Isothermal Titration Calorimetric Analysis of the Hammerhead Ribozyme†

    PubMed Central

    Mikulecky, Peter J.; Takach, Jennifer C.; Feig, Andrew L.

    2008-01-01

    Helical junctions are extremely common motifs in naturally occurring RNAs, but little is known about the thermodynamics that drive their folding. Studies of junction folding face several challenges: non-two-state folding behavior, superposition of secondary and tertiary structural energetics, and drastically opposing enthalpic and entropic contributions to folding. Here we describe a thermodynamic dissection of the folding of the hammerhead ribozyme, a three-way RNA helical junction, by using isothermal titration calorimetry of bimolecular RNA constructs. By using this method, we show that tertiary folding of the hammerhead core occurs with a highly unfavorable enthalpy change, and is therefore entropically driven. Furthermore, the enthalpies and heat capacities of core folding are the same whether supported by monovalent or divalent ions. These properties appear to be general to the core sequence of bimolecular hammerhead constructs. We present a model for the ion-induced folding of the hammerhead core that is similar to those advanced for the folding of much larger RNAs, involving ion-induced collapse to a structured, non-native state accompanied by rearrangement of core residues to produce the native fold. In agreement with previous enzymological and structural studies, our thermodynamic data suggest that the hammerhead structure is stabilized in vitro predominantly by diffusely bound ions. Our approach addresses several significant challenges that accompany the study of junction folding, and should prove useful in defining the thermodynamic determinants of stability in these important RNA motifs. PMID:15134461

  4. Entropy-driven folding of an RNA helical junction: an isothermal titration calorimetric analysis of the hammerhead ribozyme.

    PubMed

    Mikulecky, Peter J; Takach, Jennifer C; Feig, Andrew L

    2004-05-18

    Helical junctions are extremely common motifs in naturally occurring RNAs, but little is known about the thermodynamics that drive their folding. Studies of junction folding face several challenges: non-two-state folding behavior, superposition of secondary and tertiary structural energetics, and drastically opposing enthalpic and entropic contributions to folding. Here we describe a thermodynamic dissection of the folding of the hammerhead ribozyme, a three-way RNA helical junction, by using isothermal titration calorimetry of bimolecular RNA constructs. By using this method, we show that tertiary folding of the hammerhead core occurs with a highly unfavorable enthalpy change, and is therefore entropically driven. Furthermore, the enthalpies and heat capacities of core folding are the same whether supported by monovalent or divalent ions. These properties appear to be general to the core sequence of bimolecular hammerhead constructs. We present a model for the ion-induced folding of the hammerhead core that is similar to those advanced for the folding of much larger RNAs, involving ion-induced collapse to a structured, non-native state accompanied by rearrangement of core residues to produce the native fold. In agreement with previous enzymological and structural studies, our thermodynamic data suggest that the hammerhead structure is stabilized in vitro predominantly by diffusely bound ions. Our approach addresses several significant challenges that accompany the study of junction folding, and should prove useful in defining the thermodynamic determinants of stability in these important RNA motifs.

  5. Control of syntectonic erosion and sedimentation on kinematic evolution of a multidecollement fold and thrust zone: Analogue modeling of folding in the southern subandean of Bolivia

    NASA Astrophysics Data System (ADS)

    Darnault, Romain; Callot, Jean-Paul; Ballard, Jean-François; Fraisse, Guillaume; Mengus, Jean-Marie; Ringenbach, Jean-Claude

    2016-08-01

    Several analogue modeling studies have been conducted during the past fifteen years with the aim to discuss the effects of sedimentation and erosion on Foreland Fold and Thrust Belt, among which a few have analyzed these processes at kilometric scale (Malavieille et al., 1993; Nalpas et al., 1999; Barrier et al., 2002; Pichot and Nalpas, 2009). The influence of syn-deformation sedimentation and erosion on the structural evolution of FFTB has been clearly demonstrated. Here, we propose to go further in this approach by the study of a more complex system with a double decollement level. The natural study case is the Bolivian sub-Andean thrust and fold belt, which present all the required criteria, such as the double decollement level. A set of analogue models performed under a CT-scan have been used to test the influence of several parameters on a fold and thrust belt system, among which: (i) the spatial variation of the sediment input, (ii) the spatial variation of the erosion rate, (iii) the relative distribution of sedimentation between foreland and hinterland. These experiments led to the following observations: 1. The upper decollement level acts as a decoupling level in case of increased sedimentation rate: it results in the verticalization of the shallower part (above the upper decollement level), while the deeper parts are not impacted. 2. Similarly, the increase of the erosion rate involves the uplift of the deeper part (below the upper decollement level), whereas the shallower parts are not impacted. 3. A high sedimentation rate in the foreland involves a fault and fold vergence reversal, followed by a back-thrusting of the shallower part. 4. A high sedimentation rate in the hinterland favours thrust development toward the foreland in the shallower parts.

  6. Altered vocal fold kinematics in synthetic self-oscillating models that employ adipose tissue as a lateral boundary condition.

    NASA Astrophysics Data System (ADS)

    Saidi, Hiba; Erath, Byron D.

    2015-11-01

    The vocal folds play a major role in human communication by initiating voiced sound production. During voiced speech, the vocal folds are set into sustained vibrations. Synthetic self-oscillating vocal fold models are regularly employed to gain insight into flow-structure interactions governing the phonation process. Commonly, a fixed boundary condition is applied to the lateral, anterior, and posterior sides of the synthetic vocal fold models. However, physiological observations reveal the presence of adipose tissue on the lateral surface between the thyroid cartilage and the vocal folds. The goal of this study is to investigate the influence of including this substrate layer of adipose tissue on the dynamics of phonation. For a more realistic representation of the human vocal folds, synthetic multi-layer vocal fold models have been fabricated and tested while including a soft lateral layer representative of adipose tissue. Phonation parameters have been collected and are compared to those of the standard vocal fold models. Results show that vocal fold kinematics are affected by adding the adipose tissue layer as a new boundary condition.

  7. Generic folding and transition hierarchies for surface adsorption of hydrophobic-polar lattice model proteins.

    PubMed

    Li, Ying Wai; Wüst, Thomas; Landau, David P

    2013-01-01

    The thermodynamic behavior and structural properties of hydrophobic-polar (HP) lattice proteins interacting with attractive surfaces are studied by means of Wang-Landau sampling. Three benchmark HP sequences (48mer, 67mer, and 103mer) are considered with different types of surfaces, each of which attract either all monomers, only hydrophobic (H) monomers, or only polar (P) monomers, respectively. The diversity of folding behavior in dependence of surface strength is discussed. Analyzing the combined patterns of various structural observables, such as, e.g., the derivatives of the numbers of surface contacts, together with the specific heat, we are able to identify generic categories of folding and transition hierarchies. We also infer a connection between these transition categories and the relative surface strengths, i.e., the ratio of the surface attractive strength to the interchain attraction among H monomers. The validity of our proposed classification scheme is reinforced by the analysis of additional benchmark sequences. We thus believe that the folding hierarchies and identification scheme are generic for HP proteins interacting with attractive surfaces, regardless of chain length, sequence, or surface attraction.

  8. Generic folding and transition hierarchies for surface adsorption of hydrophobic-polar lattice model proteins

    NASA Astrophysics Data System (ADS)

    Li, Ying Wai; Wüst, Thomas; Landau, David P.

    2013-01-01

    The thermodynamic behavior and structural properties of hydrophobic-polar (HP) lattice proteins interacting with attractive surfaces are studied by means of Wang-Landau sampling. Three benchmark HP sequences (48mer, 67mer, and 103mer) are considered with different types of surfaces, each of which attract either all monomers, only hydrophobic (H) monomers, or only polar (P) monomers, respectively. The diversity of folding behavior in dependence of surface strength is discussed. Analyzing the combined patterns of various structural observables, such as, e.g., the derivatives of the numbers of surface contacts, together with the specific heat, we are able to identify generic categories of folding and transition hierarchies. We also infer a connection between these transition categories and the relative surface strengths, i.e., the ratio of the surface attractive strength to the interchain attraction among H monomers. The validity of our proposed classification scheme is reinforced by the analysis of additional benchmark sequences. We thus believe that the folding hierarchies and identification scheme are generic for HP proteins interacting with attractive surfaces, regardless of chain length, sequence, or surface attraction.

  9. A discriminative feature selection approach for shape analysis: Application to fetal brain cortical folding.

    PubMed

    Pontabry, J; Rousseau, F; Studholme, C; Koob, M; Dietemann, J-L

    2017-01-01

    The development of post-processing reconstruction techniques has opened new possibilities for the study of in-utero fetal brain MRI data. Recent cortical surface analysis have led to the computation of quantitative maps characterizing brain folding of the developing brain. In this paper, we describe a novel feature selection-based approach that is used to extract the most discriminative and sparse set of features of a given dataset. The proposed method is used to sparsely characterize cortical folding patterns of an in-utero fetal MR dataset, labeled with heterogeneous gestational age ranging from 26 weeks to 34 weeks. The proposed algorithm is validated on a synthetic dataset with both linear and non-linear dynamics, supporting its ability to capture deformation patterns across the dataset within only a few features. Results on the fetal brain dataset show that the temporal process of cortical folding related to brain maturation can be characterized by a very small set of points, located in anatomical regions changing across time. Quantitative measurements of growth against time are extracted from the set selected features to compare multiple brain regions (e.g. lobes and hemispheres) during the considered period of gestation.

  10. Hidden Markov models that use predicted local structure for fold recognition: alphabets of backbone geometry.

    PubMed

    Karchin, Rachel; Cline, Melissa; Mandel-Gutfreund, Yael; Karplus, Kevin

    2003-06-01

    An important problem in computational biology is predicting the structure of the large number of putative proteins discovered by genome sequencing projects. Fold-recognition methods attempt to solve the problem by relating the target proteins to known structures, searching for template proteins homologous to the target. Remote homologs that may have significant structural similarity are often not detectable by sequence similarities alone. To address this, we incorporated predicted local structure, a generalization of secondary structure, into two-track profile hidden Markov models (HMMs). We did not rely on a simple helix-strand-coil definition of secondary structure, but experimented with a variety of local structure descriptions, following a principled protocol to establish which descriptions are most useful for improving fold recognition and alignment quality. On a test set of 1298 nonhomologous proteins, HMMs incorporating a 3-letter STRIDE alphabet improved fold recognition accuracy by 15% over amino-acid-only HMMs and 23% over PSI-BLAST, measured by ROC-65 numbers. We compared two-track HMMs to amino-acid-only HMMs on a difficult alignment test set of 200 protein pairs (structurally similar with 3-24% sequence identity). HMMs with a 6-letter STRIDE secondary track improved alignment quality by 62%, relative to DALI structural alignments, while HMMs with an STR track (an expanded DSSP alphabet that subdivides strands into six states) improved by 40% relative to CE.

  11. Modeling and experimental verification of a fan-folded vibration energy harvester for leadless pacemakers

    NASA Astrophysics Data System (ADS)

    Ansari, M. H.; Karami, M. Amin

    2016-03-01

    This paper studies energy harvesting from heartbeat vibrations for powering leadless pacemakers. Unlike traditional pacemakers, leadless pacemakers are implanted inside the heart and the pacemaker is in direct contact with the myocardium. A leadless pacemaker is in the shape of a cylinder. Thus, in order to utilize the available 3-dimensional space for the energy harvester, we choose a fan-folded 3D energy harvester. The proposed device consists of several piezoelectric beams stacked on top of each other. The volume of the energy harvester is 1 cm3 and its dimensions are 2 cm × 0.5 cm × 1 cm. Although high natural frequency is generally a major concern with micro-scale energy harvesters, by utilizing the fan-folded geometry and adding tip mass and link mass to the configuration, we reduced the natural frequency to the desired range. This fan-folded design makes it possible to generate more than 10 μ W of power per cubic centimeter. The proposed device is compatible with Magnetic Resonance Imaging. Although the proposed device is a linear energy harvester, it is relatively insensitive to the heart rate. The natural frequencies and the mode shapes of the device are calculated analytically. The accuracy of the analytical model is verified by experimental investigations. We use a closed loop shaker system to precisely replicate heartbeat vibrations in vitro.

  12. Competition between protein folding and aggregation: A three-dimensional lattice-model simulation

    NASA Astrophysics Data System (ADS)

    Bratko, D.; Blanch, H. W.

    2001-01-01

    Aggregation of protein molecules resulting in the loss of biological activity and the formation of insoluble deposits represents a serious problem for the biotechnology and pharmaceutical industries and in medicine. Considerable experimental and theoretical efforts are being made in order to improve our understanding of, and ability to control, the process. In the present work, we describe a Monte Carlo study of a multichain system of coarse-grained model proteins akin to lattice models developed for simulations of protein folding. The model is designed to examine the competition between intramolecular interactions leading to the native protein structure, and intermolecular association, resulting in the formation of aggregates of misfolded chains. Interactions between the segments are described by a variation of the Go potential [N. Go and H. Abe, Biopolymers 20, 1013 (1981)] that extends the recognition between attracting types of segments to pairs on distinct chains. For the particular model we adopt, the global free energy minimum of a pair of protein molecules corresponds to a dimer of native proteins. When three or more molecules interact, clusters of misfolded chains can be more stable than aggregates of native folds. A considerable fraction of native structure, however, is preserved in these cases. Rates of conformational changes rapidly decrease with the size of the protein cluster. Within the timescale accessible to computer simulations, the folding-aggregation balance is strongly affected by kinetic considerations. Both the native form and aggregates can persist in metastable states, even if conditions such as temperature or concentration favor a transition to an alternative form. Refolding yield can be affected by the presence of an additional polymer species mimicking the function of a molecular chaperone.

  13. An ISO-surface folding analysis method applied to premature neonatal brain development

    NASA Astrophysics Data System (ADS)

    Rodriguez-Carranza, Claudia E.; Rousseau, Francois; Iordanova, Bistra; Glenn, Orit; Vigneron, Daniel; Barkovich, James; Studholme, Colin

    2006-03-01

    In this paper we describe the application of folding measures to tracking in vivo cortical brain development in premature neonatal brain anatomy. The outer gray matter and the gray-white matter interface surfaces were extracted from semi-interactively segmented high-resolution T1 MRI data. Nine curvature- and geometric descriptor-based folding measures were applied to six premature infants, aged 28-37 weeks, using a direct voxelwise iso-surface representation. We have shown that using such an approach it is feasible to extract meaningful surfaces of adequate quality from typical clinically acquired neonatal MRI data. We have shown that most of the folding measures, including a new proposed measure, are sensitive to changes in age and therefore applicable in developing a model that tracks development in premature infants. For the first time gyrification measures have been computed on the gray-white matter interface and on cases whose age is representative of a period of intense brain development.

  14. Communication: Role of explicit water models in the helix folding/unfolding processes

    NASA Astrophysics Data System (ADS)

    Palazzesi, Ferruccio; Salvalaglio, Matteo; Barducci, Alessandro; Parrinello, Michele

    2016-09-01

    In the last years, it has become evident that computer simulations can assume a relevant role in modelling protein dynamical motions for their ability to provide a full atomistic image of the processes under investigation. The ability of the current protein force-fields in reproducing the correct thermodynamics and kinetics systems behaviour is thus an essential ingredient to improve our understanding of many relevant biological functionalities. In this work, employing the last developments of the metadynamics framework, we compare the ability of state-of-the-art all-atom empirical functions and water models to consistently reproduce the folding and unfolding of a helix turn motif in a model peptide. This theoretical study puts in evidence that the choice of the water models can influence the thermodynamic and the kinetics of the system under investigation, and for this reason cannot be considered trivial.

  15. A Self-Assisting Protein Folding Model for Teaching Structural Molecular Biology.

    PubMed

    Davenport, Jodi; Pique, Michael; Getzoff, Elizabeth; Huntoon, Jon; Gardner, Adam; Olson, Arthur

    2017-04-04

    Structural molecular biology is now becoming part of high school science curriculum thus posing a challenge for teachers who need to convey three-dimensional (3D) structures with conventional text and pictures. In many cases even interactive computer graphics does not go far enough to address these challenges. We have developed a flexible model of the polypeptide backbone using 3D printing technology. With this model we have produced a polypeptide assembly kit to create an idealized model of the Triosephosphate isomerase mutase enzyme (TIM), which forms a structure known as TIM barrel. This kit has been used in a laboratory practical where students perform a step-by-step investigation into the nature of protein folding, starting with the handedness of amino acids to the formation of secondary and tertiary structure. Based on the classroom evidence we collected, we conclude that these models are valuable and inexpensive resource for teaching structural molecular biology.

  16. Structurally induced errors in paleomagnetic analysis of fold and thrust belts: Types, causes and detection techniques.

    NASA Astrophysics Data System (ADS)

    Pueyo, E. L.

    2008-12-01

    Paleomagnetic vectors are unique kinematics indicators allowing for the real understanding of the lateral transference of deformation processes and they are essential for a real 3D understanding of fold and thrust belts. The association with the bedding surface gives the only 3D reference system able to unambiguously relate the deformed and undeformed stages and their implications are, until now, relatively unexplored in structural geology. However paleomagnetic data are sometimes, misinterpreted or ignored due to the lack of reliability of some databases, where a geometric control of errors seems evident from the structural point of view. An analysis of the implicit assumptions in paleomagnetic studies of fold and thrust belts reveals three possible sources of error with an intrinsic structural (geometric) control: Assumption 1) The laboratory procedures are able to completely isolate of the original paleomagnetic vectors When this fails, the subsequent overlapped paleomagnetic directions (eg. primary record and the recent overprint) will display both declination and inclination errors, that will be controlled by the fold axis orientation, the degree of flank rotation (dip), the primary magnetic polarity as well as the degree of vector overlapping. Assumption 2) The rigid-body behavior during deformation and the absence of rock volume changes. When the rock volume undergoes active internal deformation during folding or shearing, the deformed paleomagnetic vectors will display again declination and inclination errors, but both polarities will behave similarly. In this case the errors will depend on the relation between the primary field orientation and the deformation tensor, which in fact, can be reduced to the orientation and magnitude of the shear in most cases. Assumption 3) The bedding correction is able to restore the bedding-vector couple to the ancient (paleo)geographical reference system. This restoration may fail in complex deformation zones affected by

  17. Nuclear mean field and double-folding model of the nucleus-nucleus optical potential

    NASA Astrophysics Data System (ADS)

    Khoa, Dao T.; Phuc, Nguyen Hoang; Loan, Doan Thi; Loc, Bui Minh

    2016-09-01

    Realistic density dependent CDM3Yn versions of the M3Y interaction have been used in an extended Hartree-Fock (HF) calculation of nuclear matter (NM), with the nucleon single-particle potential determined from the total NM energy based on the Hugenholtz-van Hove theorem that gives rise naturally to a rearrangement term (RT). Using the RT of the single-nucleon potential obtained exactly at different NM densities, the density and energy dependence of the CDM3Yn interactions was modified to account properly for both the RT and observed energy dependence of the nucleon optical potential. Based on a local density approximation, the double-folding model of the nucleus-nucleus optical potential has been extended to take into account consistently the rearrangement effect and energy dependence of the nuclear mean-field potential, using the modified CDM3Yn interactions. The extended double-folding model was applied to study the elastic 12C+12C and 16O+12C scattering at the refractive energies, where the Airy structure of the nuclear rainbow has been well established. The RT was found to affect significantly the real nucleus-nucleus optical potential at small internuclear distances, giving a potential strength close to that implied by the realistic optical model description of the Airy oscillation.

  18. Replica-exchange Wang-Landau simulations of the H0P model of protein folding

    NASA Astrophysics Data System (ADS)

    Shi, Guangjie; Landau, David P.; Wüst, Thomas; Li, Ying Wai Li

    2015-03-01

    The hydrophobic-polar (HP) model has served as a coarse-grained lattice protein folding model attracting scientists from various disciplines. However, simplification into H and P monomers may yield high ground state degeneracies which stands in contrast to the generally unique native states of natural proteins. We propose a simple modification, by introducing a new type of ``neutral'' monomer, 0, i.e. neither hydrophobic nor polar, rendering the model more realistic without increasing the difficulties of sampling significantly. With the newly developed parallel Wang-Landau (replica exchange Wang-Landau) scheme and an innovative method of estimating the ground state degeneracies, we investigated some widely studied HP proteins and their H0P counterparts. Dramatic differences in ground state and thermodynamic properties have been observed, e.g. the estimation of ground state degeneracy for the 46mer is 460,000 for the HP version and only 20 for the H0P mapping. Similarly, the specific heat and structural properties: radius of gyration and etc. show more pronounced signals associated with folding. Supported by NSF.

  19. Viscoelastic shear properties of human vocal fold mucosa: theoretical characterization based on constitutive modeling.

    PubMed

    Chan, R W; Titze, I R

    2000-01-01

    The viscoelastic shear properties of human vocal fold mucosa (cover) were previously measured as a function of frequency [Chan and Titze, J. Acoust. Soc. Am. 106, 2008-2021 (1999)], but data were obtained only in a frequency range of 0.01-15 Hz, an order of magnitude below typical frequencies of vocal fold oscillation (on the order of 100 Hz). This study represents an attempt to extrapolate the data to higher frequencies based on two viscoelastic theories, (1) a quasilinear viscoelastic theory widely used for the constitutive modeling of the viscoelastic properties of biological tissues [Fung, Biomechanics (Springer-Verlag, New York, 1993), pp. 277-292], and (2) a molecular (statistical network) theory commonly used for the rheological modeling of polymeric materials [Zhu et al., J. Biomech. 24, 1007-1018 (1991)]. Analytical expressions of elastic and viscous shear moduli, dynamic viscosity, and damping ratio based on the two theories with specific model parameters were applied to curve-fit the empirical data. Results showed that the theoretical predictions matched the empirical data reasonably well, allowing for parametric descriptions of the data and their extrapolations to frequencies of phonation.

  20. Asymmetric airflow and vibration induced by the Coanda effect in a symmetric model of the vocal folds.

    PubMed

    Tao, Chao; Zhang, Yu; Hottinger, Daniel G; Jiang, Jack J

    2007-10-01

    A model constructed from Navier-Stokes equations and a two-mass vocal fold description is proposed in this study. The composite model not only has the capability to describe the aerodynamics in a vibratory glottis but also can be used to study the vocal fold vibration under the driving of the complex airflow in the glottis. Numerical simulations show that this model can predict self-oscillations of the coupled glottal aerodynamics and vocal fold system. The Coanda effect could occur in the vibratory glottis even though the vocal folds have left-right symmetric prephonatory shape and tissue properties. The Coanda effect causes the asymmetric flow in the glottis and the difference in the driving force on the left and right vocal folds. The different pressures applied to the left and right vocal folds induce their displacement asymmetry. By using various lung pressures (0.6-2.0 kPa) to drive the composite model, it was found that the asymmetry of the vocal fold displacement is increased from 1.87% to 11.2%. These simulation results provide numerical evidence for the presence of asymmetric flow in the vibratory glottis; moreover, they indicate that glottal aerodynamics is an important factor in inducing the asymmetric vibration of the vocal folds.

  1. Influence of a constriction in the near field of the vocal folds: physical modeling and experimental validation.

    PubMed

    Bailly, Lucie; Pelorson, Xavier; Henrich, Nathalie; Ruty, Nicolas

    2008-11-01

    The involvement of the ventricular folds is often observed in human phonation and, in particular, in pathological and or some throat-singing phonation. This study aims to explore and model the possible aerodynamic interaction between the ventricular and vocal folds using suitable in vitro setups allowing steady and unsteady flow conditions. The two experimental setups consist of a rigid and a self-oscillating vocal-fold replica, coupled to a downstream rigid ventricular-fold replica in both cases. A theoretical flow modeling is proposed to quantify the aerodynamic impact of the ventricular folds on the pressure distribution and thereby on the vocal-fold vibrations. The mechanical behavior of the vocal folds is simulated by a distributed model accounting for this impact. The influence of the ventricular constriction is measured in both flow conditions and compared to the model outcome. This study objectively evaluates the additional pressure drop implied by the presence of a ventricular constriction in the larynx. It is demonstrated that such constriction can either facilitate or impede the glottal vibrations depending on the laryngeal geometrical configuration. The relevance of using static or dynamic vocal-fold replicas is discussed.

  2. Local rules for protein folding on a triangular lattice and generalized hydrophobicity in the HP model

    SciTech Connect

    Agarwala, R.; Batzoglou, S.; Dancik, V.

    1997-12-01

    A long standing problem in molecular biology is to determine the three-dimensional structure of a protein, given its amino acid sequence. A variety of simplifying models have been proposed abstracting only the {open_quotes}essential physical properties{close_quotes} of real proteins. In these models, the three dimensional space is often represented by a lattice. Residues which are adjacent in the primary sequence (i.e. covalently linked) must be placed at adjacent points in the lattice. A conformation of a protein is simply a self-avoiding walk along the lattice. The protein folding problem STRING-FOLD is that of finding a conformation of the protein sequence on the lattice such that the overall energy is minimized, for some reasonable definition of energy. This formulation leaves open the choices of a lattice and an energy function. Once these choices are made, one may then address the algorithmic complexity of optimizing the energy function for the lattice. For a variety of such simple models, this minimization problem is in fact NP-hard. In this paper, we consider the Hydrophobic-Polar (HP) Model introduced by Dill. The HP model abstracts the problem by grouping the 20 amino acids into two classes: hydrophobic (or non-polar) residues and hydrophilic (or polar) residues. For concreteness, we will take our input to be a string from (H,P){sup +}, where P represents polar residues, and H represents hydrophobic residues. Dill et.al. survey the literature analyzing this model. 8 refs., 2 figs., 1 tab.

  3. A replica exchange Monte Carlo algorithm for protein folding in the HP model

    PubMed Central

    Thachuk, Chris; Shmygelska, Alena; Hoos, Holger H

    2007-01-01

    Background The ab initio protein folding problem consists of predicting protein tertiary structure from a given amino acid sequence by minimizing an energy function; it is one of the most important and challenging problems in biochemistry, molecular biology and biophysics. The ab initio protein folding problem is computationally challenging and has been shown to be NP MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaat0uy0HwzTfgDPnwy1egaryqtHrhAL1wy0L2yHvdaiqaacqWFneVtcqqGqbauaaa@3961@-hard even when conformations are restricted to a lattice. In this work, we implement and evaluate the replica exchange Monte Carlo (REMC) method, which has already been applied very successfully to more complex protein models and other optimization problems with complex energy landscapes, in combination with the highly effective pull move neighbourhood in two widely studied Hydrophobic Polar (HP) lattice models. Results We demonstrate that REMC is highly effective for solving instances of the square (2D) and cubic (3D) HP protein folding problem. When using the pull move neighbourhood, REMC outperforms current state-of-the-art algorithms for most benchmark instances. Additionally, we show that this new algorithm provides a larger ensemble of ground-state structures than the existing state-of-the-art methods. Furthermore, it scales well with sequence length, and it finds significantly better conformations on long biological sequences and sequences with a provably unique ground-state structure, which is believed to be a characteristic of real proteins. We also present evidence that our REMC algorithm can fold sequences which exhibit significant interaction between termini in the hydrophobic core relatively easily. Conclusion We demonstrate that REMC utilizing the pull move neighbourhood

  4. Assessing groundwater availability in a folded carbonate aquifer through the development of a numerical model

    NASA Astrophysics Data System (ADS)

    Di Salvo, Cristina; Romano, Emanuele; Guyennon, Nicolas; Bruna Petrangeli, Anna; Preziosi, Elisabetta

    2015-04-01

    The study of aquifer systems from a quantitative point of view is fundamental for adopting water management plans aiming at preserving water resources and reducing environmental risks related to groundwater level and discharge changes. This is also what the European Union Water Framework Directive (WFD, 2000/60/EC) states, holding the development of numerical models as a key aspect for groundwater management. The objective of this research is to i) define a methodology for modeling a complex hydrogeological structure in a structurally folded carbonate area and ii) estimate the concurrent effects of exploitation and climate changes on groundwater availability through the implementation of a 3D groundwater flow model. This study concerns the Monte Coscerno karst aquifer located in the Apennine chain in Central Italy in the Nera River Valley.This aquifer, is planned to be exploited in the near future for water supply. Negative trends of precipitation in Central Italy have been reported in relation to global climate changes, which are expected to affect the availability of recharge to carbonate aquifers throughout the region . A great concern is the combined impact of climate change and groundwater exploitation, hence scenarios are needed taking into account the effect of possible temperature and precipitation trends on recharge rates. Following a previous experience with model conceptualization and long-term simulation of groundwater flow, an integrated three-dimensional groundwater model has been developed for the Monte Coscerno aquifer. In a previous paper (Preziosi et al 2014) the spatial distribution of recharge to this aquifer was estimated through the Thornthwaite Mather model at a daily time step using as inputs past precipitation and temperature values (1951-2013) as well as soil and landscape properties. In this paper the numerical model development is described. On the basis of well logs from private consulting companies and literature cross sections the

  5. Mola Topography Supports Drape-Folding Models for Polygonal Terrain of Utopia Planitia, Mars

    NASA Technical Reports Server (NTRS)

    McGill, George E.; Buczkowski, D. L.

    2002-01-01

    One of the most important questions we ask about Mars is whether or not there have ever been large bodies of standing water on the surface. The polygonal terrains of Utopia and Acidalia Planitiae are located in the lowest parts of the northern lowlands, the most logical places for water to pond and sediments to accumulate. Showing that polygonal terrain is sedimentary in origin would represent strong evidence in favor of a northern ocean. A number of hypotheses for the origin of the giant martian polygons have been proposed, from the cooling of lava to frost wedging to the desiccation of wet sediments, but Pechman showed that none of these familiar processes could be scaled up to martian dimensions. Two models for polygon origin attempt to explain the scale of the martian polygons by postulating drape folding of a cover material, either sedimentary or volcanic, over an uneven, buried surface. The drape folding would produce bending stresses in the surface layers that increase the probability of Fracturing over drape anticlines and suppress the probability of fracturing over drape synclines. However, both models require an additional source of extensional strain to produce the total strain needed to produce the observed troughs.

  6. Folding Beauties

    ERIC Educational Resources Information Center

    Berman, Leah Wrenn

    2006-01-01

    This article has its genesis in an MAA mini-course on origami, where a way to get a parabola by folding paper was presented. This article discusses the methods and mathematics of other curves obtained by paper-folding.

  7. Structural analysis of Bacillus pumilus phenolic acid decarboxylase, a lipocalin-fold enzyme

    SciTech Connect

    Matte, Allan; Grosse, Stephan; Bergeron, Hélène; Abokitse, Kofi; Lau, Peter C.K.

    2012-04-30

    The decarboxylation of phenolic acids, including ferulic and p-coumaric acids, to their corresponding vinyl derivatives is of importance in the flavoring and polymer industries. Here, the crystal structure of phenolic acid decarboxylase (PAD) from Bacillus pumilus strain UI-670 is reported. The enzyme is a 161-residue polypeptide that forms dimers both in the crystal and in solution. The structure of PAD as determined by X-ray crystallography revealed a -barrel structure and two -helices, with a cleft formed at one edge of the barrel. The PAD structure resembles those of the lipocalin-fold proteins, which often bind hydrophobic ligands. Superposition of structurally related proteins bound to their cognate ligands shows that they and PAD bind their ligands in a conserved location within the -barrel. Analysis of the residue-conservation pattern for PAD-related sequences mapped onto the PAD structure reveals that the conservation mainly includes residues found within the hydrophobic core of the protein, defining a common lipocalin-like fold for this enzyme family. A narrow cleft containing several conserved amino acids was observed as a structural feature and a potential ligand-binding site.

  8. Linking rates of folding in lattice models of proteins with underlying thermodynamic characteristics

    NASA Astrophysics Data System (ADS)

    Klimov, D. K.; Thirumalai, D.

    1998-09-01

    We investigate the sequence-dependent properties of proteins that determine the dual requirements of stability of the native state and its kinetic accessibility using simple cubic lattice models. Three interaction schemes are used to describe the potentials between nearest neighbor nonbonded beads. We show that, under the simulation conditions when the native basin of attraction (NBA) is the most stable, there is an excellent correlation between folding times τF and the dimensionless parameter σT=(Tθ-TF)/Tθ, where Tθ is the collapse temperature and TF is the folding transition temperature. There is also a significant correlation between τF and another dimensionless quantity Z=(EN-Ems)/δ, where EN is the energy of the native state, Ems is the average energy of the ensemble of misfolded structures, and δ is the dispersion in the contact energies. In contrast, there is no significant correlation between τF and the Z-score gap ΔZ=EN-Ems. An approximate relationship between σT and the Z-score is derived, which explains the superior correlation seen between τF and σT. For two state folders τF is linked to the free energy difference (not simply energy gap, however it is defined) between the unfolded states and the NBA.

  9. Strain and vorticity analysis using small-scale faults and associated drag folds

    NASA Astrophysics Data System (ADS)

    Gomez-Rivas, Enrique; Bons, Paul D.; Griera, Albert; Carreras, Jordi; Druguet, Elena; Evans, Lynn

    2007-12-01

    Small-scale faults with associated drag folds in brittle-ductile rocks can retain detailed information on the kinematics and amount of deformation the host rock experienced. Measured fault orientation ( α), drag angle ( β) and the ratio of the thickness of deflected layers at the fault ( L) and further away ( T) can be compared with α, β and L/ T values that are calculated with a simple analytical model. Using graphs or a numerical best-fit routine, one can then determine the kinematic vorticity number and initial fault orientation that best fits the data. The proposed method was successfully tested on both analogue experiments and numerical simulations with BASIL. Using this method, a kinematic vorticity number of one (dextral simple shear) and a minimum finite strain of 2.5-3.8 was obtained for a population of antithetic faults with associated drag folds in a case study area at Mas Rabassers de Dalt on Cap de Creus in the Variscan of the easternmost Pyrenees, Spain.

  10. Activity, stability and folding analysis of the chitinase from Entamoeba histolytica.

    PubMed

    Muñoz, Patricia L A; Minchaca, Alexis Z; Mares, Rosa E; Ramos, Marco A

    2016-02-01

    Human amebiasis, caused by the parasitic protozoan Entamoeba histolytica, remains as a significant public health issue in developing countries. The life cycle of the parasite compromises two main stages, trophozoite and cyst, linked by two major events: encystation and excystation. Interestingly, the cyst stage has a chitin wall that helps the parasite to withstand harsh environmental conditions. Since the amebic chitinase, EhCHT1, has been recognized as a key player in both encystation and excystation, it is plausible to consider that specific inhibition could arrest the life cycle of the parasite and, thus, stop the infection. However, to selectively target EhCHT1 it is important to recognize its unique biochemical features to have the ability to control its cellular function. Hence, to gain further insights into the structure-function relationship, we conducted an experimental approach to examine the effects of pH, temperature, and denaturant concentration on the enzymatic activity and protein stability. Additionally, dependence on in vivo oxidative folding was further studied using a bacterial model. Our results attest the potential of EhCHT1 as a target for the design and development of new or improved anti-amebic therapeutics. Likewise, the potential of the oxidoreductase EhPDI, involved in oxidative folding of amebic proteins, was also confirmed.

  11. Extreme Folding

    NASA Astrophysics Data System (ADS)

    Demaine, Erik

    2012-02-01

    Our understanding of the mathematics and algorithms behind paper folding, and geometric folding in general, has increased dramatically over the past several years. These developments have found a surprisingly broad range of applications. In the art of origami, it has helped spur the technical origami revolution. In engineering and science, it has helped solve problems in areas such as manufacturing, robotics, graphics, and protein folding. On the recreational side, it has led to new kinds of folding puzzles and magic. I will give an overview of the mathematics and algorithms of folding, with a focus on new mathematics and sculpture.

  12. Comparing Folding Codes in Simple Heteropolymer Models of Protein Evolutionary Landscape: Robustness of the Superfunnel Paradigm

    PubMed Central

    Wroe, Richard; Bornberg-Bauer, Erich; Chan, Hue Sun

    2005-01-01

    Understanding the evolution of biopolymers is a key element in rationalizing their structures and functions. Simple exact models (SEMs) are well-positioned to address general principles of evolution as they permit the exhaustive enumeration of both sequence and structure (conformational) spaces. The physics-based models of the complete mapping between genotypes and phenotypes afforded by SEMs have proven valuable for gaining insight into how adaptation and selection operate among large collections of sequences and structures. This study compares the properties of evolutionary landscapes of a variety of SEMs to delineate robust predictions and possible model-specific artifacts. Among the models studied, the ruggedness of evolutionary landscape is significantly model-dependent; those derived from more proteinlike models appear to be smoother. We found that a common practice of restricting protein structure space to maximally compact lattice conformations results in (i.e., “designs in”) many encodable (designable) structures that are not otherwise encodable in the corresponding unrestrained structure space. This discrepancy is especially severe for model potentials that seek to mimic the major role of hydrophobic interactions in protein folding. In general, restricting conformations to be maximally compact leads to larger changes in the model genotype-phenotype mapping than a moderate shifting of reference state energy of the model potential function to allow for more specific encoding via the “designing out” effects of repulsive interactions. Despite these variations, the superfunnel paradigm applies to all SEMs we have tested: For a majority of neutral nets across different models, there exists a funnel-like organization of native stabilities for the sequences in a neutral net encoding for the same structure, and the thermodynamically most stable sequence is also the most robust against mutation. PMID:15501948

  13. The RIP and block-RIP analysis of Nyquist folding receiver for recovering signals

    NASA Astrophysics Data System (ADS)

    Jiang, Kaili; Chen, Sujuan; Tang, Bin

    2016-12-01

    Modern radar and communication systems require the detection and parameter estimation of signal under a broadband radio frequency (RF) environment. The Nyquist folding receiver (NYFR) is an efficient analog-to-information (A2I) architecture. It can use the compressive sensing (CS) techniques to break the limitations of the analog-to-digital converter (ADC). This paper demonstrates the restricted isometry property (RIP) of the NYFR deterministically by applying the Gershgorin circle theory. And, the NYFR suffers a poor RIP for the broadband signal, which will lead the conventional CS algorithms to be invalid. So, we derive the Fourier spectrum of the broadband signal, which covered multiple Nyquist zones and received by the NYFR. Then, the broadband signal can be regarded as the block-sparse signal. And, the block CS algorithms are applied for recovering the signal based on the analysis of the block-RIP. Finally, the simulation experiments demonstrate the validity of the findings.

  14. Rf modeling and design of a folded waveguide launcher for the Alcator C-Mod tokamak

    SciTech Connect

    Bigelow, T.S.; Fogelman, C.F.; Baity, F.W.; Carter, M.D.; Hoffman, D.J.; Ryan, P.M.; Yugo, J.J.; Golovato, S.N.; Bonoli, P.

    1993-12-01

    The folded waveguide (FWG) launcher is being investigated as an improved antenna configuration for plasma heating in the ion cyclotron range of frequencies (ICRF). A development FWG launcher was successfully tested at Oak Ridge National Laboratory (ORNL) with a low-density plasma load and found to have significantly greater power density capability than current strap-type antennas operating in similar plasmas. To further test the concept on a high density tokamak plasma, a collaboration has been set up between ORNL and Massachusetts Institute of Technology (MIT) to develop and test an 80-MHz, 2-MW FWG on the Alcator C-Mod tokamak at MIT. The radio frequency (rf) electromagnetic modeling techniques and laboratory measurements used in the design of this antenna are described in this paper. A companion paper describes the mechanical design of the FWG.

  15. Central Zagros fold-thrust belt (Iran): New insights from seismic data, field observation, and sandbox modeling

    NASA Astrophysics Data System (ADS)

    Sherkati, S.; Letouzey, J.; Frizon de Lamotte, D.

    2006-08-01

    We present five generalized cross sections across the central Zagros fold-and-thrust belt (Iran). These sections show that the fold geometry varies significantly both horizontally and vertically. The style is closely related to the changes in the mechanical behavior of the lithostratigraphic horizons and, in particular, to the presence of intermediate décollements within the sedimentary pile. Restoration of the sections shows amounts of shortening of the same order from one section to the other. However, it appears to be unequally distributed, suggesting variations in basal décollement shear strength. Analogue modeling has been performed to systematically investigate the effect of an intermediate décollement level at different depths on the style of folding. The models demonstrate that the position of intermediate décollements is an important factor controlling both structural style and fold wavelength. Models with shallow intermediate décollement show regularly and widely spaced anticlines. In these models, the fold wavelength depends directly on the thickness of the dominant competent layer and short-wavelength superficial structures mask broad anticlines at depth. Models with deep intermediate décollement are characterized by the rapid propagation of deformation (with small rate of shortening) along this décollement influencing localization of forthcoming anticlines in the upper levels. Such propagation favors the development of duplexes and multiwavelength folds. On this basis, fold kinematics in central Zagros is discussed using the variation of structural style along different folds as an indicator of the sequence of deformation. Detachment folding is the main folding style at least for the initial stages of deformation and thrust faults developed only at later stages. Some of these faults, branched on décollement levels, express the progression of folding, whereas others are linked to late basement faults cutting through early structures. In general

  16. Finite Element Analysis of Folded Airbag in Frontal Impact of Adapted Vehicles for Disabled Drivers

    NASA Astrophysics Data System (ADS)

    Masiá, J.; Eixerés, B.; Dols, J. F.; Esquerdo, T. V.

    2009-11-01

    The car control adaptations are used in vehicles in order to facilitate the driving to persons with physical handicaps. This does not have to suppose a decrease of the passive safety that is required to the vehicles. In order to analyze this relation there will be characterized the different control adaptations that are in use together with the different devices of passive safety that can be mounted in the vehicles in diverse cases of impact in order to generate models of simulation. The methodology used to generate this simulation consists of the first phase in which there develops the three-dimensional model of the driving place. For it, there has been used a commercial software of three-dimensional design. Once realized this one divides, the model is imported to the finite elements software in which meshing is generated. Finally, dynamic simulation software is used to assign the most important characteristics like material properties, contact interfaces, gas expansion models, airbag fold types, etc.

  17. Deciphering the mechanisms of binding induced folding at nearly atomic resolution: The Φ value analysis applied to IDPs

    PubMed Central

    Gianni, Stefano; Dogan, Jakob; Jemth, Per

    2014-01-01

    The Φ value analysis is a method to analyze the structure of metastable states in reaction pathways. Such a methodology is based on the quantitative analysis of the effect of point mutations on the kinetics and thermodynamics of the probed reaction. The Φ value analysis is routinely used in protein folding studies and is potentially an extremely powerful tool to analyze the mechanism of binding induced folding of intrinsically disordered proteins. In this review we recapitulate the key equations and experimental advices to perform the Φ value analysis in the perspective of the possible caveats arising in intrinsically disordered systems. Finally, we briefly discuss some few examples already available in the literature.

  18. Histological Effect of Basic Fibroblast Growth Factor on Chronic Vocal Fold Scarring in a Rat Model

    PubMed Central

    Tateya, Ichiro; Tateya, Tomoko; Sohn, Jin-Ho; Bless, Diane M.

    2016-01-01

    Objectives Vocal fold scarring is one of the most challenging laryngeal disorders to treat and there are currently no consistently effective treatments available. Our previous studies have shown the therapeutic potential of basic fibroblast growth factor (bFGF) for vocal fold scarring. However, the histological effects of bFGF on scarred vocal fold have not been elucidated. The aim of this study was to examine the histological effects of bFGF on chronic vocal fold scarring. Methods Sprague-Dawley rats were divided into phosphate buffered saline (sham) and bFGF groups. Unilateral vocal fold stripping was performed and the drug was injected into the scarred vocal fold for each group 2 months postoperatively. Injections were performed weekly for 4 weeks. Two months after the last injection, larynges were harvested and histologically analyzed. Results A significant increase of hyaluronic acid was observed in the vocal fold of the bFGF group compared with that of the sham group. However, there was no remarkable change in collagen expression nor in vocal fold contraction. Conclusion Significant increase of hyaluronic acid by local bFGF injection was thought to contribute to the therapeutic effects on chronic vocal fold scarring. PMID:26976028

  19. Relevance of structural segregation and chain compaction for the thermodynamics of folding of a hydrophobic protein model.

    PubMed

    Barbosa, Marco Aurélio A; de Araújo, Antônio F Pereira

    2003-05-01

    The relevance of inside-outside segregation and chain compaction for the thermodynamics of folding of a hydrophobic protein model is probed by complete enumeration of two-dimensional chains of up to 18 monomers in the square lattice. The exact computation of Z scores for uniquely designed sequences confirms that Z tends to decrease linearly with sigma square root of N, as previously suggested by theoretical analysis and Monte Carlo simulations, where sigma, the standard deviation of the number of contacts made by different monomers in the target structure, is a measure of structural segregation and N is the chain length. The probability that the target conformation is indeed the unique global energy minimum of the designed sequence is found to increase dramatically with sigma, approaching unity at maximal segregation. However, due to the huge number of conformations with sub-maximal values of sigma, which correspond to intermediate, only mildly discriminative, values of Z, in addition to significant oscillations of Z around its estimated value, the probability that a correctly designed sequence corresponds to a maximally segregated conformation is small. This behavior of Z also explains the observed relation between sigma and different measures of folding cooperativity of correctly designed sequences.

  20. Self-oscillating Vocal Fold Model Mechanics: Healthy, Diseased, and Aging

    NASA Astrophysics Data System (ADS)

    Hiubler, Elizabeth P.; Pollok, Lucas F. E.; Apostoli, Adam G.; Hancock, Adrienne B.; Plesniak, Michael W.

    2014-11-01

    Voice disorders have been estimated to have a substantial economic impact of 2.5 billion annually. Approximately 30% of people will suffer from a voice disorder at some point in their lives. Life-sized, self-oscillating, synthetic vocal fold (VF) models are fabricated to exhibit material properties representative of human VFs. These models are created both with and without a polyp-like structure, a pathology that has been shown to produce rich viscous flow structures not normally observed for healthy VFs during normal phonation. Pressure measurements are acquired upstream of the VFs and high-speed images are captured at varying flow rates during VF oscillation to facilitate an understanding of the characteristics of healthy and diseased VFs. The images are analyzed using a videokymography line-scan technique. Clinically-relevant parameters calculated from the volume-velocity output of a circumferentially-vented mask (Rothenberg mask) are compared to human data collected from two groups of males aged 18-30 and 60-80. This study extends the use of synthetic VF models by assessing their ability to replicate behaviors observed in human subject data to advance a means of investigating changes associated with normal, pathological, and the aging voice. Supported by the GWU Institute for Biomedical Engineering (GWIBE) and GWU Center for Biomimetics and Bioinspired Engineering (COBRE).

  1. Microstructural characterization of vocal folds toward a strain-energy model of collagen remodeling.

    PubMed

    Miri, Amir K; Heris, Hossein K; Tripathy, Umakanta; Wiseman, Paul W; Mongeau, Luc

    2013-08-01

    Collagen fibrils are believed to control the immediate deformation of soft tissues under mechanical load. Most extracellular matrix proteins remain intact during frozen sectioning, which allows them to be scanned using atomic force microscopy (AFM). Collagen fibrils are distinguishable because of their periodic roughness wavelength. In the present study, the shape and organization of collagen fibrils in dissected porcine vocal folds were quantified using nonlinear laser scanning microscopy data at the micrometer scale and AFM data at the nanometer scale. Rope-shaped collagen fibrils were observed. The geometric characteristics for the fibrils were fed into a hyperelastic model to predict the biomechanical response of the tissue. The model simulates the micrometer-scale unlocking behavior of collagen bundles when extended from their unloaded configuration. Force spectroscopy using AFM was used to estimate the stiffness of collagen fibrils (1±0.5MPa). The presence of rope-shaped fibrils is postulated to change the slope of the force-deflection response near the onset of nonlinearity. The proposed model could ultimately be used to evaluate changes in elasticity of soft tissues that result from the collagen remodeling.

  2. Microstructural Characterization of Vocal Folds toward a Strain-Energy Model of Collagen Remodeling

    PubMed Central

    Miri, Amir K.; Heris, Hossein K.; Tripathy, Umakanta; Wiseman, Paul W.; Mongeau, Luc

    2013-01-01

    Collagen fibrils are believed to control the immediate deformation of soft tissues under biomechanical load. Most extracellular matrix proteins remain intact during frozen sectioning, which allows them to be scanned using atomic force microscopy (AFM). Collagen fibrils are distinguishable because of their helical shape. In the present study, the shape and organization of collagen fibrils in dissected porcine vocal folds were quantified using nonlinear laser scanning microscopy data at the micrometer scale and AFM data at the nanometer scale. Rope-shape collagen fibrils were observed. Geometric characteristics for the fibrils were fed to a hyperelastic model to predict the biomechanical response of the tissue. The model simulates the micrometer-scale unlocking behavior of collagen bundles when extended from their unloaded configuration. Force spectroscopy using AFM was used to estimate the stiffness of collagen fibrils (1 ± 0.5 MPa). The presence of rope-shape fibrils is postulated to change the slope of the force-deflection response near the onset of nonlinearity. The proposed model could ultimately be used to evaluate changes in elasticity of soft tissues that result from the collagen remodeling. PMID:23643604

  3. q-Space Deep Learning: Twelve-Fold Shorter and Model-Free Diffusion MRI Scans.

    PubMed

    Golkov, Vladimir; Dosovitskiy, Alexey; Sperl, Jonathan I; Menzel, Marion I; Czisch, Michael; Samann, Philipp; Brox, Thomas; Cremers, Daniel

    2016-05-01

    Numerous scientific fields rely on elaborate but partly suboptimal data processing pipelines. An example is diffusion magnetic resonance imaging (diffusion MRI), a non-invasive microstructure assessment method with a prominent application in neuroimaging. Advanced diffusion models providing accurate microstructural characterization so far have required long acquisition times and thus have been inapplicable for children and adults who are uncooperative, uncomfortable, or unwell. We show that the long scan time requirements are mainly due to disadvantages of classical data processing. We demonstrate how deep learning, a group of algorithms based on recent advances in the field of artificial neural networks, can be applied to reduce diffusion MRI data processing to a single optimized step. This modification allows obtaining scalar measures from advanced models at twelve-fold reduced scan time and detecting abnormalities without using diffusion models. We set a new state of the art by estimating diffusion kurtosis measures from only 12 data points and neurite orientation dispersion and density measures from only 8 data points. This allows unprecedentedly fast and robust protocols facilitating clinical routine and demonstrates how classical data processing can be streamlined by means of deep learning.

  4. Spiraling Complexity: A Test of the Snowball Effect in a Computational Model of RNA Folding.

    PubMed

    Kalirad, Ata; Azevedo, Ricardo B R

    2016-12-22

    Genetic incompatibilities can emerge as a by-product of genetic divergence. According to Dobzhansky and Muller, an allele that fixes in one population may be incompatible with an allele at a different locus in another population when the two alleles are brought together in hybrids. Orr showed that the number of Dobzhansky-Muller incompatibilities (DMIs) should accumulate faster than linearly-i.e., snowball-as two lineages diverge. Several studies have attempted to test the snowball effect using data from natural populations. One limitation of these studies is that they have focused on predictions of the Orr model but not on its underlying assumptions. Here we use a computational model of RNA folding to test both predictions and assumptions of the Orr model. Two populations are allowed to evolve in allopatry on a holey fitness landscape. We find that the number of inviable introgressions (an indicator for the number of DMIs) snowballs, but does so more slowly than expected. We show that this pattern is explained, in part, by the fact that DMIs can disappear after they have arisen, contrary to the assumptions of the Orr model. This occurs because DMIs become progressively more complex (i.e., involve alleles at more loci) as a result of later substitutions. We also find that most DMIs involve more than two loci-i.e., they are complex. Reproductive isolation does not snowball because DMIs do not act independently of each other. We conclude that the RNA model supports the central prediction of the Orr model that the number of DMIs snowballs, but challenges other predictions, as well as some of its underlying assumptions.

  5. Improvements in Markov State Model Construction Reveal Many Non-Native Interactions in the Folding of NTL9

    PubMed Central

    Schwantes, Christian R.; Pande, Vijay S.

    2013-01-01

    Markov State Models (MSMs) provide an automated framework to investigate the dynamical properties of high-dimensional molecular simulations. These models can provide a human-comprehensible picture of the underlying process, and have been successfully used to study protein folding, protein aggregation, protein ligand binding, and other biophysical systems. The MSM requires the construction of a discrete state-space such that two points are in the same state if they can interconvert rapidly. In the following, we suggest an improved method, which utilizes second order Independent Components Analysis (also known as time-structure based Independent Components Analysis, or tICA), to construct the state-space. We apply this method to simulations of NTL9 (provided by Lindorff-Larsen et al. Science 2011), and show that the MSM is an improvement over previously built models using conventional distance metrics. Additionally, the resulting model provides insight into the role of non-native contacts by revealing many slow timescales associated with compact, non-native states. PMID:23750122

  6. Direct-numerical simulation of the glottal jet and vocal-fold dynamics in a three-dimensional laryngeal model

    PubMed Central

    Zheng, X.; Mittal, R.; Xue, Q.; Bielamowicz, S.

    2011-01-01

    An immersed-boundary method based flow solver coupled with a finite-element solid dynamics solver is employed in order to conduct direct-numerical simulations of phonatory dynamics in a three-dimensional model of the human larynx. The computed features of the glottal flow including mean and peak flow rates, and the open and skewness quotients are found to be within the normal physiological range. The flow-induced vibration pattern shows the classical “convergent-divergent” glottal shape, and the vibration amplitude is also found to be typical for human phonation. The vocal fold motion is analyzed through the method of empirical eigenfunctions and this analysis indicates a 1:1 modal entrainment between the “adduction-abduction” mode and the “mucosal wave” mode. The glottal jet is found to exhibit noticeable cycle-to-cycle asymmetric deflections and the mechanism underlying this phenomenon is examined. PMID:21786908

  7. Evaluation of Synthetic Self-Oscillating Models of the Vocal Folds

    NASA Astrophysics Data System (ADS)

    Hubler, Elizabeth P.; Weiland, Kelley S.; Hancock, Adrienne B.; Plesniak, Michael W.

    2013-11-01

    Approximately 30% of people will suffer from a voice disorder at some point in their lives. The probability doubles for those who rely heavily on their voice, such as teachers and singers. Synthetic vocal fold (VF) models are fabricated and evaluated experimentally in a vocal tract simulator to replicate physiological conditions. Pressure measurements are acquired along the vocal tract and high-speed images are captured at varying flow rates during VF oscillation to facilitate understanding of the characteristics of healthy and damaged VFs. The images are analyzed using a videokymography line-scan technique that has been used to examine VF motion and mucosal wave dynamics in vivo. Clinically relevant parameters calculated from the volume-velocity output of a circumferentially-vented mask (Rothenberg mask) are compared to patient data. This study integrates speech science with engineering and flow physics to overcome current limitations of synthetic VF models to properly replicate normal phonation in order to advance the understanding of resulting flow features, progression of pathological conditions, and medical techniques. Supported by the GW Institute for Biomedical Engineering (GWIBE) and GW Center for Biomimetics and Bioinspired Engineering (COBRE).

  8. Seismic attribute analysis and its application to mapping folds and fractures

    NASA Astrophysics Data System (ADS)

    Mai, Ha Thanh

    Geometric attributes such as coherence and curvature have been very successful in delineating faults in sedimentary basins. While not a common exploration objective, fractured and faulted basement forms important reservoirs in Venezuela, USA (Southern California), Brazil, Libya, Algeria, Egypt, Russia, and Vietnam (Landes, 1960; Canh, 2008). Because of the absence of stratified, coherent reflectors, illumination of basement faults is more problematic than illumination of faults within the sedimentary column. In order to address these problems, it is important to carefully analyze alternative forms of the 3D seismic data, which in this dissertation will be primarily combinations of one or more seismic attributes, and interpret them within the context of an appropriate structural deformation model. For that purpose, in this research, I concentrate on analyzing structural dip and azimuth, amplitude energy gradients, and a large family of attributes based on curvature to better illuminate fracture 'sweet spots' and estimate their density and orientation. I develop and calibrate these attribute and interpretation workflows through application to a complexly folded and faulted, but otherwise typical, geologic target in the Chicontepec Basin of Mexico. I then apply this calibrated workflow to better characterize faults and build fracture models in the granite basement of the Cuu Long Basin, Vietnam, and the granite and rhyolite-metarhyolite basement of Osage County, Oklahoma, USA. In the Cuu Long granite basement, it forms an important unconventional reservoir. In Osage County, we suspect basement control of overlying fractures in the Mississippian chat deposits.

  9. Mechanics of Curved Folds

    NASA Astrophysics Data System (ADS)

    Dias, Marcelo A.; Santangelo, Christian D.

    2011-03-01

    Despite an almost two thousand year history, origami, the art of folding paper, remains a challenge both artistically and scientifically. Traditionally, origami is practiced by folding along straight creases. A whole new set of shapes can be explored, however, if, instead of straight creases, one folds along arbitrary curves. We present a mechanical model for curved fold origami in which the energy of a plastically-deformed crease is balanced by the bending energy of developable regions on either side of the crease. Though geometry requires that a sheet buckle when folded along a closed curve, its shape depends on the elasticity of the sheet. NSF DMR-0846582.

  10. Protein folding optimization based on 3D off-lattice model via an improved artificial bee colony algorithm.

    PubMed

    Li, Bai; Lin, Mu; Liu, Qiao; Li, Ya; Zhou, Changjun

    2015-10-01

    Protein folding is a fundamental topic in molecular biology. Conventional experimental techniques for protein structure identification or protein folding recognition require strict laboratory requirements and heavy operating burdens, which have largely limited their applications. Alternatively, computer-aided techniques have been developed to optimize protein structures or to predict the protein folding process. In this paper, we utilize a 3D off-lattice model to describe the original protein folding scheme as a simplified energy-optimal numerical problem, where all types of amino acid residues are binarized into hydrophobic and hydrophilic ones. We apply a balance-evolution artificial bee colony (BE-ABC) algorithm as the minimization solver, which is featured by the adaptive adjustment of search intensity to cater for the varying needs during the entire optimization process. In this work, we establish a benchmark case set with 13 real protein sequences from the Protein Data Bank database and evaluate the convergence performance of BE-ABC algorithm through strict comparisons with several state-of-the-art ABC variants in short-term numerical experiments. Besides that, our obtained best-so-far protein structures are compared to the ones in comprehensive previous literature. This study also provides preliminary insights into how artificial intelligence techniques can be applied to reveal the dynamics of protein folding. Graphical Abstract Protein folding optimization using 3D off-lattice model and advanced optimization techniques.

  11. Application of motion analysis in the study of the effect of botulinum toxin to rat vocal folds

    NASA Astrophysics Data System (ADS)

    Saadah, Abdul K.; Galatsanos, Nikolas P.; Inagi, K.; Bless, D.

    1997-05-01

    In the past we have proposed a system that measures the deformations of the vocal folds from videostroboscopic images of the larynx, in that system: (1) we extract the boundaries of the vocal folds, (2) we register elastically the vocal fold boundaries in successive frames. This yields the displacement vector field (DVF) between adjacent frames, and (3) we fit using a least-squares approach an affine transformation model to succinctly describe the deformations between adjacent frames. In this paper, we present as an example of the capabilities of this system, an initial study of the deformation changes in rat vocal folds pre and post injection with Botulinum toxin. For this application the generated DVF was segmented into right DVF and left DVF and the deformation of each segment is studied separately.

  12. Analysis of the distributed computing approach applied to the folding of a small beta peptide.

    PubMed

    Paci, Emanuele; Cavalli, Andrea; Vendruscolo, Michele; Caflisch, Amedeo

    2003-07-08

    In the recently proposed distributed computing approach to protein folding a very large number of short independent simulations is performed. Using this method, folding events on a time scale orders of magnitude shorter than the experimental one have been reported. However, it has also been observed that the folding process is not an elementary kinetic step and that the presence of initial lag phases can bias short simulations toward atypical pathways. We study here a 20-residue three-stranded antiparallel beta-sheet peptide whose equilibrium properties can be characterized by atomistic molecular dynamics simulations. We found that the folding rate of this peptide is estimated correctly by the distributed computing approach when trajectories > approximately 1/100 of the equilibrium folding time are considered. We also found that the fastest folding events occur through high-energy pathways, which are unlikely under equilibrium conditions. These very fast folding pathways do not relax within the equilibrium denatured state that is stabilized by the transient presence of both native and non-native interactions, and they are characterized by the nearly simultaneous formation of the two beta-hairpins and a very small number of non-native contacts.

  13. Clonal analysis reveals granule cell behaviors and compartmentalization that determine the folded morphology of the cerebellum.

    PubMed

    Legué, Emilie; Riedel, Elyn; Joyner, Alexandra L

    2015-05-01

    The mammalian cerebellum consists of folds of different sizes and shapes that house distinct neural circuits. A crucial factor underlying foliation is the generation of granule cells (gcs), the most numerous neuron type in the brain. We used clonal analysis to uncover global as well as folium size-specific cellular behaviors that underlie cerebellar morphogenesis. Unlike most neural precursors, gc precursors divide symmetrically, accounting for their massive expansion. We found that oriented cell divisions underlie an overall anteroposteriorly polarized growth of the cerebellum and gc clone geometry. Clone geometry is further refined by mediolateral oriented migration and passive dispersion of differentiating gcs. Most strikingly, the base of each fissure acts as a boundary for gc precursor dispersion, which we propose allows each folium to be regulated as a developmental unit. Indeed, the geometry and size of clones in long and short folia are distinct. Moreover, in engrailed 1/2 mutants with shorter folia, clone cell number and geometry are most similar to clones in short folia of wild-type mice. Thus, the cerebellum has a modular mode of development that allows the plane of cell division and number of divisions to be differentially regulated to ensure that the appropriate number of cells are partitioned into each folium.

  14. Conformational analysis of HAMLET, the folding variant of human α-lactalbumin associated with apoptosis

    PubMed Central

    Casbarra, Annarita; Birolo, Leila; Infusini, Giuseppe; Dal Piaz, Fabrizio; Svensson, Malin; Pucci, Piero; Svanborg, Catharina; Marino, Gennaro

    2004-01-01

    A combination of hydrogen/deuterium (H/D) exchange and limited proteolysis experiments coupled to mass spectrometry analysis was used to depict the conformation in solution of HAMLET, the folding variant of human α-lactalbumin, complexed to oleic acid, that induces apoptosis in tumor and immature cells. Although near- and far-UV CD and fluorescence spectroscopy were not able to discriminate between HAMLET and apo-α-lactalbumin, H/D exchange experiments clearly showed that they correspond to two distinct conformational states, with HAMLET incorporating a greater number of deuterium atoms than the apo and holo forms. Complementary proteolysis experiments revealed that HAMLET and apo are both accessible to proteases in the β-domain but showed substantial differences in accessibility to proteases at specific sites. The overall results indicated that the conformational changes associated with the release of Ca2+ are not sufficient to induce the HAMLET conformation. Metal depletion might represent the first event to produce a partial unfolding in the β-domain of α-lactalbumin, but some more unfolding is needed to generate the active conformation HAMLET, very likely allowing the protein to bind the C18:1 fatty acid moiety. On the basis of these data, a putative binding site of the oleic acid, which stabilizes the HAMLET conformation, is proposed. PMID:15075403

  15. Conformational analysis of HAMLET, the folding variant of human alpha-lactalbumin associated with apoptosis.

    PubMed

    Casbarra, Annarita; Birolo, Leila; Infusini, Giuseppe; Dal Piaz, Fabrizio; Svensson, Malin; Pucci, Piero; Svanborg, Catharina; Marino, Gennaro

    2004-05-01

    A combination of hydrogen/deuterium (H/D) exchange and limited proteolysis experiments coupled to mass spectrometry analysis was used to depict the conformation in solution of HAMLET, the folding variant of human alpha-lactalbumin, complexed to oleic acid, that induces apoptosis in tumor and immature cells. Although near- and far-UV CD and fluorescence spectroscopy were not able to discriminate between HAMLET and apo-alpha-lactalbumin, H/D exchange experiments clearly showed that they correspond to two distinct conformational states, with HAMLET incorporating a greater number of deuterium atoms than the apo and holo forms. Complementary proteolysis experiments revealed that HAMLET and apo are both accessible to proteases in the beta-domain but showed substantial differences in accessibility to proteases at specific sites. The overall results indicated that the conformational changes associated with the release of Ca2+ are not sufficient to induce the HAMLET conformation. Metal depletion might represent the first event to produce a partial unfolding in the beta-domain of alpha-lactalbumin, but some more unfolding is needed to generate the active conformation HAMLET, very likely allowing the protein to bind the C18:1 fatty acid moiety. On the basis of these data, a putative binding site of the oleic acid, which stabilizes the HAMLET conformation, is proposed.

  16. A Summary of Coupled, Uncoupled, and Hybrid Tectonic Models for the Yakima Fold Belt--Topical Report

    SciTech Connect

    Chamness, Michele A.; Winsor, Kelsey; Unwin, Stephen D.

    2012-08-01

    This document is one in a series of topical reports compiled by the Pacific Northwest National Laboratory to summarize technical information on selected topics important to the performance of a probabilistic seismic hazard analysis of the Hanford Site. The purpose of this report is to summarize the range of opinions and supporting information expressed by the expert community regarding whether a coupled or uncoupled model, or a combination of both, best represents structures in the Yakima Fold Belt. This issue was assessed to have a high level of contention with up to moderate potential for impact on the hazard estimate. This report defines the alternative conceptual models relevant to this technical issue and the arguments and data that support those models. It provides a brief description of the technical issue and principal uncertainties; a general overview on the nature of the technical issue, along with alternative conceptual models, supporting arguments and information, and uncertainties; and finally, suggests some possible approaches for reducing uncertainties regarding this issue.

  17. 3D numerical modeling of the lateral transition between viscous overthrusting and folding with application to the Helvetic nappe system

    NASA Astrophysics Data System (ADS)

    Spitz, Richard; Schmalholz, Stefan; Kaus, Boris

    2016-04-01

    The Helvetic nappe system of the European Alps is generally described as a complex of fold and thrust belts. While the overall geology of the system has been studied in detail, the understanding of the tectonic development and mechanical interconnection between overthrusting and folding is still incomplete. One clue comes from the mechanical stratigraphy and the corresponding lateral transition from overthrusting to folding, which is characteristic for the Helvetic nappe system. We employ a three-dimensional numerical model with linear and non-linear viscous rheology to investigate the control of the lateral variation in the thickness of a weak detachment horizon on the transition from folding to overthrusting during continental shortening. The model configuration is based on published work based on 2D numerical simulations. The simulations are conducted with the three-dimensional staggered-grid finite difference code LaMEM (Lithosphere and Mantle Evolution Model), which allows for coupled nonlinear thermo-mechanical modeling of lithospheric deformation with visco-elasto-plastic rheology and computation on massive parallel machines. Our model configuration consists of a stiff viscous layer, with a pre-existing weak zone, resting within a weaker viscous matrix. The reference viscosity ratio μL/μM (for the same strain rate) between the layer and matrix ranges from 10 to 200. The simulations were run with several distinct initial geometries by altering the thickness of the detachment horizon below the stiff layer across the configurations. Shortening with a constant bulk rate is induced by the prescription of a horizontal velocity on one side of the model. The first results of our simulations highlight the general importance of the initial geometry on the lateral transition from overthrusting to folding. Additionally, models with a stepwise lateral variation of the detachment horizon indicate a fold development orthogonal to the main compressional axis.

  18. RETRACTED: Design and analytical modeling of folded waveguide traveling wave tube

    NASA Astrophysics Data System (ADS)

    Malek, Fareq

    2009-12-01

    This article has been retracted: please see Elsevier Policy on Article Withdrawal ( http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the editors and author. The author has used without acknowledgement part of the PhD thesis by Yap Soon Tan, "Modeling of folded waveguide travelling wave", University of Liverpool, 2007, available from the British Library at http://ethos.bl.uk/ ILS catalogue number: 13826409. Shelfmark: DXN108794. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and we apologize to readers of the journal that this was not detected during the submission process. The author deeply regrets this and offers his sincere and unreserved apologies to the readers of the journal, and especially to Dr. Yap S. Tan, author of the above-mentioned thesis.

  19. Implementation of a 3d numerical model of a folded multilayer carbonate aquifer

    NASA Astrophysics Data System (ADS)

    Di Salvo, Cristina; Guyennon, Nicolas; Romano, Emanuele; Bruna Petrangeli, Anna; Preziosi, Elisabetta

    2016-04-01

    The main objective of this research is to present a case study of the numerical model implementation of a complex carbonate, structurally folded aquifer, with a finite difference, porous equivalent model. The case study aquifer (which extends over 235 km2 in the Apennine chain, Central Italy) provides a long term average of 3.5 m3/s of good quality groundwater to the surface river network, sustaining the minimum vital flow, and it is planned to be exploited in the next years for public water supply. In the downstream part of the river in the study area, a "Site of Community Importance" include the Nera River for its valuable aquatic fauna. However, the possible negative effects of the foreseen exploitation on groundwater dependent ecosystems are a great concern and model grounded scenarios are needed. This multilayer aquifer was conceptualized as five hydrostratigraphic units: three main aquifers (the uppermost unconfined, the central and the deepest partly confined), are separated by two locally discontinuous aquitards. The Nera river cuts through the two upper aquifers and acts as the main natural sink for groundwater. An equivalent porous medium approach was chosen. The complex tectonic structure of the aquifer requires several steps in defining the conceptual model; the presence of strongly dipping layers with very heterogeneous hydraulic conductivity, results in different thicknesses of saturated portions. Aquifers can have both unconfined or confined zones; drying and rewetting must be allowed when considering recharge/discharge cycles. All these characteristics can be included in the conceptual and numerical model; however, being the number of flow and head target scarce, the over-parametrization of the model must be avoided. Following the principle of parsimony, three steady state numerical models were developed, starting from a simple model, and then adding complexity: 2D (single layer), QUASI -3D (with leackage term simulating flow through aquitards) and

  20. Analysis of proteins with the 'hot dog' fold: Prediction of function and identification of catalytic residues of hypothetical proteins

    PubMed Central

    Pidugu, Lakshmi S; Maity, Koustav; Ramaswamy, Karthikeyan; Surolia, Namita; Suguna, Kaza

    2009-01-01

    Background The hot dog fold has been found in more than sixty proteins since the first report of its existence about a decade ago. The fold appears to have a strong association with fatty acid biosynthesis, its regulation and metabolism, as the proteins with this fold are predominantly coenzyme A-binding enzymes with a variety of substrates located at their active sites. Results We have analyzed the structural features and sequences of proteins having the hot dog fold. This study reveals that though the basic architecture of the fold is well conserved in these proteins, significant differences exist in their sequence, nature of substrate and oligomerization. Segments with certain conserved sequence motifs seem to play crucial structural and functional roles in various classes of these proteins. Conclusion The analysis led to predictions regarding the functional classification and identification of possible catalytic residues of a number of hot dog fold-containing hypothetical proteins whose structures were determined in high throughput structural genomics projects. PMID:19473548

  1. Fold-related-fracturing at the Livingstone River anticline (AB; Canada) by coupling field surveying and numerical modelling

    NASA Astrophysics Data System (ADS)

    Humair, Florian; Epard, Jean-Luc; Bauville, Arthur; Jaboyedoff, Michel; Pana, Dinu; Kaus, Boris; Schmalholz, Stefan

    2016-04-01

    The interpretation of fold-related joints and faults is of primary importance in terms of fluids prospection (e.g. water, oil, gas, C02) since anticlines are potential structural trap while fracturing can strongly influence the storage capacity as well as the migration pathways. Located at the front of the Foothills of the Rocky Mountains in Alberta (Canada), the Livingstone Range (LRA) is analogous to hydrocarbon reservoir that occur elsewhere in the Foothills (Cooley et al., 2011). The Livingstone Range fold system is related to the development of the Livingstone thrust that cuts around 1000m up-section from a regional decollement in the Palliser Formation (Devonian) to another in the Fernie Formation (Jurassic). Our study focuses on the detailed structural investigation of the Livingstone River anticline (northern part of the LRA). It aims at characterizing the anticline geometry as well as the fracturing pattern (orientation, mode, infilling, spacing, trace length, density, and cross-cutting relationships) in order to propose a kinematic interpretation of the fold-related fracturing genesis. The study area is investigated at different scales by combining field surveys with remote sensing (HR-Digital Elevation Model, Ground-based LiDAR, Gigapixel photography) and thin-sections analyses. In a second step we performed finite difference 3D numerical simulations in order to compute the evolution of local principal stress orientation during folding. We compared the fracture (or plastic bands) distribution in the field with 1) a dynamic numerical model of detachment folding; and 2) an instantaneous numerical model based on the final fold geometry. Cooley, M.A., Price, R.A., Dixon, J.M., Kyser, T.K. 2011. Along-strike variations and internal details of chevron-style flexural slip thrust-propagation folds within the southern Livingstone Range anticlinorium, a paleo-hydrocarbon reservoir in southern Alberta Foothills, Canada. AAPG bulletin, 95 (11), 1821-1849.

  2. Direct assay for endo-α-mannosidase substrate preference on correctly folded and misfolded model glycoproteins.

    PubMed

    Dedola, Simone; Izumi, Masayuki; Makimura, Yutaka; Seko, Akira; Kanamori, Akiko; Takeda, Yoichi; Ito, Yukishige; Kajihara, Yasuhiro

    2016-11-03

    We previously reported a unique assay system for UDP-glucose glycoprotein glucosyltransferase (UGGT) toward glycoprotein folding intermediates during the folding process. The assay involved the in vitro folding of both high-mannose type oligosaccharyl crambin, which yielded only the correctly folded glycoprotein form (M9-glycosyl-native-crambin), and its mutant, which yielded misfolded glycoproteins (M9-glycosyl-misfolded-crambin), in the presence of UGGT. The process successfully yielded both mono-glucosylated M9-glycosyl-native-crambin (G1M9-glycosyl-native-crambin) and M9-glycosyl-misfolded-crambin (G1M9-glycosyl-misfolded-crambin). Here, we report the use of our in vitro folding system to evaluate the substrate preference of Golgi endo-α-mannosidase against G1M9-native and -misfolded glycoprotein forms. In our assay Golgi endo-α-mannosidase removed Glc-α-1-3-Man unit from G1M9-native and -misfolded-crambins clearly proving that Golgi endo-α-mannosidase does not have specific preference for correctly folded or misfolded protein structure.

  3. Fold-Related Fractures and Postfolding Fracturing, Rock Mass Condition Analyses and Geological Modelling in Turtle Mountain (Alberta Canada).

    NASA Astrophysics Data System (ADS)

    Humair, Florian; Epard, Jean-Luc; Jaboyedoff, Michel; Pedrazzini, Andrea; Froese, Corey

    2010-05-01

    Turtle Mountain is located in the Foothills in southwest Alberta and is formed by highly fractured Paleozoic carbonates rocks and Mesozoic clastic rocks. This area is mainly affected by two major geological structures that are the Turtle Mountain anticline and the Turtle Mountain thrust. This site has become famous after a 30 M m3 rock avalanche of massive limestone and dolostone affecting the eastern mountainside of Turtle Mountain on April 1903. This resulted in more than 70 casualties and buried part of the Frank village. A detailed analysis of predisposing factors leading to failure has been performed using a structural and rock mass condition field analysis (geological and geotechnical mapping, rock mass classification, Schmidt hammer). In addition remote sensing analyses have been provided (High Resolution Digital Elevation Model, Coltop 3D software). The local variations of discontinuity sets and rock mass conditions has been estimated in order to separate the study zone into homogenous structural domains and to correlate them with unstable areas (volumes and failure mechanisms). The aim of this study is to build a theoretical model that shows the relationship between the anticline geometry and the fracturating density. It should be able to determine the origin and the chronology of the discontinuity sets in relation to the tectonic phases (mainly the folding one). A 3D geological model based on several geological profiles performed perpendicular to the Turtle Mountain anticline is necessary to make a detailed analysis. The preliminary results indicate the role of discontinuity sets in the failure mechanisms of the mountain. Moreover if some sets only appear in one limb of the anticline, some others are present in both limbs indicating their posteriority compared with the first ones. Furthermore, a relation between the distance to the fold axis and the quality of the rock mass (Geological Strength Index) has been statistically pointed out, illustrating the

  4. Space-time evolution of a growth fold (Betic Cordillera, Spain). Evidences from 3D geometrical modelling

    NASA Astrophysics Data System (ADS)

    Martin-Rojas, Ivan; Alfaro, Pedro; Estévez, Antonio

    2014-05-01

    We present a study that encompasses several software tools (iGIS©, ArcGIS©, Autocad©, etc.) and data (geological mapping, high resolution digital topographic data, high resolution aerial photographs, etc.) to create a detailed 3D geometric model of an active fault propagation growth fold. This 3D model clearly shows structural features of the analysed fold, as well as growth relationships and sedimentary patterns. The results obtained permit us to discuss the kinematics and structural evolution of the fold and the fault in time and space. The study fault propagation fold is the Crevillente syncline. This fold represents the northern limit of the Bajo Segura Basin, an intermontane basin in the Eastern Betic Cordillera (SE Spain) developed from upper Miocene on. 3D features of the Crevillente syncline, including growth pattern, indicate that limb rotation and, consequently, fault activity was higher during Messinian than during Tortonian; consequently, fault activity was also higher. From Pliocene on our data point that limb rotation and fault activity steadies or probably decreases. This in time evolution of the Crevillente syncline is not the same all along the structure; actually the 3D geometric model indicates that observed lateral heterogeneity is related to along strike variation of fault displacement.

  5. Folding analysis of the most complex Stevedore’s protein knot

    PubMed Central

    Wang, Iren; Chen, Szu-Yu; Hsu, Shang-Te Danny

    2016-01-01

    DehI is a homodimeric haloacid dehalogenase from Pseudomonas putida that contains the most complex 61 Stevedore’s protein knot within its folding topology. To examine how DehI attains such an intricate knotted topology we combined far-UV circular dichroism (CD), intrinsic fluorescence spectroscopy and small angle X-ray scattering (SAXS) to investigate its folding mechanism. Equilibrium unfolding of DehI by chemical denaturation indicated the presence of two highly populated folding intermediates, I and I’. While the two intermediates vary in secondary structure contents and tertiary packing according to CD and intrinsic fluorescence, respectively, their overall dimension and compactness are similar according to SAXS. Three single-tryptophan variants (W34, W53, and W196) were generated to probe non-cooperative unfolding events localized around the three fluorophores. Kinetic fluorescence measurements indicated that the transition from the intermediate I’ to the unfolded state is rate limiting. Our multiparametric folding analyses suggest that DehI unfolds through a linear folding pathway with two distinct folding intermediates by initial hydrophobic collapse followed by nucleation condensation, and that knotting precedes the formation of secondary structures. PMID:27527519

  6. Common Structural Errors in Paleomagnetic Analysis of Fold-And Belts

    NASA Astrophysics Data System (ADS)

    Pueyo, E.

    2013-05-01

    Paleomagnetism is essential to decipher vertical axis rotations (VAR) in orogens, an elusive variable in tectonic studies. While unraveling the significance of VAR in the internal parts of orogenic belts might be made difficult due to the complex superposition of deformation events, it has provided timely insights into the geometry and kinematics of the external parts; the fold-and-thrust belts (FAT belts). Accurate quantification of VAR demands a reliable recording of the Earth's magnetic field. Inclination flattening or non-dipolar geometries of the geomagnetic field are well known to affect the reliability of paleomagnetic directions. Other factors are related to the geometry and mechanisms of deformation and are often overlooked: 1) Overlapping of vectors has to do with the technical limitation to isolating components in the laboratory. Secondary remagnetizations may be a common post tectonic process. The orientation of the overlapped vector will change along the fold geometry. Their restoration will result in different DEC and INC errors depending upon the degree of overlapping, the fold axis orientation (FAO), dip of the beds and the polarity of the components. 2) Many paleomagnetic studies implicitly assume the rigid-body behavior of rock volumes during deformation (absence of internal strain). However, pure shear may appear at the fold hinges and simple shear is frequent at the fold limbs and around fault planes. The bedding correction (BC) will induce DEC and INC errors controlled by the FAO and shear magnitude. 3) Different stages of folding and thrusting may happen in FAT belts and may be responsible for the superposition of non-coaxial axis of deformation. Besides, folds are not always cylindrical. These factors are responsible for the generation of plunging, conical and superposed folds, etc… The BC, instead of the reverse sequential restoration, will produce declination errors that depend upon the non-coaxility angle and the folding and tilting

  7. Quasi-atomic model of bacteriophage t7 procapsid shell: insights into the structure and evolution of a basic fold.

    PubMed

    Agirrezabala, Xabier; Velázquez-Muriel, Javier A; Gómez-Puertas, Paulino; Scheres, Sjors H W; Carazo, José M; Carrascosa, José L

    2007-04-01

    The existence of similar folds among major structural subunits of viral capsids has shown unexpected evolutionary relationships suggesting common origins irrespective of the capsids' host life domain. Tailed bacteriophages are emerging as one such family, and we have studied the possible existence of the HK97-like fold in bacteriophage T7. The procapsid structure at approximately 10 A resolution was used to obtain a quasi-atomic model by fitting a homology model of the T7 capsid protein gp10 that was based on the atomic structure of the HK97 capsid protein. A number of fold similarities, such as the fitting of domains A and P into the L-shaped procapsid subunit, are evident between both viral systems. A different feature is related to the presence of the amino-terminal domain of gp10 found at the inner surface of the capsid that might play an important role in the interaction of capsid and scaffolding proteins.

  8. Multivariate high-dimensional cortical folding analysis, combining complexity and shape, in neonates with congenital heart disease.

    PubMed

    Awate, Suyash P; Yushkevich, Paul; Song, Zhuang; Licht, Daniel; Gee, James C

    2009-01-01

    The paper presents a novel statistical framework for cortical folding pattern analysis that relies on a rich multivariate descriptor of folding patterns in a region of interest (ROI). The ROI-based approach avoids problems faced by spatial-normalization-based approaches stemming from the severe deficiency of homologous features between typical human cerebral cortices. Unlike typical ROI-based methods that summarize folding complexity or shape by a single number, the proposed descriptor unifies complexity and shape of the surface in a high-dimensional space. In this way, the proposed framework couples the reliability of ROI-based analysis with the richness of the novel cortical folding pattern descriptor. Furthermore, the descriptor can easily incorporate additional variables, e.g. cortical thickness. The paper proposes a novel application of a nonparametric permutation-based approach for statistical hypothesis testing for any multivariate high-dimensional descriptor. While the proposed framework has a rigorous theoretical underpinning, it is straightforward to implement. The framework is validated via simulated and clinical data. The paper is the first to quantitatively evaluate cortical folding in neonates with complex congenital heart disease.

  9. Structural modeling of the Zagros fold-and-thrust belt (Iraq) combining field work and remote sensing techniques

    NASA Astrophysics Data System (ADS)

    Reif, D.; Grasemann, B.; Faber, R.; Lockhart, D.

    2009-04-01

    The Zagros fold-and-thrust belt is known for its spectacular fold trains, which have formed in detached Phanerozoic sedimentary cover rocks above a shortened crystalline Precambrian basement. Orogeny evolved through the Late Cretaceous to Miocene collision between the Arabian and Eurasian plate, during which the Neotethys oceanic basin was closed. Still active deformation shortening in the order of 2-2.5 cm/yr is partitioned in S-SW directed folding and thrusting of the Zagros fold-and-thrust belt and NW-SE to N-S trending dextral strike slip faults. The sub-cylindrical doubly-plunging fold trains with wavelengths of 5 - 10 km host more than half of the world's hydrocarbon reserves in mostly anticlinal traps. In this work we investigate the three dimensional structure of the Zagros fold-and-thrust belt in the Kurdistan region of Iraq. The mapped region is situated NE from the city of Erbil and comprises mainly Cretaceous to Cenozoic folded sediments consisting of mainly limestones, dolomites, sandstones, siltstones, claystones and conglomerates. Although the overall security situation in Kurdistan is much better than in the rest of Iraq, structural field mapping was restricted to sections along the main roads perpendicular to the strike of the fold trains, mainly because of the contamination of the area with landmines and unexploded ordnance, a problem that dates back to the end of World War Two. Landmines were also used by the central government in the 1960s and 1970s in order to subdue Kurdish groups. During the 1980-1988 Iran-Iraq War, the north was mined again. In order to extend the structural measurements statistically over the investigated area resulting in a three-dimensional model of the fold trains, we used the Fault Trace module of the WinGeol software (www.terramath.com). This package allows the interactive mapping and visualization of the spatial orientations (i.e. dip and strike) of geological finite planar structures (e.g. faults, lithological

  10. Single-molecule analysis of Mss116-mediated group II intron folding

    PubMed Central

    Karunatilaka, Krishanthi S.; Solem, Amanda; Pyle, Anna Marie; Rueda, David

    2015-01-01

    DEAD-box helicases are conserved enzymes involved in nearly all aspects of RNA metabolism, but their mechanisms of action remain unclear. Here, we investigated the mechanism of the DEAD-box protein Mss116 on its natural substrate, the group II intron ai5γ. Group II introns are structurally complex catalytic RNAs considered evolutionarily related to the eukaryotic spliceosome, and an interesting paradigm for large RNA folding. We used single-molecule fluorescence to monitor the effect of Mss116 on folding dynamics of a minimal active construct, ai5γ–D135. The data show that Mss116 stimulates dynamic sampling between states along the folding pathway, an effect previously observed only with high Mg2+ concentrations. Furthermore, the data indicate that Mss116 promotes folding through discrete ATP-independent and ATP-dependent steps. We propose that Mss116 stimulates group II intron folding through a multi-step process that involves electrostatic stabilization of early intermediates and ATP hydrolysis during the final stages of native state assembly. PMID:20944626

  11. Comparative analysis of clinical profile: chronic cough vs paradoxical vocal fold motion

    PubMed Central

    Hartley, Naomi A.; Petty, Brian E.; Johnson, Bethany; Thibeault, Susan L.

    2015-01-01

    Background Ongoing contention surrounding typical demographic and clinical attributes of chronic cough (CC) and paradoxical vocal fold motion (PVFM) impedes timely diagnosis and optimum patient care. Designed to reduce preventable patient morbidity through improved recognition and differentiation, the current study aimed to determine representative clinical profiles for CC and PVFM, with identification of distinctive attributes from the general population and risk factors associated with each diagnosis. Methods Self-reported medical questionnaires, demographic and lifestyle attributes of CC and PVFM cases from a disease-specific outcomes database were compared to US population data and published normative values. Univariate comparison and multivariate regression modelling of age, sex, alcohol intake, smoking, Reflux Symptom Index (RSI), Voice Handicap Index (VHI), and Generalized Anxiety Disorder 7-item Scale (GAD-7) determined distinguishing features between the clinical groups, including odds ratios for presenting with CC versus PVFM. Results Clinical profiles developed from 283 (128 CC, 155 PVFM) adults (18–91years) were significantly different from the general population across each demographic, lifestyle and clinical variable (all p<.01), with the exception of obesity. Age (55.39 ± 13.54 vs 45.07 ± 16.51years, p<.01) and mean RSI score (21.5 ±9.02 vs 18.1±9.08, p<.01) most reliably distinguished CC from PVFM, with those aged 60–69 years (OR=9.45) most likely to be diagnosed with CC. Conclusions Standard clinical profiles of CC and PVFM are distinct from the general population, aiding determination of relative probabilities and risk factors in the differential diagnostic process. Variations between CC and PVFM were subtle, reliably distinguished by age and relative severity of laryngopharyngeal reflux symptomatology. PMID:26507903

  12. Facies analysis and diagenetic features of the Aptian Dariyan Formation in Zagros Fold-Thrust Belt, SW Iran

    NASA Astrophysics Data System (ADS)

    Haghighi, Arash Shaabanpour; Sahraeyan, Mohammad

    2014-12-01

    The Aptian Dariyan Formation (upper part of the Khami Group), is one of the important reservoir rocks in the Zagros Fold-Thrust Belt. The Zagros Fold-Thrust Belt is located on the boundary between the Arabian and Eurasian lithospheric plates and formed from collision between Eurasia and advancing Arabia during the Cenozoic. In these studied area, the Dariyan Formation with a thickness of 136 meters (Fahliyan section) and 100 meters (Kuh-e-Rahmat section), consists of carbonate rocks. Based on the facies analysis and sedimentological data, 16 microfacies were identified. The microfacies are attributed to five facies belts: tidal flat (lime mudstone, dolomitic mudstone and stromatolitic boundstone), lagoon (bioclastic packstone, orbitolinids bioclastic packstone and orbitolinids peloidal packstone), shoal (orbitolinids grainstone and peloidal grainstone), restricted (peloidal packstone, rudist floatstone/rudstone and orbitolinid wackestone), and open marine (orbitolinid floatstone, dasycladacean algae floatstone, bioclast pelagic foraminiferal wackestone/packstone, pelagic foraminiferal mudstone/wackestone, and calcispere packstone/wackestone). The depositional model relates to the carbonate ramp. The allochems of the Dariyan Formation are dominated by foraminifera, bioclasts and green algae. Peloids, and intraclasts are less abundant in this formation. Due to the great diversity and abundance of the foraminifera, this carbonate ramp is referred to as a "foraminifera-dominated carbonate ramp system". This carbonate system reflects a local regression in the Fahliyan section which can be related to the vertical movement of the Kazeroon Fault. The carbonates of Dariyan Formation have been affected by a variety of diagenetic processes such as compaction, dissolution, cementation, neomorphism, and dolomitization.

  13. Use of integrated analogue and numerical modelling to predict tridimensional fracture intensity in fault-related-folds.

    NASA Astrophysics Data System (ADS)

    Pizzati, Mattia; Cavozzi, Cristian; Magistroni, Corrado; Storti, Fabrizio

    2016-04-01

    Fracture density pattern predictions with low uncertainty is a fundamental issue for constraining fluid flow pathways in thrust-related anticlines in the frontal parts of thrust-and-fold belts and accretionary prisms, which can also provide plays for hydrocarbon exploration and development. Among the drivers that concur to determine the distribution of fractures in fold-and-thrust-belts, the complex kinematic pathways of folded structures play a key role. In areas with scarce and not reliable underground information, analogue modelling can provide effective support for developing and validating reliable hypotheses on structural architectures and their evolution. In this contribution, we propose a working method that combines analogue and numerical modelling. We deformed a sand-silicone multilayer to eventually produce a non-cylindrical thrust-related anticline at the wedge toe, which was our test geological structure at the reservoir scale. We cut 60 serial cross-sections through the central part of the deformed model to analyze faults and folds geometry using dedicated software (3D Move). The cross-sections were also used to reconstruct the 3D geometry of reference surfaces that compose the mechanical stratigraphy thanks to the use of the software GoCad. From the 3D model of the experimental anticline, by using 3D Move it was possible to calculate the cumulative stress and strain underwent by the deformed reference layers at the end of the deformation and also in incremental steps of fold growth. Based on these model outputs it was also possible to predict the orientation of three main fractures sets (joints and conjugate shear fractures) and their occurrence and density on model surfaces. The next step was the upscaling of the fracture network to the entire digital model volume, to create DFNs.

  14. Metal induced folding: synthesis and conformational analysis of the lanthanide complexes of two 44-membered hydrazone macrocycles.

    PubMed

    Klein, Jörg M; Clegg, Jack K; Saggiomo, Vittorio; Reck, Lisa; Lüning, Ulrich; Sanders, Jeremy K M

    2012-04-07

    Six new lanthanide complexes of two 44-membered macrocycles have been prepared and characterised in solution. An analysis of the conformations of the free macrocycles and their lanthanide complexes both in solution (2D NMR) and in solid state (X-ray crystallography) demonstrate that the complexation induces changes in folding of the macrocycles.

  15. A bionic approach to mathematical modeling the fold geometry of deployable reflector antennas on satellites

    NASA Astrophysics Data System (ADS)

    Feng, C. M.; Liu, T. S.

    2014-10-01

    Inspired from biology, this study presents a method for designing the fold geometry of deployable reflectors. Since the space available inside rockets for transporting satellites with reflector antennas is typically cylindrical in shape, and its cross-sectional area is considerably smaller than the reflector antenna after deployment, the cross-sectional area of the folded reflector must be smaller than the available rocket interior space. Membrane reflectors in aerospace are a type of lightweight structure that can be packaged compactly. To design membrane reflectors from the perspective of deployment processes, bionic applications from morphological changes of plants are investigated. Creating biologically inspired reflectors, this paper deals with fold geometry of reflectors, which imitate flower buds. This study uses mathematical formulation to describe geometric profiles of flower buds. Based on the formulation, new designs for deployable membrane reflectors derived from bionics are proposed. Adjusting parameters in the formulation of these designs leads to decreases in reflector area before deployment.

  16. Effects of vocal fold epithelium removal on vibration in an excised human larynx model

    PubMed Central

    Tse, Justin R.; Zhang, Zhaoyan; Long, Jennifer L.

    2015-01-01

    This study investigated the impact of selective epithelial injury on phonation in an excised human larynx apparatus. With intact epithelium, the vocal folds exhibited a symmetrical vibration pattern with complete glottal closure during vibration. The epithelium was then enzymatically removed from one, then both vocal folds, which led to left-right asymmetric vibration and a decreased closed quotient. Although the mechanisms underlying these vibratory changes are unclear, these results demonstrate that some component of an intact surface layer may play an important role in achieving normal symmetric vibration and glottal closure. PMID:26233062

  17. Relation of Structural and Vibratory Kinematics of the Vocal Folds to Two Acoustic Measures of Breathy Voice Based on Computational Modeling

    ERIC Educational Resources Information Center

    Samlan, Robin A.; Story, Brad H.

    2011-01-01

    Purpose: To relate vocal fold structure and kinematics to 2 acoustic measures: cepstral peak prominence (CPP) and the amplitude of the first harmonic relative to the second (H1-H2). Method: The authors used a computational, kinematic model of the medial surfaces of the vocal folds to specify features of vocal fold structure and vibration in a…

  18. Moving control volume analysis of compressible flow-structure interactions - An application to sustained vocal folds vibration in glottis

    NASA Astrophysics Data System (ADS)

    Zhang, Lucy; Yang, Jubiao; Krane, Michael

    2016-11-01

    The fundamental mechanism of a self-sustained vibration can be analyzed and explained using a moving control volume analysis. In contrast to the conventional "textbook" derivation of control volume analysis, this work shows the derivation of a moving control volume based the "first principles" of physics where the control volume changes its size and location with time. This generalized derivation is demonstrated in a framework for compressible flow-structure interactions where the structure moves and deforms in a compressible fluid medium, e.g. air, within a control volume. The moving control volume analysis helps explain self-sustained vibrations of structures in fluid. An application to the vocal folds vibration in glottis is studied, where the interaction between laryngeal airflow and vocal folds are successfully simulated using the modified Immersed Finite Element Method (mIFEM), a fully coupled approach to simulate fluid-structure interactions. Control volume equations are derived for compressible airflow in a moving control volume in the vicinity of the moving vocal folds. Utilization of mechanical energy is evaluated to understand how vocal folds vibration is self-sustained. We acknowledge the funding support of NIH 2R01DC005642-10A1.

  19. Microscopic Description of the Exotic Nuclei Reactions by Using Folding model Potentials

    SciTech Connect

    Ibraheem, Awad A.; Hassanain, M. A.; Mokhtar, S. R.; El-Azab Farid, M.; Zaki, M. A.; Mahmoud, Zakaria M. M.

    2011-10-27

    A microscopic folding approach based upon the effective M3Y nucleon-nucleon interaction and the nuclear matter densities of the interacting nuclei has been carried out to explain recently measured experimental data of the {sup 6}He+{sup 120}Sn elastic scattering reaction at four different laboratory energies near the Coulomb barrier. The corresponding reaction cross sections are also considered.

  20. Mechanics of non-critical fold-thrust belts based on finite element models

    NASA Astrophysics Data System (ADS)

    Simpson, Guy

    2011-03-01

    The mechanics of fold-thrust belts and accretionary wedges is investigated using a two dimensional, plane strain, elastic-plastic (cohesive Mohr-Coulomb) mechanical model solved with the Finite Element Method. Results show that when a layer with an initially non-critical geometry is compressed from the rear, it does not form a wedge that is at failure throughout, as assumed in critical wedge theory. Rather, the wedge consists of narrow plastic shear zones that propagate sequentially outward with time, loading rocks ahead while unloading rocks behind. Not only are stress states within the wedge not everywhere at failure but principal stress orientations vary strongly in time and space, particularly across shear zones, near the basal detachment and in the hanging wall of active structures, where local surface extension may be observed. The reason the investigated wedges are not stressed to compressive failure throughout is related to strength reduction associated with strain localisation that enables material outside shear zones to unload and return to an elastic stress state. This mechanism is intrinsic to elastic-plastic materials and occurs regardless of any material degradation such as loss of cohesion. Even though the stress state of the investigated wedges is generally non-critical, the overall geometry may still be consistent with cohesionless critical wedge theory, since the local surface slope is created when a particular part of the wedge is at a limit state. Prowedge tapers display non self-similar growth through time but eventually evolve to the minimum critical taper. Retrowedges on the other hand, may get caught within this initial transient state and thus may have tapers anywhere between the minimum and maximum critical taper. However, if the basal detachment is such that lateral propagation is not kinematically inhibited, retrowedges are shown to also eventually evolve towards minimum critical tapers, resulting in a symmetrical doubly-vergent orogen

  1. The occurrence of the Coanda effect in pulsatile flow through static models of the human vocal folds.

    PubMed

    Erath, Byron D; Plesniak, Michael W

    2006-08-01

    Pulsatile flow through a one-sided diffuser and static divergent vocal-fold models is investigated to ascertain the relevance of viscous-driven flow asymmetries in the larynx. The models were 7.5 times real size, and the flow was scaled to match Reynolds and Strouhal numbers, as well as the translaryngeal pressure drop. The Reynolds number varied from 0-2000, for flow oscillation frequencies corresponding to 100 and 150 Hz life-size. Of particular interest was the development of glottal flow skewing by attachment to the bounding walls, or Coanda effect, in a pulsatile flow field, and its impact on speech. The vocal folds form a divergent passage during phases of the phonation cycle when viscous effects such as flow separation are important. It was found that for divergence angles of less than 20 degrees, the attachment of the flow to the vocal-fold walls occurred when the acceleration of the forcing function was zero, and the flow had reached maximum velocity. For a divergence angle of 40 degrees, the fully separated central jet never attached to the vocal-fold walls. Inferences are made regarding the impact of the Coanda effect on the sound source contribution in speech.

  2. Chain folding and A:T pairing in human telomeric DNA: a model-building and molecular dynamics study.

    PubMed Central

    Mohanty, D; Bansal, M

    1995-01-01

    The various types of chain folding and possible intraloop as well as interloop base pairing in human telomeric DNA containing d(TTAG3) repeats have been investigated by model-building, molecular mechanics, and molecular dynamics techniques. Model-building and molecular mechanics studies indicate that it is possible to build a variety of energetically favorable folded-back structures with the two TTA loops on same side and the 5' end thymines in the two loops forming TATA tetrads involving a number of different intraloop as well as interloop A:T pairing schemes. In these folded-back structures, although both intraloop and interloop Watson-Crick pairing is feasible, no structure is possible with interloop Hoogsteen pairing. MD studies of representative structures indicate that the guanine-tetraplex stem is very rigid and, while the loop regions are relatively much more flexible, most of the hydrogen bonds remain intact throughout the 350-ps in vacuo simulation. The various possible TTA loop structures, although they are energetically similar, have characteristic inter proton distances, which could give rise to unique cross-peaks in two-dimensional nuclear Overhauser effect spectroscopy (NOESY) experiments. These folded-back structures with A:T pairings in the loop region help in rationalizing the data from chemical probing and other biochemical studies on human telomeric DNA. PMID:8519959

  3. Effect of the thermostat in the molecular dynamics simulation on the folding of the model protein chignolin.

    PubMed

    Fuzo, Carlos A; Degrève, Léo

    2012-06-01

    Molecular dynamics simulations of the model protein chignolin with explicit solvent were carried out, in order to analyze the influence of the Berendsen thermostat on the evolution and folding of the peptide. The dependence of the peptide behavior on temperature was tested with the commonly employed thermostat scheme consisting of one thermostat for the protein and another for the solvent. The thermostat coupling time of the protein was increased to infinity, when the protein is not in direct contact with the thermal bath, a situation known as minimally invasive thermostat. In agreement with other works, it was observed that only in the last situation the instantaneous temperature of the model protein obeys a canonical distribution. As for the folding studies, it was shown that, in the applications of the commonly utilized thermostat schemes, the systems are trapped in local minima regions from which it has difficulty escaping. With the minimally invasive thermostat the time that the protein needs to fold was reduced by two to three times. These results show that the obstacles to the evolution of the extended peptide to the folded structure can be overcome when the temperature of the peptide is not directly controlled.

  4. Unprecedented folding in linker based flexible tripodal molecule and their conformational analysis

    NASA Astrophysics Data System (ADS)

    Gaurav, Archana; Kumar, Ranjeet; Gupta, Hariom; Ravikumar, K.; Sridhar, B.; Tewari, Ashish Kumar

    2017-04-01

    Here, we first time report the flexible tripodal molecules, contained propylene as a linker, thiocyanuric acid as central core and, p-nitro phenol 1 and pyridazinone 2 as terminal for conformational studies. The conformational studies of these tripodal molecules have been carried by X-ray crystallography, 2D-NOESY spectra and computational studies. Both the molecules have shown folded conformations in solid and solution state however solid state conformation is not stable in gaseous state.

  5. FRalanyzer: a tool for functional analysis of fold-recognition sequence–structure alignments

    PubMed Central

    Saini, Harpreet Kaur; Fischer, Daniel

    2007-01-01

    We describe FRalanyzer (Fold Recognition alignment analyzer), a new web tool to visually inspect sequence–structure alignments in order to predict functionally important residues in a query sequence of unknown function. This tool is aimed at helping to infer functional relationships between a query sequence and a template structure, and is particularly useful in analyzing fold recognition (FR) results. Because similar folds do not necessarily share the same function, it is not always straightforward to infer a function from an FR result alone. Manual inspection of the FR sequence-structure alignment is often required in order to search for conservation of functionally important residues. FRalanyzer automates parts of this time-consuming process. FRalanyzer takes as input a sequence–structure alignment, automatically searches annotated databases, displays functionally significant residues and highlights the functionally important positions that are identical in the alignment. FRalanyzer can also be used with sequence-structure alignments obtained by other methods, and with structure–structure alignments obtained from structural comparison of newly determined 3D-structures of unknown function. Fralanyzer is available at http://fralanyzer.cse.buffalo.edu/. PMID:17537819

  6. Optimized Wang-Landau sampling of lattice polymers: ground state search and folding thermodynamics of HP model proteins.

    PubMed

    Wüst, Thomas; Landau, David P

    2012-08-14

    Coarse-grained (lattice-) models have a long tradition in aiding efforts to decipher the physical or biological complexity of proteins. Despite the simplicity of these models, however, numerical simulations are often computationally very demanding and the quest for efficient algorithms is as old as the models themselves. Expanding on our previous work [T. Wüst and D. P. Landau, Phys. Rev. Lett. 102, 178101 (2009)], we present a complete picture of a Monte Carlo method based on Wang-Landau sampling in combination with efficient trial moves (pull, bond-rebridging, and pivot moves) which is particularly suited to the study of models such as the hydrophobic-polar (HP) lattice model of protein folding. With this generic and fully blind Monte Carlo procedure, all currently known putative ground states for the most difficult benchmark HP sequences could be found. For most sequences we could also determine the entire energy density of states and, together with suitably designed structural observables, explore the thermodynamics and intricate folding behavior in the virtually inaccessible low-temperature regime. We analyze the differences between random and protein-like heteropolymers for sequence lengths up to 500 residues. Our approach is powerful both in terms of robustness and speed, yet flexible and simple enough for the study of many related problems in protein folding.

  7. Optimized Wang-Landau sampling of lattice polymers: Ground state search and folding thermodynamics of HP model proteins

    NASA Astrophysics Data System (ADS)

    Wüst, Thomas; Landau, David P.

    2012-08-01

    Coarse-grained (lattice-) models have a long tradition in aiding efforts to decipher the physical or biological complexity of proteins. Despite the simplicity of these models, however, numerical simulations are often computationally very demanding and the quest for efficient algorithms is as old as the models themselves. Expanding on our previous work [T. Wüst and D. P. Landau, Phys. Rev. Lett. 102, 178101 (2009)], 10.1103/PhysRevLett.102.178101, we present a complete picture of a Monte Carlo method based on Wang-Landau sampling in combination with efficient trial moves (pull, bond-rebridging, and pivot moves) which is particularly suited to the study of models such as the hydrophobic-polar (HP) lattice model of protein folding. With this generic and fully blind Monte Carlo procedure, all currently known putative ground states for the most difficult benchmark HP sequences could be found. For most sequences we could also determine the entire energy density of states and, together with suitably designed structural observables, explore the thermodynamics and intricate folding behavior in the virtually inaccessible low-temperature regime. We analyze the differences between random and protein-like heteropolymers for sequence lengths up to 500 residues. Our approach is powerful both in terms of robustness and speed, yet flexible and simple enough for the study of many related problems in protein folding.

  8. Protein folding pathways and state transitions described by classical equations of motion of an elastic network model.

    PubMed

    Williams, Gareth; Toon, Andrew J

    2010-12-01

    Protein topology defined by the matrix of residue contacts has proved to be a fruitful basis for the study of protein dynamics. The widely implemented coarse-grained elastic network model of backbone fluctuations has been used to describe crystallographic temperature factors, allosteric couplings, and some aspects of the folding pathway. In the present study, we develop a model of protein dynamics based on the classical equations of motion of a damped network model (DNM) that describes the folding path from a completely unfolded state to the native conformation through a single-well potential derived purely from the native conformation. The kinetic energy gained through the collapse of the protein chain is dissipated through a friction term in the equations of motion that models the water bath. This approach is completely general and sufficiently fast that it can be applied to large proteins. Folding pathways for various proteins of different classes are described and shown to correlate with experimental observations and molecular dynamics and Monte Carlo simulations. Allosteric transitions between alternative protein structures are also modeled within the DNM through an asymmetric double-well potential.

  9. Quantitative analysis of the ion-dependent folding stability of DNA triplexes

    NASA Astrophysics Data System (ADS)

    Chen, Gengsheng; Chen, Shi-Jie

    2011-12-01

    A DNA triplex is formed through binding of a third strand to the major groove of a duplex. Due to the high charge density of a DNA triplex, metal ions are critical for its stability. We recently developed the tightly bound ion (TBI) model for ion-nucleic acids interactions. The model accounts for the potential correlation and fluctuations of the ion distribution. We now apply the TBI model to analyze the ion dependence of the thermodynamic stability for DNA triplexes. We focus on two experimentally studied systems: a 24-base DNA triplex and a pair of interacting 14-base triplexes. Our theoretical calculations for the number of bound ions indicate that the TBI model provides improved predictions for the number of bound ions than the classical Poisson-Boltzmann (PB) equation. The improvement is more significant for a triplex, which has a higher charge density than a duplex. This is possibly due to the higher ion concentration around the triplex and hence a stronger ion correlation effect for a triplex. In addition, our analysis for the free energy landscape for a pair of 14-mer triplexes immersed in an ionic solution shows that divalent ions could induce an attractive force between the triplexes. Furthermore, we investigate how the protonated cytosines in the triplexes affect the stability of the triplex helices.

  10. Quantitative analysis of the ion-dependent folding stability of DNA triplexes.

    PubMed

    Chen, Gengsheng; Chen, Shi-Jie

    2011-12-01

    A DNA triplex is formed through binding of a third strand to the major groove of a duplex. Due to the high charge density of a DNA triplex, metal ions are critical for its stability. We recently developed the tightly bound ion (TBI) model for ion-nucleic acids interactions. The model accounts for the potential correlation and fluctuations of the ion distribution. We now apply the TBI model to analyze the ion dependence of the thermodynamic stability for DNA triplexes. We focus on two experimentally studied systems: a 24-base DNA triplex and a pair of interacting 14-base triplexes. Our theoretical calculations for the number of bound ions indicate that the TBI model provides improved predictions for the number of bound ions than the classical Poisson-Boltzmann (PB) equation. The improvement is more significant for a triplex, which has a higher charge density than a duplex. This is possibly due to the higher ion concentration around the triplex and hence a stronger ion correlation effect for a triplex. In addition, our analysis for the free energy landscape for a pair of 14-mer triplexes immersed in an ionic solution shows that divalent ions could induce an attractive force between the triplexes. Furthermore, we investigate how the protonated cytosines in the triplexes affect the stability of the triplex helices.

  11. Diffusion maps, clustering and fuzzy Markov modeling in peptide folding transitions

    SciTech Connect

    Nedialkova, Lilia V.; Amat, Miguel A.; Kevrekidis, Ioannis G. E-mail: gerhard.hummer@biophys.mpg.de; Hummer, Gerhard E-mail: gerhard.hummer@biophys.mpg.de

    2014-09-21

    Using the helix-coil transitions of alanine pentapeptide as an illustrative example, we demonstrate the use of diffusion maps in the analysis of molecular dynamics simulation trajectories. Diffusion maps and other nonlinear data-mining techniques provide powerful tools to visualize the distribution of structures in conformation space. The resulting low-dimensional representations help in partitioning conformation space, and in constructing Markov state models that capture the conformational dynamics. In an initial step, we use diffusion maps to reduce the dimensionality of the conformational dynamics of Ala5. The resulting pretreated data are then used in a clustering step. The identified clusters show excellent overlap with clusters obtained previously by using the backbone dihedral angles as input, with small—but nontrivial—differences reflecting torsional degrees of freedom ignored in the earlier approach. We then construct a Markov state model describing the conformational dynamics in terms of a discrete-time random walk between the clusters. We show that by combining fuzzy C-means clustering with a transition-based assignment of states, we can construct robust Markov state models. This state-assignment procedure suppresses short-time memory effects that result from the non-Markovianity of the dynamics projected onto the space of clusters. In a comparison with previous work, we demonstrate how manifold learning techniques may complement and enhance informed intuition commonly used to construct reduced descriptions of the dynamics in molecular conformation space.

  12. The novel double-folded structure of d(GCATGCATGC): a possible model for triplet-repeat sequences.

    PubMed

    Thirugnanasambandam, Arunachalam; Karthik, Selvam; Mandal, Pradeep Kumar; Gautham, Namasivayam

    2015-10-01

    The structure of the decadeoxyribonucleotide d(GCATGCATGC) is presented at a resolution of 1.8 Å. The decamer adopts a novel double-folded structure in which the direction of progression of the backbone changes at the two thymine residues. Intra-strand stacking interactions (including an interaction between the endocylic O atom of a ribose moiety and the adjacent purine base), hydrogen bonds and cobalt-ion interactions stabilize the double-folded structure of the single strand. Two such double-folded strands come together in the crystal to form a dimer. Inter-strand Watson-Crick hydrogen bonds form four base pairs. This portion of the decamer structure is similar to that observed in other previously reported oligonucleotide structures and has been dubbed a `bi-loop'. Both the double-folded single-strand structure, as well as the dimeric bi-loop structure, serve as starting points to construct models for triplet-repeat DNA sequences, which have been implicated in many human diseases.

  13. Investigating acoustic correlates of human vocal fold vibratory phase asymmetry through modeling and laryngeal high-speed videoendoscopya

    PubMed Central

    Mehta, Daryush D.; Zañartu, Matías; Quatieri, Thomas F.; Deliyski, Dimitar D.; Hillman, Robert E.

    2011-01-01

    Vocal fold vibratory asymmetry is often associated with inefficient sound production through its impact on source spectral tilt. This association is investigated in both a computational voice production model and a group of 47 human subjects. The model provides indirect control over the degree of left–right phase asymmetry within a nonlinear source–filter framework, and high-speed videoendoscopy provides in vivo measures of vocal fold vibratory asymmetry. Source spectral tilt measures are estimated from the inverse-filtered spectrum of the simulated and recorded radiated acoustic pressure. As expected, model simulations indicate that increasing left–right phase asymmetry induces steeper spectral tilt. Subject data, however, reveal that none of the vibratory asymmetry measures correlates with spectral tilt measures. Probing further into physiological correlates of spectral tilt that might be affected by asymmetry, the glottal area waveform is parameterized to obtain measures of the open phase (open/plateau quotient) and closing phase (speed/closing quotient). Subjects’ left–right phase asymmetry exhibits low, but statistically significant, correlations with speed quotient (r = 0.45) and closing quotient (r = −0.39). Results call for future studies into the effect of asymmetric vocal fold vibration on glottal airflow and the associated impact on voice source spectral properties and vocal efficiency. PMID:22225054

  14. A first-principles model of early evolution: emergence of gene families, species, and preferred protein folds.

    PubMed

    Zeldovich, Konstantin B; Chen, Peiqiu; Shakhnovich, Boris E; Shakhnovich, Eugene I

    2007-07-01

    In this work we develop a microscopic physical model of early evolution where phenotype--organism life expectancy--is directly related to genotype--the stability of its proteins in their native conformations-which can be determined exactly in the model. Simulating the model on a computer, we consistently observe the "Big Bang" scenario whereby exponential population growth ensues as soon as favorable sequence-structure combinations (precursors of stable proteins) are discovered. Upon that, random diversity of the structural space abruptly collapses into a small set of preferred proteins. We observe that protein folds remain stable and abundant in the population at timescales much greater than mutation or organism lifetime, and the distribution of the lifetimes of dominant folds in a population approximately follows a power law. The separation of evolutionary timescales between discovery of new folds and generation of new sequences gives rise to emergence of protein families and superfamilies whose sizes are power-law distributed, closely matching the same distributions for real proteins. On the population level we observe emergence of species--subpopulations that carry similar genomes. Further, we present a simple theory that relates stability of evolving proteins to the sizes of emerging genomes. Together, these results provide a microscopic first-principles picture of how first-gene families developed in the course of early evolution.

  15. Folding of apomyoglobin: Analysis of transient intermediate structure during refolding using quick hydrogen deuterium exchange and NMR.

    PubMed

    Nishimura, Chiaki

    2017-01-01

    The structures of apomyoglobin folding intermediates have been widely analyzed using physical chemistry methods including fluorescence, circular dichroism, small angle X-ray scattering, NMR, mass spectrometry, and rapid mixing. So far, at least two intermediates (on sub-millisecond- and millisecond-scales) have been demonstrated for apomyoglobin folding. The combination of pH-pulse labeling and NMR is a useful tool for analyzing the kinetic intermediates at the atomic level. Its use has revealed that the latter-phase kinetic intermediate of apomyoglobin (6 ms) was composed of helices A, B, G and H, whereas the equilibrium intermediate, called the pH 4 molten-globule intermediate, was composed mainly of helices A, G and H. The improved strategy for the analysis of the kinetic intermediate was developed to include (1) the dimethyl sulfoxide method, (2) data processing with the various labeling times, and (3) a new in-house mixer. Particularly, the rapid mixing revealed that helices A and G were significantly more protected at the earlier stage (400 µs) of the intermediate (former-phase intermediate) than the other helices. Mutation studies, where each hydrophobic residue was replaced with an alanine in helices A, B, E, F, G and H, indicated that both non-native and native-like structures exist in the latter-phase folding intermediate. The N-terminal part of helix B is a weak point in the intermediate, and the docking of helix E residues to the core of the A, B, G and H helices was interrupted by a premature helix B, resulting in the accumulation of the intermediate composed of helices A, B, G and H. The prediction-based protein engineering produced important mutants: Helix F in a P88K/A90L/S92K/A94L mutant folded in the latter-phase intermediate, although helix F in the wild type does not fold even at the native state. Furthermore, in the L11G/W14G/A70L/G73W mutant, helix A did not fold but helix E did, which is similar to what was observed in the kinetic

  16. Structural and thermodynamic investigations on the aggregation and folding of acylphosphatase by molecular dynamics simulations and solvation free energy analysis.

    PubMed

    Chong, Song-Ho; Lee, Chewook; Kang, Guipeun; Park, Mirae; Ham, Sihyun

    2011-05-11

    Protein engineering method to study the mutation effects on muscle acylphosphatase (AcP) has been actively applied to describe kinetics and thermodynamics associated with AcP aggregation as well as folding processes. Despite the extensive mutation experiments, the molecular origin and the structural motifs for aggregation and folding kinetics as well as thermodynamics of AcP have not been rationalized at the atomic resolution. To this end, we have investigated the mutation effects on the structures and thermodynamics for the aggregation and folding of AcP by using the combination of fully atomistic, explicit-water molecular dynamics simulations, and three-dimensional reference interaction site model theory. The results indicate that the A30G mutant with the fastest experimental aggregation rate displays considerably decreased α1-helical contents as well as disrupted hydrophobic core compared to the wild-type AcP. Increased solvation free energy as well as hydrophobicity upon A30G mutation is achieved due to the dehydration of hydrophilic side chains in the disrupted α1-helix region of A30G. In contrast, the Y91Q mutant with the slowest aggregation rate shows a non-native H-bonding network spanning the mutation site to hydrophobic core and α1-helix region, which rigidifies the native state protein conformation with the enhanced α1-helicity. Furthermore, Y91Q exhibits decreased solvation free energy and hydrophobicity compared to wild type due to more exposed and solvated hydrophilic side chains in the α1-region. On the other hand, the experimentally observed slower folding rates in both mutants are accompanied by decreased helicity in α2-helix upon mutation. We here provide the atomic-level structures and thermodynamic quantities of AcP mutants and rationalize the structural origin for the changes that occur upon introduction of those mutations along the AcP aggregation and folding processes.

  17. Folding above faults, Rocky Mountains

    SciTech Connect

    McConnell, D.A. . Dept. of Geology)

    1992-01-01

    Asymmetric folds formed above basement faults can be observed throughout the Rocky Mountains. Several previous interpretations of the folding process made the implicit assumption that one or both fold hinges migrated or rolled'' through the steep forelimb of the fold as the structure evolved (rolling hinge model). Results of mapping in the Bighorn and Seminoe Mountains, WY, and Sangre de Cristo Range, CO, do not support this hypothesis. An alternative interpretation is presented in which fold hinges remained fixed in position during folding (fixed hinge model). Mapped folds share common characteristics: (1) axial traces of the folds intersect faults at or near the basement/cover interface, and diverge from faults upsection; (2) fold hinges are narrow and interlimb angles cluster around 80--100[degree] regardless of fold location; (3) fold shape is typically angular, despite published cross sections that show concentric folds; and, (4) beds within the folds show thickening and/or thinning, most commonly adjacent to fold hinges. The rolling hinge model requires that rocks in the fold forelimbs bend through narrow fold hinges as deformation progressed. Examination of massive, competent rock units such as the Ord. Bighorn Dolomite, Miss. Madison Limestone, and, Penn. Tensleep Sandstone reveals no evidence of the extensive internal deformation that would be expected if hinges rolled through rocks of the forelimb. The hinges of some folds (e.g. Golf Creek anticline, Bighorn Mountains) are offset by secondary faults, effectively preventing the passage of rocks from backlimb to forelimb. The fixed hinge model proposes that the fold hinges were defined early in fold evolution, and beds were progressively rotated and steepened as the structure grew.

  18. Entropy reduction effect imposed by hydrogen bond formation on protein folding cooperativity: Evidence from a hydrophobic minimalist model

    NASA Astrophysics Data System (ADS)

    Barbosa, Marco Aurélio A.; Garcia, Leandro G.; Pereira de Araújo, Antônio F.

    2005-11-01

    Conformational restrictions imposed by hydrogen bond formation during protein folding are investigated by Monte Carlo simulations of a non-native-centric, two-dimensional, hydrophobic model in which the formation of favorable contacts is coupled to an effective reduction in lattice coordination. This scheme is intended to mimic the requirement that polar backbone groups of real proteins must form hydrogen bonds concomitantly to their burial inside the apolar protein core. In addition to the square lattice, with z=3 conformations per monomer, we use extensions in which diagonal step vectors are allowed, resulting in z=5 and z=7 . Thermodynamics are governed by the hydrophobic energy function, according to which hydrophobic monomers tend to make contacts unspecifically while the reverse is true for hydrophilic monomers, with the additional restriction that only contacts between monomers adopting one of zhfolding transition abruptness and van’t Hoff-to-calorimetric-enthalpy ratio are found to increase dramatically by this simple and physically motivated mechanism. The observed increase in folding cooperativity is correlated to an increase in the convexity of the underlying microcanonical conformational entropy as a function of energy. Preliminary simulations in three dimensions, even though using a smaller relative reduction in lattice effective coordination zh/z=4/5 , display a slight increase in cooperativity for a hydrophobic model of 40 monomers and a more pronounced increase in cooperativity for a native-centric Go-model with the same native conformation, suggesting that this purely entropic effect is not an artifact of dimensionality and is likely to be of fundamental importance in the theoretical understanding of folding cooperativity.

  19. Effect of Cohesion Uncertainty of Granular Materials on the Kinematics of Scaled Models of Fold-and-Thrust Belts

    NASA Astrophysics Data System (ADS)

    Nilfouroushan, F.; Pysklywec, R.; Cruden, S.

    2009-05-01

    Cohesionless or very low cohesion granular materials are widely used in analogue/physical models to simulate brittle rocks in the upper crust. Selection of materials with appropriate cohesion values in such models is important for the simulation of the dynamics of brittle rock deformation in nature. Uncertainties in the magnitude of cohesion (due to measurement errors, extrapolations at low normal stresses, or model setup) in laboratory experiments can possibly result in misinterpretation of the styles and mechanisms of deformation in natural fold-and thrust belts. We ran a series of 2-D numerical models to investigate systematically the effect of cohesion uncertainties on the evolution of models of fold-and-thrust belts. The analyses employ SOPALE, a geodynamic code based on the arbitrary Lagrangian-Eulerian (ALE) finite element method. Similar to analogue models, the material properties of sand and transparent silicone (PDMS) are used to simulate brittle and viscous behaviors of upper crustal rocks. The suite of scaled brittle and brittle-viscous numerical experiments have the same initial geometry but the cohesion value of the brittle layers is increased systematically from 0 to 100 Pa. The stress and strain distribution in different sets of models with different cohesion values are compared and analyzed. The kinematics and geometry of thrust wedges including the location and number of foreland- and hinterland- verging thrust faults, pop-up structures, tapers and topography are also explored and their sensitivity to cohesion value is discussed.

  20. Advancing the Accuracy of Protein Fold Recognition by Utilizing Profiles From Hidden Markov Models.

    PubMed

    Lyons, James; Dehzangi, Abdollah; Heffernan, Rhys; Yang, Yuedong; Zhou, Yaoqi; Sharma, Alok; Paliwal, Kuldip

    2015-10-01

    Protein fold recognition is an important step towards solving protein function and tertiary structure prediction problems. Among a wide range of approaches proposed to solve this problem, pattern recognition based techniques have achieved the best results. The most effective pattern recognition-based techniques for solving this problem have been based on extracting evolutionary-based features. Most studies have relied on the Position Specific Scoring Matrix (PSSM) to extract these features. However it is known that profile-profile sequence alignment techniques can identify more remote homologs than sequence-profile approaches like PSIBLAST. In this study we use a profile-profile sequence alignment technique, namely HHblits, to extract HMM profiles. We will show that unlike previous studies, using the HMM profile to extract evolutionary information can significantly enhance the protein fold prediction accuracy. We develop a new pattern recognition based system called HMMFold which extracts HMM based evolutionary information and captures remote homology information better than previous studies. Using HMMFold we achieve up to 93.8% and 86.0% prediction accuracies when the sequential similarity rates are less than 40% and 25%, respectively. These results are up to 10% better than previously reported results for this task. Our results show significant enhancement especially for benchmarks with sequential similarity as low as 25% which highlights the effectiveness of HMMFold to address this problem and its superiority over previously proposed approaches found in the literature. The HMMFold is available online at: http://sparks-lab.org/pmwiki/download/index.php?Download =HMMFold.tar.bz2.

  1. Analysis of RNA folding and ligand binding by conventional and high-throughput calorimetry.

    PubMed

    Sokoloski, Joshua E; Bevilacqua, Philip C

    2012-01-01

    Noncoding RNAs serve myriad functions in the cell, but their biophysical properties are not well understood. Calorimetry offers direct and label-free means for characterizing the ligand-binding and thermostability properties of these RNA. We apply two main types of calorimetry--isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC)--to the characterization of these functional RNA molecules. ITC can describe ligand binding in terms of stoichiometry, affinity, and heat (enthalpy), while DSC can provide RNA stability in terms of heat capacity, melting temperature, and folding enthalpy. Here, we offer detailed experimental protocols for studying such RNA systems with commercially available conventional and high-throughput ITC and DSC instruments.

  2. High-speed PIV measurements of the flow downstream of a dynamic mechanical model of the human vocal folds

    NASA Astrophysics Data System (ADS)

    Triep, M.; Brücker, Ch.; Schröder, W.

    2005-08-01

    The objective of the present study is the detailed analysis of the unsteady vortex dynamics downstream of the human glottis during phonation at typical fundamental frequencies of the male voice of about 120 Hz. A hydraulic respiratory mock circuit has been built, including a factor of three up-scaled realistic dynamic model of the vocal folds. Time-resolving flow measurements were carried out downstream of the glottis by means of high-speed particle image velocimetry (PIV). The function of the human glottis is reproduced by two counter-rotating cams, each of which is covered with a stretched silicone membrane. The three-dimensional (3-D) geometry of the cams is designed such that the rotation leads to a realistic time-varying motion and profile of the glottis and waveform of the glottal cycle. Using high-speed PIV, the velocity field is captured with high spatial and temporal resolution to investigate the unsteady vortex dynamics of the cyclic jet-like flow in the vocal tract. The results help us to understand the vorticity interaction within the pulsating jet and, consequently, the generated sound in a human voice. In addition, changing the 3-D contours of the cams enables us to investigate basic pathological differences of the glottis function and the resulting alterations of the velocity and vorticity field in the vocal tract. The results are presented for typical physiological flow conditions in the human glottis. The frequencies of periodic vortex structures generated downstream of the glottis are fivefold higher than the fundamental frequency of the vocal folds’ oscillation. The highest vorticity fluctuations have a phase shift of 35% relative to the opening of the glottis. Finally, the flow field in the vocal tract is identified to be highly three-dimensional.

  3. Native-like in vivo folding of a circularly permuted jellyroll protein shown by crystal structure analysis.

    PubMed Central

    Hahn, M; Piotukh, K; Borriss, R; Heinemann, U

    1994-01-01

    A jellyroll beta-sandwich protein, the Bacillus beta-glucanase H(A16-M), is used to probe the role of N-terminal peptide regions in protein folding in vivo. A gene encoding H(A16-M) is rearranged to place residues 1-58 of the protein behind a signal peptide and residues 59-214. The rearranged gene is expressed in Escherichia coli. The resultant circularly permuted protein, cpA16M-59, is secreted into the periplasm, correctly processed, and folded into a stable and active enzyme. Crystal structure analysis at 2.0-A resolution, R = 15.3%, shows cpA16M-59 to have a three-dimensional structure nearly identical with that of the parent beta-glucanase. An analogous experiment based on the wild-type Bacillus macerans beta-glucanase, giving rise to the circularly permuted variant cpMAC-57, yields the same results. Folding of these proteins, therefore, is not a vectorial process depending on the conformation adopted by their native N-terminal oligopeptides after ribosomal synthesis and translocation through the cytoplasmic membrane. Images PMID:7937966

  4. Role of the Closing Base Pair for d(GCA) Hairpin Stability: Free Energy Analysis and Folding Simulations

    SciTech Connect

    Kannan, Srinivasaraghavan; Zacharias, Martin W.

    2011-06-30

    Hairpin loops belong to the most important structural motifs in folded nucleic acids. The d(GNA) sequence in DNA can form very stable trinucleotide hairpin loops depending, however, strongly on the closing base pair. Replica-exchange molecular dynamics (REMD) were employed to study hairpin folding of two DNA sequences, d(gcGCAgc) and d(cgGCAcg), with the same central loop motif but different closing base pairs starting from singlestranded structures. In both cases, conformations of the most populated conformational cluster at the lowest temperature showed close agreement with available experimental structures. For the loop sequence with the less stable G:C closing base pair, an alternative loop topology accumulated as second most populated conformational state indicating a possible loop structural heterogeneity. Comparative-free energy simulations on induced loop unfolding indicated higher stability of the loop with a C:G closing base pair by 3 kcal mol1 (compared to a G:C closing base pair) in very good agreement with experiment. The comparative energetic analysis of sampled unfolded, intermediate and folded conformational states identified electrostatic and packing interactions as the main contributions to the closing base pair dependence of the d(GCA) loop stability.

  5. Alpine fold-and-thrust structures revealed: A 3D model from the Helvetic Zone (Säntis area, Switzerland)

    NASA Astrophysics Data System (ADS)

    Sala, Paola; Pfiffner, Adrian; Frehner, Marcel

    2013-04-01

    To investigate the geometrical relationships between folding and thrust faulting, a 3D model of the Helvetic fold-and-thrust belt in Eastern Switzerland is built from several cross-sections in the Säntis area, between Hoher Kasten and Wildhaus. Existing cross-sections from Schlatter (1941), Kempf (1966), and Pfiffner (2000; 2011) were partly redrawn and cross-checked for line length balancing. Additional cross-sections based on surface geology were newly constructed to fill areas with a low cross-section density and to solve geological problems. The interpolation of the formation interfaces and the thrusts between the cross-sections allowed generating six main surfaces corresponding to the base of the Öhrli and Betlis Limestones, the Helvetic Kieselkalk, the Schrattenkalk and Garschella Formations, and the Seewen Limestone. The main structural elements in the Säntis area, such as the Säntis Thrust or the Sax-Schwende Fault, are also implemented in the model. The 3D model highlights the shape of the main anticline-syncline pairs (e.g., Altmann-Wildseeli, Schafberg-Moor, Roslenfirst-Mutschen, etc...) and how these fold trains vary in amplitude and wavelength along strike. The model also clearly shows the lateral extension, the trend, and the variation in displacement of the principal faults. The reconstruction of 3D horizons allows the geologists investigating cross-sections along any given direction. The 3D model is useful to understand how the changes of the internal nappe structures, namely folds and thrust faults, change along strike. Such changes occur either across transverse faults or in a more gradual manner. The model can and will also be used as a base to perform retrodeformation and strain estimation. Shortening will be calculated using the base Schrattenkalk as the reference horizon. REFERENCES Pfiffner, O.A., 2000: Cross-sections in Funk, H., Habich, J.K., Hantke, R. & Pfiffner, O.A., 2000: Blatt 1115 Säntis - Geologischer Atlas der Schweiz 1

  6. Epithelial cells are active participants in vocal fold wound healing: an in vivo animal model of injury.

    PubMed

    Leydon, Ciara; Imaizumi, Mitsuyoshi; Bartlett, Rebecca S; Wang, Sarah F; Thibeault, Susan L

    2014-01-01

    Vocal fold epithelial cells likely play an important, yet currently poorly defined, role in healing following injury, irritation and inflammation. In the present study, we sought to identify a possible role for growth factors, epidermal growth factor (EGF) and transforming growth factor-beta 1 (TGFβ1), in epithelial regeneration during wound healing as a necessary first step for uncovering potential signaling mechanisms of vocal fold wound repair and remodeling. Using a rat model, we created unilateral vocal fold injuries and examined the timeline for epithelial healing and regeneration during early and late stages of wound healing using immunohistochemistry (IHC). We observed time-dependent secretion of the proliferation marker, ki67, growth factors EGF and TGFβ1, as well as activation of the EGF receptor (EGFR), in regenerating epithelium during the acute phase of injury. Ki67, growth factor, and EGFR expression peaked at day 3 post-injury. Presence of cytoplasmic and intercellular EGF and TGFβ1 staining occurred up to 5 days post-injury, consistent with a role for epithelial cells in synthesizing and secreting these growth factors. To confirm that epithelial cells contributed to the cytokine secretion, we examined epithelial cell growth factor secretion in vitro using polymerase chain reaction (PCR). Cultured pig vocal fold epithelial cells expressed both EGF and TGFβ1. Our in vivo and in vitro findings indicate that epithelial cells are active participants in the wound healing process. The exact mechanisms underlying their roles in autocrine and paracrine signaling guiding wound healing await study in a controlled, in vitro environment.

  7. Biochemical and structural analysis of Helix pomatia agglutinin. A hexameric lectin with a novel fold.

    PubMed

    Sanchez, Jean-Frederic; Lescar, Julien; Chazalet, Valérie; Audfray, Aymeric; Gagnon, Jean; Alvarez, Richard; Breton, Christelle; Imberty, Anne; Mitchell, Edward P

    2006-07-21

    Helix pomatia agglutinin (HPA) is a N-acetylgalactosamine (GalNAc) binding lectin found in the albumen gland of the roman snail. As a constituent of perivitelline fluid, HPA protects fertilized eggs from bacteria and is part of the innate immunity system of the snail. The peptide sequence deduced from gene cloning demonstrates that HPA belongs to a family of carbohydrate-binding proteins recently identified in several invertebrates. This domain is also present in discoidin from the slime mold Dictyostelium discoideum. Investigation of the lectin specificity was performed with the use of glycan arrays, demonstrating that several GalNAc-containing oligosaccharides are bound and rationalizing the use of this lectin as a cancer marker. Titration microcalorimetry performed on the interaction between HPA and GalNAc indicates an affinity in the 10(-4) M range with an enthalpy-driven binding mechanism. The crystal structure of HPA demonstrates the occurrence of a new beta-sandwich lectin fold. The hexameric quaternary state was never observed previously for a lectin. The high resolution structure complex of HPA with GalNAc characterizes a new carbohydrate binding site and rationalizes the observed preference for alphaGalNAc-containing oligosaccharides.

  8. Evolution of a fold-thrust belt deforming a unit with pre-existing linear asperities: Insights from analog models

    NASA Astrophysics Data System (ADS)

    Burberry, Caroline M.; Swiatlowski, Jerlyn L.

    2016-06-01

    Heterogeneity, whether geometric or rheologic, in crustal material undergoing compression affects the geometry of the structures produced. This study documents the thrust fault geometries produced when discrete linear asperities are introduced into an analog model, scaled to represent bulk upper crustal properties, and compressed. Varying obliquities of the asperities are used, relative to the imposed compression, and the resultant development of thrust fault traces and branch lines in map view is tracked. Once the model runs are completed, cross-sections are created and analyzed. The models show that asperities confined to the base layer promote the clustering of branch lines in the surface thrusts. Strong clustering in branch lines is also noted where several asperities are in close proximity or cross. Slight reverse-sense reactivation of asperities cut through the sedimentary sequence is noted in cross-section, where the asperity and the subsequent thrust belt interact. The model results are comparable to the situation in the Dinaric Alps, where pre-existing faults to the SW of the NE Adriatic Fault Zone contribute to the clustering of branch lines developed in the surface fold-thrust belt. These results can therefore be used to evaluate the evolution of other basement-involved fold-thrust belts worldwide.

  9. A Hybrid All-Atom Structure-Based Model for Protein Folding and Large Scale Conformational Transitions.

    PubMed

    Sutto, Ludovico; Mereu, Ilaria; Gervasio, Francesco Luigi

    2011-12-13

    Structure-based models are successful at conjugating the essence of the energy landscape theory of protein folding with an easy and efficient implementation. Recently, their realm expanded beyond a single protein structure, and structure-based potentials have been used profitably to widely study complex conformational transitions. Still, when dealing with structural rearrangements between two, or more, well-defined structures, an unbiased and transferable description of the local backbone and side chain interactions could be advantageous. Here, we propose an all-atom model that merges a classical force field description of these local interactions with a structure-based long-range potential that takes into account the different conformations. We first validate the model simulating and characterizing the folding reaction and the transition state of two well-known proteins: the villin headpiece and the SH3 domain. Then, we characterize the activation mechanism of the catalytic domain of c-Src kinase. Such a process involves the conformational rearrangement of a large loop and the swing of an α helix. The appearance of a stable intermediate state in the free energy landscape between the two conformational end points suggests the mechanism of the loop opening. The low computational cost of the model together with the satisfactory accuracy of the results make it a promising approach to studying conformational transitions in large protein systems.

  10. High precision analysis of an embryonic extensional fault-related fold using 3D orthorectified virtual outcrops: The viewpoint importance in structural geology

    NASA Astrophysics Data System (ADS)

    Tavani, Stefano; Corradetti, Amerigo; Billi, Andrea

    2016-05-01

    Image-based 3D modeling has recently opened the way to the use of virtual outcrop models in geology. An intriguing application of this method involves the production of orthorectified images of outcrops using almost any user-defined point of view, so that photorealistic cross-sections suitable for numerous geological purposes and measurements can be easily generated. These purposes include the accurate quantitative analysis of fault-fold relationships starting from imperfectly oriented and partly inaccessible real outcrops. We applied the method of image-based 3D modeling and orthorectification to a case study from the northern Apennines, Italy, where an incipient extensional fault affecting well-layered limestones is exposed on a 10-m-high barely accessible cliff. Through a few simple steps, we constructed a high-quality image-based 3D model of the outcrop. In the model, we made a series of measurements including fault and bedding attitudes, which allowed us to derive the bedding-fault intersection direction. We then used this direction as viewpoint to obtain a distortion-free photorealistic cross-section, on which we measured bed dips and thicknesses as well as fault stratigraphic separations. These measurements allowed us to identify a slight difference (i.e. only 0.5°) between the hangingwall and footwall cutoff angles. We show that the hangingwall strain required to compensate the upward-decreasing displacement of the fault was accommodated by this 0.5° rotation (i.e. folding) and coeval 0.8% thickening of strata in the hangingwall relatively to footwall strata. This evidence is consistent with trishear fault-propagation folding. Our results emphasize the viewpoint importance in structural geology and therefore the potential of using orthorectified virtual outcrops.

  11. A new computational model for protein folding based on atomic solvation.

    PubMed Central

    Wang, Y.; Zhang, H.; Scott, R. A.

    1995-01-01

    A new model for calculating the solvation energy of proteins is developed and tested for its ability to identify the native conformation as the global energy minimum among a group of thousands of computationally generated compact non-native conformations for a series of globular proteins. In the model (called the WZS model), solvation preferences for a set of 17 chemically derived molecular fragments of the 20 amino acids are learned by a training algorithm based on maximizing the solvation energy difference between native and non-native conformations for a training set of proteins. The performance of the WZS model confirms the success of this learning approach; the WZS model misrecognizes (as more stable than native) only 7 of 8,200 non-native structures. Possible applications of this model to the prediction of protein structure from sequence are discussed. PMID:7670381

  12. BIMOLECULAR FLUORESCENCE COMPLEMENTATION ANALYSIS OF INDUCIBLE PROTEIN INTERACTIONS: EFFECTS OF FACTORS AFFECTING PROTEIN FOLDING ON FLUORESCENT PROTEIN FRAGMENT ASSOCIATION

    PubMed Central

    Robida, Aaron M; Kerppola, Tom K

    2009-01-01

    Bimolecular fluorescence complementation (BiFC) analysis enables visualization of the subcellular locations of protein interactions in living cells. We investigated the temporal resolution and the quantitative accuracy of BiFC analysis using fragments of different fluorescent proteins. We determined the kinetics of BiFC complex formation in response to the rapamycin-inducible interaction between the FK506 binding protein (FKBP) and the FKBP-rapamycin binding domain (FRB). Fragments of YFP fused to FKBP and FRB produced detectable BiFC complex fluorescence 10 minutes after rapamycin addition and a ten-fold increase in the mean fluorescence intensity in 8 hours. The N-terminal fragment of the Venus fluorescent protein fused to FKBP produced constitutive BiFC complexes with several C-terminal fragments fused to FRB. A chimeric N-terminal fragment containing residues from Venus and YFP produced either constitutive or inducible BiFC complexes depending on the temperature at which the cells were cultured. The concentrations of inducers required for half-maximal induction of BiFC complex formation by all fluorescent protein fragments tested were consistent with the affinities of the inducers for unmodified FKBP and FRB. Treatment of the FK506 inhibitor of FKBP-FRB interaction prevented the formation of BiFC complexes by FKBP and FRB fusions, but did not disrupt existing BiFC complexes. Proteins synthesized prior to rapamycin addition formed BiFC complexes with the same efficiency as newly synthesized proteins. Inhibitors of protein synthesis attenuated BiFC complex formation independent of their effects on fusion protein synthesis. The kinetics at which they inhibited BiFC complex formation suggest that they prevented association of the fluorescent protein fragments, but not the slow maturation of BiFC complex fluorescence. Agents that induce the unfolded protein response also reduced formation of BiFC complexes. The effects of these agents were suppressed by cellular

  13. Network measures for protein folding state discrimination

    PubMed Central

    Menichetti, Giulia; Fariselli, Piero; Remondini, Daniel

    2016-01-01

    Proteins fold using a two-state or multi-state kinetic mechanisms, but up to now there is not a first-principle model to explain this different behavior. We exploit the network properties of protein structures by introducing novel observables to address the problem of classifying the different types of folding kinetics. These observables display a plain physical meaning, in terms of vibrational modes, possible configurations compatible with the native protein structure, and folding cooperativity. The relevance of these observables is supported by a classification performance up to 90%, even with simple classifiers such as discriminant analysis. PMID:27464796

  14. Symmetric Fold/Super-Hopf Bursting, Chaos and Mixed-Mode Oscillations in Pernarowski Model of Pancreatic Beta-Cells

    NASA Astrophysics Data System (ADS)

    Fallah, Haniyeh

    Pancreatic beta-cells produce insulin to regularize the blood glucose level. Bursting is important in beta cells due to its relation to the release of insulin. Pernarowski model is a simple polynomial model of beta-cell activities indicating bursting oscillations in these cells. This paper presents bursting behaviors of symmetric type in this model. In addition, it is shown that the current system exhibits the phenomenon of period doubling cascades of canards which is a route to chaos. Canards are also observed symmetrically near folds of slow manifold which results in a chaotic transition between n and n + 1 spikes symmetric bursting. Furthermore, mixed-mode oscillations (MMOs) and combination of symmetric bursting together with MMOs are illustrated during the transition between symmetric bursting and continuous spiking.

  15. NoFold: RNA structure clustering without folding or alignment.

    PubMed

    Middleton, Sarah A; Kim, Junhyong

    2014-11-01

    Structures that recur across multiple different transcripts, called structure motifs, often perform a similar function-for example, recruiting a specific RNA-binding protein that then regulates translation, splicing, or subcellular localization. Identifying common motifs between coregulated transcripts may therefore yield significant insight into their binding partners and mechanism of regulation. However, as most methods for clustering structures are based on folding individual sequences or doing many pairwise alignments, this results in a tradeoff between speed and accuracy that can be problematic for large-scale data sets. Here we describe a novel method for comparing and characterizing RNA secondary structures that does not require folding or pairwise alignment of the input sequences. Our method uses the idea of constructing a distance function between two objects by their respective distances to a collection of empirical examples or models, which in our case consists of 1973 Rfam family covariance models. Using this as a basis for measuring structural similarity, we developed a clustering pipeline called NoFold to automatically identify and annotate structure motifs within large sequence data sets. We demonstrate that NoFold can simultaneously identify multiple structure motifs with an average sensitivity of 0.80 and precision of 0.98 and generally exceeds the performance of existing methods. We also perform a cross-validation analysis of the entire set of Rfam families, achieving an average sensitivity of 0.57. We apply NoFold to identify motifs enriched in dendritically localized transcripts and report 213 enriched motifs, including both known and novel structures.

  16. NoFold: RNA structure clustering without folding or alignment

    PubMed Central

    Middleton, Sarah A.

    2014-01-01

    Structures that recur across multiple different transcripts, called structure motifs, often perform a similar function—for example, recruiting a specific RNA-binding protein that then regulates translation, splicing, or subcellular localization. Identifying common motifs between coregulated transcripts may therefore yield significant insight into their binding partners and mechanism of regulation. However, as most methods for clustering structures are based on folding individual sequences or doing many pairwise alignments, this results in a tradeoff between speed and accuracy that can be problematic for large-scale data sets. Here we describe a novel method for comparing and characterizing RNA secondary structures that does not require folding or pairwise alignment of the input sequences. Our method uses the idea of constructing a distance function between two objects by their respective distances to a collection of empirical examples or models, which in our case consists of 1973 Rfam family covariance models. Using this as a basis for measuring structural similarity, we developed a clustering pipeline called NoFold to automatically identify and annotate structure motifs within large sequence data sets. We demonstrate that NoFold can simultaneously identify multiple structure motifs with an average sensitivity of 0.80 and precision of 0.98 and generally exceeds the performance of existing methods. We also perform a cross-validation analysis of the entire set of Rfam families, achieving an average sensitivity of 0.57. We apply NoFold to identify motifs enriched in dendritically localized transcripts and report 213 enriched motifs, including both known and novel structures. PMID:25234928

  17. An investigation of asymmetric flow features in a scaled-up driven model of the human vocal folds

    NASA Astrophysics Data System (ADS)

    Erath, Byron D.; Plesniak, Michael W.

    2010-07-01

    Flow through a driven, 7.5 times life-size vocal fold model was investigated at corresponding life-size flow rates of Q mean = 89.1 ml/s, 159.4 ml/s, and 253.0 ml/s. The flow was scaled to match physiological values for Reynolds, Strouhal, and Euler numbers. The models were driven at a life-size frequency of 94 Hz. Particle image velocimetry (PIV) data were acquired in the anterior-posterior midplane of the glottis, and the unsteady transglottal pressure drop across the vocal folds was simultaneously measured. Flow and pressure data were obtained at four discrete instances during the closing phases of the phonatory cycle for which t/T open = 0.60, 0.70, 0.80, and 0.90. The glottal jet trajectory exhibited a bimodal distribution of flow attachment between the two medial surfaces of the glottis. Vortex shedding at the trailing edge separation point generated instabilities in the shear layer, which caused large oscillations in the glottal jet orientation downstream of the glottal exit. The development of the Coanda effect during the glottal cycle was found to have minimal impact on the transglottal pressure drop, suggesting that flow orientation does not directly influence the dipole sound source. The change in transglottal pressure drop as a result of jet trajectory was less than 2% for all three investigated flow rates.

  18. Protein Folding and Structure Prediction from the Ground Up: The Atomistic Associative Memory, Water Mediated, Structure and Energy Model.

    PubMed

    Chen, Mingchen; Lin, Xingcheng; Zheng, Weihua; Onuchic, José N; Wolynes, Peter G

    2016-08-25

    The associative memory, water mediated, structure and energy model (AWSEM) is a coarse-grained force field with transferable tertiary interactions that incorporates local in sequence energetic biases using bioinformatically derived structural information about peptide fragments with locally similar sequences that we call memories. The memory information from the protein data bank (PDB) database guides proper protein folding. The structural information about available sequences in the database varies in quality and can sometimes lead to frustrated free energy landscapes locally. One way out of this difficulty is to construct the input fragment memory information from all-atom simulations of portions of the complete polypeptide chain. In this paper, we investigate this approach first put forward by Kwac and Wolynes in a more complete way by studying the structure prediction capabilities of this approach for six α-helical proteins. This scheme which we call the atomistic associative memory, water mediated, structure and energy model (AAWSEM) amounts to an ab initio protein structure prediction method that starts from the ground up without using bioinformatic input. The free energy profiles from AAWSEM show that atomistic fragment memories are sufficient to guide the correct folding when tertiary forces are included. AAWSEM combines the efficiency of coarse-grained simulations on the full protein level with the local structural accuracy achievable from all-atom simulations of only parts of a large protein. The results suggest that a hybrid use of atomistic fragment memory and database memory in structural predictions may well be optimal for many practical applications.

  19. A Three Dimension Model to Demonstrate Head and Tail Fold Formation in Mammalian Embryos

    ERIC Educational Resources Information Center

    Bressler, Robert S.

    1977-01-01

    Many students have difficulty visualizing the delineation of the embryonic body from the flat germ disc. An easily-constructed model is described that has been used successfully to convey the dynamics of embryological events at Mount Sinai School of Medicine. (LBH)

  20. A Three-Fold Approach to the Heat Equation: Data, Modeling, Numerics

    ERIC Educational Resources Information Center

    Spayd, Kimberly; Puckett, James

    2016-01-01

    This article describes our modeling approach to teaching the one-dimensional heat (diffusion) equation in a one-semester undergraduate partial differential equations course. We constructed the apparatus for a demonstration of heat diffusion through a long, thin metal rod with prescribed temperatures at each end. The students observed the physical…

  1. Alternative models for describing the acid unfolding of the apomyoglobin folding intermediate.

    PubMed

    Kay, M S; Baldwin, R L

    1998-05-26

    The acid-induced unfolding of the pH 4 intermediate of apomyoglobin (I) is described by either of two models: (1) a Monod-Wyman-Changeux-based model (MWC) where salt bridges perturb the pKa values of specific ionizable side chains, causing unfolding of I as these salt bridges are broken at low pH, and (2) the Linderstrom-Lang smeared charge model (L-L), which attributes acid unfolding of I to charge repulsion caused by the accumulation of positive charge on the surface of the protein. Both models fit earlier acid unfolding data well, but they make differing predictions about the effects of electrostatic mutants, which have been made and tested. Deletions of positive charge within I are found to stabilize I, but disruptions of potential salt bridges have little effect. These results show that the acid unfolding of I (I<-->U) is largely caused by generalized charge effects rather than by the loss of specific salt bridges. Acid unfolding of the native form, which is caused largely by a single histidine with a severely depressed pKa, is a sensitive indicator of changes in stability produced by mutations. In contrast, the I <--> U transition is caused by a number of groups with smaller pKa perturbations and both models predict that the pH midpoint of the I right harpoon over left harpoon U transition is an insensitive indicator of stability. This result reconciles previous conflicting results, in urea and acid unfolding studies of hydrophobic contact mutants, by showing that changes in the stability of I are poorly detected by acid unfolding.

  2. Modelling of the serine-proteinase fold by X-ray and neutron scattering and sedimentation analyses: occurrence of the fold in factor D of the complement system.

    PubMed Central

    Perkins, S J; Smith, K F; Kilpatrick, J M; Volanakis, J E; Sim, R B

    1993-01-01

    Solution scattering is a powerful means of determining the overall arrangement of domains in the multidomain proteins of complement. the serine-proteinase domain is central to all proteolytic events during complement activation. As models of this domain, bovine beta-trypsin, trypsinogen, alpha-chymotrypsin and chymotrypsinogen A were studied by neutron and X-ray synchrotron solution scattering. At pH 7, all the X-ray and neutron M(r) values corresponded to monomeric proteins. The X-ray radii of gyration, RG, of beta-trypsin, trypsinogen, alpha-chymotrypsin and chymotrypsinogen A (measured in positive solute-solvent contrasts) were 1.59 nm, 1.78 nm, 1.71 nm and 1.76 nm (+/- 0.05-0.11 nm) in that order. Neutron contrast variation showed that the RG at infinite contrast, RC, for these four proteins were 1.57 nm, 1.70 nm, 1.67 nm and 1.78 nm (+/- 0.03 nm) in that same order. The radial inhomogeneity of neutron-scattering density, alpha, was positive at (5-13) x 10(-5), and corresponds to the preponderance of hydrophilic residues near the protein surface. On trypsinogen activation, a small reduction in the RG value of 0.13 +/- 0.07 nm was just detectable, while the RG of chymotrypsinogen A was unchanged after activation. The RC and alpha values of the four proteins can be calculated by using crystallographic co-ordinates. The reduced RG of beta-trypsin relative to trypsinogen was explained in terms of the removal of the extended N-terminal hexapeptide of trypsinogen. The full X-ray and neutron-scattering curves in positive and negative contrasts agreed well with scattering curves calculated from crystallographic coordinates to a nominal structural resolution of 4.5 nm, provided that the internal structure was considered in neutron modelling, and that the hydration was considered in X-ray modelling. Sedimentation-coefficient data also provide information on the disposition of domains in multidomain proteins. It was found that the hydrated X-ray sphere model could be

  3. Techniques for the Analysis of Cysteine Sulfhydryls and Oxidative Protein Folding

    PubMed Central

    Sherma, Nisha D.

    2014-01-01

    Abstract Significance: Modification of cysteine thiols dramatically affects protein function and stability. Hence, the abilities to quantify specific protein sulfhydryl groups within complex biological samples and map disulfide bond structures are crucial to gaining greater insights into how proteins operate in human health and disease. Recent Advances: Many different molecular probes are now commercially available to label and track cysteine residues at great sensitivity. Coupled with mass spectrometry, stable isotope-labeled sulfhydryl-specific reagents can provide previously unprecedented molecular insights into the dynamics of cysteine modification. Likewise, the combined application of modern mass spectrometers with improved sample preparation techniques and novel data mining algorithms is beginning to routinize the analysis of complex protein disulfide structures. Critical Issues: Proper application of these modern tools and techniques, however, still requires fundamental understanding of sulfhydryl chemistry as well as the assumptions that accompany sample preparation and underlie effective data interpretation. Future Directions: The continued development of tools, technical approaches, and corresponding data processing algorithms will, undoubtedly, facilitate site-specific protein sulfhydryl quantification and disulfide structure analysis from within complex biological mixtures with ever-improving accuracy and sensitivity. Fully routinizing disulfide structure analysis will require an equal but balanced focus on sample preparation and corresponding mass spectral dataset reproducibility. Antioxid. Redox Signal. 21, 511–531. PMID:24383618

  4. Haustral fold segmentation with curvature-guided level set evolution.

    PubMed

    Zhu, Hongbin; Barish, Matthew; Pickhardt, Perry; Liang, Zhengrong

    2013-02-01

    Human colon has complex structures mostly because of the haustral folds. The folds are thin flat protrusions on the colon wall, which complicate the shape analysis for computer-aided detection (CAD) of colonic polyps. Fold segmentation may help reduce the structural complexity, and the folds can serve as an anatomic reference for computed tomographic colonography (CTC). Therefore, in this study, based on a model of the haustral fold boundaries, we developed a level-set approach to automatically segment the fold surfaces. To evaluate the developed fold segmentation algorithm, we first established the ground truth of haustral fold boundaries by experts' drawing on 15 patient CTC datasets without severe under/over colon distention from two medical centers. The segmentation algorithm successfully detected 92.7% of the folds in the ground truth. In addition to the sensitivity measure, we further developed a merit of segmented-area ratio (SAR), i.e., the ratio between the area of the intersection and union of the expert-drawn folds and the area of the automatically segmented folds, to measure the segmentation accuracy. The segmentation algorithm reached an average value of SAR = 86.2%, showing a good match with the ground truth on the fold surfaces. We believe the automatically segmented fold surfaces have the potential to benefit many postprocedures in CTC, such as CAD, taenia coli extraction, supine-prone registration, etc.

  5. Protein folding of the HOP model: A parallel Wang—Landau study

    NASA Astrophysics Data System (ADS)

    Shi, G.; Wüst, T.; Li, Y. W.; Landau, D. P.

    2015-09-01

    We propose a simple modification to the hydrophobic-polar (HP) protein model, by introducing a new type of monomer, “0”, with intermediate hydrophobicity of some amino acids between H and P. With the replica-exchange Wang-Landau sampling method, we investigate some widely studied HP sequences as well as their H0P counterparts and observe that the H0P sequences exhibit dramatically reduced ground state degeneracy and more significant transition signals at low temperature for some thermodynamic properties, such as the specific heat.

  6. Protein folding of the H0P model: A parallel Wang-Landau study

    SciTech Connect

    Shi, Guangjie; Wuest, Thomas; Li, Ying Wai; Landau, David P

    2015-01-01

    We propose a simple modication to the hydrophobic-polar (HP) protein model, by introducing a new type of monomer, "0", with intermediate hydrophobicity of some amino acids between H and P. With the replica-exchange Wang-Landau sampling method, we investigate some widely studied HP sequences as well as their H0P counterparts and observe that the H0P sequences exhibit dramatically reduced ground state degeneracy and more signicant transition signals at low temperature for some thermodynamic properties, such as the specific heat.

  7. Modeling of the Kinetics of Metal Film Growth on 5-Fold Surfaces of Icosohedral Quasicrystals

    NASA Astrophysics Data System (ADS)

    Evans, J. W.; Unal, B.; Fournee, V.; Ghosh, C.; Liu, D.-J.; Jenks, C. J.; Thiel, P. A.

    2007-03-01

    During submonolayer deposition of metals on 5-f icosohedral Al- Pd-Mn and Al-Cu-Fe surfaces, experimental evidence for several system points to heterogeneous nucleation of islands at specific ``dark star'' trap sites. We model this phenomenon using a mean-field rate equation formulation for Ag on Al-Pd-Mn, where data is available for both the flux and temperature dependence of the island density. We also utilize a more sophisticated kinetic Monte Carlo simulation approach to analyze an atomistic lattice-gas model (for an appropriate ``disordered-bond-network'' of nearest-neighbor adsorption sites) describing nucleation of starfish islands observed by STM for Al on Al-Cu-Fe. Finally, we briefly describe multilayer growth morphologies (which can display kinetic roughening or quantum size effects), but which also generally reflect the submonolayer island distribution. B. Unal et al. PRB 75 (2007); C. Ghosh et al. Phil. Mag. 86 (2006) 831; Surf. Sci. 600 (2006) 1110; V. Fournee et al. PRL 95 (2005) 155504.

  8. Computational study of false vocal folds effects on unsteady airflows through static models of the human larynx.

    PubMed

    Farbos de Luzan, Charles; Chen, Jie; Mihaescu, Mihai; Khosla, Sid M; Gutmark, Ephraim

    2015-05-01

    Compressible large eddy simulation is employed to numerically investigate the laryngeal flow. Symmetric static models of the human larynx with a divergent glottis are considered, with the presence of false vocal folds (FVFs). The compressible study agrees well with that of the incompressible study. Due to the high enough Reynolds number, the flow is unsteady and develops asymmetric states downstream of the glottis. The glottal jet curvature decreases with the presence of FVFs or the ventricular folds. The gap between the FVFs stretches the flow structure and reduces the jet curvature. The presence of FVFs has a significant effect on the laryngeal flow resistance. The intra-glottal vortex structures are formed on the divergent wall of the glottis, immediately downstream of the separation point. The vortices are then convected downstream and characterized by a significant negative static pressure. The FVFs are a main factor in the generation of stronger vortices, and thus on the closure of the TVFs. The direct link between the FVFs geometry and the motion of the TVFs, and by extension to the voice production, is of interest for medical applications as well as future research works. The presence of the FVFs also changes the dominant frequencies in the velocity and pressure spectra.

  9. Computational study of false vocal folds effects on unsteady airflows through static models of the human larynx

    PubMed Central

    de Luzan, Charles Farbos; Chen, Jie; Mihaescu, Mihai; Khosla, Sid M.; Gutmark, Ephraim

    2016-01-01

    Compressible large eddy simulation is employed to numerically investigate the laryngeal flow. Symmetric static models of the human larynx with a divergent glottis are considered, with the presence of false vocal folds (FVFs). The compressible study agrees well with that of the incompressible study. Due to the high enough Reynolds number, the flow is unsteady and develops asymmetric states downstream of the glottis. The glottal jet curvature decreases with the presence of FVFs or the ventricular folds. The gap between the FVFs stretches the flow structure and reduces the jet curvature. The presence of FVFs has a significant effect on the laryngeal flow resistance. The intra-glottal vortex structures are formed on the divergent wall of the glottis, immediately downstream of the separation point. The vortices are then convected downstream and characterized by a significant negative static pressure. The FVFs are a main factor in the generation of stronger vortices, and thus on the closure of the TVFs. The direct link between the FVFs geometry and the motion of the TVFs, and by extension to the voice production, is of interest for medical applications as well as future research works. The presence of the FVFs also changes the dominant frequencies in the velocity and pressure spectra. PMID:25835787

  10. Single-Molecule Protein Folding: A Study of the Surface-Mediated Conformational Dynamics of a Model Amphipathic Peptide

    NASA Astrophysics Data System (ADS)

    Cunningham, Joy; English, Douglas

    2004-03-01

    Most surface-active polypeptides, composed of 10-50 amino acids, are devoid of well-defined tertiary structure. The conformation of these proteins is greatly dependent upon their environment and may assume totally different characteristics in an aqueous environment, in a detergent micelle, or in an organic solvent. Most antimicrobial peptides are helix-forming and are activated upon interaction with a membrane-mimicking environment. We are seeking to physically characterize the mechanism of membrane-peptide interaction through studying a simple model peptide, MT-1. MT-1 was designed as a nonhomologous analogue of melittin, the principle component in bee venom. We are using single molecule spectroscopy to examine the induction of secondary structure upon interaction of MT-1 with various membrane-mimicking interfaces. Specifically, we monitor coil-to-helix transition through single molecule fluorescence resonance energy transfer (sm-FRET) to determine conformational distributions of folded and unfolded peptides at an interface. Studies with MT-1 will focus upon the biologically relevant issues of orientation, aggregation, and folding at surfaces using both ensemble and single molecule experiments.

  11. Using COMSOL Multiphysics Software to Model Anisotropic Dielectric and Metamaterial Effects in Folded-Waveguide Traveling-Wave Tube Slow-Wave Circuits

    NASA Technical Reports Server (NTRS)

    Starinshak, David P.; Smith, Nathan D.; Wilson, Jeffrey D.

    2008-01-01

    The electromagnetic effects of conventional dielectrics, anisotropic dielectrics, and metamaterials were modeled in a terahertz-frequency folded-waveguide slow-wave circuit. Results of attempts to utilize these materials to increase efficiency are presented.

  12. New insights into chromatin folding and dynamics from multi-scale modeling

    NASA Astrophysics Data System (ADS)

    Olson, Wilma

    The dynamic organization of chromatin plays an essential role in the regulation of gene expression and in other fundamental cellular processes. The underlying physical basis of these activities lies in the sequential positioning, chemical composition, and intermolecular interactions of the nucleosomes-the familiar assemblies of roughly 150 DNA base pairs and eight histone proteins-found on chromatin fibers. We have developed a mesoscale model of short nucleosomal arrays and a computational framework that make it possible to incorporate detailed structural features of DNA and histones in simulations of short chromatin constructs with 3-25 evenly spaced nucleosomes. The correspondence between the predicted and observed effects of nucleosome composition, spacing, and numbers on long-range communication between regulatory proteins bound to the ends of designed nucleosome arrays lends credence to the model and to the molecular insights gleaned from the simulated structures. We have extracted effective nucleosome-nucleosome potentials from the mesoscale simulations and introduced the potentials in a larger scale computational treatment of regularly repeating chromatin fibers. Our results reveal a remarkable influence of nucleosome spacing on chromatin flexibility. Small changes in the length of the DNA fragments linking successive nucleosomes introduce marked changes in the local interactions of the nucleosomes and in the spatial configurations of the fiber as a whole. The changes in nucleosome positioning influence the statistical properties of longer chromatin constructs with 100-10,000 nucleosomes. We are investigating the extent to which the `local' interactions of regularly spaced nucleosomes contribute to the corresponding interactions in chains with mixed spacings as a step toward the treatment of fibers with nucleosomes positioned at the sites mapped at base-pair resolution on genomic sequences. Support of the work by USPHS R01 GM 34809 is gratefully acknowledged.

  13. Folding mechanisms of individual beta-hairpins in a Go model of Pin1 WW domain by all-atom molecular dynamics simulations.

    PubMed

    Luo, Zhonglin; Ding, Jiandong; Zhou, Yaoqi

    2008-06-14

    This paper examines the folding mechanism of an individual beta-hairpin in the presence of other hairpins by using an off-lattice model of a small triple-stranded antiparallel beta-sheet protein, Pin1 WW domain. The turn zipper model and the hydrophobic collapse model originally developed for a single beta-hairpin in literature is confirmed to be useful in describing beta-hairpins in model Pin1 WW domain. We find that the mechanism for folding a specific hairpin is independent of whether it folds first or second, but the formation process are significantly dependent on temperature. More specifically, beta1-beta2 hairpin folds via the turn zipper model at a low temperature and the hydrophobic collapse model at a high temperature, while the folding of beta2-beta3 hairpin follows the turn zipper model at both temperatures. The change in folding mechanisms is interpreted by the interplay between contact stability (enthalpy) and loop lengths (entropy), the effect of which is temperature dependent.

  14. Molecular rotors as simple models to study amide NH-aromatic interactions and their role in the folding of peptide-like structures.

    PubMed

    Alfonso, Ignacio; Burguete, M Isabel; Galindo, Francisco; Luis, Santiago V; Vigara, Laura

    2007-10-12

    The conformational behavior of designed macrocyclic naphthalenophanes (1a,b and 2a,b) derived from amino acids (Phe and Val) has been used for studying NH...pi interactions. The cycles having 16- and 17-membered rings showed a dynamic process within the NMR time scale, produced by the flipping of the aromatic naphthalene moiety with respect to the macrocyclic main plane. We used the temperature dependence of 1H NMR to obtain activation parameters of the energetic barrier for the process (variable temperature NMR and line shape analysis). The rate of the movement clearly depends on the macrocyclic ring size and, more interestingly, on the nature of the peptidomimetic side chain, the energetic barrier being higher for the compounds bearing aromatic side chains. A largely negative entropic contribution to the free energy of activation was observed, with clear differences due to the side chain nature. Molecular modeling studies suggest that the aromatic rings interact with intramolecularly H-bonded amide NH groups, protecting them from solvation and thus leading to a larger unfavorable activation entropy. This NH...pi interaction has been exploited for the preparation of new systems (1c and meso-1b) with designed conformational preferences, in which aromatic rings tend to fold over amide NH groups. Thus, these minimalistic molecular rotors have served us as simple model systems for the study of NH...pi interactions and their implication in the folding of peptide-like molecules.

  15. Osmolyte-induced folding of an intrinsically disordered protein: folding mechanism in the absence of ligand.

    PubMed

    Chang, Yu-Chu; Oas, Terrence G

    2010-06-29

    Understanding the interconversion between thermodynamically distinguishable states present in a protein folding pathway provides not only the kinetics and energetics of protein folding but also insights into the functional roles of these states in biological systems. The protein component of the bacterial RNase P holoenzyme from Bacillus subtilis (P protein) was previously shown to be unfolded in the absence of its cognate RNA or other anionic ligands. P protein was used in this study as a model system to explore general features of intrinsically disordered protein (IDP) folding mechanisms. The use of trimethylamine N-oxide (TMAO), an osmolyte that stabilizes the unliganded folded form of the protein, enabled us to study the folding process of P protein in the absence of ligand. Transient stopped-flow kinetic traces at various final TMAO concentrations exhibited multiphasic kinetics. Equilibrium "cotitration" experiments were performed using both TMAO and urea during the titration to produce a urea-TMAO titration surface of P protein. Both kinetic and equilibrium studies show evidence of a previously undetected intermediate state in the P protein folding process. The intermediate state is significantly populated, and the folding rate constants are relatively slow compared to those of intrinsically folded proteins similar in size and topology. The experiments and analysis described serve as a useful example for mechanistic folding studies of other IDPs.

  16. Protein folding simulations of 2D HP model by the genetic algorithm based on optimal secondary structures.

    PubMed

    Huang, Chenhua; Yang, Xiangbo; He, Zhihong

    2010-06-01

    In this paper, based on the evolutionary Monte Carlo (EMC) algorithm, we have made four points of ameliorations and propose a so-called genetic algorithm based on optimal secondary structure (GAOSS) method to predict efficiently the protein folding conformations in the two-dimensional hydrophobic-hydrophilic (2D HP) model. Nine benchmarks are tested to verify the effectiveness of the proposed approach and the results show that for the listed benchmarks GAOSS can find the best solutions so far. It means that reasonable, effective and compact secondary structures (SSs) can avoid blind searches and can reduce time consuming significantly. On the other hand, as examples, we discuss the diversity of protein GSC for the 24-mer and 85-mer sequences. Several GSCs have been found by GAOSS and some of the conformations are quite different from each other. It would be useful for the designing of protein molecules. GAOSS would be an efficient tool for the protein structure predictions (PSP).

  17. Folding of apominimyoglobin.

    PubMed Central

    De Sanctis, G; Ascoli, F; Brunori, M

    1994-01-01

    The acid unfolding pathway of apominimyoglobin (apo-mini-Mb), a 108-aa fragment (aa 32-139) of horse heart apomyoglobin has been studied by means of circular dichroism, in comparison with the native apoprotein. Similar to sperm whale apomyoglobin [Hughson, F. M., Wright, P. E. & Baldwin, R. L. (1990) Science 249, 1544-1548], a partly folded intermediate (alpha-helical content approximately 35%) is populated at pH 4.2 for horse heart apomyoglobin. For this intermediate, Hughson et al. proposed a structural model with a compact subdomain involving tertiary interactions between the folded A, G, and H helices, with the remainder of the protein essentially unfolded. As described in this paper, a folding intermediate with an alpha-helical content of approximately 33% is populated at pH 4.3-5.0 also in apo-mini-Mb. The acid unfolding pathway is similarly affected in both the native and the mini apoprotein by 15% trifluoroethanol, a helix-stabilizing compound. Thus, the folding of the apo-mini-Mb intermediate is similar to that observed for the native apoprotein, in spite of the absence in the miniprotein of the A helix and of a large part of the H helix, which are crucial for the stability of apo-Mb intermediate. Our results suggest that acquisition of a folded state in apo-mini-Mb occurs through an alternative pathway, which may or may not be shared also by apo-Mb. PMID:7972092

  18. Detachment folding, fold amplification, and diapirism in thrust wedge experiments

    NASA Astrophysics Data System (ADS)

    Bonini, Marco

    2003-12-01

    The relations between detachment folding, fold amplification, and salt diapirism in contractional settings have been investigated by means of scaled analogue models. The viscosity of the silicone layer simulating salt in nature and the shortening rates were combined in order to reproduce weak (type 1 models) and strong (type 2 models) décollements. Deformation patterns in the roof sequence exhibited two contrasting styles, (1) outward propagation of detachment folding along the décollement (OFP mode) and (2) passive roof duplex (PRD mode). In type 2 models, detachment folding propagated away from the most external thrust in the floor sequence, while in type 1 models, long-lived detachment folds almost invariably localized amplified above a floor thrust tip as a result of strain localization. A silicone wall intruded occasionally into the crestal graben of detachment folds in type 1 and OFP models. Best fitting of transition models data points indicates nonlinear relations with regression curves close to the equilateral hyperbola equation for both OFP-PRD and amplified detachment folds-box folds transitions. A quantitative comparison of model results with nature has been attempted by plotting salt-based fold-and-thrust belts data points on the scaled transition curves obtained from the modeling. Such a comparison relates shear stress products and ratios to the conditions favoring the amplification of detachment folds and the potential emplacement of ductile diapirs in their core. By reducing the roof sequence strength, pore fluid pressure λb is inferred to shift the equilibrium of fold-and-thrust belts toward the field of OFP and diapirism.

  19. Protein Folding and Structure Prediction from the Ground Up: The Atomistic Associative Memory, Water Mediated, Structure and Energy Model

    PubMed Central

    Chen, Mingchen; Lin, Xingcheng; Zheng, Weihua; Onuchic, José N.; Wolynes, Peter G.

    2016-01-01

    The associative memory, water mediated, structure and energy model (AWSEM) is a coarse-grained force field with transferable tertiary interactions that incorporates local in sequence energetic biases using bioinformatically derived structural information about peptide fragments with locally similar sequence that we call memories. The memory information from the protein data bank (PDB) database guides proper protein folding. The structural information about available sequences in the database varies in quality and can sometimes lead to frustrated free energy landscapes locally. One way out of this difficulty is to construct the input fragment memory information from all-atom simulations of portions of the complete polypeptide chain. In this paper, we investigate this approach first put forward by Kwac and Wolynes in a more complete way by studying the structure prediction capabilities of this approach for six alpha-helical proteins. This scheme which we call the atomistic associative memory, water mediated, structure and energy model (AAWSEM) amounts to an ab initio protein structure prediction method that starts from the ground-up without using bioinformatic input. The free energy profiles from AAWSEM show that atomistic fragment memories are sufficient to guide the correct folding when tertiary forces are included. AAWSEM combines the efficiency of coarse-grained simulations on the full protein level with the local structural accuracy achievable from all-atom simulations of only parts of a large protein. The results suggest that a hybrid use of atomistic fragment memory and database memory in structural predictions may well be optimal for many practical applications. PMID:27148634

  20. Soliton behavior for a generalized mixed nonlinear Schrödinger model with N-fold Darboux transformation

    NASA Astrophysics Data System (ADS)

    Lü, Xing

    2013-09-01

    A spectral problem, the x-derivative part of which is a simple generalization of the standard Ablowitz-Kaup-Newell-Segur and Kaup-Newell spectral problems, is presented with its associated generalized mixed nonlinear Schrödinger (GMNLS) model. The N-fold Darboux transformation with multi-parameters for the spectral problem is constructed with the help of gauge transformation. According to the Darboux transformation, the solution of the GMNLS model is reduced to solving a linear algebraic system and two first-order ordinary differential equations. As an example of application, we list the modulus formulae of the envelope one- and two-soliton solutions. Note that our model is a generalized one with the inclusion of four coefficients (a, b, c, and d), which involves abundant NLS-type models such as the standard cubic NLS equation, the Gerdjikov-Ivanov equation, the Chen-Lee-Liu equation, the Kaup-Newell equation, and the mixed NLS of Wadati and/or Kundu, among others.

  1. Soliton behavior for a generalized mixed nonlinear Schrödinger model with N-fold Darboux transformation.

    PubMed

    Lü, Xing

    2013-09-01

    A spectral problem, the x-derivative part of which is a simple generalization of the standard Ablowitz-Kaup-Newell-Segur and Kaup-Newell spectral problems, is presented with its associated generalized mixed nonlinear Schrödinger (GMNLS) model. The N-fold Darboux transformation with multi-parameters for the spectral problem is constructed with the help of gauge transformation. According to the Darboux transformation, the solution of the GMNLS model is reduced to solving a linear algebraic system and two first-order ordinary differential equations. As an example of application, we list the modulus formulae of the envelope one- and two-soliton solutions. Note that our model is a generalized one with the inclusion of four coefficients (a, b, c, and d), which involves abundant NLS-type models such as the standard cubic NLS equation, the Gerdjikov-Ivanov equation, the Chen-Lee-Liu equation, the Kaup-Newell equation, and the mixed NLS of Wadati and/or Kundu, among others.

  2. A transgenic mouse model expressing an ERα folding biosensor reveals the effects of Bisphenol A on estrogen receptor signaling

    PubMed Central

    Sekar, Thillai V.; Foygel, Kira; Massoud, Tarik F.; Gambhir, Sanjiv S.; Paulmurugan, Ramasamy

    2016-01-01

    Estrogen receptor-α (ERα) plays an important role in normal and abnormal physiology of the human reproductive system by interacting with the endogenous ligand estradiol (E2). However, other ligands, either analogous or dissimilar to E2, also bind to ERα. This may create unintentional activation of ER signaling in reproductive tissues that can lead to cancer development. We developed a transgenic mouse model that constitutively expresses a firefly luciferase (FLuc) split reporter complementation biosensor (NFLuc-ER-LBDG521T-CFLuc) to simultaneously evaluate the dynamics and potency of ligands that bind to ERα. We first validated this model using various ER ligands, including Raloxifene, Diethylstilbestrol, E2, and 4-hydroxytamoxifen, by employing FLuc-based optical bioluminescence imaging of living mice. We then used the model to investigate the carcinogenic property of Bisphenol A (BPA), an environmental estrogen, by long-term exposure at full and half environmental doses. We showed significant carcinogenic effects on female animals while revealing activated downstream ER signaling as measured by bioluminescence imaging. BPA induced tumor-like outgrowths in female transgenic mice, histopathologically confirmed to be neoplastic and epithelial in origin. This transgenic mouse model expressing an ERα folding-biosensor is useful in evaluation of estrogenic ligands and their downstream effects, and in studying environmental estrogen induced carcinogenesis in vivo. PMID:27721470

  3. Modelling "reality" in tectonics: Simulation of the mechanical evolution of the Jura Mountains-Molasse Basin system, and routes to forward-inverse modelling of fold thrust belts.

    NASA Astrophysics Data System (ADS)

    Hindle, David; Kley, Jonas

    2016-04-01

    The ultimate validation of any numerical model of any geological process comes when it can accurately forward model a case study from the geological record. However, as the example of the Jura-Molasse fold thrust belt demonstrates, geological information on even the most basic aspects of the present day state of such systems is highly incomplete and usually known only with large uncertainties. Fold thrust-belts are studied and understood by geologists in an iterative process of constructing their subsurface geometries and structures (folds, faults, bedding etc) based on limited subsurface information from boreholes, tunnels or seismic data where available, and surface information on outcrops of different layers and their dips. This data is usually processed through geometric models which involve conservation of line length of different beds over the length of an entire cross section. Constructing such sections is the art of cross section balancing. A balanced cross section can be easily restored to its pre-deformation state, assuming (usually) originally horizontal bedding to remove the effects of folding and faulting. Such a pre-deformation state can then form an initial condition for a forward mechanical model of the section. A mechanical model introduces new parameters into the system such as rock elasticity, cohesion, and frictional properties. However, a forward mechanical model can also potentially show the continuous evolution of a fold thrust belt, including dynamic quantities like stress. Moreover, a forward mechanical model, if correct in most aspects, should match in its final state, the present day geological cross section it is simulating. However, when attempting to achieve a match between geometric and mechanical models, it becomes clear that many more aspects of the geodynamic history of a fold thrust belt have to be taken into account. Erosion of the uppermost layers of an evolving thrust belt is the most obvious one of these. This can potentially

  4. Evolution of the Chos Malal and Agrio fold and thrust belts, Andes of Neuquén: Insights from structural analysis and apatite fission track dating

    NASA Astrophysics Data System (ADS)

    Rojas Vera, E. A.; Mescua, J.; Folguera, A.; Becker, T. P.; Sagripanti, L.; Fennell, L.; Orts, D.; Ramos, V. A.

    2015-12-01

    The Chos Malal and Agrio fold and thrust belts are located in the western part of the Neuquén basin, an Andean retroarc basin of central-western Argentina. Both belts show evidence of tectonic inversion at the western part during Late Cretaceous times. The eastern part is dominated by late Miocene deformation which also partially reactivated the western structures. This work focuses on the study of the regional structure and the deformational event that shaped the relief of this part of the Andes. Based on new field work and structural data and previously published works a detailed map of the central part of the Neuquén basin is presented. Three regional structural cross sections were surveyed and balanced using the 2d Move™ software. In order to define a more accurate uplift history, new apatite fission track analyses were carried on selected structures. These data was used for new thermal history modeling of the inner part of the Agrio and Chos Malal fold and thrust belts. The results of the fission track analyses improve the knowledge of how these fold and thrust belts have grown trough time. Two main deformational events are defined in Late Cretaceous to Paleocene and Late Miocene times. Based on this regional structural analysis and the fission track data the precise location of the orogenic front for the Late Cretaceous-Paleocene times is reconstructed and it is proposed a structural evolution of this segment of the Andes. This new exhumation data show how the Late Cretaceous to Paleocene event was a continuous and uninterrupted deformational event.

  5. Models of Glycoprotein Folding

    DTIC Science & Technology

    1993-07-23

    steps and deprotection, the overall yield from oligosaccharide to glycopeptide is low. This may be acceptable for monosaccharides or for...in Figure 3. GlcNAcNH 2 (1) is commercially available. Chitobiose constitutes the disaccharide core of N-linked sugars; the peracetylated compound (2...glycopeptides containing this sugar cannot be easily prepared by non- convergent methods. 43 The peracetylated disaccharide (5) was synthesized from L

  6. [THE MODEL OF NUCLEOSOME STRUCTURE BASED ON THE LOCAL ROTATION OF THE NUCLEOHISTONE CHAIN, WHICH INDUCES ITS FOLDING].

    PubMed

    Priyatkina, T N

    2015-01-01

    An alternative model to the "double turn of DNA on the histone core" approach is forwarded based on the biochemical, cytological, and crystallographic data on the structural organization of the chromatin units--nucleosomes. The model assumes that the initial structure is a linear nucleohistone cord with a repeating symmetrical histone sequence. The compact (core) particle (a minimal nucleosome) is forming upon a stepwise rotation of DNA (kinks) at the centre and at two symmetrical sites into each repeating fragment stemming from the electrostatic binding of the lysine ε-NH2-groups with the followed one by one phosphates of the sugar-phosphate chain. As a result, we have a rhomboid structure composed of two counter-symmetrical DNA folds stabilized by histone-histone interactions. Based on disposable data, the histone sequence along nucleosome DNA is deduced. The following characteristics of the sequence are considered: continuity, non-overlapping, versatility, and dyadic symmetry in dispose of two every kind histone molecules and the sequence on the whole. The model is in agreement with a topology of nucleosome DNA, as well as the pattern of DNA-histone and histone-histone interactions in chromatin.

  7. MicroRNA expression analysis of rosette and folding leaves in Chinese cabbage using high-throughput Solexa sequencing.

    PubMed

    Wang, Fengde; Li, Huayin; Zhang, Yihui; Li, Jingjuan; Li, Libin; Liu, Lifeng; Wang, Lihua; Wang, Cuihua; Gao, Jianwei

    2013-12-15

    In this study, a global analysis of miRNA expression from rosette leaves (RLs) and folding leaves (FLs) of Chinese cabbage (Brassica rapa L. ssp. pekinensis) was conducted using high-throughput Solexa sequencing. In total, over 12 million clean reads were obtained from each library. Sequence analysis identified 64 conserved miRNA families in each leaf type and 104 and 95 novel miRNAs from RLs and FLs, respectively. Among these, 61 conserved miRNAs and 61 novel miRNAs were detected in both types of leaves. Furthermore, six conserved and 21 novel miRNAs were differentially expressed between the two libraries. Target gene annotation suggested that these differentially expressed miRNAs targeted transcription factors, F-box proteins, auxin and Ca(2+) signaling pathway proteins, protein kinases and other proteins that may function in governing leafy head formation. This study advanced our understanding of the important roles of miRNAs in regulating leafy head development in Chinese cabbage.

  8. Heuristic-based tabu search algorithm for folding two-dimensional AB off-lattice model proteins.

    PubMed

    Liu, Jingfa; Sun, Yuanyuan; Li, Gang; Song, Beibei; Huang, Weibo

    2013-12-01

    The protein structure prediction problem is a classical NP hard problem in bioinformatics. The lack of an effective global optimization method is the key obstacle in solving this problem. As one of the global optimization algorithms, tabu search (TS) algorithm has been successfully applied in many optimization problems. We define the new neighborhood conformation, tabu object and acceptance criteria of current conformation based on the original TS algorithm and put forward an improved TS algorithm. By integrating the heuristic initialization mechanism, the heuristic conformation updating mechanism, and the gradient method into the improved TS algorithm, a heuristic-based tabu search (HTS) algorithm is presented for predicting the two-dimensional (2D) protein folding structure in AB off-lattice model which consists of hydrophobic (A) and hydrophilic (B) monomers. The tabu search minimization leads to the basins of local minima, near which a local search mechanism is then proposed to further search for lower-energy conformations. To test the performance of the proposed algorithm, experiments are performed on four Fibonacci sequences and two real protein sequences. The experimental results show that the proposed algorithm has found the lowest-energy conformations so far for three shorter Fibonacci sequences and renewed the results for the longest one, as well as two real protein sequences, demonstrating that the HTS algorithm is quite promising in finding the ground states for AB off-lattice model proteins.

  9. Atomistic modeling of a KRT35/KRT85 keratin dimer: folding in aqueous solution and unfolding under tensile load.

    PubMed

    Duchstein, Patrick; Clark, Tim; Zahn, Dirk

    2015-09-14

    We present an atomistic model of a full KRT35/KRT85 dimer, a fundamental building block of human hair. For both monomers initial structures were generated using empirical tools based on homology considerations, followed by the formulation of a naiïve dimer model from docking the monomers in vacuum. Relaxation in aqueous solution was then explored from molecular dynamics simulation. Driven by hydrophobic segregation and protein-protein hydrogen bonding relaxation dynamics result in a folded dimer arrangement which shows a striking encounter of cystein groups. Our simulations hence suggests that (i) cystein groups in the coil regions of keratin are well suited to establish disulfide bonds between the two monomers that constitute the dimer, and (ii) the particularly large number of cystein groups in the head and tail regions promotes the connection of dimers to establish meso- to macroscale fibers. Moreover, we show the molecular mechanisms of elastic and plastic deformation under tensile load. Upon elongation beyond the elastic regime, unfolding was identified as the exposure of hydrophobic moieties and the breaking of protein-protein hydrogen bonds. Therein, the step-wise character of the series of unfolding events leads to a broad regime of constant force in response to further elongation.

  10. Nonlinear dynamic-based analysis of severe dysphonia in patients with vocal fold scar and sulcus vocalis

    PubMed Central

    Choi, Seong Hee; Zhang, Yu; Jiang, Jack J.; Bless, Diane M.; Welham, Nathan V.

    2011-01-01

    Objective The primary goal of this study was to evaluate a nonlinear dynamic approach to the acoustic analysis of dysphonia associated with vocal fold scar and sulcus vocalis. Study Design Case-control study. Methods Acoustic voice samples from scar/sulcus patients and age/sex-matched controls were analyzed using correlation dimension (D2) and phase plots, time-domain based perturbation indices (jitter, shimmer, signal-to-noise ratio [SNR]), and an auditory-perceptual rating scheme. Signal typing was performed to identify samples with bifurcations and aperiodicity. Results Type 2 and 3 acoustic signals were highly represented in the scar/sulcus patient group. When data were analyzed irrespective of signal type, all perceptual and acoustic indices successfully distinguished scar/sulcus patients from controls. Removal of type 2 and 3 signals eliminated the previously identified differences between experimental groups for all acoustic indices except D2. The strongest perceptual-acoustic correlation in our dataset was observed for SNR; the weakest correlation was observed for D2. Conclusions These findings suggest that D2 is inferior to time-domain based perturbation measures for the analysis of dysphonia associated with scar/sulcus; however, time-domain based algorithms are inherently susceptible to inflation under highly aperiodic (i.e., type 2 and 3) signal conditions. Auditory-perceptual analysis, unhindered by signal aperiodicity, is therefore a robust strategy for distinguishing scar/sulcus patient voices from normal voices. Future acoustic analysis research in this area should consider alternative (e.g., frequency- and quefrency-domain based) measures alongside additional nonlinear approaches. PMID:22516315

  11. High-resolution protein folding with a transferable potential.

    PubMed

    Hubner, Isaac A; Deeds, Eric J; Shakhnovich, Eugene I

    2005-12-27

    A generalized computational method for folding proteins with a fully transferable potential and geometrically realistic all-atom model is presented and tested on seven helix bundle proteins. The protocol, which includes graph-theoretical analysis of the ensemble of resulting folded conformations, was systematically applied and consistently produced structure predictions of approximately 3 A without any knowledge of the native state. To measure and understand the significance of the results, extensive control simulations were conducted. Graph theoretic analysis provides a means for systematically identifying the native fold and provides physical insight, conceptually linking the results to modern theoretical views of protein folding. In addition to presenting a method for prediction of structure and folding mechanism, our model suggests that an accurate all-atom amino acid representation coupled with a physically reasonable atomic interaction potential and hydrogen bonding are essential features for a realistic protein model.

  12. Evolutionary Optimization of Protein Folding

    PubMed Central

    Debès, Cédric; Wang, Minglei; Caetano-Anollés, Gustavo; Gräter, Frauke

    2013-01-01

    Nature has shaped the make up of proteins since their appearance, 3.8 billion years ago. However, the fundamental drivers of structural change responsible for the extraordinary diversity of proteins have yet to be elucidated. Here we explore if protein evolution affects folding speed. We estimated folding times for the present-day catalog of protein domains directly from their size-modified contact order. These values were mapped onto an evolutionary timeline of domain appearance derived from a phylogenomic analysis of protein domains in 989 fully-sequenced genomes. Our results show a clear overall increase of folding speed during evolution, with known ultra-fast downhill folders appearing rather late in the timeline. Remarkably, folding optimization depends on secondary structure. While alpha-folds showed a tendency to fold faster throughout evolution, beta-folds exhibited a trend of folding time increase during the last 1.5 billion years that began during the “big bang” of domain combinations. As a consequence, these domain structures are on average slow folders today. Our results suggest that fast and efficient folding of domains shaped the universe of protein structure. This finding supports the hypothesis that optimization of the kinetic and thermodynamic accessibility of the native fold reduces protein aggregation propensities that hamper cellular functions. PMID:23341762

  13. Modeling the effect of codon translation rates on co-translational protein folding mechanisms of arbitrary complexity

    NASA Astrophysics Data System (ADS)

    Caniparoli, Luca; O'Brien, Edward P.

    2015-04-01

    In a cell, the folding of a protein molecule into tertiary structure can begin while it is synthesized by the ribosome. The rate at which individual amino acids are incorporated into the elongating nascent chain has been shown to affect the likelihood that proteins will populate their folded state, indicating that co-translational protein folding is a far from equilibrium process. Developing a theoretical framework to accurately describe this process is, therefore, crucial for advancing our understanding of how proteins acquire their functional conformation in living cells. Current state-of-the-art computational approaches, such as molecular dynamics simulations, are very demanding in terms of the required computer resources, making the simulation of co-translational protein folding difficult. Here, we overcome this limitation by introducing an efficient approach that predicts the effects that variable codon translation rates have on co-translational folding pathways. Our approach is based on Markov chains. By using as an input a relatively small number of molecular dynamics simulations, it allows for the computation of the probability that a nascent protein is in any state as a function of the translation rate of individual codons along a mRNA's open reading frame. Due to its computational efficiency and favorable scalability with the complexity of the folding mechanism, this approach could enable proteome-wide computational studies of the influence of translation dynamics on co-translational folding.

  14. Evolution of pore-fluid pressure during folding and basin contraction in overpressured reservoirs assessed by combined fracture analysis and calcite twinning paleopiezometry

    NASA Astrophysics Data System (ADS)

    Beaudoin, Nicolas; Lacombe, Olivier; Bellahsen, Nicolas; Amrouch, Khalid; Daniel, Jean-Marc

    2014-05-01

    enhancement of vertical hydraulic permeability that affect the strata during the curvature-related fracture development. Another result of our approach is the possible estimate of syn-folding exhumation of strata. The inferred exhumation values range from 0,6 km to 1,3 km at Sheep Mountain and from 0,8 km to 2,0 km at Rattlesnake Mountain. These values are consistent with fold growth models predicting exhumation rates ranging from 0.03 to 0.40 mm/yr and with published exhumation rates from fission track studies in other Laramide uplifts. This case study illustrates how the combination of stress inversion of fault-slip and calcite twin data with rock mechanics can be used to discuss which are the natural factors that control the pressure evolution in a carbonate reservoir during its large-scale deformation in an orogenic foreland.

  15. Graphene folding on flat substrates

    SciTech Connect

    Chen, Xiaoming; Zhao, Yadong; Ke, Changhong; Zhang, Liuyang; Wang, Xianqiao

    2014-10-28

    We present a combined experimental-theoretical study of graphene folding on flat substrates. The structure and deformation of the folded graphene sheet are experimentally characterized by atomic force microscopy. The local graphene folding behaviors are interpreted based on nonlinear continuum mechanics modeling and molecular dynamics simulations. Our study on self-folding of a trilayer graphene sheet reports a bending stiffness of about 6.57 eV, which is about four times the reported values for monolayer graphene. Our results reveal that an intriguing free sliding phenomenon occurs at the interlayer van der Waals interfaces during the graphene folding process. This work demonstrates that it is a plausible venue to quantify the bending stiffness of graphene based on its self-folding conformation on flat substrates. The findings reported in this work are useful to a better understanding of the mechanical properties of graphene and in the pursuit of its applications.

  16. Direct folding simulation of a long helix in explicit water

    NASA Astrophysics Data System (ADS)

    Gao, Ya; Lu, Xiaoliang; Duan, Lili; Zhang, Dawei; Mei, Ye; Zhang, John Z. H.

    2013-05-01

    A recently proposed Polarizable Hydrogen Bond (PHB) method has been employed to simulate the folding of a 53 amino acid helix (PDB ID 2KHK) in explicit water. Under PHB simulation, starting from a fully extended structure, the peptide folds into the native state as confirmed by measured time evolutions of radius of gyration, root mean square deviation (RMSD), and native hydrogen bond. Free energy and cluster analysis show that the folded helix is thermally stable under the PHB model. Comparison of simulation results under, respectively, PHB and standard nonpolarizable force field demonstrates that polarization is critical for stable folding of this long α-helix.

  17. Correlation of the Vocal Fold Vibratory Pattern to the Post-Operative Surgical Wound in the Porcine Model.

    DTIC Science & Technology

    1992-02-15

    functional layers within the vocal folds. To do this, videostroboscopy (VS) and electroglottography ( EGG ) were used to record glottal function during...of air is formed as the lower margin opens first , followed by opening of the upper margin and release of the puff. This fluid-like movement is defined...normal laryngeal anatomy. The first surgical procedure on the right true vocal fold utilized microsurgical instruments. The surgical incision and/or

  18. Structural analysis of hanging wall and footwall blocks within the Río Guanajibo fold-and-thrust belt in Southwest Puerto Rico

    NASA Astrophysics Data System (ADS)

    Laó-Dávila, Daniel A.; Llerandi-Román, Pablo A.

    2017-01-01

    The Río Guanajibo fold-and-thrust belt (RGFT), composed of Cretaceous serpentinite and volcano-sedimentary rocks, represents the deformation front of a contractional event in SW Puerto Rico during the Paleogene. Previous studies inferred structural and stratigraphic relationships from poorly exposed outcrops. New road cuts exposed the Yauco (YF) and El Rayo Formations (ERF) providing insights on the deformation of the hanging wall and footwall. We described the nature and orientation of faults and folds and analyzed the kinematic indicators to characterize the deformation. The YF occurs in the hanging wall and shows a sequence of folded, medium-bedded mudstone and thinly bedded shale and sandstone. Major folds strike NW-SE and are gentle with steeply inclined axial planes and sub-horizontal fold axes. Minor folds are open with moderately inclined axial planes and gently to moderately inclined SE-plunging fold axes. NW-SE striking reverse and thrust faults cut layers and show movement to the SW. Steep left-lateral faults strike NW-SE and NE-SW, and smaller right-lateral strike-slip faults strike NNE-SSW. At the footwall, the ERF consists of bioclastic limestone and polymictic orthoconglomerates and paraconglomerates. Reverse and strike-slip faults cut along lithological contacts. Results suggest that the hanging wall and footwall accommodated strain along preexisting weaknesses, which are dependent on lithology and sedimentary structures. The kinematic analysis suggests that shortening in the NE-SW direction was partitioned between folding and interlayer shortening, accommodated by flexural slip, and reverse and left-lateral faults that resulted from contraction. The RGFT represents the Paleogene back arc deformation of a bivergent thrust system.

  19. Energy landscape analysis of native folding of the prion protein yields the diffusion constant, transition path time, and rates.

    PubMed

    Yu, Hao; Gupta, Amar Nath; Liu, Xia; Neupane, Krishna; Brigley, Angela M; Sosova, Iveta; Woodside, Michael T

    2012-09-04

    Protein folding is described conceptually in terms of diffusion over a configurational free-energy landscape, typically reduced to a one-dimensional profile along a reaction coordinate. In principle, kinetic properties can be predicted directly from the landscape profile using Kramers theory for diffusive barrier crossing, including the folding rates and the transition time for crossing the barrier. Landscape theory has been widely applied to interpret the time scales for protein conformational dynamics, but protein folding rates and transition times have not been calculated directly from experimentally measured free-energy profiles. We characterized the energy landscape for native folding of the prion protein using force spectroscopy, measuring the change in extension of a single protein molecule at high resolution as it unfolded/refolded under tension. Key parameters describing the landscape profile were first recovered from the distributions of unfolding and refolding forces, allowing the diffusion constant for barrier crossing and the transition path time across the barrier to be calculated. The full landscape profile was then reconstructed from force-extension curves, revealing a double-well potential with an extended, partially unfolded transition state. The barrier height and position were consistent with the previous results. Finally, Kramers theory was used to predict the folding rates from the landscape profile, recovering the values observed experimentally both under tension and at zero force in ensemble experiments. These results demonstrate how advances in single-molecule theory and experiment are harnessing the power of landscape formalisms to describe quantitatively the mechanics of folding.

  20. Simulations of temporal patterns of oral airflow in men and women using a two-mass model of the vocal folds under dynamic control

    NASA Astrophysics Data System (ADS)

    Lucero, Jorge C.; Koenig, Laura L.

    2005-03-01

    In this study we use a low-dimensional laryngeal model to reproduce temporal variations in oral airflow produced by speakers in the vicinity of an abduction gesture. It attempts to characterize these temporal patterns in terms of biomechanical parameters such as glottal area, vocal fold stiffness, subglottal pressure, and gender differences in laryngeal dimensions. A two-mass model of the vocal folds coupled to a two-tube approximation of the vocal tract is fitted to oral airflow records measured in men and women during the production of /aha/ utterances, using the subglottal pressure, glottal width, and Q factor as control parameters. The results show that the model is capable of reproducing the airflow records with good approximation. A nonlinear damping characteristics is needed, to reproduce the flow variation at glottal abduction. Devoicing is achieved by the combined action of vocal fold abduction, the decrease of subglottal pressure, and the increase of vocal fold tension. In general, the female larynx has a more restricted region of vocal fold oscillation than the male one. This would explain the more frequent devoicing in glottal abduction-adduction gestures for /h/ in running speech by women, compared to men. .

  1. Ab initio RNA folding

    NASA Astrophysics Data System (ADS)

    Cragnolini, Tristan; Derreumaux, Philippe; Pasquali, Samuela

    2015-06-01

    RNA molecules are essential cellular machines performing a wide variety of functions for which a specific three-dimensional structure is required. Over the last several years, the experimental determination of RNA structures through x-ray crystallography and NMR seems to have reached a plateau in the number of structures resolved each year, but as more and more RNA sequences are being discovered, the need for structure prediction tools to complement experimental data is strong. Theoretical approaches to RNA folding have been developed since the late nineties, when the first algorithms for secondary structure prediction appeared. Over the last 10 years a number of prediction methods for 3D structures have been developed, first based on bioinformatics and data-mining, and more recently based on a coarse-grained physical representation of the systems. In this review we are going to present the challenges of RNA structure prediction and the main ideas behind bioinformatic approaches and physics-based approaches. We will focus on the description of the more recent physics-based phenomenological models and on how they are built to include the specificity of the interactions of RNA bases, whose role is critical in folding. Through examples from different models, we will point out the strengths of physics-based approaches, which are able not only to predict equilibrium structures, but also to investigate dynamical and thermodynamical behavior, and the open challenges to include more key interactions ruling RNA folding.

  2. Ab initio RNA folding.

    PubMed

    Cragnolini, Tristan; Derreumaux, Philippe; Pasquali, Samuela

    2015-06-17

    RNA molecules are essential cellular machines performing a wide variety of functions for which a specific three-dimensional structure is required. Over the last several years, the experimental determination of RNA structures through x-ray crystallography and NMR seems to have reached a plateau in the number of structures resolved each year, but as more and more RNA sequences are being discovered, the need for structure prediction tools to complement experimental data is strong. Theoretical approaches to RNA folding have been developed since the late nineties, when the first algorithms for secondary structure prediction appeared. Over the last 10 years a number of prediction methods for 3D structures have been developed, first based on bioinformatics and data-mining, and more recently based on a coarse-grained physical representation of the systems. In this review we are going to present the challenges of RNA structure prediction and the main ideas behind bioinformatic approaches and physics-based approaches. We will focus on the description of the more recent physics-based phenomenological models and on how they are built to include the specificity of the interactions of RNA bases, whose role is critical in folding. Through examples from different models, we will point out the strengths of physics-based approaches, which are able not only to predict equilibrium structures, but also to investigate dynamical and thermodynamical behavior, and the open challenges to include more key interactions ruling RNA folding.

  3. Comparative analysis of the folding dynamics and kinetics of an engineered knotted protein and its variants derived from HP0242 of Helicobacter pylori

    NASA Astrophysics Data System (ADS)

    Wang, Liang-Wei; Liu, Yu-Nan; Lyu, Ping-Chiang; Jackson, Sophie E.; Hsu, Shang-Te Danny

    2015-09-01

    Understanding the mechanism by which a polypeptide chain thread itself spontaneously to attain a knotted conformation has been a major challenge in the field of protein folding. HP0242 is a homodimeric protein from Helicobacter pylori with intertwined helices to form a unique pseudo-knotted folding topology. A tandem HP0242 repeat has been constructed to become the first engineered trefoil-knotted protein. Its small size renders it a model system for computational analyses to examine its folding and knotting pathways. Here we report a multi-parametric study on the folding stability and kinetics of a library of HP0242 variants, including the trefoil-knotted tandem HP0242 repeat, using far-UV circular dichroism and fluorescence spectroscopy. Equilibrium chemical denaturation of HP0242 variants shows the presence of highly populated dimeric and structurally heterogeneous folding intermediates. Such equilibrium folding intermediates retain significant amount of helical structures except those at the N- and C-terminal regions in the native structure. Stopped-flow fluorescence measurements of HP0242 variants show that spontaneous refolding into knotted structures can be achieved within seconds, which is several orders of magnitude faster than previously observed for other knotted proteins. Nevertheless, the complex chevron plots indicate that HP0242 variants are prone to misfold into kinetic traps, leading to severely rolled-over refolding arms. The experimental observations are in general agreement with the previously reported molecular dynamics simulations. Based on our results, kinetic folding pathways are proposed to qualitatively describe the complex folding processes of HP0242 variants.

  4. Deformation of Fold-and-Thrust Belts above a Viscous Detachment: New Insights from Analogue Modelling Experiments

    NASA Astrophysics Data System (ADS)

    Nogueira, Carlos R.; Marques, Fernando O.

    2015-04-01

    Theoretical and experimental studies on fold-and-thrusts belts (FTB) have shown that, under Coulomb conditions, deformation of brittle thrust wedges above a dry frictional basal contact is characterized by dominant frontward vergent thrusts (forethrusts) with thrust spacing and taper angle being directly influenced by the basal strength (increase in basal strength leading to narrower thrust spacing and higher taper angles); whereas thrust wedges deformed above a weak viscous detachment, such as salt, show a more symmetric thrust style (no prevailing vergence of thrusting) with wider thrust spacing and shallower wedges. However, different deformation patterns can be found on this last group of thrust wedges both in nature and experimentally. Therefore we focused on the strength (friction) of the wedge basal contact, the basal detachment. We used a parallelepiped box with four fixed walls and one mobile that worked as a vertical piston drove by a computer controlled stepping motor. Fine dry sand was used as the analogue of brittle rocks and silicone putty (PDMS) with Newtonian behaviour as analogue of the weak viscous detachment. To investigate the strength of basal contact on thrust wedge deformation, two configurations were used: 1) a horizontal sand pack with a dry frictional basal contact; and 2) a horizontal sand pack above a horizontal PDMS layer, acting as a basal weak viscous contact. Results of the experiments show that: the model with a dry frictional basal detachment support the predictions for the Coulomb wedges, showing a narrow wedge with dominant frontward vergence of thrusting, close spacing between FTs and high taper angle. The model with a weak viscous frictional basal detachment show that: 1) forethrusts (FT) are dominant showing clearly an imbricate asymmetric geometry, with wider spaced thrusts than the dry frictional basal model; 2) after FT initiation, the movement on the thrust can last up to 15% model shortening, leading to great amount of

  5. The protein folding network

    NASA Astrophysics Data System (ADS)

    Rao, Francesco; Caflisch, Amedeo

    2004-03-01

    Networks are everywhere. The conformation space of a 20-residue antiparallel beta-sheet peptide [1], sampled by molecular dynamics simulations, is mapped to a network. Conformations are nodes of the network, and the transitions between them are links. As previously found for the World-Wide Web as well as for social and biological networks , the conformation space contains highly connected hubs like the native state which is the most populated free energy basin. Furthermore, the network shows a hierarchical modularity [2] which is consistent with the funnel mechanism of folding [3] and is not observed for a random heteropolymer lacking a native state. Here we show that the conformation space network describes the free energy landscape without requiring projections into arbitrarily chosen reaction coordinates. The network analysis provides a basis for understanding the heterogeneity of the folding transition state and the existence of multiple pathways. [1] P. Ferrara and A. Caflisch, Folding simulations of a three-stranded antiparallel beta-sheet peptide, PNAS 97, 10780-10785 (2000). [2] Ravasz, E. and Barabási, A. L. Hierarchical organization in complex networks. Phys. Rev. E 67, 026112 (2003). [3] Dill, K. and Chan, H From Levinthal to pathways to funnels. Nature Struct. Biol. 4, 10-19 (1997)

  6. Changes of protein stiffness during folding detect protein folding intermediates.

    PubMed

    Małek, Katarzyna E; Szoszkiewicz, Robert

    2014-01-01

    Single-molecule force-quench atomic force microscopy (FQ-AFM) is used to detect folding intermediates of a simple protein by detecting changes of molecular stiffness of the protein during its folding process. Those stiffness changes are obtained from shape and peaks of an autocorrelation of fluctuations in end-to-end length of the folding molecule. The results are supported by predictions of the equipartition theorem and agree with existing Langevin dynamics simulations of a simplified model of a protein folding. In the light of the Langevin simulations the experimental data probe an ensemble of random-coiled collapsed states of the protein, which are present both in the force-quench and thermal-quench folding pathways.

  7. 3D-model of complex km-scale fold structures using laserscanning images: The Achensee region, western Northern Calcareous Alps, Austria

    NASA Astrophysics Data System (ADS)

    Ortner, H.; Gruber, A.

    2012-04-01

    The Northern Calcareous Alps (NCA) are a fold-and-thrust belt built by Permomesozoic rocks. It was affected by Early Jurassic rifting prior to Late Creatceous stacking of thrust sheets. The inversion of Jurassic basins resulted in complex fold structures. One of the enigmatic areas is the Achensee region, where a major kilometric W-E trending anticline-syncline system (Montschein-anticline, Karwendel-syncline) is offset to the north east of lake Achensee (Guffert-anticline, Thiersee syncline). The anticlines and synclines west and east of the transfer zone are recumbent, but no thrust is visible. In the transfer zone, the axis of the anticline curves to a N-S orientation (Unnutz anticline), whereas the syncline evolves to a thrust with 5km offset in E-W cross section (Achental thrust) that superimposes Triassic on Cretaceous rocks. The 3D-model in this low-budget project was constructed to understand the kinematic evolution of the fold and thrust system. Input data were: (1) a tectonic map with a dense network of orientation data, (2) a map of the trace of bedding mapped from 1m resolution laserscanning images, (3) a DEM with approximately 30m resolution.(1) and (2) were prepared in a GIS system, and then imported into the Midland Valleys Move software. Our intention was to create a data-oriented model, to prevent any model-induced bias. Thrust planes were constructed using the intersection lines with the DEM. Bedding in folds was modelled by extruding the intersection lines with the DEM parallel to the fold axis. In both cases errors were introduced into the model as the DEM has not enough resolution. Orientation data are displayed as discs in 3D space. The 3D-model shows that the Achental thrust cuts progressively into deeper structural levels of the Unnutz anticline to the south, therefore the thrust dips shallower to the south than the fold axis. Therefore the Achental thrust superimposes pre-existing folds onto the footwall toward the north, as established

  8. From static to dynamic: The need for structural ensembles and a predictive model of RNA folding and function

    PubMed Central

    Herschlag, Daniel; Allred, Benjamin E.; Gowrishankar, Seshadri

    2015-01-01

    To understand RNA, it is necessary to move beyond a descriptive categorization towards quantitative predictions of its molecular conformations and functional behavior. An incisive approach to understanding the function and folding of biological RNA systems involves characterizing small, simple components that are largely responsible for the behavior of complex systems including helix-junction-helix elements and tertiary motifs. State-of-the-art methods have permitted unprecedented insight into the conformational ensembles of these elements revealing, for example, that conformations of helix-junction-helix elements are confined to a small region of the ensemble, that this region is highly dependent on the junction’s topology, and that the correct alignment of tertiary motifs may be a rare conformation on the overall folding landscape. Further characterization of RNA components and continued development of experimental and computational methods with the goal of quantitatively predicting RNA folding and functional behavior will be critical to understanding biological RNA systems. PMID:25744941

  9. Active folding and thrusting in North Africa: A framework for a seismotectonic model of the Atlas Mountains

    NASA Astrophysics Data System (ADS)

    Meghraoui, Mustapha; Maouche, Said; Timoulali, Youssef; Bouhadad, Youcef; Bouaziz, Samir

    2013-04-01

    Large earthquakes in the Atlas Mountains of North Africa are often generated on thrust or reverse faults. For inland faults, surface ruptures and long-term active tectonics appear as a thrust escarpment and fold-related faulting visible in the field and using remote sensing images, or measured using space-borne geodesy (GPS or INSAR). For coastal faults, major uplifts of late Quaternary marine terraces and folding with steplike morphology are exposed indicating the incremental development of coastal active deformation. We have investigated the similarities and differences between different active fault-related folding along the Africa - Eurasia convergent plate boundary. These active structures are seismogenic and the striking case studies are the 1960 Agadir (Mw 5.9), the 1954 Orleansville (Mw 6.7), the 1980 El Asnam (Mw 7.3), the 1992 Gafsa (Mw 5.3), the 1999 Ain Temouchent (Mw 6.0), and the 2003 Zemmouri (Mw 6.8) earthquakes. From paleoseismic investigations the El Asnam active fold shows 0.6 to 1.0 mm/yr uplift rate. West of Algiers on the Sahel anticline, the levelling of uplifted successive coastal benches and notches document the incremental folding uplift with ~ 0.84 - 1.2 mm/yr uplift rate in the last 120-140 ka. The relatively fast folding growth during late Pleistocene and Holocene in the Atlas Mountains attests for the significance of earthquake activity and the importance of convergent movements between Africa and Eurasia in the Western Mediterranean. This work is prepared in the framework of the UNESCO (SIDA) - IGCP Project 601 "Seismotectonics and Seismic Hazards in Africa".

  10. Kinematic 3-D Retro-Modeling of an Orogenic Bend in the South Limón Fold-and-Thrust Belt, Eastern Costa Rica: Prediction of the Incremental Internal Strain Distribution

    NASA Astrophysics Data System (ADS)

    Brandes, Christian; Tanner, David C.; Winsemann, Jutta

    2016-10-01

    The South Limón fold-and-thrust belt, in the back-arc area of southern Costa Rica, is characterized by a 90° curvature of the strike of the thrust planes and is therefore a natural laboratory for the analysis of curved orogens. The analysis of curved fold-and-thrust belts is a challenge because of the varying structural orientations within the belt. Based on seismic reflection lines, we created a 3-D subsurface model containing three major thrust faults and three stratigraphic horizons. 3-D kinematic retro-deformation modeling was carried out to analyze the spatial evolution of the fold-and-thrust belt. The maximum amount of displacement on each of the faults is (from hinterland to foreland); thrust 1: 800 m; thrust 2: 600 m; thrust 3: 250 m. The model was restored sequentially to its pre-deformational state. The strain history of the stratigraphic horizons in the model was calculated at every step. This shows that the internal strain pattern has an abrupt change at the orogenic bend. Contractional strain occurs in the forelimbs of the hanging-wall anticlines, while a zone of dilative strain spreads from the anticline crests to the backlimbs. The modeling shows that a NNE-directed transport direction best explains the structural evolution of the bend. This would require a left-lateral strike-slip zone in the North to compensate for the movement and thereby decoupling the South Limón fold-and-thrust belt from northern Costa Rica. Therefore, our modeling supports the presence of the Trans-Isthmic fault system, at least during the Plio-Pleistocene.

  11. Protein Aggregation/Folding: The Role of Deterministic Singularities of Sequence Hydrophobicity as Determined by Nonlinear Signal Analysis of Acylphosphatase and Aβ(1–40)

    PubMed Central

    Zbilut, Joseph P.; Colosimo, Alfredo; Conti, Filippo; Colafranceschi, Mauro; Manetti, Cesare; Valerio, MariaCristina; Webber, Charles L.; Giuliani, Alessandro

    2003-01-01

    The problem of protein folding vs. aggregation was investigated in acylphosphatase and the amyloid protein Aβ(1–40) by means of nonlinear signal analysis of their chain hydrophobicity. Numerical descriptors of recurrence patterns provided the basis for statistical evaluation of folding/aggregation distinctive features. Static and dynamic approaches were used to elucidate conditions coincident with folding vs. aggregation using comparisons with known protein secondary structure classifications, site-directed mutagenesis studies of acylphosphatase, and molecular dynamics simulations of amyloid protein, Aβ(1–40). The results suggest that a feature derived from principal component space characterized by the smoothness of singular, deterministic hydrophobicity patches plays a significant role in the conditions governing protein aggregation. PMID:14645049

  12. A Hamiltonian Replica Exchange Molecular Dynamics (MD) Method for the Study of Folding, Based on the Analysis of the Stabilization Determinants of Proteins

    PubMed Central

    Meli, Massimiliano; Colombo, Giorgio

    2013-01-01

    Herein, we present a novel Hamiltonian replica exchange protocol for classical molecular dynamics simulations of protein folding/unfolding. The scheme starts from the analysis of the energy-networks responsible for the stabilization of the folded conformation, by means of the energy-decomposition approach. In this framework, the compact energetic map of the native state is generated by a preliminary short molecular dynamics (MD) simulation of the protein in explicit solvent. This map is simplified by means of an eigenvalue decomposition. The highest components of the eigenvector associated with the lowest eigenvalue indicate which sites, named “hot spots”, are likely to be responsible for the stability and correct folding of the protein. In the Hamiltonian replica exchange protocol, we use modified force-field parameters to treat the interparticle non-bonded potentials of the hot spots within the protein and between protein and solvent atoms, leaving unperturbed those relative to all other residues, as well as solvent-solvent interactions. We show that it is possible to reversibly simulate the folding/unfolding behavior of two test proteins, namely Villin HeadPiece HP35 (35 residues) and Protein A (62 residues), using a limited number of replicas. We next discuss possible implications for the study of folding mechanisms via all atom simulations. PMID:23743827

  13. Pseudoknots in RNA folding landscapes

    PubMed Central

    Kucharík, Marcel; Hofacker, Ivo L.; Stadler, Peter F.; Qin, Jing

    2016-01-01

    Motivation: The function of an RNA molecule is not only linked to its native structure, which is usually taken to be the ground state of its folding landscape, but also in many cases crucially depends on the details of the folding pathways such as stable folding intermediates or the timing of the folding process itself. To model and understand these processes, it is necessary to go beyond ground state structures. The study of rugged RNA folding landscapes holds the key to answer these questions. Efficient coarse-graining methods are required to reduce the intractably vast energy landscapes into condensed representations such as barrier trees or basin hopping graphs (BHG) that convey an approximate but comprehensive picture of the folding kinetics. So far, exact and heuristic coarse-graining methods have been mostly restricted to the pseudoknot-free secondary structures. Pseudoknots, which are common motifs and have been repeatedly hypothesized to play an important role in guiding folding trajectories, were usually excluded. Results: We generalize the BHG framework to include pseudoknotted RNA structures and systematically study the differences in predicted folding behavior depending on whether pseudoknotted structures are allowed to occur as folding intermediates or not. We observe that RNAs with pseudoknotted ground state structures tend to have more pseudoknotted folding intermediates than RNAs with pseudoknot-free ground state structures. The occurrence and influence of pseudoknotted intermediates on the folding pathway, however, appear to depend very strongly on the individual RNAs so that no general rule can be inferred. Availability and implementation: The algorithms described here are implemented in C++ as standalone programs. Its source code and Supplemental material can be freely downloaded from http://www.tbi.univie.ac.at/bhg.html. Contact: qin@bioinf.uni-leipzig.de Supplementary information: Supplementary data are available at Bioinformatics online. PMID

  14. How do chaperonins fold protein?

    PubMed Central

    Motojima, Fumihiro

    2015-01-01

    Protein folding is a biological process that is essential for the proper functioning of proteins in all living organisms. In cells, many proteins require the assistance of molecular chaperones for their folding. Chaperonins belong to a class of molecular chaperones that have been extensively studied. However, the mechanism by which a chaperonin mediates the folding of proteins is still controversial. Denatured proteins are folded in the closed chaperonin cage, leading to the assumption that denatured proteins are completely encapsulated inside the chaperonin cage. In contrast to the assumption, we recently found that denatured protein interacts with hydrophobic residues at the subunit interfaces of the chaperonin, and partially protrude out of the cage. In this review, we will explain our recent results and introduce our model for the mechanism by which chaperonins accelerate protein folding, in view of recent findings. PMID:27493521

  15. Bilayered graphene/h-BN with folded holes as new nanoelectronic materials: modeling of structures and electronic properties

    NASA Astrophysics Data System (ADS)

    Chernozatonskii, Leonid A.; Demin сtor A., Vi; Bellucci, Stefano

    2016-11-01

    The latest achievements in 2-dimensional (2D) material research have shown the perspective use of sandwich structures in nanodevices. We demonstrate the following generation of bilayer materials for electronics and optoelectronics. The atomic structures, the stability and electronic properties of Moiré graphene (G)/h-BN bilayers with folded nanoholes have been investigated theoretically by ab-initio DFT method. These perforated bilayers with folded hole edges may present electronic properties different from the properties of both graphene and monolayer nanomesh structures. The closing of the edges is realized by C-B(N) bonds that form after folding the borders of the holes. Stable ≪round≫ and ≪triangle≫ holes organization are studied and compared with similar hole forms in single layer graphene. The electronic band structures of the considered G/BN nanomeshes reveal semiconducting or metallic characteristics depending on the sizes and edge terminations of the created holes. This investigation of the new types of G/BN nanostructures with folded edges might provide a directional guide for the future of this emerging area.

  16. Bilayered graphene/h-BN with folded holes as new nanoelectronic materials: modeling of structures and electronic properties

    PubMed Central

    Chernozatonskii, Leonid A.; Demin, Viсtor A.; Bellucci, Stefano

    2016-01-01

    The latest achievements in 2-dimensional (2D) material research have shown the perspective use of sandwich structures in nanodevices. We demonstrate the following generation of bilayer materials for electronics and optoelectronics. The atomic structures, the stability and electronic properties of Moiré graphene (G)/h-BN bilayers with folded nanoholes have been investigated theoretically by ab-initio DFT method. These perforated bilayers with folded hole edges may present electronic properties different from the properties of both graphene and monolayer nanomesh structures. The closing of the edges is realized by C-B(N) bonds that form after folding the borders of the holes. Stable ≪round≫ and ≪triangle≫ holes organization are studied and compared with similar hole forms in single layer graphene. The electronic band structures of the considered G/BN nanomeshes reveal semiconducting or metallic characteristics depending on the sizes and edge terminations of the created holes. This investigation of the new types of G/BN nanostructures with folded edges might provide a directional guide for the future of this emerging area. PMID:27897237

  17. Enhanced protein folding by removal of kinetic traps

    NASA Astrophysics Data System (ADS)

    Liu, Yanxin; Chapagain, Prem; Parra, Jose; Gerstman, Bernard

    2007-03-01

    The presence of non-native kinetic traps along the free energy landscape of a protein may significantly lengthen the overall folding time so that the folding process becomes unreliable. We used a computational 3-D lattice model to investigate the free energy landscape of a model alpha helical hairpin peptide. We used two slightly different sequences and show that strategic substitutions of only a few amino acid residues greatly enhance the folding process. These strategic substitutions prevent the formation of long-lived misfolded configurations which not only lengthen the folding time but also may cause unwanted aggregation. Detailed kinetic and thermodynamic analysis was carried out for the folding of these two sequences and the results are consistent with the experimental and molecular dynamics simulations of small helical bundle proteins.

  18. 3D Reservoir Modeling of Semutang Gas Field: A lonely Gas field in Chittagong-Tripura Fold Belt, with Integrated Well Log, 2D Seismic Reflectivity and Attributes.

    NASA Astrophysics Data System (ADS)

    Salehin, Z.; Woobaidullah, A. S. M.; Snigdha, S. S.

    2015-12-01

    Bengal Basin with its prolific gas rich province provides needed energy to Bangladesh. Present energy situation demands more Hydrocarbon explorations. Only 'Semutang' is discovered in the high amplitude structures, where rest of are in the gentle to moderate structures of western part of Chittagong-Tripura Fold Belt. But it has some major thrust faults which have strongly breached the reservoir zone. The major objectives of this research are interpretation of gas horizons and faults, then to perform velocity model, structural and property modeling to obtain reservoir properties. It is needed to properly identify the faults and reservoir heterogeneities. 3D modeling is widely used to reveal the subsurface structure in faulted zone where planning and development drilling is major challenge. Thirteen 2D seismic and six well logs have been used to identify six gas bearing horizons and a network of faults and to map the structure at reservoir level. Variance attributes were used to identify faults. Velocity model is performed for domain conversion. Synthetics were prepared from two wells where sonic and density logs are available. Well to seismic tie at reservoir zone shows good match with Direct Hydrocarbon Indicator on seismic section. Vsh, porosity, water saturation and permeability have been calculated and various cross plots among porosity logs have been shown. Structural modeling is used to make zone and layering accordance with minimum sand thickness. Fault model shows the possible fault network, those liable for several dry wells. Facies model have been constrained with Sequential Indicator Simulation method to show the facies distribution along the depth surfaces. Petrophysical models have been prepared with Sequential Gaussian Simulation to estimate petrophysical parameters away from the existing wells to other parts of the field and to observe heterogeneities in reservoir. Average porosity map for each gas zone were constructed. The outcomes of the research

  19. Timing analysis by model checking

    NASA Technical Reports Server (NTRS)

    Naydich, Dimitri; Guaspari, David

    2000-01-01

    The safety of modern avionics relies on high integrity software that can be verified to meet hard real-time requirements. The limits of verification technology therefore determine acceptable engineering practice. To simplify verification problems, safety-critical systems are commonly implemented under the severe constraints of a cyclic executive, which make design an expensive trial-and-error process highly intolerant of change. Important advances in analysis techniques, such as rate monotonic analysis (RMA), have provided a theoretical and practical basis for easing these onerous restrictions. But RMA and its kindred have two limitations: they apply only to verifying the requirement of schedulability (that tasks meet their deadlines) and they cannot be applied to many common programming paradigms. We address both these limitations by applying model checking, a technique with successful industrial applications in hardware design. Model checking algorithms analyze finite state machines, either by explicit state enumeration or by symbolic manipulation. Since quantitative timing properties involve a potentially unbounded state variable (a clock), our first problem is to construct a finite approximation that is conservative for the properties being analyzed-if the approximation satisfies the properties of interest, so does the infinite model. To reduce the potential for state space explosion we must further optimize this finite model. Experiments with some simple optimizations have yielded a hundred-fold efficiency improvement over published techniques.

  20. Folding mechanism of a multiple independently-folding domain protein: double B domain of protein A.

    PubMed

    Arora, Pooja; Hammes, Gordon G; Oas, Terrence G

    2006-10-10

    The antibody binding properties of staphylococcal protein A (SpA) can be attributed to the presence of five highly homologous domains (E, D, A, B, and C). Although the folding of the B domain of protein A (BdpA) is well-characterized, the folding behavior of this domain in the context of full-length SpA in the cell remains unexplored. The sequence of the B domain is 89 and 91% identical to those of domains A and C, respectively. We have fused B domain sequences (BBdpA) as a close approximation of the A-B or B-C portion of SpA. Circular dichroism and fluorescence-detected denaturation curves of BBdpA are experimentally indistinguishable from those of BdpA. The rate constants for folding and unfolding from NMR line shape analysis for the single- and double-domain proteins are the same within experimental uncertainties (+/-20%). These results support the designation of SpA as a multiple independently-folding domain (MIFD) protein. We develop a mathematical model that describes the folding thermodynamics and kinetics of MIFD proteins. The model depicts MIFD protein folding and unfolding as a parallel network and explicitly calculates the flux through all parallel pathways. These fluxes are combined to give a complete description of the global thermodynamics and kinetics of the folding and unfolding of MIFD proteins. The global rates for complete folding and unfolding of a MIFD protein and those of the individual domains depend on the stability of the protein. We show that the global unfolding rate of a MIFD protein may be many orders of magnitude slower than that of the constituent domains.

  1. Efficient molecular mechanics simulations of the folding, orientation, and assembly of peptides in lipid bilayers using an implicit atomic solvation model

    NASA Astrophysics Data System (ADS)

    Bordner, Andrew J.; Zorman, Barry; Abagyan, Ruben

    2011-10-01

    Membrane proteins comprise a significant fraction of the proteomes of sequenced organisms and are the targets of approximately half of marketed drugs. However, in spite of their prevalence and biomedical importance, relatively few experimental structures are available due to technical challenges. Computational simulations can potentially address this deficit by providing structural models of membrane proteins. Solvation within the spatially heterogeneous membrane/solvent environment provides a major component of the energetics driving protein folding and association within the membrane. We have developed an implicit solvation model for membranes that is both computationally efficient and accurate enough to enable molecular mechanics predictions for the folding and association of peptides within the membrane. We derived the new atomic solvation model parameters using an unbiased fitting procedure to experimental data and have applied it to diverse problems in order to test its accuracy and to gain insight into membrane protein folding. First, we predicted the positions and orientations of peptides and complexes within the lipid bilayer and compared the simulation results with solid-state NMR structures. Additionally, we performed folding simulations for a series of host-guest peptides with varying propensities to form alpha helices in a hydrophobic environment and compared the structures with experimental measurements. We were also able to successfully predict the structures of amphipathic peptides as well as the structures for dimeric complexes of short hexapeptides that have experimentally characterized propensities to form beta sheets within the membrane. Finally, we compared calculated relative transfer energies with data from experiments measuring the effects of mutations on the free energies of translocon-mediated insertion of proteins into lipid bilayers and of combined folding and membrane insertion of a beta barrel protein.

  2. Three-dimensional analysis of potential vorticity associated with tropopause folds and observed variations of ozone and carbon monoxide

    NASA Technical Reports Server (NTRS)

    Danielsen, Edwin F.; Hipskind, R. Stephen; Gaines, Steven E.; Sachse, Glen W.; Gregory, Gerald L.; Hill, G. F.

    1987-01-01

    The usability and reliability of potential vorticity as a meteorological stratospheric tracer are evaluated. The concept of potential vorticity conservation during transport in which stratospheric and tropospheric air are mixing is tested. Aircraft data collected on April 20, 1984 in the western and southwestern U.S. are analyzed in order to derive potential vorticity data; vertical cross sections of constant-pressure data and temperature and wind speed gradients are examined. The tropopause fold observed during the April 20, 1984 aircraft flights is described. The potential vorticity, ozone mixing ratio, and carbon monoxide mixing ratio are compared; a positive correlation between potential vorticity and the ozone mixing ratio and a negative correlation between the potential vorticity and the carbon monoxide mixing ratio are detected. The data support the concepts of the conservation of potential vorticity, the entrainment and mixing of tropospheric air across the boundaries of the fold, and the applicability of potential vorticity as a stratospheric tracer.

  3. How Does Your Protein Fold? Elucidating the Apomyoglobin Folding Pathway.

    PubMed

    Dyson, H Jane; Wright, Peter E

    2017-01-17

    conformational ensembles formed in the presence of denaturing agents and low pH can be characterized as models for the unfolded states of the protein. Newer NMR techniques such as measurement of residual dipolar couplings in the various partly folded states, and relaxation dispersion measurements to probe invisible states present at low concentrations, have contributed to providing a detailed picture of the apomyoglobin folding pathway. The research summarized in this Account was aimed at characterizing and comparing the equilibrium and kinetic intermediates both structurally and dynamically, as well as delineating the complete folding pathway at a residue-specific level, in order to answer the question: "What is it about the amino acid sequence that causes each molecule in the unfolded protein ensemble to start folding, and, once started, to proceed towards the formation of the correctly folded three-dimensional structure?"

  4. Understanding complex structures in fold-and-thrust belts. Integration of geometric and growth strata analyses, paleomagnetism, AMS and analogue models in the Western termination of the Southern Pyrenees

    NASA Astrophysics Data System (ADS)

    Pueyo, Emilio L.; Sánchez, Elisa; Oliva-Urcia, Belén; José Ramón, Ma

    2014-05-01

    Classic 2D approaches have helped the understanding of the geometry and kinematics of fold-and-thrust belts belts (FAT belts) but are insufficient to unravel many natural cases. This is because deformation is 3D from the geometric point of view and, thus, cylindrical features may be considered as a simplification. On the other hand, deformation kinematics is usually complex, diachronic and poliphasic in real cases. Therefore, FAT belts have to be always considered in 4D. In this sense, the Southern Pyrenees is a perfect location to study the evolution of FAT belts because of the exceptional outcropping conditions of growth strata, the proven diachronic kinematics and the non-coaxial interference of deformation events. Within the vast catalogue of complex structures that includes superposed folding, conical and plunging folds, oblique thrust ramps, etc here, we have selected the westernmost termination of the South Pyrenean sole thrust to illustrate how the integration of geometric and kinematic analysis can help unraveling complex structures in FAT belts. The San Marzal pericline (4 km2 surface extension) is the lateral termination of the Sto. Domingo deca-kilometric fold. San Marzal looks like a large 70° plunging cylindrical structure. However the large magnitude (≡ 60-70°) of vertical axis rotations accommodated between its flanks cannot be explained without a conical geometry. In this work we will show how the structural analysis performed on this structure has disentangled its complex geometry. This analyses comprises several hundreds of bedding data, joints and veins and more than 150 standard paleomagnetic and AMS sites. Besides, we will show how the kinematic information derived from magnetostratigraphic sections (more than 8 km of sampled profiles) has helped to constraint the folding and rotation ages and velocities. Finally, all these complex geometric and kinematic features have inspired us to build an analogue model where we can explore the 3D

  5. Tectonic evolution of the Lachlan Fold Belt, southeastern Australia: constraints from coupled numerical models of crustal deformation and surface erosion driven by subduction of the underlying mantle

    NASA Astrophysics Data System (ADS)

    Braun, Jean; Pauselli, Cristina

    2004-04-01

    We have used a coupled thermo-mechanical finite-element (FE) model of crustal deformation driven by mantle/oceanic subduction to demonstrate that the tectonic evolution of the Lachlan Fold Belt (LFB) during the Mid-Palaeozoic (Late Ordovician to Early Carboniferous) can be linked to continuous subduction along a single subduction zone. This contrasts with most models proposed to date which assume that separate subduction zones were active beneath the western, central and eastern sections of the Lachlan Orogen. We demonstrate how the existing data on the structural, volcanic and erosional evolution of the Lachlan Fold Belt can be accounted for by our model. We focus particularly on the timing of fault movement in the various sectors of the orogen. We demonstrate that the presence of the weak basal decollement on which most of the Lachlan Fold Belt is constructed effectively decouples crustal structures from those in the underlying mantle. The patterns of faulting in the upper crust appears therefore to be controlled by lateral strength contrasts inherited from previous orogenic events rather than the location of one or several subduction zones. The model also predicts that the uplift and deep exhumation of the Wagga-Omeo Metamorphic Belt (WOMB) is associated with the advection of this terrane above the subduction point and is the only tectonic event that gives us direct constraints on the location of the subduction zone. We also discuss the implications of our model for the nature of the basement underlying the present-day orogen.

  6. An FFT-based method for modeling protein folding and binding under crowding: benchmarking on ellipsoidal and all-atom crowders

    PubMed Central

    Qin, Sanbo; Zhou, Huan-Xiang

    2013-01-01

    It is now well recognized that macromolecular crowding can exert significant effects on protein folding and binding stability. In order to calculate such effects in direct simulations of proteins mixed with bystander macromolecules, the latter (referred to as crowders) are usually modeled as spheres and the proteins represented at a coarse-grained level. Our recently developed postprocessing approach allows the proteins to be represented at the all-atom level but, for computational efficiency, has only been implemented for spherical crowders. Modeling crowder molecules in cellular environments and in vitro experiments as spheres may distort their effects on protein stability. Here we present a new method that is capable for treating aspherical crowders. The idea, borrowed from protein-protein docking, is to calculate the excess chemical potential of the proteins in crowded solution by fast Fourier transform (FFT). As the first application, we studied the effects of ellipsoidal crowders on the folding and binding free energies of all-atom proteins, and found, in agreement with previous direct simulations with coarse-grained protein models, that the aspherical crowders exert greater stabilization effects than spherical crowders of the same volume. Moreover, as demonstrated here, the FFT-based method has the important property that its computational cost does not increase strongly even when the level of details in representing the crowders is increased all the way to all-atom, thus significantly accelerating realistic modeling of protein folding and binding in cell-like environments. PMID:24187527

  7. An FFT-based method for modeling protein folding and binding under crowding: benchmarking on ellipsoidal and all-atom crowders.

    PubMed

    Qin, Sanbo; Zhou, Huan-Xiang

    2013-10-01

    It is now well recognized that macromolecular crowding can exert significant effects on protein folding and binding stability. In order to calculate such effects in direct simulations of proteins mixed with bystander macromolecules, the latter (referred to as crowders) are usually modeled as spheres and the proteins represented at a coarse-grained level. Our recently developed postprocessing approach allows the proteins to be represented at the all-atom level but, for computational efficiency, has only been implemented for spherical crowders. Modeling crowder molecules in cellular environments and in vitro experiments as spheres may distort their effects on protein stability. Here we present a new method that is capable for treating aspherical crowders. The idea, borrowed from protein-protein docking, is to calculate the excess chemical potential of the proteins in crowded solution by fast Fourier transform (FFT). As the first application, we studied the effects of ellipsoidal crowders on the folding and binding free energies of all-atom proteins, and found, in agreement with previous direct simulations with coarse-grained protein models, that the aspherical crowders exert greater stabilization effects than spherical crowders of the same volume. Moreover, as demonstrated here, the FFT-based method has the important property that its computational cost does not increase strongly even when the level of details in representing the crowders is increased all the way to all-atom, thus significantly accelerating realistic modeling of protein folding and binding in cell-like environments.

  8. Kinematics and thermodynamics of a folding heteropolymer.

    PubMed Central

    Fukugita, M; Lancaster, D; Mitchard, M G

    1993-01-01

    In order to elucidate the folding dynamics of protein, we have carried out numerical simulations of a heteropolymer model of self-interacting random chains. We find that folding propensity depends strongly on sequence and that both folding and nonfolding sequences exist. Furthermore we show that folding is a two-step process: the transition from coil state to unique folded state takes place through a globule phase. In addition to the continuous coil-globule transition, there exists an abrupt transition that separates the unique folded state from the globule state and ensures the stability of the native state. PMID:8327518

  9. Improving protein fold recognition by random forest

    PubMed Central

    2014-01-01

    Background Recognizing the correct structural fold among known template protein structures for a target protein (i.e. fold recognition) is essential for template-based protein structure modeling. Since the fold recognition problem can be defined as a binary classification problem of predicting whether or not the unknown fold of a target protein is similar to an already known template protein structure in a library, machine learning methods have been effectively applied to tackle this problem. In our work, we developed RF-Fold that uses random forest - one of the most powerful and scalable machine learning classification methods - to recognize protein folds. Results RF-Fold consists of hundreds of decision trees that can be trained efficiently on very large datasets to make accurate predictions on a highly imbalanced dataset. We evaluated RF-Fold on the standard Lindahl's benchmark dataset comprised of 976 × 975 target-template protein pairs through cross-validation. Compared with 17 different fold recognition methods, the performance of RF-Fold is generally comparable to the best performance in fold recognition of different difficulty ranging from the easiest family level, the medium-hard superfamily level, and to the hardest fold level. Based on the top-one template protein ranked by RF-Fold, the correct recognition rate is 84.5%, 63.4%, and 40.8% at family, superfamily, and fold levels, respectively. Based on the top-five template protein folds ranked by RF-Fold, the correct recognition rate increases to 91.5%, 79.3% and 58.3% at family, superfamily, and fold levels. Conclusions The good performance achieved by the RF-Fold demonstrates the random forest's effectiveness for protein fold recognition. PMID:25350499

  10. PREFACE Protein folding: lessons learned and new frontiers Protein folding: lessons learned and new frontiers

    NASA Astrophysics Data System (ADS)

    Pappu, Rohit V.; Nussinov, Ruth

    2009-03-01

    In appropriate physiological milieux proteins spontaneously fold into their functional three-dimensional structures. The amino acid sequences of functional proteins contain all the information necessary to specify the folds. This remarkable observation has spawned research aimed at answering two major questions. (1) Of all the conceivable structures that a protein can adopt, why is the ensemble of native-like structures the most favorable? (2) What are the paths by which proteins manage to robustly and reproducibly fold into their native structures? Anfinsen's thermodynamic hypothesis has guided the pursuit of answers to the first question whereas Levinthal's paradox has influenced the development of models for protein folding dynamics. Decades of work have led to significant advances in the folding problem. Mean-field models have been developed to capture our current, coarse grain understanding of the driving forces for protein folding. These models are being used to predict three-dimensional protein structures from sequence and stability profiles as a function of thermodynamic and chemical perturbations. Impressive strides have also been made in the field of protein design, also known as the inverse folding problem, thereby testing our understanding of the determinants of the fold specificities of different sequences. Early work on protein folding pathways focused on the specific sequence of events that could lead to a simplification of the search process. However, unifying principles proved to be elusive. Proteins that show reversible two-state folding-unfolding transitions turned out to be a gift of natural selection. Focusing on these simple systems helped researchers to uncover general principles regarding the origins of cooperativity in protein folding thermodynamics and kinetics. On the theoretical front, concepts borrowed from polymer physics and the physics of spin glasses led to the development of a framework based on energy landscape theories. These

  11. Approach to the unfolding and folding dynamics of add A-riboswitch upon adenine dissociation using a coarse-grained elastic network model.

    PubMed

    Li, Chunhua; Lv, Dashuai; Zhang, Lei; Yang, Feng; Wang, Cunxin; Su, Jiguo; Zhang, Yang

    2016-07-07

    Riboswitches are noncoding mRNA segments that can regulate the gene expression via altering their structures in response to specific metabolite binding. We proposed a coarse-grained Gaussian network model (GNM) to examine the unfolding and folding dynamics of adenosine deaminase (add) A-riboswitch upon the adenine dissociation, in which the RNA is modeled by a nucleotide chain with interaction networks formed by connecting adjoining atomic contacts. It was shown that the adenine binding is critical to the folding of the add A-riboswitch while the removal of the ligand can result in drastic increase of the thermodynamic fluctuations especially in the junction regions between helix domains. Under the assumption that the native contacts with the highest thermodynamic fluctuations break first, the iterative GNM simulations showed that the unfolding process of the adenine-free add A-riboswitch starts with the denature of the terminal helix stem, followed by the loops and junctions involving ligand binding pocket, and then the central helix domains. Despite the simplified coarse-grained modeling, the unfolding dynamics and pathways are shown in close agreement with the results from atomic-level MD simulations and the NMR and single-molecule force spectroscopy experiments. Overall, the study demonstrates a new avenue to investigate the binding and folding dynamics of add A-riboswitch molecule which can be readily extended for other RNA molecules.

  12. Approach to the unfolding and folding dynamics of add A-riboswitch upon adenine dissociation using a coarse-grained elastic network model

    NASA Astrophysics Data System (ADS)

    Li, Chunhua; Lv, Dashuai; Zhang, Lei; Yang, Feng; Wang, Cunxin; Su, Jiguo; Zhang, Yang

    2016-07-01

    Riboswitches are noncoding mRNA segments that can regulate the gene expression via altering their structures in response to specific metabolite binding. We proposed a coarse-grained Gaussian network model (GNM) to examine the unfolding and folding dynamics of adenosine deaminase (add) A-riboswitch upon the adenine dissociation, in which the RNA is modeled by a nucleotide chain with interaction networks formed by connecting adjoining atomic contacts. It was shown that the adenine binding is critical to the folding of the add A-riboswitch while the removal of the ligand can result in drastic increase of the thermodynamic fluctuations especially in the junction regions between helix domains. Under the assumption that the native contacts with the highest thermodynamic fluctuations break first, the iterative GNM simulations showed that the unfolding process of the adenine-free add A-riboswitch starts with the denature of the terminal helix stem, followed by the loops and junctions involving ligand binding pocket, and then the central helix domains. Despite the simplified coarse-grained modeling, the unfolding dynamics and pathways are shown in close agreement with the results from atomic-level MD simulations and the NMR and single-molecule force spectroscopy experiments. Overall, the study demonstrates a new avenue to investigate the binding and folding dynamics of add A-riboswitch molecule which can be readily extended for other RNA molecules.

  13. Petroleum generation and migration in the Mesopotamian Basin and Zagros fold belt of Iraq: Results from a basin-modeling study

    USGS Publications Warehouse

    Pitman, J.K.; Steinshouer, D.; Lewan, M.D.

    2004-01-01

    A regional 3-D total petroleum-system model was developed to evaluate petroleum generation and migration histories in the Mesopotamian Basin and Zagros fold belt in Iraq. The modeling was undertaken in conjunction with Middle East petroleum assessment studies conducted by the USGS. Regional structure maps, isopach and facies maps, and thermal maturity data were used as input to the model. The oil-generation potential of Jurassic source-rocks, the principal known source of the petroleum in Jurassic, Cretaceous, and Tertiary reservoirs in these regions, was modeled using hydrous pyrolysis (Type II-S) kerogen kinetics. Results showed that oil generation in source rocks commenced in the Late Cretaceous in intrashelf basins, peak expulsion took place in the late Miocene and Pliocene when these depocenters had expanded along the Zagros foredeep trend, and generation ended in the Holocene when deposition in the foredeep ceased. The model indicates that, at present, the majority of Jurassic source rocks in Iraq have reached or exceeded peak oil generation and most rocks have completed oil generation and expulsion. Flow-path simulations demonstrate that virtually all oil and gas fields in the Mesopotamian Basin and Zagros fold belt overlie mature Jurassic source rocks (vertical migration dominated) and are situated on, or close to, modeled migration pathways. Fields closest to modeled pathways associated with source rocks in local intrashelf basins were charged earliest from Late Cretaceous through the middle Miocene, and other fields filled later when compression-related traps were being formed. Model results confirm petroleum migration along major, northwest-trending folds and faults, and oil migration loss at the surface.

  14. Observation and analysis of in vivo vocal fold tissue instabilities produced by nonlinear source-filter coupling: a case study.

    PubMed

    Zañartu, Matías; Mehta, Daryush D; Ho, Julio C; Wodicka, George R; Hillman, Robert E

    2011-01-01

    Different source-related factors can lead to vocal fold instabilities and bifurcations referred to as voice breaks. Nonlinear coupling in phonation suggests that changes in acoustic loading can also be responsible for this unstable behavior. However, no in vivo visualization of tissue motion during these acoustically induced instabilities has been reported. Simultaneous recordings of laryngeal high-speed videoendoscopy, acoustics, aerodynamics, electroglottography, and neck skin acceleration are obtained from a participant consistently exhibiting voice breaks during pitch glide maneuvers. Results suggest that acoustically induced and source-induced instabilities can be distinguished at the tissue level. Differences in vibratory patterns are described through kymography and phonovibrography; measures of glottal area, open/speed quotient, and amplitude/phase asymmetry; and empirical orthogonal function decomposition. Acoustically induced tissue instabilities appear abruptly and exhibit irregular vocal fold motion after the bifurcation point, whereas source-induced ones show a smoother transition. These observations are also reflected in the acoustic and acceleration signals. Added aperiodicity is observed after the acoustically induced break, and harmonic changes appear prior to the bifurcation for the source-induced break. Both types of breaks appear to be subcritical bifurcations due to the presence of hysteresis and amplitude changes after the frequency jumps. These results are consistent with previous studies and the nonlinear source-filter coupling theory.

  15. Structural analysis of the synaptic protein neuroligin and its beta-neurexin complex: determinants for folding and cell adhesion.

    PubMed

    Fabrichny, Igor P; Leone, Philippe; Sulzenbacher, Gerlind; Comoletti, Davide; Miller, Meghan T; Taylor, Palmer; Bourne, Yves; Marchot, Pascale

    2007-12-20

    The neuroligins are postsynaptic cell adhesion proteins whose associations with presynaptic neurexins participate in synaptogenesis. Mutations in the neuroligin and neurexin genes appear to be associated with autism and mental retardation. The crystal structure of a neuroligin reveals features not found in its catalytically active relatives, such as the fully hydrophobic interface forming the functional neuroligin dimer; the conformations of surface loops surrounding the vestigial active center; the location of determinants that are critical for folding and processing; and the absence of a macromolecular dipole and presence of an electronegative, hydrophilic surface for neurexin binding. The structure of a beta-neurexin-neuroligin complex reveals the precise orientation of the bound neurexin and, despite a limited resolution, provides substantial information on the Ca2+-dependent interactions network involved in trans-synaptic neurexin-neuroligin association. These structures exemplify how an alpha/beta-hydrolase fold varies in surface topography to confer adhesion properties and provide templates for analyzing abnormal processing or recognition events associated with autism.

  16. Insights into function, catalytic mechanism, and fold evolution of selenoprotein methionine sulfoxide reductase B1 through structural analysis.

    PubMed

    Aachmann, Finn L; Sal, Lena S; Kim, Hwa-Young; Marino, Stefano M; Gladyshev, Vadim N; Dikiy, Alexander

    2010-10-22

    Methionine sulfoxide reductases protect cells by repairing oxidatively damaged methionine residues in proteins. Here, we report the first three-dimensional structure of the mammalian selenoprotein methionine sulfoxide reductase B1 (MsrB1), determined by high resolution NMR spectroscopy. Heteronuclear multidimensional spectra yielded NMR spectral assignments for the reduced form of MsrB1 in which catalytic selenocysteine (Sec) was replaced with cysteine (Cys). MsrB1 consists of a central structured core of two β-sheets and a highly flexible, disordered N-terminal region. Analysis of pH dependence of NMR signals of catalytically relevant residues, comparison with the data for bacterial MsrBs, and NMR-based structural analysis of methionine sulfoxide (substrate) and methionine sulfone (inhibitor) binding to MsrB1 at the atomic level reveal a mechanism involving catalytic Sec(95) and resolving Cys(4) residues in catalysis. The MsrB1 structure differs from the structures of Cys-containing MsrBs in the use of distal selenenylsulfide, residues needed for catalysis, and the mode in which the active form of the enzyme is regenerated. In addition, this is the first structure of a eukaryotic zinc-containing MsrB, which highlights the structural role of this metal ion bound to four conserved Cys. We integrated this information into a structural model of evolution of MsrB superfamily.

  17. Analogue modeling of the role of multi-level decollement layers on the geometry of orogenic wedge: an application to the Zagros Fold-Thrust Belt, SW Iran

    NASA Astrophysics Data System (ADS)

    Ghanadian, Mostafa; Faghih, Ali; Grasemann, Bernhard; Fard, Iraj Abdollahie; Maleki, Mehrdad

    2017-03-01

    The presence of evaporate and incompetent formations (i.e., decollement horizons) within the sedimentary sequence of fold-thrust belts can control their structural style and deformation evolution. In the present study, the influence of the decollement layers (e.g., basal and internal decollement layers) on the deformation style of several segments of the Zagros Fold-Thrust Belt (ZFTB), SW Iran (e.g., Fars Arc, Dezful Embayment, and Izeh Zone) was investigated using a series of analogue models of accretionary wedges. The study of seismic profiles to understand the structural evolution of these segments of the belt, where several decollement intervals acted as basal and internal decollements, is complemented by the analogue model results. The experimental results reveal that the thickness of the internal decollement layers influences the creation of fold-dominated or thrust-dominated deformations, respectively. Experimental models and seismic data highlight that incompetent layers act as barrier units against fault propagation (in-sequence and/or out-of-sequence faults) into overlying strata towards southwest by fore-deformation and control the rate of deformation propagation in the ZFTB. The presence of both the basal and internal decollement layers located at different stratigraphic levels is required to form disharmonic decollement folds in the foreland of the ZFTB. In addition, the geometry, spacing, activity, and propagation of faults as well as the topographic height of the critical wedges are directly controlled by low-frictional decollements (Geophys J Int, 165(1):336-356 2006; Geochem Geophys Geosyst, 14:1131-1155 2013). The seismic profiles of the ZFTB showed that in addition to lithological contrasts, the existence and activity of deep-seated and basement faults had a big impact on the structural styles of the region.

  18. Chevron folding patterns and heteroclinic orbits

    NASA Astrophysics Data System (ADS)

    Budd, Christopher J.; Chakhchoukh, Amine N.; Dodwell, Timothy J.; Kuske, Rachel

    2016-09-01

    We present a model of multilayer folding in which layers with bending stiffness EI are separated by a very stiff elastic medium of elasticity k2 and subject to a horizontal load P. By using a dynamical system analysis of the resulting fourth order equation, we show that as the end shortening per unit length E is increased, then if k2 is large there is a smooth transition from small amplitude sinusoidal solutions at moderate values of P to larger amplitude chevron folds, with straight limbs separated by regions of high curvature when P is large. The chevron solutions take the form of near heteroclinic connections in the phase-plane. By means of this analysis, values for P and the slope of the limbs are calculated in terms of E and k2.

  19. Folding of synthetic homogeneous glycoproteins in the presence of a glycoprotein folding sensor enzyme.

    PubMed

    Dedola, Simone; Izumi, Masayuki; Makimura, Yutaka; Seko, Akira; Kanamori, Akiko; Sakono, Masafumi; Ito, Yukishige; Kajihara, Yasuhiro

    2014-03-10

    UDP-glucose:glycoprotein glucosyltransferase (UGGT) plays a key role in recognizing folded and misfolded glycoproteins in the glycoprotein quality control system of the endoplasmic reticulum. UGGT detects misfolded glycoproteins and re-glucosylates them as a tag for misfolded glycoproteins. A flexible model to reproduce in vitro folding of a glycoprotein in the presence of UGGT in a mixture containing correctly folded, folding intermediates, and misfolded glycoproteins is described. The data demonstrates that UGGT can re-glucosylate all intermediates in the in vitro folding experiments, thus indicating that UGGT inspects not only final folded products, but also the glycoprotein folding intermediates.

  20. Size dependence of the folding of multiply charged sodium cationized polylactides revealed by ion mobility mass spectrometry and molecular modelling.

    PubMed

    De Winter, Julien; Lemaur, Vincent; Ballivian, Renaud; Chirot, Fabien; Coulembier, Olivier; Antoine, Rodolphe; Lemoine, Jérôme; Cornil, Jérôme; Dubois, Philippe; Dugourd, Philippe; Gerbaux, Pascal

    2011-08-22

    Ion mobility spectrometry coupled with mass spectrometry was used to experimentally determine the three-dimensional structure of multiply charged sodium cationized polylactides (PLA). In particular, the experiments were conducted to evaluate the influence of the charge state and the size on the gas-phase conformation of cationized PLA. The measured collision cross sections were then compared to calculated values obtained by computational chemistry methods. The most striking feature was the experimental and theoretical observation of a breaking point in the quasilinear relationship between the average collision cross sections and the number of monomer units for the triply charged cations. This breaking point was theoretically demonstrated, for the doubly and triply charged cations, to be associated with a significant folding of the polymer chains around the cationizing agents. The occurrence of such breaking points could be exploited to correlate the charge state of the most intense ion series observed upon electrospray ionization with the number-average molecular mass of a polymer.

  1. Further Development of the FFT-based Method for Atomistic Modeling of Protein Folding and Binding under Crowding: Optimization of Accuracy and Speed.

    PubMed

    Qin, Sanbo; Zhou, Huan-Xiang

    2014-07-08

    Recently, we (Qin, S.; Zhou, H. X. J. Chem. Theory Comput.2013, 9, 4633-4643) developed the FFT-based method for Modeling Atomistic Proteins-crowder interactions, henceforth FMAP. Given its potential wide use for calculating effects of crowding on protein folding and binding free energies, here we aimed to optimize the accuracy and speed of FMAP. FMAP is based on expressing protein-crowder interactions as correlation functions and evaluating the latter via fast Fourier transform (FFT). The numerical accuracy of FFT improves as the grid spacing for discretizing space is reduced, but at increasing computational cost. We sought to speed up FMAP calculations by using a relatively coarse grid spacing of 0.6 Å and then correcting for discretization errors. This strategy was tested for different types of interactions (hard-core repulsion, nonpolar attraction, and electrostatic interaction) and over a wide range of protein-crowder systems. We were able to correct for the numerical errors on hard-core repulsion and nonpolar attraction by an 8% inflation of atomic hard-core radii and on electrostatic interaction by a 5% inflation of the magnitudes of protein atomic charges. The corrected results have higher accuracy and enjoy a speedup of more than 100-fold over those obtained using a fine grid spacing of 0.15 Å. With this optimization of accuracy and speed, FMAP may become a practical tool for realistic modeling of protein folding and binding in cell-like environments.

  2. Numerical study of human vocal folds vibration using Immersed Finite Element Method

    NASA Astrophysics Data System (ADS)

    Wang, Xingshi; Zhang, Lucy; Krane, Michael

    2011-11-01

    The voice production procedure is a self-oscillating, fluid-structure interaction problem. In this study, the vocal folds vibration during phonation will be simulated by self-oscillated layered-structure vocal folds model, using Immersed Finite Element Method. With the numerical results, we will find out the vocal folds vibration pattern, and also show how the lung pressure, stiffness and geometry of vocal folds will affect the vocal folds vibration. With further analysis, we shall get better understanding of the dynamics of voice production. National Institute on Deafness and Other Communication Disorders.

  3. Elbow Synovial Fold Syndrome

    DTIC Science & Technology

    2007-12-01

    Density MR with arrows The clinical differential diagnosis of plica syndrome includes lateral epicondylitis (aka tennis elbow ), loose bodies... Elbow Synovial Fold Syndrome Radiology Corner Elbow Synovial Fold Syndrome Guarantor: CPT Amit Sanghi, USA, MC FS Contributors: CPT Amit...the case of a 17 year old female with elbow synovial fold syndrome (aka plica synovialis). The etiology is thought to be related to repetitive

  4. Targeting Fold Stiffness to Design Enhanced Origami Structures

    NASA Astrophysics Data System (ADS)

    Buskohl, Philip; Bazzan, Giorgio; Abbott, Andrew; Durstock, Michael; Vaia, Richard

    2014-03-01

    Structures with adaptive geometry are increasingly of interest for actuation, sensing and packaging applications. Origami structures, by definition, can ``shape-shift'' between multiple geometric configurations that are predefined by a pattern of folds. Plastic deformation and local failure at the fold lines transform an originally homogenous material into a grid with locally tailored mechanical properties that bias the response of the overall structure to external loading. Typically, origami structures focus on uniformly stiff fold lines with rigid facets. In this study, we discuss how localized variations in stiffness can influence global properties, including energy budget to transition from flat to folded structure, the preferred path through configuration space, and the final mechanical response of the folded architecture. A simple, bi-stable origami fold pattern is laser machined into polypropylene sheets of different compliance and the critical load of the transition is measured. We model the structure as a truss with bar elongation, folding, and facet bending in order to predict ways to enhance or mitigate the critical load. Targeting local folding properties to modify global performance directly extends to the analysis of more complex architectures.

  5. Fast protein folding kinetics

    PubMed Central

    Gelman, Hannah; Gruebele, Martin

    2014-01-01

    Fast folding proteins have been a major focus of computational and experimental study because they are accessible to both techniques: they are small and fast enough to be reasonably simulated with current computational power, but have dynamics slow enough to be observed with specially developed experimental techniques. This coupled study of fast folding proteins has provided insight into the mechanisms which allow some proteins to find their native conformation well less than 1 ms and has uncovered examples of theoretically predicted phenomena such as downhill folding. The study of fast folders also informs our understanding of even “slow” folding processes: fast folders are small, relatively simple protein domains and the principles that govern their folding also govern the folding of more complex systems. This review summarizes the major theoretical and experimental techniques used to study fast folding proteins and provides an overview of the major findings of fast folding research. Finally, we examine the themes that have emerged from studying fast folders and briefly summarize their application to protein folding in general as well as some work that is left to do. PMID:24641816

  6. A galaxy of folds

    PubMed Central

    Alva, Vikram; Remmert, Michael; Biegert, Andreas; Lupas, Andrei N; Söding, Johannes

    2010-01-01

    Many protein classification systems capture homologous relationships by grouping domains into families and superfamilies on the basis of sequence similarity. Superfamilies with similar 3D structures are further grouped into folds. In the absence of discernable sequence similarity, these structural similarities were long thought to have originated independently, by convergent evolution. However, the growth of databases and advances in sequence comparison methods have led to the discovery of many distant evolutionary relationships that transcend the boundaries of superfamilies and folds. To investigate the contributions of convergent versus divergent evolution in the origin of protein folds, we clustered representative domains of known structure by their sequence similarity, treating them as point masses in a virtual 2D space which attract or repel each other depending on their pairwise sequence similarities. As expected, families in the same superfamily form tight clusters. But often, superfamilies of the same fold are linked with each other, suggesting that the entire fold evolved from an ancient prototype. Strikingly, some links connect superfamilies with different folds. They arise from modular peptide fragments of between 20 and 40 residues that co-occur in the connected folds in disparate structural contexts. These may be descendants of an ancestral pool of peptide modules that evolved as cofactors in the RNA world and from which the first folded proteins arose by amplification and recombination. Our galaxy of folds summarizes, in a single image, most known and many yet undescribed homologous relationships between protein superfamilies, providing new insights into the evolution of protein domains. PMID:19937658

  7. A galaxy of folds.

    PubMed

    Alva, Vikram; Remmert, Michael; Biegert, Andreas; Lupas, Andrei N; Söding, Johannes

    2010-01-01

    Many protein classification systems capture homologous relationships by grouping domains into families and superfamilies on the basis of sequence similarity. Superfamilies with similar 3D structures are further grouped into folds. In the absence of discernable sequence similarity, these structural similarities were long thought to have originated independently, by convergent evolution. However, the growth of databases and advances in sequence comparison methods have led to the discovery of many distant evolutionary relationships that transcend the boundaries of superfamilies and folds. To investigate the contributions of convergent versus divergent evolution in the origin of protein folds, we clustered representative domains of known structure by their sequence similarity, treating them as point masses in a virtual 2D space which attract or repel each other depending on their pairwise sequence similarities. As expected, families in the same superfamily form tight clusters. But often, superfamilies of the same fold are linked with each other, suggesting that the entire fold evolved from an ancient prototype. Strikingly, some links connect superfamilies with different folds. They arise from modular peptide fragments of between 20 and 40 residues that co-occur in the connected folds in disparate structural contexts. These may be descendants of an ancestral pool of peptide modules that evolved as cofactors in the RNA world and from which the first folded proteins arose by amplification and recombination. Our galaxy of folds summarizes, in a single image, most known and many yet undescribed homologous relationships between protein superfamilies, providing new insights into the evolution of protein domains.

  8. Image Analysis and Modeling

    DTIC Science & Technology

    1976-03-01

    This report summarizes the results of the research program on Image Analysis and Modeling supported by the Defense Advanced Research Projects Agency...The objective is to achieve a better understanding of image structure and to use this knowledge to develop improved image models for use in image ... analysis and processing tasks such as information extraction, image enhancement and restoration, and coding. The ultimate objective of this research is

  9. KM+, a mannose-binding lectin from Artocarpus integrifolia: amino acid sequence, predicted tertiary structure, carbohydrate recognition, and analysis of the beta-prism fold.

    PubMed Central

    Rosa, J. C.; De Oliveira, P. S.; Garratt, R.; Beltramini, L.; Resing, K.; Roque-Barreira, M. C.; Greene, L. J.

    1999-01-01

    The complete amino acid sequence of the lectin KM+ from Artocarpus integrifolia (jackfruit), which contains 149 residues/mol, is reported and compared to those of other members of the Moraceae family, particularly that of jacalin, also from jackfruit, with which it shares 52% sequence identity. KM+ presents an acetyl-blocked N-terminus and is not posttranslationally modified by proteolytic cleavage as is the case for jacalin. Rather, it possesses a short, glycine-rich linker that unites the regions homologous to the alpha- and beta-chains of jacalin. The results of homology modeling implicate the linker sequence in sterically impeding rotation of the side chain of Asp141 within the binding site pocket. As a consequence, the aspartic acid is locked into a conformation adequate only for the recognition of equatorial hydroxyl groups on the C4 epimeric center (alpha-D-mannose, alpha-D-glucose, and their derivatives). In contrast, the internal cleavage of the jacalin chain permits free rotation of the homologous aspartic acid, rendering it capable of accepting hydrogen bonds from both possible hydroxyl configurations on C4. We suggest that, together with direct recognition of epimeric hydroxyls and the steric exclusion of disfavored ligands, conformational restriction of the lectin should be considered to be a new mechanism by which selectivity may be built into carbohydrate binding sites. Jacalin and KM+ adopt the beta-prism fold already observed in two unrelated protein families. Despite presenting little or no sequence similarity, an analysis of the beta-prism reveals a canonical feature repeatedly present in all such structures, which is based on six largely hydrophobic residues within a beta-hairpin containing two classic-type beta-bulges. We suggest the term beta-prism motif to describe this feature. PMID:10210179

  10. Analogue modeling of 3-D structural segmentation in fold-and-thrust belts: interactions between frictional and viscous provinces in foreland basins

    NASA Astrophysics Data System (ADS)

    Borderie, Sandra; Graveleau, Fabien; Witt, César; Vendeville, Bruno C.

    2016-04-01

    Accretionary wedges are generally segmented both across and along strike because of diverse factors including tectonic and stratigraphic inheritance. In fold-and-thrust belts, along-strike stratigraphic changes in the foreland sequence are classically observed and cause a curvature of the deformation front. Although the parameters controlling this curvature are well documented, the structural interactions and mutual influences between adjacent provinces are much less analyzed. To investigate this question, we deformed analogue models in a compressional box equipped with digital cameras and a topographic measurement apparatus. Models where shortened above a basal frictional detachment (glass microbeads) and segmentation was tested by having a region in which we added an interbedded viscous level (silicone polymer) within the sedimentary cover (dry sand). By changing the number (2 or 3) and the relative width of the purely frictional and viscous provinces, our goal was to characterize geometrically and kinematically the interactions between the viscous and the purely frictional provinces. We used a commercial geomodeller to generate 3-D geometrical models. The results indicate that regardless of the relative width of the purely frictional vs. viscous provinces, the deformation style in the frictional province is not influenced by the presence of the adjacent viscous province. On the contrary, the structural style and the deformation kinematics in the viscous province is significantly impacted by the presence or absence of an adjacent purely frictional province. At first order, the deformation style in the viscous province depends on its width, and three structural styles can be defined along strike. Far from the frictional area, structures are primarily of salt-massif type, and they do not seem to be influenced by the frictional wedge province. Towards the frictional province, deformation changes gradually to a zone of purely forethrusts (foreland verging), and

  11. From fold-related fracture population analysis to paleofluid flow reconstruction at basin-scale : a case study in the Bighorn Basin (Wyoming, USA)

    NASA Astrophysics Data System (ADS)

    Beaudoin, N.; Bellahsen, N.; Lacombe, O.; Emmanuel, L.; Pironon, J.

    2012-04-01

    While fluid flows associated with thin-skinned folded structures have been extensively studied, reconstructions of paleofluid systems associated with thick-skinned tectonics remain scarce. In addition, major thrusts are usually considered as the preferential channels for fluids: investigating the role of diffuse fracture sets as potential drains for fluids has received poor attention. In this work, we tentatively reconstruct the paleofluid system related to the Bighorn basin (Wyoming, USA), a Sevier-Laramide foreland basin affected by large basement uplifts during the Laramide thick-skinned tectonic event. Fracture pattern and related paleofluid flow were studied in selected folds within this basin. For this purpose, Oxygen, Carbon and Strontium isotopic studies were performed on host rocks as well as on pre-folding and on fold-related calcite veins; these studies were combined to fluid inclusion chemical and microthermometric analysis. The results suggest a strong control of fluid chemistry by the tectonic style: our work evidences migration of exotic hydrothermal fluids (temperatures of homogenisation of fluid inclusion reaching 140°C) in basement-cored, thrust-related folds, while in detachment folds, only intra-formational fluids were characterized.At the scale of the entire basin, the open paleofluid system reconstructed in basement-cored folds appears to be consistent, with oxygen isotopic signature ranging from -25‰ to -5‰ PDB. Indeed, the scattering of oxygen isotopic signatures in cemented veins shows different degree of mixing between local basinal fluids and exotic hydrothermal fluids remaining unequilibrated with surrounding limestones. Strontium isotopic analyses suggest that these exotic hydrothermal fluids are a mixing of meteoric fluids and basinal fluids that havemigrated in basement rocks, likely deeper than the basement/cover interface. The timing of the fast upward flow of these fluids through the cover is given by, and related to

  12. A sensitivity analysis of RNA folding nearest neighbor parameters identifies a subset of free energy parameters with the greatest impact on RNA secondary structure prediction.

    PubMed

    Zuber, Jeffrey; Sun, Hongying; Zhang, Xiaoju; McFadyen, Iain; Mathews, David H

    2017-03-15

    Nearest neighbor parameters for estimating the folding energy changes of RNA secondary structures are used in structure prediction and analysis. Despite their widespread application, a comprehensive analysis of the impact of each parameter on the precision of calculations had not been conducted. To identify the parameters with greatest impact, a sensitivity analysis was performed on the 291 parameters that compose the 2004 version of the free energy nearest neighbor rules. Perturbed parameter sets were generated by perturbing each parameter independently. Then the effect of each individual parameter change on predicted base-pair probabilities and secondary structures as compared to the standard parameter set was observed for a set of sequences including structured ncRNA, mRNA and randomized sequences. The results identify for the first time the parameters with the greatest impact on secondary structure prediction, and the subset which should be prioritized for further study in order to improve the precision of structure prediction. In particular, bulge loop initiation, multibranch loop initiation, AU/GU internal loop closure and AU/GU helix end parameters were particularly important. An analysis of parameter usage during folding free energy calculations of stochastic samples of secondary structures revealed a correlation between parameter usage and impact on structure prediction precision.

  13. Reciprocal insulation analysis of Hi-C data shows that TADs represent a functionally but not structurally privileged scale in the hierarchical folding of chromosomes.

    PubMed

    Zhan, Yinxiu; Mariani, Luca; Barozzi, Iros; Schulz, Edda G; Blüthgen, Nils; Stadler, Michael; Tiana, Guido; Giorgetti, Luca

    2017-03-01

    Understanding how regulatory sequences interact in the context of chromosomal architecture is a central challenge in biology. Chromosome conformation capture revealed that mammalian chromosomes possess a rich hierarchy of structural layers, from multi-megabase compartments to sub-megabase topologically associating domains (TADs) and sub-TAD contact domains. TADs appear to act as regulatory microenvironments by constraining and segregating regulatory interactions across discrete chromosomal regions. However, it is unclear whether other (or all) folding layers share similar properties, or rather TADs constitute a privileged folding scale with maximal impact on the organization of regulatory interactions. Here, we present a novel algorithm named CaTCH that identifies hierarchical trees of chromosomal domains in Hi-C maps, stratified through their reciprocal physical insulation, which is a single and biologically relevant parameter. By applying CaTCH to published Hi-C data sets, we show that previously reported folding layers appear at different insulation levels. We demonstrate that although no structurally privileged folding level exists, TADs emerge as a functionally privileged scale defined by maximal boundary enrichment in CTCF and maximal cell-type conservation. By measuring transcriptional output in embryonic stem cells and neural precursor cells, we show that the likelihood that genes in a domain are coregulated during differentiation is also maximized at the scale of TADs. Finally, we observe that regulatory sequences occur at genomic locations corresponding to optimized mutual interactions at the same scale. Our analysis suggests that the architectural functionality of TADs arises from the interplay between their ability to partition interactions and the specific genomic position of regulatory sequences.

  14. Radiation Fibrosis of the Vocal Fold: From Man to Mouse

    PubMed Central

    Johns, Michael M.; Kolachala, Vasantha; Berg, Eric; Muller, Susan; Creighton, Frances X.; Branski, Ryan C.

    2013-01-01

    Objectives To characterize fundamental late tissue effects in the human vocal fold following radiation therapy. To develop a murine model of radiation fibrosis to ultimately develop both treatment and prevention paradigms. Design Translational study using archived human and fresh murine irradiated vocal fold tissue. Methods 1) Irradiated vocal fold tissue from patients undergoing laryngectomy for loss of function from radiation fibrosis were identified from pathology archives. Histomorphometry, immunohistochemistry, and whole-genome microarray as well as real-time transcriptional analyses was performed. 2) Focused radiation to the head and neck was delivered to mice in a survival fashion. One month following radiation, vocal fold tissue was analyzed with histomorphometry, immunohistochemistry, and real-time PCR transcriptional analysis for selected markers of fibrosis. Results Human irradiated vocal folds demonstrated increased collagen transcription with increased deposition and disorganization of collagen in both the thyroarytenoid muscle and the superficial lamina propria. Fibronectin were increased in the superficial lamina propria. Laminin decreased in the thyroarytenoid muscle. Whole genome microarray analysis demonstrated increased transcription of markers for fibrosis, oxidative stress, inflammation, glycosaminoglycan production and apoptosis. Irradiated murine vocal folds demonstrated increases in collagen and fibronectin transcription and deposition in the lamina propria. Transforming growth factor (TGF)-β increased in the lamina propria. Conclusion Human irradiated vocal folds demonstrate molecular changes leading to fibrosis that underlie loss of vocal fold pliability that occurs in patients following laryngeal irradiation. Irradiated murine tissue demonstrates similar findings, and this mouse model may have utility in creating prevention and treatment strategies for vocal fold radiation fibrosis. PMID:23242839

  15. Pulse shape analysis of a two fold clover detector with an EMD based new algorithm: A comparison

    NASA Astrophysics Data System (ADS)

    Siwal, Davinder; Mandal, S.; Palit, R.; Sethi, J.; Garg, R.; Saha, S.; Prasad, Awadhesh; Chavan, P. B.; Naidu, B. S.; Jadhav, S.; Donthi, R.; Schaffner, H.; Adamczewski-Musch, J.; Kurz, N.; Wollersheim, H. J.; Singh, R.

    2014-03-01

    An investigation of Empirical Mode Decomposition (EMD) based noise filtering algorithm has been carried out on a mirror signal from a two fold germanium clover detector. EMD technique can decompose linear as well as nonlinear and chaotic signals with a precise frequency resolution. It allows to decompose the preamplifier signal (charge pulse) on an event-by-event basis. The filtering algorithm provides the information about the Intrinsic Mode Functions (IMFs) mainly dominated by the noise. It preserves the signal information and separates the overriding noise oscillations from the signals. The identification of noise structure is based on the frequency distributions of different IMFs. The preamplifier noise components which distort the azimuthal co-ordinates information have been extracted on the basis of the correlation between the different IMFs and the mirror signal. The correlation studies have been carried out both in frequency and time domain. The extracted correlation coefficient provides an important information regarding the pulse shape of the γ-ray interaction in the detector. A comparison between the EMD based and state-of-the-art wavelet based denoising techniques has also been made and discussed. It has been observed that the fractional noise strength distribution varies with the position of the collimated gamma-ray source. Above trend has been reproduced by both the denoising techniques.

  16. How the genome folds

    NASA Astrophysics Data System (ADS)

    Lieberman Aiden, Erez

    2012-02-01

    I describe Hi-C, a novel technology for probing the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. Working with collaborators at the Broad Institute and UMass Medical School, we used Hi-C to construct spatial proximity maps of the human genome at a resolution of 1Mb. These maps confirm the presence of chromosome territories and the spatial proximity of small, gene-rich chromosomes. We identified an additional level of genome organization that is characterized by the spatial segregation of open and closed chromatin to form two genome-wide compartments. At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus. The fractal globule is distinct from the more commonly used globular equilibrium model. Our results demonstrate the power of Hi-C to map the dynamic conformations of whole genomes.

  17. Distinguishing between sequential and nonsequentially folded proteins: implications for folding and misfolding.

    PubMed Central

    Tsai, C. J.; Maizel, J. V.; Nussinov, R.

    1999-01-01

    We describe here an algorithm for distinguishing sequential from nonsequentially folding proteins. Several experiments have recently suggested that most of the proteins that are synthesized in the eukaryotic cell may fold sequentially. This proposed folding mechanism in vivo is particularly advantageous to the organism. In the absence of chaperones, the probability that a sequentially folding protein will misfold is reduced significantly. The problem we address here is devising a procedure that would differentiate between the two types of folding patterns. Footprints of sequential folding may be found in structures where consecutive fragments of the chain interact with each other. In such cases, the folding complexity may be viewed as being lower. On the other hand, higher folding complexity suggests that at least a portion of the polypeptide backbone folds back upon itself to form three-dimensional (3D) interactions with noncontiguous portion(s) of the chain. Hence, we look at the mechanism of folding of the molecule via analysis of its complexity, that is, through the 3D interactions formed by contiguous segments on the polypeptide chain. To computationally splice the structure into consecutively interacting fragments, we either cut it into compact hydrophobic folding units or into a set of hypothetical, transient, highly populated, contiguous fragments ("building blocks" of the structure). In sequential folding, successive building blocks interact with each other from the amino to the carboxy terminus of the polypeptide chain. Consequently, the results of the parsing differentiate between sequentially vs. nonsequentially folded chains. The automated assessment of the folding complexity provides insight into both the likelihood of misfolding and the kinetic folding rate of the given protein. In terms of the funnel free energy landscape theory, a protein that truly follows the mechanism of sequential folding, in principle, encounters smoother free energy barriers

  18. RNA 3D Structure Modeling by Combination of Template-Based Method ModeRNA, Template-Free Folding with SimRNA, and Refinement with QRNAS.

    PubMed

    Piatkowski, Pawel; Kasprzak, Joanna M; Kumar, Deepak; Magnus, Marcin; Chojnowski, Grzegorz; Bujnicki, Janusz M

    2016-01-01

    RNA encompasses an essential part of all known forms of life. The functions of many RNA molecules are dependent on their ability to form complex three-dimensional (3D) structures. However, experimental determination of RNA 3D structures is laborious and challenging, and therefore, the majority of known RNAs remain structurally uncharacterized. To address this problem, computational structure prediction methods were developed that either utilize information derived from known structures of other RNA molecules (by way of template-based modeling) or attempt to simulate the physical process of RNA structure formation (by way of template-free modeling). All computational methods suffer from various limitations that make theoretical models less reliable than high-resolution experimentally determined structures. This chapter provides a protocol for computational modeling of RNA 3D structure that overcomes major limitations by combining two complementary approaches: template-based modeling that is capable of predicting global architectures based on similarity to other molecules but often fails to predict local unique features, and template-free modeling that can predict the local folding, but is limited to modeling the structure of relatively small molecules. Here, we combine the use of a template-based method ModeRNA with a template-free method SimRNA. ModeRNA requires a sequence alignment of the target RNA sequence to be modeled with a template of the known structure; it generates a model that predicts the structure of a conserved core and provides a starting point for modeling of variable regions. SimRNA can be used to fold small RNAs (<80 nt) without any additional structural information, and to refold parts of models for larger RNAs that have a correctly modeled core. ModeRNA can be either downloaded, compiled and run locally or run through a web interface at http://genesilico.pl/modernaserver/ . SimRNA is currently available to download for local use as a precompiled

  19. Spectral analysis of the gravity and elevation along the western Africa-Eurasia plate tectonic limit: Continental versus oceanic lithospheric folding signals

    NASA Astrophysics Data System (ADS)

    Muñoz-Martín, A.; De Vicente, G.; Fernández-Lozano, J.; Cloetingh, S.; Willingshofer, E.; Sokoutis, D.; Beekman, F.

    2010-12-01

    Large-scale folding is a key mechanism of lithospheric deformation and has been described in many parts of the Earth, both for the continental and oceanic lithospheres. Some aspects of this process such as the presence of coupling/decoupling between the crustal deformation and the mantle lithosphere, or between different lithospheres, make it necessary to accurately control the periodic characteristics of the elevation and of the gravity signal. 1D spectral analysis of gravity and topography profiles is sensitive to a series of factors: the location, length and orientation of the profiles, as well as the number of samples taken. We carry out a systematic analysis of the periodicities in the topography and gravity, both 1D and 2D, along the western border of the Africa-Eurasia plate tectonic boundary. We analyze the sensitivity of the 1D and 2D spectral analysis in order to compare the results along a plate boundary where oceanic and continental lithospheres are in contact with different tectonic, kinematic and rheological aspects. Our 1D spectral results indicate that the greater the profile length, the longer the wavelength peaks that are found. Nevertheless there are some periodic signals that appear in almost all the analyzed profiles: 100-250 km for the N-S profiles across oceanic plate boundary and 150-250 km where the plate boundary is developed over continental lithospheres. The 2D spectral analysis avoids the problems found in relation to the particular location of the profile but the resulting wavelengths are slightly higher than those obtained from the 1D spectral analysis. The wavelengths estimated for both oceanic and continental lithospheres at the Africa-Eurasia boundary (> 250 km) show low values of mean mantle strength (< 10 13 Pa m). The presence of lithospheric folds means that the continental and oceanic lithospheres are mechanically coupled. This had previously been suggested for Iberia but not for the limit between S Iberia and the Terceira

  20. A statistical model for iTRAQ data analysis.

    PubMed

    Hill, Elizabeth G; Schwacke, John H; Comte-Walters, Susana; Slate, Elizabeth H; Oberg, Ann L; Eckel-Passow, Jeanette E; Therneau, Terry M; Schey, Kevin L

    2008-08-01

    We describe biological and experimental factors that induce variability in reporter ion peak areas obtained from iTRAQ experiments. We demonstrate how these factors can be incorporated into a statistical model for use in evaluating differential protein expression and highlight the benefits of using analysis of variance to quantify fold change. We demonstrate the model's utility based on an analysis of iTRAQ data derived from a spike-in study.

  1. Turbulent phenomena in protein folding.

    PubMed

    Kalgin, Igor V; Chekmarev, Sergei F

    2011-01-01

    Protein folding and hydrodynamic turbulence are two long-standing challenges, in molecular biophysics and fluid dynamics, respectively. The theories of these phenomena have been developed independently and used different formalisms. Here we show that the protein folding flows can be surprisingly similar to turbulent fluid flows. Studying a benchmark model protein (an SH3 domain), we have found that the flows for the slow folding trajectories of the protein, in which a partly formed N- and C-terminal β sheet hinders the RT loop from attaching to the protein core, have many properties of turbulent flows of a fluid. The flows are analyzed in a three-dimensional (3D) space of collective variables, which are the numbers of native contacts between the terminal β strands, between the RT loop and the protein core, and the rest of the native contacts. We have found that the flows have fractal nature and are filled with 3D eddies; the latter contain strange attractors, at which the tracer flow paths behave as saddle trajectories. Two regions of the space increment have been observed, in which the flux variations are self-similar with the scaling exponent h=1/3, in surprising agreement with the Kolmogorov inertial range theory of turbulence. In one region, the cascade of protein rearrangements is directed from larger to smaller scales (net folding), and in the other, it is oppositely directed (net unfolding). Folding flows for the fast trajectories are essentially "laminar" and do not have the property of self-similarity. Based on the results of our study, we infer, and support this inference by simulations, that the origin of the similarity between the protein folding and turbulent motion of a fluid is in a cascade mechanism of structural transformations in the systems that underlies these phenomena.

  2. Computational Modeling and Analysis of Phonation in a Diseased Larynx

    NASA Astrophysics Data System (ADS)

    Xue, Qian; Zheng, Xudong; Mittal, Rajat; Bielamowicz, Steven

    2009-11-01

    The goal of our current research is to study the fundamental biophysics of phonation in healthy and pathological larynges. We have developed a coupled flow-structure interaction solver to help gain insight into the fundamental biophysics underlying unilateral laryngeal paralysis. The solver models the incompressible Navier-Stokes equations for the glottal aerodynamics and employs the classic two-mass model for the vocal folds. The effect of tension imbalance and subglottal pressure on the vocal fold dynamics is investigated. An analysis of the vibration modes as well as the frequency spectra and sound quality has been conducted. Results from these studies will be presented.

  3. Folded supersymmetry with a twist

    DOE PAGES

    Cohen, Timothy; Craig, Nathaniel; Lou, Hou Keong; ...

    2016-03-30

    Folded supersymmetry (f-SUSY) stabilizes the weak scale against radiative corrections from the top sector via scalar partners whose gauge quantum numbers differ from their Standard Model counterparts. This non-trivial pairing of states can be realized in extra-dimensional theories with appropriate supersymmetry-breaking boundary conditions. We present a class of calculable f-SUSY models that are parametrized by a non-trivial twist in 5D boundary conditions and can accommodate the observed Higgs mass and couplings. Although the distinctive phenomenology associated with the novel folded states should provide strong evidence for this mechanism, the most stringent constraints are currently placed by conventional supersymmetry searches. Asmore » a result, these models remain minimally fine-tuned in light of LHC8 data and provide a range of both standard and exotic signatures accessible at LHC13.« less

  4. Folded supersymmetry with a twist

    SciTech Connect

    Cohen, Timothy; Craig, Nathaniel; Lou, Hou Keong; Pinner, David

    2016-03-30

    Folded supersymmetry (f-SUSY) stabilizes the weak scale against radiative corrections from the top sector via scalar partners whose gauge quantum numbers differ from their Standard Model counterparts. This non-trivial pairing of states can be realized in extra-dimensional theories with appropriate supersymmetry-breaking boundary conditions. We present a class of calculable f-SUSY models that are parametrized by a non-trivial twist in 5D boundary conditions and can accommodate the observed Higgs mass and couplings. Although the distinctive phenomenology associated with the novel folded states should provide strong evidence for this mechanism, the most stringent constraints are currently placed by conventional supersymmetry searches. As a result, these models remain minimally fine-tuned in light of LHC8 data and provide a range of both standard and exotic signatures accessible at LHC13.

  5. Multiscale modeling of cellular epigenetic states: stochasticity in molecular networks, chromatin folding in cell nuclei, and tissue pattern formation of cells

    PubMed Central

    Liang, Jie; Cao, Youfang; Gürsoy, Gamze; Naveed, Hammad; Terebus, Anna; Zhao, Jieling

    2016-01-01

    Genome sequences provide the overall genetic blueprint of cells, but cells possessing the same genome can exhibit diverse phenotypes. There is a multitude of mechanisms controlling cellular epigenetic states and that dictate the behavior of cells. Among these, networks of interacting molecules, often under stochastic control, depending on the specific wirings of molecular components and the physiological conditions, can have a different landscape of cellular states. In addition, chromosome folding in three-dimensional space provides another important control mechanism for selective activation and repression of gene expression. Fully differentiated cells with different properties grow, divide, and interact through mechanical forces and communicate through signal transduction, resulting in the formation of complex tissue patterns. Developing quantitative models to study these multi-scale phenomena and to identify opportunities for improving human health requires development of theoretical models, algorithms, and computational tools. Here we review recent progress made in these important directions. PMID:27480462

  6. Response to "Comments on 'A theoretical model of the pressure distributions arising from asymmetric intraglottal flows applied to a two-mass model of the vocal folds'" [J. Acoust. Soc. Am. 130, 389-403 (2011)].

    PubMed

    Erath, Byron D; Peterson, Sean D; Zañartu, Matías; Wodicka, George R; Stewart, Kelley C; Plesniak, Michael W

    2013-08-01

    Hirschberg [J. Acoust. Soc. Am. 134, 9-12 (2013)] presents a commentary and criticisms of the viscous flow model presented by Erath et al. [J. Acoust. Soc. Am. 130, 389-403 (2011)] that solves for the asymmetric pressure loading on the vocal fold walls. This pressure loading arises from asymmetric flow attachment to one vocal fold wall when the glottal channel forms a divergent configuration. Hirschberg proposes an alternative model for the asymmetric loading based upon inviscid flow curvature at the glottal inlet. In this manuscript further evidence is provided in support of the model of Erath et al. and the underlying assumptions, and demonstrates that the primary criticisms presented by Hirschberg are unwarranted. The model presented by Hirschberg is compared with the model from the original paper by Erath et al., and it is shown that each model describes different and complementary aspects of divergent glottal flows.

  7. Modeling spatially and temporally varied hydraulic behavior of a folded karst system with dominant conduit drainage at catchment scale, Hochifen-Gottesacker, Alps

    NASA Astrophysics Data System (ADS)

    Chen, Zhao; Goldscheider, Nico

    2014-06-01

    Karst aquifers are important for freshwater supply, but difficult to manage, due to highly variable water levels and spring discharge rates. Conduits are crucial for groundwater flow in karst aquifers, but their location is often unknown, thus limiting the applicability and validity of numerical models. We have applied a conduit model (SWMM) to simulate highly variable flow in a folded alpine karst aquifer system, where the underground drainage pattern is comparatively well-known from previous tracer studies. The conduit model was coupled with a reservoir model representing recharge, storage and transfer of water in the epikarst and unsaturated zone. The global optimization approach (GA) was applied to achieve an efficient model calibration. It was possible to simultaneously simulate the highly variable discharge characteristics of an estavelle, and overflow spring and a permanent spring draining the conduit system. The model allowed for the collection of spatially differentiated information on recharge, rapid flow and slow flow in four individual sub-catchments. The formation of backwater upgradient from conduit restrictions turned out to be a key process in activating overflow springs. The proposed modeling approach appears to be transferrable to other karst systems with predominant conduit drainage, but requires previous knowledge of the configuration of the conduit system.

  8. Programmable matter by folding

    PubMed Central

    Hawkes, E.; An, B.; Benbernou, N. M.; Tanaka, H.; Kim, S.; Demaine, E. D.; Rus, D.; Wood, R. J.

    2010-01-01

    Programmable matter is a material whose properties can be programmed to achieve specific shapes or stiffnesses upon command. This concept requires constituent elements to interact and rearrange intelligently in order to meet the goal. This paper considers achieving programmable sheets that can form themselves in different shapes autonomously by folding. Past approaches to creating transforming machines have been limited by the small feature sizes, the large number of components, and the associated complexity of communication among the units. We seek to mitigate these difficulties through the unique concept of self-folding origami with universal crease patterns. This approach exploits a single sheet composed of interconnected triangular sections. The sheet is able to fold into a set of predetermined shapes using embedded actuation. To implement this self-folding origami concept, we have developed a scalable end-to-end planning and fabrication process. Given a set of desired objects, the system computes an optimized design for a single sheet and multiple controllers to achieve each of the desired objects. The material, called programmable matter by folding, is an example of a system capable of achieving multiple shapes for multiple functions. PMID:20616049

  9. Combining Structural Modeling with Ensemble Machine Learning to Accurately Predict Protein Fold Stability and Binding Affinity Effects upon Mutation

    PubMed Central

    Garcia Lopez, Sebastian; Kim, Philip M.

    2014-01-01

    Advances in sequencing have led to a rapid accumulation of mutations, some of which are associated with diseases. However, to draw mechanistic conclusions, a biochemical understanding of these mutations is necessary. For coding mutations, accurate prediction of significant changes in either the stability of proteins or their affinity to their binding partners is required. Traditional methods have used semi-empirical force fields, while newer methods employ machine learning of sequence and structural features. Here, we show how combining both of these approaches leads to a marked boost in accuracy. We introduce ELASPIC, a novel ensemble machine learning approach that is able to predict stability effects upon mutation in both, domain cores and domain-domain interfaces. We combine semi-empirical energy terms, sequence conservation, and a wide variety of molecular details with a Stochastic Gradient Boosting of Decision Trees (SGB-DT) algorithm. The accuracy of our predictions surpasses existing methods by a considerable margin, achieving correlation coefficients of 0.77 for stability, and 0.75 for affinity predictions. Notably, we integrated homology modeling to enable proteome-wide prediction and show that accurate prediction on modeled structures is possible. Lastly, ELASPIC showed significant differences between various types of disease-associated mutations, as well as between disease and common neutral mutations. Unlike pure sequence-based prediction methods that try to predict phenotypic effects of mutations, our predictions unravel the molecular details governing the protein instability, and help us better understand the molecular causes of diseases. PMID:25243403

  10. Noninvasive evaluation of the vascular response to transplantation of alginate encapsulated islets using the dorsal skin-fold model.

    PubMed

    Krishnan, Rahul; Arora, Rajan P; Alexander, Michael; White, Sean M; Lamb, Morgan W; Foster, Clarence E; Choi, Bernard; Lakey, Jonathan R T

    2014-01-01

    Alginate encapsulation reduces the risk of transplant rejection by evading immune-mediated cell injury and rejection; however, poor vascular perfusion results in graft failure. Since existing imaging models are incapable of quantifying the vascular response to biomaterial implants after transplantation, in this study, we demonstrate the use of in vivo laser speckle imaging (LSI) and wide-field functional imaging (WiFI) to monitor the microvascular environment surrounding biomaterial implants. The vascular response to two islet-containing biomaterial encapsulation devices, alginate microcapsules and a high-guluronate alginate sheet, was studied and compared after implantation into the mouse dorsal window chamber (N = 4 per implant group). Images obtained over a 14-day period using LSI and WiFI were analyzed using algorithms to quantify blood flow, hemoglobin oxygen saturation and vascular density. Using our method, we were able to monitor the changes in the peri-implant microvasculature noninvasively without the use of fluorescent dyes. Significant changes in blood flow, hemoglobin oxygen saturation and vascular density were noted as early as the first week post-transplant. The dorsal window chamber model enables comparison of host responses to transplanted biomaterials. Future experiments will study the effect of changes in alginate composition on the vascular and immune responses.

  11. On the origin of south polar folds on Enceladus

    NASA Astrophysics Data System (ADS)

    Barr, Amy C.; Preuss, Lauren J.

    2010-07-01

    Recent high-resolution Cassini images of the south polar terrain of Enceladus reveal regions of short-wavelength deformation, inferred to be compressional folds between the Baghdad and Damascus tiger stripes (Spencer, J.R., Barr, A.C., Esposito, L.W., Helfenstein, P., Ingersoll, A.P., Jaumann, R., McKay, C.P., Nimmo, F., Waite, J.H. [2009a]. Enceladus: An active cryovolcanic satellite. In: Saturn after Cassini-Huygens. Springer, New York, pp. 683-722). Here, we use Fourier analysis of the bright/dark variations to show that the folds have a dominant wavelength of 1.1 ± 0.4 km. We use the simple model of lava flow folding from Fink (Fink, J. [1980]. Geology 8, 250-254) to show that the folds could form in an ice shell with an upper high-viscosity boundary layer of thickness <400 m, with a driving stress of 40-80 kPa, and strain rate between 10 -14 s -1 and 10 -12 s -1. Such deformation rates imply resurfacing of the SPT in 0.05-5 Myr, consistent with its estimated surface age. Measurements of fold topography and more sophisticated numerical modeling can narrow down the conditions of fold formation and provide valuable constraints on the thermal structure of the ice shell on Enceladus.

  12. AIR Model Preflight Analysis

    NASA Technical Reports Server (NTRS)

    Tai, H.; Wilson, J. W.; Maiden, D. L.

    2003-01-01

    The atmospheric ionizing radiation (AIR) ER-2 preflight analysis, one of the first attempts to obtain a relatively complete measurement set of the high-altitude radiation level environment, is described in this paper. The primary thrust is to characterize the atmospheric radiation and to define dose levels at high-altitude flight. A secondary thrust is to develop and validate dosimetric techniques and monitoring devices for protecting aircrews. With a few chosen routes, we can measure the experimental results and validate the AIR model predictions. Eventually, as more measurements are made, we gain more understanding about the hazardous radiation environment and acquire more confidence in the prediction models.

  13. Automated protein structure modeling in CASP9 by I-TASSER pipeline combined with QUARK-based ab initio folding and FG-MD-based structure refinement.

    PubMed

    Xu, Dong; Zhang, Jian; Roy, Ambrish; Zhang, Yang

    2011-01-01

    I-TASSER is an automated pipeline for protein tertiary structure prediction using multiple threading alignments and iterative structure assembly simulations. In CASP9 experiments, two new algorithms, QUARK and fragment-guided molecular dynamics (FG-MD), were added to the I-TASSER pipeline for improving the structural modeling accuracy. QUARK is a de novo structure prediction algorithm used for structure modeling of proteins that lack detectable template structures. For distantly homologous targets, QUARK models are found useful as a reference structure for selecting good threading alignments and guiding the I-TASSER structure assembly simulations. FG-MD is an atomic-level structural refinement program that uses structural fragments collected from the PDB structures to guide molecular dynamics simulation and improve the local structure of predicted model, including hydrogen-bonding networks, torsion angles, and steric clashes. Despite considerable progress in both the template-based and template-free structure modeling, significant improvements on protein target classification, domain parsing, model selection, and ab initio folding of β-proteins are still needed to further improve the I-TASSER pipeline.

  14. New insight in the structural features of haloadaptation in α-amylases from halophilic Archaea following homology modeling strategy: folded and stable conformation maintained through low hydrophobicity and highly negative charged surface.

    PubMed

    Zorgani, Mohamed Amine; Patron, Kevin; Desvaux, Mickaël

    2014-07-01

    Proteins from halophilic archaea, which live in extreme saline conditions, have evolved to remain folded, active and stable at very high ionic strengths. Understanding the mechanism of haloadaptation is the first step toward engineering of halostable biomolecules. Amylases are one of the main enzymes used in industry. Yet, no three-dimensional structure has been experimentally resolved for α-amylases from halophilic archaea. In this study, homology structure modeling of α-amylases from the halophilic archaea Haloarcula marismortui, Haloarcula hispanica, and Halalkalicoccus jeotgali were performed. The resulting models were subjected to energy minimization, evaluation, and structural analysis. Calculations of the amino acid composition, salt bridges and hydrophobic interactions were also performed and compared to a set of non-halophilic counterparts. It clearly appeared that haloarchaeal α-amylases exhibited lower propensities for helix formation and higher propensities for coil-forming regions. Furthermore, they could maintain a folded and stable conformation in high salt concentration through highly negative charged surface with over representation of acidic residues, especially Asp, and low hydrophobicity with increase of salt bridges and decrease in hydrophobic interactions on the protein surface. This study sheds some light on the stability of α-amylases from halophilic archaea and provides strong basis not only to understand haloadaptation mechanisms of proteins in microorganisms from hypersalines environments but also for biotechnological applications.

  15. New insight in the structural features of haloadaptation in α-amylases from halophilic Archaea following homology modeling strategy: folded and stable conformation maintained through low hydrophobicity and highly negative charged surface

    NASA Astrophysics Data System (ADS)

    Zorgani, Mohamed Amine; Patron, Kevin; Desvaux, Mickaël

    2014-07-01

    Proteins from halophilic archaea, which live in extreme saline conditions, have evolved to remain folded, active and stable at very high ionic strengths. Understanding the mechanism of haloadaptation is the first step toward engineering of halostable biomolecules. Amylases are one of the main enzymes used in industry. Yet, no three-dimensional structure has been experimentally resolved for α-amylases from halophilic archaea. In this study, homology structure modeling of α-amylases from the halophilic archaea Haloarcula marismortui, Haloarcula hispanica, and Halalkalicoccus jeotgali were performed. The resulting models were subjected to energy minimization, evaluation, and structural analysis. Calculations of the amino acid composition, salt bridges and hydrophobic interactions were also performed and compared to a set of non-halophilic counterparts. It clearly appeared that haloarchaeal α-amylases exhibited lower propensities for helix formation and higher propensities for coil-forming regions. Furthermore, they could maintain a folded and stable conformation in high salt concentration through highly negative charged surface with over representation of acidic residues, especially Asp, and low hydrophobicity with increase of salt bridges and decrease in hydrophobic interactions on the protein surface. This study sheds some light on the stability of α-amylases from halophilic archaea and provides strong basis not only to understand haloadaptation mechanisms of proteins in microorganisms from hypersalines environments but also for biotechnological applications.

  16. Sandbox modelling of sequential thrusting in a mechanically two-layered system and its implications in fold-and-thrust belts

    NASA Astrophysics Data System (ADS)

    Saha, Puspendu; Bose, Santanu; Mandal, Nibir

    2016-10-01

    Many fold-and-thrust belts display multi-storied thrust sequences, characterizing a composite architecture of the thrust wedges. Despite dramatic progress in sandbox modelling over the last three decades, our understanding of such composite thrust-wedge mechanics is limited and demands a re-visit to the problem of sequential thrusting in mechanically layered systems. This study offers a new approach to sandbox modelling, designed with a two-layered sandpack simulating a mechanically weak Coulomb layer, resting coherently upon a stronger Coulomb layer. Our experimental models reproduce strikingly similar styles of the multi-storied frontal thrust sequences observed in natural fold-and- thrust belts. The upper weak horizon undergoes sequential thrusting at a high spatial frequency, forming numerous, closely spaced frontal thrusts, whereas the lower strong horizon produces widely spaced thrusts with progressive horizontal shortening. This contrasting thrust progression behaviour gives rise to composite thrust architecture in the layered sandpack. We show the evolution of such composite thrust sequences as a function of frictional strength (μb) at the basal detachment and thickness ratio (Tr) between the weak and strong layers. For any given values of Tr and μb, the two thrust sequences progress at different rates; the closely-spaced, upper thrust sequence advances forelandward at a faster rate than the widely-spaced, lower thrust sequence. Basal friction (μb) has little effects on the vergence of thrusts in the upper weak layer; they verge always towards foreland, irrespective of Tr values. But, the lower strong layer develops back-vergent thrusts when μb is low (∼0.36). In our experiments, closely spaced thrusts in the upper sequence experience intense reactivation due to their interaction with widely spaced thrusts in the lower sequence. The interaction eventually affects the wedge topography, leading to two distinct parts: inner and outer wedges

  17. Quantitative Morphology of Epithelial Folds

    PubMed Central

    Štorgel, Nick; Krajnc, Matej; Mrak, Polona; Štrus, Jasna; Ziherl, Primož

    2016-01-01

    The shape of spatially modulated epithelial morphologies such as villi and crypts is usually associated with the epithelium-stroma area mismatch leading to buckling. We propose an alternative mechanical model based on intraepithelial stresses generated by differential tensions of apical, lateral, and basal sides of cells as well as on the elasticity of the basement membrane. We use it to theoretically study longitudinal folds in simple epithelia and we identify four types of corrugated morphologies: compact, invaginated, evaginated, and wavy. The obtained tissue contours and thickness profiles are compared to epithelial folds observed in invertebrates and vertebrates, and for most samples, the agreement is within the estimated experimental error. Our model establishes the groove-crest modulation of tissue thickness as a morphometric parameter that can, together with the curvature profile, be used to estimate the relative differential apicobasal tension in the epithelium. PMID:26745429

  18. Using Sequential Kinematic and Thermochronometric Modeling to Temporally and Spatially Link Thrust Belt Exhumation with Basin Development in the Bolivian Fold-Thrust-Belt-Foreland Basin System.

    NASA Astrophysics Data System (ADS)

    Rak, A. J.; McQuarrie, N.

    2014-12-01

    Applying isostasy and erosion to sequentially deformed balanced cross sections links the growth of hinterland structures to the developing foreland basins (FB) adjacent to fold-thrust belts (FTB), adding geologic constraints to modeled exhumation pathways. We sequentially deform the Rio Beni cross section in northern Bolivia (McQuarrie et al., 2008) with kinematic modeling software Move. In our model, topography evolves and basins develop for each model step as deformation, erosion, and isostasy are applied; and are a direct function of the geometry and kinematics of the cross section. The model is constrained by the depth of the foreland and hinterland basins, geology present at the surface, the depth and angle of the decollement, and the shape of the modern observed topography. Topography develops as thrusting occurs and loads the crust, producing a flexural wave and creating accommodation space in adjacent basins. Erosion of material above a newly generated topographic profile unloads the section while basin space is filled. Once the model sufficiently duplicates geologic constraints, a 0.5 km X 0.5 km grid of unique points is deformed with the model and used to determine displacement vectors for each 10 km shortening step. These displacement vectors, in conjunction with a prescribed time interval for each step, determine a velocity field that can be used in a modified version of the advection diffusion modeling software Pecube. Cooling ages predicted using this method are based on deformation rates, geometry, topography, and thermal parameters, and offer insight into possible rates of deformation, erosion, and deposition throughout FTB and FB development. Incorporating erosion, deposition, and isostasy in sequentially deformed balanced cross sections highlights the spatiotemporal aspects of sedimentary wedge propagation, identifies necessary external negative buoyancy affects, and provides additional geologic constraints to modeled exhumation pathways.

  19. Solvent–amino acid interaction energies in three-dimensional-lattice Monte Carlo simulations of a model 27-mer protein: Folding thermodynamics and kinetics

    PubMed Central

    Leonhard, Kai; Prausnitz, John M.; Radke, Clayton J.

    2004-01-01

    Amino acid residue–solvent interactions are required for lattice Monte Carlo simulations of model proteins in water. In this study, we propose an interaction-energy scale that is based on the interaction scale by Miyazawa and Jernigan. It permits systematic variation of the amino acid–solvent interactions by introducing a contrast parameter for the hydrophobicity, Cs, and a mean attraction parameter for the amino acids, ω. Changes in the interaction energies strongly affect many protein properties. We present an optimized energy parameter set for best representing realistic behavior typical for many proteins (fast folding and high cooperativity for single chains). Our optimal parameters feature a much weaker hydrophobicity contrast and mean attraction than does the original interaction scale. The proposed interaction scale is designed for calculating the behavior of proteins in bulk and at interfaces as a function of solvent characteristics, as well as protein size and sequence. PMID:14739322

  20. Protein Folding and Self-Organized Criticality

    NASA Astrophysics Data System (ADS)

    Bajracharya, Arun; Murray, Joelle

    Proteins are known to fold into tertiary structures that determine their functionality in living organisms. However, the complex dynamics of protein folding and the way they consistently fold into the same structures is not fully understood. Self-organized criticality (SOC) has provided a framework for understanding complex systems in various systems (earthquakes, forest fires, financial markets, and epidemics) through scale invariance and the associated power law behavior. In this research, we use a simple hydrophobic-polar lattice-bound computational model to investigate self-organized criticality as a possible mechanism for generating complexity in protein folding.

  1. Folds and Etudes

    ERIC Educational Resources Information Center

    Bean, Robert

    2007-01-01

    In this article, the author talks about "Folds" and "Etudes" which are images derived from anonymous typing exercises that he found in a used copy of "Touch Typing Made Simple". "Etudes" refers to the musical tradition of studies for a solo instrument, which is a typewriter. Typing exercises are repetitive attempts to type words and phrases…

  2. The effect of foreland palaeo-uplift on deformation mechanism in the Wupoer fold-and-thrust belt, NE Pamir: Constraints from analogue modelling

    NASA Astrophysics Data System (ADS)

    Wang, Chunyang; Cheng, Xiaogan; Chen, Hanlin; Ding, Weiwei; Lin, Xiubin; Wu, Lei; Li, Kang; Shi, Jun; Li, Yong

    2016-10-01

    Palaeo-uplifts often exist in fold-and-thrust belts. However, their effects on the deformational process have not yet been well understood. To evaluate such effects, six analogue models were systematically run based on geological features of the Wupoer fold-and-thrust belt (FTB), NE Pamir, where the Wulagen palaeo-uplift with overlying gypsum bed has been clearly identified. Our analogue results demonstrated that the palaeo-uplift (its location and inhomogenous distribution), accompanied with overlying gypsum bed that serves as ductile décollement, plays a critical role in localizing the front thrust fault and shaping it into arc form. The results indicate that the front thrust fault slides along the ductile décollement (gypsum bed), and breaks through onto the surface at the region where the palaeo-uplift develops, forming a piggy-back basin in the hanging wall. It suggests that the palaeo-uplift with consequent topographic variation of the overlying ductile décollement localizes the breakthrough point of the front thrust fault. In addition, the results indicate that the front thrust fault (Pamir Front Thrust, PFT) initially broke through in the location where it develops the Wulagen palaeo-uplift and propagated aside. This resulted in the distance between the PFT and the basement-involved fault (Main Pamir Thrust, MPT) to decrease from the region with palaeo-uplift to the areas aside without palaeo-uplift, thereby forming the arc-shaped PFT in map view. The results of this study also provide a revised geological model, which emphasizes the effect of décollement layer on absorbing the slip along the PFT. Our results provide a new mechanical interpretation of the deformation of Wupoer FTB, NE Pamir.

  3. Nonlinear dynamic mechanism of vocal tremor from voice analysis and model simulations

    PubMed Central

    Zhang, Yu; Jiang, Jack J.

    2009-01-01

    Nonlinear dynamic analysis and model simulations are used to study the nonlinear dynamic characteristics of vocal folds with vocal tremor, which can typically be characterized by low frequency modulation and aperiodicity. Tremor voices from patients with disorders such as paresis, Parkinson's disease, hyperfunction, and adductor spasmodic dysphonia show low-dimensional characteristics, differing from random noise. Correlation dimension analysis statistically distinguishes tremor voices from normal voices. Furthermore, a nonlinear tremor model is proposed to study the vibrations of the vocal folds with vocal tremor. Fractal dimensions and positive Lyapunov exponents demonstrate the evidence of chaos in the tremor model, where amplitude and frequency play important roles in governing vocal fold dynamics. Nonlinear dynamic voice analysis and vocal fold modeling may provide a useful set of tools for understanding the dynamic mechanism of vocal tremor in patients with laryngeal diseases. PMID:22505778

  4. Nonlinear dynamic mechanism of vocal tremor from voice analysis and model simulations

    NASA Astrophysics Data System (ADS)

    Zhang, Yu; Jiang, Jack J.

    2008-09-01

    Nonlinear dynamic analysis and model simulations are used to study the nonlinear dynamic characteristics of vocal folds with vocal tremor, which can typically be characterized by low-frequency modulation and aperiodicity. Tremor voices from patients with disorders such as paresis, Parkinson's disease, hyperfunction, and adductor spasmodic dysphonia show low-dimensional characteristics, differing from random noise. Correlation dimension analysis statistically distinguishes tremor voices from normal voices. Furthermore, a nonlinear tremor model is proposed to study the vibrations of the vocal folds with vocal tremor. Fractal dimensions and positive Lyapunov exponents demonstrate the evidence of chaos in the tremor model, where amplitude and frequency play important roles in governing vocal fold dynamics. Nonlinear dynamic voice analysis and vocal fold modeling may provide a useful set of tools for understanding the dynamic mechanism of vocal tremor in patients with laryngeal diseases.

  5. Objective Quantification of Pre-and Postphonosurgery Vocal Fold Vibratory Characteristics Using High-Speed Videoendoscopy and a Harmonic Waveform Model

    ERIC Educational Resources Information Center

    Ikuma, Takeshi; Kunduk, Melda; McWhorter, Andrew J.

    2014-01-01

    Purpose: The model-based quantitative analysis of high-speed videoendoscopy (HSV) data at a low frame rate of 2,000 frames per second was assessed for its clinical adequacy. Stepwise regression was employed to evaluate the HSV parameters using harmonic models and their relationships to the Voice Handicap Index (VHI). Also, the model-based HSV…

  6. Local vs global motions in protein folding

    PubMed Central

    Maisuradze, Gia G.; Liwo, Adam; Senet, Patrick; Scheraga, Harold A.

    2013-01-01

    It is of interest to know whether local fluctuations in a polypeptide chain play any role in the mechanism by which the chain folds to the native structure of a protein. This question is addressed by analyzing folding and non-folding trajectories of a protein; as an example, the analysis is applied to the 37-residue triple β-strand WW domain from the Formin binding protein 28 (FBP28) (PDB ID: 1E0L). Molecular dynamics (MD) trajectories were generated with the coarse-grained united-residue force field, and one- and two-dimensional free-energy landscapes (FELs) along the backbone virtual-bond angle θ and backbone virtual-bond-dihedral angle γ of each residue, and principal components, respectively, were analyzed. The key residues involved in the folding of the FBP28 WW domain are elucidated by this analysis. The correlations between local and global motions are found. It is shown that most of the residues in the folding trajectories of the system studied here move in a concerted fashion, following the dynamics of the whole system. This demonstrates how the choice of a pathway has to involve concerted movements in order for this protein to fold. This finding also sheds light on the effectiveness of principal component analysis (PCA) for the description of the folding dynamics of the system studied. It is demonstrated that the FEL along the PCs, computed by considering only several critically-placed residues, can correctly describe the folding dynamics. PMID:23914144

  7. Cooperativity and modularity in protein folding

    PubMed Central

    Sasai, Masaki; Chikenji, George; Terada, Tomoki P.

    2016-01-01

    A simple statistical mechanical model proposed by Wako and Saitô has explained the aspects of protein folding surprisingly well. This model was systematically applied to multiple proteins by Muñoz and Eaton and has since been referred to as the Wako-Saitô-Muñoz-Eaton (WSME) model. The success of the WSME model in explaining the folding of many proteins has verified the hypothesis that the folding is dominated by native interactions, which makes the energy landscape globally biased toward native conformation. Using the WSME and other related models, Saitô emphasized the importance of the hierarchical pathway in protein folding; folding starts with the creation of contiguous segments having a native-like configuration and proceeds as growth and coalescence of these segments. The Φ-values calculated for barnase with the WSME model suggested that segments contributing to the folding nucleus are similar to the structural modules defined by the pattern of native atomic contacts. The WSME model was extended to explain folding of multi-domain proteins having a complex topology, which opened the way to comprehensively understanding the folding process of multi-domain proteins. The WSME model was also extended to describe allosteric transitions, indicating that the allosteric structural movement does not occur as a deterministic sequential change between two conformations but as a stochastic diffusive motion over the dynamically changing energy landscape. Statistical mechanical viewpoint on folding, as highlighted by the WSME model, has been renovated in the context of modern methods and ideas, and will continue to provide insights on equilibrium and dynamical features of proteins.

  8. SDI CFD MODELING ANALYSIS

    SciTech Connect

    Lee, S.

    2011-05-05

    The Savannah River Remediation (SRR) Organization requested that Savannah River National Laboratory (SRNL) develop a Computational Fluid Dynamics (CFD) method to mix and blend the miscible contents of the blend tanks to ensure the contents are properly blended before they are transferred from the blend tank; such as, Tank 50H, to the Salt Waste Processing Facility (SWPF) feed tank. The work described here consists of two modeling areas. They are the mixing modeling analysis during miscible liquid blending operation, and the flow pattern analysis during transfer operation of the blended liquid. The transient CFD governing equations consisting of three momentum equations, one mass balance, two turbulence transport equations for kinetic energy and dissipation rate, and one species transport were solved by an iterative technique until the species concentrations of tank fluid were in equilibrium. The steady-state flow solutions for the entire tank fluid were used for flow pattern analysis, for velocity scaling analysis, and the initial conditions for transient blending calculations. A series of the modeling calculations were performed to estimate the blending times for various jet flow conditions, and to investigate the impact of the cooling coils on the blending time of the tank contents. The modeling results were benchmarked against the pilot scale test results. All of the flow and mixing models were performed with the nozzles installed at the mid-elevation, and parallel to the tank wall. From the CFD modeling calculations, the main results are summarized as follows: (1) The benchmark analyses for the CFD flow velocity and blending models demonstrate their consistency with Engineering Development Laboratory (EDL) and literature test results in terms of local velocity measurements and experimental observations. Thus, an application of the established criterion to SRS full scale tank will provide a better, physically-based estimate of the required mixing time, and

  9. First passage analysis of the folding of a β-sheet miniprotein: is it more realistic than the standard equilibrium approach?

    PubMed

    Kalgin, Igor V; Chekmarev, Sergei F; Karplus, Martin

    2014-04-24

    Simulations of first-passage folding of the antiparallel β-sheet miniprotein beta3s, which has been intensively studied under equilibrium conditions by A. Caflisch and co-workers, show that the kinetics and dynamics are significantly different from those for equilibrium folding. Because the folding of a protein in a living system generally corresponds to the former (i.e., the folded protein is stable and unfolding is a rare event), the difference is of interest. In contrast to equilibrium folding, the Ch-curl conformations become very rare because they contain unfavorable parallel β-strand arrangements, which are difficult to form dynamically due to the distant N- and C-terminal strands. At the same time, the formation of helical conformations becomes much easier (particularly in the early stage of folding) due to short-range contacts. The hydrodynamic descriptions of the folding reaction have also revealed that while the equilibrium flow field presented a collection of local vortices with closed "streamlines", the first-passage folding is characterized by a pronounced overall flow from the unfolded states to the native state. The flows through the locally stable structures Cs-or and Ns-or, which are conformationally close to the native state, are negligible due to detailed balance established between these structures and the native state. Although there are significant differences in the general picture of the folding process from the equilibrium and first-passage folding simulations, some aspects of the two are in agreement. The rate of transitions between the clusters of characteristic protein conformations in both cases decreases approximately exponentially with the distance between the clusters in the hydrogen bond distance space of collective variables, and the folding time distribution in the first-passage segments of the equilibrium trajectory is in good agreement with that for the first-passage folding simulations.

  10. Mechanical stability model of progradational carbonate platform margins under tectonic loads: Deformation of Cretaceous carbonate platforms in the Sierra Madre Oriental fold-thrust belt (east central Mexico)

    NASA Astrophysics Data System (ADS)

    Contreras, Juan; Suter, Max

    2015-02-01

    Shortening in the Sierra Madre Oriental fold-thrust belt (east central Mexico) is localized along the margins of Cretaceous carbonate platforms and controlled by mechanical stratigraphy. The platform margins are deformed by imbricate series of thrust ramps, whereas the coeval basins and platform interiors are deformed by map-scale detachment folds. Here we present a finite element model to evaluate the influence of the boundary geometry and boundary conditions on the style of deformation observed at these basinward progradational platform margins. We calculate the stress distribution in a linearly elastic platform-basin transition zone under the action of horizontal tectonic stress, taking into account changes of rock mechanical properties across the platform margin, as well as their dependence on direction, and infer the resulting fracture patterns based on the Mohr-Coulomb failure criterion. Stress concentrations are predicted at the contacts between the massive rocks of the platform margin and the well-layered rocks of both, the platform interior and the adjacent basin. Brittle failure of the platform border can be mostly attributed to three effects: mechanical coupling between the carbonate platform and a substratum of moderate to low viscosity, variations in layering and texture that governed the mechanical properties of the involved carbonates as well as their dependence on direction, and the development of sharp domain boundary corners associated with progradational facies changes. In contrast, the dip of the basement and a possible taper of the overlying Upper Cretaceous shale toward the basin appear to have little influence on the mechanical failure of the platform margin.

  11. Real-Time Agent-Based Modeling Simulation with in-situ Visualization of Complex Biological Systems: A Case Study on Vocal Fold Inflammation and Healing.

    PubMed

    Seekhao, Nuttiiya; Shung, Caroline; JaJa, Joseph; Mongeau, Luc; Li-Jessen, Nicole Y K

    2016-05-01

    We present an efficient and scalable scheme for implementing agent-based modeling (ABM) simulation with In Situ visualization of large complex systems on heterogeneous computing platforms. The scheme is designed to make optimal use of the resources available on a heterogeneous platform consisting of a multicore CPU and a GPU, resulting in minimal to no resource idle time. Furthermore, the scheme was implemented under a client-server paradigm that enables remote users to visualize and analyze simulation data as it is being generated at each time step of the model. Performance of a simulation case study of vocal fold inflammation and wound healing with 3.8 million agents shows 35× and 7× speedup in execution time over single-core and multi-core CPU respectively. Each iteration of the model took less than 200 ms to simulate, visualize and send the results to the client. This enables users to monitor the simulation in real-time and modify its course as needed.

  12. PLS/OPLS models in metabolomics: the impact of permutation of dataset rows on the K-fold cross-validation quality parameters.

    PubMed

    Triba, Mohamed N; Le Moyec, Laurence; Amathieu, Roland; Goossens, Corentine; Bouchemal, Nadia; Nahon, Pierre; Rutledge, Douglas N; Savarin, Philippe

    2015-01-01

    Among all the software packages available for discriminant analyses based on projection to latent structures (PLS-DA) or orthogonal projection to latent structures (OPLS-DA), SIMCA (Umetrics, Umeå Sweden) is the more widely used in the metabolomics field. SIMCA proposes many parameters or tests to assess the quality of the computed model (the number of significant components, R2, Q2, pCV-ANOVA, and the permutation test). Significance thresholds for these parameters are strongly application-dependent. Concerning the Q2 parameter, a significance threshold of 0.5 is generally admitted. However, during the last few years, many PLS-DA/OPLS-DA models built using SIMCA have been published with Q2 values lower than 0.5. The purpose of this opinion note is to point out that, in some circumstances frequently encountered in metabolomics, the values of these parameters strongly depend on the individuals that constitute the validation subsets. As a result of the way in which the software selects members of the calibration and validation subsets, a simple permutation of dataset rows can, in several cases, lead to contradictory conclusions about the significance of the models when a K-fold cross-validation is used. We believe that, when Q2 values lower than 0.5 are obtained, SIMCA users should at least verify that the quality parameters are stable towards permutation of the rows in their dataset.

  13. Folded waveguide coupler

    DOEpatents

    Owens, Thomas L.

    1988-03-01

    A resonant cavity waveguide coupler for ICRH of a magnetically confined plasma. The coupler consists of a series of inter-leaved metallic vanes disposed withn an enclosure analogous to a very wide, simple rectangular waveguide that has been "folded" several times. At the mouth of the coupler, a polarizing plate is provided which has coupling apertures aligned with selected folds of the waveguide through which rf waves are launched with magnetic fields of the waves aligned in parallel with the magnetic fields confining the plasma being heated to provide coupling to the fast magnetosonic wave within the plasma in the frequency usage of from about 50-200 mHz. A shorting plate terminates the back of the cavity at a distance approximately equal to one-half the guide wavelength from the mouth of the coupler to ensure that the electric field of the waves launched through the polarizing plate apertures are small while the magnetic field is near a maximum. Power is fed into the coupler folded cavity by means of an input coaxial line feed arrangement at a point which provides an impedance match between the cavity and the coaxial input line.

  14. Model Analysis ToolKit

    SciTech Connect

    Harp, Dylan R.

    2015-05-15

    MATK provides basic functionality to facilitate model analysis within the Python computational environment. Model analysis setup within MATK includes: - define parameters - define observations - define model (python function) - define samplesets (sets of parameter combinations) Currently supported functionality includes: - forward model runs - Latin-Hypercube sampling of parameters - multi-dimensional parameter studies - parallel execution of parameter samples - model calibration using internal Levenberg-Marquardt algorithm - model calibration using lmfit package - model calibration using levmar package - Markov Chain Monte Carlo using pymc package MATK facilitates model analysis using: - scipy - calibration (scipy.optimize) - rpy2 - Python interface to R

  15. High sensitivity of an Ha-RAS transgenic model of superficial bladder cancer to metformin is associated with ~ 240-fold higher drug concentration in urine than serum

    PubMed Central

    Liu, Zhongbo; Yokoyama, Noriko N.; Blair, Chris A.; Li, Xuesen; Avizonis, Daina; Wu, Xue-Ru; Uchio, Edward; Youssef, Ramy; McClelland, Michael; Pollak, Michael; Zi, Xiaolin

    2016-01-01

    While pharmacoepidemiologic and laboratory studies have supported the hypothesis that the anti-diabetic drug metformin may be useful in treating or preventing cancer, there is limited evidence to suggest which specific cancer sites may be particularly sensitive. Sensitivity likely is determined both by features of tumor pathophysiology and by pharmacokinetic factors. We used UPII mutant Ha-ras transgenic mice that develop hyperplasia and low-grade, papillary urothelial cell carcinoma to determine if metformin has activity in a model of superficial bladder cancer. Metformin significantly improved survival, reduced urinary tract obstruction, reduced bladder weight (a surrogate for tumor volume) and led to clear activation of AMP α kinase and inhibition of mTOR signaling in neoplastic tissue. We investigated the basis of the unusual sensitivity of this model to metformin, and observed that following oral dosing, urothelium is exposed to drug concentrations via the urine that are ~ 240 fold higher than those in the circulation. In addition, we observed that bladder cancer cell lines (RT4, UMUC-3 and J82) with homozygous deletion of either TSC1 or PTEN are more sensitive to metformin than those (TEU2, TCCSUP and HT1376) with wild-type TSC1 and PTEN genes. Our findings provide a strong rationale for clinical trials of oral metformin in treatment of superficial bladder cancer. PMID:26921394

  16. Impact of Thermostats on Folding and Aggregation Properties of Peptides Using the Optimized Potential for Efficient Structure Prediction Coarse-Grained Model.

    PubMed

    Spill, Yannick G; Pasquali, Samuela; Derreumaux, Philippe

    2011-05-10

    The simulation of amyloid fibril formation is impossible if one takes into account all chemical details of the amino acids and their detailed interactions with the solvent. We investigate the folding and aggregation of two model peptides using the optimized potential for efficient structure prediction (OPEP) coarse-grained model and replica exchange molecular dynamics (REMD) simulations coupled with either the Langevin or the Berendsen thermostat. For both the monomer of blocked penta-alanine and the trimer of the 25-35 fragment of the Alzheimer's amyloid β protein, we find little variations in the equilibrium structures and heat capacity curves using the two thermostats. Despite this high similarity, we detect significant differences in the populations of the dominant conformations at low temperatures, whereas the configurational distributions remain the same in proximity of the melting temperature. Aβ25-35 trimers at 300 K have an averaged β-sheet content of 12% and are primarily characterized by fully disordered peptides or a small curved two-stranded β-sheet stabilized by a disordered peptide. In addition, OPEP molecular dynamics simulations of Aβ25-35 hexamers at 300 K with a small curved six-stranded antiparallel β-sheet do not show any extension of the β-sheet content. These data support the idea that the mechanism of Aβ25-35 amyloid formation does not result from a high fraction of extended β-sheet-rich trimers and hexamers.

  17. FOLD PROFILER: A MATLAB ®—based program for fold shape classification

    NASA Astrophysics Data System (ADS)

    Lisle, R. J.; Fernández Martínez, J. L.; Bobillo-Ares, N.; Menéndez, O.; Aller, J.; Bastida, F.

    2006-02-01

    FOLD PROFILER is a MATLAB code for classifying the shapes of profiles of folded surfaces. The classification is based on the comparison of the natural fold profile with curves representing mathematical functions. The user is offered a choice of four methods, each based on a different type of function: cubic Bezier curves, conic sections, power functions and superellipses. The comparison is carried out by the visual matching of the fold profile displayed on-screen from an imported digital image and computed theoretical curves which are superimposed on the image of the fold. To improve the fit with the real fold shape, the parameters of the theoretical curves are changed by simple mouse actions. The parameters of the mathematical function that best fits the real folds are used to classify the fold shape. FOLD PROFILER allows the rapid implementation of four existing methods for fold shape analysis. The attractiveness of this analytical tool lies in the way it gives an instant visual appreciation of the effect of changing the parameters that are used to classify fold geometry.

  18. Understanding the folding-function tradeoff in proteins.

    PubMed

    Gosavi, Shachi

    2013-01-01

    When an amino-acid sequence cannot be optimized for both folding and function, folding can get compromised in favor of function. To understand this tradeoff better, we devise a novel method for extracting the "function-less" folding-motif of a protein fold from a set of structurally similar but functionally diverse proteins. We then obtain the β-trefoil folding-motif, and study its folding using structure-based models and molecular dynamics simulations. CompariA protein sequence serves two purpson with the folding of wild-type β-trefoil proteins shows that function affects folding in two ways: In the slower folding interleukin-1β, binding sites make the fold more complex, increase contact order and slow folding. In the faster folding hisactophilin, residues which could have been part of the folding-motif are used for function. This reduces the density of native contacts in functional regions and increases folding rate. The folding-motif helps identify subtle structural deviations which perturb folding. These may then be used for functional annotation. Further, the folding-motif could potentially be used as a first step in the sequence design of function-less scaffold proteins. Desired function can then be engineered into these scaffolds.

  19. Folding, Binding, Misfolding and Aggregation with AWSEM

    NASA Astrophysics Data System (ADS)

    Schafer, Nicholas P.

    This thesis discusses our recent results using the Associative-memory, Water-mediated, Structure and Energy Model (AWSEM), an optimized, coarse-grained molecular dynamics protein folding model, to fold, bind, and predict the misfolding behavior of proteins. AWSEM is capable of performing de novo structure prediction on small alpha-helical protein domains and predict the binding interfaces of homo- and hetero-dimers. More recent work demonstrates how the misfolding behavior of tandem constructs in AWSEM is consistent with crucial aspects of ensemble and single molecule experiments on the aggregation and misfolding of these constructs. The first chapter is a review of the energy landscape theory of protein folding as it applies to the problem of protein structure prediction, and more specifically how energy landscape theory and the principle of minimal frustration can be used to optimize parameters of coarse-grained protein folding simulation models. The subsequent four chapters are reports of novel research performed with one such model.

  20. Small scale folding observed in the NEEM ice core

    NASA Astrophysics Data System (ADS)

    Jansen, Daniela; Llorens, Maria-Gema; Westhoff, Julien; Steinbach, Florian; Bons, Paul D.; Kipfstuhl, Sepp; Griera, Albert; Weikusat, Ilka

    2015-04-01

    Disturbances on the centimeter scale in the layering of the NEEM ice core (North Greenland) can be mapped by means of visual stratigraphy as long as the ice does have a visual layering, such as, for example, cloudy bands. Different focal depths of the visual stratigraphy method allow, to a certain extent, a three dimensional view of the structures. In this study we present a structural analysis of the visible folds, discuss characteristics and frequency and present examples of typical fold structures. With this study we aim to quantify the potential impact of small scale folding on the integrity of climate proxy data. We also analyze the structures with regard to the stress environment under which they formed. The structures evolve from gentle waves at about 1700 m to overturned z-folds with increasing depth. Occasionally, the folding causes significant thickening of layers. Their shape indicates that they are passive features and are probably not initiated by rheology differences between layers. Layering is heavily disturbed and tracing of single layers is no longer possible below a depth of 2160 m. Lattice orientation distributions for the corresponding core sections were analyzed where available in addition to visual stratigraphy. The data show axial-plane parallel strings of grains with c.axis orientations that deviate from that of the matrix, which has more or less a single-maximum fabric at the depth where the folding occurs. We conclude from these data that folding is a consequence of deformation along localized shear planes and kink bands. The findings are compared with results from other deep ice cores. The observations presented are supplemented by microstructural modeling using a crystal plasticity code that reproduces deformation, applying a Fast Fourier Transform (FFT), coupled with ELLE to include dynamic recrystallization processes. The model results reproduce the development of bands of grains with a tilted orientation relative to the single maximum

  1. Operations and Modeling Analysis

    NASA Technical Reports Server (NTRS)

    Ebeling, Charles

    2005-01-01

    The Reliability and Maintainability Analysis Tool (RMAT) provides NASA the capability to estimate reliability and maintainability (R&M) parameters and operational support requirements for proposed space vehicles based upon relationships established from both aircraft and Shuttle R&M data. RMAT has matured both in its underlying database and in its level of sophistication in extrapolating this historical data to satisfy proposed mission requirements, maintenance concepts and policies, and type of vehicle (i.e. ranging from aircraft like to shuttle like). However, a companion analyses tool, the Logistics Cost Model (LCM) has not reached the same level of maturity as RMAT due, in large part, to nonexistent or outdated cost estimating relationships and underlying cost databases, and it's almost exclusive dependence on Shuttle operations and logistics cost input parameters. As a result, the full capability of the RMAT/LCM suite of analysis tools to take a conceptual vehicle and derive its operations and support requirements along with the resulting operating and support costs has not been realized.

  2. Chaperonin-mediated Protein Folding

    PubMed Central

    Horwich, Arthur L.

    2013-01-01

    We have been studying chaperonins these past twenty years through an initial discovery of an action in protein folding, analysis of structure, and elucidation of mechanism. Some of the highlights of these studies were presented recently upon sharing the honor of the 2013 Herbert Tabor Award with my early collaborator, Ulrich Hartl, at the annual meeting of the American Society for Biochemistry and Molecular Biology in Boston. Here, some of the major findings are recounted, particularly recognizing my collaborators, describing how I met them and how our great times together propelled our thinking and experiments. PMID:23803606

  3. Dual folding pathways of an α /β protein from all-atom ab initio folding simulations

    NASA Astrophysics Data System (ADS)

    Lei, Hongxing; Wang, Zhi-Xiang; Wu, Chun; Duan, Yong

    2009-10-01

    Successful ab initio folding of proteins with both α-helix and β-sheet requires a delicate balance among a variety of forces in the simulation model, which may explain that the successful folding of any α /β proteins to within experimental error has yet to be reported. Here we demonstrate that it is an achievable goal to fold α /β proteins with a force field emphasizing the balance between the two major secondary structures. Using our newly developed force field, we conducted extensive ab initio folding simulations on an α /β protein full sequence design (FSD) employing both conventional molecular dynamics and replica exchange molecular dynamics in combination with a generalized-Born solvation model. In these simulations, the folding of FSD to the native state with high population (>64.2%) and high fidelity (Cα-Root Mean Square Deviation of 1.29 Å for the most sampled conformation when compared to the experimental structure) was achieved. The folding of FSD was found to follow two pathways. In the major pathway, the folding started from the formation of the helix. In the minor pathway, however, folding of the β-hairpin started first. Further examination revealed that the helix initiated from the C-terminus and propagated toward the N-terminus. The formation of the hydrophobic contacts coincided with the global folding. Therefore the hydrophobic force does not appear to be the driving force of the folding of this protein.

  4. Folding and Finding RNA Secondary Structure

    PubMed Central

    Mathews, David H.; Moss, Walter N.; Turner, Douglas H.

    2010-01-01

    SUMMARY Optimal exploitation of the expanding database of sequences requires rapid finding and folding of RNAs. Methods are reviewed that automate folding and discovery of RNAs with algorithms that couple thermodynamics with chemical mapping, NMR, and/or sequence comparison. New functional noncoding RNAs in genome sequences can be found by combining sequence comparison with the assumption that functional noncoding RNAs will have more favorable folding free energies than other RNAs. When a new RNA is discovered, experiments and sequence comparison can restrict folding space so that secondary structure can be rapidly determined with the help of predicted free energies. In turn, secondary structure restricts folding in three dimensions, which allows modeling of three-dimensional structure. An example from a domain of a retrotransposon is described. Discovery of new RNAs and their structures will provide insights into evolution, biology, and design of therapeutics. Applications to studies of evolution are also reviewed. PMID:20685845

  5. Composition-based effective chain length for prediction of protein folding rates

    NASA Astrophysics Data System (ADS)

    Chang, Le; Wang, Jun; Wang, Wei

    2010-11-01

    Folding rate prediction is a useful way to find the key factors affecting folding kinetics of proteins. Structural information is more or less required in the present prediction methods, which limits the application of these methods to various proteins. In this work, an “effective length” is defined solely based on the composition of a protein, namely, the number of specific types of amino acids in a protein. A physical theory based on a minimalist model is employed to describe the relation between the folding rates and the effective length of proteins. Based on the resultant relationship between folding rates and effective length, the optimal sets of amino acids are found through the enumeration over all possible combinations of amino acids. This optimal set achieves a high correlation (with the coefficient of 0.84) between the folding rates and the optimal effective length. The features of these amino acids are consistent with our model and landscape theory. Further comparisons between our effective length and other factors are carried out. The effective length is physically consistent with structure-based prediction methods and has the best predictability for folding rates. These results all suggest that both entropy and energetics contribute importantly to folding kinetics. The ability to accurately and efficiently predict folding rates from composition enables the analysis of the kinetics for various kinds of proteins. The underlying physics in our method may be helpful to stimulate further understanding on the effects of various amino acids in folding dynamics.

  6. Stochastic Resonance in Protein Folding Dynamics.

    PubMed

    Davtyan, Aram; Platkov, Max; Gruebele, Martin; Papoian, Garegin A

    2016-05-04

    Although protein folding reactions are usually studied under static external conditions, it is likely that proteins fold in a locally fluctuating cellular environment in vivo. To mimic such behavior in in vitro experiments, the local temperature of the solvent can be modulated either harmonically or using correlated noise. In this study, coarse-grained molecular simulations are used to investigate these possibilities, and it is found that both periodic and correlated random fluctuations of the environment can indeed accelerate folding kinetics if the characteristic frequencies of the applied fluctuations are commensurate with the internal timescale of the folding reaction; this is consistent with the phenomenon of stochastic resonance observed in many other condensed-matter processes. To test this theoretical prediction, the folding dynamics of phosphoglycerate kinase under harmonic temperature fluctuations are experimentally probed using Förster resonance energy transfer fluorescence measurements. To analyze these experiments, a combination of theoretical approaches is developed, including stochastic simulations of folding kinetics and an analytical mean-field kinetic theory. The experimental observations are consistent with the theoretical predictions of stochastic resonance in phosphoglycerate kinase folding. When combined with an alternative experiment on the protein VlsE using a power spectrum analysis, elaborated in Dave et al., ChemPhysChem 2016, 10.1002/cphc.201501041, the overall data overwhelmingly point to the experimental confirmation of stochastic resonance in protein folding dynamics.

  7. Characterization of Folding Cores in the Cyclophilin A-Cyclosporin A Complex

    PubMed Central

    Heal, Jack W.; Wells, Stephen A.; Blindauer, Claudia A.; Freedman, Robert B.; Römer, Rudolf A.

    2015-01-01

    Determining the folding core of a protein yields information about its folding process and dynamics. The experimental procedures for identifying the amino acids that make up the folding core include hydrogen-deuterium exchange and Φ-value analysis and can be expensive and time consuming. Because of this, there is a desire to improve upon existing methods for determining protein folding cores theoretically. We have obtained HDX data for the complex of cyclophilin A with the immunosuppressant cyclosporin A. We compare these data, as well as literature values for uncomplexed cyclophilin A, to theoretical predictions using a combination of rigidity analysis and coarse-grained simulations of protein motion. We find that in this case, the most specific prediction of folding cores comes from a combined approach that models the rigidity of the protein using the first software suite and the dynamics of the protein using the froda tool. PMID:25863065

  8. Fractures Sets Associated to Buckle Folds

    NASA Astrophysics Data System (ADS)

    Liu, X.; Eckert, A.; Connolly, P. T.

    2014-12-01

    Buckle folds of single and multilayered sedimentary strata in the literature are commonly associated to a variety of different fracture sets, both shear and tensile. Amongst the most noticeable fractures are tensile fractures occurring in the outer hinges of the fold crest and shear fractures in the bottom of fold hinge zones. These fractures are well explained and understood by the extensional and compressional strain/stress pattern in the fold hinge. However, tensile fractures parallel to the fold axis, tensile fractures cutting through the limb, normal faults on the fold hinge, and shear fractures of different orientations in the fold limb cannot intuitively be linked to the stress regime occurring during the buckling process. This study utilizes a 2D and 3D finite element modeling approach using Maxwell visco-elastic rheology to study the stress conditions during single and multilayer buckling for each fracture set to occur. The numerical simulations include sensitivity analyses on material parameters such as permeability, viscosity and overburden thickness. For fracture sets not likely to occur during the buckling process pre- and post folding processes such as initial overpressure, extensional unfolding, and erosional unloading are studied.

  9. Frustration in Condensed Matter and Protein Folding

    NASA Astrophysics Data System (ADS)

    Li, Z.; Tanner, S.; Conroy, B.; Owens, F.; Tran, M. M.; Boekema, C.

    2014-03-01

    By means of computer modeling, we are studying frustration in condensed matter and protein folding, including the influence of temperature and Thomson-figure formation. Frustration is due to competing interactions in a disordered state. The key issue is how the particles interact to reach the lowest frustration. The relaxation for frustration is mostly a power function (randomly assigned pattern) or an exponential function (regular patterns like Thomson figures). For the atomic Thomson model, frustration is predicted to decrease with the formation of Thomson figures at zero kelvin. We attempt to apply our frustration modeling to protein folding and dynamics. We investigate the homogeneous protein frustration that would cause the speed of the protein folding to increase. Increase of protein frustration (where frustration and hydrophobicity interplay with protein folding) may lead to a protein mutation. Research is supported by WiSE@SJSU and AFC San Jose.

  10. Application of a folding-model optical potential to analyzing inelastic pion-nucleus scattering and the in-medium effect on a pion-nucleon amplitude

    NASA Astrophysics Data System (ADS)

    Lukyanov, V. K.; Zemlyanaya, E. V.; Lukyanov, K. V.; Abdul-Magead, I. A. M.

    2016-11-01

    The folding-model optical potential is generalized in such a way as to apply it to calculating the cross sections for inelastic scattering of π ±-mesons on 28Si, 40Ca, 58Ni, and 208Pb nuclei at the energies of 162, 180, 226, and 291 MeV leading to the excitation of the 2+ and 3- collective states. In doing this, use is made of known nucleon-density distributions in nuclei and the pion-nucleon scattering amplitude whose parameters were obtained previously by fitting the elastic scattering cross sections for the same nuclei. Thus, the values of quadrupole ( β 2) and octupole ( β 3) deformations of nuclei appear here as the only adjustable parameters. The scattering cross section is calculated by solving the relativistic wave equation, whereby effects of relativization and distortion in the entrance and exit scattering channels are taken exactly into account. The cross sections calculated in this way for inelastic scattering are in good agreement with respective experimental data. The importance of the inclusion of in-medium effects in choosing parameters of the pion-nucleon amplitude is emphasized.

  11. Sequencing and G-Quadruplex Folding of the Canine Proto-Oncogene KIT Promoter Region: Might Dog Be Used as a Model for Human Disease?

    PubMed Central

    Da Ros, Silvia; Zorzan, Eleonora; Giantin, Mery; Zorro Shahidian, Lara; Palumbo, Manlio; Dacasto, Mauro; Sissi, Claudia

    2014-01-01

    Downregulation of gene expression by induction of non-canonical DNA structures at promotorial level is a novel attractive anticancer strategy. In human, two guanine-rich sequences (h_kit1 and h_kit2) were identified in the promotorial region of oncogene KIT. Their stabilization into G-quadruplex structures can find applications in the treatment of leukemias, mastocytosis, gastrointestinal stromal tumor, and lung carcinomas which are often associated to c-kit mis-regulation. Also the most common skin cancer in domestic dog, mast cell tumor, is linked to a mutation and/or to an over-expression of c-kit, thus supporting dog as an excellent animal model. In order to assess if the G-quadruplex mediated mechanism of regulation of c-kit expression is conserved among the two species, herein we cloned and sequenced the canine KIT promoter region and we compared it with the human one in terms of sequence and conformational equilibria in physiologically relevant conditions. Our results evidenced a general conserved promotorial sequence between the two species. As experimentally confirmed, this grants that the conformational features of the canine kit1 sequence are substantially shared with the human one. Conversely, two isoforms of the kit2 sequences were identified in the analyzed dog population. In comparison with the human counterpart, both of them showed an altered distribution among several folded conformations. PMID:25084283

  12. Prediction of folding pathway and kinetics among plant hemoglobins using an average distance map method.

    PubMed

    Nakajima, Shunsuke; Alvarez-Salgado, Emma; Kikuchi, Takeshi; Arredondo-Peter, Raúl

    2005-11-15

    Computational methods, such as the ADM (average distance map) method, have been developed to predict folding of homologous proteins. In this work we used the ADM method to predict the folding pathway and kinetics among selected plant nonsymbiotic (nsHb), symbiotic (Lb), and truncated (tHb) hemoglobins (Hbs). Results predicted that (1) folding of plant Hbs occurs throughout the formation of compact folding modules mostly formed by helices A, B, and C, and E, F, G, and H (folding modules A/C and E/H, respectively), and (2) primitive (moss) nsHbs fold in the C-->N direction, evolved (monocot and dicot) nsHbs fold either in the C-->N or N-->C direction, and Lbs and plant tHbs fold in the C-->N direction. We also predicted relative folding rates of plant Hbs from qualitative analyses of the stability of subdomains and classified plant Hbs into fast and moderate folding. ADM analysis of nsHbs predicted that prehelix A plays a role during folding of the N-terminal domain of Ceratodon nsHb, and that CD-loop plays a role in folding of primitive (Physcomitrella and Ceratodon) but not evolved nsHbs. Modeling of the rice Hb1 A/C and E/H modules showed that module E/H overlaps to the Mycobacterium tuberculosis HbO two-on-two folding. This observation suggests that module E/H is an ancient tertiary structure in plant Hbs.

  13. Fold-and-thrust belt evolution influenced by along and across strike thickness variations: new insights from brittle-ductile centrifuge analogue models

    NASA Astrophysics Data System (ADS)

    Santolaria Otin, Pablo; Harris, Lyal; Casas, Antonio; Soto, Ruth

    2014-05-01

    Using a new centrifuge analogue modelling approach, 38 models were performed to study the influence of along and across strike thickness variations of a ductile-brittle layered sequence on the kinematics and deformation style of fold-and-thrust belts. Four different series, changing the brittle-ductile thickness ratio in models with i) constant thickness, ii) across strike varying thickness, iii) along strike varying thickness and iv) along and across-strike varying thickness, were performed. The brittle sedimentary cover was simulated by "Moon Sand™", regular fine-grained quartz sand coated by polymer and synthetic rubber binders, allowing layers to be placed vertically in the centrifuge (impossible with normal sand). The ductile décollement (evaporites) was simulated by silicone putty (Crazy Aaron Enterprise's Thinking Putty™). Models were run step by step in a high-acceleration centrifuge attaining 900 g, what allows to drastically reduce the experimental time. In addition to surface observation and serial cross-sections at the end of the models, CT scans portray the progressive 3- and 4-dimensional evolution of several models. With constant thickness, the increase of the brittle-ductile ratio results in the decrease of the number of structures where shortening is accommodated and the development of structures does not follow a linear sequence. Across-strike thickness variations trigger the location of deformation towards the wedge front, precluding the emplacement of structures in the hinterland. Along-strike thickness changes result in the lateral variation of the number of structure and a differential displacement of the deformation front. The occurrence of oblique structures is enhanced in wedges with across and along strike thickness variations where, in addition, rotational domains are observed. Comparison with the South Pyrenean Central Unit, in the Southern Pyrenees, characterized by a west- and southward thinning of the pretectonic Mesozoic series

  14. Folds on Europa

    NASA Technical Reports Server (NTRS)

    2000-01-01

    This image, acquired by NASA's Galileo spacecraft on September 26, 1998, shows features on the surface of Jupiter's moon Europa that a scientific report published today interprets as signs of compressive folding.

    The imaged area is in the Astypalaea Linea region of Europa's southern hemisphere, seen with low-angle sunshine coming from the upper right. North is toward the top.

    Astypalaea Linea is the smooth, gray area that stretches from north to south across the image mosaic. It is thought to have formed by a combination of pulling apart and sliding of the icy surface. The telltale fold features are within the smoother portions of the surface between the more dominant ridges, which are attributed to upwelling of material through surface ice. In the smooth areas, the surface has gentle swells and dips, which show most clearly in the version on the right, processed to accentuate broader-scale shapes. For example, a dip about 15 kilometers (about 10 miles) wide cuts diagonally across the northern half of the largest smooth area, and a rise runs parallel to that in the southern half of the smooth area. closeup detail

    Louise M. Prockter, at Johns Hopkins University, and Robert T. Pappalardo, at Brown University, report in the journal Science today that those rises, or anticlines, and dips, or synclines, appear to be the result of compression causing the crust to fold.

    Additional evidence comes from smaller features more visible in the version on the left, covering the same area. At the crest of the gentle rise in the largest smooth area are small fractures that could be caused by the stretching stress of bending the surface layer upwards. Similarly, at the bottom of the adjacent dip are small, wrinkle-like ridges that could be caused by stress from bending the surface layer downwards.

    The Jet Propulsion Laboratory, Pasadena, Calif., manages the Galileo mission for NASA's Office of Space Science, Washington, D.C. JPL is a division of the California

  15. Quantification of a Helical Origami Fold

    NASA Astrophysics Data System (ADS)

    Dai, Eric; Han, Xiaomin; Chen, Zi

    2015-03-01

    Origami, the Japanese art of paper folding, is traditionally viewed as an amusing pastime and medium of artistic expression. However, in recent years, origami has served as a source of inspiration for innovations in science and engineering. Here, we present the geometric and mechanical properties of a twisting origami fold. The origami structure created by the fold exhibits several interesting properties, including rigid foldibility, local bistability and finely tunable helical coiling, with control over pitch, radius and handedness of the helix. In addition, the pattern generated by the fold closely mimics the twist buckling patterns shown by thin materials, for example, a mobius strip. We use six parameters of the twisting origami pattern to generate a fully tunable graphical model of the fold. Finally, we present a mathematical model of the local bistability of the twisting origami fold. Our study elucidates the mechanisms behind the helical coiling and local bistability of the twisting origami fold, with potential applications in robotics and deployable structures. Acknowledgment to Branco Weiss Fellowship for funding.

  16. Protein photo-folding and quantum folding theory.

    PubMed

    Luo, Liaofu

    2012-06-01

    The rates of protein folding with photon absorption or emission and the cross section of photon -protein inelastic scattering are calculated from quantum folding theory by use of a field-theoretical method. All protein photo-folding processes are compared with common protein folding without the interaction of photons (non-radiative folding). It is demonstrated that there exists a common factor (thermo-averaged overlap integral of the vibration wave function, TAOI) for protein folding and protein photo-folding. Based on this finding it is predicted that (i) the stimulated photo-folding rates and the photon-protein resonance Raman scattering sections show the same temperature dependence as protein folding; (ii) the spectral line of the electronic transition is broadened to a band that includes an abundant vibration spectrum without and with conformational transitions, and the width of each vibration spectral line is largely reduced. The particular form of the folding rate-temperature relation and the abundant spectral structure imply the existence of quantum tunneling between protein conformations in folding and photo-folding that demonstrates the quantum nature of the motion of the conformational-electronic system.

  17. Folding at the birth of the nascent chain: coordinating translation with co-translational folding.

    PubMed

    Zhang, Gong; Ignatova, Zoya

    2011-02-01

    In the living cells, the folding of many proteins is largely believed to begin co-translationally, during their biosynthesis at the ribosomes. In the ribosomal tunnel, the nascent peptide may establish local interactions and stabilize α-helical structures. Long-range contacts are more likely outside the ribosomes after release of larger segments of the nascent chain. Examples suggest that domains can attain native-like structure on the ribosome with and without population of folding intermediates. The co-translational folding is limited by the speed of the gradual extrusion of the nascent peptide which imposes conformational restraints on its folding landscape. Recent experimental and in silico modeling studies indicate that translation kinetics fine-tunes co-translational folding by providing a time delay for sequential folding of distinct portions of the nascent chain.

  18. Spin glasses and the statistical mechanics of protein folding.

    PubMed Central

    Bryngelson, J D; Wolynes, P G

    1987-01-01

    The theory of spin glasses was used to study a simple model of protein folding. The phase diagram of the model was calculated, and the results of dynamics calculations are briefly reported. The relation of these results to folding experiments, the relation of these hypotheses to previous protein folding theories, and the implication of these hypotheses for protein folding prediction schemes are discussed. PMID:3478708

  19. Folded MEMS approach to NMRG

    NASA Astrophysics Data System (ADS)

    Gundeti, Venu Madhav

    Atomic gyroscopes have a potential for good performance advantages and several attempts are being made to miniaturize them. This thesis describes the efforts made in implementing a Folded MEMS based NMRG. The micro implementations of all the essential components for NMRG (Nuclear Magnetic Resonance Gyroscope) are described in detail in regards to their design, fabrication, and characterization. A set of micro-scale Helmholtz coils are described and the homogeneity of the generated magnetic field is analyzed for different designs of heaters. The dielectric mirrors and metallic mirrors are compared in terms of reflectivity and polarization change up on reflection. A pyramid shaped folded backbone structure is designed, fabricated, and assembled along with all the required components. A novel double-folded structure 1/4th the size of original version is fabricated and assembled. Design and modeling details of a 5 layered shield with shielding factor > 106 and total volume of around 90 cc are also presented. A table top setup for characterization of atomic vapor cell is described in detail. A micro vapor cell based Rb magnetometer with a sensitivity of 108 pT/√Hz is demonstrated. The challenges due to DC heating are addressed and mitigated using an AC heater. Several experiments related to measuring the relaxation time of Xe are provided along with results. For Xe131, relaxation times of T1 = 23.78 sec, T2 = 18.06 sec and for Xe129, T1 = 21.65 sec and T2 = 20.45 sec are reported.

  20. Folded dielectric elastomer actuators

    NASA Astrophysics Data System (ADS)

    Carpi, Federico; Salaris, Claudio; DeRossi, Danilo

    2007-04-01

    Polymer-based linear actuators with contractile ability are currently demanded for several types of applications. Within the class of dielectric elastomer actuators, two basic configurations are available today for such a purpose: the multi-layer stack and the helical structure. The first consists of several layers of elementary planar actuators stacked in series mechanically and parallel electrically. The second configuration relies on a couple of helical compliant electrodes alternated with a couple of helical dielectrics. The fabrication of both these configurations presents some specific drawbacks today, arising from the peculiarity of each structure. Accordingly, the availability of simpler solutions may boost the short-term use of contractile actuators in practical applications. For this purpose, a new configuration is here described. It consists of a monolithic structure made of an electroded sheet, which is folded up and compacted. The resulting device is functionally equivalent to a multi-layer stack with interdigitated electrodes. However, with respect to a stack the new configuration is advantageously not discontinuous and can be manufactured in one single phase, avoiding layer-by-layer multi-step procedures. The development and preliminary testing of prototype samples of this new actuator made of a silicone elastomer are presented here.

  1. Statistical properties of a folded elastic rod

    NASA Astrophysics Data System (ADS)

    Bayart, Elsa; Deboeuf, Stéphanie; Boué, Laurent; Corson, Francis; Boudaoud, Arezki; Adda-Bedia, Mokhtar

    2010-03-01

    A large variety of elastic structures naturally seem to be confined into environments too small to accommodate them; the geometry of folded structures span a wide range of length-scales. The elastic properties of these confined systems are further constrained by self-avoidance as well as by the dimensionality of both structures and container. To mimic crumpled paper, we devised an experimental setup to study the packing of a dimensional elastic object in 2D geometries: an elastic rod is folded at the center of a circular Hele-Shaw cell by a centripetal force. The initial configuration of the rod and the acceleration of the rotating disk allow to span different final folded configurations while the final rotation speed controls the packing intensity. Using image analysis we measure geometrical and mechanical properties of the folded configurations, focusing on length, curvature and energy distributions.

  2. Model-Based Safety Analysis

    NASA Technical Reports Server (NTRS)

    Joshi, Anjali; Heimdahl, Mats P. E.; Miller, Steven P.; Whalen, Mike W.

    2006-01-01

    System safety analysis techniques are well established and are used extensively during the design of safety-critical systems. Despite this, most of the techniques are highly subjective and dependent on the skill of the practitioner. Since these analyses are usually based on an informal system model, it is unlikely that they will be complete, consistent, and error free. In fact, the lack of precise models of the system architecture and its failure modes often forces the safety analysts to devote much of their effort to gathering architectural details about the system behavior from several sources and embedding this information in the safety artifacts such as the fault trees. This report describes Model-Based Safety Analysis, an approach in which the system and safety engineers share a common system model created using a model-based development process. By extending the system model with a fault model as well as relevant portions of the physical system to be controlled, automated support can be provided for much of the safety analysis. We believe that by using a common model for both system and safety engineering and automating parts of the safety analysis, we can both reduce the cost and improve the quality of the safety analysis. Here we present our vision of model-based safety analysis and discuss the advantages and challenges in making this approach practical.

  3. 3-D numerical models of viscous flow applied to fold nappes and the Rawil depression in the Helvetic nappe system (western Switzerland)

    NASA Astrophysics Data System (ADS)

    von Tscharner, M.; Schmalholz, S. M.; Epard, J.-L.

    2016-05-01

    The Helvetic nappe system exhibits three-dimensional (3-D) features such as the lateral variation in geometry between the Morcles and Doldenhorn fold nappes or the Rawil depression. We perform 3-D finite element simulations of linear and power-law viscous flow to investigate fold nappe formation during shortening of a half graben with laterally varying thickness. 3-D ellipsoids and corresponding 2-D intersection ellipses are used to quantify finite strain. Fold nappes which formed above a thicker graben have (i) larger amplitudes, (ii) a less sheared and thinned overturned limb, and (iii) a larger thickness than fold nappes formed above a thinner graben. These results agree with observations for the Morcles and Doldenhorn nappes. We also perform 3-D simulations for a tectonic scenario suggested for the evolution of the Rawil depression. The basement is shortened and extended laterally and includes a graben which is oblique to the shortening direction and acts as mechanical weak zone. The graben causes laterally varying basement uplift generating a depression whose amplitude depends on the graben orientation and the stress exponent of basement and sediments. The axial plunge of the depression is smaller (approximately 10°) than the observed plunge (approximately 30°) indicating that additional processes are required to explain the geometry of the Rawil depression.

  4. Non-cylindrical fold growth in the Zagros fold and thrust belt (Kurdistan, NE-Iraq)

    NASA Astrophysics Data System (ADS)

    Bartl, Nikolaus; Bretis, Bernhard; Grasemann, Bernhard; Lockhart, Duncan

    2010-05-01

    The Zagros mountains extends over 1800 km from Kurdistan in N-Iraq to the Strait of Hormuz in Iran and is one of the world most promising regions for the future hydrocarbon exploration. The Zagros Mountains started to form as a result of the collision between the Eurasian and Arabian Plates, whose convergence began in the Late Cretaceous as part of the Alpine-Himalayan orogenic system. Geodetic and seismological data document that both plates are still converging and that the fold and thrust belt of the Zagros is actively growing. Extensive hydrocarbon exploration mainly focuses on the antiforms of this fold and thrust belt and therefore the growth history of the folds is of great importance. This work investigates by means of structural field work and quantitative geomorphological techniques the progressive fold growth of the Permam, Bana Bawi- and Safeen- Anticlines located in the NE of the city of Erbil in the Kurdistan region of Northern Iraq. This part of the Zagros fold and thrust belt belongs to the so-called Simpl