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Sample records for intrinsic energy landscapes

  1. Intrinsically Disordered Energy Landscapes

    NASA Astrophysics Data System (ADS)

    Chebaro, Yassmine; Ballard, Andrew J.; Chakraborty, Debayan; Wales, David J.

    2015-05-01

    Analysis of an intrinsically disordered protein (IDP) reveals an underlying multifunnel structure for the energy landscape. We suggest that such ‘intrinsically disordered’ landscapes, with a number of very different competing low-energy structures, are likely to characterise IDPs, and provide a useful way to address their properties. In particular, IDPs are present in many cellular protein interaction networks, and several questions arise regarding how they bind to partners. Are conformations resembling the bound structure selected for binding, or does further folding occur on binding the partner in a induced-fit fashion? We focus on the p53 upregulated modulator of apoptosis (PUMA) protein, which adopts an -helical conformation when bound to its partner, and is involved in the activation of apoptosis. Recent experimental evidence shows that folding is not necessary for binding, and supports an induced-fit mechanism. Using a variety of computational approaches we deduce the molecular mechanism behind the instability of the PUMA peptide as a helix in isolation. We find significant barriers between partially folded states and the helix. Our results show that the favoured conformations are molten-globule like, stabilised by charged and hydrophobic contacts, with structures resembling the bound state relatively unpopulated in equilibrium.

  2. Intrinsically Disordered Energy Landscapes

    PubMed Central

    Chebaro, Yassmine; Ballard, Andrew J.; Chakraborty, Debayan; Wales, David J.

    2015-01-01

    Analysis of an intrinsically disordered protein (IDP) reveals an underlying multifunnel structure for the energy landscape. We suggest that such ‘intrinsically disordered’ landscapes, with a number of very different competing low-energy structures, are likely to characterise IDPs, and provide a useful way to address their properties. In particular, IDPs are present in many cellular protein interaction networks, and several questions arise regarding how they bind to partners. Are conformations resembling the bound structure selected for binding, or does further folding occur on binding the partner in a induced-fit fashion? We focus on the p53 upregulated modulator of apoptosis (PUMA) protein, which adopts an -helical conformation when bound to its partner, and is involved in the activation of apoptosis. Recent experimental evidence shows that folding is not necessary for binding, and supports an induced-fit mechanism. Using a variety of computational approaches we deduce the molecular mechanism behind the instability of the PUMA peptide as a helix in isolation. We find significant barriers between partially folded states and the helix. Our results show that the favoured conformations are molten-globule like, stabilised by charged and hydrophobic contacts, with structures resembling the bound state relatively unpopulated in equilibrium. PMID:25999294

  3. Quantifying the topography of the intrinsic energy landscape of flexible biomolecular recognition.

    PubMed

    Chu, Xiakun; Gan, Linfeng; Wang, Erkang; Wang, Jin

    2013-06-25

    Biomolecular functions are determined by their interactions with other molecules. Biomolecular recognition is often flexible and associated with large conformational changes involving both binding and folding. However, the global and physical understanding for the process is still challenging. Here, we quantified the intrinsic energy landscapes of flexible biomolecular recognition in terms of binding-folding dynamics for 15 homodimers by exploring the underlying density of states, using a structure-based model both with and without considering energetic roughness. By quantifying three individual effective intrinsic energy landscapes (one for interfacial binding, two for monomeric folding), the association mechanisms for flexible recognition of 15 homodimers can be classified into two-state cooperative "coupled binding-folding" and three-state noncooperative "folding prior to binding" scenarios. We found that the association mechanism of flexible biomolecular recognition relies on the interplay between the underlying effective intrinsic binding and folding energy landscapes. By quantifying the whole global intrinsic binding-folding energy landscapes, we found strong correlations between the landscape topography measure Λ (dimensionless ratio of energy gap versus roughness modulated by the configurational entropy) and the ratio of the thermodynamic stable temperature versus trapping temperature, as well as between Λ and binding kinetics. Therefore, the global energy landscape topography determines the binding-folding thermodynamics and kinetics, crucial for the feasibility and efficiency of realizing biomolecular function. We also found "U-shape" temperature-dependent kinetic behavior and a dynamical cross-over temperature for dividing exponential and nonexponential kinetics for two-state homodimers. Our study provides a unique way to bridge the gap between theory and experiments.

  4. Single-molecule imaging of DNA curtains reveals intrinsic energy landscapes for nucleosome deposition

    PubMed Central

    Visnapuu, Mari-Liis; Greene, Eric C.

    2009-01-01

    Here we use single-molecule imaging to determine coarse-grained intrinsic energy landscapes for nucleosome deposition on model DNA substrates. Our results reveal distributions that are correlated with recent in silico predictions, reinforcing the hypothesis that DNA contains some intrinsic positioning information. We also show that cis-regulatory sequences in human DNA coincide with peaks in the intrinsic landscape, whereas valleys correspond to non-regulatory regions, and we present evidence arguing that nucleosome deposition in vertebrates is influenced by factors not accounted for by current theory. Finally, we demonstrate that intrinsic landscapes of nucleosomes containing the centromere-specific variant CenH3 are correlated with patterns observed for canonical nucleosomes, arguing that CenH3 does not alter sequence preferences of centromeric nucleosomes. However, the non-histone protein Scm3 alters the intrinsic landscape of CenH3-containing nucleosomes, enabling them to overcome the otherwise exclusionary effects of poly(dA–dT) tracts, which are enriched in centromeric DNA. PMID:19734899

  5. The inverted free energy landscape of an intrinsically disordered peptide by simulations and experiments.

    PubMed

    Granata, Daniele; Baftizadeh, Fahimeh; Habchi, Johnny; Galvagnion, Celine; De Simone, Alfonso; Camilloni, Carlo; Laio, Alessandro; Vendruscolo, Michele

    2015-10-26

    The free energy landscape theory has been very successful in rationalizing the folding behaviour of globular proteins, as this representation provides intuitive information on the number of states involved in the folding process, their populations and pathways of interconversion. We extend here this formalism to the case of the Aβ40 peptide, a 40-residue intrinsically disordered protein fragment associated with Alzheimer's disease. By using an advanced sampling technique that enables free energy calculations to reach convergence also in the case of highly disordered states of proteins, we provide a precise structural characterization of the free energy landscape of this peptide. We find that such landscape has inverted features with respect to those typical of folded proteins. While the global free energy minimum consists of highly disordered structures, higher free energy regions correspond to a large variety of transiently structured conformations with secondary structure elements arranged in several different manners, and are not separated from each other by sizeable free energy barriers. From this peculiar structure of the free energy landscape we predict that this peptide should become more structured and not only more compact, with increasing temperatures, and we show that this is the case through a series of biophysical measurements.

  6. Constructing the Energy Landscape for Genetic Switching System Driven by Intrinsic Noise

    PubMed Central

    Li, Fangting; Li, Tiejun

    2014-01-01

    Genetic switching driven by noise is a fundamental cellular process in genetic regulatory networks. Quantitatively characterizing this switching and its fluctuation properties is a key problem in computational biology. With an autoregulatory dimer model as a specific example, we design a general methodology to quantitatively understand the metastability of gene regulatory system perturbed by intrinsic noise. Based on the large deviation theory, we develop new analytical techniques to describe and calculate the optimal transition paths between the on and off states. We also construct the global quasi-potential energy landscape for the dimer model. From the obtained quasi-potential, we can extract quantitative results such as the stationary distributions of mRNA, protein and dimer, the noise strength of the expression state, and the mean switching time starting from either stable state. In the final stage, we apply this procedure to a transcriptional cascades model. Our results suggest that the quasi-potential energy landscape and the proposed methodology are general to understand the metastability in other biological systems with intrinsic noise. PMID:24551081

  7. Free-energy landscape of intrinsically disordered proteins investigated by all-atom multicanonical molecular dynamics.

    PubMed

    Higo, Junichi; Umezawa, Koji

    2014-01-01

    We introduce computational studies on intrinsically disordered proteins (IDPs). Especially, we present our multicanonical molecular dynamics (McMD) simulations of two IDP-partner systems: NRSF-mSin3 and pKID-KIX. McMD is one of enhanced conformational sampling methods useful for conformational sampling of biomolecular systems. IDP adopts a specific tertiary structure upon binding to its partner molecule, although it is unstructured in the unbound state (i.e. the free state). This IDP-specific property is called "coupled folding and binding". The McMD simulation treats the biomolecules with an all-atom model immersed in an explicit solvent. In the initial configuration of simulation, IDP and its partner molecules are set to be distant from each other, and the IDP conformation is disordered. The computationally obtained free-energy landscape for coupled folding and binding has shown that native- and non-native-complex clusters distribute complicatedly in the conformational space. The all-atom simulation suggests that both of induced-folding and population-selection are coupled complicatedly in the coupled folding and binding. Further analyses have exemplified that the conformational fluctuations (dynamical flexibility) in the bound and unbound states are essentially important to characterize IDP functioning.

  8. Landscaping for energy efficiency

    SciTech Connect

    1995-04-01

    This publication by the National Renewable Energy Laboratory addresses the use of landscaping for energy efficiency. The topics of the publication include minimizing energy expenses; landscaping for a cleaner environment; climate, site, and design considerations; planning landscape; and selecting and planting trees and shrubs. A source list for more information on landscaping for energy efficiency and a reading list are included.

  9. Familial Alzheimer A2 V mutation reduces the intrinsic disorder and completely changes the free energy landscape of the Aβ1-28 monomer.

    PubMed

    Nguyen, Phuong H; Tarus, Bogdan; Derreumaux, Philippe

    2014-01-16

    The self-assembly of the amyloid-β (Aβ) peptide of 39-43 amino acids into senile plaques is one hallmark of Alzheimer's disease (AD) pathology. While A2 V carriers remain healthy in the heterozygous state, they suffer from early onset AD in the homozygous state. As a first toward understanding the impact of A2 V on Aβ at its earlier stage, we characterized the equilibrium ensemble of the Aβ1-28 wild type and Aβ1-28 A2 V monomers by means of extensive atomistic replica exchange molecular dynamics simulations. While global conformational properties such as the radius of gyration and the average secondary structure content of the whole peptides are very similar, the population of β-hairpins is increased by a factor of 4 in A2 V, and this may explain the enhanced Aβ1-40 A2 V aggregation kinetics with respect to Aβ1-40 wild type. Both peptides display a non-negligible population of extended metastable conformations differing however in their atomic details that represent ideal seeds for polymerization. Remarkably, upon A2 V mutation, the intrinsic disorder of Aβ1-28 monomer is reduced by a factor of 2, and the free energy landscape is completely different. This difference in the conformational ensembles of the two peptides may explain in part why the mixture of the Aβ40 WT and A2 V peptides protects against AD.

  10. Potential flux landscapes determine the global stability of a Lorenz chaotic attractor under intrinsic fluctuations

    NASA Astrophysics Data System (ADS)

    Li, Chunhe; Wang, Erkang; Wang, Jin

    2012-05-01

    We developed a potential flux landscape theory to investigate the dynamics and the global stability of a chemical Lorenz chaotic strange attractor under intrinsic fluctuations. Landscape was uncovered to have a butterfly shape. For chaotic systems, both landscape and probabilistic flux are crucial to the dynamics of chaotic oscillations. Landscape attracts the system down to the chaotic attractor, while flux drives the coherent motions along the chaotic attractors. Barrier heights from the landscape topography provide a quantitative measure for the robustness of chaotic attractor. We also found that the entropy production rate and phase coherence increase as the molecular numbers increase. Power spectrum analysis of autocorrelation function provides another way to quantify the global stability of chaotic attractor. We further found that limit cycle requires more flux and energy to sustain than the chaotic strange attractor. Finally, by detailed analysis we found that the curl probabilistic flux may provide the origin of the chaotic attractor.

  11. Energy Landscape of Social Balance

    NASA Astrophysics Data System (ADS)

    Marvel, Seth A.; Strogatz, Steven H.; Kleinberg, Jon M.

    2009-11-01

    We model a close-knit community of friends and enemies as a fully connected network with positive and negative signs on its edges. Theories from social psychology suggest that certain sign patterns are more stable than others. This notion of social “balance” allows us to define an energy landscape for such networks. Its structure is complex: numerical experiments reveal a landscape dimpled with local minima of widely varying energy levels. We derive rigorous bounds on the energies of these local minima and prove that they have a modular structure that can be used to classify them.

  12. Energy landscapes for machine learning.

    PubMed

    Ballard, Andrew J; Das, Ritankar; Martiniani, Stefano; Mehta, Dhagash; Sagun, Levent; Stevenson, Jacob D; Wales, David J

    2017-04-03

    Machine learning techniques are being increasingly used as flexible non-linear fitting and prediction tools in the physical sciences. Fitting functions that exhibit multiple solutions as local minima can be analysed in terms of the corresponding machine learning landscape. Methods to explore and visualise molecular potential energy landscapes can be applied to these machine learning landscapes to gain new insight into the solution space involved in training and the nature of the corresponding predictions. In particular, we can define quantities analogous to molecular structure, thermodynamics, and kinetics, and relate these emergent properties to the structure of the underlying landscape. This Perspective aims to describe these analogies with examples from recent applications, and suggest avenues for new interdisciplinary research.

  13. Energy landscapes and persistent minima

    SciTech Connect

    Carr, Joanne M.; Wales, David J.; Mazauric, Dorian; Cazals, Frédéric

    2016-02-07

    We consider a coarse-graining of high-dimensional potential energy landscapes based upon persistences, which correspond to lowest barrier heights to lower-energy minima. Persistences can be calculated efficiently for local minima in kinetic transition networks that are based on stationary points of the prevailing energy landscape. The networks studied here represent peptides, proteins, nucleic acids, an atomic cluster, and a glassy system. Minima with high persistence values are likely to represent some form of alternative structural morphology, which, if appreciably populated at the prevailing temperature, could compete with the global minimum (defined as infinitely persistent). Threshold values on persistences (and in some cases equilibrium occupation probabilities) have therefore been used in this work to select subsets of minima, which were then analysed to see how well they can represent features of the full network. Simplified disconnectivity graphs showing only the selected minima can convey the funnelling (including any multiple-funnel) characteristics of the corresponding full graphs. The effect of the choice of persistence threshold on the reduced disconnectivity graphs was considered for a system with a hierarchical, glassy landscape. Sets of persistent minima were also found to be useful in comparing networks for the same system sampled under different conditions, using minimum oriented spanning forests.

  14. Energy landscapes and functions of supramolecular systems

    NASA Astrophysics Data System (ADS)

    Tantakitti, Faifan; Boekhoven, Job; Wang, Xin; Kazantsev, Roman V.; Yu, Tao; Li, Jiahe; Zhuang, Ellen; Zandi, Roya; Ortony, Julia H.; Newcomb, Christina J.; Palmer, Liam C.; Shekhawat, Gajendra S.; de La Cruz, Monica Olvera; Schatz, George C.; Stupp, Samuel I.

    2016-04-01

    By means of two supramolecular systems--peptide amphiphiles engaged in hydrogen-bonded β-sheets, and chromophore amphiphiles driven to assemble by π-orbital overlaps--we show that the minima in the energy landscapes of supramolecular systems are defined by electrostatic repulsion and the ability of the dominant attractive forces to trap molecules in thermodynamically unfavourable configurations. These competing interactions can be selectively switched on and off, with the order of doing so determining the position of the final product in the energy landscape. Within the same energy landscape, the peptide-amphiphile system forms a thermodynamically favoured product characterized by long bundled fibres that promote biological cell adhesion and survival, and a metastable product characterized by short monodisperse fibres that interfere with adhesion and can lead to cell death. Our findings suggest that, in supramolecular systems, functions and energy landscapes are linked, superseding the more traditional connection between molecular design and function.

  15. Evidence for an intrinsic factor promoting landscape genetic divergence in Madagascan leaf-litter frogs

    PubMed Central

    Wollenberg Valero, Katharina C.

    2015-01-01

    The endemic Malagasy frog radiations are an ideal model system to study patterns and processes of speciation in amphibians. Large-scale diversity patterns of these frogs, together with other endemic animal radiations, led to the postulation of new and the application of known hypotheses of species diversification causing diversity patterns in this biodiversity hotspot. Both extrinsic and intrinsic factors have been studied in a comparative framework, with extrinsic factors usually being related to the physical environment (landscape, climate, river catchments, mountain chains), and intrinsic factors being clade-specific traits or constraints (reproduction, ecology, morphology, physiology). Despite some general patterns emerging from such large-scale comparative analyses, it became clear that the mechanism of diversification in Madagascar may vary among clades, and may be a multifactorial process. In this contribution, I test for intrinsic factors promoting population-level divergence within a clade of terrestrial, diurnal leaf-litter frogs (genus Gephyromantis) that has previously been shown to diversify according to extrinsic factors. Landscape genetic analyses of the microendemic species Gephyromantis enki and its widely distributed, larger sister species Gephyromantis boulengeri over a rugged landscape in the Ranomafana area shows that genetic variance of the smaller species cannot be explained by landscape resistance alone. Both topographic and riverine barriers are found to be important in generating this divergence. This case study yields additional evidence for the probable importance of body size in lineage diversification. PMID:26136766

  16. Evidence for an intrinsic factor promoting landscape genetic divergence in Madagascan leaf-litter frogs.

    PubMed

    Wollenberg Valero, Katharina C

    2015-01-01

    The endemic Malagasy frog radiations are an ideal model system to study patterns and processes of speciation in amphibians. Large-scale diversity patterns of these frogs, together with other endemic animal radiations, led to the postulation of new and the application of known hypotheses of species diversification causing diversity patterns in this biodiversity hotspot. Both extrinsic and intrinsic factors have been studied in a comparative framework, with extrinsic factors usually being related to the physical environment (landscape, climate, river catchments, mountain chains), and intrinsic factors being clade-specific traits or constraints (reproduction, ecology, morphology, physiology). Despite some general patterns emerging from such large-scale comparative analyses, it became clear that the mechanism of diversification in Madagascar may vary among clades, and may be a multifactorial process. In this contribution, I test for intrinsic factors promoting population-level divergence within a clade of terrestrial, diurnal leaf-litter frogs (genus Gephyromantis) that has previously been shown to diversify according to extrinsic factors. Landscape genetic analyses of the microendemic species Gephyromantis enki and its widely distributed, larger sister species Gephyromantis boulengeri over a rugged landscape in the Ranomafana area shows that genetic variance of the smaller species cannot be explained by landscape resistance alone. Both topographic and riverine barriers are found to be important in generating this divergence. This case study yields additional evidence for the probable importance of body size in lineage diversification.

  17. Graph representation of protein free energy landscape

    SciTech Connect

    Li, Minghai; Duan, Mojie; Fan, Jue; Huo, Shuanghong; Han, Li

    2013-11-14

    The thermodynamics and kinetics of protein folding and protein conformational changes are governed by the underlying free energy landscape. However, the multidimensional nature of the free energy landscape makes it difficult to describe. We propose to use a weighted-graph approach to depict the free energy landscape with the nodes on the graph representing the conformational states and the edge weights reflecting the free energy barriers between the states. Our graph is constructed from a molecular dynamics trajectory and does not involve projecting the multi-dimensional free energy landscape onto a low-dimensional space defined by a few order parameters. The calculation of free energy barriers was based on transition-path theory using the MSMBuilder2 package. We compare our graph with the widely used transition disconnectivity graph (TRDG) which is constructed from the same trajectory and show that our approach gives more accurate description of the free energy landscape than the TRDG approach even though the latter can be organized into a simple tree representation. The weighted-graph is a general approach and can be used on any complex system.

  18. Graph representation of protein free energy landscape.

    PubMed

    Li, Minghai; Duan, Mojie; Fan, Jue; Han, Li; Huo, Shuanghong

    2013-11-14

    The thermodynamics and kinetics of protein folding and protein conformational changes are governed by the underlying free energy landscape. However, the multidimensional nature of the free energy landscape makes it difficult to describe. We propose to use a weighted-graph approach to depict the free energy landscape with the nodes on the graph representing the conformational states and the edge weights reflecting the free energy barriers between the states. Our graph is constructed from a molecular dynamics trajectory and does not involve projecting the multi-dimensional free energy landscape onto a low-dimensional space defined by a few order parameters. The calculation of free energy barriers was based on transition-path theory using the MSMBuilder2 package. We compare our graph with the widely used transition disconnectivity graph (TRDG) which is constructed from the same trajectory and show that our approach gives more accurate description of the free energy landscape than the TRDG approach even though the latter can be organized into a simple tree representation. The weighted-graph is a general approach and can be used on any complex system.

  19. Constructing and exploring wells of energy landscapes

    NASA Astrophysics Data System (ADS)

    Aubin, Jean-Pierre; Lesne, Annick

    2005-04-01

    Landscape paradigm is ubiquitous in physics and other natural sciences, but it has to be supplemented with both quantitative and qualitatively meaningful tools for analyzing the topography of a given landscape. We here consider dynamic explorations of the relief and introduce as basic topographic features "wells of duration T and altitude y." We determine an intrinsic exploration mechanism governing the evolutions from an initial state in the well up to its rim in a prescribed time, whose finite-difference approximations on finite grids yield a constructive algorithm for determining the wells. Our main results are thus (i) a quantitative characterization of landscape topography rooted in a dynamic exploration of the landscape, (ii) an alternative to stochastic gradient dynamics for performing such an exploration, (iii) a constructive access to the wells, and (iv) the determination of some bare dynamic features inherent to the landscape. The mathematical tools used here are not familiar in physics: They come from set-valued analysis (differential calculus of set-valued maps and differential inclusions) and viability theory (capture basins of targets under evolutionary systems) that have been developed during the last two decades; we therefore propose a minimal Appendix exposing them at the end of this paper to bridge the possible gap.

  20. Local energy landscape in a simple liquid

    DOE PAGES

    Iwashita, T.; Egami, Takeshi

    2014-11-26

    It is difficult to relate the properties of liquids and glasses directly to their structure because of complexity in the structure that defies precise definition. The potential energy landscape (PEL) approach is a very insightful way to conceptualize the structure-property relationship in liquids and glasses, particularly the effect of temperature and history. However, because of the highly multidimensional nature of the PEL it is hard to determine, or even visualize, the actual details of the energy landscape. In this article we introduce a modified concept of the local energy landscape (LEL), which is limited in phase space, and demonstrate itsmore » usefulness using molecular dynamics simulation on a simple liquid at high temperatures. The local energy landscape is given as a function of the local coordination number, the number of the nearest-neighbor atoms. The excitation in the LEL corresponds to the so-called β-relaxation process. The LEL offers a simple but useful starting point to discuss complex phenomena in liquids and glasses.« less

  1. Local energy landscape in a simple liquid

    SciTech Connect

    Iwashita, T.; Egami, Takeshi

    2014-11-26

    It is difficult to relate the properties of liquids and glasses directly to their structure because of complexity in the structure that defies precise definition. The potential energy landscape (PEL) approach is a very insightful way to conceptualize the structure-property relationship in liquids and glasses, particularly the effect of temperature and history. However, because of the highly multidimensional nature of the PEL it is hard to determine, or even visualize, the actual details of the energy landscape. In this article we introduce a modified concept of the local energy landscape (LEL), which is limited in phase space, and demonstrate its usefulness using molecular dynamics simulation on a simple liquid at high temperatures. The local energy landscape is given as a function of the local coordination number, the number of the nearest-neighbor atoms. The excitation in the LEL corresponds to the so-called β-relaxation process. The LEL offers a simple but useful starting point to discuss complex phenomena in liquids and glasses.

  2. Exploring the conformational energy landscape of proteins

    SciTech Connect

    Nienhaus, G.U. |; Mueller, J.D.; McMahon, B.H.

    1997-04-01

    Proteins possess a complex energy landscape with a large number of local minima called conformational substates that are arranged in a hierarchical fashion. Here we discuss experiments aimed at the elucidation of the energy landscape in carbonmonoxy myoglobin (MbCO). In the highest tier of the hierarchy, a few taxonomic substates exist. Because of their small number, these substates are accessible to detailed structural investigations. Spectroscopic experiments are discussed that elucidate the role of protonations of amino acid side chains in creating the substates. The lower tiers of the hierarchy contain a large number of statistical substates. Substate interconversions are observed in the entire temperature range from below 1 K up to the denaturation temperature, indicating a wide spectrum of energy barriers that separate the substates.

  3. Archetypal energy landscapes: dynamical diagnosis.

    PubMed

    Despa, Florin; Wales, David J; Berry, R Stephen

    2005-01-08

    Recent studies have identified several motifs for potential energy surfaces corresponding to distinct dynamic and thermodynamic properties. The corresponding disconnectivity graphs were identified as "palm tree," "willow tree," and "banyan tree" patterns. In the present contribution we present a quantitative analysis of the relation between the topography and dynamics for each of these motifs. For the palm tree and willow tree forms we find that the arrangement of the stationary points in the monotonic sequences with respect to the global minimum is the most important factor in establishing the kinetic properties. However, the results are somewhat different for motifs involving a rough surface with several deep basins (banyan tree motif), with large barriers relative to the energy differences between minima. Here it is the size of the barrier for escape from the region relative to the barriers at the bottom that is most important. The present results may be helpful in distinguishing between the dynamics of "structure seeking" and "glass forming" systems.

  4. Potential energy landscapes of tetragonal pyramid molecules

    NASA Astrophysics Data System (ADS)

    Yoshida, Yuichiro; Sato, Hirofumi; Morgan, John W. R.; Wales, David J.

    2016-11-01

    Hiraoka et al. have developed a self-assembling system referred to as a nanocube (Hiraoka et al., 2008). In the present contribution a coarse-grained model for this system is analysed, focusing on how the potential energy landscape for self-assembly is related to the geometry of the building blocks. We find that six molecules assemble to form various clusters, with cubic and sheet structures the most stable. The relative stability is determined by the geometry of the building blocks.

  5. Energy landscape in protein folding and unfolding

    PubMed Central

    Mallamace, Francesco; Corsaro, Carmelo; Mallamace, Domenico; Vasi, Sebastiano; Vasi, Cirino; Baglioni, Piero; Buldyrev, Sergey V.; Chen, Sow-Hsin; Stanley, H. Eugene

    2016-01-01

    We use 1H NMR to probe the energy landscape in the protein folding and unfolding process. Using the scheme ⇄ reversible unfolded (intermediate) → irreversible unfolded (denatured) state, we study the thermal denaturation of hydrated lysozyme that occurs when the temperature is increased. Using thermal cycles in the range 295energy surface, we observe that the hydrophilic (the amide NH) and hydrophobic (methyl CH3 and methine CH) peptide groups evolve and exhibit different behaviors. We also discuss the role of water and hydrogen bonding in the protein configurational stability. PMID:26957601

  6. Energy Landscape Topography Reveals the Underlying Link Between Binding Specificity and Activity of Enzymes.

    PubMed

    Chu, Wen-Ting; Wang, Jin

    2016-06-14

    Enzyme activity (often quantified by kcat/Km) is the main function of enzyme when it is active against the specific substrate. Higher or lower activities are highly desired for the design of novel enzyme and drug resistance. However, it is difficult to measure the activities of all possible variants and find the "hot-spot" within the limit of experimental time. In this study, we explore the underlying energy landscape of enzyme-substrate interactions and introduce the intrinsic specificity ratio (ISR), which reflects the landscape topography. By studying two concrete systems, we uncover the statistical correlation between the intrinsic specificity and the enzyme activity kcat/Km. This physics-based concept and method show that the energy landscape topography is valuable for understanding the relationship between enzyme specificity and activity. In addition, it can reveal the underlying mechanism of enzyme-substrate actions and has potential applications on enzyme design.

  7. Energy Landscape Topography Reveals the Underlying Link Between Binding Specificity and Activity of Enzymes

    NASA Astrophysics Data System (ADS)

    Chu, Wen-Ting; Wang, Jin

    2016-06-01

    Enzyme activity (often quantified by kcat/Km) is the main function of enzyme when it is active against the specific substrate. Higher or lower activities are highly desired for the design of novel enzyme and drug resistance. However, it is difficult to measure the activities of all possible variants and find the “hot-spot” within the limit of experimental time. In this study, we explore the underlying energy landscape of enzyme-substrate interactions and introduce the intrinsic specificity ratio (ISR), which reflects the landscape topography. By studying two concrete systems, we uncover the statistical correlation between the intrinsic specificity and the enzyme activity kcat/Km. This physics-based concept and method show that the energy landscape topography is valuable for understanding the relationship between enzyme specificity and activity. In addition, it can reveal the underlying mechanism of enzyme-substrate actions and has potential applications on enzyme design.

  8. Energy Landscape Topography Reveals the Underlying Link Between Binding Specificity and Activity of Enzymes

    PubMed Central

    Chu, Wen-Ting; Wang, Jin

    2016-01-01

    Enzyme activity (often quantified by kcat/Km) is the main function of enzyme when it is active against the specific substrate. Higher or lower activities are highly desired for the design of novel enzyme and drug resistance. However, it is difficult to measure the activities of all possible variants and find the “hot-spot” within the limit of experimental time. In this study, we explore the underlying energy landscape of enzyme-substrate interactions and introduce the intrinsic specificity ratio (ISR), which reflects the landscape topography. By studying two concrete systems, we uncover the statistical correlation between the intrinsic specificity and the enzyme activity kcat/Km. This physics-based concept and method show that the energy landscape topography is valuable for understanding the relationship between enzyme specificity and activity. In addition, it can reveal the underlying mechanism of enzyme-substrate actions and has potential applications on enzyme design. PMID:27298067

  9. Energy landscape of relaxed amorphous silicon

    NASA Astrophysics Data System (ADS)

    Valiquette, Francis; Mousseau, Normand

    2003-09-01

    We analyze the structure of the energy landscape of a well-relaxed 1000-atom model of amorphous silicon using the activation-relaxation technique (ART nouveau). Generating more than 40 000 events starting from a single minimum, we find that activated mechanisms are local in nature, that they are distributed uniformly throughout the model, and that the activation energy is limited by the cost of breaking one bond, independently of the complexity of the mechanism. The overall shape of the activation-energy-barrier distribution is also insensitive to the exact details of the configuration, indicating that well-relaxed configurations see essentially the same environment. These results underscore the localized nature of relaxation in this material.

  10. 'Energy landscapes': Meeting energy demands and human aspirations.

    PubMed

    Blaschke, Thomas; Biberacher, Markus; Gadocha, Sabine; Schardinger, Ingrid

    2013-08-01

    Renewable energy will play a crucial role in the future society of the 21st century. The various renewable energy sources need to be balanced and their use carefully planned since they are characterized by high temporal and spatial variability that will pose challenges to maintaining a well balanced supply and to the stability of the grid. This article examines the ways that future 'energy landscapes' can be modelled in time and space. Biomass needs a great deal of space per unit of energy produced but it is an energy carrier that may be strategically useful in circumstances where other renewable energy carriers are likely to deliver less. A critical question considered in this article is whether a massive expansion in the use of biomass will allow us to construct future scenarios while repositioning the 'energy landscape' as an object of study. A second important issue is the utilization of heat from biomass energy plants. Biomass energy also has a larger spatial footprint than other carriers such as, for example, solar energy. This article seeks to provide a bridge between energy modelling and spatial planning while integrating research and techniques in energy modelling with Geographic Information Science. This encompasses GIS, remote sensing, spatial disaggregation techniques and geovisualization. Several case studies in Austria and Germany demonstrate a top-down methodology and some results while stepwise calculating potentials from theoretical to technically feasible potentials and setting the scene for the definition of economic potentials based on scenarios and assumptions.

  11. Energy Landscape Reveals That the Budding Yeast Cell Cycle Is a Robust and Adaptive Multi-stage Process

    PubMed Central

    Lv, Cheng; Li, Xiaoguang; Li, Fangting; Li, Tiejun

    2015-01-01

    Quantitatively understanding the robustness, adaptivity and efficiency of cell cycle dynamics under the influence of noise is a fundamental but difficult question to answer for most eukaryotic organisms. Using a simplified budding yeast cell cycle model perturbed by intrinsic noise, we systematically explore these issues from an energy landscape point of view by constructing an energy landscape for the considered system based on large deviation theory. Analysis shows that the cell cycle trajectory is sharply confined by the ambient energy barrier, and the landscape along this trajectory exhibits a generally flat shape. We explain the evolution of the system on this flat path by incorporating its non-gradient nature. Furthermore, we illustrate how this global landscape changes in response to external signals, observing a nice transformation of the landscapes as the excitable system approaches a limit cycle system when nutrients are sufficient, as well as the formation of additional energy wells when the DNA replication checkpoint is activated. By taking into account the finite volume effect, we find additional pits along the flat cycle path in the landscape associated with the checkpoint mechanism of the cell cycle. The difference between the landscapes induced by intrinsic and extrinsic noise is also discussed. In our opinion, this meticulous structure of the energy landscape for our simplified model is of general interest to other cell cycle dynamics, and the proposed methods can be applied to study similar biological systems. PMID:25794282

  12. Intrinsic Changes: Energy Saving Behaviour among Resident University Students

    ERIC Educational Resources Information Center

    Black, Rosemary; Davidson, Penny; Retra, Karen

    2010-01-01

    This paper presents the results of a study that explored the effectiveness of three intervention strategies in facilitating energy saving behaviour among resident undergraduate university students. In contrast to a dominant practice of motivating with rewards or competition this study sought to appeal to students' intrinsic motivations. An…

  13. Evolution, Energy Landscapes and the Paradoxes of Protein Folding

    PubMed Central

    Wolynes, Peter G.

    2014-01-01

    Protein folding has been viewed as a difficult problem of molecular self-organization. The search problem involved in folding however has been simplified through the evolution of folding energy landscapes that are funneled. The funnel hypothesis can be quantified using energy landscape theory based on the minimal frustration principle. Strong quantitative predictions that follow from energy landscape theory have been widely confirmed both through laboratory folding experiments and from detailed simulations. Energy landscape ideas also have allowed successful protein structure prediction algorithms to be developed. The selection constraint of having funneled folding landscapes has left its imprint on the sequences of existing protein structural families. Quantitative analysis of co-evolution patterns allows us to infer the statistical characteristics of the folding landscape. These turn out to be consistent with what has been obtained from laboratory physicochemical folding experiments signalling a beautiful confluence of genomics and chemical physics. PMID:25530262

  14. Enhanced stochastic fluctuations to measure steep adhesive energy landscapes.

    PubMed

    Haider, Ahmad; Potter, Daniel; Sulchek, Todd A

    2016-12-13

    Free-energy landscapes govern the behavior of all interactions in the presence of thermal fluctuations in the fields of physical chemistry, materials sciences, and the biological sciences. From the energy landscape, critical information about an interaction, such as the reaction kinetic rates, bond lifetimes, and the presence of intermediate states, can be determined. Despite the importance of energy landscapes to understanding reaction mechanisms, most experiments do not directly measure energy landscapes, particularly for interactions with steep force gradients that lead to premature jump to contact of the probe and insufficient sampling of transition regions. Here we present an atomic force microscopy (AFM) approach for measuring energy landscapes that increases sampling of strongly adhesive interactions by using white-noise excitation to enhance the cantilever's thermal fluctuations. The enhanced fluctuations enable the recording of subtle deviations from a harmonic potential to accurately reconstruct interfacial energy landscapes with steep gradients. Comparing the measured energy landscape with adhesive force measurements reveals the existence of an optimal excitation voltage that enables the cantilever fluctuations to fully sample the shape and depth of the energy surface.

  15. Enhanced stochastic fluctuations to measure steep adhesive energy landscapes

    PubMed Central

    Haider, Ahmad; Potter, Daniel; Sulchek, Todd A.

    2016-01-01

    Free-energy landscapes govern the behavior of all interactions in the presence of thermal fluctuations in the fields of physical chemistry, materials sciences, and the biological sciences. From the energy landscape, critical information about an interaction, such as the reaction kinetic rates, bond lifetimes, and the presence of intermediate states, can be determined. Despite the importance of energy landscapes to understanding reaction mechanisms, most experiments do not directly measure energy landscapes, particularly for interactions with steep force gradients that lead to premature jump to contact of the probe and insufficient sampling of transition regions. Here we present an atomic force microscopy (AFM) approach for measuring energy landscapes that increases sampling of strongly adhesive interactions by using white-noise excitation to enhance the cantilever’s thermal fluctuations. The enhanced fluctuations enable the recording of subtle deviations from a harmonic potential to accurately reconstruct interfacial energy landscapes with steep gradients. Comparing the measured energy landscape with adhesive force measurements reveals the existence of an optimal excitation voltage that enables the cantilever fluctuations to fully sample the shape and depth of the energy surface. PMID:27911778

  16. An energy landscape approach to protein aggregation

    NASA Astrophysics Data System (ADS)

    Buell, Alexander; Knowles, Tuomas

    2012-02-01

    Protein aggregation into ordered fibrillar structures is the hallmark of a class of diseases, the most prominent examples of which are Alzheimer's and Parkinson's disease. Recent results (e.g. Baldwin et al. J. Am. Chem. Soc. 2011) suggest that the aggregated state of a protein is in many cases thermodynamically more stable than the soluble state. Therefore the solubility of proteins in a cellular context appears to be to a large extent under kinetic control. Here, we first present a conceptual framework for the description of protein aggregation ( see AK Buell et al., Phys. Rev. Lett. 2010) that is an extension to the generally accepted energy landscape model for protein folding. Then we apply this model to analyse and interpret a large set of experimental data on the kinetics of protein aggregation, acquired mainly with a novel biosensing approach (see TPJK Knowles et al, Proc. Nat. Acad. Sc. 2007). We show how for example the effect of sequence modifications on the kinetics and thermodynamics of human lysozyme aggregation can be understood and quantified (see AK Buell et al., J. Am. Chem. Soc. 2011). These results have important implications for therapeutic strategies against protein aggregation disorders, in this case lysozyme systemic amyloidosis.

  17. Noise induced transitions in rugged energy landscapes

    NASA Astrophysics Data System (ADS)

    Pradas, Marc; Duncan, Andrew; Kalliadasis, Serafim; Pavliotis, Greg

    2016-11-01

    External or internal random fluctuations are ubiquitous in many physical and technological systems and can play a key role in their dynamics often inducing a wide variety of complex spatiotemporal phenomena, including noise-induced spatial patterns and noise-induced phase transitions. Many of these phenomena can be modelled by noisy multiscale systems characterized by the presence of a wide range of different time- and lengthscales interacting nontrivially with each other. Here we analyse the effects of additive noise on systems that are described in terms of a rugged energy landscape, modelled as a slowly-varying multiscale potential perturbed by periodic multiscale fluctuations. Some examples of this problem include the dynamics of sessile droplets on heterogeneous substrates, crystallization and the evolution of protein folding. We demonstrate that the interplay between noise and the small scale fluctuations in the potential can give rise to a dramatically different bifurcation structure and dynamical behaviour compared to that of the original, unperturbed model. For instance, we observe several nontrivial and largely unexpected dynamic-state transitions controlled by the noise intensity. We characterize these transitions in terms of critical exponents.

  18. Energy landscapes in proteins and glasses

    NASA Astrophysics Data System (ADS)

    Singh, Sadanand

    Soft materials are ubiquitous in our day-to-day life. They include liquids, colloids, polymers, foams, gels, granular systems, and a number of biological materials. While these materials exhibit a wide range of textures and morphologies, many of their properties have common physicochemical origins. A better understanding of such origins would lead to rational design and engineering of functional soft materials. A common feature of soft materials is the wide range of time and length scales that characterizes their behavior. Unfortunately, available molecular modeling techniques are often ill-suited for problems that exhibit multiple length and time scales. In this thesis, we introduce and implement new simulation methods that have enabled molecular-level studies of soft materials. Such methods permit calculation of free energy surfaces, and we demonstrate their usefulness in the context of proteins and glasses, both of which exhibit rugged free energy landscapes. A first application is concerned with human amylin, a protein associated with Type II diabetes. Patients with Type II diabetes exhibit fibrillar deposits of human amylin protein in the pancreas. By applying the advanced simulation methods and algorithms developed in this work, we investigate the structure and folding dynamics of human amylin. A detailed mechanism is presented at the atomic-level for the nucleation and aggregation of the peptide. The results presented in this work could help in development of therapeutic strategies for Type II diabetes. The second application is concerned with the study of vapor-deposited ultrastable glasses. These stable glasses have, far below the conventional glass transition temperature, the properties expected from the equilibrium supercooled liquid state. Our results indicate that optimal stability is attained when deposition occurs near the Kauzmann temperature. We also show that the extraordinary stability of model vapor deposited glasses is associated with distinct

  19. Enzyme activation through the utilization of intrinsic dianion binding energy.

    PubMed

    Amyes, T L; Malabanan, M M; Zhai, X; Reyes, A C; Richard, J P

    2016-11-29

    We consider 'the proposition that the intrinsic binding energy that results from the noncovalent interaction of a specific substrate with the active site of the enzyme is considerably larger than is generally believed. An important part of this binding energy may be utilized to provide the driving force for catalysis, so that the observed binding energy represents only what is left over after this utilization' [Jencks,W.P. (1975) Adv. Enzymol. Relat. Areas. Mol. Biol., 43: , 219-410]. The large ~12 kcal/mol intrinsic substrate phosphodianion binding energy for reactions catalyzed by triosephosphate isomerase (TIM), orotidine 5'-monophosphate decarboxylase and glycerol-3-phosphate dehydrogenase is divided into 4-6 kcal/mol binding energy that is expressed on the formation of the Michaelis complex in anchoring substrates to the respective enzyme, and 6-8 kcal/mol binding energy that is specifically expressed at the transition state in activating the respective enzymes for catalysis. A structure-based mechanism is described where the dianion binding energy drives a conformational change that activates these enzymes for catalysis. Phosphite dianion plays the active role of holding TIM in a high-energy closed active form, but acts as passive spectator in showing no effect on transition-state structure. The result of studies on mutant enzymes is presented, which support the proposal that the dianion-driven enzyme conformational change plays a role in enhancing the basicity of side chain of E167, the catalytic base, by clamping the base between a pair of hydrophobic side chains. The insight these results provide into the architecture of enzyme active sites and the development of strategies for the de novo design of protein catalysts is discussed.

  20. Aging, memory, and nonhierarchical energy landscape of spin jam.

    PubMed

    Samarakoon, Anjana; Sato, Taku J; Chen, Tianran; Chern, Gai-Wei; Yang, Junjie; Klich, Israel; Sinclair, Ryan; Zhou, Haidong; Lee, Seung-Hun

    2016-10-18

    The notion of complex energy landscape underpins the intriguing dynamical behaviors in many complex systems ranging from polymers, to brain activity, to social networks and glass transitions. The spin glass state found in dilute magnetic alloys has been an exceptionally convenient laboratory frame for studying complex dynamics resulting from a hierarchical energy landscape with rugged funnels. Here, we show, by a bulk susceptibility and Monte Carlo simulation study, that densely populated frustrated magnets in a spin jam state exhibit much weaker memory effects than spin glasses, and the characteristic properties can be reproduced by a nonhierarchical landscape with a wide and nearly flat but rough bottom. Our results illustrate that the memory effects can be used to probe different slow dynamics of glassy materials, hence opening a window to explore their distinct energy landscapes.

  1. Aging, memory, and nonhierarchical energy landscape of spin jam

    PubMed Central

    Samarakoon, Anjana; Sato, Taku J.; Chen, Tianran; Chern, Gai-Wei; Yang, Junjie; Klich, Israel; Sinclair, Ryan; Zhou, Haidong; Lee, Seung-Hun

    2016-01-01

    The notion of complex energy landscape underpins the intriguing dynamical behaviors in many complex systems ranging from polymers, to brain activity, to social networks and glass transitions. The spin glass state found in dilute magnetic alloys has been an exceptionally convenient laboratory frame for studying complex dynamics resulting from a hierarchical energy landscape with rugged funnels. Here, we show, by a bulk susceptibility and Monte Carlo simulation study, that densely populated frustrated magnets in a spin jam state exhibit much weaker memory effects than spin glasses, and the characteristic properties can be reproduced by a nonhierarchical landscape with a wide and nearly flat but rough bottom. Our results illustrate that the memory effects can be used to probe different slow dynamics of glassy materials, hence opening a window to explore their distinct energy landscapes. PMID:27698141

  2. Aging, memory, and nonhierarchical energy landscape of spin jam

    NASA Astrophysics Data System (ADS)

    Samarakoon, Anjana; Sato, Taku J.; Chen, Tianran; Chern, Gai-Wei; Yang, Junjie; Klich, Israel; Sinclair, Ryan; Zhou, Haidong; Lee, Seung-Hun

    2016-10-01

    The notion of complex energy landscape underpins the intriguing dynamical behaviors in many complex systems ranging from polymers, to brain activity, to social networks and glass transitions. The spin glass state found in dilute magnetic alloys has been an exceptionally convenient laboratory frame for studying complex dynamics resulting from a hierarchical energy landscape with rugged funnels. Here, we show, by a bulk susceptibility and Monte Carlo simulation study, that densely populated frustrated magnets in a spin jam state exhibit much weaker memory effects than spin glasses, and the characteristic properties can be reproduced by a nonhierarchical landscape with a wide and nearly flat but rough bottom. Our results illustrate that the memory effects can be used to probe different slow dynamics of glassy materials, hence opening a window to explore their distinct energy landscapes.

  3. Effect of correlations between minima on a complex energy landscape

    NASA Astrophysics Data System (ADS)

    Pusuluri, Sai Teja; Lang, Alex H.; Mehta, Pankaj; Castillo, Horacio E.

    We recently modeled cellular interconvertion dynamics by using an epigenetic landscape model inspired by neural network models. Given an arbitrary set of patterns, the model can be used to construct an energy landscape in which those patterns are the global minima. We study the possible stable states and metastable states of the landscapes thus constructed. We consider three different cases: i) choosing the patterns to be random and independently distributed ii) choosing a set of patterns directly derived from the experimental cellular transcription factor expression data for a representative set of cell types in an organism and iii) choosing randomly generated trees of hierarchically correlated patterns, inspired by biology. For each of the three cases, we study the energy landscapes. In particular we study the basins of attraction of both the stable states and the metastable states, we compute the configurational entropy as a function of energy, and we demonstrate how those results depend on the correlations between the patterns.

  4. Intrinsic Energy Dissipation Limits in Nano and Micromechanical Resonators

    NASA Astrophysics Data System (ADS)

    Iyer, Srikanth Subramanian

    Resonant microelectromechanical Systems (MEMS) have enabled miniaturization of high-performance inertial sensors, radio-frequency filters, timing references and mass-based chemical sensors. Despite the increasing prevalence of MEMS resonators for these applications, the energy dissipation in these structures is not well-understood. Accurate prediction of the energy loss and the resulting quality factor (Q) has significant design implications because it is directly related to device performance metrics including sensitivity for resonant sensors, bandwidth for radio-frequency filters and phase-noise for timing references. In order to assess the future potential for MEMS resonators it is critically important to evaluate the energy dissipation limits, which will dictate the ultimate performance resonant MEMS devices can achieve. This work focuses on the derivation and evaluation of the intrinsic mechanical energy dissipation limit for single-crystal nano and micromechanical resonators due to anharmonic phonon-phonon scattering in the Akhiezer regime. The energy loss is derived using perturbation theory and the linearized Boltzmann transport equation for phonons, and includes the direction and polarization dependent mode-Gruneisen parameters in order to capture the strain-induced anharmonicity among phonon branches. Evaluation of the quality factor limit reveals that Akhiezer damping, previously thought to depend only on material properties, has a strong dependence on crystal orientation and resonant mode shape. The robust model provides a dissipation limit for all resonant modes including shear-mode vibrations, which have significantly reduced energy loss because dissipative phonon-phonon scattering is restricted to volume-preserving phonon branches, indicating that Lame or wine-glass mode resonators will have the highest upper limit on mechanical efficiency. Finally, the analytical dissipation model is integrated with commercial finite element software in order to

  5. Decoding heat capacity features from the energy landscape

    NASA Astrophysics Data System (ADS)

    Wales, David J.

    2017-03-01

    A general scheme is derived to connect transitions in configuration space with features in the heat capacity. A formulation in terms of occupation probabilities for local minima that define the potential energy landscape provides a quantitative description of how contributions arise from competition between different states. The theory does not rely on a structural interpretation for the local minima, so it is equally applicable to molecular energy landscapes and the landscapes defined by abstract functions. Applications are presented for low-temperature solid-solid transitions in atomic clusters, which involve just a few local minima with different morphologies, and for cluster melting, which is driven by the landscape entropy associated with the more numerous high-energy minima. Analyzing these features in terms of the balance between states with increasing and decreasing occupation probabilities provides a direct interpretation of the underlying transitions. This approach enables us to identify a qualitatively different transition that is caused by a single local minimum associated with an exceptionally large catchment volume in configuration space for a machine learning landscape.

  6. 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.

  7. Understanding soft glassy materials using an energy landscape approach.

    PubMed

    Hwang, Hyun Joo; Riggleman, Robert A; Crocker, John C

    2016-09-01

    Many seemingly different soft materials-such as soap foams, mayonnaise, toothpaste and living cells-display strikingly similar viscoelastic behaviour. A fundamental physical understanding of such soft glassy rheology and how it can manifest in such diverse materials, however, remains unknown. Here, by using a model soap foam consisting of compressible spherical bubbles, whose sizes slowly evolve and whose collective motion is simply dictated by energy minimization, we study the foam's dynamics as it corresponds to downhill motion on an energy landscape function spanning a high-dimensional configuration space. We find that these downhill paths, when viewed in this configuration space, are, surprisingly, fractal. The complex behaviour of our model, including power-law rheology and non-diffusive bubble motion and avalanches, stems directly from the fractal dimension and energy function of these paths. Our results suggest that ubiquitous soft glassy rheology may be a consequence of emergent fractal geometry in the energy landscapes of many complex fluids.

  8. Understanding soft glassy materials using an energy landscape approach

    NASA Astrophysics Data System (ADS)

    Hwang, Hyun Joo; Riggleman, Robert A.; Crocker, John C.

    2016-09-01

    Many seemingly different soft materials--such as soap foams, mayonnaise, toothpaste and living cells--display strikingly similar viscoelastic behaviour. A fundamental physical understanding of such soft glassy rheology and how it can manifest in such diverse materials, however, remains unknown. Here, by using a model soap foam consisting of compressible spherical bubbles, whose sizes slowly evolve and whose collective motion is simply dictated by energy minimization, we study the foam's dynamics as it corresponds to downhill motion on an energy landscape function spanning a high-dimensional configuration space. We find that these downhill paths, when viewed in this configuration space, are, surprisingly, fractal. The complex behaviour of our model, including power-law rheology and non-diffusive bubble motion and avalanches, stems directly from the fractal dimension and energy function of these paths. Our results suggest that ubiquitous soft glassy rheology may be a consequence of emergent fractal geometry in the energy landscapes of many complex fluids.

  9. Landscaping for energy conservation: plan an energy-saving yard

    SciTech Connect

    Not Available

    1983-01-01

    This illustrated brochure covers the following aspects of landscaping: summer cooling, winter warming with emphasis on windbreaks, earth shettering, and materials for do-it-yourself planning. Lists of useful deciduous, and evergreen trees, vines, and shrubs are included with a chart of their characteristics. (MHR)

  10. Distributed energy tapestry for heating the landscape

    NASA Astrophysics Data System (ADS)

    Rocha, L. A. O.; Lorente, S.; Bejan, A.

    2010-12-01

    Here we show that the production and use of heating on an area must be distributed in clusters organized such that the losses associated with centers of production are balanced by the losses associated with distribution lines. The energy needs increase in time because the population density and the individual need increase. We consider only the increase in the individual need in time. We illustrate the "distributed energy systems" concept with the production and distribution of hot water on an area. Four classes of designs are analyzed and compared: (0) individual, i.e., one water heater for one user, (r) radial, i.e., N users supplied via radial pipes from a central heater, (2) dendritic network constructed by pairing N users around a central heating, and (4) dendritic network constructed by quadrupling the elemental areas occupied by the users. We show that there is an optimal cluster size (N) as a tradeoff between central losses and distributed losses. We also discover that several distinct (abrupt) design "transitions" must exist: the recommended design changes through designs 0, r, 2, and 4, as the amount of water used by each individual increases in time with the standard of living.

  11. Folding Free Energy Landscape of the Decapeptide Chignolin

    NASA Astrophysics Data System (ADS)

    Dou, Xianghua; Wang, Jihua

    Chignolin is an artificially designed ten-residue (GYDPETGTWG) folded peptide, which is the smallest protein and provides a good template for protein folding. In this work, we completed four explicit water molecular dynamics simulations of Chignolin folding using GROMOS and OPLS-AA force fields from extended initial states without any experiment informations. The four-folding free energy landscapes of the peptide has been drawn. The folded state of Chignolin has been successfully predicated based on the free energy landscapes. The four independent simulations gave similar results. (i) The four free energy landscapes have common characters. They are fairly smooth, barrierless, funnel-like and downhill without intermediate state, which consists with the experiment. (ii) The different extended initial structures converge at similar folded structures with the lowest free energy under GROMOS and OPLS-AA force fields. In the GROMOS force field, the backbone RMSD of the folded structures from the NMR native structure of Chignolin is only 0.114 nm, which is a stable structure in this force field. In the OPLS-AA force field, the similar results have been obtained. In addition, the smallest RMSD structure is in better agreement with the NMR native structure but unlikely stable in the force field.

  12. Magnesium Dependence of the RNA Free Energy Landscape

    NASA Astrophysics Data System (ADS)

    Hayes, Ryan; Noel, Jeffrey; Mandic, Ana; Whitford, Paul; Sanbonmatsu, Karissa; Mohanty, Udayan; Onuchic, José

    2015-03-01

    The RNA free energy landscape is highly sensitive to ionic concentrations, and especially to Mg2+, as most RNA tertiary structure will not form in the absence of Mg2+. At physiological concentrations, the energy landscape must be smooth and funneled to fold on biological time scales, but changes in ionic concentration may affect the relative stability of alternative states. We perturb a structure-based model, which captures the funneled nature of the energy landscape, to include electrostatic effects. Our model includes explicit Mg2+ and screening by implicit KCl. A dynamic model for the local competition between Manning condensed Mg2+ and KCl is introduced, which makes the model more broadly applicable and transferable than a previous static model. We use the excess Mg2+ ions associated with the RNA (Γ2 +) to test the model. Γ2 + is an ideal metric because it is closely related to the Mg2+-RNA interaction free energy, and is easily measurable in both experiment and simulation. The model captures intermediate states of a small pseudoknot missed by models without electrostatics.

  13. Free Energy Landscape - Settlements of Key Residues.

    NASA Astrophysics Data System (ADS)

    Aroutiounian, Svetlana

    2007-03-01

    FEL perspective in studies of protein folding transitions reflects notion that since there are ˜10^N conformations to scan in search of lowest free energy state, random search is beyond biological timescale. Protein folding must follow certain fel pathways and folding kinetics of evolutionary selected proteins dominates kinetic traps. Good model for functional robustness of natural proteins - coarse-grained model protein is not very accurate but affords bringing simulations closer to biological realm; Go-like potential secures the fel funnel shape; biochemical contacts signify the funnel bottleneck. Boltzmann-weighted ensemble of protein conformations and histogram method are used to obtain from MC sampling of protein conformational space the approximate probability distribution. The fel is F(rmsd) = -1/βLn[Hist(rmsd)], β=kBT and rmsd is root-mean-square-deviation from native conformation. The sperm whale myoglobin has rich dynamic behavior, is small and large - on computational scale, has a symmetry in architecture and unusual sextet of residue pairs. Main idea: there is a mathematical relation between protein fel and a key residues set providing stability to folding transition. Is the set evolutionary conserved also for functional reasons? Hypothesis: primary sequence determines the key residues positions conserved as stabilizers and the fel is the battlefield for the folding stability. Preliminary results: primary sequence - not the architecture, is the rule settler, indeed.

  14. Deaging and Asymmetric Energy Landscapes in Electrically Biased Ferroelectrics

    SciTech Connect

    Tutuncu, Goknur; Damjanovic, Dragan; Chen, Jun; Jones, Jacob L.

    2015-09-01

    In ferroic materials, the dielectric, piezoelectric, magnetic, and elastic coefficients are significantly affected by the motion of domain walls. This motion can be described as the propagation of a wall across various types and strengths of pinning centers that collectively constitute a force profile or energetic landscape. Biased domain structures and asymmetric energy landscapes can be created through application of high fields (such as during electrical poling), and the material behavior in such states is often highly asymmetric. In some cases, this behavior can be considered as the electric analogue to the Bauschinger effect. The present Letter uses time-resolved, high-energy x-ray Bragg scattering to probe this asymmetry and the associated deaging effect in the ferroelectric morphotropic phase boundary composition 0.36BiScO{sub 3}-0.64PbTiO{sub 3}.

  15. The energy landscape of adenylate kinase during catalysis

    PubMed Central

    Kerns, S. Jordan; Agafonov, Roman V.; Cho, Young-Jin; Pontiggia, Francesco; Otten, Renee; Pachov, Dimitar V.; Kutter, Steffen; Phung, Lien A.; Murphy, Padraig N.; Thai, Vu; Alber, Tom; Hagan, Michael F.; Kern, Dorothee

    2014-01-01

    Kinases perform phosphoryl-transfer reactions in milliseconds; without enzymes, these reactions would take about 8000 years under physiological conditions. Despite extensive studies, a comprehensive understanding of kinase energy landscapes, including both chemical and conformational steps, is lacking. Here we scrutinize the microscopic steps in the catalytic cycle of adenylate kinase, through a combination of NMR measurements during catalysis, pre-steady-state kinetics, MD simulations, and crystallography of active complexes. We find that the Mg2+ cofactor activates two distinct molecular events, phosphoryl transfer (>105-fold) and lid-opening (103-fold). In contrast, mutation of an essential active-site arginine decelerates phosphoryl transfer 103-fold without substantially affecting lid-opening. Our results highlight the importance of the entire energy landscape in catalysis and suggest that adenylate kinases have evolved to activate key processes simultaneously by precise placement of a single, charged and very abundant cofactor in a pre-organized active site. PMID:25580578

  16. Deaging and asymmetric energy landscapes in electrically biased ferroelectrics.

    PubMed

    Tutuncu, Goknur; Damjanovic, Dragan; Chen, Jun; Jones, Jacob L

    2012-04-27

    In ferroic materials, the dielectric, piezoelectric, magnetic, and elastic coefficients are significantly affected by the motion of domain walls. This motion can be described as the propagation of a wall across various types and strengths of pinning centers that collectively constitute a force profile or energetic landscape. Biased domain structures and asymmetric energy landscapes can be created through application of high fields (such as during electrical poling), and the material behavior in such states is often highly asymmetric. In some cases, this behavior can be considered as the electric analogue to the Bauschinger effect. The present Letter uses time-resolved, high-energy x-ray Bragg scattering to probe this asymmetry and the associated deaging effect in the ferroelectric morphotropic phase boundary composition 0.36BiScO3 - 0.64PbTiO3.

  17. Energy landscapes for shells assembled from pentagonal and hexagonal pyramids.

    PubMed

    Fejer, Szilard N; James, Tim R; Hernández-Rojas, Javier; Wales, David J

    2009-03-28

    We present new rigid body potentials that should favour efficient self-assembly of pentagonal and hexagonal pyramids into icosahedral shells over a wide range of temperature. By adding an extra repulsive site opposite the existing apex sites of the pyramids considered in a previously published model, frustrated energy landscapes are transformed into systems identified with self-assembling properties. The extra interaction may be considered analogous to a hydrophobic-hydrophilic repulsion, as in micelle formation.

  18. BarMap: RNA folding on dynamic energy landscapes

    PubMed Central

    Hofacker, Ivo L.; Flamm, Christoph; Heine, Christian; Wolfinger, Michael T.; Scheuermann, Gerik; Stadler, Peter F.

    2010-01-01

    Dynamical changes of RNA secondary structures play an important role in the function of many regulatory RNAs. Such kinetic effects, especially in time-variable and externally triggered systems, are usually investigated by means of extensive and expensive simulations of large sets of individual folding trajectories. Here we describe the theoretical foundations of a generic approach that not only allows the direct computation of approximate population densities but also reduces the efforts required to analyze the folding energy landscapes to a one-time preprocessing step. The basic idea is to consider the kinetics on individual landscapes and to model external triggers and environmental changes as small but discrete changes in the landscapes. A “barmap” links macrostates of temporally adjacent landscapes and defines the transfer of population densities from one “snapshot” to the next. Implemented in the BarMap software, this approach makes it feasible to study folding processes at the level of basins, saddle points, and barriers for many nonstationary scenarios, including temperature changes, cotranscriptional folding, refolding in consequence to degradation, and mechanically constrained kinetics, as in the case of the translocation of a polymer through a pore. PMID:20504954

  19. Energy landscapes, folding mechanisms, and kinetics of RNA tetraloop hairpins.

    PubMed

    Chakraborty, Debayan; Collepardo-Guevara, Rosana; Wales, David J

    2014-12-31

    RNA hairpins play a pivotal role in a diverse range of cellular functions, and are integral components of ribozymes, mRNA, and riboswitches. However, the mechanistic and kinetic details of RNA hairpin folding, which are key determinants of most of its biological functions, are poorly understood. In this work, we use the discrete path sampling (DPS) approach to explore the energy landscapes of two RNA tetraloop hairpins, and provide insights into their folding mechanisms and kinetics in atomistic detail. Our results show that the potential energy landscapes have a distinct funnel-like bias toward the folded hairpin state, consistent with efficient structure-seeking properties. Mechanistic and kinetic information is analyzed in terms of kinetic transition networks. We find microsecond folding times, consistent with temperature jump experiments, for hairpin folding initiated from relatively compact unfolded states. This process is essentially driven by an initial collapse, followed by rapid zippering of the helix stem in the final phase. Much lower folding rates are predicted when the folding is initiated from extended chains, which undergo longer excursions on the energy landscape before nucleation events can occur. Our work therefore explains recent experiments and coarse-grained simulations, where the folding kinetics exhibit precisely this dependency on the initial conditions.

  20. Predictive energy landscapes for folding membrane protein assemblies

    NASA Astrophysics Data System (ADS)

    Truong, Ha H.; Kim, Bobby L.; Schafer, Nicholas P.; Wolynes, Peter G.

    2015-12-01

    We study the energy landscapes for membrane protein oligomerization using the Associative memory, Water mediated, Structure and Energy Model with an implicit membrane potential (AWSEM-membrane), a coarse-grained molecular dynamics model previously optimized under the assumption that the energy landscapes for folding α-helical membrane protein monomers are funneled once their native topology within the membrane is established. In this study we show that the AWSEM-membrane force field is able to sample near native binding interfaces of several oligomeric systems. By predicting candidate structures using simulated annealing, we further show that degeneracies in predicting structures of membrane protein monomers are generally resolved in the folding of the higher order assemblies as is the case in the assemblies of both nicotinic acetylcholine receptor and V-type Na+-ATPase dimers. The physics of the phenomenon resembles domain swapping, which is consistent with the landscape following the principle of minimal frustration. We revisit also the classic Khorana study of the reconstitution of bacteriorhodopsin from its fragments, which is the close analogue of the early Anfinsen experiment on globular proteins. Here, we show the retinal cofactor likely plays a major role in selecting the final functional assembly.

  1. Graph theoretical analysis of the energy landscape of model polymers.

    PubMed

    Baiesi, Marco; Bongini, Lorenzo; Casetti, Lapo; Tattini, Lorenzo

    2009-07-01

    In systems characterized by a rough potential-energy landscape, local energetic minima and saddles define a network of metastable states whose topology strongly influences the dynamics. Changes in temperature, causing the merging and splitting of metastable states, have nontrivial effects on such networks and must be taken into account. We do this by means of a recently proposed renormalization procedure. This method is applied to analyze the topology of the network of metastable states for different polypeptidic sequences in a minimalistic polymer model. A smaller spectral dimension emerges as a hallmark of stability of the global energy minimum and highlights a nonobvious link between dynamic and thermodynamic properties.

  2. THEORY OF PROTEIN FOLDING: The Energy Landscape Perspective

    NASA Astrophysics Data System (ADS)

    Onuchic, Jose Nelson; Luthey-Schulten, Zaida; Wolynes, Peter G.

    1997-10-01

    The energy landscape theory of protein folding is a statistical description of a protein's potential surface. It assumes that folding occurs through organizing an ensemble of structures rather than through only a few uniquely defined structural intermediates. It suggests that the most realistic model of a protein is a minimally frustrated heteropolymer with a rugged funnel-like landscape biased toward the native structure. This statistical description has been developed using tools from the statistical mechanics of disordered systems, polymers, and phase transitions of finite systems. We review here its analytical background and contrast the phenomena in homopolymers, random heteropolymers, and protein-like heteropolymers that are kinetically and thermodynamically capable of folding. The connection between these statistical concepts and the results of minimalist models used in computer simulations is discussed. The review concludes with a brief discussion of how the theory helps in the interpretation of results from fast folding experiments and in the practical task of protein structure prediction.

  3. New Methods for Exploring QM:MM Potential Energy Landscapes

    NASA Astrophysics Data System (ADS)

    Hratchian, Hrant P.

    2010-06-01

    In recent years, the applicability of quantum chemical methods for large system studies has been greatly enhanced by the development of hybrid QM:MM techniques. Despite these advancements, exploring the associated potential energy surfaces continues to present two key challenges. First, the QM energy and derivative evaluations may be too costly for simulations; and second, the system size for many QM:MM cases are too large to effectively store or use second-order information, an approach often used in QM studies to allow for larger integration steps and fewer QM evaluations of the potential energy surface. Our most recent work is focused on overcoming both computational bottlenecks. Using surface fitting models together with direct Hessian-vector and diagonalization algorithms, we are developing models that can accurately and efficiently explore QM:MM potential energy landscapes for very large systems. Our current development status and results from initial applications will be described.

  4. Energy landscape of an electron hole in hydrated DNA.

    PubMed

    Bongiorno, Angelo

    2008-11-06

    First-principles/molecular mechanics, force-field, and 1-D lattice model schemes are used to address the energy landscape of an electron hole in hydrated DNA. Force-field calculations are used to derive a statistical description of the electrostatic fluctuations in DNA yielded by the polar environment, and a periodic first-principles/molecular mechanics scheme is employed to calculate the hole energy at uniform DNA segments embedded in hydrated DNA double helices. The results are then mapped onto 1-D lattice models to address issues relevant to charge transfer in hydrated DNA. It is shown that the polar environment generates an intense dynamical energy disorder along the DNA strands, exhibiting exponential spatio-temporal correlations. The fluctuations of the polar environment lead to hole states localized over a few DNA bases and compete evenly with the DNA sequence to define the hole energy landscape. The spatial correlations of the environment-induced fluctuations are also shown to influence strongly the hole transfer dynamics in DNA.

  5. Topology, structures, and energy landscapes of human chromosomes

    PubMed Central

    Zhang, Bin; Wolynes, Peter G.

    2015-01-01

    Chromosome conformation capture experiments provide a rich set of data concerning the spatial organization of the genome. We use these data along with a maximum entropy approach to derive a least-biased effective energy landscape for the chromosome. Simulations of the ensemble of chromosome conformations based on the resulting information theoretic landscape not only accurately reproduce experimental contact probabilities, but also provide a picture of chromosome dynamics and topology. The topology of the simulated chromosomes is probed by computing the distribution of their knot invariants. The simulated chromosome structures are largely free of knots. Topologically associating domains are shown to be crucial for establishing these knotless structures. The simulated chromosome conformations exhibit a tendency to form fibril-like structures like those observed via light microscopy. The topologically associating domains of the interphase chromosome exhibit multistability with varying liquid crystalline ordering that may allow discrete unfolding events and the landscape is locally funneled toward “ideal” chromosome structures that represent hierarchical fibrils of fibrils. PMID:25918364

  6. Topology, structures, and energy landscapes of human chromosomes.

    PubMed

    Zhang, Bin; Wolynes, Peter G

    2015-05-12

    Chromosome conformation capture experiments provide a rich set of data concerning the spatial organization of the genome. We use these data along with a maximum entropy approach to derive a least-biased effective energy landscape for the chromosome. Simulations of the ensemble of chromosome conformations based on the resulting information theoretic landscape not only accurately reproduce experimental contact probabilities, but also provide a picture of chromosome dynamics and topology. The topology of the simulated chromosomes is probed by computing the distribution of their knot invariants. The simulated chromosome structures are largely free of knots. Topologically associating domains are shown to be crucial for establishing these knotless structures. The simulated chromosome conformations exhibit a tendency to form fibril-like structures like those observed via light microscopy. The topologically associating domains of the interphase chromosome exhibit multistability with varying liquid crystalline ordering that may allow discrete unfolding events and the landscape is locally funneled toward "ideal" chromosome structures that represent hierarchical fibrils of fibrils.

  7. RNA folding pathways and kinetics using 2D energy landscapes.

    PubMed

    Senter, Evan; Dotu, Ivan; Clote, Peter

    2015-01-01

    RNA folding pathways play an important role in various biological processes, such as (i) the hok/sok (host-killing/suppression of killing) system in E. coli to check for sufficient plasmid copy number, (ii) the conformational switch in spliced leader (SL) RNA from Leptomonas collosoma, which controls trans splicing of a portion of the '5 exon, and (iii) riboswitches--portions of the 5' untranslated region of messenger RNA that regulate genes by allostery. Since RNA folding pathways are determined by the energy landscape, we describe a novel algorithm, FFTbor2D, which computes the 2D projection of the energy landscape for a given RNA sequence. Given two metastable secondary structures A, B for a given RNA sequence, FFTbor2D computes the Boltzmann probability p(x, y) = Z(x,y)/Z that a secondary structure has base pair distance x from A and distance y from B. Using polynomial interpolationwith the fast Fourier transform,we compute p(x, y) in O(n(5)) time and O(n(2)) space, which is an improvement over an earlier method, which runs in O(n(7)) time and O(n(4)) space. FFTbor2D has potential applications in synthetic biology, where one might wish to design bistable switches having target metastable structures A, B with favorable pathway kinetics. By inverting the transition probability matrix determined from FFTbor2D output, we show that L. collosoma spliced leader RNA has larger mean first passage time from A to B on the 2D energy landscape, than 97.145% of 20,000 sequences, each having metastable structures A, B. Source code and binaries are freely available for download at http://bioinformatics.bc.edu/clotelab/FFTbor2D. The program FFTbor2D is implemented in C++, with optional OpenMP parallelization primitives.

  8. Kinetic reconstruction of the free-energy landscape.

    PubMed

    Wedekind, Jan; Reguera, David

    2008-09-04

    We present a new general method to trace back a lot of valuable information from direct simulations and experiments of activated processes. In particular, it allows the reconstruction of the free-energy landscape for an arbitrary reaction coordinate directly from the out-of-equilibrium dynamics of the process. We demonstrate the power of this concept by its application to a molecular dynamics simulation of nucleation of a Lennard-Jones vapor. The same method can be also applied to Brownian dynamics and stochastic simulations.

  9. Biomolecular Dynamics: Order-Disorder Transitions and Energy Landscapes

    PubMed Central

    Whitford, Paul C.; Sanbonmatsu, Karissa Y.; Onuchic, José N.

    2013-01-01

    While the energy landscape theory of protein folding is now a widely accepted view for understanding how relatively-weak molecular interactions lead to rapid and cooperative protein folding, such a framework must be extended to describe the large-scale functional motions observed in molecular machines. In this review, we discuss 1) the development of the energy landscape theory of biomolecular folding, 2) recent advances towards establishing a consistent understanding of folding and function, and 3) emerging themes in the functional motions of enzymes, biomolecular motors, and other biomolecular machines. Recent theoretical, computational, and experimental lines of investigation are providing a very dynamic picture of biomolecular motion. In contrast to earlier ideas, where molecular machines were thought to function similarly to macroscopic machines, with rigid components that move along a few degrees of freedom in a deterministic fashion, biomolecular complexes are only marginally stable. Since the stabilizing contribution of each atomic interaction is on the order of the thermal fluctuations in solution, the rigid body description of molecular function must be revisited. An emerging theme is that functional motions encompass order-disorder transitions and structural flexibility provide significant contributions to the free-energy. In this review, we describe the biological importance of order-disorder transitions and discuss the statistical-mechanical foundation of theoretical approaches that can characterize such transitions. PMID:22790780

  10. New Energy Landscapes of Pennsylvania: Forests to Farms to Fracking

    NASA Astrophysics Data System (ADS)

    Johnson, Deborah A.

    This dissertation adds to the literature on energy needed by industry, government, and citizens for decision-making. The pursuit to access or create new energy resources spawns new landscapes of energy in the early 21st century. The combination of hydraulic fracturing and horizontal drilling technologies---popularly called "fracking"---enables entry into previously inaccessible natural gas reserves such as the Marcellus shale much of which lies beneath Pennsylvania. Although this unconventional method offers a promising source of domestic energy and job growth, the potential for negative impacts raises concerns and questions. The questions include: What is the controversy about fracking in Pennsylvania? What are the impacts of fracking? What costs is Pennsylvania paying as it shifts to shale gas extraction? Are there activities taking place or material signs that point to the emerging new landscapes? Are the individuals and organizations that resist shale gas extraction---the so-called "Green Forces"---and others who live within the region of development more or less attuned to these costs? A mixed methods approach consists of landscape and stakeholder analyses including visual examination of GIS-generated maps, satellite images, and photos taken in the field specifically from four counties: Washington, Warren, McKean, and Bradford. Research captures stakeholders' voices across the public, government, and private sectors at different scales. A stakeholder matrix facilitates data organization and analysis. Data include 114 individual statements from an EPA Public Meeting, texts from 40 online-newspaper articles or blogs, and face-to-face interviews or focus group participation of 36 individuals. Further data come from a public health conference, industry convention, and public protest. The new energy landscape covers spaces in Pennsylvania where oil and gas development previously had not been present. It obscures as well as exposes the legacy of past energy

  11. 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.

  12. Protein energy landscapes determined by five-dimensional crystallography

    PubMed Central

    Schmidt, Marius; Srajer, Vukica; Henning, Robert; Ihee, Hyotcherl; Purwar, Namrta; Tenboer, Jason; Tripathi, Shailesh

    2013-01-01

    Free-energy landscapes decisively determine the progress of enzymatically catalyzed reactions [Cornish-Bowden (2012 ▶), Fundamentals of Enzyme Kinetics, 4th ed.]. Time-resolved macromolecular crystallography unifies transient-state kinetics with structure determination [Moffat (2001 ▶), Chem. Rev. 101, 1569–1581; Schmidt et al. (2005 ▶), Methods Mol. Biol. 305, 115–154; Schmidt (2008 ▶), Ultrashort Laser Pulses in Medicine and Biology] because both can be determined from the same set of X-ray data. Here, it is demonstrated how barriers of activation can be determined solely from five-dimensional crystallo­graphy, where in addition to space and time, temperature is a variable as well [Schmidt et al. (2010 ▶), Acta Cryst. A66, 198–206]. Directly linking molecular structures with barriers of activation between them allows insight into the structural nature of the barrier to be gained. Comprehensive time series of crystallo­graphic data at 14 different temperature settings were analyzed and the entropy and enthalpy contributions to the barriers of activation were determined. One hundred years after the discovery of X-ray scattering, these results advance X-ray structure determination to a new frontier: the determination of energy landscapes. PMID:24311594

  13. Protein energy landscapes determined by five-dimensional crystallography

    SciTech Connect

    Schmidt, Marius; Srajer, Vukica; Henning, Robert; Ihee, Hyotcherl; Purwar, Namrta; Tenboer, Jason; Tripathi, Shailesh

    2013-12-01

    Barriers of activation within the photocycle of a photoactive protein were extracted from comprehensive time courses of time resolved crystallographic data collected at multiple temperature settings. Free-energy landscapes decisively determine the progress of enzymatically catalyzed reactions [Cornish-Bowden (2012 ▶), Fundamentals of Enzyme Kinetics, 4th ed.]. Time-resolved macromolecular crystallography unifies transient-state kinetics with structure determination [Moffat (2001 ▶), Chem. Rev.101, 1569–1581; Schmidt et al. (2005 ▶), Methods Mol. Biol.305, 115–154; Schmidt (2008 ▶), Ultrashort Laser Pulses in Medicine and Biology] because both can be determined from the same set of X-ray data. Here, it is demonstrated how barriers of activation can be determined solely from five-dimensional crystallography, where in addition to space and time, temperature is a variable as well [Schmidt et al. (2010 ▶), Acta Cryst. A66, 198–206]. Directly linking molecular structures with barriers of activation between them allows insight into the structural nature of the barrier to be gained. Comprehensive time series of crystallographic data at 14 different temperature settings were analyzed and the entropy and enthalpy contributions to the barriers of activation were determined. One hundred years after the discovery of X-ray scattering, these results advance X-ray structure determination to a new frontier: the determination of energy landscapes.

  14. Landscape of Future Accelerators at the Energy and Intensity Frontier

    SciTech Connect

    Syphers, M. J.; Chattopadhyay, S.

    2016-11-21

    An overview is provided of the currently envisaged landscape of charged particle accelerators at the energy and intensity frontiers to explore particle physics beyond the standard model via 1-100 TeV-scale lepton and hadron colliders and multi-Megawatt proton accelerators for short- and long- baseline neutrino experiments. The particle beam physics, associated technological challenges and progress to date for these accelerator facilities (LHC, HL-LHC, future 100 TeV p-p colliders, Tev-scale linear and circular electron-positron colliders, high intensity proton accelerator complex PIP-II for DUNE and future upgrade to PIP-III) are outlined. Potential and prospects for advanced “nonlinear dynamic techniques” at the multi-MW level intensity frontier and advanced “plasma- wakefield-based techniques” at the TeV-scale energy frontier and are also described.

  15. Hierarchical Protein Free Energy Landscapes from Variationally Enhanced Sampling.

    PubMed

    Shaffer, Patrick; Valsson, Omar; Parrinello, Michele

    2016-12-13

    In recent work, we demonstrated that it is possible to obtain approximate representations of high-dimensional free energy surfaces with variationally enhanced sampling ( Shaffer, P.; Valsson, O.; Parrinello, M. Proc. Natl. Acad. Sci. , 2016 , 113 , 17 ). The high-dimensional spaces considered in that work were the set of backbone dihedral angles of a small peptide, Chignolin, and the high-dimensional free energy surface was approximated as the sum of many two-dimensional terms plus an additional term which represents an initial estimate. In this paper, we build on that work and demonstrate that we can calculate high-dimensional free energy surfaces of very high accuracy by incorporating additional terms. The additional terms apply to a set of collective variables which are more coarse than the base set of collective variables. In this way, it is possible to build hierarchical free energy surfaces, which are composed of terms that act on different length scales. We test the accuracy of these free energy landscapes for the proteins Chignolin and Trp-cage by constructing simple coarse-grained models and comparing results from the coarse-grained model to results from atomistic simulations. The approach described in this paper is ideally suited for problems in which the free energy surface has important features on different length scales or in which there is some natural hierarchy.

  16. Free energy landscape and molecular pathways of gas hydrate nucleation

    NASA Astrophysics Data System (ADS)

    Bi, Yuanfei; Porras, Anna; Li, Tianshu

    2016-12-01

    Despite the significance of gas hydrates in diverse areas, a quantitative knowledge of hydrate formation at a molecular level is missing. The impediment to acquiring this understanding is primarily attributed to the stochastic nature and ultra-fine scales of nucleation events, posing a great challenge for both experiment and simulation to explore hydrate nucleation. Here we employ advanced molecular simulation methods, including forward flux sampling (FFS), pB histogram analysis, and backward flux sampling, to overcome the limit of direct molecular simulation for exploring both the free energy landscape and molecular pathways of hydrate nucleation. First we test the half-cage order parameter (H-COP) which we developed for driving FFS, through conducting the pB histogram analysis. Our results indeed show that H-COP describes well the reaction coordinates of hydrate nucleation. Through the verified order parameter, we then directly compute the free energy landscape for hydrate nucleation by combining both forward and backward flux sampling. The calculated stationary distribution density, which is obtained independently of nucleation theory, is found to fit well against the classical nucleation theory (CNT). Subsequent analysis of the obtained large ensemble of hydrate nucleation trajectories show that although on average, hydrate formation is facilitated by a two-step like mechanism involving a gradual transition from an amorphous to a crystalline structure, there also exist nucleation pathways where hydrate crystallizes directly, without going through the amorphous stage. The CNT-like free energy profile and the structural diversity suggest the existence of multiple active transition pathways for hydrate nucleation, and possibly also imply the near degeneracy in their free energy profiles among different pathways. Our results thus bring a new perspective to the long standing question of how hydrates crystallize.

  17. Energy Landscapes and Catalysis in Nitric-oxide Synthase*

    PubMed Central

    Sobolewska-Stawiarz, Anna; Leferink, Nicole G. H.; Fisher, Karl; Heyes, Derren J.; Hay, Sam; Rigby, Stephen E. J.; Scrutton, Nigel S.

    2014-01-01

    Nitric oxide (NO) plays diverse roles in mammalian physiology. It is involved in blood pressure regulation, neurotransmission, and immune response, and is generated through complex electron transfer reactions catalyzed by NO synthases (NOS). In neuronal NOS (nNOS), protein domain dynamics and calmodulin binding are implicated in regulating electron flow from NADPH, through the FAD and FMN cofactors, to the heme oxygenase domain, the site of NO generation. Simple models based on crystal structures of nNOS reductase have invoked a role for large scale motions of the FMN-binding domain in shuttling electrons from the FAD-binding domain to the heme oxygenase domain. However, molecular level insight of the dynamic structural transitions in NOS enzymes during enzyme catalysis is lacking. We use pulsed electron-electron double resonance spectroscopy to derive inter-domain distance relationships in multiple conformational states of nNOS. These distance relationships are correlated with enzymatic activity through variable pressure kinetic studies of electron transfer and turnover. The binding of NADPH and calmodulin are shown to influence interdomain distance relationships as well as reaction chemistry. An important effect of calmodulin binding is to suppress adventitious electron transfer from nNOS to molecular oxygen and thereby preventing accumulation of reactive oxygen species. A complex landscape of conformations is required for nNOS catalysis beyond the simple models derived from static crystal structures of nNOS reductase. Detailed understanding of this landscape advances our understanding of nNOS catalysis/electron transfer, and could provide new opportunities for the discovery of small molecule inhibitors that bind at dynamic protein interfaces of this multidimensional energy landscape. PMID:24610812

  18. Directed Magnetic Particle Transport above Artificial Magnetic Domains Due to Dynamic Magnetic Potential Energy Landscape Transformation.

    PubMed

    Holzinger, Dennis; Koch, Iris; Burgard, Stefan; Ehresmann, Arno

    2015-07-28

    An approach for a remotely controllable transport of magnetic micro- and/or nanoparticles above a topographically flat exchange-bias (EB) thin film system, magnetically patterned into parallel stripe domains, is presented where the particle manipulation is achieved by sub-mT external magnetic field pulses. Superparamagnetic core-shell particles are moved stepwise by the dynamic transformation of the particles' magnetic potential energy landscape due to the external magnetic field pulses without affecting the magnetic state of the thin film system. The magnetic particle velocity is adjustable in the range of 1-100 μm/s by the design of the substrate's magnetic field landscape (MFL), the particle-substrate distance, and the magnitude of the applied external magnetic field pulses. The agglomeration of magnetic particles is avoided by the intrinsic magnetostatic repulsion of particles due to the parallel alignment of the particles' magnetic moments perpendicular to the transport direction and parallel to the surface normal of the substrate during the particle motion. The transport mechanism is modeled by a quantitative theory based on the precise knowledge of the sample's MFL and the particle-substrate distance.

  19. Folding energy landscape of the thiamine pyrophosphate riboswitch aptamer.

    PubMed

    Anthony, Peter C; Perez, Christian F; García-García, Cuauhtémoc; Block, Steven M

    2012-01-31

    Riboswitches are motifs in the untranslated regions (UTRs) of RNA transcripts that sense metabolite levels and modulate the expression of the corresponding genes for metabolite import, export, synthesis, or degradation. All riboswitches contain an aptamer: an RNA structure that, upon binding ligand, folds to expose or sequester regulatory elements in the adjacent sequence through alternative nucleotide pairing. The coupling between ligand binding and aptamer folding is central to the regulatory mechanisms of thiamine pyrophosphate (TPP) riboswitches and has not been fully characterized. Here, we show that TPP aptamer folding can be decomposed into ligand-independent and -dependent steps that correspond to the formation of secondary and tertiary structures, respectively. We reconstructed the full energy landscape for folding of the wild-type (WT) aptamer and measured perturbations of this landscape arising from mutations or ligand binding. We show that TPP binding proceeds in two steps, from a weakly to a strongly bound state. Our data imply a hierarchical folding sequence, and provide a framework for understanding molecular mechanism throughout the TPP riboswitch family.

  20. Nonequilibrium study of the intrinsic free-energy profile across a liquid-vapour interface

    SciTech Connect

    Braga, Carlos Muscatello, Jordan Lau, Gabriel Müller, Erich A. Jackson, George

    2016-01-28

    We calculate an atomistically detailed free-energy profile across a heterogeneous system using a nonequilibrium approach. The path-integral formulation of Crooks fluctuation theorem is used in conjunction with the intrinsic sampling method to calculate the free-energy profile for the liquid-vapour interface of the Lennard-Jones fluid. Free-energy barriers are found corresponding to the atomic layering in the liquid phase as well as a barrier associated with the presence of an adsorbed layer as revealed by the intrinsic density profile. Our findings are in agreement with profiles calculated using Widom’s potential distribution theorem applied to both the average and the intrinsic profiles as well as the literature values for the excess chemical potential.

  1. Nonequilibrium study of the intrinsic free-energy profile across a liquid-vapour interface

    NASA Astrophysics Data System (ADS)

    Braga, Carlos; Muscatello, Jordan; Lau, Gabriel; Müller, Erich A.; Jackson, George

    2016-01-01

    We calculate an atomistically detailed free-energy profile across a heterogeneous system using a nonequilibrium approach. The path-integral formulation of Crooks fluctuation theorem is used in conjunction with the intrinsic sampling method to calculate the free-energy profile for the liquid-vapour interface of the Lennard-Jones fluid. Free-energy barriers are found corresponding to the atomic layering in the liquid phase as well as a barrier associated with the presence of an adsorbed layer as revealed by the intrinsic density profile. Our findings are in agreement with profiles calculated using Widom's potential distribution theorem applied to both the average and the intrinsic profiles as well as the literature values for the excess chemical potential.

  2. Learning To Fold Proteins Using Energy Landscape Theory

    PubMed Central

    Schafer, N.P.; Kim, B.L.; Zheng, W.; Wolynes, P.G.

    2014-01-01

    This review is a tutorial for scientists interested in the problem of protein structure prediction, particularly those interested in using coarse-grained molecular dynamics models that are optimized using lessons learned from the energy landscape theory of protein folding. We also present a review of the results of the AMH/AMC/AMW/AWSEM family of coarse-grained molecular dynamics protein folding models to illustrate the points covered in the first part of the article. Accurate coarse-grained structure prediction models can be used to investigate a wide range of conceptual and mechanistic issues outside of protein structure prediction; specifically, the paper concludes by reviewing how AWSEM has in recent years been able to elucidate questions related to the unusual kinetic behavior of artificially designed proteins, multidomain protein misfolding, and the initial stages of protein aggregation. PMID:25308991

  3. Approximate scaling properties of RNA free energy landscapes

    NASA Technical Reports Server (NTRS)

    Baskaran, S.; Stadler, P. F.; Schuster, P.

    1996-01-01

    RNA free energy landscapes are analysed by means of "time-series" that are obtained from random walks restricted to excursion sets. The power spectra, the scaling of the jump size distribution, and the scaling of the curve length measured with different yard stick lengths are used to describe the structure of these "time series". Although they are stationary by construction, we find that their local behavior is consistent with both AR(1) and self-affine processes. Random walks confined to excursion sets (i.e., with the restriction that the fitness value exceeds a certain threshold at each step) exhibit essentially the same statistics as free random walks. We find that an AR(1) time series is in general approximately self-affine on timescales up to approximately the correlation length. We present an empirical relation between the correlation parameter rho of the AR(1) model and the exponents characterizing self-affinity.

  4. Monte Carlo simulations of systems with complex energy landscapes

    NASA Astrophysics Data System (ADS)

    Wüst, T.; Landau, D. P.; Gervais, C.; Xu, Y.

    2009-04-01

    Non-traditional Monte Carlo simulations are a powerful approach to the study of systems with complex energy landscapes. After reviewing several of these specialized algorithms we shall describe the behavior of typical systems including spin glasses, lattice proteins, and models for "real" proteins. In the Edwards-Anderson spin glass it is now possible to produce probability distributions in the canonical ensemble and thermodynamic results of high numerical quality. In the hydrophobic-polar (HP) lattice protein model Wang-Landau sampling with an improved move set (pull-moves) produces results of very high quality. These can be compared with the results of other methods of statistical physics. A more realistic membrane protein model for Glycophorin A is also examined. Wang-Landau sampling allows the study of the dimerization process including an elucidation of the nature of the process.

  5. Programmable energy landscapes for kinetic control of DNA strand displacement.

    PubMed

    Machinek, Robert R F; Ouldridge, Thomas E; Haley, Natalie E C; Bath, Jonathan; Turberfield, Andrew J

    2014-11-10

    DNA is used to construct synthetic systems that sense, actuate, move and compute. The operation of many dynamic DNA devices depends on toehold-mediated strand displacement, by which one DNA strand displaces another from a duplex. Kinetic control of strand displacement is particularly important in autonomous molecular machinery and molecular computation, in which non-equilibrium systems are controlled through rates of competing processes. Here, we introduce a new method based on the creation of mismatched base pairs as kinetic barriers to strand displacement. Reaction rate constants can be tuned across three orders of magnitude by altering the position of such a defect without significantly changing the stabilities of reactants or products. By modelling reaction free-energy landscapes, we explore the mechanistic basis of this control mechanism. We also demonstrate that oxDNA, a coarse-grained model of DNA, is capable of accurately predicting and explaining the impact of mismatches on displacement kinetics.

  6. Measuring the energy landscape of complex bonds using AFM

    NASA Astrophysics Data System (ADS)

    Mayyas, Essa; Hoffmann, Peter; Runyan, Lindsay

    2009-03-01

    We measured rupture force of a complex bond of two interacting proteins with atomic force microscopy. Proteins of interest were active and latent Matrix metalloproteinases (MMPs), type 2 and 9, and their tissue inhibitors TIMP1 and TIMP2. Measurements show that the rupture force depends on the pulling speed; it ranges from 30 pN to 150 pN at pulling speeds 30nm/s to 48000nm/s. Analyzing data using an extended theory enabled us to understand the mechanism of MMP-TIMP interaction; we determined all physical parameters that form the landscape energy of the interaction, in addition to the life time of the bond and its length. Moreover, we used the pulling experiment to study the interaction of TIMP2 with the receptor MT1-MMP on the surface of living cells.

  7. Temporal disconnectivity of the energy landscape in glassy systems

    NASA Astrophysics Data System (ADS)

    Lempesis, Nikolaos; Boulougouris, Georgios C.; Theodorou, Doros N.

    2013-03-01

    An alternative graphical representation of the potential energy landscape (PEL) has been developed and applied to a binary Lennard-Jones glassy system, providing insight into the unique topology of the system's potential energy hypersurface. With the help of this representation one is able to monitor the different explored basins of the PEL, as well as how - and mainly when - subsets of basins communicate with each other via transitions in such a way that details of the prior temporal history have been erased, i.e., local equilibration between the basins in each subset has been achieved. In this way, apart from detailed information about the structure of the PEL, the system's temporal evolution on the PEL is described. In order to gather all necessary information about the identities of two or more basins that are connected with each other, we consider two different approaches. The first one is based on consideration of the time needed for two basins to mutually equilibrate their populations according to the transition rate between them, in the absence of any effect induced by the rest of the landscape. The second approach is based on an analytical solution of the master equation that explicitly takes into account the entire explored landscape. It is shown that both approaches lead to the same result concerning the topology of the PEL and dynamical evolution on it. Moreover, a "temporal disconnectivity graph" is introduced to represent a lumped system stemming from the initial one. The lumped system is obtained via a specially designed algorithm [N. Lempesis, D. G. Tsalikis, G. C. Boulougouris, and D. N. Theodorou, J. Chem. Phys. 135, 204507 (2011), 10.1063/1.3663207]. The temporal disconnectivity graph provides useful information about both the lumped and the initial systems, including the definition of "metabasins" as collections of basins that communicate with each other via transitions that are fast relative to the observation time. Finally, the two examined

  8. Energy landscape of LeuT from molecular simulations

    NASA Astrophysics Data System (ADS)

    Gur, Mert; Zomot, Elia; Cheng, Mary Hongying; Bahar, Ivet

    2015-12-01

    The bacterial sodium-coupled leucine transporter (LeuT) has been broadly used as a structural model for understanding the structure-dynamics-function of mammalian neurotransmitter transporters as well as other solute carriers that share the same fold (LeuT fold), as the first member of the family crystallographically resolved in multiple states: outward-facing open, outward-facing occluded, and inward-facing open. Yet, a complete picture of the energy landscape of (sub)states visited along the LeuT transport cycle has been elusive. In an attempt to visualize the conformational spectrum of LeuT, we performed extensive simulations of LeuT dimer dynamics in the presence of substrate (Ala or Leu) and co-transported Na+ ions, in explicit membrane and water. We used both conventional molecular dynamics (MD) simulations (with Anton supercomputing machine) and a recently introduced method, collective MD, that takes advantage of collective modes of motions predicted by the anisotropic network model. Free energy landscapes constructed based on ˜40 μs trajectories reveal multiple substates occluded to the extracellular (EC) and/or intracellular (IC) media, varying in the levels of exposure of LeuT to EC or IC vestibules. The IC-facing transmembrane (TM) helical segment TM1a shows an opening, albeit to a smaller extent and in a slightly different direction than that observed in the inward-facing open crystal structure. The study provides insights into the spectrum of conformational substates and paths accessible to LeuT and highlights the differences between Ala- and Leu-bound substates.

  9. Energy landscape of LeuT from molecular simulations.

    PubMed

    Gur, Mert; Zomot, Elia; Cheng, Mary Hongying; Bahar, Ivet

    2015-12-28

    The bacterial sodium-coupled leucine transporter (LeuT) has been broadly used as a structural model for understanding the structure-dynamics-function of mammalian neurotransmitter transporters as well as other solute carriers that share the same fold (LeuT fold), as the first member of the family crystallographically resolved in multiple states: outward-facing open, outward-facing occluded, and inward-facing open. Yet, a complete picture of the energy landscape of (sub)states visited along the LeuT transport cycle has been elusive. In an attempt to visualize the conformational spectrum of LeuT, we performed extensive simulations of LeuT dimer dynamics in the presence of substrate (Ala or Leu) and co-transported Na(+) ions, in explicit membrane and water. We used both conventional molecular dynamics (MD) simulations (with Anton supercomputing machine) and a recently introduced method, collective MD, that takes advantage of collective modes of motions predicted by the anisotropic network model. Free energy landscapes constructed based on ∼40 μs trajectories reveal multiple substates occluded to the extracellular (EC) and/or intracellular (IC) media, varying in the levels of exposure of LeuT to EC or IC vestibules. The IC-facing transmembrane (TM) helical segment TM1a shows an opening, albeit to a smaller extent and in a slightly different direction than that observed in the inward-facing open crystal structure. The study provides insights into the spectrum of conformational substates and paths accessible to LeuT and highlights the differences between Ala- and Leu-bound substates.

  10. Energy landscape of LeuT from molecular simulations

    PubMed Central

    Gur, Mert; Zomot, Elia; Cheng, Mary Hongying; Bahar, Ivet

    2015-01-01

    The bacterial sodium-coupled leucine transporter (LeuT) has been broadly used as a structural model for understanding the structure-dynamics-function of mammalian neurotransmitter transporters as well as other solute carriers that share the same fold (LeuT fold), as the first member of the family crystallographically resolved in multiple states: outward-facing open, outward-facing occluded, and inward-facing open. Yet, a complete picture of the energy landscape of (sub)states visited along the LeuT transport cycle has been elusive. In an attempt to visualize the conformational spectrum of LeuT, we performed extensive simulations of LeuT dimer dynamics in the presence of substrate (Ala or Leu) and co-transported Na+ ions, in explicit membrane and water. We used both conventional molecular dynamics (MD) simulations (with Anton supercomputing machine) and a recently introduced method, collective MD, that takes advantage of collective modes of motions predicted by the anisotropic network model. Free energy landscapes constructed based on ∼40 μs trajectories reveal multiple substates occluded to the extracellular (EC) and/or intracellular (IC) media, varying in the levels of exposure of LeuT to EC or IC vestibules. The IC-facing transmembrane (TM) helical segment TM1a shows an opening, albeit to a smaller extent and in a slightly different direction than that observed in the inward-facing open crystal structure. The study provides insights into the spectrum of conformational substates and paths accessible to LeuT and highlights the differences between Ala- and Leu-bound substates. PMID:26723619

  11. Energy conversion modeling of the intrinsic persistent luminescence of solids via energy transfer paths between transition levels.

    PubMed

    Huang, Bolong; Sun, Mingzi

    2017-04-05

    An energy conversion model has been established for the intrinsic persistent luminescence in solids related to the native point defect levels, formations, and transitions. In this study, we showed how the recombination of charge carriers between different defect levels along the zero phonon line (ZPL) can lead to energy conversions supporting the intrinsic persistent phosphorescence in solids. This suggests that the key driving force for this optical phenomenon is the pair of electrons hopping between different charged defects with negative-Ueff. Such a negative correlation energy will provide a sustainable energy source for electron-holes to further recombine in a new cycle with a specific quantum yield. This will help us to understand the intrinsic persistent luminescence with respect to native point defect levels as well as the correlations of electronics and energetics.

  12. Role of Northern Lakes in Landscape Energy Balance

    NASA Astrophysics Data System (ADS)

    Rouse, W. R.; Oswald, C. J.; Spence, C.; Blanken, P. D.; Bussières, N.; Schertzer, W. M.; Duguay, C. R.; Binyamin, J.

    2004-05-01

    In the central Mackenzie River Valley of western Canada, from which most of the data used in this study are derived, there are about 32,370 lakes. For the specific study region used to determine the landscape energy balance, lakes comprise 37% of the landscape. They are classified as small (<1 km2), medium (1-100 km2) and large (>100 km2). The large lake is represented by the central portion of Great Slave Lake. The non-lake components of the landscape are divided into wetlands (8%) and uplands (55%). With such abundance, lakes are important features in regional climatic, meteorological and biogeochemical cycling. The purpose of this paper is to examine the regional role of lakes in the surface energy and water balance, to link this to the frequency-size distribution of lakes, and to cast some light on how the surface energy balance may influence regional climate and weather processes. Toward this end we employ recently-gathered data from northern lakes of various sizes, characterize their surface energy balances for both magnitude and temporal behavior of fluxes, and examine the impacts of combinations of various-size lakes and land-lake distributions on regional energy balances and evaporation cycles. The analysis is limited to the ice-free period. Net radiation was substantially greater over all water-dominated surfaces compared with uplands (U). Seasonal differences were 16% greater for wetlands (W), 25% greater for small (SL) and medium (ML) lakes and 73% greater for Great Slave Lake (LL). At maximum, the seasonal heat storage relative to net radiation was 6, 9, 26, 55 and 76 % for U, W, SL, ML and LL respectively. ML and LL are slow to warm in summer but their large cumulative heat storage near summer's end has a major impact on the regional energy balance, because this heat is available to feed convective heat fluxes in fall and early winter. The evaporation season for U, W, SL, ML and LL lasts for 19, 21, 22, 24 and 30 weeks respectively. The effects of

  13. Hybrid Topological Lie-Hamiltonian Learning in Evolving Energy Landscapes

    NASA Astrophysics Data System (ADS)

    Ivancevic, Vladimir G.; Reid, Darryn J.

    2015-11-01

    In this Chapter, a novel bidirectional algorithm for hybrid (discrete + continuous-time) Lie-Hamiltonian evolution in adaptive energy landscape-manifold is designed and its topological representation is proposed. The algorithm is developed within a geometrically and topologically extended framework of Hopfield's neural nets and Haken's synergetics (it is currently designed in Mathematica, although with small changes it could be implemented in Symbolic C++ or any other computer algebra system). The adaptive energy manifold is determined by the Hamiltonian multivariate cost function H, based on the user-defined vehicle-fleet configuration matrix W, which represents the pseudo-Riemannian metric tensor of the energy manifold. Search for the global minimum of H is performed using random signal differential Hebbian adaptation. This stochastic gradient evolution is driven (or, pulled-down) by `gravitational forces' defined by the 2nd Lie derivatives of H. Topological changes of the fleet matrix W are observed during the evolution and its topological invariant is established. The evolution stops when the W-topology breaks down into several connectivity-components, followed by topology-breaking instability sequence (i.e., a series of phase transitions).

  14. Effects of relaxation on the energy landscape of amorphous silicon

    NASA Astrophysics Data System (ADS)

    Kallel, Houssem; Mousseau, Normand; Schiettekatte, Francois

    2008-03-01

    Amorphous silicon is used in many devices around us, included as a thin-film transistor in most flat screens, it also serves as the reference for the study of disordered network systems. Recently, differential scanning calorimetry and nanocalorimetry measurements (DSC) ^1 have shown that the heat released as the temperature of the sample is raised following implantation, is temperature independent. To understand this behaviour, we characterize the energy landscape of model a-Si. Using the activation-relaxation technique (ART nouveau) with the modified Stillinger-Weber potential, we generate models at four levels of relaxation and identify the relaxation mechanisms by analysing 100 000 events for each model. We find that while the distribution of the activation barriers shifts to higher energy as the system is relaxed, the distribution of the relaxation energies is almost unchanged. The relation between these two phenomena is consistent with the DSC measurements. This work is supported, in part, by NSERC, FQRNT and the CRC Foundation. HK is grateful for a scholarship from the Tunisian Ministry of Higher Education, Scientific Research and Technology. ^1 R. Karmouch et al., Phys. Rev. B 75, 075304 (2007)

  15. Statistical theory for protein ensembles with designed energy landscapes

    NASA Astrophysics Data System (ADS)

    Biswas, Parbati; Zou, Jinming; Saven, Jeffery G.

    2005-10-01

    Combinatorial protein libraries provide a promising route to investigate the determinants and features of protein folding and to identify novel folding amino acid sequences. A library of sequences based on a pool of different monomer types are screened for folding molecules, consistent with a particular foldability criterion. The number of sequences grows exponentially with the length of the polymer, making both experimental and computational tabulations of sequences infeasible. Herein a statistical theory is extended to specify the properties of sequences having particular values of global energetic quantities that specify their energy landscape. The theory yields the site-specific monomer probabilities. A foldability criterion is derived that characterizes the properties of sequences by quantifying the energetic separation of the target state from low-energy states in the unfolded ensemble and the fluctuations of the energies in the unfolded state ensemble. For a simple lattice model of proteins, excellent agreement is observed between the theory and the results of exact enumeration. The theory may be used to provide a quantitative framework for the design and interpretation of combinatorial experiments.

  16. Using Semantic Web Technologies to Develop Intrinsically Resilient Energy Control Systems

    SciTech Connect

    Sheldon, Frederick T; Huang, Jingshan; Fetzer, Daniel T; Morris, Thomas H; Jonathan, Kirsch; Goose, Stuart; Wei, Dong; Dang, Jiangbo; Manz, David

    2012-01-01

    To preserve critical energy control functions while under attack, it is necessary to perform comprehensive analysis on root causes and impacts of cyber intrusions without sacrificing the availability of energy delivery. We propose to design an intrinsically resilient energy control system where we extensively utilize Semantic Web technologies, which play critical roles in knowledge representation and acquisition. While our ultimate goal is to ensure availability/resiliency of energy delivery functions and the capability to assess root causes and impacts of cyber intrusions, the focus of this paper is to demonstrate a proof of concept of how Semantic Web technologies can significantly contribute to resilient energy control systems.

  17. Free energy landscape of a minimalist salt bridge model.

    PubMed

    Li, Xubin; Lv, Chao; Corbett, Karen M; Zheng, Lianqing; Wu, Dongsheng; Yang, Wei

    2016-01-01

    Salt bridges are essential to protein stability and dynamics. Despite the importance, there has been scarce of detailed discussion on how salt bridge partners interact with each other in distinct solvent exposed environments. In this study, employing a recent generalized orthogonal space tempering (gOST) method, we enabled efficient molecular dynamics simulation of repetitive breaking and reforming of salt bridge structures within a minimalist salt-bridge model, the Asp-Arg dipeptide and thereby were able to map its detailed free energy landscape in aqueous solution. Free energy surface analysis shows that although individually-solvated states are more favorable, salt-bridge states still occupy a noticeable portion of the overall population. Notably, the competing forces, e.g. intercharge attractions that drive the formation of salt bridges and solvation forces that pull the charged groups away from each other, are energetically comparable. As the result, the salt bridge stability is highly tunable by local environments; for instance when local water molecules are perturbed to interact more strongly with each other, the population of the salt-bridge states is likely to increase. Our results reveal the critical role of local solvent structures in modulating salt-bridge partner interactions and imply the importance of water fluctuations on conformational dynamics that involves solvent accessible salt bridge formations.

  18. The Energy Landscape of Hyperstable LacI-DNA Loops

    NASA Astrophysics Data System (ADS)

    Kahn, Jason

    2009-03-01

    The Escherichia coli LacI protein represses transcription of the lac operon by blocking access to the promoter through binding at a promoter-proximal DNA operator. The affinity of tetrameric LacI (and therefore the repression efficiency) is enhanced by simultaneous binding to an auxiliary operator, forming a DNA loop. Hyperstable LacI-DNA loops were previously shown to be formed on DNA constructs that include a sequence-directed bend flanked by operators. Biochemical experiments showed that two such constructs (9C14 and 11C12) with different helical phasing between the operators and the DNA bend form different DNA loop shapes. The geometry and topology of the loops and the relevance of alternative conformations suggested by probable flexible linkers in LacI remain unclear. Bulk and single molecule fluorescence resonance energy transfer (SM-FRET, with D. English) experiments on a dual fluorophore-labeled 9C14-LacI loop demonstrate that it adopts a single, stable, rigid closed-form loop conformation. Here, we characterize the LacI-9C14 loop by SM-FRET as a function of inducer isopropyl-β,D-thiogalactoside (IPTG) concentration. Energy transfer measurements reveal partial but incomplete destabilization of loop formation by IPTG. Surprisingly, there is no change in the energy transfer efficiency of the remaining looped population. Models for the regulation of the lac operon often assume complete disruption of LacI-operator complexes upon inducer binding to LacI. Our work shows that even at saturating IPTG there is still a significant population of LacI-DNA complexes in a looped state, in accord with previous in vivo experiments that show incomplete induction (with J. Maher). Finally, we will report progress on characterizing the ``energy landscape'' for DNA looping upon systematic variation of the DNA linkers between the operators and the bending locus. Rod mechanics simulations (with N. Perkins) provide testable predictions on loop stability, topology, and FRET.

  19. Free-Energy Landscape of the Amino-Terminal Fragment of Huntingtin in Aqueous Solution

    PubMed Central

    Binette, Vincent; Côté, Sébastien; Mousseau, Normand

    2016-01-01

    The first exon of Huntingtin—a protein with multiple biological functions whose misfolding is related to Huntington’s disease—modulates its localization, aggregation, and function within the cell. It is composed of a 17-amino-acid amphipathic segment (Htt17), an amyloidogenic segment of consecutive glutamines (QN), and a proline-rich segment. Htt17 is of fundamental importance: it serves as a membrane anchor to control the localization of huntingtin, it modulates huntingtin’s function through posttranslational modifications, and it controls the self-assembly of the amyloidogenic QN segment into oligomers and fibrils. Experimentally, the conformational ensemble of the Htt17 monomer, as well as the impact of the polyglutamine and proline-rich segments, remains, however, mostly uncharacterized at the atomic level due to its intrinsic flexibility. Here, we unveil the free-energy landscape of Htt17, Htt17Q17, and Htt17Q17P11 using Hamiltonian replica exchange combined with well-tempered metadynamics. We characterize the free-energy landscape of these three fragments in terms of a few selected collective variables. Extensive simulations reveal that the free energy of Htt17 is dominated by a broad ensemble of configurations that agree with solution NMR chemical shifts. Addition of Q17 at its carboxy-terminus reduces the extent of the main basin to more extended configurations of Htt17 with lower helix propensity. Also, the aliphatic carbons of Q17 partially sequester the nonpolar amino acids of Htt17. For its part, addition of Q17P11 shifts the overall landscape to a more extended and helical Htt17 stabilized by interactions with Q17 and P11, which almost exclusively form a PPII-helix, as well as by intramolecular H-bonds and salt bridges. Our characterization of Huntingtin’s amino-terminus provides insights into the structural origin of its ability to oligomerize and interact with phospholipid bilayers, processes closely linked to the biological functions of

  20. Bayesian Energy Landscape Tilting: Towards Concordant Models of Molecular Ensembles

    PubMed Central

    Beauchamp, Kyle A.; Pande, Vijay S.; Das, Rhiju

    2014-01-01

    Predicting biological structure has remained challenging for systems such as disordered proteins that take on myriad conformations. Hybrid simulation/experiment strategies have been undermined by difficulties in evaluating errors from computational model inaccuracies and data uncertainties. Building on recent proposals from maximum entropy theory and nonequilibrium thermodynamics, we address these issues through a Bayesian energy landscape tilting (BELT) scheme for computing Bayesian hyperensembles over conformational ensembles. BELT uses Markov chain Monte Carlo to directly sample maximum-entropy conformational ensembles consistent with a set of input experimental observables. To test this framework, we apply BELT to model trialanine, starting from disagreeing simulations with the force fields ff96, ff99, ff99sbnmr-ildn, CHARMM27, and OPLS-AA. BELT incorporation of limited chemical shift and 3J measurements gives convergent values of the peptide’s α, β, and PPII conformational populations in all cases. As a test of predictive power, all five BELT hyperensembles recover set-aside measurements not used in the fitting and report accurate errors, even when starting from highly inaccurate simulations. BELT’s principled framework thus enables practical predictions for complex biomolecular systems from discordant simulations and sparse data. PMID:24655513

  1. Energy and the Transformation of a Metropolitan Landscape: Contrasting Contemporary and Future Settlement Geographies.

    ERIC Educational Resources Information Center

    Zeigler, Donald J.

    Because of the rising real cost of energy, geographic patterns that have dominated the contemporary metropolitan landscape are in a state of change. A conceptual model of the contemporary and future metropolitan landscape is presented to stimulate thought about the changes which may evolve in the spatial organization of urban regions as the real…

  2. A new heuristic method for approximating the number of local minima in partial RNA energy landscapes.

    PubMed

    Albrecht, Andreas A; Day, Luke; Abdelhadi Ep Souki, Ouala; Steinhöfel, Kathleen

    2016-02-01

    The analysis of energy landscapes plays an important role in mathematical modelling, simulation and optimisation. Among the main features of interest are the number and distribution of local minima within the energy landscape. Granier and Kallel proposed in 2002 a new sampling procedure for estimating the number of local minima. In the present paper, we focus on improved heuristic implementations of the general framework devised by Granier and Kallel with regard to run-time behaviour and accuracy of predictions. The new heuristic method is demonstrated for the case of partial energy landscapes induced by RNA secondary structures. While the computation of minimum free energy RNA secondary structures has been studied for a long time, the analysis of folding landscapes has gained momentum over the past years in the context of co-transcriptional folding and deeper insights into cell processes. The new approach has been applied to ten RNA instances of length between 99 nt and 504 nt and their respective partial energy landscapes defined by secondary structures within an energy offset ΔE above the minimum free energy conformation. The number of local minima within the partial energy landscapes ranges from 1440 to 3441. Our heuristic method produces for the best approximations on average a deviation below 3.0% from the true number of local minima.

  3. Shape Transitions and Chiral Symmetry Breaking in the Energy Landscape of the Mitotic Chromosome

    NASA Astrophysics Data System (ADS)

    Zhang, Bin; Wolynes, Peter G.

    2016-06-01

    We derive an unbiased information theoretic energy landscape for chromosomes at metaphase using a maximum entropy approach that accurately reproduces the details of the experimentally measured pairwise contact probabilities between genomic loci. Dynamical simulations using this landscape lead to cylindrical, helically twisted structures reflecting liquid crystalline order. These structures are similar to those arising from a generic ideal homogenized chromosome energy landscape. The helical twist can be either right or left handed so chiral symmetry is broken spontaneously. The ideal chromosome landscape when augmented by interactions like those leading to topologically associating domain formation in the interphase chromosome reproduces these behaviors. The phase diagram of this landscape shows that the helical fiber order and the cylindrical shape persist at temperatures above the onset of chiral symmetry breaking, which is limited by the topologically associating domain interaction strength.

  4. The energy landscape of uranyl-peroxide species.

    PubMed

    Tiferet, Eitan; Gil, Adrià; Bo, Carles; Shvareva, Tatiana Y; Nyman, May; Navrotsky, Alexandra

    2014-03-24

    Nanoscale uranyl peroxide clusters containing UO2(2+) groups bonded through peroxide bridges to form polynuclear molecular species (polyoxometalates) exist both in solution and in the solid state. There is an extensive family of clusters containing 28 uranium atoms (U28 clusters), with an encapsulated anion in the center, for example, [UO2(O2)(3-x)(OH)(x)(4-)], [Nb(O2)4(3-)], or [Ta(O2)4(3-)]. The negative charge of these clusters is balanced by alkali ions, both encapsulated, and located exterior to the cluster. The present study reports measurement of enthalpy of formation for two such U28 compounds, one of which is uranyl centered and the other is peroxotantalate centered. The [(Ta(O2)4]-centered U28 capsule is energetically more stable than the [(UO2)(O2)3]-centered capsule. These data, along with our prior studies on other uranyl-peroxide solids, are used to explore the energy landscape and define thermochemical trends in alkali-uranyl-peroxide systems. It was suggested that the energetic role of charge-balancing alkali ions and their electrostatic interactions with the negatively charged uranyl-peroxide species is the dominant factor in defining energetic stability. These experimental data were supported by DFT calculations, which agree that the [(Ta(O2)4]-centered U28 capsule is more stable than the uranyl-centered capsule. Moreover, the relative stability is controlled by the interactions of the encapsulated alkalis with the encapsulated anion. Thus, the role of alkali-anion interactions was shown to be important at all length scales of uranyl-peroxide species: in both comparing clusters to clusters; and clusters to monomers or extended solids.

  5. The Free Energy Landscape of Small Molecule Unbinding

    PubMed Central

    Huang, Danzhi; Caflisch, Amedeo

    2011-01-01

    The spontaneous dissociation of six small ligands from the active site of FKBP (the FK506 binding protein) is investigated by explicit water molecular dynamics simulations and network analysis. The ligands have between four (dimethylsulphoxide) and eleven (5-diethylamino-2-pentanone) non-hydrogen atoms, and an affinity for FKBP ranging from 20 to 0.2 mM. The conformations of the FKBP/ligand complex saved along multiple trajectories (50 runs at 310 K for each ligand) are grouped according to a set of intermolecular distances into nodes of a network, and the direct transitions between them are the links. The network analysis reveals that the bound state consists of several subbasins, i.e., binding modes characterized by distinct intermolecular hydrogen bonds and hydrophobic contacts. The dissociation kinetics show a simple (i.e., single-exponential) time dependence because the unbinding barrier is much higher than the barriers between subbasins in the bound state. The unbinding transition state is made up of heterogeneous positions and orientations of the ligand in the FKBP active site, which correspond to multiple pathways of dissociation. For the six small ligands of FKBP, the weaker the binding affinity the closer to the bound state (along the intermolecular distance) are the transition state structures, which is a new manifestation of Hammond behavior. Experimental approaches to the study of fragment binding to proteins have limitations in temporal and spatial resolution. Our network analysis of the unbinding simulations of small inhibitors from an enzyme paints a clear picture of the free energy landscape (both thermodynamics and kinetics) of ligand unbinding. PMID:21390201

  6. Intrinsic errors in several ab initio methods. The dissociation energy of N{sub 2}

    SciTech Connect

    Peterson, K.A. |; Dunning, T.H. Jr.

    1995-03-23

    Using sequences of correlation consistent basis sets, complete basis set (CBS) limits for the dissociation energy D{sub c} of N{sub 2} have been estimated for a variety of commonly used electron correlation methods. After extrapolation to the CBS limit, the difference between theory and experiment corresponds to the error intrinsic to the chosen theoretical method. Correlated wave functions (valence electrons correlated only) for which intrinsic errors have been estimated include internally contracted multireference configuration interaction (CMRCI), singles and doubles coupled cluster theory with and without perturbative triple excitations [CCSD, CCSD(T)], and second-, third-, and fourth-order Moller-Plesset perturbation theory (MP2, MP3, MP4). For CMRCI and CCSD(T), D{sub c} converges smoothly from below the experimental value and yields the smallest intrinsic errors, -0.8 and -1.6 kcal/mol, respectively. In contrast, for MP2 and MP4, D{sub c} exhibits fortuitously good agreement with experiment for small basis sets but leads to CBS limits that are 11.6 and 3.4 kcal/mol larger than experiment, respectively. Correlation of the 1s core electrons is predicted to yield intrinsic errors of less than 1 kcal/mol for CMRCI and CCSD(T), while those for MP2 and MP4 increase still further. 38 refs., 1 fig., 1 tab.

  7. Free-energy landscape of ion-channel voltage-sensor-domain activation.

    PubMed

    Delemotte, Lucie; Kasimova, Marina A; Klein, Michael L; Tarek, Mounir; Carnevale, Vincenzo

    2015-01-06

    Voltage sensor domains (VSDs) are membrane-bound protein modules that confer voltage sensitivity to membrane proteins. VSDs sense changes in the transmembrane voltage and convert the electrical signal into a conformational change called activation. Activation involves a reorganization of the membrane protein charges that is detected experimentally as transient currents. These so-called gating currents have been investigated extensively within the theoretical framework of so-called discrete-state Markov models (DMMs), whereby activation is conceptualized as a series of transitions across a discrete set of states. Historically, the interpretation of DMM transition rates in terms of transition state theory has been instrumental in shaping our view of the activation process, whose free-energy profile is currently envisioned as composed of a few local minima separated by steep barriers. Here we use atomistic level modeling and well-tempered metadynamics to calculate the configurational free energy along a single transition from first principles. We show that this transition is intrinsically multidimensional and described by a rough free-energy landscape. Remarkably, a coarse-grained description of the system, based on the use of the gating charge as reaction coordinate, reveals a smooth profile with a single barrier, consistent with phenomenological models. Our results bridge the gap between microscopic and macroscopic descriptions of activation dynamics and show that choosing the gating charge as reaction coordinate masks the topological complexity of the network of microstates participating in the transition. Importantly, full characterization of the latter is a prerequisite to rationalize modulation of this process by lipids, toxins, drugs, and genetic mutations.

  8. Free-energy landscape of ion-channel voltage-sensor–domain activation

    PubMed Central

    Delemotte, Lucie; Kasimova, Marina A.; Klein, Michael L.; Tarek, Mounir; Carnevale, Vincenzo

    2015-01-01

    Voltage sensor domains (VSDs) are membrane-bound protein modules that confer voltage sensitivity to membrane proteins. VSDs sense changes in the transmembrane voltage and convert the electrical signal into a conformational change called activation. Activation involves a reorganization of the membrane protein charges that is detected experimentally as transient currents. These so-called gating currents have been investigated extensively within the theoretical framework of so-called discrete-state Markov models (DMMs), whereby activation is conceptualized as a series of transitions across a discrete set of states. Historically, the interpretation of DMM transition rates in terms of transition state theory has been instrumental in shaping our view of the activation process, whose free-energy profile is currently envisioned as composed of a few local minima separated by steep barriers. Here we use atomistic level modeling and well-tempered metadynamics to calculate the configurational free energy along a single transition from first principles. We show that this transition is intrinsically multidimensional and described by a rough free-energy landscape. Remarkably, a coarse-grained description of the system, based on the use of the gating charge as reaction coordinate, reveals a smooth profile with a single barrier, consistent with phenomenological models. Our results bridge the gap between microscopic and macroscopic descriptions of activation dynamics and show that choosing the gating charge as reaction coordinate masks the topological complexity of the network of microstates participating in the transition. Importantly, full characterization of the latter is a prerequisite to rationalize modulation of this process by lipids, toxins, drugs, and genetic mutations. PMID:25535341

  9. Reconstructing Folding Energy Landscape Profiles from Nonequilibrium Pulling Curves with an Inverse Weierstrass Integral Transform

    NASA Astrophysics Data System (ADS)

    Engel, Megan C.; Ritchie, Dustin B.; Foster, Daniel A. N.; Beach, Kevin S. D.; Woodside, Michael T.

    2014-12-01

    The energy landscapes that drive structure formation in biopolymers are difficult to measure. Here we validate experimentally a novel method to reconstruct landscape profiles from single-molecule pulling curves using an inverse Weierstrass transform (IWT) of the Jarzysnki free-energy integral. The method was applied to unfolding measurements of a DNA hairpin, replicating the results found by the more-established weighted histogram (WHAM) and inverse Boltzmann methods. Applying both WHAM and IWT methods to reconstruct the folding landscape for a RNA pseudoknot having a stiff energy barrier, we found that landscape features with sharper curvature than the force probe stiffness could not be recovered with the IWT method. The IWT method is thus best for analyzing data from stiff force probes such as atomic force microscopes.

  10. The splitting of intrinsic energy and the origin of mass density in continuum mechanics

    NASA Astrophysics Data System (ADS)

    Fosdick, Roger; Serrin, James

    2013-05-01

    We show that the total intrinsic energy of a body must split into the sum of two terms—an internal energy which depends upon `state' and a kinetic energy which is quadratic in the square of the particle speed.We use the non-relativistic group invariance structure of a generalized form of the balance of energy in continuum thermomechanics, together with a fundamental axiomatic requirement. The fundamental concepts of motion, force, power, heating and intrinsic energy are introduced as primitive, and we derive the notion of mass and its balance. When James Serrin died on August 23, 2012, this work had just been completed. Jim was my close, personal and treasured friend for over 40 years. We collaborated on several works over those years, and we often talked together and socialized on various occasions. I had highest respect for him in all human and professional ways, and there was a definite mutual expression of affection and appreciation. A friendship could not contain more. This paper drew him back to a subject he had worked on years ago, and he was happy to be involved again with a fundamental issue in continuum mechanics. My efforts in this work are dedicated to the memory of James Serrin. He was such a scholar of great breadth and depth—He was wise and witty, and I benefited greatly from his presence. Roger Fosdick

  11. 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.

  12. Tropomyosin movement on F-actin during muscle activation explained by energy landscapes.

    PubMed

    Orzechowski, Marek; Moore, Jeffrey R; Fischer, Stefan; Lehman, William

    2014-03-01

    Muscle contraction is regulated by tropomyosin movement across the thin filament surface, which exposes or blocks myosin-binding sites on actin. Recent atomic structures of F-actin-tropomyosin have yielded the positions of tropomyosin on myosin-free and myosin-decorated actin. Here, the repositioning of α-tropomyosin between these locations on F-actin was systematically examined by optimizing the energy of the complex for a wide range of tropomyosin positions on F-actin. The resulting energy landscape provides a full-map of the F-actin surface preferred by tropomyosin, revealing a broad energy basin associated with the tropomyosin position that blocks myosin-binding. This is consistent with previously proposed low-energy oscillations of semi-rigid tropomyosin, necessary for shifting of tropomyosin following troponin-binding. In contrast, the landscape shows much less favorable energies when tropomyosin locates near its myosin-induced "open-state" position. This indicates that spontaneous movement of tropomyosin away from its energetic "ground-state" to the open-state is unlikely in absence of myosin. Instead, myosin-binding must drive tropomyosin toward the open-state to activate the thin filament. Additional energy landscapes were computed for disease-causing actin mutants that distort the topology of the actin-tropomyosin energy landscape, explaining their phenotypes. Thus, the computation of such energy landscapes offers a sensitive way to estimate the impact of mutations.

  13. Energy Landscape of Fullerene Materials: A Comparison of Boron to Boron Nitride and Carbon

    NASA Astrophysics Data System (ADS)

    de, Sandip; Willand, Alexander; Amsler, Maximilian; Pochet, Pascal; Genovese, Luigi; Goedecker, Stefan

    2011-06-01

    Using the minima hopping global geometry optimization method on the density functional potential energy surface we show that the energy landscape of boron clusters is glasslike. Larger boron clusters have many structures which are lower in energy than the cages. This is in contrast to carbon and boron nitride systems which can be clearly identified as structure seekers. The differences in the potential energy landscape explain why carbon and boron nitride systems are found in nature whereas pure boron fullerenes have not been found. We thus present a methodology which can make predictions on the feasibility of the synthesis of new nanostructures.

  14. Geometry of the energy landscape of the self-gravitating ring.

    PubMed

    Monechi, Bernardo; Casetti, Lapo

    2012-10-01

    We study the global geometry of the energy landscape of a simple model of a self-gravitating system, the self-gravitating ring (SGR). This is done by endowing the configuration space with a metric such that the dynamical trajectories are identified with geodesics. The average curvature and curvature fluctuations of the energy landscape are computed by means of Monte Carlo simulations and, when possible, of a mean-field method, showing that these global geometric quantities provide a clear geometric characterization of the collapse phase transition occurring in the SGR as the transition from a flat landscape at high energies to a landscape with mainly positive but fluctuating curvature in the collapsed phase. Moreover, curvature fluctuations show a maximum in correspondence with the energy of a possible further transition, occurring at lower energies than the collapsed one, whose existence had been previously conjectured on the basis of a local analysis of the energy landscape and whose effect on the usual thermodynamic quantities, if any, is extremely weak. We also estimate the largest Lyapunov exponent λ of the SGR using the geometric observables. The geometric estimate always gives the correct order of magnitude of λ and is also quantitatively correct at small energy densities and, in the limit N→∞, in the whole homogeneous phase.

  15. Free energy landscape and transition pathways from Watson-Crick to Hoogsteen base pairing in free duplex DNA.

    PubMed

    Yang, Changwon; Kim, Eunae; Pak, Youngshang

    2015-09-18

    Houghton (HG) base pairing plays a central role in the DNA binding of proteins and small ligands. Probing detailed transition mechanism from Watson-Crick (WC) to HG base pair (bp) formation in duplex DNAs is of fundamental importance in terms of revealing intrinsic functions of double helical DNAs beyond their sequence determined functions. We investigated a free energy landscape of a free B-DNA with an adenosine-thymine (A-T) rich sequence to probe its conformational transition pathways from WC to HG base pairing. The free energy landscape was computed with a state-of-art two-dimensional umbrella molecular dynamics simulation at the all-atom level. The present simulation showed that in an isolated duplex DNA, the spontaneous transition from WC to HG bp takes place via multiple pathways. Notably, base flipping into the major and minor grooves was found to play an important role in forming these multiple transition pathways. This finding suggests that naked B-DNA under normal conditions has an inherent ability to form HG bps via spontaneous base opening events.

  16. Transforming the Energy Landscape of a Coiled-Coil Peptide via Point Mutations.

    PubMed

    Röder, Konstantin; Wales, David J

    2017-03-14

    We analyze the effect of point mutations on the energy landscape of a coiled-coil peptide, GCN4-pLI, where the native state is a parallel tetrameric configuration formed from two identical dimers. Experimentally, a single mutation, E20S, supports both antiparallel and parallel structures. Here, we analyze the potential energy landscapes of the dimeric units for the parent sequence and four mutants, namely E20S, E20A, E20P, and E20G. Despite sharing characteristic funnels containing the parallel and antiparallel structures, the point mutations change some parts of the landscape quite dramatically, and we predict new intermediate structures and characterize the associated heat capacities. For the mutants we predict that kinked intermediate structures facilitate the transition between parallel and antiparallel morphologies, in contrast to the parent sequence. Furthermore, we predict a change from a multifunnel energy landscape in the E20S mutant to a landscape dominated by an underlying single funnel in the parent sequence, with accompanying heat capacity signatures. Our results imply that changes in the landscape due to mutations might provide useful tools for functional protein design.

  17. 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.

  18. Energy landscape analysis of the subcortical brain network unravels system properties beneath resting state dynamics.

    PubMed

    Kang, Jiyoung; Pae, Chongwon; Park, Hae-Jeong

    2017-04-01

    The configuration of the human brain system at rest, which is in a transitory phase among multistable states, remains unknown. To investigate the dynamic systems properties of the human brain at rest, we constructed an energy landscape for the state dynamics of the subcortical brain network, a critical center that modulates whole brain states, using resting state fMRI. We evaluated alterations in energy landscapes following perturbation in network parameters, which revealed characteristics of the state dynamics in the subcortical brain system, such as maximal number of attractors, unequal temporal occupations, and readiness for reconfiguration of the system. Perturbation in the network parameters, even those as small as the ones in individual nodes or edges, caused a significant shift in the energy landscape of brain systems. The effect of the perturbation on the energy landscape depended on the network properties of the perturbed nodes and edges, with greater effects on hub nodes and hubs-connecting edges in the subcortical brain system. Two simultaneously perturbed nodes produced perturbation effects showing low sensitivity in the interhemispheric homologous nodes and strong dependency on the more primary node among the two. This study demonstrated that energy landscape analysis could be an important tool to investigate alterations in brain networks that may underlie certain brain diseases, or diverse brain functions that may emerge due to the reconfiguration of the default brain network at rest.

  19. Comparing the energy landscapes for native folding and aggregation of PrP.

    PubMed

    Dee, Derek R; Woodside, Michael T

    2016-05-03

    Protein sequences are evolved to encode generally one folded structure, out of a nearly infinite array of possible folds. Underlying this code is a funneled free energy landscape that guides folding to the native conformation. Protein misfolding and aggregation are also a manifestation of free-energy landscapes. The detailed mechanisms of these processes are poorly understood, but often involve rare, transient species and a variety of different pathways. The inherent complexity of misfolding has hampered efforts to measure aggregation pathways and the underlying energy landscape, especially using traditional methods where ensemble averaging obscures important rare and transient events. We recently studied the misfolding and aggregation of prion protein by examining 2 monomers tethered in close proximity as a dimer, showing how the steps leading to the formation of a stable aggregated state can be resolved in the single-molecule limit and the underlying energy landscape thereby reconstructed. This approach allows a more quantitative comparison of native folding versus misfolding, including fundamental differences in the dynamics for misfolding. By identifying key steps and interactions leading to misfolding, it should help to identify potential drug targets. Here we describe the importance of characterizing free-energy landscapes for aggregation and the challenges involved in doing so, and we discuss how single-molecule studies can help test proposed structural models for PrP aggregates.

  20. High energy product permanent magnet having improved intrinsic coercivity and method of making same

    DOEpatents

    Ramesh, Ramamoorthy; Thomas, Gareth

    1990-01-01

    A high energy rare earth-ferromagnetic metal permanent magnet is disclosed which is characterized by improved intrinsic coercivity and is made by forming a particulate mixture of a permanent magnet alloy comprising one or more rare earth elements and one or more ferromagnetic metals and forming a second particulate mixture of a sintering alloy consisting essentially of 92-98 wt. % of one or more rare earth elements selected from the class consisting of Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, and mixtures of two or more of such rare earth elements, and 2-8 wt. % of one or more alloying metals selected from the class consisting of Al, Nb, Zr, V, Ta, Mo, and mixtures of two or more of such metals. The permanent magnet alloy particles and sintering aid alloy are mixed together and magnetically oriented by immersing the mixture in an axially aligned magnetic field while cold pressing the mixture. The compressed mixture is then sintered at a temperature above the melting point of the sintering aid and below the melting point of the permanent magnet alloy to thereby coat the particle surfaces of the permanent magnetic alloy particles with the sintering aid while inhibiting migration of the rare earth element in the sintering aid into the permanent magnet alloy particles to thereby raise the intrinsic coercivity of the permanent magnet alloy without substantially lowering the high energy of the permanent magnet alloy.

  1. Resonance saturation in the odd-intrinsic parity sector of low-energy QCD

    NASA Astrophysics Data System (ADS)

    Kampf, Karol; Novotný, Jiří

    2011-07-01

    Using the large NC approximation we have constructed the most general chiral resonance Lagrangian in the odd-intrinsic parity sector that can generate low-energy chiral constants up to O(p6). Integrating out the resonance fields these O(p6) constants are expressed in terms of resonance couplings and masses. The role of η' is discussed and its contribution is explicitly factorized. Using the resonance basis we have also calculated two QCD Green functions of currents, ⟨VVP⟩ and ⟨VAS⟩, and found, imposing high-energy constraints, additional relations for resonance couplings. We have studied several phenomenological implications based on these correlators which provided, for example, a prediction for the π0-pole contribution to the muon g-2 factor: aμπ0=65.8(1.2)×10-11.

  2. Intrinsic deep hole trap levels in Cu2O with self-consistent repulsive Coulomb energy

    NASA Astrophysics Data System (ADS)

    Huang, Bolong

    2016-03-01

    The large error of the DFT+U method on full-filled shell metal oxides is due to the residue of self-energy from the localized d orbitals of cations and p orbitals of the anions. U parameters are selfconsistently found to achieve the analytical self-energy cancellation. The improved band structures based on relaxed lattices of Cu2O are shown based on minimization of self-energy error. The experimentally reported intrinsic p-type trap levels are contributed by both Cu-vacancy and the O-interstitial defects in Cu2O. The latter defect has the lowest formation energy but contributes a deep hole trap level while the Cuvacancy has higher energy cost but acting as a shallow acceptor. Both present single-particle levels spread over nearby the valence band edge, consistent to the trend of defects transition levels. By this calculation approach, we also elucidated the entanglement of strong p-d orbital coupling to unravel the screened Coulomb potential of fully filled shells.

  3. Energy landscape and phase transitions in the self-gravitating ring model.

    PubMed

    Nardini, Cesare; Casetti, Lapo

    2009-12-01

    We apply a recently proposed criterion for the existence of phase transitions, which is based on the properties of the saddles of the energy landscape, to a simplified model of a system with gravitational interactions referred to as the self-gravitating ring model. We show analytically that the criterion correctly singles out the phase transition between a homogeneous and a clustered phase and also suggests the presence of another phase transition not previously known. On the basis of the properties of the energy landscape we conjecture on the nature of the latter transition.

  4. Exploring the energy landscape of proteins: A characterization of the activation-relaxation technique

    NASA Astrophysics Data System (ADS)

    Wei, Guanghong; Mousseau, Normand; Derreumaux, Philippe

    2002-12-01

    Finding the global energy minimum region of a polypeptide chain, independently of the starting conformation and in a reasonable computational time, is of fundamental interest. As the energy landscape of proteins is very rugged, sampling is hindered by the vast number of minima existing on this multidimensional landscape. In this study, we use activation-relaxation technique (ART) to explore the energy landscape of a series of peptide models with 14, 26, and 28 amino acids. Peptides are modeled by a reduced off-lattice representation and a simplified OPEP-like (optimized potential for efficient peptide-structure prediction) energy model. ART defines moves directly in the energy landscape and can generate with equal efficiency events with root-mean-square deviation as small as 0.1 or as large as 4 Å. Our results show that (i) ART trajectories are reversible and provide real activated paths; (ii) ART simulations converge to the same low-energy minimum region, for a wide range of starting configurations; (iii) ART method can sample the phase space effectively, going through many hyper-basins, and can generate significant moves in a single event. Possible applications of ART method to biomolecules are discussed.

  5. Surveying the free energy landscapes of continuum models: Application to soft matter systems.

    PubMed

    Kusumaatmaja, Halim

    2015-03-28

    A variety of methods are developed for characterising the free energy landscapes of continuum, Landau-type free energy models. Using morphologies of lipid vesicles and a multistable liquid crystal device as examples, I show that the methods allow systematic study of not only the most relevant minimum energy configurations, but also the transition pathways between any two minima, as well as their corresponding energy barriers and transition state configurations. A global view of the free energy landscapes can then be visualized using either a disconnectivity graph or a network representation. Different forms of free energy functionals and boundary conditions can be readily implemented, thus allowing these tools to be utilised for a broad range of problems.

  6. Resonant nature of intrinsic defect energy levels in PbTe revealed by infrared photoreflectance spectroscopy

    NASA Astrophysics Data System (ADS)

    Zhang, Bingpo; Cai, Chunfeng; Jin, Shuqiang; Ye, Zhenyu; Wu, Huizhen; Qi, Zhen

    2014-07-01

    Step-scan Fourier-transform infrared photoreflectance and modulated photoluminescence spectroscopy were used to characterize the optical transitions of the epitaxial PbTe thin film grown by molecular beam epitaxy on BaF2 (111) substrate in the vicinity of energy gap of lead telluride at 77 K. It is found that the intrinsic defect energy levels in the electronic structure are of resonant nature. The Te-vacancy energy level is located above the conduction band minimum by 29.1 meV. Another defect (VX) energy level situated below valance band maximum by 18.1 meV is also revealed. Whether it is associated with the Pb vacancy is still not clear. It might also be related to the misfit dislocations stemming from the lattice mismatch between PbTe and BaF2 substrate. The experimental results support the theory prediction (N. J. Parada and G. W. Pratt, Jr., Phys. Rev. Lett. 22, 180 (1969), N. J. Parada, Phys. Rev. B 3, 2042 (1971)) and are consistent with the reported Hall experimental results (G. Bauer, H. Burkhard, H. Heinrich, and A. Lopez-Otero, J. Appl. Phys. 47, 1721 (1976)).

  7. Influence of the membrane potential on the free energy of an intrinsic protein.

    PubMed Central

    Roux, B

    1997-01-01

    A modified Poisson-Boltzmann equation is developed from statistical mechanical considerations to describe the influence of the transmembrane potential on macromolecular systems. Using a Green's function formalism, the electrostatic free energy of a protein associated with the membrane is expressed as the sum of three terms: a contribution from the energy required to charge the system's capacitance, a contribution corresponding to the interaction of the protein charges with the membrane potential, and a contribution corresponding to a voltage-independent reaction field free energy. The membrane potential, which is due to the polarization interface, is calculated in the absence of the protein charges, whereas the reaction field is calculated in the absence of transmembrane potential. Variations in the capacitive energy associated with typical molecular processes are negligible under physiological conditions. The formulation of the theory is closely related to standard algorithms used to solve the Poisson-Boltzmann equation and only small modifications to current source codes are required for its implementation. The theory is illustrated by examining the voltage-dependent membrane insertion of a simple polyalanine alpha-helix and by computing the electrostatic potential across a 60-A-diameter sphere meant to represent a large intrinsic protein. Images FIGURE 2 PMID:9414213

  8. Crystal growth nucleation and Fermi energy equalization of intrinsic spherical nuclei in glass-forming melts.

    PubMed

    Tournier, Robert F

    2009-02-01

    The energy saving resulting from the equalization of Fermi energies of a crystal and its melt is added to the Gibbs free-energy change ΔG2ls associated with a crystal formation in glass-forming melts. This negative contribution being a fraction ε ls(T) of the fusion heat is created by the electrostatic potential energy -U0 resulting from the electron transfer from the crystal to the melt and is maximum at the melting temperature Tm in agreement with a thermodynamics constraint. The homogeneous nucleation critical temperature T2, the nucleation critical barrier ΔG2ls∗/kBT and the critical radius R∗2ls are determined as functions of εls(T). In bulk metallic glass forming melts, εls(T) and T2 only depend on the free-volume disappearance temperature T0l, and εls(Tm) is larger than 1 (T0l>Tm/3); in conventional undercooled melts εls(Tm) is smaller than 1 (T0l>Tm/3). Unmelted intrinsic crystals act as growth nuclei reducing ΔG2ls∗/kBT and the nucleation time. The temperature-time transformation diagrams of Mg65Y10Cu25, Zr41.2Ti13.8Cu12.5Ni10Be22.5, Pd43Cu27 Ni10P20, Fe83B17 and Ni melts are predicted using classic nucleation models including time lags in transient nucleation, by varying the intrinsic nucleus contribution to the reduction of ΔG2ls∗/kBT. The energy-saving coefficient ε nm(T) of an unmelted crystal of radius Rnm is reduced when Rnm ≪R∗2ls; εnm is quantified and corresponds to the first energy level of one s-electron moving in vacuum in the same spherical attractive potential -U0 despite the fact that the charge screening is built by many-body effects.

  9. McFadden, Wyoming: A case study in narrating our changing energy landscapes

    NASA Astrophysics Data System (ADS)

    Anderson, Carly-Ann Marie

    This thesis uses McFadden, Wyoming, and the Rock Creek Valley to discuss Wyoming's changing energy landscapes and argues that a cultural landscape approach to documenting our historic and cultural resources can contribute to properly siting energy developments. Though Wyoming stands to gain from the construction of wind farms, they should be carefully sited in order to balance environmental and cultural resource preservation with energy needs. Wyoming has a long history as an energy hinterland and provides a significant portion of energy to the U.S. However, the nation's demand for energy should not take precedence over preserving the cultural resources and vast open landscapes that represent Wyoming's heritage. A history of the Rock Creek Valley as a home to Native Americans, a transportation corridor, oil field, and wind farm site is presented along with a discussion of energy consumption and Wyoming's role in the energy market. The thesis also considers the importance of education, public discourse, and narrative as tools for planning a sustainable future with regard to energy, the environment, and cultural resources.

  10. Direct design of an energy landscape with bistable DNA origami mechanisms.

    PubMed

    Zhou, Lifeng; Marras, Alexander E; Su, Hai-Jun; Castro, Carlos E

    2015-03-11

    Structural DNA nanotechnology provides a feasible technique for the design and fabrication of complex geometries even exhibiting controllable dynamic behavior. Recently we have demonstrated the possibility of implementing macroscopic engineering design approaches to construct DNA origami mechanisms (DOM) with programmable motion and tunable flexibility. Here, we implement the design of compliant DNA origami mechanisms to extend from prescribing motion to prescribing an energy landscape. Compliant mechanisms facilitate motion via deformation of components with tunable stiffness resulting in well-defined mechanical energy stored in the structure. We design, fabricate, and characterize a DNA origami nanostructure with an energy landscape defined by two stable states (local energy minima) separated by a designed energy barrier. This nanostructure is a four-bar bistable mechanism with two undeformed states. Traversing between those states requires deformation, and hence mechanical energy storage, in a compliant arm of the linkage. The energy barrier for switching between two states was obtained from the conformational distribution based on a Boltzmann probability function and closely follows a predictive mechanical model. Furthermore, we demonstrated the ability to actuate the mechanism into one stable state via additional DNA inputs and then release the actuation via DNA strand displacement. This controllable multistate system establishes a foundation for direct design of energy landscapes that regulate conformational dynamics similar to biomolecular complexes.

  11. Enhanced conformational sampling to visualize a free-energy landscape of protein complex formation

    PubMed Central

    Iida, Shinji; Nakamura, Haruki; Higo, Junichi

    2016-01-01

    We introduce various, recently developed, generalized ensemble methods, which are useful to sample various molecular configurations emerging in the process of protein–protein or protein–ligand binding. The methods introduced here are those that have been or will be applied to biomolecular binding, where the biomolecules are treated as flexible molecules expressed by an all-atom model in an explicit solvent. Sampling produces an ensemble of conformations (snapshots) that are thermodynamically probable at room temperature. Then, projection of those conformations to an abstract low-dimensional space generates a free-energy landscape. As an example, we show a landscape of homo-dimer formation of an endothelin-1-like molecule computed using a generalized ensemble method. The lowest free-energy cluster at room temperature coincided precisely with the experimentally determined complex structure. Two minor clusters were also found in the landscape, which were largely different from the native complex form. Although those clusters were isolated at room temperature, with rising temperature a pathway emerged linking the lowest and second-lowest free-energy clusters, and a further temperature increment connected all the clusters. This exemplifies that the generalized ensemble method is a powerful tool for computing the free-energy landscape, by which one can discuss the thermodynamic stability of clusters and the temperature dependence of the cluster networks. PMID:27288028

  12. Energy landscapes of a hairpin peptide including NMR chemical shift restraints.

    PubMed

    Carr, Joanne M; Whittleston, Chris S; Wade, David C; Wales, David J

    2015-08-21

    Methods recently introduced to improve the efficiency of protein structure prediction simulations by adding a restraint potential to a molecular mechanics force field introduce additional input parameters that can affect the performance. Here we investigate the changes in the energy landscape as the relative weight of the two contributions, force field and restraint potential, is systematically altered, for restraint functions constructed from calculated nuclear magnetic resonance chemical shifts. Benchmarking calculations were performed on a 12-residue peptide, tryptophan zipper 1, which features both secondary structure (a β-hairpin) and specific packing of tryptophan sidechains. Basin-hopping global optimization was performed to assess the efficiency with which lowest-energy structures are located, and the discrete path sampling approach was employed to survey the energy landscapes between unfolded and folded structures. We find that inclusion of the chemical shift restraints improves the efficiency of structure prediction because the energy landscape becomes more funnelled and the proportion of local minima classified as native increases. However, the funnelling nature of the landscape is reduced as the relative contribution of the chemical shift restraint potential is increased past an optimal value.

  13. Linking habitat selection to fitness-related traits in herbivores: the role of the energy landscape.

    PubMed

    Long, Ryan A; Bowyer, R T; Porter, Warren P; Mathewson, Paul; Monteith, Kevin L; Findholt, Scott L; Dick, Brian L; Kie, John G

    2016-07-01

    Animals may partially overcome environmental constraints on fitness by behaviorally adjusting their exposure to costs and supplies of energy. Few studies, however, have linked spatiotemporal variation in the energy landscape to behaviorally mediated measures of performance that ostensibly influence individual fitness. We hypothesized that strength of selection by North American elk (Cervus elaphus) for areas that reduced costs of thermoregulation and activity, and increased access to high-quality forage, would influence four energetically mediated traits related to fitness: birth mass of young, nutritional condition of adult females at the onset of winter, change in nutritional condition of females between spring and winter, and neonatal survival. We used a biophysical model to map spatiotemporally explicit costs of thermoregulation and activity experienced by elk in a heterogeneous landscape. We then combined model predictions with data on forage characteristics, animal locations, nutritional condition, and mass and survival of young to evaluate behaviorally mediated effects of the energy landscape on fitness-related traits. During spring, when high-quality forage was abundant, female elk that consistently selected low-cost areas before parturition gave birth to larger young than less-selective individuals, and birth mass had a strong, positive influence on probability of survival. As forage quality declined during autumn, however, lactating females that consistently selected the highest quality forage available accrued more fat and entered winter in better condition than less-selective individuals. Results of our study highlight the importance of understanding the dynamic nature of energy landscapes experienced by free-ranging animals.

  14. Enhanced conformational sampling to visualize a free-energy landscape of protein complex formation.

    PubMed

    Iida, Shinji; Nakamura, Haruki; Higo, Junichi

    2016-06-15

    We introduce various, recently developed, generalized ensemble methods, which are useful to sample various molecular configurations emerging in the process of protein-protein or protein-ligand binding. The methods introduced here are those that have been or will be applied to biomolecular binding, where the biomolecules are treated as flexible molecules expressed by an all-atom model in an explicit solvent. Sampling produces an ensemble of conformations (snapshots) that are thermodynamically probable at room temperature. Then, projection of those conformations to an abstract low-dimensional space generates a free-energy landscape. As an example, we show a landscape of homo-dimer formation of an endothelin-1-like molecule computed using a generalized ensemble method. The lowest free-energy cluster at room temperature coincided precisely with the experimentally determined complex structure. Two minor clusters were also found in the landscape, which were largely different from the native complex form. Although those clusters were isolated at room temperature, with rising temperature a pathway emerged linking the lowest and second-lowest free-energy clusters, and a further temperature increment connected all the clusters. This exemplifies that the generalized ensemble method is a powerful tool for computing the free-energy landscape, by which one can discuss the thermodynamic stability of clusters and the temperature dependence of the cluster networks.

  15. Free-energy landscape of mono- and dinucleosomes: Enhanced rotational flexibility of interconnected nucleosomes

    NASA Astrophysics Data System (ADS)

    Nam, Gi-Moon; Arya, Gaurav

    2016-03-01

    The nucleosome represents the basic unit of eukaryotic genome organization, and its conformational fluctuations play a crucial role in various cellular processes. Here we provide insights into the flipping transition of a nucleosome by computing its free-energy landscape as a function of the linking number and nucleosome orientation using the density-of-states Monte Carlo approach. To investigate how the energy landscape is affected by the presence of neighboring nucleosomes in a chromatin fiber, we also compute the free-energy landscape for a dinucleosome array. We find that the mononucleosome is bistable between conformations with negatively and positively crossed linkers while the conformation with open linkers appears as a transition state. The dinucleosome exhibits a markedly different energy landscape in which the conformation with open linkers populates not only the transition state but also the global minimum. This enhanced stability of the open state is attributed to increased rotational flexibility of nucleosomes arising from their mechanical coupling with neighboring nucleosomes. Our results provide a possible mechanism by which chromatin may enhance the accessibility of its DNA and facilitate the propagation and mitigation of DNA torsional stresses.

  16. Model energy landscapes of low-temperature fluids: Dipolar hard spheres.

    PubMed

    Matyushov, Dmitry V

    2007-07-01

    An analytical model of non-Gaussian energy landscape of low-temperature fluids is developed based on the thermodynamics of the fluid of dipolar hard spheres. The entire excitation profile of the liquid, from the high-temperature liquid to the point of ideal-glass transition, has been obtained from Monte Carlo simulations. The fluid of dipolar hard spheres loses stability close to the point of ideal-glass transition transforming via a first-order transition into a columnar liquid phase of dipolar chains locally arranged in a body-centered-tetragonal order. Significant non-Gaussianity of the energy landscape is responsible for narrowing of the distribution of potential energies and energies of inherent structures with decreasing temperature. We suggest that the proposed functionality of the enumeration function is widely applicable to both polar and nonpolar low-temperature liquids.

  17. Europe's battery: The making of the Alpine energy landscape, 1870-1955

    NASA Astrophysics Data System (ADS)

    Landry, Marc D., II

    This study examines the environmental history of hydropower development in the Alps from the mid-nineteenth to the mid-twentieth centuries. Analyzing government archival files, associational journals, conference proceedings, and published contemporary material from several Alpine countries, it seeks to determine how and why Europeans modified the Alpine landscape to generate hydropower, and to explore the consequences of these decisions. I argue that during this time period, Europeans thoroughly transformed the Alpine environment, creating what I call "Europe's Battery": a gigantic system for storing hydropower and distributing it on a continental scale. This study shows how nineteenth-century innovations in energy technology contributed to a dramatic shift in the perception of the Alps as a landscape of "white coal." It demonstrates how at the outset of electrification, Europeans modified Alpine waterways on an unprecedented scale in order to tap into the power of flowing Alpine water. I show how after the turn of the twentieth century, Europeans took advantage of the unique mountain environment to store water, first by converting existing lakes into reservoirs. The practice countered what was perceived to be the greatest disadvantage of white coal: its climate-influenced inconstancy. This study shows the importance of war, and especially the First World War, in the forging of the new Alpine landscape. Finally, this study illustrates how from the interwar period to the aftermath of the Second World War, Europeans put the finishing touches on the new Alpine energy landscape by creating large reservoirs behind dams and feeding Alpine hydroelectricity into a burgeoning European electricity grid. By 1955 the Alps had become one of the most important energy landscapes in Europe. This history of the Alpine energy landscape contributes to a number of historiographical fields. It represents an important chapter in the environmental history of one of the world's most

  18. Attracting cavities for docking. Replacing the rough energy landscape of the protein by a smooth attracting landscape

    PubMed Central

    Schuepbach, Thierry; Bovigny, Christophe; Chaskar, Prasad; Daina, Antoine; Röhrig, Ute F.

    2015-01-01

    Molecular docking is a computational approach for predicting the most probable position of ligands in the binding sites of macromolecules and constitutes the cornerstone of structure‐based computer‐aided drug design. Here, we present a new algorithm called Attracting Cavities that allows molecular docking to be performed by simple energy minimizations only. The approach consists in transiently replacing the rough potential energy hypersurface of the protein by a smooth attracting potential driving the ligands into protein cavities. The actual protein energy landscape is reintroduced in a second step to refine the ligand position. The scoring function of Attracting Cavities is based on the CHARMM force field and the FACTS solvation model. The approach was tested on the 85 experimental ligand–protein structures included in the Astex diverse set and achieved a success rate of 80% in reproducing the experimental binding mode starting from a completely randomized ligand conformer. The algorithm thus compares favorably with current state‐of‐the‐art docking programs. © 2015 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc. PMID:26558715

  19. Attracting cavities for docking. Replacing the rough energy landscape of the protein by a smooth attracting landscape.

    PubMed

    Zoete, Vincent; Schuepbach, Thierry; Bovigny, Christophe; Chaskar, Prasad; Daina, Antoine; Röhrig, Ute F; Michielin, Olivier

    2016-02-05

    Molecular docking is a computational approach for predicting the most probable position of ligands in the binding sites of macromolecules and constitutes the cornerstone of structure-based computer-aided drug design. Here, we present a new algorithm called Attracting Cavities that allows molecular docking to be performed by simple energy minimizations only. The approach consists in transiently replacing the rough potential energy hypersurface of the protein by a smooth attracting potential driving the ligands into protein cavities. The actual protein energy landscape is reintroduced in a second step to refine the ligand position. The scoring function of Attracting Cavities is based on the CHARMM force field and the FACTS solvation model. The approach was tested on the 85 experimental ligand-protein structures included in the Astex diverse set and achieved a success rate of 80% in reproducing the experimental binding mode starting from a completely randomized ligand conformer. The algorithm thus compares favorably with current state-of-the-art docking programs.

  20. Distributions of experimental protein structures on coarse-grained free energy landscapes

    NASA Astrophysics Data System (ADS)

    Sankar, Kannan; Liu, Jie; Wang, Yuan; Jernigan, Robert L.

    2015-12-01

    Predicting conformational changes of proteins is needed in order to fully comprehend functional mechanisms. With the large number of available structures in sets of related proteins, it is now possible to directly visualize the clusters of conformations and their conformational transitions through the use of principal component analysis. The most striking observation about the distributions of the structures along the principal components is their highly non-uniform distributions. In this work, we use principal component analysis of experimental structures of 50 diverse proteins to extract the most important directions of their motions, sample structures along these directions, and estimate their free energy landscapes by combining knowledge-based potentials and entropy computed from elastic network models. When these resulting motions are visualized upon their coarse-grained free energy landscapes, the basis for conformational pathways becomes readily apparent. Using three well-studied proteins, T4 lysozyme, serum albumin, and sarco-endoplasmic reticular Ca2+ adenosine triphosphatase (SERCA), as examples, we show that such free energy landscapes of conformational changes provide meaningful insights into the functional dynamics and suggest transition pathways between different conformational states. As a further example, we also show that Monte Carlo simulations on the coarse-grained landscape of HIV-1 protease can directly yield pathways for force-driven conformational changes.

  1. Calculation of the Local Free Energy Landscape in the Restricted Region by the Modified Tomographic Method.

    PubMed

    Chen, Changjun

    2016-03-31

    The free energy landscape is the most important information in the study of the reaction mechanisms of the molecules. However, it is difficult to calculate. In a large collective variable space, a molecule must take a long time to obtain the sufficient sampling during the simulation. To save the calculation quantity, decreasing the sampling region and constructing the local free energy landscape is required in practice. However, the restricted region in the collective variable space may have an irregular shape. Simply restricting one or more collective variables of the molecule cannot satisfy the requirement. In this paper, we propose a modified tomographic method to perform the simulation. First, it divides the restricted region by some hyperplanes and connects the centers of hyperplanes together by a curve. Second, it forces the molecule to sample on the curve and the hyperplanes in the simulation and calculates the free energy data on them. Finally, all the free energy data are combined together to form the local free energy landscape. Without consideration of the area outside the restricted region, this free energy calculation can be more efficient. By this method, one can further optimize the path quickly in the collective variable space.

  2. The potential energy landscape for crystallisation of a Lennard-Jones fluid

    NASA Astrophysics Data System (ADS)

    de Souza, Vanessa K.; Wales, David J.

    2016-07-01

    Crystallisation pathways are explored by direct analysis of the potential energy landscape for a system of Lennard-Jones particles with periodic boundary conditions. A database of minima and transition states linking liquid and crystalline states is constructed using discrete path sampling and the entire potential energy landscape from liquid to crystal is visualised. We demonstrate that there is a strong negative correlation between the number of atoms in the largest crystalline cluster and the potential energy. In common with previous results we find a strong bias towards the growth of FCC rather than HCP clusters, despite a very small potential energy difference. We characterise three types of perfect crystals with very similar energies: pure FCC, pure HCP, and combinations of FCC and HCP layers. There are also many slightly defective crystalline structures. The effect of the simulation box is analysed for a supercell containing 864 atoms. There are low barriers between some of the different crystalline structures via pathways involving sliding layers, and many different defective structures with FCC layers stacked at an angle to the periodic box. Finally, we compare a binary Lennard-Jones system and visualise the potential energy landscape from supercooled liquid to crystal.

  3. Intrinsic potential for immediate biodegradation of toluene in a pristine, energy-limited aquifer.

    PubMed

    Herzyk, Agnieszka; Maloszewski, Piotr; Qiu, Shiran; Elsner, Martin; Griebler, Christian

    2014-06-01

    Pristine and energy-limited aquifers are considered to have a low resistance and resilience towards organic pollution. An experiment in an indoor aquifer system revealed an unexpected high intrinsic potential for the attenuation of a short-term toluene contamination. A 30 h pulse of 486 mg of toluene, used as a model contaminant, and deuterated water (D2O) through an initially pristine, oxic, and organic carbon poor sandy aquifer revealed an immediate aerobic toluene degradation potential. Based on contaminant and tracer break-through curves, as well as mass balance analyses and reactive transport modelling, a contaminant removal of 40 % over a transport distance of only 4.2 m in less than one week of travel time was obtained. The mean first-order degradation rate constant was λ = 0.178 day(-1), corresponding to a half-life time constant T1/2 of 3.87 days. Toluene-specific stable carbon isotope analysis independently proved that the contaminant mass removal can be attributed to microbial biodegradation. Since average doubling times of indigenous bacterial communities were in the range of months to years, the aerobic biodegradation potential observed is assumed to be present and active in the pristine, energy-limited groundwater ecosystems at any time. Follow-up experiments and field studies will help to quantify the immediate natural attenuation potential of aquifers for selected priority contaminants and will try to identify the key-degraders within the autochthonous microbial communities.

  4. Low energy supersymmetry from the heterotic string landscape.

    PubMed

    Lebedev, Oleg; Nilles, Hans-Peter; Raby, Stuart; Ramos-Sánchez, Saúl; Ratz, Michael; Vaudrevange, Patrick K S; Wingerter, Akin

    2007-05-04

    We study possible correlations between properties of the observable and hidden sectors in heterotic string theory. Specifically, we analyze the case of the Z6-II orbifold compactification which produces a significant number of models with the spectrum of the supersymmetric standard model. We find that requiring realistic features does affect the hidden sector such that hidden sector gauge group factors SU(4) and SO(8) are favored. In the context of gaugino condensation, this implies low energy supersymmetry breaking.

  5. 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.

  6. Modeling energy fluxes in heterogeneous landscapes employing a mosaic approach

    NASA Astrophysics Data System (ADS)

    Klein, Christian; Thieme, Christoph; Priesack, Eckart

    2015-04-01

    Recent studies show that uncertainties in regional and global climate and weather simulations are partly due to inadequate descriptions of the energy flux exchanges between the land surface and the atmosphere. One major shortcoming is the limitation of the grid-cell resolution, which is recommended to be about at least 3x3 km² in most models due to limitations in the model physics. To represent each individual grid cell most models select one dominant soil type and one dominant land use type. This resolution, however, is often too coarse in regions where the spatial diversity of soil and land use types are high, e.g. in Central Europe. An elegant method to avoid the shortcoming of grid cell resolution is the so called mosaic approach. This approach is part of the recently developed ecosystem model framework Expert-N 5.0. The aim of this study was to analyze the impact of the characteristics of two managed fields, planted with winter wheat and potato, on the near surface soil moistures and on the near surface energy flux exchanges of the soil-plant-atmosphere interface. The simulated energy fluxes were compared with eddy flux tower measurements between the respective fields at the research farm Scheyern, North-West of Munich, Germany. To perform these simulations, we coupled the ecosystem model Expert-N 5.0 to an analytical footprint model. The coupled model system has the ability to calculate the mixing ratio of the surface energy fluxes at a given point within one grid cell (in this case at the flux tower between the two fields). This approach accounts for the differences of the two soil types, of land use managements, and of canopy properties due to footprint size dynamics. Our preliminary simulation results show that a mosaic approach can improve modeling and analyzing energy fluxes when the land surface is heterogeneous. In this case our applied method is a promising approach to extend weather and climate models on the regional and on the global scale.

  7. Protein folding trajectories can be described quantitatively by one-dimensional diffusion over measured energy landscapes

    NASA Astrophysics Data System (ADS)

    Neupane, Krishna; Manuel, Ajay P.; Woodside, Michael T.

    2016-07-01

    Protein folding features a diffusive search over a multidimensional energy landscape in conformational space for the minimum-energy structure. Experiments, however, are usually interpreted in terms of a one-dimensional (1D) projection of the full landscape onto a practical reaction coordinate. Although simulations have shown that folding kinetics can be described well by diffusion over a 1D projection, 1D approximations have not yet been fully validated experimentally. We used folding trajectories of single molecules held under tension in optical tweezers to compare the conditional probability of being on a transition path, calculated from the trajectory, with the prediction for ideal 1D diffusion over the measured 1D landscape, calculated from committor statistics. We found good agreement for the protein PrP (refs ,) and for one of the structural transitions in a leucine-zipper coiled-coil, but not for a second transition in the coiled-coil, owing to poor reaction-coordinate quality. These results show that 1D descriptions of folding can indeed be good, even for complex tertiary structures. More fundamentally, they also provide a fully experimental validation of the basic physical picture of folding as diffusion over a landscape.

  8. Potential energy landscapes identify the information-theoretic nature of the epigenome.

    PubMed

    Jenkinson, Garrett; Pujadas, Elisabet; Goutsias, John; Feinberg, Andrew P

    2017-03-27

    Epigenetics is the study of biochemical modifications carrying information independent of DNA sequence, which are heritable through cell division. In 1940, Waddington coined the term "epigenetic landscape" as a metaphor for pluripotency and differentiation, but methylation landscapes have not yet been rigorously computed. Using principles from statistical physics and information theory, we derive epigenetic energy landscapes from whole-genome bisulfite sequencing (WGBS) data that enable us to quantify methylation stochasticity genome-wide using Shannon's entropy, associating it with chromatin structure. Moreover, we consider the Jensen-Shannon distance between sample-specific energy landscapes as a measure of epigenetic dissimilarity and demonstrate its effectiveness for discerning epigenetic differences. By viewing methylation maintenance as a communications system, we introduce methylation channels and show that higher-order chromatin organization can be predicted from their informational properties. Our results provide a fundamental understanding of the information-theoretic nature of the epigenome that leads to a powerful approach for studying its role in disease and aging.

  9. Graphene, a material for high temperature devices – intrinsic carrier density, carrier drift velocity, and lattice energy

    PubMed Central

    Yin, Yan; Cheng, Zengguang; Wang, Li; Jin, Kuijuan; Wang, Wenzhong

    2014-01-01

    Heat has always been a killing matter for traditional semiconductor machines. The underlining physical reason is that the intrinsic carrier density of a device made from a traditional semiconductor material increases very fast with a rising temperature. Once reaching a temperature, the density surpasses the chemical doping or gating effect, any p-n junction or transistor made from the semiconductor will fail to function. Here, we measure the intrinsic Fermi level (|EF| = 2.93 kBT) or intrinsic carrier density (nin = 3.87 × 106 cm−2K−2·T2), carrier drift velocity, and G mode phonon energy of graphene devices and their temperature dependencies up to 2400 K. Our results show intrinsic carrier density of graphene is an order of magnitude less sensitive to temperature than those of Si or Ge, and reveal the great potentials of graphene as a material for high temperature devices. We also observe a linear decline of saturation drift velocity with increasing temperature, and identify the temperature coefficients of the intrinsic G mode phonon energy. Above knowledge is vital in understanding the physical phenomena of graphene under high power or high temperature. PMID:25044003

  10. Free Energy Landscapes of Alanine Oligopeptides in Rigid-Body and Hybrid Water Models.

    PubMed

    Nayar, Divya; Chakravarty, Charusita

    2015-08-27

    Replica exchange molecular dynamics is used to study the effect of different rigid-body (mTIP3P, TIP4P, SPC/E) and hybrid (H1.56, H3.00) water models on the conformational free energy landscape of the alanine oligopeptides (acAnme and acA5nme), in conjunction with the CHARMM22 force field. The free energy landscape is mapped out as a function of the Ramachandran angles. In addition, various secondary structure metrics, solvation shell properties, and the number of peptide-solvent hydrogen bonds are monitored. Alanine dipeptide is found to have similar free energy landscapes in different solvent models, an insensitivity which may be due to the absence of possibilities for forming i-(i + 4) or i-(i + 3) intrapeptide hydrogen bonds. The pentapeptide, acA5nme, where there are three intrapeptide backbone hydrogen bonds, shows a conformational free energy landscape with a much greater degree of sensitivity to the choice of solvent model, though the three rigid-body water models differ only quantitatively. The pentapeptide prefers nonhelical, non-native PPII and β-sheet populations as the solvent is changed from SPC/E to the less tetrahedral liquid (H1.56) to an LJ-like liquid (H3.00). The pentapeptide conformational order metrics indicate a preference for open, solvent-exposed, non-native structures in hybrid solvent models at all temperatures of study. The possible correlations between the properties of solvent models and secondary structure preferences of alanine oligopeptides are discussed, and the competition between intrapeptide, peptide-solvent, and solvent-solvent hydrogen bonding is shown to be crucial in the relative free energies of different conformers.

  11. Towards a microscopic description of the free-energy landscape of water

    NASA Astrophysics Data System (ADS)

    Prada-Gracia, Diego; Shevchuk, Roman; Hamm, Peter; Rao, Francesco

    2012-10-01

    Free-energy landscape theory is often used to describe complex molecular systems. Here, a microscopic description of water structure and dynamics based on configuration-space-networks and molecular dynamics simulations of the TIP4P/2005 model is applied to investigate the free-energy landscape of water. The latter is built on top of a large set of water microstates describing the kinetic stability of local hydrogen-bond arrangements up to the second solvation shell. In temperature space, the landscape displays three different regimes. At around ambient conditions, the free-energy surface is characterized by many short-lived basins of attraction which are structurally well-defined (inhomogeneous regime). At lower temperatures instead, the liquid rapidly becomes homogeneous. In this regime, the free energy is funneled-like, with fully coordinated water arrangements at the bottom of the funnel. Finally, a third regime develops below the temperature of maximal compressibility (Widom line) where the funnel becomes steeper with few interconversions between microstates other than the fully coordinated ones. Our results present a way to manage the complexity of water structure and dynamics, connecting microscopic properties to its ensemble behavior.

  12. Towards a microscopic description of the free-energy landscape of water.

    PubMed

    Prada-Gracia, Diego; Shevchuk, Roman; Hamm, Peter; Rao, Francesco

    2012-10-14

    Free-energy landscape theory is often used to describe complex molecular systems. Here, a microscopic description of water structure and dynamics based on configuration-space-networks and molecular dynamics simulations of the TIP4P/2005 model is applied to investigate the free-energy landscape of water. The latter is built on top of a large set of water microstates describing the kinetic stability of local hydrogen-bond arrangements up to the second solvation shell. In temperature space, the landscape displays three different regimes. At around ambient conditions, the free-energy surface is characterized by many short-lived basins of attraction which are structurally well-defined (inhomogeneous regime). At lower temperatures instead, the liquid rapidly becomes homogeneous. In this regime, the free energy is funneled-like, with fully coordinated water arrangements at the bottom of the funnel. Finally, a third regime develops below the temperature of maximal compressibility (Widom line) where the funnel becomes steeper with few interconversions between microstates other than the fully coordinated ones. Our results present a way to manage the complexity of water structure and dynamics, connecting microscopic properties to its ensemble behavior.

  13. Energy landscape scheme for an intuitive understanding of complex domain dynamics in ferroelectric thin films.

    PubMed

    Kim, Tae Heon; Yoon, Jong-Gul; Baek, Seung Hyub; Park, Woong-kyu; Yang, Sang Mo; Yup Jang, Seung; Min, Taeyuun; Chung, Jin-Seok; Eom, Chang-Beom; Noh, Tae Won

    2015-07-01

    Fundamental understanding of domain dynamics in ferroic materials has been a longstanding issue because of its relevance to many systems and to the design of nanoscale domain-wall devices. Despite many theoretical and experimental studies, a full understanding of domain dynamics still remains incomplete, partly due to complex interactions between domain-walls and disorder. We report domain-shape-preserving deterministic domain-wall motion, which directly confirms microscopic return point memory, by observing domain-wall breathing motion in ferroelectric BiFeO3 thin film using stroboscopic piezoresponse force microscopy. Spatial energy landscape that provides new insights into domain dynamics is also mapped based on the breathing motion of domain walls. The evolution of complex domain structure can be understood by the process of occupying the lowest available energy states of polarization in the energy landscape which is determined by defect-induced internal fields. Our result highlights a pathway for the novel design of ferroelectric domain-wall devices through the engineering of energy landscape using defect-induced internal fields such as flexoelectric fields.

  14. Exploring the aggregation free energy landscape of the amyloid-β protein (1-40).

    PubMed

    Zheng, Weihua; Tsai, Min-Yeh; Chen, Mingchen; Wolynes, Peter G

    2016-10-18

    A predictive coarse-grained protein force field [associative memory, water-mediated, structure, and energy model for molecular dynamics (AWSEM)-MD] is used to study the energy landscapes and relative stabilities of amyloid-β protein (1-40) in the monomer and all of its oligomeric forms up to an octamer. We find that an isolated monomer is mainly disordered with a short α-helix formed at the central hydrophobic core region (L17-D23). A less stable hairpin structure, however, becomes increasingly more stable in oligomers, where hydrogen bonds can form between neighboring monomers. We explore the structure and stability of both prefibrillar oligomers that consist of mainly antiparallel β-sheets and fibrillar oligomers with only parallel β-sheets. Prefibrillar oligomers are polymorphic but typically take on a cylindrin-like shape composed of mostly antiparallel β-strands. At the concentration of the simulation, the aggregation free energy landscape is nearly downhill. We use umbrella sampling along a structural progress coordinate for interconversion between prefibrillar and fibrillar forms to identify a conversion pathway between these forms. The fibrillar oligomer only becomes favored over its prefibrillar counterpart in the pentamer where an interconversion bottleneck appears. The structural characterization of the pathway along with statistical mechanical perturbation theory allow us to evaluate the effects of concentration on the free energy landscape of aggregation as well as the effects of the Dutch and Arctic mutations associated with early onset of Alzheimer's disease.

  15. Autonomous oscillation in supramolecular assemblies: Role of free energy landscape and fluctuations

    NASA Astrophysics Data System (ADS)

    Sereda, Yuriy V.; Ortoleva, Peter J.

    2015-11-01

    Molecular dynamics studies demonstrated that a supramolecular assembly can express autonomous structural oscillations about equilibrium. It is demonstrated here that for nanosystems such oscillations can result from the interplay of free energy landscape and structural fluctuations. Furthermore, these oscillations have intermittent character, reflecting the conflict between a tendency to oscillate due to features in the free energy landscape, and the Second Law's repression of perpetual oscillation in an isothermal, equilibrium system. The demonstration system is a T = 1 icosahedral structure constituted of 12 protein pentamers in contact with a bath at fixed temperature. The oscillations are explained in terms of a Langevin model accounting for interactions among neighboring pentamers. The model is based on a postulated free energy landscape in the 24-dimensional space of variables describing the centrifugal and rotational motion of each pentamer. The model includes features such as basins of attraction and low free energy corridors. When the system is driven slightly out of equilibrium, the oscillations are transformed into a limit cycle, as expressed in terms of power spectrum narrowing.

  16. Multifractality and freezing phenomena in random energy landscapes: An introduction

    NASA Astrophysics Data System (ADS)

    Fyodorov, Yan V.

    2010-10-01

    We start our lectures with introducing and discussing the general notion of multifractality spectrum for random measures on lattices, and how it can be probed using moments of that measure. Then we show that the Boltzmann-Gibbs probability distributions generated by logarithmically correlated random potentials provide a simple yet non-trivial example of disorder-induced multifractal measures. The typical values of the multifractality exponents can be extracted from calculating the free energy of the associated Statistical Mechanics problem. To succeed in such a calculation we introduce and discuss in some detail two analytically tractable models for logarithmically correlated potentials. The first model uses a special definition of distances between points in space and is based on the idea of multiplicative cascades which originated in theory of turbulent motion. It is essentially equivalent to statistical mechanics of directed polymers on disordered trees studied long ago by Derrida and Spohn (1988) in Ref. [12]. In this way we introduce the notion of the freezing transition which is identified with an abrupt change in the multifractality spectrum. Second model which allows for explicit analytical evaluation of the free energy is the infinite-dimensional version of the problem which can be solved by employing the replica trick. In particular, the latter version allows one to identify the freezing phenomenon with a mechanism of the replica symmetry breaking (RSB) and to elucidate its physical meaning. The corresponding one-step RSB solution turns out to be marginally stable everywhere in the low-temperature phase. We finish with a short discussion of recent developments and extensions of models with logarithmic correlations, in particular in the context of extreme value statistics. The first appendix summarizes the standard elementary information about Gaussian integrals and related subjects, and introduces the notion of the Gaussian free field characterized by

  17. Evolving landscape of low-energy nuclear physics publications

    SciTech Connect

    Pritychenko, B.

    2016-10-01

    Evolution of low-energy nuclear physics publications over the last 120 years has been analyzed using nuclear physics databases. An extensive study of Nuclear Science References, Experimental Nuclear Reaction Data (EXFOR), and Evaluated Nuclear Structure Data File (ENSDF) contents provides a unique picture of refereed and non-refereed nuclear physics references. Significant fractional contributions of non-refereed reports, private communications and conference proceedings in EXFOR and ENSDF databases in the 1970’s reflect extensive experimental campaigns and an insufficient number of research journals. This trend has been reversed in recent years because the number of measurements is much lower, while number of journals is higher. In addition, nuclear physics results are mainly published in a limited number of journals, such as Physical Review C and Nuclear Physics A. In the present work, historic publication trends and averages have been extracted and analyzed using nuclear data mining techniques. Lastly, the results of this study and implications are discussed and conclusions presented.

  18. Evolving landscape of low-energy nuclear physics publications

    DOE PAGES

    Pritychenko, B.

    2016-10-01

    Evolution of low-energy nuclear physics publications over the last 120 years has been analyzed using nuclear physics databases. An extensive study of Nuclear Science References, Experimental Nuclear Reaction Data (EXFOR), and Evaluated Nuclear Structure Data File (ENSDF) contents provides a unique picture of refereed and non-refereed nuclear physics references. Significant fractional contributions of non-refereed reports, private communications and conference proceedings in EXFOR and ENSDF databases in the 1970’s reflect extensive experimental campaigns and an insufficient number of research journals. This trend has been reversed in recent years because the number of measurements is much lower, while number of journals ismore » higher. In addition, nuclear physics results are mainly published in a limited number of journals, such as Physical Review C and Nuclear Physics A. In the present work, historic publication trends and averages have been extracted and analyzed using nuclear data mining techniques. Lastly, the results of this study and implications are discussed and conclusions presented.« less

  19. Unsupervised machine learning on atomistic configurations: examples on amorphous defects and energy landscapes

    NASA Astrophysics Data System (ADS)

    Cubuk, Ekin; Schoenholz, Samuel; Liu, Andrea; Kaxiras, Efthimios

    2015-03-01

    Due to the recent availability of very large datasets, machine learning (ML) methods are gaining popularity as approximation and optimization tools in solid state physics. We have recently shown that supervised ML can also be used to identify and analyze soft particles, particles susceptible to rearrangement, in amorphous solids. Our method can be used to understand what makes certain configurations of particles more prone to rearrangement, and design stronger materials. We use unsupervised ML and nonlinear dimensionality reduction methods, where we do not need a ``training set'' to train the algorithm, to explore better representations of atomic configurations. These representations are shown to provide important physical insights into the structure of soft spots and stable regions in several computational and experimental glassy systems, as well as the energy landscapes of quantum mechanical systems based on Density Functional Theory calculations. By discovering an improved representation and visualization of relevant energy landscapes, discovery and optimization efforts can be simplified.

  20. The potential of computed crystal energy landscapes to aid solid-form development.

    PubMed

    Price, Sarah L; Reutzel-Edens, Susan M

    2016-06-01

    Solid-form screening to identify all solid forms of an active pharmaceutical ingredient (API) has become increasingly important in ensuring the quality by design of pharmaceutical products and their manufacturing processes. However, despite considerable enlargement of the range of techniques that have been shown capable of producing novel solid forms, it is possible that practically important forms might not be found in the short timescales currently allowed for solid-form screening. Here, we report on the state-of-the-art use of computed crystal energy landscapes to complement pharmaceutical solid-form screening. We illustrate how crystal energy landscapes can help establish molecular-level understanding of the crystallization behavior of APIs and enhance the ability of solid-form screening to facilitate pharmaceutical development.

  1. The energy landscape of modular repeat proteins: topology determines folding mechanism in the ankyrin family.

    PubMed

    Ferreiro, Diego U; Cho, Samuel S; Komives, Elizabeth A; Wolynes, Peter G

    2005-12-02

    Proteins consisting of repeating amino acid motifs are abundant in all kingdoms of life, especially in higher eukaryotes. Repeat-containing proteins self-organize into elongated non-globular structures. Do the same general underlying principles that dictate the folding of globular domains apply also to these extended topologies? Using a simplified structure-based model capturing a perfectly funneled energy landscape, we surveyed the predicted mechanism of folding for ankyrin repeat containing proteins. The ankyrin family is one of the most extensively studied classes of non-globular folds. The model based only on native contacts reproduces most of the experimental observations on the folding of these proteins, including a folding mechanism that is reminiscent of a nucleation propagation growth. The confluence of simulation and experimental results suggests that the folding of non-globular proteins is accurately described by a funneled energy landscape, in which topology plays a determinant role in the folding mechanism.

  2. Global exploration of the energy landscape of solids on the ab initio level.

    PubMed

    Doll, K; Schön, J C; Jansen, M

    2007-12-14

    Predicting which crystalline modifications can be present in a chemical system requires the global exploration of its energy landscape. Due to the large computational effort involved, in the past this search for sufficiently stable minima has been performed employing a variety of empirical potentials and cost functions followed by a local optimization on the ab initio level. However, this entails the risk of overlooking important modifications that are not modeled accurately using empirical potentials. In order to overcome this critical limitation, we develop an approach to employ ab initio energy functions during the global optimization phase of the structure prediction. As an example, we perform a global exploration of the landscape of LiF on the ab initio level and show that the relevant crystalline modifications are found during the search.

  3. Real-time control of the energy landscape by force directs the folding of RNA molecules

    PubMed Central

    Li, Pan T. X.; Bustamante, Carlos; Tinoco, Ignacio

    2007-01-01

    The rugged folding-energy landscapes of RNAs often display many competing minima. How do RNAs discriminate among competing conformations in their search for the native state? By using optical tweezers, we show that the folding-energy landscape can be manipulated to control the fate of an RNA: individual RNA molecules can be induced into either native or misfolding pathways by modulating the relaxation rate of applied force and even be redirected during the folding process to switch from misfolding to native folding pathways. Controlling folding pathways at the single-molecule level provides a way to survey the manifold of folding trajectories and intermediates, a capability that previously was available only to theoretical studies. PMID:17438300

  4. Shock compression of organic polymers and proteins: Ultrafast structural relaxation dynamics and energy landscapes

    SciTech Connect

    Kim, H.; Hambir, S.A.; Dlott, D.D.

    2000-05-04

    The response of organic polymers and proteins including poly(methyl methacrylate) and the protein bovine serum albumin (BSA) to a short duration 4.5 GPa shock pulse, termed a nanoshock, is studied using ultrafast coherent Raman spectroscopy (CARS) to monitor density-dependent vibrational frequency shifts of a dye molecule probe. In conventional shock compression experiments, a two-part response of PMMA to fast compression is usually explained with a phenomenological viscoelastic model. The molecular basis for this two-part response is discussed here using an energy landscape model to describe large-amplitude structural relaxation of shocked supercooled liquids. The polymers and the protein show an instantaneous response to the steeply rising shock front, viewed as a vertical transition to a new region of the energy landscape with radically different topography. A slower {approximately}300 ps response is also observed, attributed to large-amplitude structural relaxation along the rugged shocked energy landscape. A viscoelastic model is used to determine an effective shock viscosity {eta} {approx} 3 Pa{center_dot}s for the solid samples. This extremely small value (compared to {eta} > 10{sup 12} Pa{center_dot}s expected for supercooled liquids) is explained as a result of the very large strain rate and the extensive plastic deformation, which causes even seemingly rigid solids to flow. After the short duration ({approximately}2 ns) nanoshock unloads and the samples become frozen, for at least tens of nanoseconds, in a state where the dye vibrational shift indicates a negative pressure of about {minus}1 GPa. The negative pressure means the local density near the dye has decreased, the sample has become more permeable, and the sample is unstable to spontaneous expansion of the polymer chains. The energy landscape model provides a framework for understanding the fast cycle of compression and expansion and how to optimize the generation and detection of large

  5. Autonomously Folding Protein Fragments Reveal Differences in the Energy Landscapes of Homologous RNases H

    PubMed Central

    Rosen, Laura E.; Marqusee, Susan

    2015-01-01

    An important approach to understanding how a protein sequence encodes its energy landscape is to compare proteins with different sequences that fold to the same general native structure. In this work, we compare E. coli and T. thermophilus homologs of the protein RNase H. Using protein fragments, we create equilibrium mimics of two different potential partially-folded intermediates (Icore and Icore+1) hypothesized to be present on the energy landscapes of these two proteins. We observe that both T. thermophilus RNase H (ttRNH) fragments are folded and have distinct stabilities, indicating that both regions are capable of autonomous folding and that both intermediates are present as local minima on the ttRNH energy landscape. In contrast, the two E. coli RNase H (ecRNH) fragments have very similar stabilities, suggesting that the presence of additional residues in the Icore+1 fragment does not affect the folding or structure as compared to Icore. NMR experiments provide additional evidence that only the Icore intermediate is populated by ecRNH. This is one of the biggest differences that has been observed between the energy landscapes of these two proteins. Additionally, we used a FRET experiment in the background of full-length ttRNH to specifically monitor the formation of the Icore+1 intermediate. We determine that the ttRNH Icore+1 intermediate is likely the intermediate populated prior to the rate-limiting barrier to global folding, in contrast to E. coli RNase H for which Icore is the folding intermediate. This result provides new insight into the nature of the rate-limiting barrier for the folding of RNase H. PMID:25803034

  6. A Rough Energy Landscape to Describe Surface-Linked Antibody and Antigen Bond Formation

    PubMed Central

    Limozin, Laurent; Bongrand, Pierre; Robert, Philippe

    2016-01-01

    Antibodies and B cell receptors often bind their antigen at cell-cell interface while both molecular species are surface-bound, which impacts bond kinetics and function. Despite the description of complex energy landscapes for dissociation kinetics which may also result in significantly different association kinetics, surface-bound molecule (2D) association kinetics usually remain described by an on-rate due to crossing of a single free energy barrier, and few experimental works have measured association kinetics under conditions implying force and two-dimensional relative ligand-receptor motion. We use a new laminar flow chamber to measure 2D bond formation with systematic variation of the distribution of encounter durations between antigen and antibody, in a range from 0.1 to 10 ms. Under physiologically relevant forces, 2D association is 100-fold slower than 3D association as studied by surface plasmon resonance assays. Supported by brownian dynamics simulations, our results show that a minimal encounter duration is required for 2D association; an energy landscape featuring a rough initial part might be a reasonable way of accounting for this. By systematically varying the temperature of our experiments, we evaluate roughness at 2kBT, in the range of previously proposed rough parts of landscapes models during dissociation. PMID:27731375

  7. A New Approach to Quantify Semiochemical Effects on Insects Based on Energy Landscapes

    PubMed Central

    Wilson, Rory P.; Richards, Rebecca; Hartnell, Angharad; King, Andrew J.; Piasecka, Justyna; Gaihre, Yogendra K.; Butt, Tariq

    2014-01-01

    Introduction Our ability to document insect preference for semiochemicals is pivotal in pest control as these agents can improve monitoring and be deployed within integrated pest management programmes for more efficacious control of pest species. However, methods used to date have drawbacks that limit their utility. We present and test a new concept for determining insect motivation to move towards, or away from, semiochemicals by noting direction and speed of movement as animals work against a defined energy landscape (environmentally dependent variation in the cost of transport) requiring different powers to negotiate. We conducted trials with the pine weevils Hylobius abietis and peach-potato aphids Myzus persicae exposed to various attractants and repellents and placed so that they either moved up defined slopes against gravity or had to travel over variously rough surfaces. Results Linear Mixed Models demonstrated clear reductions in travel speed by insects moving along increasingly energetically taxing energy landscapes but also that responses varied according to different semiochemicals, thus highlighting the value of energy landscapes as a new concept to help measure insect motivation to access or avoid different attractants or repellents across individuals. Conclusions New sensitive, detailed indicators of insect motivation derived from this approach should prove important in pest control across the world. PMID:25171062

  8. A Rough Energy Landscape to Describe Surface-Linked Antibody and Antigen Bond Formation

    NASA Astrophysics Data System (ADS)

    Limozin, Laurent; Bongrand, Pierre; Robert, Philippe

    2016-10-01

    Antibodies and B cell receptors often bind their antigen at cell-cell interface while both molecular species are surface-bound, which impacts bond kinetics and function. Despite the description of complex energy landscapes for dissociation kinetics which may also result in significantly different association kinetics, surface-bound molecule (2D) association kinetics usually remain described by an on-rate due to crossing of a single free energy barrier, and few experimental works have measured association kinetics under conditions implying force and two-dimensional relative ligand-receptor motion. We use a new laminar flow chamber to measure 2D bond formation with systematic variation of the distribution of encounter durations between antigen and antibody, in a range from 0.1 to 10 ms. Under physiologically relevant forces, 2D association is 100-fold slower than 3D association as studied by surface plasmon resonance assays. Supported by brownian dynamics simulations, our results show that a minimal encounter duration is required for 2D association; an energy landscape featuring a rough initial part might be a reasonable way of accounting for this. By systematically varying the temperature of our experiments, we evaluate roughness at 2kBT, in the range of previously proposed rough parts of landscapes models during dissociation.

  9. 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.

  10. Intrinsic charge trapping in organic and polymeric semiconductors: a physical chemistry perspective

    SciTech Connect

    Kaake, Loren; Barbara, Paul F.; Zhu, Xiaoyang

    2010-01-12

    We aim to understand the origins of intrinsic charge carrier traps in organic and polymeric semiconductor materials from a physical chemistry perspective. In crystalline organic semiconductors, we point out some of the inadequacies in the description of intrinsic charge traps using language and concepts developed for inorganic semiconductors. In π-conjugated polymeric semiconductors, we suggest the presence of a two-tier electronic energy landscape, a bimodal majority landscape due to two dominant structural motifs and a minority electronic energy landscape from intrinsic charged defects. The bimodal majority electronic energy landscape results from a combination of amorphous domains and microcrystalline or liquid-crystalline domains. The minority tier of the electronic density of states is comprised of deep Coulomb traps embedded in the majority electronic energy landscape. This minority electronic energy landscape may dominate transport properties at low charge carrier densities, such as those expected for organic photovoltaic devices, while the bimodal majority electronic energy landscape becomes significant at high carrier densities, that is, in organic field effect transistors.

  11. Landscape of finite-temperature equilibrium behaviour of curvature-inducing proteins on a bilayer membrane explored using a linearized elastic free energy model

    PubMed Central

    Agrawal, Neeraj J.; Weinstein, Joshua; Radhakrishnan, Ravi

    2011-01-01

    Using a recently developed multiscale simulation methodology, we describe the equilibrium behaviour of bilayer membranes under the influence of curvature-inducing proteins using a linearized elastic free energy model. In particular, we describe how the cooperativity associated with a multitude of protein–membrane interactions and protein diffusion on a membrane-mediated energy landscape elicits emergent behaviour in the membrane phase. Based on our model simulations, we predict that, depending on the density of membrane-bound proteins and the degree to which a single protein molecule can induce intrinsic mean curvature in the membrane, a range of membrane phase behaviour can be observed including two different modes of vesicle-bud nucleation and repressed membrane undulations. A state diagram as a function of experimentally tunable parameters to classify the underlying states is proposed. PMID:21243078

  12. Variation of free‐energy landscape of the p53 C‐terminal domain induced by acetylation: Enhanced conformational sampling

    PubMed Central

    Iida, Shinji; Mashimo, Tadaaki; Kurosawa, Takashi; Hojo, Hironobu; Muta, Hiroya; Goto, Yuji; Fukunishi, Yoshifumi; Nakamura, Haruki

    2016-01-01

    The C‐terminal domain (CTD) of tumor suppressor protein p53 is an intrinsically disordered region that binds to various partner proteins, where lysine of CTD is acetylated/nonacetylated and histidine neutralized/non‐neutralized. Because of the flexibility of the unbound CTD, a free‐energy landscape (FEL) is a useful quantity for determining its statistical properties. We conducted enhanced conformational sampling of CTD in the unbound state via virtual system coupled multicanonical molecular dynamics, in which the lysine was acetylated or nonacetylated and histidine was charged or neutralized. The fragments were expressed by an all‐atom model and were immersed in an explicit solvent. The acetylation and charge‐neutralization varied FEL greatly, which might be convenient to exert a hub property. The acetylation slightly enhanced alpha‐helix structures that are more compact than sheet/loop conformations. The charge‐neutralization produced hairpins. Additionally, circular dichroism experiments confirmed the computational results. We propose possible binding mechanisms of CTD to partners by investigating FEL. © 2016 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc. PMID:27735058

  13. Energy landscape of all-atom protein-protein interactions revealed by multiscale enhanced sampling.

    PubMed

    Moritsugu, Kei; Terada, Tohru; Kidera, Akinori

    2014-10-01

    Protein-protein interactions are regulated by a subtle balance of complicated atomic interactions and solvation at the interface. To understand such an elusive phenomenon, it is necessary to thoroughly survey the large configurational space from the stable complex structure to the dissociated states using the all-atom model in explicit solvent and to delineate the energy landscape of protein-protein interactions. In this study, we carried out a multiscale enhanced sampling (MSES) simulation of the formation of a barnase-barstar complex, which is a protein complex characterized by an extraordinary tight and fast binding, to determine the energy landscape of atomistic protein-protein interactions. The MSES adopts a multicopy and multiscale scheme to enable for the enhanced sampling of the all-atom model of large proteins including explicit solvent. During the 100-ns MSES simulation of the barnase-barstar system, we observed the association-dissociation processes of the atomistic protein complex in solution several times, which contained not only the native complex structure but also fully non-native configurations. The sampled distributions suggest that a large variety of non-native states went downhill to the stable complex structure, like a fast folding on a funnel-like potential. This funnel landscape is attributed to dominant configurations in the early stage of the association process characterized by near-native orientations, which will accelerate the native inter-molecular interactions. These configurations are guided mostly by the shape complementarity between barnase and barstar, and lead to the fast formation of the final complex structure along the downhill energy landscape.

  14. A Data-Driven Evolutionary Algorithm for Mapping Multibasin Protein Energy Landscapes.

    PubMed

    Clausen, Rudy; Shehu, Amarda

    2015-09-01

    Evidence is emerging that many proteins involved in proteinopathies are dynamic molecules switching between stable and semistable structures to modulate their function. A detailed understanding of the relationship between structure and function in such molecules demands a comprehensive characterization of their conformation space. Currently, only stochastic optimization methods are capable of exploring conformation spaces to obtain sample-based representations of associated energy surfaces. These methods have to address the fundamental but challenging issue of balancing computational resources between exploration (obtaining a broad view of the space) and exploitation (going deep in the energy surface). We propose a novel algorithm that strikes an effective balance by employing concepts from evolutionary computation. The algorithm leverages deposited crystal structures of wildtype and variant sequences of a protein to define a reduced, low-dimensional search space from where to rapidly draw samples. A multiscale technique maps samples to local minima of the all-atom energy surface of a protein under investigation. Several novel algorithmic strategies are employed to avoid premature convergence to particular minima and obtain a broad view of a possibly multibasin energy surface. Analysis of applications on different proteins demonstrates the broad utility of the algorithm to map multibasin energy landscapes and advance modeling of multibasin proteins. In particular, applications on wildtype and variant sequences of proteins involved in proteinopathies demonstrate that the algorithm makes an important first step toward understanding the impact of sequence mutations on misfunction by providing the energy landscape as the intermediate explanatory link between protein sequence and function.

  15. Computed crystal energy landscapes for understanding and predicting organic crystal structures and polymorphism.

    PubMed

    Price, Sarah Sally L

    2009-01-20

    The phenomenon of polymorphism, the ability of a molecule to adopt more than one crystal structure, is a well-established property of crystalline solids. The possible variations in physical properties between polymorphs make the reliable reproduction of a crystalline form essential for all research using organic materials, as well as quality control in manufacture. Thus, the last two decades have seen both an increase in interest in polymorphism and the availability of the computer power needed to make the computational prediction of organic crystal structures a practical possibility. In the past decade, researchers have made considerable improvements in the theoretical basis for calculating the sets of structures that are within the energy range of possible polymorphism, called crystal energy landscapes. It is common to find that a molecule has a wide variety of ways of packing with lattice energy within a few kilojoules per mole of the most stable structure. However, as we develop methods to search for and characterize "all" solid forms, it is also now usual for polymorphs and solvates to be found. Thus, the computed crystal energy landscape reflects and to an increasing extent "predicts" the emerging complexity of the solid state observed for many organic molecules. This Account will discuss the ways in which the calculation of the crystal energy landscape of a molecule can be used as a complementary technique to solid form screening for polymorphs. Current methods can predict the known crystal structure, even under "blind test" conditions, but such successes are generally restricted to those structures that are the most stable over a wide range of thermodynamic conditions. The other low-energy structures can be alternative polymorphs, which have sometimes been found in later experimental studies. Examining the computed structures reveals the various compromises between close packing, hydrogen bonding, and pi-pi stacking that can result in energetically feasible

  16. Simple solvable energy-landscape model that shows a thermodynamic phase transition and a glass transition.

    PubMed

    Naumis, Gerardo G

    2012-06-01

    When a liquid melt is cooled, a glass or phase transition can be obtained depending on the cooling rate. Yet, this behavior has not been clearly captured in energy-landscape models. Here, a model is provided in which two key ingredients are considered in the landscape, metastable states and their multiplicity. Metastable states are considered as in two level system models. However, their multiplicity and topology allows a phase transition in the thermodynamic limit for slow cooling, while a transition to the glass is obtained for fast cooling. By solving the corresponding master equation, the minimal speed of cooling required to produce the glass is obtained as a function of the distribution of metastable states.

  17. Energy landscapes for a machine-learning prediction of patient discharge

    NASA Astrophysics Data System (ADS)

    Das, Ritankar; Wales, David J.

    2016-06-01

    The energy landscapes framework is applied to a configuration space generated by training the parameters of a neural network. In this study the input data consists of time series for a collection of vital signs monitored for hospital patients, and the outcomes are patient discharge or continued hospitalisation. Using machine learning as a predictive diagnostic tool to identify patterns in large quantities of electronic health record data in real time is a very attractive approach for supporting clinical decisions, which have the potential to improve patient outcomes and reduce waiting times for discharge. Here we report some preliminary analysis to show how machine learning might be applied. In particular, we visualize the fitting landscape in terms of locally optimal neural networks and the connections between them in parameter space. We anticipate that these results, and analogues of thermodynamic properties for molecular systems, may help in the future design of improved predictive tools.

  18. Energy landscapes shape microbial communities in hydrothermal systems on the Arctic Mid-Ocean Ridge.

    PubMed

    Dahle, Håkon; Økland, Ingeborg; Thorseth, Ingunn H; Pederesen, Rolf B; Steen, Ida H

    2015-07-01

    Methods developed in geochemical modelling combined with recent advances in molecular microbial ecology provide new opportunities to explore how microbial communities are shaped by their chemical surroundings. Here, we present a framework for analyses of how chemical energy availability shape chemotrophic microbial communities in hydrothermal systems through an investigation of two geochemically different basalt-hosted hydrothermal systems on the Arctic Mid-Ocean Ridge: the Soria Moria Vent field (SMVF) and the Loki's Castle Vent Field (LCVF). Chemical energy landscapes were evaluated through modelling of the Gibbs energy from selected redox reactions under different mixing ratios between seawater and hydrothermal fluids. Our models indicate that the sediment-influenced LCVF has a much higher potential for both anaerobic and aerobic methane oxidation, as well as aerobic ammonium and hydrogen oxidation, than the SMVF. The modelled energy landscapes were used to develop microbial community composition models, which were compared with community compositions in environmental samples inside or on the exterior of hydrothermal chimneys, as assessed by pyrosequencing of partial 16S rRNA genes. We show that modelled microbial communities based solely on thermodynamic considerations can have a high predictive power and provide a framework for analyses of the link between energy availability and microbial community composition.

  19. Energy landscapes shape microbial communities in hydrothermal systems on the Arctic Mid-Ocean Ridge

    PubMed Central

    Dahle, Håkon; Økland, Ingeborg; Thorseth, Ingunn H; Pederesen, Rolf B; Steen, Ida H

    2015-01-01

    Methods developed in geochemical modelling combined with recent advances in molecular microbial ecology provide new opportunities to explore how microbial communities are shaped by their chemical surroundings. Here, we present a framework for analyses of how chemical energy availability shape chemotrophic microbial communities in hydrothermal systems through an investigation of two geochemically different basalt-hosted hydrothermal systems on the Arctic Mid-Ocean Ridge: the Soria Moria Vent field (SMVF) and the Loki's Castle Vent Field (LCVF). Chemical energy landscapes were evaluated through modelling of the Gibbs energy from selected redox reactions under different mixing ratios between seawater and hydrothermal fluids. Our models indicate that the sediment-influenced LCVF has a much higher potential for both anaerobic and aerobic methane oxidation, as well as aerobic ammonium and hydrogen oxidation, than the SMVF. The modelled energy landscapes were used to develop microbial community composition models, which were compared with community compositions in environmental samples inside or on the exterior of hydrothermal chimneys, as assessed by pyrosequencing of partial 16S rRNA genes. We show that modelled microbial communities based solely on thermodynamic considerations can have a high predictive power and provide a framework for analyses of the link between energy availability and microbial community composition. PMID:25575309

  20. Molecular mechanism of polyacrylate helix sense switching across its free energy landscape.

    PubMed

    Pietropaolo, Adriana; Nakano, Tamaki

    2013-04-17

    Helical polymers with switchable screw sense are versatile frameworks for chiral functional materials. In this work, we reconstructed the free energy landscape of helical poly(2,7-bis(4-tert-butylphenyl)fluoren-9-yl acrylate) [poly(BBPFA)], as its racemization is selectively driven by light without any rearrangement of chemical bonds. The chirality inversion was enforced by atomistic free energy simulations using chirality indices as reaction coordinates. The free energy landscape reproduced the experimental electronic circular dichroism spectra. We propose that the chirality inversion of poly(BBPFA) proceeds from a left-handed 31 helix via multistate free energy pathways to reach the right-handed 31 helix. The inversion is triggered by the rotation of biphenyl units with an activation barrier of 38 kcal/mol. To the best of our knowledge, this is the first report on the chiral inversion mechanism of a helical polymer determined in a quantitative way in the framework of atomistic free energy simulations.

  1. Free-Energy Landscape and Proton Transfer Pathways in Oxidative Deamination by Methylamine Dehydrogenase.

    PubMed

    Zelleke, Theodros; Marx, Dominik

    2017-01-18

    The rate-determining step in the reductive half-reaction of the bacterial enzyme methylamine dehydrogenase, which is proton abstraction from the native substrate methylamine, is investigated using accelerated QM/MM molecular dynamics simulations at room temperature. Generation of the multidimensional thermal free-energy landscape without restriction of the degrees of freedom beyond a multidimensional reaction subspace maps two rather similar pathways for the underlying proton transfer to one of two aspartate carboxyl oxygen atoms, termed OD1 and OD2, which hydrogen bond with Thr122 and Trp108, respectively. Despite significant large-amplitude motion perpendicular to the one-dimensional proton transfer coordinate, due to fluctuations of the donor-acceptor distance of about 3 Å, it is found that the one-dimensional proton transfer free-energy profiles are essentially identical to the minimum free-energy pathways on the multidimensional free-energy landscapes for both proton transfer channels. Proton transfer to one of the acceptor oxygen atoms-the OD2 site-is slightly favored in methylamine dehydrogenase by approximately 2 kcal mol(-1) , both kinetically and thermodynamically. Mechanistic analyses reveal that the hydrogen bond between Thr122β and OD1 is always present in the transition state independently of the proton transfer channel. Population analysis confirms that the electronic charge gained upon oxidation of the substrate is delocalized within the ring systems of the tryptophan tryptophylquinone cofactor.

  2. Free energy landscapes of sodium ions bound to DMPC-cholesterol membrane surfaces at infinite dilution.

    PubMed

    Yang, Jing; Bonomi, Massimiliano; Calero, Carles; Martí, Jordi

    2016-04-07

    Exploring the free energy landscapes of metal cations on phospholipid membrane surfaces is important for the understanding of chemical and biological processes in cellular environments. Using metadynamics simulations we have performed systematic free energy calculations of sodium cations bound to DMPC phospholipid membranes with cholesterol concentration varying between 0% (cholesterol-free) and 50% (cholesterol-rich) at infinite dilution. The resulting free energy landscapes reveal the competition between binding of sodium to water and to lipid head groups. Moreover, the binding competitiveness of lipid head groups is diminished by cholesterol contents. As cholesterol concentration increases, the ionic affinity to membranes decreases. When cholesterol concentration is greater than 30%, the ionic binding is significantly reduced, which coincides with the phase transition point of DMPC-cholesterol membranes from a liquid-disordered phase to a liquid-ordered phase. We have also evaluated the contributions of different lipid head groups to the binding free energy separately. The DMPC's carbonyl group is the most favorable binding site for sodium, followed by DMPC's phosphate group and then the hydroxyl group of cholesterol.

  3. The environmental benefits of cellulosic energy crops at a landscape scale

    SciTech Connect

    Graham, R.L.; Liu, W.; English, B.C.

    1995-12-31

    The objective of this paper is to present a broad overview of the potential environmental impacts of biomass energy from energy crops--particularly the cellulosic energy crops current under development. For this discussion, the term energy crop refers to a crop grown primarily to create feedstock for either making biofuels such as ethanol or burning in a heat or electricity generation facility. Cellulosic energy crops are designed to be used in cellulose-based ethanol conversion processes (as opposed to starch or sugar-based ethanol conversion processes). As more cellulose can be produced per hectare of land than can sugar or starch, the cellulose-based ethanol conversion process is a more efficient sue of land for ethanol production. Assessing the environmental impacts of biomass energy from energy crops is complex because the environmental impact of using biomass for energy must be considered in the context of alternative energy options while the environmental impact of producing biomass from energy crops must be considered in the context of alternative land-uses. Using biomass-derived energy can reduce greenhouse gas emissions or increase them; growing biomass energy crops can enhance soil fertility or degrade it. Without knowing the context of the biomass energy, one can say little about its specific environmental impacts. The primary focus of this paper is an evaluation of the environmental impacts of growing cellulosic energy crops especially at the landscape or regional scale. However, to set the stage for this discussion, the authors begin by comparing the environmental advantages and disadvantages of biomass-derived energy relative to other energy alternatives such as coal, hydropower, nuclear power, oil/gasoline, natural gas and photovoltaics.

  4. Dynamics of driven transitions between minima of a complex energy landscapes

    NASA Astrophysics Data System (ADS)

    Pusuluri, Sai Teja; Lang, Alex H.; Mehta, Pankaj; Castillo, Horacio E.

    We recently modeled cellular interconvertion dynamics by using an epigenetic landscape model inspired by neural network models. Given an arbitrary set of patterns, the model can be used to construct an energy landscape in which those patterns are the global minima. Here we study the transitions between stable states of the landscapes thus constructed, under the effect of an external driving force. We consider three different cases: i) choosing the patterns to be random and independendently distributed ii) choosing a set of patterns directly derived from the experimental cellular transcription factor expression data for a representative set of cell types in an organism and iii) choosing randomly generated trees of hierarchically correlated patterns, inspired by biology. For each of the three cases, we study the stability of the global minima against thermal fluctuations and external driving forces, and the dynamics of the driven transitions away from global minima. We compare the results obtained in the three cases defined above, and in particular we explore to what degree the correlations between patterns affect the transition dynamics.

  5. Measurement of two-state energy landscapes on amorphous hafnium diboride surface by direct observation of dynamics

    NASA Astrophysics Data System (ADS)

    Nguyen, Duc; Mallek, Justin; Cloud, Andrew; Abelson, John; Girolami, Gregory; Lyding, Joseph; Gruebele, Martin

    2014-03-01

    Direct visualization of free energy landscape for individual Cooperatively Rearranging Regions (CRRs) is important in glassy dynamics, both for the bulk and the surface. We used scanning tunneling microscopy to track individual CRRs on amorphous hafnium diboride surface, temporally from microseconds to hours with sub-nanometer spatial resolution. CRRs have a diameter of ~5 atoms and mostly relax in a two-state fashion. From single cluster tunneling current traces, we can reconstruct local free energy landscapes, complete with energy difference, barrier height, a numerically defined reaction corrdinate and shape of the free energy minima.

  6. Snow, Shrubs, Grasses, and Footprint Theory: Measuring Moisture and Energy Fluxes in Patchy Landscapes

    NASA Astrophysics Data System (ADS)

    Strack, J. E.; Liston, G. E.; Hiemstra, C. A.; Pielke, R. A.

    2004-12-01

    When measuring sensible and latent heat flux from a tower within a heterogeneous landscape, one must consider which part of the landscape influences the flux sampled by the instruments. This variable landscape fraction, known as a footprint, is dependent upon wind direction, wind speed and atmospheric stability (thermal and mechanical). From 1 December 2002 - 31 March 2003, the FLuxes Over Snow Surfaces II (FLOSS II) field campaign measured sensible and latent heat fluxes at various heights on a 34 m tower in North Park, Colorado. North Park is an intermountain basin covered with a mixture of shrubs and graminoids (grasses and sedges) that interact with winter snow and wind to produce heterogeneous snow covers and, depending on the depth, protruding vegetation. During this period, snow depth measurements were made along transects extending 400-600 m upwind of the tower roughly every ten days. These snow depth data, in combination with blowing-snow model (SnowTran-3D) simulations, provided daily snow-depth distributions on a 1-meter grid over the area surrounding the flux tower. In addition, shrub height and vertical biomass profiles were measured and combined with a vegetation map having a 1-meter sampling scale. Merging the snow-depth distributions with the vegetation-height map allowed us to quantify the amount of vegetation protruding above the snow. This, in turn, allowed us to analyze the influence of exposed vegetation on observed energy and moisture fluxes. In this poster we describe our model for identifying the landscape fraction gauged by the flux-tower instruments as a function of commonly observed atmospheric conditions.

  7. Exploring the energy landscape of the charge transport levels in organic semiconductors at the molecular scale.

    PubMed

    Cornil, J; Verlaak, S; Martinelli, N; Mityashin, A; Olivier, Y; Van Regemorter, T; D'Avino, G; Muccioli, L; Zannoni, C; Castet, F; Beljonne, D; Heremans, P

    2013-02-19

    strongly interacting electron-hole pairs can potentially escape from their Coulomb well, a process that is at the heart of photoconversion or molecular doping. Yet they do, with near-quantitative yield in some cases. Limited screening by the low dielectric medium in organic materials leads to subtle static and dynamic electronic polarization effects that strongly impact the energy landscape for charges, which offers a rationale for this apparent inconsistency. In this Account, we use different theoretical approaches to predict the energy landscape of charge carriers at the molecular level and review a few case studies highlighting the role of electrostatic interactions in conjugated organic molecules. We describe the pros and cons of different theoretical approaches that provide access to the energy landscape defining the motion of charge carriers. We illustrate the applications of these approaches through selected examples involving OFETs, OLEDs, and solar cells. The three selected examples collectively show that energetic disorder governs device performances and highlights the relevance of theoretical tools to probe energy landscapes in molecular assemblies.

  8. Correlations between the dynamics of parallel tempering and the free-energy landscape in spin glasses

    NASA Astrophysics Data System (ADS)

    Yucesoy, Burcu; Machta, Jonathan; Katzgraber, Helmut G.

    2013-01-01

    We present the results of a large-scale numerical study of the equilibrium three-dimensional Edwards-Anderson Ising spin glass with Gaussian disorder. Using parallel tempering (replica exchange) Monte Carlo we measure various static, as well as dynamical quantities, such as the autocorrelation times and round-trip times for the parallel tempering Monte Carlo method. The correlation between static and dynamic observables for 5000 disorder realizations and up to 1000 spins down to temperatures at 20% of the critical temperature is examined. Our results show that autocorrelation times are directly correlated with the roughness of the free-energy landscape.

  9. How main-chains of proteins explore the free-energy landscape in native states

    PubMed Central

    Senet, Patrick; Maisuradze, Gia G.; Foulie, Colette; Delarue, Patrice; Scheraga, Harold A.

    2008-01-01

    Understanding how a single native protein diffuses on its free-energy landscape is essential to understand protein kinetics and function. The dynamics of a protein is complex, with multiple relaxation times reflecting a hierarchical free-energy landscape. Using all-atom molecular dynamics simulations of an α/β protein (crambin) and a β-sheet polypeptide (BS2) in their “native” states, we demonstrate that the mean-square displacement of dihedral angles, defined by 4 successive Cα atoms, increases as a power law of time, tα, with an exponent α between 0.08 and 0.39 (α = 1 corresponds to Brownian diffusion), at 300 K. Residues with low exponents are located mainly in well-defined secondary elements and adopt 1 conformational substate. Residues with high exponents are found in loops/turns and chain ends and exist in multiple conformational substates, i.e., they move on multiple-minima free-energy profiles. PMID:19073932

  10. How main-chains of proteins explore the free-energy landscape in native states.

    PubMed

    Senet, Patrick; Maisuradze, Gia G; Foulie, Colette; Delarue, Patrice; Scheraga, Harold A

    2008-12-16

    Understanding how a single native protein diffuses on its free-energy landscape is essential to understand protein kinetics and function. The dynamics of a protein is complex, with multiple relaxation times reflecting a hierarchical free-energy landscape. Using all-atom molecular dynamics simulations of an alpha/beta protein (crambin) and a beta-sheet polypeptide (BS2) in their "native" states, we demonstrate that the mean-square displacement of dihedral angles, defined by 4 successive C(alpha) atoms, increases as a power law of time, t(alpha), with an exponent alpha between 0.08 and 0.39 (alpha = 1 corresponds to Brownian diffusion), at 300 K. Residues with low exponents are located mainly in well-defined secondary elements and adopt 1 conformational substate. Residues with high exponents are found in loops/turns and chain ends and exist in multiple conformational substates, i.e., they move on multiple-minima free-energy profiles.

  11. A Scalable Algorithm to Explore the Gibbs Energy Landscape of Genome-Scale Metabolic Networks

    PubMed Central

    De Martino, Daniele; Figliuzzi, Matteo

    2012-01-01

    The integration of various types of genomic data into predictive models of biological networks is one of the main challenges currently faced by computational biology. Constraint-based models in particular play a key role in the attempt to obtain a quantitative understanding of cellular metabolism at genome scale. In essence, their goal is to frame the metabolic capabilities of an organism based on minimal assumptions that describe the steady states of the underlying reaction network via suitable stoichiometric constraints, specifically mass balance and energy balance (i.e. thermodynamic feasibility). The implementation of these requirements to generate viable configurations of reaction fluxes and/or to test given flux profiles for thermodynamic feasibility can however prove to be computationally intensive. We propose here a fast and scalable stoichiometry-based method to explore the Gibbs energy landscape of a biochemical network at steady state. The method is applied to the problem of reconstructing the Gibbs energy landscape underlying metabolic activity in the human red blood cell, and to that of identifying and removing thermodynamically infeasible reaction cycles in the Escherichia coli metabolic network (iAF1260). In the former case, we produce consistent predictions for chemical potentials (or log-concentrations) of intracellular metabolites; in the latter, we identify a restricted set of loops (23 in total) in the periplasmic and cytoplasmic core as the origin of thermodynamic infeasibility in a large sample () of flux configurations generated randomly and compatibly with the prior information available on reaction reversibility. PMID:22737065

  12. Effect of TMAO and betaine on the energy landscape of photosystem I.

    PubMed

    Nieder, Jana B; Hussels, Martin; Bittl, Robert; Brecht, Marc

    2014-06-01

    The accumulation of organic co-solvents in cells is a basic strategy for organisms from various species to increase stress tolerance in extreme environments. Widespread representatives of this class of co-solvents are trimethylamine-N-oxide (TMAO) and betaine; these small molecules are able to stabilize the native conformation of proteins and prevent their aggregation. Despite their importance, detailed experimental studies on the impact of these co-solvents on the energy landscape of proteins have not yet been carried out. We use single-molecule spectroscopy at cryogenic temperatures to examine the influence of these physiological relevant co-solvents on photosystem I (PSI) from Thermosynechococcus elongatus. In contrast to PSI ensemble spectra, which are almost unaffected by the addition of TMAO and betaine, statistical analysis of the fluorescence emission from individual PSI trimers yields insight into the interaction of the co-solvents with PSI. The results show an increased homogeneity upon addition of TMAO or betaine. The number of detectable zero-phonon lines (ZPLs) is reduced, indicating spectral diffusion processes with faster rates. In the framework of energy landscape model these findings indicate that co-solvents lead to reduced barrier heights between energy valleys, and thus efficient screening of protein conformations can take place.

  13. Generalized evolutionary metadynamics for sampling the energy landscapes and its applications

    NASA Astrophysics Data System (ADS)

    Zhu, Qiang; Oganov, Artem R.; Lyakhov, Andriy O.; Yu, Xiaoxiang

    2015-07-01

    We present an automated scheme to systematically sample energy landscapes of crystalline solids, based on the ideas of metadynamics and evolutionary algorithms. Phase transitions are driven by the evolution of the order parameter (in this case, 6-dimensional order parameters composed of cell vectors components) and aided by atomic displacements corresponding to both zero and nonzero wave vectors, enabling cell size to spontaneously change during simulation. Our technique can be used for efficient prediction of stable crystal structures, and is particularly powerful for mining numerous low-energy configurations and phase transition pathways. By applying this method to boron, we find numerous energetically competitive configurations, based on various packings of B12 icosahedra. We also observed a low-energy metastable structure of Si(T32) which is likely to be a product of decompression on Si-II. T32 is calculated to have a quasidirect band gap of 1.28 eV, making it promising for photovoltaic applications.

  14. Nudged-elastic band method with two climbing images: Finding transition states in complex energy landscapes

    SciTech Connect

    Zarkevich, Nikolai A.; Johnson, Duane D.

    2015-01-09

    The nudged-elastic band (NEB) method is modified with concomitant two climbing images (C2-NEB) to find a transition state (TS) in complex energy landscapes, such as those with a serpentine minimal energy path (MEP). If a single climbing image (C1-NEB) successfully finds the TS, then C2-NEB finds it too. Improved stability of C2-NEB makes it suitable for more complex cases, where C1-NEB misses the TS because the MEP and NEB directions near the saddle point are different. Generally, C2-NEB not only finds the TS, but guarantees, by construction, that the climbing images approach it from the opposite sides along the MEP. In addition, C2-NEB provides an accuracy estimate from the three images: the highest-energy one and its climbing neighbors. C2-NEB is suitable for fixed-cell NEB and the generalized solid-state NEB.

  15. Nudged-elastic band method with two climbing images: Finding transition states in complex energy landscapes

    DOE PAGES

    Zarkevich, Nikolai A.; Johnson, Duane D.

    2015-01-09

    The nudged-elastic band (NEB) method is modified with concomitant two climbing images (C2-NEB) to find a transition state (TS) in complex energy landscapes, such as those with a serpentine minimal energy path (MEP). If a single climbing image (C1-NEB) successfully finds the TS, then C2-NEB finds it too. Improved stability of C2-NEB makes it suitable for more complex cases, where C1-NEB misses the TS because the MEP and NEB directions near the saddle point are different. Generally, C2-NEB not only finds the TS, but guarantees, by construction, that the climbing images approach it from the opposite sides along the MEP.more » In addition, C2-NEB provides an accuracy estimate from the three images: the highest-energy one and its climbing neighbors. C2-NEB is suitable for fixed-cell NEB and the generalized solid-state NEB.« less

  16. Intrinsic Tryptophan Fluorescence in the Detection and Analysis of Proteins: A Focus on Förster Resonance Energy Transfer Techniques

    PubMed Central

    Ghisaidoobe, Amar B. T.; Chung, Sang J.

    2014-01-01

    Förster resonance energy transfer (FRET) occurs when the distance between a donor fluorophore and an acceptor is within 10 nm, and its application often necessitates fluorescent labeling of biological targets. However, covalent modification of biomolecules can inadvertently give rise to conformational and/or functional changes. This review describes the application of intrinsic protein fluorescence, predominantly derived from tryptophan (λEX ∼ 280 nm, λEM ∼ 350 nm), in protein-related research and mainly focuses on label-free FRET techniques. In terms of wavelength and intensity, tryptophan fluorescence is strongly influenced by its (or the protein’s) local environment, which, in addition to fluorescence quenching, has been applied to study protein conformational changes. Intrinsic Förster resonance energy transfer (iFRET), a recently developed technique, utilizes the intrinsic fluorescence of tryptophan in conjunction with target-specific fluorescent probes as FRET donors and acceptors, respectively, for real time detection of native proteins. PMID:25490136

  17. Power-law distributions for the areas of the basins of attraction on a potential energy landscape.

    PubMed

    Massen, Claire P; Doye, Jonathan P K

    2007-03-01

    Energy landscape approaches have become increasingly popular for analyzing a wide variety of chemical physics phenomena. Basic to many of these applications has been the inherent structure mapping, which divides up the potential energy landscape into basins of attraction surrounding the minima. Here, we probe the nature of this division by introducing a method to compute the basin area distribution and applying it to some archetypal supercooled liquids. We find that this probability distribution is a power law over a large number of decades with the lower-energy minima having larger basins of attraction. Interestingly, the exponent for this power law is approximately the same as that for a high-dimensional Apollonian packing, providing further support for the suggestion that there is a strong analogy between the way the energy landscape is divided into basins, and the way that space is packed in self-similar, space-filling hypersphere packings, such as the Apollonian packing. These results suggest that the basins of attraction provide a fractal-like tiling of the energy landscape, and that a scale-free pattern of connections between the minima is a general property of energy landscapes.

  18. Intrinsic ultraviolet (912-3200 A) energy distribution of OB stars

    NASA Technical Reports Server (NTRS)

    Longo, Renata; Stalio, Roberto; Polidan, Ronald S.; Rossi, Lucio

    1989-01-01

    Low-dispersion 500-3200-A spectra of 20 OB stars are used to derive three individual extinction curves in the wavelength range 912-1200 A. The dependence of the intrinsic UV fluxes of OB stars on both spectral type and luminosity is demonstrated. UV color indices are proposed. The results confirm the previous finding that O star spectra are not significantly bluer than the spectrum of the B0 main-sequence star Upsilon Ori.

  19. A Tale of Two Regions: Landscape Ecological Planning for Shale Gas Energy Futures

    NASA Astrophysics Data System (ADS)

    Murtha, T., Jr.; Schroth, O.; Orland, B.; Goldberg, L.; Mazurczyk, T.

    2015-12-01

    As we increasingly embrace deep shale gas deposits to meet global energy demands new and dispersed local and regional policy and planning challenges emerge. Even in regions with long histories of energy extraction, such as coal, shale gas and the infrastructure needed to produce the gas and transport it to market offers uniquely complex transformations in land use and landcover not previously experienced. These transformations are fast paced, dispersed and can overwhelm local and regional planning and regulatory processes. Coupled to these transformations is a structural confounding factor. While extraction and testing are carried out locally, regulation and decision-making is multilayered, often influenced by national and international factors. Using a geodesign framework, this paper applies a set of geospatial landscape ecological planning tools in two shale gas settings. First, we describe and detail a series of ongoing studies and tools that we have developed for communities in the Marcellus Shale region of the eastern United States, specifically the northern tier of Pennsylvania. Second, we apply a subset of these tools to potential gas development areas of the Fylde region in Lancashire, United Kingdom. For the past five years we have tested, applied and refined a set of place based and data driven geospatial models for forecasting, envisioning, analyzing and evaluating shale gas activities in northern Pennsylvania. These models are continuously compared to important landscape ecological planning challenges and priorities in the region, e.g. visual and cultural resource preservation. Adapting and applying these tools to a different landscape allow us to not only isolate and define important regulatory and policy exigencies in each specific setting, but also to develop and refine these models for broader application. As we continue to explore increasingly complex energy solutions globally, we need an equally complex comparative set of landscape ecological

  20. The switching mechanism of the mitochondrial ADP/ATP carrier explored by free-energy landscapes.

    PubMed

    Pietropaolo, Adriana; Pierri, Ciro Leonardo; Palmieri, Ferdinando; Klingenberg, Martin

    2016-06-01

    The ADP/ATP carrier (AAC) of mitochondria has been an early example for elucidating the transport mechanism alternating between the external (c-) and internal (m-) states (M. Klingenberg, Biochim. Biophys. Acta 1778 (2008) 1978-2021). An atomic resolution crystal structure of AAC is available only for the c-state featuring a three repeat transmembrane domain structure. Modeling of transport mechanism remained hypothetical for want of an atomic structure of the m-state. Previous molecular dynamics studies simulated the binding of ADP or ATP to the AAC remaining in the c-state. Here, a full description of the AAC switching from the c- to the m-state is reported using well-tempered metadynamics simulations. Free-energy landscapes of the entire translocation from the c- to the m-state, based on the gyration radii of the c- and m-gates and of the center of mass, were generated. The simulations revealed three free-energy basins attributed to the c-, intermediate- and m-states separated by activation barriers. These simulations were performed with the empty and with the ADP- and ATP-loaded AAC as well as with the poorly transported AMP and guanine nucleotides, showing in the free energy landscapes that ADP and ATP lowered the activation free-energy barriers more than the other substrates. Upon binding AMP and guanine nucleotides a deeper free-energy level stabilized the intermediate-state of the AAC2 hampering the transition to the m-state. The structures of the substrate binding sites in the different states are described producing a full picture of the translocation events in the AAC.

  1. Predicting low-temperature free energy landscapes with flat-histogram Monte Carlo methods

    NASA Astrophysics Data System (ADS)

    Mahynski, Nathan A.; Blanco, Marco A.; Errington, Jeffrey R.; Shen, Vincent K.

    2017-02-01

    We present a method for predicting the free energy landscape of fluids at low temperatures from flat-histogram grand canonical Monte Carlo simulations performed at higher ones. We illustrate our approach for both pure and multicomponent systems using two different sampling methods as a demonstration. This allows us to predict the thermodynamic behavior of systems which undergo both first order and continuous phase transitions upon cooling using simulations performed only at higher temperatures. After surveying a variety of different systems, we identify a range of temperature differences over which the extrapolation of high temperature simulations tends to quantitatively predict the thermodynamic properties of fluids at lower ones. Beyond this range, extrapolation still provides a reasonably well-informed estimate of the free energy landscape; this prediction then requires less computational effort to refine with an additional simulation at the desired temperature than reconstruction of the surface without any initial estimate. In either case, this method significantly increases the computational efficiency of these flat-histogram methods when investigating thermodynamic properties of fluids over a wide range of temperatures. For example, we demonstrate how a binary fluid phase diagram may be quantitatively predicted for many temperatures using only information obtained from a single supercritical state.

  2. Fragility of the free-energy landscape of a directed polymer in random media

    NASA Astrophysics Data System (ADS)

    Sales, Marta; Yoshino, Hajime

    2002-06-01

    We examine the sensitiveness of the free-energy landscape of a directed polymer in random media with respect to various kinds of infinitesimally weak perturbation including the intriguing case of temperature chaos. To this end, we combine the replica Bethe Ansatz approach outlined by Sales and Yoshino (e-print cond-mat/0112384), the mapping to a modified Sinai model, and numerically exact calculations by the transfer-matrix method. Our results imply that for all the perturbations under study there is a slow crossover from a weakly perturbed regime, where rare events take place, to a strongly perturbed regime at larger length scales beyond the so-called overlap length, where typical events take place leading to chaos, i.e., a complete reshuffling of the free-energy landscape. Within the replica space, the evidence for chaos is found in the factorization of the replicated partition function induced by infinitesimal perturbations. This is the reflex of explicit replica-symmetry breaking.

  3. A cavitation transition in the energy landscape of simple cohesive liquids and glasses

    NASA Astrophysics Data System (ADS)

    Altabet, Y. Elia; Stillinger, Frank H.; Debenedetti, Pablo G.

    2016-12-01

    In particle systems with cohesive interactions, the pressure-density relationship of the mechanically stable inherent structures sampled along a liquid isotherm (i.e., the equation of state of an energy landscape) will display a minimum at the Sastry density ρS. The tensile limit at ρS is due to cavitation that occurs upon energy minimization, and previous characterizations of this behavior suggested that ρS is a spinodal-like limit that separates all homogeneous and fractured inherent structures. Here, we revisit the phenomenology of Sastry behavior and find that it is subject to considerable finite-size effects, and the development of the inherent structure equation of state with system size is consistent with the finite-size rounding of an athermal phase transition. What appears to be a continuous spinodal-like point at finite system sizes becomes discontinuous in the thermodynamic limit, indicating behavior akin to a phase transition. We also study cavitation in glassy packings subjected to athermal expansion. Many individual expansion trajectories averaged together produce a smooth equation of state, which we find also exhibits features of finite-size rounding, and the examples studied in this work give rise to a larger limiting tension than for the corresponding landscape equation of state.

  4. Mapping the energy landscape for second-stage folding of a single membrane protein

    PubMed Central

    Min, Duyoung; Jefferson, Robert E; Bowie, James U; Yoon, Tae-Young

    2016-01-01

    Membrane proteins are designed to fold and function in a lipid membrane, yet folding experiments within a native membrane environment are challenging to design. Here we show that single-molecule forced unfolding experiments can be adapted to study helical membrane protein folding under native-like bicelle conditions. Applying force using magnetic tweezers, we find that a transmembrane helix protein, Escherichia coli rhomboid protease GlpG, unfolds in a highly cooperative manner, largely unraveling as one physical unit in response to mechanical tension above 25 pN. Considerable hysteresis is observed, with refolding occurring only at forces below 5 pN. Characterizing the energy landscape reveals only modest thermodynamic stability (ΔG = 6.5 kBT) but a large unfolding barrier (21.3 kBT) that can maintain the protein in a folded state for long periods of time (t1/2 ~3.5 h). The observed energy landscape may have evolved to limit the existence of troublesome partially unfolded states and impart rigidity to the structure. PMID:26479439

  5. Chiral effects on helicity studied via the energy landscape of short (D, L)-alanine peptides.

    PubMed

    Neelamraju, Sridhar; Oakley, Mark T; Johnston, Roy L

    2015-10-28

    The homochirality of natural amino acids facilitates the formation of regular secondary structures such as α-helices and β-sheets. Here, we study the relationship between chirality and backbone structure for the example of hexa-alanine. The most stable stereoisomers are identified through global optimisation. Further, the energy landscape, a database of connected low-energy local minima and transition points, is constructed for various neutral and zwitterionic stereoisomers of hexa-alanine. Three order parameters for partial helicity are applied and metric disconnectivity graphs are presented with partial helicity as a metric. We also apply the Zimm-Bragg model to derive average partial helicities for Ace-(L-Ala)6-NHMe, Ace-(D-Ala-L-Ala)3-NHMe, and Ace-(L-Ala)3-(D-Ala)3-NHMe from the database of local minima and compare with previous studies.

  6. Communication: Theoretical prediction of free-energy landscapes for complex self-assembly

    SciTech Connect

    Jacobs, William M.; Reinhardt, Aleks; Frenkel, Daan

    2015-01-14

    We present a technique for calculating free-energy profiles for the nucleation of multicomponent structures that contain as many species as building blocks. We find that a key factor is the topology of the graph describing the connectivity of the target assembly. By considering the designed interactions separately from weaker, incidental interactions, our approach yields predictions for the equilibrium yield and nucleation barriers. These predictions are in good agreement with corresponding Monte Carlo simulations. We show that a few fundamental properties of the connectivity graph determine the most prominent features of the assembly thermodynamics. Surprisingly, we find that polydispersity in the strengths of the designed interactions stabilizes intermediate structures and can be used to sculpt the free-energy landscape for self-assembly. Finally, we demonstrate that weak incidental interactions can preclude assembly at equilibrium due to the combinatorial possibilities for incorrect association.

  7. Simulations of thermodynamics and kinetics on rough energy landscapes with milestoning.

    PubMed

    Bello-Rivas, Juan M; Elber, Ron

    2016-03-05

    We investigated by computational means the kinetics and stationary behavior of stochastic dynamics on an ensemble of rough two-dimensional energy landscapes. There are no obvious separations of temporal scales in these systems, which constitute a simple model for the behavior of glasses and some biomaterials. Even though there are significant computational challenges present in these systems due to the large number of metastable states, the Milestoning method is able to compute their kinetic and thermodynamic properties exactly. We observe two clearly distinguished regimes in the overall kinetics: one in which diffusive behavior dominates and another that follows an Arrhenius law (despite the absence of a dominant barrier). We compare our results with those obtained with an exactly-solvable one-dimensional model, and with the results from the rough one-dimensional energy model introduced by Zwanzig. © 2015 Wiley Periodicals, Inc.

  8. Alternating access mechanisms of LeuT-fold transporters: trailblazing towards the promised energy landscapes.

    PubMed

    Kazmier, Kelli; Claxton, Derek P; Mchaourab, Hassane S

    2016-12-29

    Secondary active transporters couple the uphill translocation of substrates to electrochemical ion gradients. Transporter conformational motion, generically referred to as alternating access, enables a central ligand binding site to change its orientation relative to the membrane. Here we review themes of alternating access and the transduction of ion gradient energy to power this process in the LeuT-fold class of transporters where crystallographic, computational and spectroscopic approaches have converged to yield detailed models of transport cycles. Specifically, we compare findings for the Na(+)-coupled amino acid transporter LeuT and the Na(+)-coupled hydantoin transporter Mhp1. Although these studies have illuminated multiple aspects of transporter structures and dynamics, a number of questions remain unresolved that so far hinder understanding transport mechanisms in an energy landscape perspective.

  9. Energy and Water Fluxes across a Heterogeneous Landscape in the Southern Great Plains

    NASA Astrophysics Data System (ADS)

    Bagley, J. E.; Williams, I. N.; Kueppers, L. M.; Lu, Y.; Torn, M. S.; Biraud, S.

    2015-12-01

    Fluxes of energy and water between the atmosphere and the land surface influence weather and climate. These fluxes depend on the state of the landscape, which contributes to differences in land-atmosphere coupling strength over space and time. One region with potentially strong land-atmosphere coupling is the Southern Great Plains (SGP) in North America. In this region, managed vegetation plays a key role in moderating the surface energy through effects on surface albedo, transpiration, precipitation interception, and other surface properties. However accurately modeling these effects is challenging because the vegetation in this region is very heterogeneous. Winter wheat is the dominant crop, but pasture, hayfields, corn, and recently introduced crops such as canola cover significant portions of the landscape as well. Winter wheat has a unique phenology with fall planting, maximum leaf area in late spring, and harvest in early summer. This phenology contrasts significantly with most other crops and with pastures and hayfields in the region, which have more typical spring-fall growing seasons. Therefore, to sufficiently model and assess land-atmosphere interactions in this region accurate characterization of differences in the seasonality of water and energy fluxes between vegetation types are necessary. We used observations including eddy covariance flux estimates, soil moisture data, state-of-the-art longwave and shortwave radiation measurements, and other observations available for several facilities within the SGP Atmospheric Radiation Measurement (ARM) site in north-central Oklahoma and southern Kansas. We compared the timing and variations in fluxes of water and energy between winter wheat and other land cover types, focusing on vegetation influences on rates of soil dry-down following precipitation events. We found distinct differences in fluxes between winter wheat and other land types. These flux differences had a nonlinear dependency on disparities in

  10. Characterization of the dynamics of glass-forming liquids from the properties of the potential energy landscape.

    PubMed

    Banerjee, Sumilan; Dasgupta, Chandan

    2012-02-01

    We develop a framework for understanding the difference between strong and fragile behavior in the dynamics of glass-forming liquids from the properties of the potential energy landscape. Our approach is based on a master equation description of the activated jump dynamics among the local minima of the potential energy (the so-called inherent structures) that characterize the potential energy landscape of the system. We study the dynamics of a small atomic cluster using this description as well as molecular dynamics simulations and demonstrate the usefulness of our approach for this system. Many of the remarkable features of the complex dynamics of glassy systems emerge from the activated dynamics in the potential energy landscape of the atomic cluster. The dynamics of the system exhibits typical characteristics of a strong supercooled liquid when the system is allowed to explore the full configuration space. This behavior arises because the dynamics is dominated by a few lowest-lying minima of the potential energy and the potential energy barriers between these minima. When the system is constrained to explore only a limited region of the potential energy landscape that excludes the basins of attraction of a few lowest-lying minima, the dynamics is found to exhibit the characteristics of a fragile liquid.

  11. Landscape, kinetics, paths and statistics of curl flux, coherence, entanglement and energy transfer in non-equilibrium quantum systems

    NASA Astrophysics Data System (ADS)

    Zhang, Zhedong; Wang, Jin

    2015-04-01

    We develop a population and flux landscape theory for general non-equilibrium quantum systems. We illustrate our theory by modelling the quantum transport of donor-acceptor energy transfer. We find two driving forces for the non-equilibrium quantum dynamics. The symmetric part of the driving force corresponds to the population landscape contribution which mainly governs the equilibrium part of dynamics while the anti-symmetric part of the driving force generates the non-equilibrium curl quantum flux which leads to the detailed-balance-breaking and time-irreversibility. The multi-loop structure of the flux emerges forms the flux-landscape. We study the trend of changes in population and flux-landscape with respect to the voltage (temperature difference induced by environments) and electronic coupling. Improving the voltage and electronic coupling in general facilitates the quantum transport by reducing the population landscape barriers between major states and increasing the mean value of the flux. A limit-cycle mode emerges when the underlying flux-landscape becomes funnelled with a significant gap between the largest flux loop and the rest of them. On the kinetic level, we find that multiple kinetic paths between quantum states emerge and illustrate the interference effects. The degree of interference is determined by the landscape and flux. Furthermore, we quantify kinetic rate which strongly correlates with the population landscape and flux. For quantum transport, we demonstrate that as the coherence or the quantum entanglement is enhanced, the flux and energy transfer efficiency are increased. Finally it is surprising that the non-equilibriumness quantified by voltage has a non-trivial contribution on strengthening the entanglement, which is attributed to the non-local feature of the quantum curl flux.

  12. Free energy landscape of rim-pore expansion in membrane fusion.

    PubMed

    Risselada, Herre Jelger; Smirnova, Yuliya; Grubmüller, Helmut

    2014-11-18

    The productive fusion pore in membrane fusion is generally thought to be toroidally shaped. Theoretical studies and recent experiments suggest that its formation, in some scenarios, may be preceded by an initial pore formed near the rim of the extended hemifusion diaphragm (HD), a rim-pore. This rim-pore is characterized by a nontoroidal shape that changes with size. To determine this shape as well as the free energy along the pathway of rim-pore expansion, we derived a simple analytical free energy model. We argue that dilation of HD material via expansion of a rim-pore is favored over a regular, circular pore. Further, the expanding rim-pore faces a free energy barrier that linearly increases with HD size. In contrast, the tension required to expand the rim-pore decreases with HD size. Pore flickering, followed by sudden opening, occurs when the tension in the HD competes with the line energy of the rim-pore, and the rim-pore reaches its equilibrium size before reaching the critical pore size. The experimental observation of flickering and closing fusion pores (kiss-and-run) is very well explained by the observed behavior of rim-pores. Finally, the free energy landscape of rim-pore expansion/HD dilation may very well explain why some cellular fusion reactions, in their attempt to minimize energetic costs, progress via alternative formation and dilation of microscopic hemifusion intermediates.

  13. Perspective: Insight into reaction coordinates and dynamics from the potential energy landscape

    SciTech Connect

    Wales, D. J.

    2015-04-07

    This perspective focuses on conceptual and computational aspects of the potential energy landscape framework. It has two objectives: first to summarise some key developments of the approach and second to illustrate how such techniques can be applied using a specific example that exploits knowledge of pathways. Recent developments in theory and simulation within the landscape framework are first outlined, including methods for structure prediction, analysis of global thermodynamic properties, and treatment of rare event dynamics. We then develop a connection between the kinetic transition network treatment of dynamics and a potential of mean force defined by a reaction coordinate. The effect of projection from the full configuration space to low dimensionality is illustrated for an atomic cluster. In this example, where a relatively successful structural order parameter is available, the principal change in cluster morphology is reproduced, but some details are not faithfully represented. In contrast, a profile based on configurations that correspond to the discrete path defined geometrically retains all the barriers and minima. This comparison provides insight into the physical origins of “friction” effects in low-dimensionality descriptions of dynamics based upon a reaction coordinate.

  14. Protein misfolding occurs by slow diffusion across multiple barriers in a rough energy landscape

    PubMed Central

    Yu, Hao; Dee, Derek R.; Liu, Xia; Brigley, Angela M.; Sosova, Iveta; Woodside, Michael T.

    2015-01-01

    The timescale for the microscopic dynamics of proteins during conformational transitions is set by the intrachain diffusion coefficient, D. Despite the central role of protein misfolding and aggregation in many diseases, it has proven challenging to measure D for these processes because of their heterogeneity. We used single-molecule force spectroscopy to overcome these challenges and determine D for misfolding of the prion protein PrP. Observing directly the misfolding of individual dimers into minimal aggregates, we reconstructed the energy landscape governing nonnative structure formation. Remarkably, rather than displaying multiple pathways, as typically expected for aggregation, PrP dimers were funneled into a thermodynamically stable misfolded state along a single pathway containing several intermediates, one of which blocked native folding. Using Kramers’ rate theory, D was found to be 1,000-fold slower for misfolding than for native folding, reflecting local roughening of the misfolding landscape, likely due to increased internal friction. The slow diffusion also led to much longer transit times for barrier crossing, allowing transition paths to be observed directly for the first time to our knowledge. These results open a new window onto the microscopic mechanisms governing protein misfolding. PMID:26109573

  15. Hybridizing rapidly exploring random trees and basin hopping yields an improved exploration of energy landscapes.

    PubMed

    Roth, Christine-Andrea; Dreyfus, Tom; Robert, Charles H; Cazals, Frédéric

    2016-03-30

    The number of local minima of the potential energy landscape (PEL) of molecular systems generally grows exponentially with the number of degrees of freedom, so that a crucial property of PEL exploration algorithms is their ability to identify local minima, which are low lying and diverse. In this work, we present a new exploration algorithm, retaining the ability of basin hopping (BH) to identify local minima, and that of transition based rapidly exploring random trees (T-RRT) to foster the exploration of yet unexplored regions. This ability is obtained by interleaving calls to the extension procedures of BH and T-RRT, and we show tuning the balance between these two types of calls allows the algorithm to focus on low lying regions. Computational efficiency is obtained using state-of-the art data structures, in particular for searching approximate nearest neighbors in metric spaces. We present results for the BLN69, a protein model whose conformational space has dimension 207 and whose PEL has been studied exhaustively. On this system, we show that the propensity of our algorithm to explore low lying regions of the landscape significantly outperforms those of BH and T-RRT.

  16. Energy landscape theory for Alzheimer's amyloid beta-peptide fibril elongation.

    PubMed

    Massi, F; Straub, J E

    2001-02-01

    Recent experiments on the kinetics of deposition and fibril elongation of the Alzheimer's beta-amyloid peptide on preexisting fibrils are analyzed. A mechanism is developed based on the dock-and-lock scheme recently proposed by Maggio and coworkers to organize their experimental observations of the kinetics of deposition of beta-peptide on preexisting amyloid fibrils and deposits. Our mechanism includes channels for (1) a one-step prion-like direct deposition on fibrils of activated monomeric peptide in solution, and (2) a two-step deposition of unactivated peptide on fibrils and subsequent reorganization of the peptide-fibril complex. In this way, the mechanism and implied "energy landscape" unify a number of schemes proposed to describe the process of fibril elongation. This beta-amyloid landscape mechanism (beta ALM) is found to be in good agreement with existing experimental data. A number of experimental tests of the mechanism are proposed. The mechanism leads to a clear definition of overall equilibrium or rate constants in terms of the energetics of the elementary underlying processes. Analysis of existing experimental data suggests that fibril elongation occurs through a two-step mechanism of nonspecific peptide absorption and reorganization. The mechanism predicts a turnover in the rate of fibril elongation as a function of temperature and denaturant concentration. Proteins 2001;42:217-229.

  17. Mapping transiently formed and sparsely populated conformations on a complex energy landscape

    PubMed Central

    Wang, Yong; Papaleo, Elena; Lindorff-Larsen, Kresten

    2016-01-01

    Determining the structures, kinetics, thermodynamics and mechanisms that underlie conformational exchange processes in proteins remains extremely difficult. Only in favourable cases is it possible to provide atomic-level descriptions of sparsely populated and transiently formed alternative conformations. Here we benchmark the ability of enhanced-sampling molecular dynamics simulations to determine the free energy landscape of the L99A cavity mutant of T4 lysozyme. We find that the simulations capture key properties previously measured by NMR relaxation dispersion methods including the structure of a minor conformation, the kinetics and thermodynamics of conformational exchange, and the effect of mutations. We discover a new tunnel that involves the transient exposure towards the solvent of an internal cavity, and show it to be relevant for ligand escape. Together, our results provide a comprehensive view of the structural landscape of a protein, and point forward to studies of conformational exchange in systems that are less characterized experimentally. DOI: http://dx.doi.org/10.7554/eLife.17505.001 PMID:27552057

  18. Control over Structure and Function of Peptide Amphiphile Supramolecular Assemblies through Molecular Design and Energy Landscapes

    NASA Astrophysics Data System (ADS)

    Tantakitti, Faifan

    Supramolecular chemistry is a powerful tool to create a material of a defined structure with tunable properties. This strategy has led to catalytically active, bioactive, and environment-responsive materials, among others, that are valuable in applications ranging from sensor technology to energy and medicine. Supramolecular polymers formed by peptide amphiphiles (PAs) have been especially relevant in tissue regeneration due to their ability to form biocompatible structures and mimic many important signaling molecules in biology. These supramolecular polymers can form nanofibers that create networks which mimic natural extracellular matrices. PA materials have been shown to induce growth of blood vessels, bone, cartilage, and nervous tissue, among others. The work described in this thesis not only studied the relationship between molecular structure and functions of PA assemblies, but also uncovered a powerful link between the energy landscape of their supramolecular self-assembly and the ability of PA materials to interact with cells. In chapter 2, it is argued that fabricating fibrous nanostructures with defined mechanical properties and decoration with bioactive molecules is not sufficient to create a material that can effectively communicate with cells. By systemically placing the fibronectin-derived RGDS epitope at increasing distances from the surface of PA nanofibers through a linker of one to five glycine residues, integrin-mediated RGDS signaling was enhanced. The results suggested that the spatial presentation of an epitope on PA nanofibers strongly influences the bioactivity of the PA substrates. In further improving functionality of a PA-based scaffold to effectively direct cell growth and differentiation, chapter 3 explored the use of a cell microcarrier to compartmentalize and simultaneously tune insoluble and soluble signals in a single matrix. PA nanofibers were incorporated at the surface of the microcarrier in order to promote cell adhesion, while

  19. Homogenous Nucleation and Crystal Growth in a Model Liquid from Direct Energy Landscape Sampling Simulation

    NASA Astrophysics Data System (ADS)

    Walter, Nathan; Zhang, Yang

    Nucleation and crystal growth are understood to be activated processes involving the crossing of free-energy barriers. Attempts to capture the entire crystallization process over long timescales with molecular dynamic simulations have met major obstacles because of molecular dynamics' temporal constraints. Herein, we circumvent this temporal limitation by using a brutal-force, metadynamics-like, adaptive basin-climbing algorithm and directly sample the free-energy landscape of a model liquid Argon. The algorithm biases the system to evolve from an amorphous liquid like structure towards an FCC crystal through inherent structure, and then traces back the energy barriers. Consequently, the sampled timescale is macroscopically long. We observe that the formation of a crystal involves two processes, each with a unique temperature-dependent energy barrier. One barrier corresponds to the crystal nucleus formation; the other barrier corresponds to the crystal growth. We find the two processes dominate in different temperature regimes. Compared to other computation techniques, our method requires no assumptions about the shape or chemical potential of the critical crystal nucleus. The success of this method is encouraging for studying the crystallization of more complex

  20. Protein structure prediction and potential energy landscape analysis using continuous global minimization

    SciTech Connect

    Dill, K.A.; Phillips, A.T.; Rosen, J.B.

    1997-12-01

    Proteins require specific three-dimensional conformations to function properly. These {open_quotes}native{close_quotes} conformations result primarily from intramolecular interactions between the atoms in the macromolecule, and also intermolecular interactions between the macromolecule and the surrounding solvent. Although the folding process can be quite complex, the instructions guiding this process are specified by the one-dimensional primary sequence of the protein or nucleic acid: external factors, such as helper (chaperone) proteins, present at the time of folding have no effect on the final state of the protein. Many denatured proteins spontaneously refold into functional conformations once denaturing conditions are removed. Indeed, the existence of a unique native conformation, in which residues distant in sequence but close in proximity exhibit a densely packed hydrophobic core, suggests that this three-dimensional structure is largely encoded within the sequential arrangement of these specific amino acids. In any case, the native structure is often the conformation at the global minimum energy. In addition to the unique native (minimum energy) structure, other less stable structures exist as well, each with a corresponding potential energy. These structures, in conjunction with the native structure, make up an energy landscape that can be used to characterize various aspects of the protein structure. 22 refs., 10 figs., 2 tabs.

  1. Proton transfer pathways, energy landscape, and kinetics in creatine-water systems.

    PubMed

    Ivchenko, Olga; Whittleston, Chris S; Carr, Joanne M; Imhof, Petra; Goerke, Steffen; Bachert, Peter; Wales, David J

    2014-02-27

    We study the exchange processes of the metabolite creatine, which is present in both tumorous and normal tissues and has NH2 and NH groups that can transfer protons to water. Creatine produces chemical exchange saturation transfer (CEST) contrast in magnetic resonance imaging (MRI). The proton transfer pathway from zwitterionic creatine to water is examined using a kinetic transition network constructed from the discrete path sampling approach and an approximate quantum-chemical energy function, employing the self-consistent-charge density-functional tight-binding (SCC-DFTB) method. The resulting potential energy surface is visualized by constructing disconnectivity graphs. The energy landscape consists of two distinct regions corresponding to the zwitterionic creatine structures and deprotonated creatine. The activation energy that characterizes the proton transfer from the creatine NH2 group to water was determined from an Arrhenius fit of rate constants as a function of temperature, obtained from harmonic transition state theory. The result is in reasonable agreement with values obtained in water exchange spectroscopy (WEX) experiments.

  2. Up and away in the potential landscape of diatomic molecule potential energy curves

    NASA Astrophysics Data System (ADS)

    Stwalley, William C.

    2016-12-01

    The understanding of the potential curves of a given molecule has expanded in many ways during my last 52 years as an experimental and theoretical molecular chemist/physicist in graduate school in Chemistry at Harvard and in both the Chemistry and Physics Departments at University of Iowa and University of Connecticut. This expansion has been up in energy and vibrational and rotational quantum numbers and away from Re to long range as well. It is clear that Prof. Robert Le Roy, who I have known since the late 1960s, has made many important and greatly appreciated contributions to the landscape I describe below from my personal perspective, especially with regard to long range molecules and solution of the radial Schrödinger equations and related calculations.

  3. Free energy landscape of activation in a signalling protein at atomic resolution

    NASA Astrophysics Data System (ADS)

    Pontiggia, F.; Pachov, D. V.; Clarkson, M. W.; Villali, J.; Hagan, M. F.; Pande, V. S.; Kern, D.

    2015-06-01

    The interconversion between inactive and active protein states, traditionally described by two static structures, is at the heart of signalling. However, how folded states interconvert is largely unknown due to the inability to experimentally observe transition pathways. Here we explore the free energy landscape of the bacterial response regulator NtrC by combining computation and nuclear magnetic resonance, and discover unexpected features underlying efficient signalling. We find that functional states are defined purely in kinetic and not structural terms. The need of a well-defined conformer, crucial to the active state, is absent in the inactive state, which comprises a heterogeneous collection of conformers. The transition between active and inactive states occurs through multiple pathways, facilitated by a number of nonnative transient hydrogen bonds, thus lowering the transition barrier through both entropic and enthalpic contributions. These findings may represent general features for functional conformational transitions within the folded state.

  4. Navigating membrane protein structure, dynamics, and energy landscapes using spin labeling and EPR spectroscopy

    PubMed Central

    Claxton, Derek P; Kazmier, Kelli; Mishra, Smriti; Mchaourab, Hassane S

    2017-01-01

    A detailed understanding of the functional mechanism of a protein entails the characterization of its energy landscape. Achieving this ambitious goal requires the integration of multiple approaches including determination of high resolution crystal structures, uncovering conformational sampling under distinct biochemical conditions, characterizing the kinetics and thermodynamics of transitions between functional intermediates using spectroscopic techniques, and interpreting and harmonizing the data into novel computational models. With increasing sophistication in solution-based and ensemble-oriented biophysical approaches such as electron paramagnetic resonance (EPR) spectroscopy, atomic resolution structural information can be directly linked to conformational sampling in solution. Here, we detail how recent methodological and technological advances in EPR spectroscopy have contributed to the elucidation of membrane protein mechanisms. Furthermore, we aim to assist investigators interested in pursuing EPR studies by providing an introduction to the technique, a primer on experimental design, and a description of the practical considerations of the method towards generating high quality data. PMID:26477257

  5. The energy landscape of glassy dynamics on the amorphous hafnium diboride surface

    NASA Astrophysics Data System (ADS)

    Nguyen, Duc; Mallek, Justin; Cloud, Andrew N.; Abelson, John R.; Girolami, Gregory S.; Lyding, Joseph; Gruebele, Martin

    2014-11-01

    Direct visualization of the dynamics of structural glasses and amorphous solids on the sub-nanometer scale provides rich information unavailable from bulk or conventional single molecule techniques. We study the surface of hafnium diboride, a conductive ultrahigh temperature ceramic material that can be grown in amorphous films. Our scanning tunneling movies have a second-to-hour dynamic range and single-point current measurements extend that to the millisecond-to-minute time scale. On the a-HfB2 glass surface, two-state hopping of 1-2 nm diameter cooperatively rearranging regions or "clusters" occurs from sub-milliseconds to hours. We characterize individual clusters in detail through high-resolution (<0.5 nm) imaging, scanning tunneling spectroscopy and voltage modulation, ruling out individual atoms, diffusing adsorbates, or pinned charges as the origin of the observed two-state hopping. Smaller clusters are more likely to hop, larger ones are more likely to be immobile. HfB2 has a very high bulk glass transition temperature Tg, and we observe no three-state hopping or sequential two-state hopping previously seen on lower Tg glass surfaces. The electronic density of states of clusters does not change when they hop up or down, allowing us to calibrate an accurate relative z-axis scale. By directly measuring and histogramming single cluster vertical displacements, we can reconstruct the local free energy landscape of individual clusters, complete with activation barrier height, a reaction coordinate in nanometers, and the shape of the free energy landscape basins between which hopping occurs. The experimental images are consistent with the compact shape of α-relaxors predicted by random first order transition theory, whereas the rapid hopping rate, even taking less confined motion at the surface into account, is consistent with β-relaxations. We make a proposal of how "mixed" features can show up in surface dynamics of glasses.

  6. The potential and flux landscape theory of evolution

    NASA Astrophysics Data System (ADS)

    Zhang, Feng; Xu, Li; Zhang, Kun; Wang, Erkang; Wang, Jin

    2012-08-01

    We established the potential and flux landscape theory for evolution. We found explicitly the conventional Wright's gradient adaptive landscape based on the mean fitness is inadequate to describe the general evolutionary dynamics. We show the intrinsic potential as being Lyapunov function(monotonically decreasing in time) does exist and can define the adaptive landscape for general evolution dynamics for studying global stability. The driving force determining the dynamics can be decomposed into gradient of potential landscape and curl probability flux. Non-zero flux causes detailed balance breaking and measures how far the evolution from equilibrium state. The gradient of intrinsic potential and curl flux are perpendicular to each other in zero fluctuation limit resembling electric and magnetic forces on electrons. We quantified intrinsic energy, entropy and free energy of evolution and constructed non-equilibrium thermodynamics. The intrinsic non-equilibrium free energy is a Lyapunov function. Both intrinsic potential and free energy can be used to quantify the global stability and robustness of evolution. We investigated an example of three allele evolutionary dynamics with frequency dependent selection (detailed balance broken). We uncovered the underlying single, triple, and limit cycle attractor landscapes. We found quantitative criterions for stability through landscape topography. We also quantified evolution pathways and found paths do not follow potential gradient and are irreversible due to non-zero flux. We generalized the original Fisher's fundamental theorem to the general (i.e., frequency dependent selection) regime of evolution by linking the adaptive rate with not only genetic variance related to the potential but also the flux. We show there is an optimum potential where curl flux resulting from biotic interactions of individuals within a species or between species can sustain an endless evolution even if the physical environment is unchanged. We

  7. ENERGY-DEPENDENT GAMMA-RAY BURST PULSE WIDTH DUE TO THE CURVATURE EFFECT AND INTRINSIC BAND SPECTRUM

    SciTech Connect

    Peng, Z. Y.; Ma, L.; Zhao, X. H.; Yin, Y.; Bao, Y. Y.

    2012-06-20

    Previous studies have found that the width of the gamma-ray burst (GRB) pulse is energy dependent and that it decreases as a power-law function with increasing photon energy. In this work we have investigated the relation between the energy dependence of the pulse and the so-called Band spectrum by using a sample including 51 well-separated fast rise and exponential decay long-duration GRB pulses observed by BATSE (Burst and Transient Source Experiment on the Compton Gamma Ray Observatory). We first decompose these pulses into rise and decay phases and find that the rise widths and the decay widths also behave as a power-law function with photon energy. Then we investigate statistically the relations between the three power-law indices of the rise, decay, and total width of the pulse (denoted as {delta}{sub r}, {delta}{sub d}, and {delta}{sub w}, respectively) and the three Band spectral parameters, high-energy index ({alpha}), low-energy index ({beta}), and peak energy (E{sub p} ). It is found that (1) {alpha} is strongly correlated with {delta}{sub w} and {delta}{sub d} but seems uncorrelated with {delta}{sub r}; (2) {beta} is weakly correlated with the three power-law indices, and (3) E{sub p} does not show evident correlations with the three power-law indices. We further investigate the origin of {delta}{sub d}-{alpha} and {delta}{sub w}-{alpha}. We show that the curvature effect and the intrinsic Band spectrum could naturally lead to the energy dependence of the GRB pulse width and also the {delta}{sub d}-{alpha} and {delta}{sub w}-{alpha} correlations. Our results hold so long as the shell emitting gamma rays has a curved surface and the intrinsic spectrum is a Band spectrum or broken power law. The strong {delta}{sub d}-{alpha} correlation and inapparent correlations between {delta}{sub r} and the three Band spectral parameters also suggest that the rise and decay phases of the GRB pulses have different origins.

  8. Resting and Energy Reserves of Aedes albopictus Collected in Common Landscaping Vegetation in St. Augustine, Florida

    PubMed Central

    Samson, Dayana M.; Qualls, Whitney A.; Roque, Deborah; Naranjo, Diana P.; Alimi, Temitope; Arheart, Kristopher L.; Müller, Günter C.; Beier, John C.

    2014-01-01

    The resting behavior of Aedes albopictus was evaluated by aspirating diurnal resting mosquitoes from common landscape vegetation in residential communities in St. Augustine, FL. Energy reserves of the resting mosquitoes were analyzed to determine if there was a correlation between mosquito resting habitat and energy accumulation. Six species of plants were selected and 9 collections of resting mosquitoes were aspirated from each plant using a modified John W. Hock backpack aspirator during June and July 2012. Eight mosquito species were collected, with Ae. albopictus representing 74% of the overall collection. The number of Ae. albopictus collected varied significantly with the species of vegetation. When comparing the vegetation and abundance of resting mosquitoes, the highest percentages of Ae. albopictus were collected resting on Ruellia brittoniana (Mexican petunia), Asplenium platyneuron (fern), Gibasis geniculate (Tahitian bridal veil), followed by Plumba goauriculata (plumbago), Setcreasea pallida (purple heart), and Hibiscus tiliaceus (hibiscus). There were significant differences in lipid and glycogen accumulation based on type of vegetation Ae. albopictus was found resting in. Resting mosquitoes' sugar reserves were not influenced by species of vegetation. However, there was an overall correlation between vegetation that serves as a resting habitat and energy reserve accumulation. The results of our study demonstrate the potential to target specific vegetation for control of diurnal resting mosquitoes. PMID:24199497

  9. Landscapes for Energy and Wildlife: Conservation Prioritization for Golden Eagles across Large Spatial Scales

    PubMed Central

    Tack, Jason D.; Fedy, Bradley C.

    2015-01-01

    Proactive conservation planning for species requires the identification of important spatial attributes across ecologically relevant scales in a model-based framework. However, it is often difficult to develop predictive models, as the explanatory data required for model development across regional management scales is rarely available. Golden eagles are a large-ranging predator of conservation concern in the United States that may be negatively affected by wind energy development. Thus, identifying landscapes least likely to pose conflict between eagles and wind development via shared space prior to development will be critical for conserving populations in the face of imposing development. We used publically available data on golden eagle nests to generate predictive models of golden eagle nesting sites in Wyoming, USA, using a suite of environmental and anthropogenic variables. By overlaying predictive models of golden eagle nesting habitat with wind energy resource maps, we highlight areas of potential conflict among eagle nesting habitat and wind development. However, our results suggest that wind potential and the relative probability of golden eagle nesting are not necessarily spatially correlated. Indeed, the majority of our sample frame includes areas with disparate predictions between suitable nesting habitat and potential for developing wind energy resources. Map predictions cannot replace on-the-ground monitoring for potential risk of wind turbines on wildlife populations, though they provide industry and managers a useful framework to first assess potential development. PMID:26262876

  10. The energy landscape, folding pathways and the kinetics of a knotted protein.

    PubMed

    Prentiss, Michael C; Wales, David J; Wolynes, Peter G

    2010-07-01

    The folding pathway and rate coefficients of the folding of a knotted protein are calculated for a potential energy function with minimal energetic frustration. A kinetic transition network is constructed using the discrete path sampling approach, and the resulting potential energy surface is visualized by constructing disconnectivity graphs. Owing to topological constraints, the low-lying portion of the landscape consists of three distinct regions, corresponding to the native knotted state and to configurations where either the N or C terminus is not yet folded into the knot. The fastest folding pathways from denatured states exhibit early formation of the N terminus portion of the knot and a rate-determining step where the C terminus is incorporated. The low-lying minima with the N terminus knotted and the C terminus free therefore constitute an off-pathway intermediate for this model. The insertion of both the N and C termini into the knot occurs late in the folding process, creating large energy barriers that are the rate limiting steps in the folding process. When compared to other protein folding proteins of a similar length, this system folds over six orders of magnitude more slowly.

  11. Landscapes for energy and wildlife: conservation prioritization for golden eagles across large spatial scales

    USGS Publications Warehouse

    Tack, Jason D.; Fedy, Bradley C.

    2015-01-01

    Proactive conservation planning for species requires the identification of important spatial attributes across ecologically relevant scales in a model-based framework. However, it is often difficult to develop predictive models, as the explanatory data required for model development across regional management scales is rarely available. Golden eagles are a large-ranging predator of conservation concern in the United States that may be negatively affected by wind energy development. Thus, identifying landscapes least likely to pose conflict between eagles and wind development via shared space prior to development will be critical for conserving populations in the face of imposing development. We used publically available data on golden eagle nests to generate predictive models of golden eagle nesting sites in Wyoming, USA, using a suite of environmental and anthropogenic variables. By overlaying predictive models of golden eagle nesting habitat with wind energy resource maps, we highlight areas of potential conflict among eagle nesting habitat and wind development. However, our results suggest that wind potential and the relative probability of golden eagle nesting are not necessarily spatially correlated. Indeed, the majority of our sample frame includes areas with disparate predictions between suitable nesting habitat and potential for developing wind energy resources. Map predictions cannot replace on-the-ground monitoring for potential risk of wind turbines on wildlife populations, though they provide industry and managers a useful framework to first assess potential development.

  12. Exploring the Energy Landscapes of Protein Folding Simulations with Bayesian Computation

    PubMed Central

    Burkoff, Nikolas S.; Várnai, Csilla; Wells, Stephen A.; Wild, David L.

    2012-01-01

    Nested sampling is a Bayesian sampling technique developed to explore probability distributions localized in an exponentially small area of the parameter space. The algorithm provides both posterior samples and an estimate of the evidence (marginal likelihood) of the model. The nested sampling algorithm also provides an efficient way to calculate free energies and the expectation value of thermodynamic observables at any temperature, through a simple post processing of the output. Previous applications of the algorithm have yielded large efficiency gains over other sampling techniques, including parallel tempering. In this article, we describe a parallel implementation of the nested sampling algorithm and its application to the problem of protein folding in a Gō-like force field of empirical potentials that were designed to stabilize secondary structure elements in room-temperature simulations. We demonstrate the method by conducting folding simulations on a number of small proteins that are commonly used for testing protein-folding procedures. A topological analysis of the posterior samples is performed to produce energy landscape charts, which give a high-level description of the potential energy surface for the protein folding simulations. These charts provide qualitative insights into both the folding process and the nature of the model and force field used. PMID:22385859

  13. Landscapes for Energy and Wildlife: Conservation Prioritization for Golden Eagles across Large Spatial Scales.

    PubMed

    Tack, Jason D; Fedy, Bradley C

    2015-01-01

    Proactive conservation planning for species requires the identification of important spatial attributes across ecologically relevant scales in a model-based framework. However, it is often difficult to develop predictive models, as the explanatory data required for model development across regional management scales is rarely available. Golden eagles are a large-ranging predator of conservation concern in the United States that may be negatively affected by wind energy development. Thus, identifying landscapes least likely to pose conflict between eagles and wind development via shared space prior to development will be critical for conserving populations in the face of imposing development. We used publically available data on golden eagle nests to generate predictive models of golden eagle nesting sites in Wyoming, USA, using a suite of environmental and anthropogenic variables. By overlaying predictive models of golden eagle nesting habitat with wind energy resource maps, we highlight areas of potential conflict among eagle nesting habitat and wind development. However, our results suggest that wind potential and the relative probability of golden eagle nesting are not necessarily spatially correlated. Indeed, the majority of our sample frame includes areas with disparate predictions between suitable nesting habitat and potential for developing wind energy resources. Map predictions cannot replace on-the-ground monitoring for potential risk of wind turbines on wildlife populations, though they provide industry and managers a useful framework to first assess potential development.

  14. Anomalous dimensionality dependence of diffusion in a rugged energy landscape: How pathological is one dimension?

    NASA Astrophysics Data System (ADS)

    Seki, Kazuhiko; Bagchi, Kaushik; Bagchi, Biman

    2016-05-01

    Diffusion in one dimensional rugged energy landscape (REL) is predicted to be pathologically different (from any higher dimension) with a much larger chance of encountering broken ergodicity [D. L. Stein and C. M. Newman, AIP Conf. Proc. 1479, 620 (2012)]. However, no quantitative study of this difference has been reported, despite the prevalence of multidimensional physical models in the literature (like a high dimensional funnel guiding protein folding/unfolding). Paradoxically, some theoretical studies of these phenomena still employ a one dimensional diffusion description for analytical tractability. We explore the dimensionality dependent diffusion on REL by carrying out an effective medium approximation based analytical calculations and compare them with the available computer simulation results. We find that at an intermediate level of ruggedness (assumed to have a Gaussian distribution), where diffusion is well-defined, the value of the effective diffusion coefficient depends on dimensionality and changes (increases) by several factors (˜5-10) in going from 1d to 2d. In contrast, the changes in subsequent transitions (like 2d to 3d and 3d to 4d and so on) are far more modest, of the order of 10-20% only. When ruggedness is given by random traps with an exponential distribution of barrier heights, the mean square displacement (MSD) is sub-diffusive (a well-known result), but the growth of MSD is described by different exponents in one and higher dimensions. The reason for such strong ruggedness induced retardation in the case of one dimensional REL is discussed. We also discuss the special limiting case of infinite dimension (d = ∞) where the effective medium approximation becomes exact and where theoretical results become simple. We discuss, for the first time, the role of spatial correlation in the landscape on diffusion of a random walker.

  15. Anomalous dimensionality dependence of diffusion in a rugged energy landscape: How pathological is one dimension?

    PubMed

    Seki, Kazuhiko; Bagchi, Kaushik; Bagchi, Biman

    2016-05-21

    Diffusion in one dimensional rugged energy landscape (REL) is predicted to be pathologically different (from any higher dimension) with a much larger chance of encountering broken ergodicity [D. L. Stein and C. M. Newman, AIP Conf. Proc. 1479, 620 (2012)]. However, no quantitative study of this difference has been reported, despite the prevalence of multidimensional physical models in the literature (like a high dimensional funnel guiding protein folding/unfolding). Paradoxically, some theoretical studies of these phenomena still employ a one dimensional diffusion description for analytical tractability. We explore the dimensionality dependent diffusion on REL by carrying out an effective medium approximation based analytical calculations and compare them with the available computer simulation results. We find that at an intermediate level of ruggedness (assumed to have a Gaussian distribution), where diffusion is well-defined, the value of the effective diffusion coefficient depends on dimensionality and changes (increases) by several factors (∼5-10) in going from 1d to 2d. In contrast, the changes in subsequent transitions (like 2d to 3d and 3d to 4d and so on) are far more modest, of the order of 10-20% only. When ruggedness is given by random traps with an exponential distribution of barrier heights, the mean square displacement (MSD) is sub-diffusive (a well-known result), but the growth of MSD is described by different exponents in one and higher dimensions. The reason for such strong ruggedness induced retardation in the case of one dimensional REL is discussed. We also discuss the special limiting case of infinite dimension (d = ∞) where the effective medium approximation becomes exact and where theoretical results become simple. We discuss, for the first time, the role of spatial correlation in the landscape on diffusion of a random walker.

  16. Charting molecular free-energy landscapes with an atlas of collective variables

    NASA Astrophysics Data System (ADS)

    Hashemian, Behrooz; Millán, Daniel; Arroyo, Marino

    2016-11-01

    Collective variables (CVs) are a fundamental tool to understand molecular flexibility, to compute free energy landscapes, and to enhance sampling in molecular dynamics simulations. However, identifying suitable CVs is challenging, and is increasingly addressed with systematic data-driven manifold learning techniques. Here, we provide a flexible framework to model molecular systems in terms of a collection of locally valid and partially overlapping CVs: an atlas of CVs. The specific motivation for such a framework is to enhance the applicability and robustness of CVs based on manifold learning methods, which fail in the presence of periodicities in the underlying conformational manifold. More generally, using an atlas of CVs rather than a single chart may help us better describe different regions of conformational space. We develop the statistical mechanics foundation for our multi-chart description and propose an algorithmic implementation. The resulting atlas of data-based CVs are then used to enhance sampling and compute free energy surfaces in two model systems, alanine dipeptide and β-D-glucopyranose, whose conformational manifolds have toroidal and spherical topologies.

  17. Hybrid organic-inorganic inks flatten the energy landscape in colloidal quantum dot solids.

    PubMed

    Liu, Mengxia; Voznyy, Oleksandr; Sabatini, Randy; García de Arquer, F Pelayo; Munir, Rahim; Balawi, Ahmed Hesham; Lan, Xinzheng; Fan, Fengjia; Walters, Grant; Kirmani, Ahmad R; Hoogland, Sjoerd; Laquai, Frédéric; Amassian, Aram; Sargent, Edward H

    2017-02-01

    Bandtail states in disordered semiconductor materials result in losses in open-circuit voltage (Voc) and inhibit carrier transport in photovoltaics. For colloidal quantum dot (CQD) films that promise low-cost, large-area, air-stable photovoltaics, bandtails are determined by CQD synthetic polydispersity and inhomogeneous aggregation during the ligand-exchange process. Here we introduce a new method for the synthesis of solution-phase ligand-exchanged CQD inks that enable a flat energy landscape and an advantageously high packing density. In the solid state, these materials exhibit a sharper bandtail and reduced energy funnelling compared with the previous best CQD thin films for photovoltaics. Consequently, we demonstrate solar cells with higher Voc and more efficient charge injection into the electron acceptor, allowing the use of a closer-to-optimum bandgap to absorb more light. These enable the fabrication of CQD solar cells made via a solution-phase ligand exchange, with a certified power conversion efficiency of 11.28%. The devices are stable when stored in air, unencapsulated, for over 1,000 h.

  18. Hybrid organic-inorganic inks flatten the energy landscape in colloidal quantum dot solids

    NASA Astrophysics Data System (ADS)

    Liu, Mengxia; Voznyy, Oleksandr; Sabatini, Randy; García de Arquer, F. Pelayo; Munir, Rahim; Balawi, Ahmed Hesham; Lan, Xinzheng; Fan, Fengjia; Walters, Grant; Kirmani, Ahmad R.; Hoogland, Sjoerd; Laquai, Frédéric; Amassian, Aram; Sargent, Edward H.

    2016-11-01

    Bandtail states in disordered semiconductor materials result in losses in open-circuit voltage (Voc) and inhibit carrier transport in photovoltaics. For colloidal quantum dot (CQD) films that promise low-cost, large-area, air-stable photovoltaics, bandtails are determined by CQD synthetic polydispersity and inhomogeneous aggregation during the ligand-exchange process. Here we introduce a new method for the synthesis of solution-phase ligand-exchanged CQD inks that enable a flat energy landscape and an advantageously high packing density. In the solid state, these materials exhibit a sharper bandtail and reduced energy funnelling compared with the previous best CQD thin films for photovoltaics. Consequently, we demonstrate solar cells with higher Voc and more efficient charge injection into the electron acceptor, allowing the use of a closer-to-optimum bandgap to absorb more light. These enable the fabrication of CQD solar cells made via a solution-phase ligand exchange, with a certified power conversion efficiency of 11.28%. The devices are stable when stored in air, unencapsulated, for over 1,000 h.

  19. Free energy landscapes for S-H bonds in Cp*2Mo2S4 complexes.

    PubMed

    Appel, Aaron M; Lee, Suh-Jane; Franz, James A; DuBois, Daniel L; DuBois, M Rakowski

    2009-04-15

    An extensive family of thermochemical data is presented for a series of complexes derived from Cp*Mo(mu-S)(2)(mu-SMe)(mu-SH)MoCp* and Cp*Mo(mu-S)(2)(mu-SH)(2)MoCp*. These data include electrochemical potentials, pK(a) values, homolytic solution bond dissociation free energies (SBDFEs), and hydride donor abilities in acetonitrile. Thermochemical data ranged from +0.6 to -2.0 V vs FeCp(2)(+/o) for electrochemical potentials, 5 to 31 for pK(a) values, 43 to 68 kcal/mol for homolytic SBDFEs, and 44 to 84 kcal/mol for hydride donor abilities. The observed values for these thermodynamic parameters are comparable to those of many transition metal hydrides, which is consistent with the many parallels in the chemistry of these two classes of compounds. The extensive set of thermochemical data is presented in free energy landscapes as a useful approach to visualizing and understanding the relative stabilities of all of the species under varying conditions of pH and H(2) overpressure. In addition to the previously studied homogeneous reactivity and catalysis, Mo(2)S(4) complexes are also models for heterogeneous molybdenum sulfide catalysts, and therefore, the present results demonstrate the dramatic range of S-H bond strengths available in both homogeneous and heterogeneous reaction pathways.

  20. Evolution of intrinsic growth and energy acquisition rates. I. Trade-offs with swimming performance in Menidia menidia.

    PubMed

    Billerbeck, J M; Lankford, T E; Conover, D O

    2001-09-01

    Latitudinal populations of the Atlantic silverside, Menidia menidia, show substantial genetic variation in rates of energy acquistion and allocation. Reared in common environments, silversides from northern latitudes consume more food, grow faster and more efficiently, store more energy, and produce greater quantities of eggs than their southern conspecifics. The persistence of seemingly inferior southern genotypes in the face of ostensibly superior northern genotypes suggest that there are hidden evolutionary trade-offs associated with these elevated acquisition and allocation rates. We tested the hypothesis that rapid growth and high levels of food consumption trade-off against locomotory performance in M. menidia. We compared both aerobic (prolonged and endurance) and anaerobic (burst) swimming capacities between intrinsically fast-growing fish from the north (Nova Scotia, NS) and intrinsically slow-growing fish from the south (South Carolina, SC) and between growth-manipulated phenotypes within each population. We also compared swimming speeds and endurance between fasted and recently fed fish within populations. Maximum prolonged and burst swimming speeds of NS fish were significantly lower than those of SC fish, and swimming speeds of fast-growing phenotypes were lower than those of slow-growing phenotypes within populations. Fed fish had lower burst speeds and less endurance than fasted fish from the same population. Thus, high rates of growth and the consumption of large meals clearly diminish swimming performance, which likely increases vulnerability to predation and decreases survival and relative fitness. The submaximal growth rate of southern M. menidia appears to be adaptive, resulting from balancing selection on rates of somatic growth.

  1. Intrinsic Information Processing and Energy Dissipation in Stochastic Input-Output Dynamical Systems

    DTIC Science & Technology

    2015-07-09

    intelligent” control can convert information to energy. However, these approaches have yet to account for the diverse kinds of information that complex...Army Research Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 input-output processes, controlled thermodynamics systems, nonlinear...be subject to any oenalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE

  2. A New Polymer Nanoprobe Based on Chemiluminescence Resonance Energy Transfer for Ultrasensitive Imaging of Intrinsic Superoxide Anion in Mice.

    PubMed

    Li, Ping; Liu, Lu; Xiao, Haibin; Zhang, Wei; Wang, Lulin; Tang, Bo

    2016-03-09

    Despite significant developments in optical imaging of superoxide anion (O2(•-)) as the preliminary reactive oxygen species, novel visualizing strategies that offer ultrahigh sensitivity are still imperative. This is mainly because intrinsic concentrations of O2(•-) are extremely low in living systems. Herein, we present the rational design and construction of a new polymer nanoprobe PCLA-O2(•-) for detecting O2(•-) based on chemiluminescence (CL) resonance energy transfer without an external excitation source. Structurally, PCLA-O2(•-) contains two moieties linked covalently, namely imidazopyrazinone that is capable of CL triggered by O2(•-) as the energy donor and conjugated polymers with light-amplifying property as the energy acceptor. Experiment results demonstrate that PCLA-O2(•-) exhibits ultrahigh sensitivity at the picomole level, dramatically prolonged luminescence time, specificity, and excellent biocompatibility. Without exogenous stimulation, this probe for the first time in situ visualizes O2(•-) level differences between normal and tumor tissues of mice. These exceptional features ensure that PCLA-O2(•-) as a self-luminescing probe is an alternative in vivo imaging approach for ultralow level O2(•-).

  3. The energy landscape of glassy dynamics on the amorphous hafnium diboride surface

    SciTech Connect

    Nguyen, Duc; Girolami, Gregory S.; Mallek, Justin; Cloud, Andrew N.; Abelson, John R.; Lyding, Joseph; Gruebele, Martin

    2014-11-28

    Direct visualization of the dynamics of structural glasses and amorphous solids on the sub-nanometer scale provides rich information unavailable from bulk or conventional single molecule techniques. We study the surface of hafnium diboride, a conductive ultrahigh temperature ceramic material that can be grown in amorphous films. Our scanning tunneling movies have a second-to-hour dynamic range and single-point current measurements extend that to the millisecond-to-minute time scale. On the a-HfB{sub 2} glass surface, two-state hopping of 1–2 nm diameter cooperatively rearranging regions or “clusters” occurs from sub-milliseconds to hours. We characterize individual clusters in detail through high-resolution (<0.5 nm) imaging, scanning tunneling spectroscopy and voltage modulation, ruling out individual atoms, diffusing adsorbates, or pinned charges as the origin of the observed two-state hopping. Smaller clusters are more likely to hop, larger ones are more likely to be immobile. HfB{sub 2} has a very high bulk glass transition temperature T{sub g}, and we observe no three-state hopping or sequential two-state hopping previously seen on lower T{sub g} glass surfaces. The electronic density of states of clusters does not change when they hop up or down, allowing us to calibrate an accurate relative z-axis scale. By directly measuring and histogramming single cluster vertical displacements, we can reconstruct the local free energy landscape of individual clusters, complete with activation barrier height, a reaction coordinate in nanometers, and the shape of the free energy landscape basins between which hopping occurs. The experimental images are consistent with the compact shape of α-relaxors predicted by random first order transition theory, whereas the rapid hopping rate, even taking less confined motion at the surface into account, is consistent with β-relaxations. We make a proposal of how “mixed” features can show up in surface dynamics of glasses.

  4. Biodelignification of lignocellulose substrates: An intrinsic and sustainable pretreatment strategy for clean energy production.

    PubMed

    Chandel, Anuj K; Gonçalves, Bruna C M; Strap, Janice L; da Silva, Silvio S

    2015-01-01

    Lignocellulosic biomass (LB) is a promising sugar feedstock for biofuels and other high-value chemical commodities. The recalcitrance of LB, however, impedes carbohydrate accessibility and its conversion into commercially significant products. Two important factors for the overall economization of biofuel production is LB pretreatment to liberate fermentable sugars followed by conversion into ethanol. Sustainable biofuel production must overcome issues such as minimizing water and energy usage, reducing chemical usage and process intensification. Amongst available pretreatment methods, microorganism-mediated pretreatments are the safest, green, and sustainable. Native biodelignifying agents such as Phanerochaete chrysosporium, Pycnoporous cinnabarinus, Ceriporiopsis subvermispora and Cyathus stercoreus can remove lignin, making the remaining substrates amenable for saccharification. The development of a robust, integrated bioprocessing (IBP) approach for economic ethanol production would incorporate all essential steps including pretreatment, cellulase production, enzyme hydrolysis and fermentation of the released sugars into ethanol. IBP represents an inexpensive, environmentally friendly, low energy and low capital approach for second-generation ethanol production. This paper reviews the advancements in microbial-assisted pretreatment for the delignification of lignocellulosic substrates, system metabolic engineering for biorefineries and highlights the possibilities of process integration for sustainable and economic ethanol production.

  5. Probing the energy landscape of alanine dipeptide and decalanine using temperature as a tunable parameter in molecular dynamics

    NASA Astrophysics Data System (ADS)

    Chatterjee, A.; Bhattacharya, S.

    2016-10-01

    We perform several molecular dynamics (MD) calculations of solvated alanine dipeptide and decalanine in vacuum with temperature as a tunable parameter and in the process, generate Markov state models (MSMs) at each temperature. An interesting observation that the kinetic rates appear to obey the Arrhenius rate law allows us to predict the dynamics of alanine dipeptide at 300 K at the microsecond timescales using the nanoseconds long high temperature calculations without actually performing MD simulations at 300 K. We conclude that the energy landscape of alanine dipeptide contains superbasins deeper than kBT and determine the energy barriers associated with the moves from the Arrhenius rate expression. Similar insights regarding the energy landscape associated with folding/unfolding pathways of a deca-alanine molecule are obtained using kinetic rates calculated at different temperatures.

  6. Error-based Extraction of States and Energy Landscapes from Experimental Single-Molecule Time-Series

    PubMed Central

    Taylor, J. Nicholas; Li, Chun-Biu; Cooper, David R.; Landes, Christy F.; Komatsuzaki, Tamiki

    2015-01-01

    Characterization of states, the essential components of the underlying energy landscapes, is one of the most intriguing subjects in single-molecule (SM) experiments due to the existence of noise inherent to the measurements. Here we present a method to extract the underlying state sequences from experimental SM time-series. Taking into account empirical error and the finite sampling of the time-series, the method extracts a steady-state network which provides an approximation of the underlying effective free energy landscape. The core of the method is the application of rate-distortion theory from information theory, allowing the individual data points to be assigned to multiple states simultaneously. We demonstrate the method's proficiency in its application to simulated trajectories as well as to experimental SM fluorescence resonance energy transfer (FRET) trajectories obtained from isolated agonist binding domains of the AMPA receptor, an ionotropic glutamate receptor that is prevalent in the central nervous system. PMID:25779909

  7. Error-based Extraction of States and Energy Landscapes from Experimental Single-Molecule Time-Series

    NASA Astrophysics Data System (ADS)

    Taylor, J. Nicholas; Li, Chun-Biu; Cooper, David R.; Landes, Christy F.; Komatsuzaki, Tamiki

    2015-03-01

    Characterization of states, the essential components of the underlying energy landscapes, is one of the most intriguing subjects in single-molecule (SM) experiments due to the existence of noise inherent to the measurements. Here we present a method to extract the underlying state sequences from experimental SM time-series. Taking into account empirical error and the finite sampling of the time-series, the method extracts a steady-state network which provides an approximation of the underlying effective free energy landscape. The core of the method is the application of rate-distortion theory from information theory, allowing the individual data points to be assigned to multiple states simultaneously. We demonstrate the method's proficiency in its application to simulated trajectories as well as to experimental SM fluorescence resonance energy transfer (FRET) trajectories obtained from isolated agonist binding domains of the AMPA receptor, an ionotropic glutamate receptor that is prevalent in the central nervous system.

  8. Characterization of the relation between energy landscape and the time evolution of complex materials using kinetic ART

    NASA Astrophysics Data System (ADS)

    N'tsouaglo, Kokou; Joly, Jean-Francois; Beland, Laurent; Brommer, Peter; Mousseau, Normand

    2013-03-01

    In the last two decades, there has been a considerable interest in the development of accelerated numerical methods for sampling the energy landscape of complex materials. Many of these methods are based on the kinetic Monte Carlo (KMC) algorithm introduced 40 years ago. This is the case of kinetic ART, for example, which uses a very efficient transition-state searching method, ART nouveau, coupled with a topological tool, NAUTY, to offer an off-lattice KMC method with on-the-fly catalog building to study complex systems, such as ion-bombarded and amorphous materials, on timescales of a second or more. Looking at two systems, vacancy aggregation in Fe and energy relaxation in ion-bombarded c-Si, we characterize the changes in the energy landscape and the relation to its time evolution with kinetic ART and its correspondence with the well-known Bell-Evans-Polanyi principle used in chemistry.

  9. Energy-landscape paving for prediction of face-centered-cubic hydrophobic-hydrophilic lattice model proteins

    NASA Astrophysics Data System (ADS)

    Liu, Jingfa; Song, Beibei; Liu, Zhaoxia; Huang, Weibo; Sun, Yuanyuan; Liu, Wenjie

    2013-11-01

    Protein structure prediction (PSP) is a classical NP-hard problem in computational biology. The energy-landscape paving (ELP) method is a class of heuristic global optimization algorithm, and has been successfully applied to solving many optimization problems with complex energy landscapes in the continuous space. By putting forward a new update mechanism of the histogram function in ELP and incorporating the generation of initial conformation based on the greedy strategy and the neighborhood search strategy based on pull moves into ELP, an improved energy-landscape paving (ELP+) method is put forward. Twelve general benchmark instances are first tested on both two-dimensional and three-dimensional (3D) face-centered-cubic (fcc) hydrophobic-hydrophilic (HP) lattice models. The lowest energies by ELP+ are as good as or better than those of other methods in the literature for all instances. Then, five sets of larger-scale instances, denoted by S, R, F90, F180, and CASP target instances on the 3D FCC HP lattice model are tested. The proposed algorithm finds lower energies than those by the five other methods in literature. Not unexpectedly, this is particularly pronounced for the longer sequences considered. Computational results show that ELP+ is an effective method for PSP on the fcc HP lattice model.

  10. Graded activation and free energy landscapes of a muscarinic G-protein-coupled receptor.

    PubMed

    Miao, Yinglong; McCammon, J Andrew

    2016-10-25

    G-protein-coupled receptors (GPCRs) recognize ligands of widely different efficacies, from inverse to partial and full agonists, which transduce cellular signals at differentiated levels. However, the mechanism of such graded activation remains unclear. Using the Gaussian accelerated molecular dynamics (GaMD) method that enables both unconstrained enhanced sampling and free energy calculation, we have performed extensive GaMD simulations (∼19 μs in total) to investigate structural dynamics of the M2 muscarinic GPCR that is bound by the full agonist iperoxo (IXO), the partial agonist arecoline (ARC), and the inverse agonist 3-quinuclidinyl-benzilate (QNB), in the presence or absence of the G-protein mimetic nanobody. In the receptor-nanobody complex, IXO binding leads to higher fluctuations in the protein-coupling interface than ARC, especially in the receptor transmembrane helix 5 (TM5), TM6, and TM7 intracellular domains that are essential elements for GPCR activation, but less flexibility in the receptor extracellular region due to stronger binding compared with ARC. Two different binding poses are revealed for ARC in the orthosteric pocket. Removal of the nanobody leads to GPCR deactivation that is characterized by inward movement of the TM6 intracellular end. Distinct low-energy intermediate conformational states are identified for the IXO- and ARC-bound M2 receptor. Both dissociation and binding of an orthosteric ligand are observed in a single all-atom GPCR simulation in the case of partial agonist ARC binding to the M2 receptor. This study demonstrates the applicability of GaMD for exploring free energy landscapes of large biomolecules and the simulations provide important insights into the GPCR functional mechanism.

  11. Study on the Dynamics of Influenza Hemagglutinin Based on Energy Landscape Theory

    NASA Astrophysics Data System (ADS)

    Lin, Xingcheng; Eddy, Nathanial; Noel, Jeffrey; Whitford, Paul; Ma, Jianpeng; Onuchic, Jose

    2014-03-01

    Hemagglutinin (HA2), a homotrimeric influenza surface protein crucial for membrane fusion, undergoes an drastic structural rearrangement during viral invasion of the host. X-ray crystallography shows that the pre- and post-fusion configurations have largely disparate secondary, tertiary and quaternary structures. Simulations allow us to explore the time-dependent high resolution structural information and function of HA2 dynamics. Here we use an approach based on energy landscape theory that combines the native information from both the starting and end points. Our simulation shows two key events in the conformational transition of HA2: The extension of its fusion peptides away from the viral membrane and the melting of its globular C-terminal portion. The similar timescale and a kinetic competition between these two events lead to two main pathways and generic kinetic intermediates during this transition. Through considering the biological context of HA, we test perturbations of the baseline model that are useful in understanding the robustness of our predictions and how they translate into the function of HA. The all-atom explicit solvent simulation is performed and convince the cracking phenomenon at the start of this protein dynamics. Center for Theoretical Biological Physics.

  12. Protein-like folding and free energy landscape of a homopolymer chain

    NASA Astrophysics Data System (ADS)

    Taylor, Mark; Paul, Wolfgang; Binder, Kurt

    2011-03-01

    Many small proteins fold via a first-order ``all-or-none'' transition directly from an expanded coil to a compact native state. We have recently reported an analogous direct coil-to-crystallite transition for a flexible homopolymer. Wang-Landau sampling was used to construct the 1D density of states for square-well chains up to length 256 and a microcanonical analysis shows that for short-range interactions the usual polymer collapse transition is preempted by a direct freezing transition. A 2D configurational probability landscape, built via multi-canonical sampling, reveals a dominant folding pathway and an inherent configurational barrier to folding. Despite the non-unique homopolymer ground state, the thermodynamics of this direct freezing transition are identical to those of two-state protein folding. Homopolymer folding proceeds over a free energy barrier via a transition state folding nucleus, displays a protein-like Chevron plot, and satisfies the van't Hoff two-state criterion. Funding: NSF DMR-0804370, DFG SFB-625/A3.

  13. Protein-like folding and free energy landscape of a homopolymer chain

    NASA Astrophysics Data System (ADS)

    Taylor, Mark; Paul, Wolfgang; Binder, Kurt

    2011-04-01

    Many small proteins fold via a first-order "all-or-none" transition directly from an expanded coil to a compact native state. We have recently reported an analogous direct coil-to-crystallite transition for a flexible homopolymer [1]. Wang-Landau sampling was used to construct the 1D density of states for square-well chains up to length 256 and a microcanonical analysis shows that for short-range interactions the usual polymer collapse transition is preempted by a direct freezing transition. A 2D configurational probability landscape, built via multi-canonical sampling, reveals a dominant folding pathway and an inherent configurational barrier to folding. Despite the non-unique homopolymer ground state, the thermodynamics of this direct freezing transition are identical to those of two-state protein folding. Homopolymer folding proceeds over a free energy barrier via a transition state folding nucleus, displays a protein-like Chevron plot, and satisfies the van't Hoff two-state criterion.[4pt] [1] Phys. Rev. E 79, 050801(R) (2009); J. Chem. Phys. 131, 114907 (2009).

  14. Laser probes of the potential energy landscapes and conformational isomerization dynamics of flexible biomolecules

    NASA Astrophysics Data System (ADS)

    Dian, Brian; Clarkson, Jasper; Zwier, Timothy

    2003-03-01

    Using a combination of 2-color resonant two-photon ionization (R2PI), laser-induced fluorescence excitation (LIF), resonant ion-dip infrared spectroscopy (RIDIRS), fluorescence-dip infrared spectroscopy (FDIRS), and UV-UV hole-burning spectroscopy, the conformational preferences of a series of flexible biomolecules, including melatonin, N-acetyl-tryptophan methyl amide (NATMA), and their close analogs, have been determined in a molecular beam. These molecules are sufficiently complex to have hundreds of conformational minima, yet small enough that their potential energy landscapes can be explored in some detail. Once the conformational preferences of the molecules are established, these molecules are then studied using infrared-ultraviolet hole-filling and IR-induced population transfer spectroscopy. These methods utilize selective infrared excitation of single conformations of the molecule in the early portions of a gas-phase expansion, followed by collisional re-cooling of the excited population into its conformational minima for subsequent conformation-specific detection. Efficient isomerization is induced by the infrared excitation that redistributes population between the same conformations that have population in the absence of infrared excitation. Examples will be given in which the quantum yields for transfer of the population into the various conformational minima depend both on which conformation is excited and on which hydride stretch vibration is excited within a given conformation; that is, they are both conformation-selective and mode-selective.

  15. Direct Observation of Folding Energy Landscape of RNA Hairpin at Mechanical Loading Rates.

    PubMed

    Xu, Huizhong; Plaut, Benjamin; Zhu, Xiran; Chen, Maverick; Mavinkurve, Udit; Maiti, Anindita; Song, Guangtao; Murari, Krishna; Mandal, Maumita

    2017-03-16

    By applying a controlled mechanical load using optical tweezers, we measured the diffusive barrier crossing in a 49 nt long P5ab RNA hairpin. We find that in the free-energy landscape the barrier height (G(‡)) and transition distance (x(‡)) are dependent on the loading rate (r) along the pulling direction, x, as predicted by Bell. The barrier shifted toward the initial state, whereas ΔG(‡) reduced significantly from 50 to 5 kT, as r increased from 0 to 32 pN/s. However, the equilibrium work (ΔG) during strand separation, as estimated by Crook's fluctuation theorem, remained unchanged at different rates. Previously, helix formation and denaturation have been described as two-state (F ↔ U) transitions for P5ab. Herein, we report three intermediate states I1, I, and I2 located at 4, 11, and 16 nm respectively, from the folded conformation. The intermediates were observed only when the hairpin was subjected to an optimal r, 7.6 pN/s. The results indicate that the complementary strands in P5ab can zip and unzip through complex routes, whereby mismatches act as checkpoints and often impose barriers. The study highlights the significance of loading rates in force-spectroscopy experiments that are increasingly being used to measure the folding properties of biomolecules.

  16. pH-responsive self-assembly of polysaccharide through a rugged energy landscape

    PubMed Central

    Morrow, Brian H.; Payne, Gregory F.

    2015-01-01

    Self-assembling polysaccharides can form complex networks with structures and properties highly dependent on the sequence of triggering cues. Controlling the emergence of such networks provides an opportunity to create soft matter with unique features; however, it requires a detailed understanding of the subtle balance between the attractive and repulsive forces that drives the stimuli-induced self-assembly. Here we employ all-atom molecular dynamics simulations on the order of 100 ns to study the mechanisms of the pH-responsive gelation of the weakly basic aminopolysaccharide chitosan. We find that low pH induces a sharp transition from gel to soluble state, analogous to pH-dependent folding of proteins, while at neutral and high pH self-assembly occurs via a rugged energy landscape, reminiscent of RNA folding. A surprising role of salt is to lubricate conformational search for the thermodynamically stable states. Although our simulations represent the early events in the self-assembly process of chitosan, which may take seconds or minutes to complete, the atomically-detailed insights are consistent with recent experimental observations and provide a basis for understanding how environmental conditions modulate the structure and mechanical properties of the self-assembled polysaccharide systems. The ability to control structure and properties via modification of process conditions will aid in the technological efforts to create complex soft matter with applications ranging from bioelectronics to regenerative medicine. PMID:26383701

  17. Energy landscape of self-assembled superlattices of PbSe nanocrystals.

    PubMed

    Quan, Zewei; Wu, Di; Zhu, Jinlong; Evers, Wiel H; Boncella, James M; Siebbeles, Laurens D A; Wang, Zhongwu; Navrotsky, Alexandra; Xu, Hongwu

    2014-06-24

    Self-assembly of nanocrystals (NCs) into superlattices is an intriguing multiscale phenomenon that may lead to materials with novel collective properties, in addition to the unique properties of individual NCs compared with their bulk counterparts. By using different dispersion solvents, we synthesized three types of PbSe NC superlattices--body-centered cubic (bcc), body-centered tetragonal (bct), and face-centered cubic (fcc)--as confirmed by synchrotron small-angle X-ray scattering. Solution calorimetric measurements in hexane show that the enthalpy of formation of the superlattice from dispersed NCs is on the order of -2 kJ/mol. The calorimetric measurements reveal that the bcc superlattice is the energetically most stable polymorph, with the bct being 0.32 and the fcc 0.55 kJ/mol higher in enthalpy. This stability sequence is consistent with the decreased packing efficiency of PbSe NCs from bcc (17.2%) to bct (16.0%) and to fcc (15.2%). The small enthalpy differences among the three polymorphs confirm a closely spaced energy landscape and explain the ease of formation of different NC superlattices at slightly different synthesis conditions.

  18. Efficient dielectrophoretic patterning of embryonic stem cells in energy landscapes defined by hydrogel geometries.

    PubMed

    Tsutsui, Hideaki; Yu, Edmond; Marquina, Sabrina; Valamehr, Bahram; Wong, Ieong; Wu, Hong; Ho, Chih-Ming

    2010-12-01

    In this study, we have developed an integrated microfluidic platform for actively patterning mammalian cells, where poly(ethylene glycol) (PEG) hydrogels play two important roles as a non-fouling layer and a dielectric structure. The developed system has an embedded array of PEG microwells fabricated on a planar indium tin oxide (ITO) electrode. Due to its dielectric properties, the PEG microwells define electrical energy landscapes, effectively forming positive dielectrophoresis (DEP) traps in a low-conductivity environment. Distribution of DEP forces on a model cell was first estimated by computationally solving quasi-electrostatic Maxwell's equations, followed by an experimental demonstration of cell and particle patterning without an external flow. Furthermore, efficient patterning of mouse embryonic stem (mES) cells was successfully achieved in combination with an external flow. With a seeding density of 10⁷ cells/mL and a flow rate of 3 μL/min, trapping of cells in the microwells was completed in tens of seconds after initiation of the DEP operation. Captured cells subsequently formed viable and homogeneous monolayer patterns. This simple approach could provide an efficient strategy for fabricating various cell microarrays for applications such as cell-based biosensors, drug discovery, and cell microenvironment studies.

  19. Free energy landscape of the Michaelis complex of lactate dehydrogenase: A network analysis of atomistic simulations

    NASA Astrophysics Data System (ADS)

    Pan, Xiaoliang; Schwartz, Steven

    2015-03-01

    It has long been recognized that the structure of a protein is a hierarchy of conformations interconverting on multiple time scales. However, the conformational heterogeneity is rarely considered in the context of enzymatic catalysis in which the reactant is usually represented by a single conformation of the enzyme/substrate complex. Lactate dehydrogenase (LDH) catalyzes the interconversion of pyruvate and lactate with concomitant interconversion of two forms of the cofactor nicotinamide adenine dinucleotide (NADH and NAD+). Recent experimental results suggest that multiple substates exist within the Michaelis complex of LDH, and they are catalytic competent at different reaction rates. In this study, millisecond-scale all-atom molecular dynamics simulations were performed on LDH to explore the free energy landscape of the Michaelis complex, and network analysis was used to characterize the distribution of the conformations. Our results provide a detailed view of the kinetic network the Michaelis complex and the structures of the substates at atomistic scale. It also shed some light on understanding the complete picture of the catalytic mechanism of LDH.

  20. Exploration of the Energy Landscape of Acetylcholinesterase by Molecular Dynamics Simulation.

    NASA Astrophysics Data System (ADS)

    McCammon, J. Andrew

    2002-03-01

    Proteins have rough energy landscapes. Often more states than just the ground state are occupied and have biological functions. It is essential to study these conformational substates and the dynamical transitions among them. Acetylcholinesterase (AChE) is an important enzyme that has biological functions including the termination of synaptic transmission signals. X-ray structures show that it has an active site that is accessible only via a long and narrow channel from its surface. Therefore the fact that acetylcholine and larger ligands can reach the active site is believed to reflect the protein's structural fluctuation. We carried out long molecular dynamics simulations to investigate the dynamics of AChE and its relation to biological function, and compared our results with experiments. The results reveal several "doors" that open intermittantly between the active site and the surface. Instead of having simple exponential decay correlation functions, the time series of these channels reveal complex, fractal gating between conformations. We also compared the AChE dynamics data with those from an AchE-fasciculin complex. (Fasciculin is a small protein that is a natural inhibitor of AChE.) The results show remarkable effects of the protein-protein interaction, including allosteric and dynamical inhibition by fasciculin besides direct steric blocking. More information and images can be found at http://mccammon.ucsd.edu

  1. Hiking down the energy landscape: progress toward the Kauzmann temperature via vapor deposition.

    PubMed

    Kearns, Kenneth L; Swallen, Stephen F; Ediger, M D; Wu, Tian; Sun, Ye; Yu, Lian

    2008-04-24

    Physical vapor deposition was employed to prepare amorphous samples of indomethacin and 1,3,5-(tris)naphthylbenzene. By depositing onto substrates held somewhat below the glass transition temperature and varying the deposition rate from 15 to 0.2 nm/s, glasses with low enthalpies and exceptional kinetic stability were prepared. Glasses with fictive temperatures that are as much as 40 K lower than those prepared by cooling the liquid can be made by vapor deposition. As compared to an ordinary glass, the most stable vapor-deposited samples moved about 40% toward the bottom of the potential energy landscape for amorphous materials. These results support the hypothesis that enhanced surface mobility allows stable glass formation by vapor deposition. A comparison of the enthalpy content of vapor-deposited glasses with aged glasses was used to evaluate the difference between bulk and surface dynamics for indomethacin; the dynamics in the top few nanometers of the glass are about 7 orders of magnitude faster than those in the bulk at Tg - 20 K.

  2. Energy landscape of self-assembled superlattices of PbSe nanocrystals

    PubMed Central

    Quan, Zewei; Wu, Di; Zhu, Jinlong; Evers, Wiel H.; Boncella, James M.; Siebbeles, Laurens D. A.; Wang, Zhongwu; Navrotsky, Alexandra; Xu, Hongwu

    2014-01-01

    Self-assembly of nanocrystals (NCs) into superlattices is an intriguing multiscale phenomenon that may lead to materials with novel collective properties, in addition to the unique properties of individual NCs compared with their bulk counterparts. By using different dispersion solvents, we synthesized three types of PbSe NC superlattices—body-centered cubic (bcc), body-centered tetragonal (bct), and face-centered cubic (fcc)—as confirmed by synchrotron small-angle X-ray scattering. Solution calorimetric measurements in hexane show that the enthalpy of formation of the superlattice from dispersed NCs is on the order of −2 kJ/mol. The calorimetric measurements reveal that the bcc superlattice is the energetically most stable polymorph, with the bct being 0.32 and the fcc 0.55 kJ/mol higher in enthalpy. This stability sequence is consistent with the decreased packing efficiency of PbSe NCs from bcc (17.2%) to bct (16.0%) and to fcc (15.2%). The small enthalpy differences among the three polymorphs confirm a closely spaced energy landscape and explain the ease of formation of different NC superlattices at slightly different synthesis conditions. PMID:24927573

  3. The nature of the sunspot phenomenon. III - Energy consumption and energy transport. IV - The intrinsic instability of the magnetic configuration

    NASA Technical Reports Server (NTRS)

    Parker, E. N.

    1975-01-01

    The basic relation is described between conversion of thermal energy into convective fluid motion and convective transport of thermal energy, and the equilibrium configuration of a sunspot's magnetic field is shown to be unstable to the hydromagnetic exchange instability. It is determined that heat transport necessarily accompanies convective driving of fluid motion and that the formation of cool sunspots requires convection extending coherently over several scale heights, a distance of at least 500 km. Several theoretical possibilities for sunspot stabilization are reviewed, and it is suggested that a suitable redistribution of cooling in the umbra may be the stabilization mechanism. It is believed that if cooling extends to a great depth in an elongated portion of a sunspot, the magnetic pressure on the boundary will be reduced, tending to reduce the elongation.

  4. Disparate HDV ribozyme crystal structures represent intermediates on a rugged free-energy landscape.

    PubMed

    Sripathi, Kamali N; Tay, Wendy W; Banáš, Pavel; Otyepka, Michal; Šponer, Jiří; Walter, Nils G

    2014-07-01

    The hepatitis delta virus (HDV) ribozyme is a member of the class of small, self-cleaving catalytic RNAs found in a wide range of genomes from HDV to human. Both pre- and post-catalysis (precursor and product) crystal structures of the cis-acting genomic HDV ribozyme have been determined. These structures, together with extensive solution probing, have suggested that a significant conformational change accompanies catalysis. A recent crystal structure of a trans-acting precursor, obtained at low pH and by molecular replacement from the previous product conformation, conforms to the product, raising the possibility that it represents an activated conformer past the conformational change. Here, using fluorescence resonance energy transfer (FRET), we discovered that cleavage of this ribozyme at physiological pH is accompanied by a structural lengthening in magnitude comparable to previous trans-acting HDV ribozymes. Conformational heterogeneity observed by FRET in solution appears to have been removed upon crystallization. Analysis of a total of 1.8 µsec of molecular dynamics (MD) simulations showed that the crystallographically unresolved cleavage site conformation is likely correctly modeled after the hammerhead ribozyme, but that crystal contacts and the removal of several 2'-oxygens near the scissile phosphate compromise catalytic in-line fitness. A cis-acting version of the ribozyme exhibits a more dynamic active site, while a G-1 residue upstream of the scissile phosphate favors poor fitness, allowing us to rationalize corresponding changes in catalytic activity. Based on these data, we propose that the available crystal structures of the HDV ribozyme represent intermediates on an overall rugged RNA folding free-energy landscape.

  5. Disparate HDV ribozyme crystal structures represent intermediates on a rugged free-energy landscape

    PubMed Central

    Sripathi, Kamali N.; Tay, Wendy W.; Banáš, Pavel; Otyepka, Michal; Šponer, Jiří; Walter, Nils G.

    2014-01-01

    The hepatitis delta virus (HDV) ribozyme is a member of the class of small, self-cleaving catalytic RNAs found in a wide range of genomes from HDV to human. Both pre- and post-catalysis (precursor and product) crystal structures of the cis-acting genomic HDV ribozyme have been determined. These structures, together with extensive solution probing, have suggested that a significant conformational change accompanies catalysis. A recent crystal structure of a trans-acting precursor, obtained at low pH and by molecular replacement from the previous product conformation, conforms to the product, raising the possibility that it represents an activated conformer past the conformational change. Here, using fluorescence resonance energy transfer (FRET), we discovered that cleavage of this ribozyme at physiological pH is accompanied by a structural lengthening in magnitude comparable to previous trans-acting HDV ribozymes. Conformational heterogeneity observed by FRET in solution appears to have been removed upon crystallization. Analysis of a total of 1.8 µsec of molecular dynamics (MD) simulations showed that the crystallographically unresolved cleavage site conformation is likely correctly modeled after the hammerhead ribozyme, but that crystal contacts and the removal of several 2′-oxygens near the scissile phosphate compromise catalytic in-line fitness. A cis-acting version of the ribozyme exhibits a more dynamic active site, while a G-1 residue upstream of the scissile phosphate favors poor fitness, allowing us to rationalize corresponding changes in catalytic activity. Based on these data, we propose that the available crystal structures of the HDV ribozyme represent intermediates on an overall rugged RNA folding free-energy landscape. PMID:24854621

  6. Fast recovery of free energy landscapes via diffusion-map-directed molecular dynamics.

    PubMed

    Preto, Jordane; Clementi, Cecilia

    2014-09-28

    The reaction pathways characterizing macromolecular systems of biological interest are associated with high free energy barriers. Resorting to the standard all-atom molecular dynamics (MD) to explore such critical regions may be inappropriate as the time needed to observe the relevant transitions can be remarkably long. In this paper, we present a new method called Extended Diffusion-Map-directed Molecular Dynamics (extended DM-d-MD) used to enhance the sampling of MD trajectories in such a way as to rapidly cover all important regions of the free energy landscape including deep metastable states and critical transition paths. Moreover, extended DM-d-MD was combined with a reweighting scheme enabling to save on-the-fly information about the Boltzmann distribution. Our algorithm was successfully applied to two systems, alanine dipeptide and alanine-12. Due to the enhanced sampling, the Boltzmann distribution is recovered much faster than in plain MD simulations. For alanine dipeptide, we report a speedup of one order of magnitude with respect to plain MD simulations. For alanine-12, our algorithm allows us to highlight all important unfolded basins in several days of computation when one single misfolded event is barely observable within the same amount of computational time by plain MD simulations. Our method is reaction coordinate free, shows little dependence on the a priori knowledge of the system, and can be implemented in such a way that the biased steps are not computationally expensive with respect to MD simulations thus making our approach well adapted for larger complex systems from which little information is known.

  7. Kinetic control over pathway complexity in supramolecular polymerization through modulating the energy landscape by rational molecular design.

    PubMed

    Ogi, Soichiro; Fukui, Tomoya; Jue, Melinda L; Takeuchi, Masayuki; Sugiyasu, Kazunori

    2014-12-22

    Far-from-equilibrium thermodynamic systems that are established as a consequence of coupled equilibria are the origin of the complex behavior of biological systems. Therefore, research in supramolecular chemistry has recently been shifting emphasis from a thermodynamic standpoint to a kinetic one; however, control over the complex kinetic processes is still in its infancy. Herein, we report our attempt to control the time evolution of supramolecular assembly in a process in which the supramolecular assembly transforms from a J-aggregate to an H-aggregate over time. The transformation proceeds through a delicate interplay of these two aggregation pathways. We have succeeded in modulating the energy landscape of the respective aggregates by a rational molecular design. On the basis of this understanding of the energy landscape, programming of the time evolution was achieved through adjusting the balance between the coupled equilibria.

  8. Efficient Determination of Free Energy Landscapes in Multiple Dimensions from Biased Umbrella Sampling Simulations Using Linear Regression

    PubMed Central

    2015-01-01

    The weighted histogram analysis method (WHAM) is a standard protocol for postprocessing the information from biased umbrella sampling simulations to construct the potential of mean force with respect to a set of order parameters. By virtue of the WHAM equations, the unbiased density of state is determined by satisfying a self-consistent condition through an iterative procedure. While the method works very effectively when the number of order parameters is small, its computational cost grows rapidly in higher dimension. Here, we present a simple and efficient alternative strategy, which avoids solving the self-consistent WHAM equations iteratively. An efficient multivariate linear regression framework is utilized to link the biased probability densities of individual umbrella windows and yield an unbiased global free energy landscape in the space of order parameters. It is demonstrated with practical examples that free energy landscapes that are comparable in accuracy to WHAM can be generated at a small fraction of the cost. PMID:26574437

  9. Enhanced, targeted sampling of high-dimensional free-energy landscapes using variationally enhanced sampling, with an application to chignolin

    PubMed Central

    Shaffer, Patrick; Valsson, Omar; Parrinello, Michele

    2016-01-01

    The capabilities of molecular simulations have been greatly extended by a number of widely used enhanced sampling methods that facilitate escaping from metastable states and crossing large barriers. Despite these developments there are still many problems which remain out of reach for these methods which has led to a vigorous effort in this area. One of the most important problems that remains unsolved is sampling high-dimensional free-energy landscapes and systems that are not easily described by a small number of collective variables. In this work we demonstrate a new way to compute free-energy landscapes of high dimensionality based on the previously introduced variationally enhanced sampling, and we apply it to the miniprotein chignolin. PMID:26787868

  10. Efficient Determination of Free Energy Landscapes in Multiple Dimensions from Biased Umbrella Sampling Simulations Using Linear Regression.

    PubMed

    Meng, Yilin; Roux, Benoît

    2015-08-11

    The weighted histogram analysis method (WHAM) is a standard protocol for postprocessing the information from biased umbrella sampling simulations to construct the potential of mean force with respect to a set of order parameters. By virtue of the WHAM equations, the unbiased density of state is determined by satisfying a self-consistent condition through an iterative procedure. While the method works very effectively when the number of order parameters is small, its computational cost grows rapidly in higher dimension. Here, we present a simple and efficient alternative strategy, which avoids solving the self-consistent WHAM equations iteratively. An efficient multivariate linear regression framework is utilized to link the biased probability densities of individual umbrella windows and yield an unbiased global free energy landscape in the space of order parameters. It is demonstrated with practical examples that free energy landscapes that are comparable in accuracy to WHAM can be generated at a small fraction of the cost.

  11. Climatic effects of 30 years of landscape change over the Greater Phoenix, Arizona, region: 1. Surface energy budget changes

    USGS Publications Warehouse

    Georgescu, M.; Miguez-Macho, G.; Steyaert, L.T.; Weaver, C.P.

    2009-01-01

    This paper is part 1 of a two-part study that evaluates the climatic effects of recent landscape change for one of the nation's most rapidly expanding metropolitan complexes, the Greater Phoenix, Arizona, region. The region's landscape evolution over an approximate 30-year period since the early 1970s is documented on the basis of analyses of Landsat images and land use/land cover (LULC) data sets derived from aerial photography (1973) and Landsat (1992 and 2001). High-resolution, Regional Atmospheric Modeling System (RAMS), simulations (2-km grid spacing) are used in conjunction with consistently defined land cover data sets and associated biophysical parameters for the circa 1973, circa 1992, and circa 2001 time periods to quantify the impacts of intensive land use changes on the July surface temperatures and the surface radiation and energy budgets for the Greater Phoenix region. The main findings are as follows: since the early 1970s the region's landscape has been altered by a significant increase in urban/suburban land area, primarily at the expense of decreasing plots of irrigated agriculture and secondarily by the conversion of seminatural shrubland. Mean regional temperatures for the circa 2001 landscape were 0.12??C warmer than the circa 1973 landscape, with maximum temperature differences, located over regions of greatest urbanization, in excess of 1??C. The significant reduction in irrigated agriculture, for the circa 2001 relative to the circa 1973 landscape, resulted in dew point temperature decreases in excess of 1??C. The effect of distinct land use conversion themes (e.g., conversion from irrigated agriculture to urban land) was also examined to evaluate how the most important conversion themes have each contributed to the region's changing climate. The two urbanization themes studied (from an initial landscape of irrigated agriculture and seminatural shrubland) have the greatest positive effect on near-surface temperature, increasing maximum daily

  12. Energy landscape, structure and rate effects on strength properties of alpha-helical proteins

    NASA Astrophysics Data System (ADS)

    Bertaud, Jérémie; Hester, Joshua; Jimenez, Daniel D.; Buehler, Markus J.

    2010-01-01

    The strength of protein domains is crucial to identify the mechanical role of protein domains in biological processes such as mechanotransduction, tissue mechanics and tissue remodeling. Whereas the concept of strength has been widely investigated for engineered materials, the strength of fundamental protein material building blocks and how it depends on structural parameters such as the chemical bonding, the protein filament length and the timescale of observation or deformation velocity remains poorly understood. Here we report a systematic analysis of the influence of key parameters that define the energy landscape of the strength properties of alpha-helical protein domains, including energy barriers, unfolding and refolding distances, the locations of folded and unfolded states, as well as variations of the length and pulling velocity of alpha-helical protein filaments. The analysis is facilitated by the development of a double-well mesoscale potential formulation, utilized here to carry out a systematic numerical analysis of the behavior of alpha-helices. We compare the results against widely used protein strength models based on the Bell model, one of the simplest models used to characterize the strength of protein filaments. We find that, whereas Bell-type models are a reasonable approximation to describe the rupture of alpha-helical protein domains for a certain range of pulling speeds and values of energy barriers, the model ceases to hold for very large energy barriers and for very small pulling speeds, in agreement with earlier findings. We conclude with an application of our mesoscale model to investigate the effect of the length of alpha-helices on their mechanical strength. We find a weakening effect as the length of alpha-helical proteins increases, followed by an asymptotic regime in which the strength remains constant. We compare strand lengths found in biological proteins with the scaling law of strength versus alpha-helix filament length. The

  13. Energy landscape, structure and rate effects on strength properties of alpha-helical proteins.

    PubMed

    Bertaud, Jérémie; Hester, Joshua; Jimenez, Daniel D; Buehler, Markus J

    2010-01-27

    The strength of protein domains is crucial to identify the mechanical role of protein domains in biological processes such as mechanotransduction, tissue mechanics and tissue remodeling. Whereas the concept of strength has been widely investigated for engineered materials, the strength of fundamental protein material building blocks and how it depends on structural parameters such as the chemical bonding, the protein filament length and the timescale of observation or deformation velocity remains poorly understood. Here we report a systematic analysis of the influence of key parameters that define the energy landscape of the strength properties of alpha-helical protein domains, including energy barriers, unfolding and refolding distances, the locations of folded and unfolded states, as well as variations of the length and pulling velocity of alpha-helical protein filaments. The analysis is facilitated by the development of a double-well mesoscale potential formulation, utilized here to carry out a systematic numerical analysis of the behavior of alpha-helices. We compare the results against widely used protein strength models based on the Bell model, one of the simplest models used to characterize the strength of protein filaments. We find that, whereas Bell-type models are a reasonable approximation to describe the rupture of alpha-helical protein domains for a certain range of pulling speeds and values of energy barriers, the model ceases to hold for very large energy barriers and for very small pulling speeds, in agreement with earlier findings. We conclude with an application of our mesoscale model to investigate the effect of the length of alpha-helices on their mechanical strength. We find a weakening effect as the length of alpha-helical proteins increases, followed by an asymptotic regime in which the strength remains constant. We compare strand lengths found in biological proteins with the scaling law of strength versus alpha-helix filament length. The

  14. Frustration-induced protein intrinsic disorder

    NASA Astrophysics Data System (ADS)

    Matsushita, Katsuyoshi; Kikuchi, Macoto

    2013-03-01

    Spontaneous folding into a specific native structure is the most important property of protein to perform their biological functions within organisms. Spontaneous folding is understood on the basis of an energy landscape picture based on the minimum frustration principle. Therefore, frustration seemingly only leads to protein functional disorder. However, frustration has recently been suggested to have a function in allosteric regulation. Functional frustration has the possibility to be a key to our deeper understanding of protein function. To explore another functional frustration, we theoretically examined structural frustration, which is designed to induce intrinsic disorder of a protein and its function through the coupled folding and binding. We extended the Wako-Saitô-Muñoz-Eaton model to take into account a frustration effect. With the model, we analyzed the binding part of neuron-restrictive silencer factor and showed that designed structural frustration in it induces intrinsic disorder. Furthermore, we showed that the folding and the binding are cooperative in interacting with a target protein. The cooperativity enables an intrinsically disordered protein to exhibit a sharp switch-like folding response to binding chemical potential change. Through this switch-like response, the structural frustration may contribute to the regulation function of interprotein interaction of the intrinsically disordered protein.

  15. Displacement Threshold Energy and Recovery in an Al-Ti Nanolayered System with Intrinsic Point Defect Partitioning

    SciTech Connect

    Gerboth, Matthew D.; Setyawan, Wahyu; Henager, Charles H.

    2014-01-07

    A method is established and validated using molecular dynamics (MD) to determine the displacement threshold energies as Ed in nanolayered, multilayered systems of dissimilar metals. The method is applied to specifically oriented nanolayered films of Al-Ti where the crystal structure and interface orientations are varied in atomic models and Ed is calculated. Methods for defect detection are developed and discussed based on prior research in the literature and based on specific crystallographic directions available in the nanolayered systems. These are compared and contrasted to similar calculations in corresponding bulk materials, including fcc Al, fcc Ti, hcp Al, and hcp Ti. In all cases, the calculated Ed in the multilayers are intermediate to the corresponding bulk values but exhibit some important directionality. In the nanolayer, defect detection demonstrated systematic differences in the behavior of Ed in each layer. Importantly, collision cascade damage exhibits significant defect partitioning within the Al and Ti layers that is hypothesized to be an intrinsic property of dissimilar nanolayered systems. This type of partitioning could be partly responsible for observed asymmetric radiation damage responses in many multilayered systems. In addition, a pseudo-random direction was introduced to approximate the average Ed without performing numerous simulations with random directions.

  16. The extinction law in the open cluster NGC 457 and the intrinsic energy distribution of Phi Cassiopeiae (F0 Ia)

    NASA Technical Reports Server (NTRS)

    Rosenzweig, P.; Morrison, N. D.

    1986-01-01

    Five early B-type stars near the main-sequence turnoff in NGC 457 have been observed at low dispersion with the short-wavelength prime and the long-wavelength redundant cameras of the IUE satellite. The equivalent widths of spectral features that are particularly strong and sensitive to temperature and luminosity were computed in the cluster stars and in 20 lightly reddened stars of types O9-B3 and luminosity classes III-V. The comparison of the equivalent widths provides a reliable method for finding matching pairs. Having identified the best comparison star for each program star, binned fluxes were used to determine the mean extinction curve. In order to cover the visible region, monochromatic fluxes of Phi Cas were derived from observations with the intensified Reticon scanner mounted on the No. 2 0.9 m telescope of KPNO, and they were dereddened with the mean extinction curve of Savage and Mathis. Thus, the intrinsic energy distribution of Phi Cas were determined from 1500 to 5800 A for use in a detailed model-atmosphere analysis.

  17. DNA Free Energy Landscapes and RNA Nano-Self-Assembly Using Atomic Force Microscopy

    NASA Astrophysics Data System (ADS)

    Frey, Eric William

    There is an important conceptual lesson which has long been appreciated by those who work in biophysics and related interdisciplinary fields. While the extraordinary behavior of biological matter is governed by its detailed atomic structure and random fluctuations, and is therefore difficult to predict, it can nevertheless be understood within simplified frameworks. Such frameworks model the system as consisting of only one or a few components, and model the behavior of the system as the occupation of a single state out of a small number of states available. The emerging widespread application of nanotechnology, such as atomic force microscopy (AFM), has expanded this understanding in eye-opening new levels of detail by enabling nano-scale control, measurement, and visualization of biological molecules. This thesis describes two independent projects, both of which illuminate this understanding using AFM, but which do so from very different perspectives. The organization of this thesis is as follows. Chapter 1 begins with an experimental background and introduction to AFM, and then describes our setup in both single-molecule manipulation and imaging modes. In Chapter 2, we describe the first project, the motivation for which is to extend methods for the experimental determination of the free energy landscape of a molecule. This chapter relies on the analysis of single-molecule manipulation data. Chapter 3 describes the second project, the motivation for which is to create RNA-based nano-structures suitable for future applications in living mammalian cells. This chapter relies mainly on imaging. Chapters 2 and 3 can thus be read and understood separately.

  18. The Effect of Tensile Stress on the Conformational Free Energy Landscape of Disulfide Bonds

    PubMed Central

    Anjukandi, Padmesh; Dopieralski, Przemyslaw; Ribas–Arino, Jordi; Marx, Dominik

    2014-01-01

    Disulfide bridges are no longer considered to merely stabilize protein structure, but are increasingly recognized to play a functional role in many regulatory biomolecular processes. Recent studies have uncovered that the redox activity of native disulfides depends on their C–C–S–S dihedrals, and . Moreover, the interplay of chemical reactivity and mechanical stress of disulfide switches has been recently elucidated using force–clamp spectroscopy and computer simulation. The and angles have been found to change from conformations that are open to nucleophilic attack to sterically hindered, so–called closed states upon exerting tensile stress. In view of the growing evidence of the importance of C–C–S–S dihedrals in tuning the reactivity of disulfides, here we present a systematic study of the conformational diversity of disulfides as a function of tensile stress. With the help of force-clamp metadynamics simulations, we show that tensile stress brings about a large stabilization of the closed conformers, thereby giving rise to drastic changes in the conformational free energy landscape of disulfides. Statistical analysis shows that native TDi, DO and interchain Ig protein disulfides prefer open conformations, whereas the intrachain disulfide bridges in Ig proteins favor closed conformations. Correlating mechanical stress with the distance between the two –carbons of the disulfide moiety reveals that the strain of intrachain Ig protein disulfides corresponds to a mechanical activation of about 100 pN. Such mechanical activation leads to a severalfold increase of the rate of the elementary redox reaction step. All these findings constitute a step forward towards achieving a full understanding of functional disulfides. PMID:25286308

  19. The Activation of c-Src Tyrosine Kinase: Conformational Transition Pathway and Free Energy Landscape.

    PubMed

    Fajer, Mikolai; Meng, Yilin; Roux, Benoît

    2016-10-28

    Tyrosine kinases are important cellular signaling allosteric enzymes that regulate cell growth, proliferation, metabolism, differentiation, and migration. Their activity must be tightly controlled, and malfunction can lead to a variety of diseases, particularly cancer. The nonreceptor tyrosine kinase c-Src, a prototypical model system and a representative member of the Src-family, functions as complex multidomain allosteric molecular switches comprising SH2 and SH3 domains modulating the activity of the catalytic domain. The broad picture of self-inhibition of c-Src via the SH2 and SH3 regulatory domains is well characterized from a structural point of view, but a detailed molecular mechanism understanding is nonetheless still lacking. Here, we use advanced computational methods based on all-atom molecular dynamics simulations with explicit solvent to advance our understanding of kinase activation. To elucidate the mechanism of regulation and self-inhibition, we have computed the pathway and the free energy landscapes for the "inactive-to-active" conformational transition of c-Src for different configurations of the SH2 and SH3 domains. Using the isolated c-Src catalytic domain as a baseline for comparison, it is observed that the SH2 and SH3 domains, depending upon their bound orientation, promote either the inactive or active state of the catalytic domain. The regulatory structural information from the SH2-SH3 tandem is allosterically transmitted via the N-terminal linker of the catalytic domain. Analysis of the conformational transition pathways also illustrates the importance of the conserved tryptophan 260 in activating c-Src, and reveals a series of concerted events during the activation process.

  20. Energy landscapes: Coal canals, oil pipelines, and electricity transmission wires in the mid-Atlantic, 1820--1930

    NASA Astrophysics Data System (ADS)

    Jones, Christopher F.

    2009-12-01

    Coal canals, oil pipelines, and electricity transmission wires transformed the built environment of the American mid-Atlantic region between 1820 and 1930. By transporting coal, oil, and electrons cheaply, reliably, and in great quantities, these technologies reshaped the energy choices available to mid-Atlantic residents. In particular, canals, pipelines, and wires created new energy landscapes: systems of transport infrastructure that enabled the ever-increasing consumption of fossil fuels. Energy Landscapes integrates history of technology, environmental history, and business history to provide new perspectives on how Americans began to use fossil fuels and the social implications of these practices. First, I argue that the development of transport infrastructure played critical, and underappreciated, roles in shaping social energy choices. Rather than simply responding passively to the needs of producers and consumers, canals, pipelines, and wires structured how, when, where, and in what quantities energy was used. Second, I analyze the ways fossil fuel consumption transformed the society, economy, and environment of the mid-Atlantic. I link the consumption of coal, oil, and electricity to the development of an urban and industrialized region, the transition from an organic to a mineral economy, and the creation of a society dependent on fossil fuel energy.

  1. Chlorobaculum tepidum Modulates Amino Acid Composition in Response to Energy Availability, as Revealed by a Systematic Exploration of the Energy Landscape of Phototrophic Sulfur Oxidation.

    PubMed

    Levy, Amalie T; Lee, Kelvin H; Hanson, Thomas E

    2016-11-01

    Microbial sulfur metabolism, particularly the formation and consumption of insoluble elemental sulfur (S(0)), is an important biogeochemical engine that has been harnessed for applications ranging from bioleaching and biomining to remediation of waste streams. Chlorobaculum tepidum, a low-light-adapted photoautolithotrophic sulfur-oxidizing bacterium, oxidizes multiple sulfur species and displays a preference for more reduced electron donors: sulfide > S(0) > thiosulfate. To understand this preference in the context of light energy availability, an "energy landscape" of phototrophic sulfur oxidation was constructed by varying electron donor identity, light flux, and culture duration. Biomass and cellular parameters of C. tepidum cultures grown across this landscape were analyzed. From these data, a correction factor for colorimetric protein assays was developed, enabling more accurate biomass measurements for C. tepidum, as well as other organisms. C. tepidum's bulk amino acid composition correlated with energy landscape parameters, including a tendency toward less energetically expensive amino acids under reduced light flux. This correlation, paired with an observation of increased cell size and storage carbon production under electron-rich growth conditions, suggests that C. tepidum has evolved to cope with changing energy availability by tuning its proteome for energetic efficiency and storing compounds for leaner times.

  2. Ab initio modeling of the two-dimensional energy landscape of screw dislocations in bcc transition metals

    NASA Astrophysics Data System (ADS)

    Dezerald, L.; Ventelon, Lisa; Clouet, E.; Denoual, C.; Rodney, D.; Willaime, F.

    2014-01-01

    A density functional theory (DFT) study of the 1/2<111> screw dislocation was performed in the following body-centered cubic transition metals: V, Nb, Ta, Cr, Mo, W, and Fe. The energies of the easy, hard, and split core configurations, as well as the pathways between them, were investigated and used to generate the two-dimensional (2D) Peierls potential, i.e. the energy landscape seen by the dislocation as a function of its position in the (111) plane. In all investigated elements, the nondegenerate easy core is the minimum energy configuration, while the split core configuration, centered in the immediate vicinity of a <111> atomic column, has a high energy near or above that of the hard core. This unexpected result yields 2D Peierls potentials very different from the usually assumed landscapes. The 2D Peierls potential in Fe differs from the other transition metals, with a monkey saddle instead of a local maximum located at the hard core. An estimation of the Peierls stress from the shape of the Peierls barrier is presented in all investigated metals. A strong group dependence of the core energy is also evidenced, related to the position of the Fermi level with respect to the minimum of the pseudogap of the electronic density of states.

  3. Modeling long-term changes in forested landscapes and their relation to the Earth's energy balance

    NASA Technical Reports Server (NTRS)

    Shugart, H. H.; Emanuel, W. R.; Solomon, A. M.

    1984-01-01

    The dynamics of the forested parts of the Earth's surface on time scales from decades to centuries are discussed. A set of computer models developed at Oak Ridge National Laboratory and elsewhere are applied as tools. These models simulate a landscape by duplicating the dynamics of growth, death and birth of each tree living on a 0.10 ha element of the landscape. This spatial unit is generally referred to as a gap in the case of the forest models. The models were tested against and applied to a diverse array of forests and appear to provide a reasonable representation for investigating forest-cover dynamics. Because of the climate linkage, one important test is the reconstruction of paleo-landscapes. Detailed reconstructions of changes in vegetation in response to changes in climate are crucial to understanding the association of the Earth's vegetation and climate and the response of the vegetation to climate change.

  4. Calculation of the Intrinsic Solvation Free Energy Profile of an Ionic Penetrant Across a Liquid–Liquid Interface with Computer Simulations

    PubMed Central

    2013-01-01

    We introduce the novel concept of an intrinsic free energy profile, allowing one to remove the artificial smearing caused by thermal capillary waves, which renders difficulties for the calculation of free energy profiles across fluid interfaces in computer simulations. We apply this concept to the problem of a chloride ion crossing the interface between water and 1,2-dichloroethane and show that the present approach is able to reveal several important features of the free energy profile which are not detected with the usual, nonintrinsic calculations. Thus, in contrast to the nonintrinsic profile, a free energy barrier is found at the aqueous side of the (intrinsic) interface, which is attributed to the formation of a water “finger” the ion pulls with itself upon approaching the organic phase. Further, by the presence of a nonsampled region, the intrinsic free energy profile clearly indicates the coextraction of the first hydration shell water molecules of the ion when entering the organic phase. PMID:24175995

  5. The Potential and Flux Landscape Theory of Ecology

    PubMed Central

    Zhang, Kun; Wang, Erkang; Wang, Jin

    2014-01-01

    The species in ecosystems are mutually interacting and self sustainable stable for a certain period. Stability and dynamics are crucial for understanding the structure and the function of ecosystems. We developed a potential and flux landscape theory of ecosystems to address these issues. We show that the driving force of the ecological dynamics can be decomposed to the gradient of the potential landscape and the curl probability flux measuring the degree of the breaking down of the detailed balance (due to in or out flow of the energy to the ecosystems). We found that the underlying intrinsic potential landscape is a global Lyapunov function monotonically going down in time and the topology of the landscape provides a quantitative measure for the global stability of the ecosystems. We also quantified the intrinsic energy, the entropy, the free energy and constructed the non-equilibrium thermodynamics for the ecosystems. We studied several typical and important ecological systems: the predation, competition, mutualism and a realistic lynx-snowshoe hare model. Single attractor, multiple attractors and limit cycle attractors emerge from these studies. We studied the stability and robustness of the ecosystems against the perturbations in parameters and the environmental fluctuations. We also found that the kinetic paths between the multiple attractors do not follow the gradient paths of the underlying landscape and are irreversible because of the non-zero flux. This theory provides a novel way for exploring the global stability, function and the robustness of ecosystems. PMID:24497975

  6. The potential and flux landscape theory of ecology.

    PubMed

    Xu, Li; Zhang, Feng; Zhang, Kun; Wang, Erkang; Wang, Jin

    2014-01-01

    The species in ecosystems are mutually interacting and self sustainable stable for a certain period. Stability and dynamics are crucial for understanding the structure and the function of ecosystems. We developed a potential and flux landscape theory of ecosystems to address these issues. We show that the driving force of the ecological dynamics can be decomposed to the gradient of the potential landscape and the curl probability flux measuring the degree of the breaking down of the detailed balance (due to in or out flow of the energy to the ecosystems). We found that the underlying intrinsic potential landscape is a global Lyapunov function monotonically going down in time and the topology of the landscape provides a quantitative measure for the global stability of the ecosystems. We also quantified the intrinsic energy, the entropy, the free energy and constructed the non-equilibrium thermodynamics for the ecosystems. We studied several typical and important ecological systems: the predation, competition, mutualism and a realistic lynx-snowshoe hare model. Single attractor, multiple attractors and limit cycle attractors emerge from these studies. We studied the stability and robustness of the ecosystems against the perturbations in parameters and the environmental fluctuations. We also found that the kinetic paths between the multiple attractors do not follow the gradient paths of the underlying landscape and are irreversible because of the non-zero flux. This theory provides a novel way for exploring the global stability, function and the robustness of ecosystems.

  7. How dominant is the most efficient pathway through the potential energy landscape of a slowly diffusing disordered system?

    PubMed

    Nguyen, Crystal N; Isaacson, Joseph I; Shimmyo, Kayoko Beth; Chen, Andersen; Stratt, Richard M

    2012-05-14

    It has been suggested that the most-efficient pathway taken by a slowly diffusing many-body system is its geodesic path through the parts of the potential energy landscape lying below a prescribed value of the potential energy. From this perspective, slow diffusion occurs just because these optimal paths become particularly long and convoluted. We test this idea here by applying it to diffusion in two kinds of well-studied low-dimensional percolation problems: the 2d overlapping Lorentz model, and square and simple-cubic bond-dilute lattices. Although the most efficient path should be at its most dominant with the high-dimensional landscapes associated with many-body problems, it is useful to examine simpler, low-dimensional, constant-potential-energy problems such as these ones, both because the simpler models lend themselves to more accurate geodesic-path-finding approaches, and because they offer a significant contrast to many of the models used in the traditional energy-landscape literature. Neither the continuum nor the lattice percolation examples are adequately described by our geodesic-path formalism in the weakly disordered (relatively-fast-diffusion) limit, but in both cases the formalism successfully predicts the existence of the percolation transition and (to a certain extent) the slow diffusion characteristic of near-percolation behavior. The numerical results for these models are not nearly accurate enough near their transitions to describe critical exponents, but the models do showcase the qualitative validity of the geodesic perspective in that they allow us to see explicitly how tortuous and sparse the optimal pathways become as the diffusion constants begin to vanish.

  8. Land cover change in the zone of sporadic permafrost causes shift in landscape-scale turbulent energy fluxes

    NASA Astrophysics Data System (ADS)

    Helbig, M.; Wischnewski, K.; Kljun, N.; Chasmer, L.; Quinton, W. L.; Detto, M.; Sonnentag, O.

    2015-12-01

    current heterogeneous to a homogeneous bog landscape could lead to a decrease in the maximum PBL height by about 700 m and to a decrease in regional Ta by 1 to 2 K. Our results show clearly that permafrost degradation and forest cover shifts will affect local and regional surface energy balances in the boreal zone and could represent important modifiers of future climates.

  9. Water-regolith-energy Interaction in Landscape Evolution and Its Influence on Forming Asymmetric Landscape: An Example from the Shale Hills Critical Zone Observatory of Central Pennsylvania

    NASA Astrophysics Data System (ADS)

    Zhang, Y.; Slingerland, R. L.; Shi, Y.; Duffy, C.; West, N.

    2015-12-01

    Shale Hills Critical Zone Observatory (SSHCZO) is a 0.08 km2 first order experimental research catchment with relatively homogeneous bedrock, regolith and tectonic uplift, but with an asymmetric slope and thickness of regolith on the north- and south-facing hillslopes. In this paper, we use a hydrological-morphodynamic model (LE-PIHM), which links bedrock, soil, surface and subsurface water flow, plant, energy, and seasonal climate, to address the influence of water-regolith-energy interaction on soil creep process, the possible factors causing slope asymmetry and the spatial distribution of regolith transport at the SSHCZO. Two non-dimensional parameters were used to explore the competitive relationship between regolith diffusion and advection forming self-organized channel spacing, relief and slope length at steady state. Model simulation under seasonal meteorological forcing shows spatial variations of hillslope sediment fluxes. An experimental study using Beryllium 10 at the SSHCZO (West et al 2013) showed that a south-facing planar slope had a greater diffusion flux rate than a planar on north-facing slope. The model confirms this relationship in general although there are significant local variations. The largest regolith transport rate by overland flow (advection) occurs at the junctions of main channel and swales. The model simulation further suggests that north-south differences in diffusive flux may be a result of asymmetric solar insolation which affects freeze-thaw frequency and sediment transport through the process of soil creep. This study demonstrates the value of physically-based distributed landscape evolution model on estimating spatial distribution of regolith transport and highlights the critical transition zone.

  10. Defining and quantifying frustration in the energy landscape: Applications to atomic and molecular clusters, biomolecules, jammed and glassy systems

    NASA Astrophysics Data System (ADS)

    de Souza, V. K.; Stevenson, J. D.; Niblett, S. P.; Farrell, J. D.; Wales, D. J.

    2017-03-01

    The emergence of observable properties from the organisation of the underlying potential energy landscape is analysed, spanning a full range of complexity from self-organising to glassy and jammed systems. The examples include atomic and molecular clusters, a β-barrel protein, the GNNQQNY peptide dimer, and models of condensed matter that exhibit structural glass formation and jamming. We have considered measures based on several different properties, namely, the Shannon entropy, an equilibrium thermodynamic measure that uses a sample of local minima, and indices that require additional information about the connections between local minima in the form of transition states. A frustration index is defined that correlates directly with key properties that distinguish relaxation behaviour within this diverse set. The index uses the ratio of the energy barrier to the energy difference with reference to the global minimum. The contributions for each local minimum are weighted by the equilibrium occupation probabilities. Hence we obtain fundamental insight into the connections and distinctions between systems that cover the continuum from efficient structure-seekers to landscapes that exhibit broken ergodicity and rare event dynamics.

  11. Oil and Gas Development in Southwestern Wyoming - Energy Data and Services for the Wyoming Landscape Conservation Initiative (WLCI)

    USGS Publications Warehouse

    Biewick, Laura R.H.

    2009-01-01

    The purpose of this report is to explore current oil and gas energy development in the area encompassing the Wyoming Landscape Conservation Initiative. The Wyoming Landscape Conservation Initiative is a long-term science-based effort to ensure southwestern Wyoming's wildlife and habitat remain viable in areas facing development pressure. Wyoming encompasses some of the highest quality wildlife habitats in the Intermountain West. At the same time, this region is an important source of natural gas. Using Geographic Information System technology, energy data pertinent to the conservation decision-making process have been assembled to show historical oil and gas exploration and production in southwestern Wyoming. In addition to historical data, estimates of undiscovered oil and gas are included from the 2002 U.S. Geological Survey National Assessment of Oil and Gas in the Southwestern Wyoming Province. This report is meant to facilitate the integration of existing data with new knowledge and technologies to analyze energy resources development and to assist in habitat conservation planning. The well and assessment data can be accessed and shared among many different clients including, but not limited to, an online web-service for scientists and resource managers engaged in the Initiative.

  12. Origin of the Fragile-to-Strong Crossover in Liquid Silica as Expressed by its Potential-Energy Landscape

    NASA Astrophysics Data System (ADS)

    Saksaengwijit, A.; Reinisch, J.; Heuer, A.

    2004-12-01

    The origin of the fragile-to-strong crossover in liquid silica is characterized in terms of properties of the potential-energy landscape (PEL). Using the standard BKS model [B. W. H. van Beest, G. J. Kramer, and R. A. van Santen,

    Phys. Rev. Lett. 64, 1955 (1990)
    ] of silica we observe a low-energy cutoff of the PEL. It is shown that this feature of the PEL is responsible for the occurrence of the fragile-to-strong crossover and may also explain the avoidance of the Kauzmann paradox. The number of defects, i.e., deviations from the ideal tetrahedral structure, vanishes for configurations with energies close to this cutoff. This suggests a structural reason for this cutoff.

  13. Effect of Grain size on the Giant Intrinsic Coercivity of High-Energy Milled Sm(Co,Cu,Fe)5 Alloys

    NASA Astrophysics Data System (ADS)

    Sultana, Dilara; Gabay, Alexandar; Hadjipanayis, George

    2008-03-01

    The giant intrinsic magnetic hardness of Sm(Co,Cu)5 alloys have been known for a long time [1]. Previous studies suggested that this behavior is due to the crystal site disorder [2]. Our previous work has explained that the room-temperature intrinsic coercivity of 37 kOe after low-temperature aging is rather due to the intrinsic change in the Co atomic site occupation [3]. In this study, we investigated the effect of grain refinement through the high energy milling on the intrinsic coercivity of the Sm(Co,Cu,Fe)5 alloys. We have found that grain refinement does not affect the high coercivity of homogenized alloys, but strongly influences the onset of the giant coercivity during low-temperature aging. The microstructures of the samples are examined with TEM. [1] E.A. Nesbitt, R.H. Willens, R.C. Sherwood, E. Buehler, J.H. Wernick 1968 Appl.. Phys. Lett. 12, 361. [2] H. Oesterrier , F.T. Parker, M. Misroach 1979 J. Appl. Phys. 50, 4273. [3] A.M. Gabay, P. Larson, I.I. Manzin, G.C. Hadjipanayis 2005, J. Phys. D: Appl. Phys. 38, 1.

  14. Analyzing high resolution topography for advancing the understanding of mass and energy transfer through landscapes: A review

    USGS Publications Warehouse

    Passaiacquaa, Paola; Belmont, Patrick; Staley, Dennis M.; Simley, Jeffery; Arrowsmith, J. Ramon; Bode, Collin A.; Crosby, Christopher; DeLong, Stephen; Glenn, Nancy; Kelly, Sara; Lague, Dimitri; Sangireddy, Harish; Schaffrath, Keelin; Tarboton, David; Wasklewicz, Thad; Wheaton, Joseph

    2015-01-01

    The study of mass and energy transfer across landscapes has recently evolved to comprehensive considerations acknowledging the role of biota and humans as geomorphic agents, as well as the importance of small-scale landscape features. A contributing and supporting factor to this evolution is the emergence over the last two decades of technologies able to acquire high resolution topography (HRT) (meter and sub-meter resolution) data. Landscape features can now be captured at an appropriately fine spatial resolution at which surface processes operate; this has revolutionized the way we study Earth-surface processes. The wealth of information contained in HRT also presents considerable challenges. For example, selection of the most appropriate type of HRT data for a given application is not trivial. No definitive approach exists for identifying and filtering erroneous or unwanted data, yet inappropriate filtering can create artifacts or eliminate/distort critical features. Estimates of errors and uncertainty are often poorly defined and typically fail to represent the spatial heterogeneity of the dataset, which may introduce bias or error for many analyses. For ease of use, gridded products are typically preferred rather than the more information-rich point cloud representations. Thus many users take advantage of only a fraction of the available data, which has furthermore been subjected to a series of operations often not known or investigated by the user. Lastly, standard HRT analysis work-flows are yet to be established for many popular HRT operations, which has contributed to the limited use of point cloud data.In this review, we identify key research questions relevant to the Earth-surface processes community within the theme of mass and energy transfer across landscapes and offer guidance on how to identify the most appropriate topographic data type for the analysis of interest. We describe the operations commonly performed from raw data to raster products and

  15. Fugitive methane emissions from natural, urban, agricultural, and energy-production landscapes of eastern Australia

    NASA Astrophysics Data System (ADS)

    Kelly, Bryce F. J.; Iverach, Charlotte P.; Lowry, Dave; Fisher, Rebecca E.; France, James L.; Nisbet, Euan G.

    2015-04-01

    Modern cavity ringdown spectroscopy systems (CRDS) enable the continuous measurement of methane concentration. This allows for improved quantification of greenhouse gas emissions associated with various natural and human landscapes. We present a subset of over 4000 km of continuous methane surveying along the east coast of Australia, made using a Picarro G2301 CRDS, deployed in a utility vehicle with an air inlet above the roof at 2.2 mAGL. Measurements were made every 5 seconds to a precision of <0.5 ppb for CH4. These surveys were undertaken during dry daytime hours and all measurements were moisture corrected. We compare the concentration of methane in the near surface atmosphere adjacent to open-cut coal mines, unconventional gas developments (coal seam gas; CSG), and leaks detected in cities and country towns. In areas of dryland crops the median methane concentration was 1.78 ppm, while in the irrigation districts located on vertisol soils the concentration was as low as 1.76 ppm, which may indicate that these soils are a sink for methane. In the Hunter Valley, New South Wales, open-cut coal mining district we mapped a continuous 50 km interval where the concentration of methane exceeded 1.80 ppm. The median concentration in this interval was 2.02 ppm. Peak readings were beyond the range of the reliable measurement (in excess of 3.00 ppm). This extended plume is an amalgamation of plumes from 17 major pits 1 to 10 km in length. Adjacent to CSG developments in the Surat Basin, southeast Queensland, only small anomalies were detected near the well-heads. Throughout the vast majority of the gas fields the concentration of methane was below 1.80 ppm. The largest source of fugitive methane associated with CSG was off-gassing methane from the co-produced water holding ponds. At one location the down wind plume had a cross section of approximately 1 km where the concentration of methane was above 1.80 ppm. The median concentration within this section was 1.82 ppm

  16. Managing riverine landscapes as meta-ecosystems

    NASA Astrophysics Data System (ADS)

    Tockner, K.

    2014-12-01

    Aquatic and terrestrial ecosystems are tightly linked through energy, material, information, and organism flows. At the landscape scale, these reciprocal flows are controlled by the composition, configuration, boundary conditions and linkage of individual ecosystem types, thereby forming so-called meta-ecosystems. The relative importance of individual ecosystem types depends on the intrinsic properties (so-called "ecosystem traits"), the setting within the landscape, and the characteristics of interfaces that control cross-system fluxes. For example, the juxtaposition of particular ecosystem types (i.e. their composition and configuration) may alter the magnitude of landscape processes as well as the directions of flow among ecosystem types. Therefore, the meta-ecosystem concept provides a framework to quantify ecosystem diversity, a neglected component of biodiversity, and to test its effects on genetic and species diversity as well as the functional performance in coupled ecosystems. Given their topographic position at the lowest point in the landscape, aquatic ecosystems are particularly susceptible to influences exerted by their surrounding terrestrial environment, both the immediately adjacent riparian zones and the entire catchment that they drain. Questions that need to be tackled may include: What are the consequences of exchange pulses between aquatic and terrestrial ecosystems on the functional performance of individual ecosystems? What are the mechanisms and processes underlying structural and functional biodiversity at aquatic-terrestrial interfaces? In this respect, the meta-ecosystem concept might be very helpful in landscape management and in ecosystem design and engineering.

  17. Condensation transition and forced unravelling of DNA-histone H1 toroids: a multi-state free energy landscape

    NASA Astrophysics Data System (ADS)

    Mack, A. H.; Schlingman, D. J.; Salinas, R. D.; Regan, L.; Mochrie, S. G. J.

    2015-02-01

    DNA is known to condense with multivalent cations and positively charged proteins. However, the properties and energetics of DNA superstructures, such as chromatin, are poorly understood. As a model system, we investigate histone H1 condensation of DNA with tethered particle motion and force-extension measurements. We show that after the addition of H1 to DNA, a concentration dependent lag time is followed by the DNA spontaneously condensing. The trigger for this condensation phase transition can be modeled as sufficient H1s having bound to the DNA, providing insight into the 30 nm fiber condensation upon H1 binding. Furthermore, optical tweezers force-extension measurements of histone H1 condensed DNA reveals a sequence of state transitions corresponding to the unwinding of superhelical turns. We determine the complete, experimental, multi-state free energy landscape for the complex using Crooks fluctuation theorem. The measured force-versus-extension and free energy landscape are compared to predictions from a simple, theoretical model. This work encourages the theoretical description of DNA/protein structure and energetics and their role in chromatin and other, more complex, systems.

  18. Self-Learning Adaptive Umbrella Sampling Method for the Determination of Free Energy Landscapes in Multiple Dimensions.

    PubMed

    Wojtas-Niziurski, Wojciech; Meng, Yilin; Roux, Benoit; Bernèche, Simon

    2013-04-09

    The potential of mean force describing conformational changes of biomolecules is a central quantity that determines the function of biomolecular systems. Calculating an energy landscape of a process that depends on three or more reaction coordinates might require a lot of computational power, making some of multidimensional calculations practically impossible. Here, we present an efficient automatized umbrella sampling strategy for calculating multidimensional potential of mean force. The method progressively learns by itself, through a feedback mechanism, which regions of a multidimensional space are worth exploring and automatically generates a set of umbrella sampling windows that is adapted to the system. The self-learning adaptive umbrella sampling method is first explained with illustrative examples based on simplified reduced model systems, and then applied to two non-trivial situations: the conformational equilibrium of the pentapeptide Met-enkephalin in solution and ion permeation in the KcsA potassium channel. With this method, it is demonstrated that a significant smaller number of umbrella windows needs to be employed to characterize the free energy landscape over the most relevant regions without any loss in accuracy.

  19. Virtual-system-coupled adaptive umbrella sampling to compute free-energy landscape for flexible molecular docking.

    PubMed

    Higo, Junichi; Dasgupta, Bhaskar; Mashimo, Tadaaki; Kasahara, Kota; Fukunishi, Yoshifumi; Nakamura, Haruki

    2015-07-30

    A novel enhanced conformational sampling method, virtual-system-coupled adaptive umbrella sampling (V-AUS), was proposed to compute 300-K free-energy landscape for flexible molecular docking, where a virtual degrees of freedom was introduced to control the sampling. This degree of freedom interacts with the biomolecular system. V-AUS was applied to complex formation of two disordered amyloid-β (Aβ30-35 ) peptides in a periodic box filled by an explicit solvent. An interpeptide distance was defined as the reaction coordinate, along which sampling was enhanced. A uniform conformational distribution was obtained covering a wide interpeptide distance ranging from the bound to unbound states. The 300-K free-energy landscape was characterized by thermodynamically stable basins of antiparallel and parallel β-sheet complexes and some other complex forms. Helices were frequently observed, when the two peptides contacted loosely or fluctuated freely without interpeptide contacts. We observed that V-AUS converged to uniform distribution more effectively than conventional AUS sampling did.

  20. Intrinsic Geodesy

    DTIC Science & Technology

    1952-03-01

    Variation with the Height of the Principal Radii of Curvature in Somigliana’s Theory"), Bollettino di Geodesia e Scienze Affini, anno VIII, 1950 46...MARUSSI, A., "Principi di Geodesia Intrinseca applicati al campo di Somigliana" ("Principles of Intrinsic Geodesy Applied to Somigliana’s Field...34), Bollettino di Geodesia e Scienze Affini, anno VIII, 1950; and also Atti della XLII Riunione _dela Socie&Ljtsjjganaper il Progresso delle Scienze, Roma

  1. Curl flux, coherence, and population landscape of molecular systems: nonequilibrium quantum steady state, energy (charge) transport, and thermodynamics.

    PubMed

    Zhang, Zhedong; Wang, Jin; Zhang, Z D; Wang, J

    2014-06-28

    We established a theoretical framework in terms of the curl flux, population landscape, and coherence for non-equilibrium quantum systems at steady state, through exploring the energy and charge transport in molecular processes. The curl quantum flux plays the key role in determining transport properties and the system reaches equilibrium when flux vanishes. The novel curl quantum flux reflects the degree of non-equilibriumness and the time-irreversibility. We found an analytical expression for the quantum flux and its relationship to the environmental pumping (non-equilibriumness quantified by the voltage away from the equilibrium) and the quantum tunneling. Furthermore, we investigated another quantum signature, the coherence, quantitatively measured by the non-zero off diagonal element of the density matrix. Populations of states give the probabilities of individual states and therefore quantify the population landscape. Both curl flux and coherence depend on steady state population landscape. Besides the environment-assistance which can give dramatic enhancement of coherence and quantum flux with high voltage at a fixed tunneling strength, the quantum flux is promoted by the coherence in the regime of small tunneling while reduced by the coherence in the regime of large tunneling, due to the non-monotonic relationship between the coherence and tunneling. This is in contrast to the previously found linear relationship. For the systems coupled to bosonic (photonic and phononic) reservoirs the flux is significantly promoted at large voltage while for fermionic (electronic) reservoirs the flux reaches a saturation after a significant enhancement at large voltage due to the Pauli exclusion principle. In view of the system as a quantum heat engine, we studied the non-equilibrium thermodynamics and established the analytical connections of curl quantum flux to the transport quantities such as energy (charge) transfer efficiency, chemical reaction efficiency, energy

  2. Histone acetylation dependent energy landscapes in tri-nucleosome revealed by residue-resolved molecular simulations

    PubMed Central

    Chang, Le; Takada, Shoji

    2016-01-01

    Histone tail acetylation is a key epigenetic marker that tends to open chromatin folding and activate transcription. Despite intensive studies, precise roles of individual lysine acetylation in chromatin folding have only been poorly understood. Here, we revealed structural dynamics of tri-nucleosomes with several histone tail acetylation states and analyzed histone tail interactions with DNA by performing molecular simulations at an unprecedentedly high resolution. We found versatile acetylation-dependent landscapes of tri-nucleosome. The H4 and H2A tail acetylation reduced the contact between the first and third nucleosomes mediated by the histone tails. The H3 tail acetylation reduced its interaction with neighboring linker DNAs resulting in increase of the distance between consecutive nucleosomes. Notably, two copies of the same histone in a single nucleosome have markedly asymmetric interactions with DNAs, suggesting specific pattern of nucleosome docking albeit high inherent flexibility. Estimated transcription factor accessibility was significantly high for the H4 tail acetylated structures. PMID:27698366

  3. Unraveling energy conversion modeling in the intrinsic persistent upconverted luminescence of solids: a study of native point defects in antiferromagnetic Er2O3.

    PubMed

    Huang, Bolong

    2016-05-11

    We investigated the mechanism of the intrinsic persistent luminescence of Er2O3 in the A-type lattice based on first-principles calculations. We found that the native point defects were engaged in mutual subtle interactions in the form of chemical reactions between different charge states. The release of energy related to lattice distortion facilitates the conversion of energy for electrons to be transported between the valence band and the trap levels or even between the deep trap levels so as to generate persistent luminescence. The defect transitions that take place along the zero-phonon line release energy to enable optical transitions, with the exact amount of negative effective correlation energy determined by the lattice distortions. Our calculations on the thermodynamic transition levels confirm that both the visible and NIR experimentally observed intrinsic persistent luminescence (phosphor or afterglow) are related to the thermodynamic transition levels of oxygen-related defects, and the thermodynamic transition levels within different charge states for these defects are independent of the chemical potentials of the given species. Lattice distortion defects such as anion Frenkel (a-Fr) pair defects play an important role in transporting O-related defects between different lattice sites. To obtain red persistent luminescence that matches the biological therapeutic window, it is suggested to increase the electron transition levels between high-coordinated O vacancies and related metastable a-Fr defects; a close-packed core-shell structure is required to quench low-coordinated O-related defects so as to reduce the green band luminescence. We further established a conversed chain reaction (CCR) model to interpret the energy conversion process of persistent luminescence in terms of the inter-reactions of native point defects between different charge states. It is advantageous to use the study of defect levels combined with formation energies to suggest limits

  4. Covariant energy density functionals: The assessment of global performance across the nuclear landscape

    SciTech Connect

    Afanasjev, A. V.

    2015-10-15

    The assessment of the global performance of the state-of-the-art covariant energy density functionals and related theoretical uncertainties in the description of ground state observables has recently been performed. Based on these results, the correlations between global description of binding energies and nuclear matter properties of covariant energy density functionals have been studied in this contribution.

  5. Global and local aspects of the surface potential landscape for energy level alignment at organic-ZnO interfaces

    NASA Astrophysics Data System (ADS)

    Stähler, Julia; Rinke, Patrick

    2017-03-01

    Hybrid systems of organic and inorganic semiconductors are a promising route for the development of novel opto-electronic and light-harvesting devices. A key ingredient for achieving a superior functionality by means of a hybrid system is the right relative position of energy levels at the interfaces of the two material classes. In this Perspective, we address the sensitivity of the potential energy landscape at various ZnO surfaces, a key ingredient for interfacial energy level alignment, by combining one- and two-photon photoelectron spectroscopy with density-functional theory calculations (DFT). We show that even very large work function changes (>2.5 eV) do not necessarily have to be accompanied by surface band bending in ZnO. Band bending - if it does occur - may be localized to few Å or extend over hundreds of nanometers with very different results for the surface work function and energy level alignment. Managing the delicate balance of different interface manipulation mechanisms in organic-inorganic hybrid systems will be a major challenge towards future applications.

  6. Contribution of the intrinsic mechanical energy of the phosphodiester linkage to the relative stability of the A, BI and BII forms of duplex DNA

    PubMed Central

    MacKerell, Alexander D.

    2009-01-01

    Canonical forms of duplex DNA are known to sample well defined regions of the α, β, γ, ε and ζ dihedral angles that define the conformation of the phosphodiester linkage in the backbone of oligonucleotides. While extensive studies of base composition and base sequence dependent effects on the sampling of the A, BI and BII canonical forms of duplex DNA have been presented, our understanding of the intrinsic contribution of the five dihedral degrees of freedom associated with the phosphodiester linkage to the conformational properties of duplex DNA is still limited. To better understand this contribution ab initio quantum mechanical (QM) calculations were performed on a model compound representative of the phosphodiester backbone to systematically sample the energetics about the α β γ ε and ζ dihedral angles relevant to the conformational properties of duplex DNA. Low energy regions of dihedral potential energy surfaces are shown to correlate with the regions of dihedral space sampled in experimental crystal structures of the canonical forms of DNA, validating the utility of the model compound and emphasizing the contribution of the intrinsic mechanical properties of the phosphodiester backbone to the conformational properties of duplex DNA. Those contributions include the relative stability of the A, BI and BII conformations of duplex DNA, where the gas phase energetics favor the BI form over the A and BII forms. In addition, subtle features of the potential energy surfaces mimic changes in the probability distributions of α, β, γ, ε and ζ dihedral angles in A, BI and BII forms of DNA as well as with conformations sampled in single-stranded DNA. These results show that the intrinsic mechanical properties of the phosphodiester backbone make a significant contribution to conformational properties of duplex DNA observed in the condensed phase and allow for the prediction that single stranded DNA primarly samples folded conformations thereby possibly

  7. Contribution of the intrinsic mechanical energy of the phosphodiester linkage to the relative stability of the A, BI, and BII forms of duplex DNA.

    PubMed

    MacKerell, Alexander D

    2009-03-12

    Canonical forms of duplex DNA are known to sample well-defined regions of the alpha, beta, gamma, epsilon, and zeta dihedral angles that define the conformation of the phosphodiester linkage in the backbone of oligonucleotides. While extensive studies of base composition and base sequence dependent effects on the sampling of the A, B1, and BII canonical forms of duplex DNA have been presented, our understanding of the intrinsic contribution of the five dihedral degrees of freedom associated with the phosphodiester linkage to the conformational properties of duplex DNA is still limited. To better understand this contribution, ab initio quantum mechanical (QM) calculations were performed on a model compound representative of the phosphodiester backbone to systematically sample the energetics about the alpha, beta, gamma, epsilon, and zeta dihedral angles relevant to the conformational properties of duplex DNA. Low-energy regions of dihedral potential energy surfaces are shown to correlate with the regions of dihedral space sampled in experimental crystal structures of the canonical forms of DNA, validating the utility of the model compound and emphasizing the contribution of the intrinsic mechanical properties of the phosphodiester backbone to the conformational properties of duplex DNA. Those contributions include the relative stability of the A, BI, and BII conformations of duplex DNA, where the gas-phase energetics favor the BI form over the A and BII forms. In addition, subtle features of the potential energy surfaces mimic changes in the probability distributions of alpha, beta, gamma, epsilon, and zeta dihedral angles in A, BI, and BII forms of DNA as well as with conformations sampled in single-stranded DNA. These results show that the intrinsic mechanical properties of the phosphodiester backbone make a significant contribution to conformational properties of duplex DNA observed in the condensed phase and allow for the prediction that single-stranded DNA

  8. Optimal dimensionality reduction of complex dynamics: the chess game as diffusion on a free-energy landscape.

    PubMed

    Krivov, Sergei V

    2011-07-01

    Dimensionality reduction is ubiquitous in the analysis of complex dynamics. The conventional dimensionality reduction techniques, however, focus on reproducing the underlying configuration space, rather than the dynamics itself. The constructed low-dimensional space does not provide a complete and accurate description of the dynamics. Here I describe how to perform dimensionality reduction while preserving the essential properties of the dynamics. The approach is illustrated by analyzing the chess game--the archetype of complex dynamics. A variable that provides complete and accurate description of chess dynamics is constructed. The winning probability is predicted by describing the game as a random walk on the free-energy landscape associated with the variable. The approach suggests a possible way of obtaining a simple yet accurate description of many important complex phenomena. The analysis of the chess game shows that the approach can quantitatively describe the dynamics of processes where human decision-making plays a central role, e.g., financial and social dynamics.

  9. Energy landscape and band-structure tuning in realistic MoS2/MoSe2 heterostructures

    NASA Astrophysics Data System (ADS)

    Constantinescu, Gabriel C.; Hine, Nicholas D. M.

    2015-05-01

    While monolayer forms of two-dimensional materials are well characterized both experimentally and theoretically, properties of bilayer heterostructures are not nearly so well known. We employ high-accuracy linear-scaling density functional theory calculations utilizing nonlocal van der Waals functionals to explore the possible constructions of the MoS2/MoSe2 interface. Utilizing large supercells, we vary rotation, translation, and separation of the layers without introducing unrealistic strain. The energy landscape shows very low variations under rotation, with no strongly preferred alignments. By unfolding the spectral function into the primitive cells, we show that the monolayers are more independent than in homo-bilayers and that the electronic band structure of each layer is tunable through rotation, thus influencing hole effective masses.

  10. Optimal dimensionality reduction of complex dynamics: The chess game as diffusion on a free-energy landscape

    NASA Astrophysics Data System (ADS)

    Krivov, Sergei V.

    2011-07-01

    Dimensionality reduction is ubiquitous in the analysis of complex dynamics. The conventional dimensionality reduction techniques, however, focus on reproducing the underlying configuration space, rather than the dynamics itself. The constructed low-dimensional space does not provide a complete and accurate description of the dynamics. Here I describe how to perform dimensionality reduction while preserving the essential properties of the dynamics. The approach is illustrated by analyzing the chess game—the archetype of complex dynamics. A variable that provides complete and accurate description of chess dynamics is constructed. The winning probability is predicted by describing the game as a random walk on the free-energy landscape associated with the variable. The approach suggests a possible way of obtaining a simple yet accurate description of many important complex phenomena. The analysis of the chess game shows that the approach can quantitatively describe the dynamics of processes where human decision-making plays a central role, e.g., financial and social dynamics.

  11. Cellular network entropy as the energy potential in Waddington's differentiation landscape.

    PubMed

    Banerji, Christopher R S; Miranda-Saavedra, Diego; Severini, Simone; Widschwendter, Martin; Enver, Tariq; Zhou, Joseph X; Teschendorff, Andrew E

    2013-10-24

    Differentiation is a key cellular process in normal tissue development that is significantly altered in cancer. Although molecular signatures characterising pluripotency and multipotency exist, there is, as yet, no single quantitative mark of a cellular sample's position in the global differentiation hierarchy. Here we adopt a systems view and consider the sample's network entropy, a measure of signaling pathway promiscuity, computable from a sample's genome-wide expression profile. We demonstrate that network entropy provides a quantitative, in-silico, readout of the average undifferentiated state of the profiled cells, recapitulating the known hierarchy of pluripotent, multipotent and differentiated cell types. Network entropy further exhibits dynamic changes in time course differentiation data, and in line with a sample's differentiation stage. In disease, network entropy predicts a higher level of cellular plasticity in cancer stem cell populations compared to ordinary cancer cells. Importantly, network entropy also allows identification of key differentiation pathways. Our results are consistent with the view that pluripotency is a statistical property defined at the cellular population level, correlating with intra-sample heterogeneity, and driven by the degree of signaling promiscuity in cells. In summary, network entropy provides a quantitative measure of a cell's undifferentiated state, defining its elevation in Waddington's landscape.

  12. Efficient sampling over rough energy landscapes with high barriers: A combination of metadynamics with integrated tempering sampling

    NASA Astrophysics Data System (ADS)

    Yang, Y. Isaac; Zhang, Jun; Che, Xing; Yang, Lijiang; Gao, Yi Qin

    2016-03-01

    In order to efficiently overcome high free energy barriers embedded in a complex energy landscape and calculate overall thermodynamics properties using molecular dynamics simulations, we developed and implemented a sampling strategy by combining the metadynamics with (selective) integrated tempering sampling (ITS/SITS) method. The dominant local minima on the potential energy surface (PES) are partially exalted by accumulating history-dependent potentials as in metadynamics, and the sampling over the entire PES is further enhanced by ITS/SITS. With this hybrid method, the simulated system can be rapidly driven across the dominant barrier along selected collective coordinates. Then, ITS/SITS ensures a fast convergence of the sampling over the entire PES and an efficient calculation of the overall thermodynamic properties of the simulation system. To test the accuracy and efficiency of this method, we first benchmarked this method in the calculation of ϕ - ψ distribution of alanine dipeptide in explicit solvent. We further applied it to examine the design of template molecules for aromatic meta-C—H activation in solutions and investigate solution conformations of the nonapeptide Bradykinin involving slow cis-trans isomerizations of three proline residues.

  13. Identifying Greater Sage-Grouse source and sink habitats for conservation planning in an energy development landscape.

    PubMed

    Kirol, Christopher P; Beck, Jeffrey L; Huzurbazar, Snehalata V; Holloran, Matthew J; Miller, Scott N

    2015-06-01

    Conserving a declining species that is facing many threats, including overlap of its habitats with energy extraction activities, depends upon identifying and prioritizing the value of the habitats that remain. In addition, habitat quality is often compromised when source habitats are lost or fragmented due to anthropogenic development. Our objective was to build an ecological model to classify and map habitat quality in terms of source or sink dynamics for Greater Sage-Grouse (Centrocercus urophasianus) in the Atlantic Rim Project Area (ARPA), a developing coalbed natural gas field in south-central Wyoming, USA. We used occurrence and survival modeling to evaluate relationships between environmental and anthropogenic variables at multiple spatial scales and for all female summer life stages, including nesting, brood-rearing, and non-brooding females. For each life stage, we created resource selection functions (RSFs). We weighted the RSFs and combined them to form a female summer occurrence map. We modeled survival also as a function of spatial variables for nest, brood, and adult female summer survival. Our survival-models were mapped as survival probability functions individually and then combined with fixed vital rates in a fitness metric model that, when mapped, predicted habitat productivity (productivity map). Our results demonstrate a suite of environmental and anthropogenic variables at multiple scales that were predictive of occurrence and survival. We created a source-sink map by overlaying our female summer occurrence map and productivity map to predict habitats contributing to population surpluses (source habitats) or deficits (sink habitat) and low-occurrence habitats on the landscape. The source-sink map predicted that of the Sage-Grouse habitat within the ARPA, 30% was primary source, 29% was secondary source, 4% was primary sink, 6% was secondary sink, and 31% was low occurrence. Our results provide evidence that energy development and avoidance of

  14. The Shifting Landscape of Ratepayer-Funded Energy Efficiency in the U.S.

    SciTech Connect

    Barbose, Galen L; Goldman, Charles; Schlegel, Jeff

    2009-07-13

    Over the last two decades, utility ratepayer funding for energy efficiency programs - and the associated energy savings - has seen both booms and busts. Currently, about 35 states implement ratepayer-funded energy efficiency programs, with a total U.S. budget of $3.1 billion in 2008, approximately 80% of which is concentrated in just ten states (CEE 2008).2 However, a proliferation of new state-level policies enacted over the past several years suggests that the next decade may see a dramatic and sustained increase in overall funding levels, and a fundamental re-drawing of the energy efficiency map. These new state energy efficiency policies reflect a variety of concerns, including the increasing cost and siting challenges of building new generation and transmission, fuel cost and supply risks, and the potential cost of future carbon regulations. Within the past three years, for example, eleven states have adopted energy efficiency portfolio (or resource) standards (EEPS or EERS) that establish specific long-term savings targets that utilities are obligated to meet, and at least three other states are currently considering the same. A growing number of states have recently established laws requiring utilities to acquire all available cost-effective energy efficiency. Regulators in several Western states have also recently revised integrated resource planning (IRP) and demand-side management (DSM) planning rules to require more robust analysis of the resource potential and benefits of energy efficiency, which has resulted in increased savings targets for their energy efficiency portfolios (Hopper et al. 2008). Finally, regulators and utilities in many states are beginning to look more closely at regulatory incentive mechanisms to better align utility financial interests with improvements in customer energy efficiency. We examined energy efficiency policies on the books or in the pipeline in all 50 states, along with recent IRPs and DSM plans, and developed low

  15. Roadmaps through free energy landscapes calculated using the multi-dimensional vFEP approach.

    PubMed

    Lee, Tai-Sung; Radak, Brian K; Huang, Ming; Wong, Kin-Yiu; York, Darrin M

    2014-01-14

    The variational free energy profile (vFEP) method is extended to two dimensions and tested with molecular simulation applications. The proposed 2D-vFEP approach effectively addresses the two major obstacles to constructing free energy profiles from simulation data using traditional methods: the need for overlap in the re-weighting procedure and the problem of data representation. This is especially evident as these problems are shown to be more severe in two dimensions. The vFEP method is demonstrated to be highly robust and able to provide stable, analytic free energy profiles with only a paucity of sampled data. The analytic profiles can be analyzed with conventional search methods to easily identify stationary points (e.g. minima and first-order saddle points) as well as the pathways that connect these points. These "roadmaps" through the free energy surface are useful not only as a post-processing tool to characterize mechanisms, but can also serve as a basis from which to direct more focused "on-the-fly" sampling or adaptive force biasing. Test cases demonstrate that 2D-vFEP outperforms other methods in terms of the amount and sparsity of the data needed to construct stable, converged analytic free energy profiles. In a classic test case, the two dimensional free energy profile of the backbone torsion angles of alanine dipeptide, 2D-vFEP needs less than 1% of the original data set to reach a sampling accuracy of 0.5 kcal/mol in free energy shifts between windows. A new software tool for performing one and two dimensional vFEP calculations is herein described and made publicly available.

  16. Relationship between entropy and diffusion: A statistical mechanical derivation of Rosenfeld expression for a rugged energy landscape

    NASA Astrophysics Data System (ADS)

    Seki, Kazuhiko; Bagchi, Biman

    2015-11-01

    Diffusion—a measure of dynamics, and entropy—a measure of disorder in the system are found to be intimately correlated in many systems, and the correlation is often strongly non-linear. We explore the origin of this complex dependence by studying diffusion of a point Brownian particle on a model potential energy surface characterized by ruggedness. If we assume that the ruggedness has a Gaussian distribution, then for this model, one can obtain the excess entropy exactly for any dimension. By using the expression for the mean first passage time, we present a statistical mechanical derivation of the well-known and well-tested scaling relation proposed by Rosenfeld between diffusion and excess entropy. In anticipation that Rosenfeld diffusion-entropy scaling (RDES) relation may continue to be valid in higher dimensions (where the mean first passage time approach is not available), we carry out an effective medium approximation (EMA) based analysis of the effective transition rate and hence of the effective diffusion coefficient. We show that the EMA expression can be used to derive the RDES scaling relation for any dimension higher than unity. However, RDES is shown to break down in the presence of spatial correlation among the energy landscape values.

  17. Free energy landscapes for homogeneous nucleation of ice for a monatomic water model

    NASA Astrophysics Data System (ADS)

    Reinhardt, Aleks; Doye, Jonathan P. K.

    2012-02-01

    We simulate the homogeneous nucleation of ice from supercooled liquid water at 220 K in the isobaric-isothermal ensemble using the MW monatomic water potential. Monte Carlo simulations using umbrella sampling are performed in order to determine the nucleation free energy barrier. We find the Gibbs energy profile to be relatively consistent with that predicted by classical nucleation theory; the free energy barrier to nucleation was determined to be ˜18 kBT and the critical nucleus comprised ˜85 ice particles. Growth from the supercooled liquid gives clusters that are predominantly cubic, whilst starting with a pre-formed subcritical nucleus of cubic or hexagonal ice results in the growth of predominantly that phase of ice only.

  18. Evapotranspiration and surface energy balance across an agricultural-urban landscape gradient in Southern California, USA.

    NASA Astrophysics Data System (ADS)

    Shiflett, S. A.; Anderson, R. G.; Jenerette, D.

    2014-12-01

    Urbanization substantially affects energy, surface and air temperature, and hydrology due to extensive modifications in land surface properties such as vegetation, albedo, thermal capacity and soil moisture. The magnitude and direction of these alterations depends heavily on the type of urbanization that occurs. We investigated energy balance variation in a local network of agricultural and urban ecosystems using the eddy covariance method to better understand how vegetation fraction and degree of urbanization affects energy exchanges between the land surface and the atmosphere. We deployed eddy flux systems within a well-irrigated, agricultural citrus orchard, a moderately developed urban zone with a substantial amount of local vegetative cover, and an intensely developed urban zone with minimal vegetative cover and increased impervious surfaces relative to the other two sites. Latent energy (LE) fluxes in the agricultural area ranged from 7.9 ± 1.4 W m-2 (nighttime) to 168.7 ± 6.2 W m-2 (daytime) compared to 10.2 ± 3.5 W m-2 and 40.6 ± 4.1 W m-2, respectively, for the moderately developed urban area. Sensible energy (H) fluxes ranged from -9.1 ± 1.0 W m-2 (nighttime) to 119 ± 7.0 W m-2 (daytime) in the agricultural area compared to 9.6 ± 2.6 W m-2 and 134 ± 6.0 W m-2, respectively, for the moderately developed urban zone. Daytime LE is reduced with increasing urbanization; however, daily cycles of LE are less recognizable in urban areas compared to distinct daily cycles obtained above a mature citrus crop. In contrast, both daytime and nighttime H increases with increasing degree of urbanization. Reduction in vegetation and increases in impervious surfaces along an urbanization gradient leads to alterations in energy balance, which are associated with microclimate and water use changes.

  19. Navigating the new deregulated landscape: Opportunities and risks for wind energy

    SciTech Connect

    Fossum, D.J.; Hill, D.R.

    1997-12-31

    Major changes in the law governing the electric industry are underway, fundamentally altering how the generation and sale of electric power is regulated and how electric power is marketed in the United States. Legislative and regulatory initiatives promoting competition will create a variety of opportunities, and commensurate risks, for power generators, marketers, brokers, sellers, and purchasers. To succeed in the new marketplace, suppliers of renewable energy must understand the changes occurring on the state and federal levels, and position themselves to take advantage of the opportunities available. In this environment, monitoring and participating in state and federal legislative and regulatory efforts will be crucial for maximizing opportunities for wind energy.

  20. Physical mechanism of mind changes and tradeoffs among speed, accuracy, and energy cost in brain decision making: Landscape, flux, and path perspectives

    NASA Astrophysics Data System (ADS)

    Han, Yan; Kun, Zhang; Jin, Wang

    2016-07-01

    Cognitive behaviors are determined by underlying neural networks. Many brain functions, such as learning and memory, have been successfully described by attractor dynamics. For decision making in the brain, a quantitative description of global attractor landscapes has not yet been completely given. Here, we developed a theoretical framework to quantify the landscape associated with the steady state probability distributions and associated steady state curl flux, measuring the degree of non-equilibrium through the degree of detailed balance breaking for decision making. We quantified the decision-making processes with optimal paths from the undecided attractor states to the decided attractor states, which are identified as basins of attractions, on the landscape. Both landscape and flux determine the kinetic paths and speed. The kinetics and global stability of decision making are explored by quantifying the landscape topography through the barrier heights and the mean first passage time. Our theoretical predictions are in agreement with experimental observations: more errors occur under time pressure. We quantitatively explored two mechanisms of the speed-accuracy tradeoff with speed emphasis and further uncovered the tradeoffs among speed, accuracy, and energy cost. Our results imply that there is an optimal balance among speed, accuracy, and the energy cost in decision making. We uncovered the possible mechanisms of changes of mind and how mind changes improve performance in decision processes. Our landscape approach can help facilitate an understanding of the underlying physical mechanisms of cognitive processes and identify the key factors in the corresponding neural networks. Project supported by the National Natural Science Foundation of China (Grant Nos. 21190040, 91430217, and 11305176).

  1. ''Wet/dry Daisyworld'': a conceptual tool for quantifying the spatial scaling of heterogeneous landscapes and its impact on the subgrid variability of energy fluxes

    SciTech Connect

    Baldocchi, Dennis D.; Krebs, Theresa; Leclerc, Monique Y.

    2005-07-01

    We modified the ''Daisyworld'' model of Watson and Lovelock to consider the energy balance of vegetation with differing potential to evaporate water vapour across a 2-D landscape. High-resolution spatial fields of surface temperature, latent heat exchange and net radiation are computed using cellular automata (CA). The CA algorithm considers competition between actively transpiring ''wet daisies'' and ''dry daisies'' for bare ground through temperature-dependent birth and death probabilities. This paper examines how differences in biophysical properties (e.g. surface albedo and surface conductance) affect the composition and heterogeneity of the landscape and its energy exchange. And with high resolution and gridded spatial information we evaluate bias errors and scaling rules associated with the subgrid averaging of the nonlinear functions used to compute surface energy balance. Among our key findings we observe that there are critical conditions, associated with albedo and surface resistance, when wet or dry/dark or bright “daisies” dominate the landscape. Second, we find that the heterogeneity of the spatial distribution of “daisies” depends on initial conditions (e.g. a bare field versus a random assemblage of surface classes). And third, the spatial coefficient of variation of land class, latent heat exchange, net radiation and surface temperature scale with the exponential power of the size of the averaging window. Though conceptual in nature, the 2-D ''wet/dry Daisyworld'' model produces a virtual landscape whose power-law scaling exponent resembles the one derived for the spatial scaling of a normalized difference vegetation index for a heterogeneous savanna ecosystem. This observation is conditional and occurs if the initial landscape is bare with two small colonies of ''we'' and ''dry'' daisies. Bias errors associated with the nonlinear averaging of the surface energy balance equation increase as the coefficient of variation of the surface

  2. Comparison/Validation of Remote Sensing-Based Surface Energy Balance Models Over the Agricultural Landscapes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Accurate characterization of surface energy fluxes over a range of spatial and temporal scales is critical for many applications in agriculture, hydrology, meteorology, and climatology. Over the past several years, there has been a major effort devoted to the development and refinement of remote sen...

  3. Numerical Simulation of Environmental Flow over Urban Landscape for Applications to Renewable Energy

    NASA Astrophysics Data System (ADS)

    Ying, Xiaoyan

    Development of renewable energy solutions has become a major interest among environmental organizations and governments around the world due to an increase in energy consumption and global warming. One fast growing renewable energy solution is the application of wind energy in cities. To qualitative and quantitative predict wind turbine performance in urban areas, CFD simulation is performed on real-life urban geometry and wind velocity profiles are evaluated. Two geometries in Arizona is selected in this thesis to demonstrate the influence of building heights; one of the simulation models, ASU campus, is relatively low rise and without significant tall buildings; the other model, the downtown phoenix model, are high-rise and with greater building height difference. The content of this thesis focuses on using RANS computational fluid dynamics approach to simulate wind acceleration phenomenon in two complex geometries, ASU campus and Phoenix downtown model. Additionally, acceleration ratio and locations are predicted, the results are then used to calculate the best location for small wind turbine installments.

  4. Energy Efficiency and Conservation Attitudes: An Exploration of a Landscape of Choices

    NASA Astrophysics Data System (ADS)

    McClaren, Mersiha Spahic

    This study explored energy-related attitudes and energy-saving behaviors that are no- or low-cost and relatively simple to perform. This study relied on two data sources: a longitudinal but cross-sectional survey of 4,102 U.S. residents (five biennial waves of this survey were conducted from 2002 to 2010) and a 2010 cross-sectional survey of 2,000 California residents. These two surveys contained data on two no- and low-cost behaviors: changing thermostat setting to save energy (no-cost behavior) and CFL installation behavior (low-cost behavior). In terms of attitudes, two attitudinal measures emerged from these data following a Cronbach's alpha and Confirmatory Factor Analysis (CFA): the pro-environmental attitude and concern for the energy use in the U.S. society. These two attitudes, along with other socio-demographic and external factors (home ownership, weather, price of energy, etc.), were examined to assess whether attitude-behavior relationships persisted over time, were more prominent across certain groups, or were constrained by income or other socio-demographic factors. Three theoretical viewpoints of how attitudes may relate to behavior guided the analysis on how attitudes and contextual factors may inter-relate either directly or through a moderator variable to affect thermostat-setting and CFL installation behavior. Results from these analyses revealed four important patterns. First, a relationship between the pro-environmental attitude and the two behaviors (thermostat-setting and CFL installation behavior) was weak but persistent across time. Second, financial factors such as income moderated the pro-environmental attitude and CFL installation relationship, indicating that the pro-environmental attitude could influence the behavior in those situations where financial resources are sufficient to comfortably allow the consumer to participate. Third, this study documented that most people reported changing thermostat settings to save energy or having

  5. Energy Band Gap, Intrinsic Carrier Concentration and Fermi Level of CdTe Bulk Crystal between 304 K and 1067 K

    NASA Technical Reports Server (NTRS)

    Su, Ching-Hua

    2007-01-01

    Optical transmission measurements were performed on CdTe bulk single crystal. It was found that when a sliced and polished CdTe wafer was used, a white film started to develop when the sample was heated above 530 K and the sample became opaque. Therefore, a bulk crystal of CdTe was first grown in the window area by physical vapor transport; the optical transmission was then measured and from which the energy band gap was derived between 304 and 1067 K. The band gaps of CdTe can be fit well as a function of temperature using the Varshini expression: Eg (e V) = 1.5860 - 5.9117xl0(exp -4) T(sup 2)/(T + 160). Using the band gap data, the high temperature electron-hole equilibrium was calculated numerically by assuming the Kane's conduction band structure and a heavy-hole parabolic valance band. The calculated intrinsic carrier concentrations agree well with the experimental data reported previously. The calculated intrinsic Fermi levels between 270 and 1200 K were also presented.

  6. Energy landscapes of a mechanical prion and their implications for the molecular mechanism of long-term memory

    PubMed Central

    Chen, Mingchen; Zheng, Weihua; Wolynes, Peter G.

    2016-01-01

    Aplysia cytoplasmic polyadenylation element binding (CPEB) protein, a translational regulator that recruits mRNAs and facilitates translation, has been shown to be a key component in the formation of long-term memory. Experimental data show that CPEB exists in at least a low-molecular weight coiled-coil oligomeric form and an amyloid fiber form involving the Q-rich domain (CPEB-Q). Using a coarse-grained energy landscape model, we predict the structures of the low-molecular weight oligomeric form and the dynamics of their transitions to the β-form. Up to the decamer, the oligomeric structures are predicted to be coiled coils. Free energy profiles confirm that the coiled coil is the most stable form for dimers and trimers. The structural transition from α to β is shown to be concentration dependent, with the transition barrier decreasing with increased concentration. We observe that a mechanical pulling force can facilitate the α-helix to β-sheet (α-to-β) transition by lowering the free energy barrier between the two forms. Interactome analysis of the CPEB protein suggests that its interactions with the cytoskeleton could provide the necessary mechanical force. We propose that, by exerting mechanical forces on CPEB oligomers, an active cytoskeleton can facilitate fiber formation. This mechanical catalysis makes possible a positive feedback loop that would help localize the formation of CPEB fibers to active synapse areas and mark those synapses for forming a long-term memory after the prion form is established. The functional role of the CPEB helical oligomers in this mechanism carries with it implications for targeting such species in neurodegenerative diseases. PMID:27091989

  7. Energy Landscape of Alginate-Epimerase Interactions Assessed by Optical Tweezers and Atomic Force Microscopy

    PubMed Central

    Håti, Armend Gazmeno; Aachmann, Finn Lillelund; Stokke, Bjørn Torger; Skjåk-Bræk, Gudmund; Sletmoen, Marit

    2015-01-01

    Mannuronan C-5 epimerases are a family of enzymes that catalyze epimerization of alginates at the polymer level. This group of enzymes thus enables the tailor-making of various alginate residue sequences to attain various functional properties, e.g. viscosity, gelation and ion binding. Here, the interactions between epimerases AlgE4 and AlgE6 and alginate substrates as well as epimerization products were determined. The interactions of the various epimerase–polysaccharide pairs were determined over an extended range of force loading rates by the combined use of optical tweezers and atomic force microscopy. When studying systems that in nature are not subjected to external forces the access to observations obtained at low loading rates, as provided by optical tweezers, is a great advantage since the low loading rate region for these systems reflect the properties of the rate limiting energy barrier. The AlgE epimerases have a modular structure comprising both A and R modules, and the role of each of these modules in the epimerization process were examined through studies of the A- module of AlgE6, AlgE6A. Dynamic strength spectra obtained through combination of atomic force microscopy and the optical tweezers revealed the existence of two energy barriers in the alginate-epimerase complexes, of which one was not revealed in previous AFM based studies of these complexes. Furthermore, based on these spectra estimates of the locations of energy transition states (xβ), lifetimes in the absence of external perturbation (τ0) and free energies (ΔG#) were determined for the different epimerase–alginate complexes. This is the first determination of ΔG# for these complexes. The values determined were up to 8 kBT for the outer barrier, and smaller values for the inner barriers. The size of the free energies determined are consistent with the interpretation that the enzyme and substrate are thus not tightly locked at all times but are able to relocate. Together with the

  8. Daily energy expenditure in the face of predation: hedgehog energetics in rural landscapes.

    PubMed

    Pettett, Carly E; Johnson, Paul J; Moorhouse, Tom P; Hambly, Catherine; Speakman, John R; Macdonald, David W

    2017-02-01

    Failure to balance daily energy expenditure (DEE) with energy intake can have an impact on survival and reproduction, and therefore on the persistence of populations. Here we study the DEE of the European hedgehog (Erinaceus europaeus), which is declining in the UK. We hypothesise that there is a gradient of suitable habitat for hedgehogs in rural areas, which is a result of fewer food resources, a higher risk from predation by badgers (Meles meles) and colder ambient temperatures, as distance to the nearest building increases. We used the doubly labelled water method to obtain 44 measurements of DEE from hedgehogs on four predominately arable sites, to determine the energetic costs associated with proximity to buildings, on sites with and without badgers. The mean±s.e.m. DEE was 508.9±34.8 kJ day(-1) DEE increased the further a hedgehog was from buildings during the study, possibly as they ranged larger distances on arable land, supporting the hypothesis that hedgehogs select villages owing to the lower energy demands in comparison to arable farmland. Hedgehogs had an approximately 30% lower DEE on sites with badgers. We speculate that on badger-occupied sites, hedgehogs may restrict movement and foraging in response to a threat from predation and thus have reduced DEE. Therefore, hedgehogs may also seek refuge in villages where the perceived threat of predation is lower and foraging is unrestricted. In a broader context, we demonstrate that individual differences in DEE can aid in understanding habitat selection in a patchily distributed species.

  9. Energy landscape investigation by wavelet transform analysis of atomic force spectroscopy data in a biorecognition experiment.

    PubMed

    Bizzarri, Anna Rita

    2016-01-01

    Force fluctuations recorded in an atomic force spectroscopy experiment, during the approach of a tip functionalized with biotin towards a substrate charged with avidin, have been analyzed by a wavelet transform. The observation of strong transient changes only when a specific biorecognition process between the partners takes place suggests a drastic modulation of the force fluctuations when biomolecules recognize each other. Such an analysis allows to investigate the peculiar features of a biorecognition process. These results are discussed in connection with the possible role of energy minima explored by biomolecules during the biorecognition process.

  10. 3D modeling of satellite spectral images, radiation budget and energy budget of urban landscapes

    NASA Astrophysics Data System (ADS)

    Gastellu-Etchegorry, J. P.

    2008-12-01

    DART EB is a model that is being developed for simulating the 3D (3 dimensional) energy budget of urban and natural scenes, possibly with topography and atmosphere. It simulates all non radiative energy mechanisms (heat conduction, turbulent momentum and heat fluxes, water reservoir evolution, etc.). It uses DART model (Discrete Anisotropic Radiative Transfer) for simulating radiative mechanisms: 3D radiative budget of 3D scenes and their remote sensing images expressed in terms of reflectance or brightness temperature values, for any atmosphere, wavelength, sun/view direction, altitude and spatial resolution. It uses an innovative multispectral approach (ray tracing, exact kernel, discrete ordinate techniques) over the whole optical domain. This paper presents two major and recent improvements of DART for adapting it to urban canopies. (1) Simulation of the geometry and optical characteristics of urban elements (houses, etc.). (2) Modeling of thermal infrared emission by vegetation and urban elements. The new DART version was used in the context of the CAPITOUL project. For that, districts of the Toulouse urban data base (Autocad format) were translated into DART scenes. This allowed us to simulate visible, near infrared and thermal infrared satellite images of Toulouse districts. Moreover, the 3D radiation budget was used by DARTEB for simulating the time evolution of a number of geophysical quantities of various surface elements (roads, walls, roofs). Results were successfully compared with ground measurements of the CAPITOUL project.

  11. Energy landscape and dynamics of brain activity during human bistable perception.

    PubMed

    Watanabe, Takamitsu; Masuda, Naoki; Megumi, Fukuda; Kanai, Ryota; Rees, Geraint

    2014-08-28

    Individual differences in the structure of parietal and prefrontal cortex predict the stability of bistable visual perception. However, the mechanisms linking such individual differences in brain structures to behaviour remain elusive. Here we demonstrate a systematic relationship between the dynamics of brain activity, cortical structure and behaviour underpinning bistable perception. Using fMRI in humans, we find that the activity dynamics during bistable perception are well described as fluctuating between three spatially distributed energy minimums: visual-area-dominant, frontal-area-dominant and intermediate states. Transitions between these energy minimums predicted behaviour, with participants whose brain activity tend to reflect the visual-area-dominant state exhibiting more stable perception and those whose activity transits to frontal-area-dominant states reporting more frequent perceptual switches. Critically, these brain activity dynamics are correlated with individual differences in grey matter volume of the corresponding brain areas. Thus, individual differences in the large-scale dynamics of brain activity link focal brain structure with bistable perception.

  12. Theoretical and experimental exploration of the energy landscape of the quasi-binary cesium chloride/lithium chloride system.

    PubMed

    Pentin, Ilya V; Saltykov, Vyacheslav; Nuss, Jürgen; Schön, J Christian; Jansen, Martin

    2012-03-19

    As a case study, the energy landscape of the cesium chloride/lithium chloride system was investigated by combining theoretical and experimental methods. Global optimization for many compositions of this quasi-binary system gave candidates for possible modifications that constitute promising targets for subsequent syntheses based on solid-state reactions. Owing to the synergetic and complementary nature of the computational and experimental approaches, a substantially better efficiency of exploration was achieved. Several new phases were found in this system, for the compositions CsLiCl(2) and CsLi(2)Cl(3), and their thermodynamic ranking with respect to the already-known phases was clarified. In particular, the new CsLiCl(2) modification was shown to be the low-temperature phase, whilst the already-known modification for this composition corresponded to a high-temperature phase. Based on these results, an improved cesium chloride/lithium chloride phase diagram was derived, and this approach points the way to more rational and more efficient solid-state synthesis.

  13. Monotonicity, frustration, and ordered response: an analysis of the energy landscape of perturbed large-scale biological networks

    PubMed Central

    2010-01-01

    Background For large-scale biological networks represented as signed graphs, the index of frustration measures how far a network is from a monotone system, i.e., how incoherently the system responds to perturbations. Results In this paper we find that the frustration is systematically lower in transcriptional networks (modeled at functional level) than in signaling and metabolic networks (modeled at stoichiometric level). A possible interpretation of this result is in terms of energetic cost of an interaction: an erroneous or contradictory transcriptional action costs much more than a signaling/metabolic error, and therefore must be avoided as much as possible. Averaging over all possible perturbations, however, we also find that unlike for transcriptional networks, in the signaling/metabolic networks the probability of finding the system in its least frustrated configuration tends to be high also in correspondence of a moderate energetic regime, meaning that, in spite of the higher frustration, these networks can achieve a globally ordered response to perturbations even for moderate values of the strength of the interactions. Furthermore, an analysis of the energy landscape shows that signaling and metabolic networks lack energetic barriers around their global optima, a property also favouring global order. Conclusion In conclusion, transcriptional and signaling/metabolic networks appear to have systematic differences in both the index of frustration and the transition to global order. These differences are interpretable in terms of the different functions of the various classes of networks. PMID:20537143

  14. Hierarchical structure of the energy landscape of proteins revisited by time series analysis. II. Investigation of explicit solvent effects

    NASA Astrophysics Data System (ADS)

    Alakent, Burak; Camurdan, Mehmet C.; Doruker, Pemra

    2005-10-01

    Time series analysis tools are employed on the principal modes obtained from the Cα trajectories from two independent molecular-dynamics simulations of α-amylase inhibitor (tendamistat). Fluctuations inside an energy minimum (intraminimum motions), transitions between minima (interminimum motions), and relaxations in different hierarchical energy levels are investigated and compared with those encountered in vacuum by using different sampling window sizes and intervals. The low-frequency low-indexed mode relationship, established in vacuum, is also encountered in water, which shows the reliability of the important dynamics information offered by principal components analysis in water. It has been shown that examining a short data collection period (100ps) may result in a high population of overdamped modes, while some of the low-frequency oscillations (<10cm-1) can be captured in water by using a longer data collection period (1200ps). Simultaneous analysis of short and long sampling window sizes gives the following picture of the effect of water on protein dynamics. Water makes the protein lose its memory: future conformations are less dependent on previous conformations due to the lowering of energy barriers in hierarchical levels of the energy landscape. In short-time dynamics (<10ps), damping factors extracted from time series model parameters are lowered. For tendamistat, the friction coefficient in the Langevin equation is found to be around 40-60cm-1 for the low-indexed modes, compatible with literature. The fact that water has increased the friction and that on the other hand has lubrication effect at first sight contradicts. However, this comes about because water enhances the transitions between minima and forces the protein to reduce its already inherent inability to maintain oscillations observed in vacuum. Some of the frequencies lower than 10cm-1 are found to be overdamped, while those higher than 20cm-1 are slightly increased. As for the long

  15. Recent progress on intrinsic charm

    NASA Astrophysics Data System (ADS)

    Hobbs, T. J.

    2017-03-01

    Over the past ˜10 years, the topic of the nucleon's nonperturbative or intrinsic charm (IC) content has enjoyed something of a renaissance, largely motivated by theoretical developments involving quark modelers and PDF-fitters. In this talk I will briefly describe the importance of intrinsic charm to various issues in high-energy phenomenology, and survey recent progress in constraining its overall normalization and contribution to the momentum sum rule of the nucleon. I end with the conclusion that progress on the side of calculation has now placed the onus on experiment to unambiguously resolve the proton's intrinsic charm component.

  16. Trajectory Approach to Two-State Kinetics of Single Particles on Sculpted Energy Landscapes

    PubMed Central

    Wu, David; Ghosh, Kingshuk; Inamdar, Mandar; Lee, Heun Jin; Fraser, Scott; Dill, Ken; Phillips, Rob

    2012-01-01

    We study the trajectories of a single colloidal particle as it hops between two energy wells which are sculpted using optical traps. Whereas the dynamical behaviors of such systems are often treated by master-equation methods that focus on particles as actors, we analyze them instead using a trajectory-based variational method called maximum caliber (MaxCal). We show that the MaxCal strategy accurately predicts the full dynamics that we observe in the experiments: From the observed averages, it predicts second and third moments and covariances, with no free parameters. The covariances are the dynamical equivalents of Maxwell-like equilibrium reciprocal relations and Onsager-like dynamical relations. PMID:19792475

  17. Trajectory approach to two-state kinetics of single particles on sculpted energy landscapes.

    PubMed

    Wu, David; Ghosh, Kingshuk; Inamdar, Mandar; Lee, Heun Jin; Fraser, Scott; Dill, Ken; Phillips, Rob

    2009-07-31

    We study the trajectories of a single colloidal particle as it hops between two energy wells which are sculpted using optical traps. Whereas the dynamical behaviors of such systems are often treated by master-equation methods that focus on particles as actors, we analyze them instead using a trajectory-based variational method called maximum caliber (MaxCal). We show that the MaxCal strategy accurately predicts the full dynamics that we observe in the experiments: From the observed averages, it predicts second and third moments and covariances, with no free parameters. The covariances are the dynamical equivalents of Maxwell-like equilibrium reciprocal relations and Onsager-like dynamical relations.

  18. The Energy Landscape for the Self-Assembly of a Two-Dimensional DNA Origami Complex.

    PubMed

    Fern, Joshua; Lu, Jennifer; Schulman, Rebecca

    2016-02-23

    While the self-assembly of different types of DNA origami into well-defined complexes could produce nanostructures on which thousands of locations can be independently functionalized with nanometer-scale precision, current assembly processes have low yields. Biomolecular complex formation requires relatively strong interactions and reversible assembly pathways that prevent kinetic trapping. To characterize how these issues control origami complex yields, the equilibrium constants for each possible reaction for the assembly of a heterotetrameric ring, the unit cell of a rectangular lattice, were measured using fluorescence colocalization microscopy. We found that origami interface structure controlled reaction free energies. Cooperativity, measured for the first time for a DNA nanostructure assembly reaction, was weak. Simulations of assembly kinetics suggest assembly occurs via parallel pathways with the primary mechanism of assembly being hierarchical: two dimers form that then bind to one another to complete the ring.

  19. Combined Inhibitor Free-Energy Landscape and Structural Analysis Reports on the Mannosidase Conformational Coordinate**

    PubMed Central

    Williams, Rohan J; Iglesias-Fernández, Javier; Stepper, Judith; Jackson, Adam; Thompson, Andrew J; Lowe, Elisabeth C; White, Jonathan M; Gilbert, Harry J; Rovira, Carme; Davies, Gideon J; Williams, Spencer J

    2014-01-01

    Mannosidases catalyze the hydrolysis of a diverse range of polysaccharides and glycoconjugates, and the various sequence-based mannosidase families have evolved ingenious strategies to overcome the stereoelectronic challenges of mannoside chemistry. Using a combination of computational chemistry, inhibitor design and synthesis, and X-ray crystallography of inhibitor/enzyme complexes, it is demonstrated that mannoimidazole-type inhibitors are energetically poised to report faithfully on mannosidase transition-state conformation, and provide direct evidence for the conformational itinerary used by diverse mannosidases, including β-mannanases from families GH26 and GH113. Isofagomine-type inhibitors are poor mimics of transition-state conformation, owing to the high energy barriers that must be crossed to attain mechanistically relevant conformations, however, these sugar-shaped heterocycles allow the acquisition of ternary complexes that span the active site, thus providing valuable insight into active-site residues involved in substrate recognition. PMID:24339341

  20. A landscape ecology approach to assessing development impacts in the tropics: A geothermal energy example in Hawaii

    USGS Publications Warehouse

    Griffith, J.A.; Trettin, C.C.; O'Neill, R. V.

    2002-01-01

    Geographic information systems (GIS) are increasingly being used in environmental impact assessments (EIA) because GIS is useful for analysing spatial impacts of various development scenarios. Spatially representing these impacts provides another tool for landscape ecology in environmental and geographical investigations by facilitating analysis of the effects of landscape patterns on ecological processes and examining change over time. Landscape ecological principles are applied in this study to a hypothetical geothermal development project on the Island of Hawaii. Some common landscape pattern metrics were used to analyse dispersed versus condensed development scenarios and their effect on landscape pattern. Indices of fragmentation and patch shape did not appreciably change with additional development. The amount of forest to open edge, however, greatly increased with the dispersed development scenario. In addition, landscape metrics showed that a human disturbance had a greater simplifying effect on patch shape and also increased fragmentation than a natural disturbance. The use of these landscape pattern metrics can advance the methodology of applying GIS to EIA.

  1. Photovoltaic performance and the energy landscape of CH3NH3PbI3.

    PubMed

    Zhou, Yecheng; Huang, Fuzhi; Cheng, Yi-Bing; Gray-Weale, Angus

    2015-09-21

    Photovoltaic cells with absorbing layers of certain perovskites have power conversion efficiencies up to 20%. Among these materials, CH3NH3PbI3 is widely used. Here we use density-functional theory to calculate the energies and rotational energy barriers of a methylammonium ion in the α or β phase of CH3NH3PbI3 with differently oriented neighbouring methylammonium ions. Our results suggest the methylammonium ions in CH3NH3PbI3 prefer to rotate collectively, and to be parallel to their neighbours. Changes in polarization on rotation of methylammonium ions are two to three times larger than those on relaxation of the lead ion from the centre of its coordination shell. The preferences for parallel configuration and concerted rotation, with the polarisation changes, are consistent with ferroelectricity in the material, and indicate that this polarisation is governed by methylammonium orientational correlations. We show that the field due to this polarisation is strong enough to screen the field hindering charge transport, and find this screening field in agreement with experiment. We examine two possible mechanisms for the effect of methylammonium ion rotation on photovoltaic performance. One is that rearrangement of methylammoniums promotes the creation and transport of charge carriers. Some effective masses change greatly, but changes in band structure with methylammonium rotation are not large enough to explain current-voltage hysteresis behaviour. The second possible mechanism is that polarization screens the hindering electric field, which arises from charge accumulation in the transport layers. Polarization changes on methylammonium rotation favour this second mechanism, suggesting that collective reorientation of methylammonium ions in the bulk crystal are in significant part responsible for the hysteresis and power conversion characteristics of CH3NH3PbI3 photovoltaic cells.

  2. Analyzing the components of the free-energy landscape in a calcium selective ion channel by Widom's particle insertion method.

    PubMed

    Boda, Dezso; Giri, Janhavi; Henderson, Douglas; Eisenberg, Bob; Gillespie, Dirk

    2011-02-07

    The selectivity filter of the L-type calcium channel works as a Ca(2+) binding site with a very large affinity for Ca(2+) versus Na(+). Ca(2+) replaces half of the Na(+) ions in the filter even when these ions are present in 1 μM and 30 mM concentrations in the bath, respectively. The energetics of this strong selectivity is analyzed in this paper. We use Widom's particle insertion method to compute the space-dependent profiles of excess chemical potential in our grand canonical Monte Carlo simulations. These profiles define the free-energy landscape for the various ions. Following Gillespie [Biophys. J. 94, 1169 (2008)], the difference of the excess chemical potentials for the two competing ions defines the advantage that one of the ions has over the other in the competition for space in the crowded selectivity filter. These advantages depend on ionic bath concentrations: the ion that is present in the bath in larger quantity (Na(+)) has the "number" advantage which is balanced by the free-energy advantage of the other ion (Ca(2+)). The excess chemical potentials are decomposed into hard sphere exclusion and electrostatic components. The electrostatic terms correspond to interactions with the mean electric field produced by ions and induced charges as well to ionic correlations beyond the mean field description. Dielectrics are needed to produce micromolar Ca(2+) versus Na(+) selectivity in the L-type channel. We study the behavior of these terms with changes in bath concentrations of ions, charges, and diameters of ions, as well as geometrical parameters such as radius of the pore and the dielectric constant of the protein. Ion selectivity in calcium binding proteins probably has a similar mechanism.

  3. From the Cover: Simplifying the representation of complex free-energy landscapes using sketch-map.

    PubMed

    Ceriotti, Michele; Tribello, Gareth A; Parrinello, Michele

    2011-08-09

    A new scheme, sketch-map, for obtaining a low-dimensional representation of the region of phase space explored during an enhanced dynamics simulation is proposed. We show evidence, from an examination of the distribution of pairwise distances between frames, that some features of the free-energy surface are inherently high-dimensional. This makes dimensionality reduction problematic because the data does not satisfy the assumptions made in conventional manifold learning algorithms We therefore propose that when dimensionality reduction is performed on trajectory data one should think of the resultant embedding as a quickly sketched set of directions rather than a road map. In other words, the embedding tells one about the connectivity between states but does not provide the vectors that correspond to the slow degrees of freedom. This realization informs the development of sketch-map, which endeavors to reproduce the proximity information from the high-dimensionality description in a space of lower dimensionality even when a faithful embedding is not possible.

  4. Optimized energy landscape exploration using the ab initio based activation-relaxation technique

    NASA Astrophysics Data System (ADS)

    Machado-Charry, Eduardo; Béland, Laurent Karim; Caliste, Damien; Genovese, Luigi; Deutsch, Thierry; Mousseau, Normand; Pochet, Pascal

    2011-07-01

    Unbiased open-ended methods for finding transition states are powerful tools to understand diffusion and relaxation mechanisms associated with defect diffusion, growth processes, and catalysis. They have been little used, however, in conjunction with ab initio packages as these algorithms demanded large computational effort to generate even a single event. Here, we revisit the activation-relaxation technique (ART nouveau) and introduce a two-step convergence to the saddle point, combining the previously used Lanczós algorithm with the direct inversion in interactive subspace scheme. This combination makes it possible to generate events (from an initial minimum through a saddle point up to a final minimum) in a systematic fashion with a net 300-700 force evaluations per successful event. ART nouveau is coupled with BigDFT, a Kohn-Sham density functional theory (DFT) electronic structure code using a wavelet basis set with excellent efficiency on parallel computation, and applied to study the potential energy surface of C20 clusters, vacancy diffusion in bulk silicon, and reconstruction of the 4H-SiC surface.

  5. Information Resources in High-Energy Physics: Surveying the Present Landscape and Charting the Future Course

    SciTech Connect

    Gentil-Beccot, Anne; Mele, Salvatore; Holtkamp, Annette; O'Connell, Heath B.; Brooks, Travis C.

    2008-04-22

    Access to previous results is of paramount importance in the scientific process. Recent progress in information management focuses on building e-infrastructures for the optimization of the research workflow, through both policy-driven and user-pulled dynamics. For decades, High-Energy Physics (HEP) has pioneered innovative solutions in the field of information management and dissemination. In light of a transforming information environment, it is important to assess the current usage of information resources by researchers and HEP provides a unique test-bed for this assessment. A survey of about 10% of practitioners in the field reveals usage trends and information needs. Community-based services, such as the pioneering arXiv and SPIRES systems, largely answer the need of the scientists, with a limited but increasing fraction of younger users relying on Google. Commercial services offered by publishers or database vendors are essentially unused in the field. The survey offers an insight into the most important features that users require to optimize their research workflow. These results inform the future evolution of information management in HEP and, as these researchers are traditionally 'early adopters' of innovation in scholarly communication, can inspire developments of disciplinary repositories serving other communities.

  6. Optimized energy landscape exploration using the ab initio based activation-relaxation technique.

    PubMed

    Machado-Charry, Eduardo; Béland, Laurent Karim; Caliste, Damien; Genovese, Luigi; Deutsch, Thierry; Mousseau, Normand; Pochet, Pascal

    2011-07-21

    Unbiased open-ended methods for finding transition states are powerful tools to understand diffusion and relaxation mechanisms associated with defect diffusion, growth processes, and catalysis. They have been little used, however, in conjunction with ab initio packages as these algorithms demanded large computational effort to generate even a single event. Here, we revisit the activation-relaxation technique (ART nouveau) and introduce a two-step convergence to the saddle point, combining the previously used Lanczós algorithm with the direct inversion in interactive subspace scheme. This combination makes it possible to generate events (from an initial minimum through a saddle point up to a final minimum) in a systematic fashion with a net 300-700 force evaluations per successful event. ART nouveau is coupled with BigDFT, a Kohn-Sham density functional theory (DFT) electronic structure code using a wavelet basis set with excellent efficiency on parallel computation, and applied to study the potential energy surface of C(20) clusters, vacancy diffusion in bulk silicon, and reconstruction of the 4H-SiC surface.

  7. Free-Energy Landscape of Protein-Ligand Interactions Coupled with Protein Structural Changes.

    PubMed

    Moritsugu, Kei; Terada, Tohru; Kidera, Akinori

    2017-02-02

    Protein-ligand interactions are frequently coupled with protein structural changes. Focusing on the coupling, we present the free-energy surface (FES) of the ligand-binding process for glutamine-binding protein (GlnBP) and its ligand, glutamine, in which glutamine binding accompanies large-scale domain closure. All-atom simulations were performed in explicit solvents by multiscale enhanced sampling (MSES), which adopts a multicopy and multiscale scheme to achieve enhanced sampling of systems with a large number of degrees of freedom. The structural ensemble derived from the MSES simulation yielded the FES of the coupling, described in terms of both the ligand's and protein's degrees of freedom at atomic resolution, and revealed the tight coupling between the two degrees of freedom. The derived FES led to the determination of definite structural states, which suggested the dominant pathways of glutamine binding to GlnBP: first, glutamine migrates via diffusion to form a dominant encounter complex with Arg75 on the large domain of GlnBP, through strong polar interactions. Subsequently, the closing motion of GlnBP occurs to form ligand interactions with the small domain, finally completing the native-specific complex structure. The formation of hydrogen bonds between glutamine and the small domain is considered to be a rate-limiting step, inducing desolvation of the protein-ligand interface to form the specific native complex. The key interactions to attain high specificity for glutamine, the "door keeper" existing between the two domains (Asp10-Lys115) and the "hydrophobic sandwich" formed between the ligand glutamine and Phe13/Phe50, have been successfully mapped on the pathway derived from the FES.

  8. Biapenem Inactivation by B2 Metallo β-Lactamases: Energy Landscape of the Hydrolysis Reaction

    PubMed Central

    Ackerman, Sharon H.; Gatti, Domenico L.

    2013-01-01

    Background A general mechanism has been proposed for metallo β-lactamases (MβLs), in which deprotonation of a water molecule near the Zn ion(s) results in the formation of a hydroxide ion that attacks the carbonyl oxygen of the β-lactam ring. However, because of the absence of X-ray structures that show the exact position of the antibiotic in the reactant state (RS) it has been difficult to obtain a definitive validation of this mechanism. Methodology/Principal Findings We have employed a strategy to identify the RS, which does not rely on substrate docking and/or molecular dynamics. Starting from the X-ray structure of the enzyme:product complex (the product state, PS), a QM/MM scan was used to drive the reaction uphill from product back to reactant. Since in this process also the enzyme changes from PS to RS, we actually generate the enzyme:substrate complex from product and avoid the uncertainties associated with models of the reactant state. We used this strategy to study the reaction of biapenem hydrolysis by B2 MβL CphA. QM/MM simulations were carried out under 14 different ionization states of the active site, in order to generate potential energy surfaces (PESs) corresponding to a variety of possible reaction paths. Conclusions/Significance The calculations support a model for biapenem hydrolysis by CphA, in which the nucleophile that attacks the β-lactam ring is not the water molecule located in proximity of the active site Zn, but a second water molecule, hydrogen bonded to the first one, which is used up in the reaction, and thus is not visible in the X-ray structure of the enzyme:product complex. PMID:23372827

  9. The acute effect of bipolar radiofrequency energy thermal chondroplasty on intrinsic biomechanical properties and thickness of chondromalacic human articular cartilage.

    PubMed

    Dutcheshen, Nicholas; Maerz, Tristan; Rabban, Patrick; Haut, Roger C; Button, Keith D; Baker, Kevin C; Guettler, Joseph

    2012-08-01

    Radio frequency energy (RFE) thermal chondroplasty has been a widely-utilized method of cartilage debridement in the past. Little is known regarding its effect on tissue mechanics. This study investigated the acute biomechanical effects of bipolar RFE treatment on human chondromalacic cartilage. Articular cartilage specimens were extracted (n = 50) from femoral condyle samples of patients undergoing total knee arthroplasty. Chondromalacia was graded with the Outerbridge classification system. Tissue thicknesses were measured using a needle punch test. Specimens underwent pretreatment load-relaxation testing using a spherical indenter. Bipolar RFE treatment was applied for 45 s and the indentation protocol was repeated. Structural properties were derived from the force-time data. Mechanical properties were derived using a fibril-reinforced biphasic cartilage model. Statistics were performed using repeated measures ANOVA. Cartilage thickness decreased after RFE treatment from a mean of 2.61 mm to 2.20 mm in Grade II, II-III, and III specimens (P < 0.001 each). Peak force increased after RFE treatment from a mean of 3.91 N to 4.91 N in Grade II and III specimens (P = 0.002 and P = 0.003, respectively). Equilibrium force increased after RFE treatment from a mean of 0.236 N to 0.457 N (P < 0.001 each grade). Time constant decreased after RFE treatment from a mean of 0.392 to 0.234 (P < 0.001 for each grade). Matrix modulus increased in all specimens following RFE treatment from a mean 259.12 kPa to 523.36 kPa (P < 0.001 each grade). Collagen fibril modulus decreased in Grade II and II-III specimens from 60.50 MPa to 42.04 MPa (P < 0.001 and P = 0.005, respectively). Tissue permeability decreased in Grade II and III specimens from 2.04 ∗10(-15) m(4)/Ns to 0.91 ∗10(-15) m(4)/Ns (P < 0.001 and P = 0.009, respectively). RFE treatment decreased thickness, time constant, fibril modulus, permeability, but increased peak force

  10. Determination of the intrinsic energy dependence of LiF:Mg,Ti thermoluminescent dosimeters for {sup 125}I and {sup 103}Pd brachytherapy sources relative to {sup 60}Co

    SciTech Connect

    Reed, J. L. Micka, J. A.; Culberson, W. S.; DeWerd, L. A.; Rasmussen, B. E.; Davis, S. D.

    2014-12-15

    Purpose: To determine the intrinsic energy dependence of LiF:Mg,Ti thermoluminescent dosimeters (TLD-100) for {sup 125}I and {sup 103}Pd brachytherapy sources relative to {sup 60}Co. Methods: LiF:Mg,Ti TLDs were irradiated with low-energy brachytherapy sources and with a {sup 60}Co teletherapy source. The brachytherapy sources measured were the Best 2301 {sup 125}I seed, the OncoSeed 6711 {sup 125}I seed, and the Best 2335 {sup 103}Pd seed. The TLD light output per measured air-kerma strength was determined for the brachytherapy source irradiations, and the TLD light output per air kerma was determined for the {sup 60}Co irradiations. Monte Carlo (MC) simulations were used to calculate the dose-to-TLD rate per air-kerma strength for the brachytherapy source irradiations and the dose to TLD per air kerma for the {sup 60}Co irradiations. The measured and MC-calculated results for all irradiations were used to determine the TLD intrinsic energy dependence for {sup 125}I and {sup 103}Pd relative to {sup 60}Co. Results: The relative TLD intrinsic energy dependences (relative to {sup 60}Co) and associated uncertainties (k = 1) were determined to be 0.883 ± 1.3%, 0.870 ± 1.4%, and 0.871 ± 1.5% for the Best 2301 seed, OncoSeed 6711 seed, and Best 2335 seed, respectively. Conclusions: The intrinsic energy dependence of TLD-100 is dependent on photon energy, exhibiting changes of 13%–15% for {sup 125}I and {sup 103}Pd sources relative to {sup 60}Co. TLD measurements of absolute dose around {sup 125}I and {sup 103}Pd brachytherapy sources should explicitly account for the relative TLD intrinsic energy dependence in order to improve dosimetric accuracy.

  11. Communication: Low-energy free-electron driven molecular engineering: In situ preparation of intrinsically short-lived carbon-carbon covalent dimer of CO

    NASA Astrophysics Data System (ADS)

    Davis, Daly; Sajeev, Y.

    2017-02-01

    Molecular modification induced through the resonant attachment of a low energy electron (LEE) is a novel approach for molecular engineering. In this communication, we explore the possibility to use the LEE as a quantum tool for the in situ preparation of short lived molecules. Using ab initio quantum chemical methods, this possibility is best illustrated for the in situ preparation of the intrinsically short-lived carbon-carbon covalent dimer of CO from a glyoxal molecule. The chemical conversion of glyoxal to the covalent dimer of CO is initiated and driven by the resonant capture of a near 11 eV electron by the glyoxal molecule. The resulting two-particle one-hole (2p-1h) negative ion resonant state (NIRS) of the glyoxal molecule undergoes a barrierless radical dehydrogenation reaction and produces the covalent dimer of CO. The autoionization electron spectra from the 2p-1h NIRS at the dissociation limit of the dehydrogenation reaction provides access to the electronic states of the CO dimer. The overall process is an example of a catalytic electron reaction channel.

  12. Intrinsic magnetization of antiferromagnetic textures

    NASA Astrophysics Data System (ADS)

    Tveten, Erlend G.; Müller, Tristan; Linder, Jacob; Brataas, Arne

    2016-03-01

    Antiferromagnets (AFMs) exhibit intrinsic magnetization when the order parameter spatially varies. This intrinsic spin is present even at equilibrium and can be interpreted as a twisting of the homogeneous AFM into a state with a finite spin. Because magnetic moments couple directly to external magnetic fields, the intrinsic magnetization can alter the dynamics of antiferromagnetic textures under such influence. Starting from the discrete Heisenberg model, we derive the continuum limit of the free energy of AFMs in the exchange approximation and explicitly rederive that the spatial variation of the antiferromagnetic order parameter is associated with an intrinsic magnetization density. We calculate the magnetization profile of a domain wall and discuss how the intrinsic magnetization reacts to external forces. We show conclusively, both analytically and numerically, that a spatially inhomogeneous magnetic field can move and control the position of domain walls in AFMs. By comparing our model to a commonly used alternative parametrization procedure for the continuum fields, we show that the physical interpretations of these fields depend critically on the choice of parametrization procedure for the discrete-to-continuous transition. This can explain why a significant amount of recent studies of the dynamics of AFMs, including effective models that describe the motion of antiferromagnetic domain walls, have neglected the intrinsic spin of the textured order parameter.

  13. Effects of intrinsic degrees of freedom in enhancement of sub-barrier fusion excitation function data and energy-dependent one-dimensional barrier penetration model

    NASA Astrophysics Data System (ADS)

    Gautam, M. S.

    2016-03-01

    We have analyzed the role of barrier modification effects (barrier height, barrier position, barrier curvature) introduced due to the energy-dependent Woods-Saxon potential model (EDWSP model) and the coupled channel model on the sub-barrier fusion dynamics of {}_{16}^{32,36} {{S}} + {}_{40}^{90,96} {{Zr}} reactions. The influence of inelastic surface excitations of colliding pairs and multi-neutron transfer channels is found to be a dominant mode of couplings. The coupling of relative motion of colliding nuclei to these dominant intrinsic degrees of freedom leads to a substantially large fusion enhancement at below-barrier energies over the expectations of one-dimensional barrier penetration model. The coupled channel calculations based upon static Woods-Saxon potential must include the internal nuclear structure degrees of freedom of colliding nuclei for complete description of experimental data. On the other hand, theoretical calculations based upon the EDWSP model along with Wong formula provide a complete description of sub-barrier fusion enhancement of various heavy-ion fusion reactions. In EDWSP model calculations, significantly larger values of diffuseness parameter ranging from a = 0.98 fm to a = 0.85 fm are required to address the observed sub-barrier fusion enhancement of {}_{16}^{32,36} {{S}} + {}_{40}^{90,96} {{Zr}} reactions. Furthermore, within the context of EDWSP model, it is possible to achieve an agreement with the experimental fusion cross-sectional data within 10 %. For four heavy-ion fusion reactions, only at 4 fusion data points out of 90 fusion data points deviates exceeding 5 %, while 86 fusion data points lie within 5 % and hence the EDWSP model is able to account the above-barrier portion of the fusion cross-sectional data within 5 % with a probability greater than 90 %.

  14. Hierarchy of simulation models in predicting molecular recognition mechanisms from the binding energy landscapes: structural analysis of the peptide complexes with SH2 domains.

    PubMed

    Verkhivker, G M; Bouzida, D; Gehlhaar, D K; Rejto, P A; Schaffer, L; Arthurs, S; Colson, A B; Freer, S T; Larson, V; Luty, B A; Marrone, T; Rose, P W

    2001-12-01

    Computer simulations using the simplified energy function and simulated tempering dynamics have accurately determined the native structure of the pYVPML, SVLpYTAVQPNE, and SPGEpYVNIEF peptides in the complexes with SH2 domains. Structural and equilibrium aspects of the peptide binding with SH2 domains have been studied by generating temperature-dependent binding free energy landscapes. Once some native peptide-SH2 domain contacts are constrained, the underlying binding free energy profile has the funnel-like shape that leads to a rapid and consistent acquisition of the native structure. The dominant native topology of the peptide-SH2 domain complexes represents an extended peptide conformation with strong specific interactions in the phosphotyrosine pocket and hydrophobic interactions of the peptide residues C-terminal to the pTyr group. The topological features of the peptide-protein interface are primarily determined by the thermodynamically stable phosphotyrosyl group. A diversity of structurally different binding orientations has been observed for the amino-terminal residues to the phosphotyrosine. The dominant native topology for the peptide residues carboxy-terminal to the phosphotyrosine is tolerant to flexibility in this region of the peptide-SH2 domain interface observed in equilibrium simulations. The energy landscape analysis has revealed a broad, entropically favorable topology of the native binding mode for the bound peptides, which is robust to structural perturbations. This could provide an additional positive mechanism underlying tolerance of the SH2 domains to hydrophobic conservative substitutions in the peptide specificity region.

  15. Shared Solar: Current Landscape, Market Potential, and the Impact of Federal Securities Regulation; NREL (National Renewable Energy Laboratory)

    SciTech Connect

    2015-05-27

    This presentation provides a high-level overview of the current U.S. shared solar landscape, the impact that a given shared solar program's structure has on requiring federal securities oversight, as well as an estimate of market potential for U.S. shared solar deployment.

  16. Intrinsic Friction Microscopy

    NASA Astrophysics Data System (ADS)

    Knorr, Daniel; Overney, Rene

    2008-03-01

    A novel scanning probe methodology based on lateral force microscopy is presented wherein kinetic friction measurements, obtained as a function of velocity for various temperatures, are used to deduce apparent Arrhenius-type activation energies for surface and subsurface molecular mobilities. Depending on the coupling strength (cooperativity) between molecular mobilities involved the dissipation energy can carry a significant entropic energy contribution, accounting for the majority of the apparent Arrhenius activation energy. The intrinsic friction methodology also provides a means of directly separating enthalpic energy contributions from entropic ones by employing absolute rate theory. As such, the degree of cooperativity in the system is readily apparent. This methodology is illustrated with nanoscale tribological experiments on two systems, (1) monodisperse, atactic polystyrene and (2) self assembling molecular glassy chromophores. In polystyrene, dissipation was found to be a discrete function of loading, where the γ-relaxation (phenyl group rotation) was recovered for ultra low loads and the β-relaxation (local backbone translation) for higher loads in the same temperature range, indicating sensitivity to surface and subsurface mobilities. For self assembling glassy chromophores, the degree of intermolecular cooperativity was deduced using the methodology, resulting in an increased understanding of the interactions between self assembling molecules.

  17. Estimating evapotranspiration over agricultural landscapes with thermal infrared data: comparison of two approaches using Simple Energy Budget and SVAT modeling.

    NASA Astrophysics Data System (ADS)

    Bigeard, G.; Coudert, B.; Jarlan, L.; Er-Raki, S.; Khabba, S.

    2012-04-01

    Evapotranspiration (ET) monitoring presents wide range of applications from agriculture and water resources management to meteorology. Several approaches have been developed to retrieve ET based on a joint use of remote sensing data and land surface modeling, in particular with a SVAT (Soil Vegetation Atmosphere Transfers) model or a SEB (Surface Energy Budget) model. The objective of our work is to estimate spatialized ET fluxes from Thermal Infra-Red (TIR) imagery, focusing on simulating fluxes at low spatial resolution with 2 methodologies: 1. Simulating with a SEB model directly at low resolution (landscape scale: 4km) with TIR forcing. 2. Aggregating high resolution (agricultural field scale) estimates from a SVAT model constrained by TIR data and based on a high spatial resolution database (landcover, LAI, vegetation height, meteorological forcing and irrigation). In a first part we sum up previous results about in-situ capabilities of a SEB model (TSEB, Norman & al. 1995) versus a SVAT model (SEtHyS, described by Coudert & al. 2006) over crops. TSEB is driven directly with TIR forcing and does not consider soil water transfers. SEtHyS doesn't rely on TIR data availability but it has more parameters and requires more inputs for initialization. Simulations of both models were compared to in-situ Eddy-Correlation (EC) fluxes, with data from 3 sites in southern France and Morocco, covering several kinds of cultures, various vegetative states and various meteorological conditions. A sensitivity analysis on inputs was used to better characterize their capabilities and behaviors, and quantify error ranges induced by spatialization. Globally, models provide estimations of latent heat flux (LE) with RMSD of around 55W/m2 for TSEB and 45W/m2 for SEtHyS. Energy fluxes partition in TSEB was shown to be relatively less sensitive to some inputs when using only a single set of parameters. However it has lower performances on rising vegetation and stressed vegetation

  18. Landscape Solutions to School Problems.

    ERIC Educational Resources Information Center

    Spitz, Katherine

    2002-01-01

    Discusses key lessons in school landscape design. Landscapes should: (1) include trees and plants that themselves provide hands-on teaching opportunities; (2) enhance health and safety in a number of ways while performing their other functions; (3) be sensitively designed relative to location to cut energy costs; and (4) be aesthetic as well as…

  19. Quantum free energy landscapes from ab initio path integral metadynamics: Double proton transfer in the formic acid dimer is concerted but not correlated

    SciTech Connect

    Ivanov, Sergei D. Grant, Ian M.; Marx, Dominik

    2015-09-28

    With the goal of computing quantum free energy landscapes of reactive (bio)chemical systems in multi-dimensional space, we combine the metadynamics technique for sampling potential energy surfaces with the ab initio path integral approach to treating nuclear quantum motion. This unified method is applied to the double proton transfer process in the formic acid dimer (FAD), in order to study the nuclear quantum effects at finite temperatures without imposing a one-dimensional reaction coordinate or reducing the dimensionality. Importantly, the ab initio path integral metadynamics technique allows one to treat the hydrogen bonds and concomitant proton transfers in FAD strictly independently and thus provides direct access to the much discussed issue of whether the double proton transfer proceeds via a stepwise or concerted mechanism. The quantum free energy landscape we compute for this H-bonded molecular complex reveals that the two protons move in a concerted fashion from initial to product state, yet world-line analysis of the quantum correlations demonstrates that the protons are as quantum-uncorrelated at the transition state as they are when close to the equilibrium structure.

  20. Quantum free energy landscapes from ab initio path integral metadynamics: Double proton transfer in the formic acid dimer is concerted but not correlated.

    PubMed

    Ivanov, Sergei D; Grant, Ian M; Marx, Dominik

    2015-09-28

    With the goal of computing quantum free energy landscapes of reactive (bio)chemical systems in multi-dimensional space, we combine the metadynamics technique for sampling potential energy surfaces with the ab initio path integral approach to treating nuclear quantum motion. This unified method is applied to the double proton transfer process in the formic acid dimer (FAD), in order to study the nuclear quantum effects at finite temperatures without imposing a one-dimensional reaction coordinate or reducing the dimensionality. Importantly, the ab initio path integral metadynamics technique allows one to treat the hydrogen bonds and concomitant proton transfers in FAD strictly independently and thus provides direct access to the much discussed issue of whether the double proton transfer proceeds via a stepwise or concerted mechanism. The quantum free energy landscape we compute for this H-bonded molecular complex reveals that the two protons move in a concerted fashion from initial to product state, yet world-line analysis of the quantum correlations demonstrates that the protons are as quantum-uncorrelated at the transition state as they are when close to the equilibrium structure.

  1. Perspective on the reactions between F- and CH3CH2F: the free energy landscape of the E2 and SN2 reaction channels.

    PubMed

    Ensing, Bernd; Klein, Michael L

    2005-05-10

    Recently, we computed the 3D free energy surface of the base-induced elimination reaction between F(-) and CH(3)CH(2)F by using a powerful technique within Car-Parrinello molecular dynamics simulation. Here, the set of three order parameters is expanded to six, which allows the study of the competing elimination and substitution reactions simultaneously. The power of the method is exemplified by the exploration of the six-dimensional free energy landscape, sampling, and mapping out the eight stable states as well as the connecting bottlenecks. The free energy profile and barrier along the E2 and S(N)2 reaction channels are refined by using umbrella sampling. The two mechanisms do not share a common "E2C-like" transition state. Comparison with the zero temperature profiles shows a particularly significant entropy contribution to the S(N)2 channel.

  2. Mars Landscapes

    NASA Video Gallery

    Spacecraft have studied the Martian surface for decades, giving Earthlings insights into the history, climate and geology of our nearest neighbor, Mars. These images are from "Mars Landscapes," a v...

  3. Using Field Observations and Satellite Data for the Energy and Water Cycle Study over Heterogeneous Landscape of the Third Pole Region

    NASA Astrophysics Data System (ADS)

    Ma, Y.

    2014-12-01

    The exchange of energy and water vapor transportation between land surface and atmosphere over the Tibetan Plateau area play an important role in the Asian monsoon system, which in turn is a major component of both the energy and water cycles of the global climate system. Supported by the Chinese Academy of Sciences and some international organizations, a Third Pole Environment (TPE) Research Platform (TPEP) is now implementing over the Tibetan Plateau and surrounding region. The background of the establishment of the TPEP, the establishing and monitoring plan of long-term scale (5-10 years) of the TPEP will be shown firstly. Then the preliminary observational analysis results, such as the characteristics of land surface heat fluxes and evapotranspiration (ET) partitioning (diurnal variation, inter-monthly variation and vertical variation etc), the characteristics of atmospheric and soil variables, the structure of the Atmospheric Boundary Layer (ABL) and the turbulent characteristics have also been shown in this study. The study on the regional distribution of land surface heat fluxes and ET are of paramount importance over heterogeneous landscape of the Tibetan Plateau. The parameterization methods based on satellite data (AVHRR and MODIS) and Atmospheric Boundary Layer (ABL) observations have been proposed and tested for deriving surface reflectance, surface temperature, net radiation flux, soil heat flux, sensible heat flux, latent heat flux and ET over heterogeneous landscape. As cases study, the methods were applied to the whole Tibetan Plateau area. Four scenes of AVHRR data and eight scenes of MODIS data were used in this study. And the results showed that the proposed methodology is reasonable for the deriving surface heat fluxes and ET over heterogeneous landscape.

  4. Free-Energy Landscape of Reverse tRNA Translocation through the Ribosome Analyzed by Electron Microscopy Density Maps and Molecular Dynamics Simulations

    PubMed Central

    Ishida, Hisashi; Matsumoto, Atsushi

    2014-01-01

    To understand the mechanism of reverse tRNA translocation in the ribosome, all-atom molecular dynamics simulations of the ribosome-tRNAs-mRNA-EFG complex were performed. The complex at the post-translocational state was directed towards the translocational and pre-translocational states by fitting the complex into cryo-EM density maps. Between a series of the fitting simulations, umbrella sampling simulations were performed to obtain the free-energy landscape. Multistep structural changes, such as a ratchet-like motion and rotation of the head of the small subunit were observed. The free-energy landscape showed that there were two main free-energy barriers: one between the post-translocational and intermediate states, and the other between the pre-translocational and intermediate states. The former corresponded to a clockwise rotation, which was coupled to the movement of P-tRNA over the P/E-gate made of G1338, A1339 and A790 in the small subunit. The latter corresponded to an anticlockwise rotation of the head, which was coupled to the location of the two tRNAs in the hybrid state. This indicates that the coupled motion of the head rotation and tRNA translocation plays an important role in opening and closing of the P/E-gate during the ratchet-like movement in the ribosome. Conformational change of EF-G was interpreted to be the result of the combination of the external motion by L12 around an axis passing near the sarcin-ricin loop, and internal hinge-bending motion. These motions contributed to the movement of domain IV of EF-G to maintain its interaction with A/P-tRNA. PMID:24999999

  5. Quasar redshifts: the intrinsic component

    NASA Astrophysics Data System (ADS)

    Hansen, Peter M.

    2016-09-01

    The large observed redshift of quasars has suggested large cosmological distances and a corresponding enormous energy output to explain the brightness or luminosity as seen at earth. Alternative or complementary sources of redshift have not been identified by the astronomical community. This study examines one possible source of additional redshift: an intrinsic component based on the plasma characteristics of high temperature and high electron density which are believed to be present.

  6. Structures and free energy landscapes of the A53T mutant-type α-synuclein protein and impact of A53T mutation on the structures of the wild-type α-synuclein protein with dynamics.

    PubMed

    Coskuner, Orkid; Wise-Scira, Olivia

    2013-07-17

    The A53T genetic missense mutation of the wild-type α-synuclein (αS) protein was initially identified in Greek and Italian families with familial Parkinson's disease. Detailed understanding of the structures and the changes induced in the wild-type αS structure by the A53T mutation, as well as establishing the direct relationships between the rapid conformational changes and free energy landscapes of these intrinsically disordered fibrillogenic proteins, helps to enhance our fundamental knowledge and to gain insights into the pathogenic mechanism of Parkinson's disease. We employed extensive parallel tempering molecular dynamics simulations along with thermodynamic calculations to determine the secondary and tertiary structural properties as well as the conformational free energy surfaces of the wild-type and A53T mutant-type αS proteins in an aqueous solution medium using both implicit and explicit water models. The confined aqueous volume effect in the simulations of disordered proteins using an explicit model for water is addressed for a model disordered protein. We also assessed the stabilities of the residual secondary structure component interconversions in αS based on free energy calculations at the atomic level with dynamics using our recently developed theoretical strategy. To the best of our knowledge, this study presents the first detailed comparison of the structural properties linked directly to the conformational free energy landscapes of the monomeric wild-type and A53T mutant-type α-synuclein proteins in an aqueous solution environment. Results demonstrate that the β-sheet structure is significantly more altered than the helical structure upon A53T mutation of the monomeric wild-type αS protein in aqueous solution. The β-sheet content close to the mutation site in the N-terminal region is more abundant while the non-amyloid-β component (NAC) and C-terminal regions show a decrease in β-sheet abundance upon A53T mutation. Obtained results

  7. Why some fitness landscapes are fractal.

    PubMed

    Weinberger, E D; Stadler, P F

    1993-07-21

    Many biological and biochemical measurements, for example the "fitness" of a particular genome, or the binding affinity to a particular substrate, can be treated as a "fitness landscape", an assignment of numerical values to points in sequence space (or some other configuration space). As an alternative to the enormous amount of data required to completely describe such a landscape, we propose a statistical characterization, based on the properties of a random walk through the landscape and, more specifically, its autocorrelation function. Under assumptions roughly satisfied by two classes of simple model landscapes (the N-k model and the p-spin model) and by the landscape of estimated free energies of RNA secondary structures, this autocorrelation function, along with the mean and variance of individual points and the size of the landscape, completely characterize it. Having noted that these and other landscapes of estimated replication and degradation rates all have a well-defined correlation length, we propose a classification of landscapes depending on how the correlation length scales with the diameter of the landscape. The landscapes of some of the kinetic parameters of RNA molecules scale similarly to the model landscapes introduced into evolutionary studies from other fields, such as quadratic spin glasses and the traveling salesman problem, but the correlation length of RNA landscapes are considerably smaller. Nevertheless, both the model and some of the RNA landscapes satisfy a test of self-similarity proposed by Sorkin (1988).

  8. The physical determinants of the DNA conformational landscape: an analysis of the potential energy surface of single-strand dinucleotides in the conformational space of duplex DNA

    PubMed Central

    Elsawy, Karim M.; Hodgson, Michael K.; Caves, Leo S. D.

    2005-01-01

    A multivariate analysis of the backbone and sugar torsion angles of dinucleotide fragments was used to construct a 3D principal conformational subspace (PCS) of DNA duplex crystal structures. The potential energy surface (PES) within the PCS was mapped for a single-strand dinucleotide model using an empirical energy function. The low energy regions of the surface encompass known DNA forms and also identify previously unclassified conformers. The physical determinants of the conformational landscape are found to be predominantly steric interactions within the dinucleotide backbone, with medium-dependent backbone-base electrostatic interactions serving to tune the relative stability of the different local energy minima. The fidelity of the PES to duplex DNA properties is validated through a correspondence to the conformational distribution of duplex DNA crystal structures and the reproduction of observed sequence specific propensities for the formation of A-form DNA. The utility of the PES is demonstrated through its succinct and accurate description of complex conformational processes in simulations of duplex DNA. The study suggests that stereochemical considerations of the nucleic acid backbone play a role in determining conformational preferences of DNA which is analogous to the role of local steric interactions in determining polypeptide secondary structure. PMID:16214808

  9. Circular dichroism and UV resonance raman study of the impact of alcohols on the Gibbs free energy landscape of an alpha-helical peptide.

    PubMed

    Xiong, Kan; Asher, Sanford A

    2010-04-20

    We used CD and UV resonance Raman spectroscopy to study the impact of alcohols on the conformational equilibria and relative Gibbs free energy landscapes along the Ramachandran Psi-coordinate of a mainly poly-Ala peptide, AP with an AAAAA(AAARA)(3)A sequence. 2,2,2-Trifluoroethanol (TFE) most stabilizes the alpha-helix-like conformations, followed by ethanol, methanol, and pure water. The pi-bulge conformation is stabilized more than the alpha-helix, while the 3(10)-helix is destabilized due to the alcohol-increased hydrophobicity. Turns are also stabilized by alcohols. We also found that while TFE induces more alpha-helices, it favors multiple, shorter helix segments.

  10. Landscapes, tourism, and conservation

    PubMed

    Burger

    2000-04-17

    One key aspect of global change is a decrease in ecological integrity as more and more landscapes are developed, leaving a mosaic of intact refuges and degraded patches that may not be sufficient for conserving biodiversity. While increases in human population and shifts in the distribution of people affect land use, the temporary movement of people can have major implications for conservation and biodiversity. Three examples are presented where recreation/tourism can enhance the conservation of land on a landscape scale, leading to habitat protection and biodiversity preservation: (1) Shorebirds often require a matrix of different habitat types during migratory stopovers, and ecotourism can serve as a catalyst for landscape scale protection of habitat. (2) Riparian habitats can serve as corridors to link diverse habitat patches, as well as serving as biodiversity hotspots. (3) Remediation and rehabilitation of contaminated lands, such as those of the US Department of Energy, aimed at developing recreational activities on the uncontaminated portions, can be the most economical form of re-development with no increase in human or ecological risk. Since large areas on many DOE sites have been undisturbed since the Second World War, when they were acquired, they contain unique or valuable ecosystems that serve an important role within their regional landscapes. In all three cases the judicious development of recreational/tourist interests can encourage both the conservation of habitats and the wise management of habitats on a landscape scale. While some species or habitats are too fragile for sustained tourism, many can be managed so that species, ecosystems and ecotourists flourish. By contributing to the economic base of regions, ecotourists/recreationists can influence the protection of land and biodiversity on a landscape scale, contributing to ecosystem management. The human dimensions of land preservation and biodiversity protection are key to long

  11. Intrinsically irreversible heat engine

    DOEpatents

    Wheatley, J.C.; Swift, G.W.; Migliori, A.

    1984-01-01

    A class of heat engines based on an intrinsically irreversible heat transfer process is disclosed. In a typical embodiment the engine comprises a compressible fluid that is cyclically compressed and expanded while at the same time being driven in reciprocal motion by a positive displacement drive means. A second thermodynamic medium is maintained in imperfect thermal contact with the fluid and bears a broken thermodynamic symmetry with respect to the fluid. The second thermodynamic medium is a structure adapted to have a low fluid flow impedance with respect to the compressible fluid, and which is further adapted to be in only moderate thermal contact with the fluid. In operation, thermal energy is pumped along the second medium due to a phase lag between the cyclical heating and cooling of the fluid and the resulting heat conduction between the fluid and the medium. In a preferred embodiment the engine comprises an acoustical drive and a housing containing a gas which is driven at a resonant frequency so as to be maintained in a standing wave. Operation of the engine at acoustic frequencies improves the power density and coefficient of performance. The second thermodynamic medium can be coupled to suitable heat exchangers to utilize the engine as a simple refrigeration device having no mechanical moving parts. Alternatively, the engine is reversible in function so as to be utilizable as a prime mover by coupling it to suitable sources and sinks of heat.

  12. Intrinsically irreversible heat engine

    DOEpatents

    Wheatley, J.C.; Swift, G.W.; Migliori, A.

    1984-12-25

    A class of heat engines based on an intrinsically irreversible heat transfer process is disclosed. In a typical embodiment the engine comprises a compressible fluid that is cyclically compressed and expanded while at the same time being driven in reciprocal motion by a positive displacement drive means. A second thermodynamic medium is maintained in imperfect thermal contact with the fluid and bears a broken thermodynamic symmetry with respect to the fluid. The second thermodynamic medium is a structure adapted to have a low fluid flow impedance with respect to the compressible fluid, and which is further adapted to be in only moderate thermal contact with the fluid. In operation, thermal energy is pumped along the second medium due to a phase lag between the cyclical heating and cooling of the fluid and the resulting heat conduction between the fluid and the medium. In a preferred embodiment the engine comprises an acoustical drive and a housing containing a gas which is driven at a resonant frequency so as to be maintained in a standing wave. Operation of the engine at acoustic frequencies improves the power density and coefficient of performance. The second thermodynamic medium can be coupled to suitable heat exchangers to utilize the engine as a simple refrigeration device having no mechanical moving parts. Alternatively, the engine is reversible in function so as to be utilizable as a prime mover by coupling it to suitable sources and sinks of heat. 11 figs.

  13. Intrinsically irreversible heat engine

    DOEpatents

    Wheatley, John C.; Swift, Gregory W.; Migliori, Albert

    1984-01-01

    A class of heat engines based on an intrinsically irreversible heat transfer process is disclosed. In a typical embodiment the engine comprises a compressible fluid that is cyclically compressed and expanded while at the same time being driven in reciprocal motion by a positive displacement drive means. A second thermodynamic medium is maintained in imperfect thermal contact with the fluid and bears a broken thermodynamic symmetry with respect to the fluid. the second thermodynamic medium is a structure adapted to have a low fluid flow impedance with respect to the compressible fluid, and which is further adapted to be in only moderate thermal contact with the fluid. In operation, thermal energy is pumped along the second medium due to a phase lag between the cyclical heating and cooling of the fluid and the resulting heat conduction between the fluid and the medium. In a preferred embodiment the engine comprises an acoustical drive and a housing containing a gas which is driven at a resonant frequency so as to be maintained in a standing wave. Operation of the engine at acoustic frequencies improves the power density and coefficient of performance. The second thermodynamic medium can be coupled to suitable heat exchangers to utilize the engine as a simple refrigeration device having no mechanical moving parts. Alternatively, the engine is reversible in function so as to be utilizable as a prime mover by coupling it to suitable sources and sinks of heat.

  14. Using field observations and satellite data for the study of energy and water cycle over heterogeneous landscape of the Tibetan Plateau

    NASA Astrophysics Data System (ADS)

    Ma, Yaoming

    2014-05-01

    The Tibetan Plateau, with the most prominent and complicated terrain on the globe and an elevation of more than 4000 m on average above sea leave (msl), is often called the "Third Pole" due to its significance parallel with Antarctica and the Arctic. The exchange of energy and water vapor between land surface and atmosphere over the Tibetan Plateau area play an important role in the Asian monsoon system, which in turn is a major component of both the energy and water cycles of the global climate system. Supported by the Chinese Academy of Sciences and some international organizations, a Third Pole Environment (TPE) Research Platform (TPEP) is now implementing over the Tibetan Plateau and surrounding area. The background of the establishment of the TPEP, the establishing and monitoring plan of long-term scale (5-10 years) of the TPEP will be shown firstly. Then the preliminary observational analysis results, such as the characteristics of land surface heat fluxes,CO2 flux and evapotranspiration (ET) partitioning (diurnal variation, inter-monthly variation and vertical variation etc), the characteristics of atmospheric and soil variables, the structure of the Atmospheric Boundary Layer (ABL) and the turbulent characteristics have also been shown in this study. The study on the regional distribution of land surface heat fluxes and ET are of paramount importance over heterogeneous landscape of the Tibetan Plateau. The parameterization methods based on satellite data (AVHRR and MODIS) and Atmospheric Boundary Layer (ABL) observations have been proposed and tested for deriving surface reflectance, surface temperature, net radiation flux, soil heat flux, sensible heat flux, latent heat flux and ET over heterogeneous landscape. As cases study, the methods were applied to the whole Tibetan Plateau area. Four scenes of AVHRR data and four scenes of MODIS data were used in this study. To validate the proposed methods, the ground-measured surface reflectance, surface

  15. Using in-situ and satellite data for the energy and water cycle study over heterogeneous landscape of the Third Pole region

    NASA Astrophysics Data System (ADS)

    Ma, Y.

    2015-12-01

    The exchange of energy and water vapor between land surface and atmosphere over the Tibetan Plateau area play an important role in the Asian monsoon system, which in turn is a major component of both the energy and water cycles of the global climate system. Supported by the Chinese Academy of Sciences and some international organizations, a Third Pole Environment (TPE) Research Platform (TPEP) is now implementing over the Tibetan Plateau and surrounding area. The background of the establishment of the TPEP, the establishing and monitoring plan of long-term scale (5-10 years) of the TPEP will be shown firstly. Then the preliminary observational analysis results, such as the characteristics of land surface heat fluxes, and evapotranspiration (ET) partitioning, the characteristics of atmospheric variables, the structure of the Atmospheric Boundary Layer (ABL) and the turbulent characteristics have also been shown in this study. The study on the regional distribution of land surface heat fluxes and ET are of paramount importance over heterogeneous landscape of the Tibetan Plateau. The parameterization method based on satellite data and the ABL observations has been proposed and tested for deriving regional distribution and their ten years variations of land surface variables, land surface heat fluxes and ET over heterogeneous landscape of the whole Tibetan Plateau area. To validate the proposed method, the ground-measured s land surface variables and surface heat fluxes in the TPEP are compared to satellite derived values. The results show that the derived land surface variables, land surface heat fluxes and ET over the study area are in good accordance with the land surface status. These parameters show a wide range due to the strong contrast of surface features. The sensible heat flux is decreasing while the latent heat flux is increasing from 2001 to 2010 over the whole Tibetan Plateau. And the estimated land surface variables and land surface heat fluxes are in

  16. Influence of increasing active-layer depth and continued permafrost degradation on carbon, water and energy fluxes over two forested permafrost landscapes in the Taiga Plains, NWT, Canada

    NASA Astrophysics Data System (ADS)

    Sonnentag, O.; Baltzer, J.; Chasmer, L. E.; Detto, M.; Marsh, P.; Quinton, W. L.

    2012-12-01

    Recent research suggests an increase in active-layer depth (ALD) in the continuous permafrost zone and degradation of the discontinuous permafrost zone into seasonally frozen. Increasing ALD and continued permafrost degradation will have far-reaching consequences for northern ecosystems including altered regional hydrology and the exposure of additional soil organic carbon (C) to microbial decomposition. These changes might cause positive or negative net feedbacks to the climate system by altering important land surface properties and/or by releasing stored soil organic C to the atmosphere as CO2 and/or CH4. Knowledge gaps exist regarding the links between increasing ALD and/or permafrost degradation, regional hydrology, vegetation composition and structure, land surface properties, and CO2 and CH4 sink-source strengths. The goal of our interdisciplinary project is to shed light on these links by providing a mechanistic understanding of permafrost-thawing consequences for hydrological, ecophysiological and biogeochemical processes at two forested permafrost landscapes in the Taiga Plains, NWT, Canada: Scotty Creek and Havikpak Creek in the discontinuous and in the continuous permafrost zones, respectively (Fig.). The sites will be equipped with identical sets of instrumentation (start: 2013), to measure landscape-scale net exchanges of CO2, CH4, water and energy with the eddy covariance technique. These measurements will be complemented by repeated surveys of surface and frost table topography and vegetation, by land cover-type specific fluxes of CO2 and CH4 measured with a static chamber technique, and by remote sensing-based footprint analysis. With this research we will address the following questions: What is the net effect of permafrost thawing-induced biophysical and biogeochemical feedbacks to the climate system? How do these two different types of feedback differ between the discontinuous and continuous permafrost zones? Is the decrease (increase) in net CO

  17. Energy landscapes of dynamic ensembles of rolling triplet repeat bulge loops: implications for DNA expansion associated with disease states.

    PubMed

    Völker, Jens; Gindikin, Vera; Klump, Horst H; Plum, G Eric; Breslauer, Kenneth J

    2012-04-04

    DNA repeat domains can form ensembles of canonical and noncanonical states, including stable and metastable DNA secondary structures. Such sequence-induced structural diversity creates complex conformational landscapes for DNA processing pathways, including those triplet expansion events that accompany replication, recombination, and/or repair. Here we demonstrate further levels of conformational complexity within repeat domains. Specifically, we show that bulge loop structures within an extended repeat domain can form dynamic ensembles containing a distribution of loop positions, thereby yielding families of positional loop isomers, which we designate as "rollamers". Our fluorescence, absorbance, and calorimetric data are consistent with loop migration/translocation between sites within the repeat domain ("rollamerization"). We demonstrate that such "rollameric" migration of bulge loops within repeat sequences can invade and disrupt previously formed base-paired domains via an isoenthalpic, entropy-driven process. We further demonstrate that destabilizing abasic lesions alter the loop distributions so as to favor "rollamers" with the lesion positioned at the duplex/loop junction, sites where the flexibility of the abasic "universal hinge" relaxes unfavorable interactions and/or facilitates topological accommodation. Another strategic siting of an abasic site induces directed loop migration toward denaturing domains, a phenomenon that merges destabilizing domains. In the aggregate, our data reveal that dynamic ensembles within repeat domains profoundly impact the overall energetics of such DNA constructs as well as the distribution of states by which they denature/renature. These static and dynamic influences within triplet repeat domains expand the conformational space available for selection and targeting by the DNA processing machinery. We propose that such dynamic ensembles and their associated impact on DNA properties influence pathways that lead to DNA

  18. Intrinsic Nilpotent Approximation.

    DTIC Science & Technology

    1985-06-01

    RD-A1II58 265 INTRINSIC NILPOTENT APPROXIMATION(U) MASSACHUSETTS INST 1/2 OF TECH CAMBRIDGE LAB FOR INFORMATION AND, DECISION UMCLRSSI SYSTEMS C...TYPE OF REPORT & PERIOD COVERED Intrinsic Nilpotent Approximation Technical Report 6. PERFORMING ORG. REPORT NUMBER LIDS-R-1482 7. AUTHOR(.) S...certain infinite-dimensional filtered Lie algebras L by (finite-dimensional) graded nilpotent Lie algebras or g . where x E M, (x,,Z) E T*M/O. It

  19. Molecular Structure and Free Energy Landscape for Electron Transport in the Deca-Heme Cytochrome MtrF

    SciTech Connect

    Breuer, Marian; Zarzycki, Piotr P.; Shi, Liang; Clarke, Thomas; Edwards, Marcus; Butt, Julea N.; Richardson, David J.; Fredrickson, Jim K.; Zachara, John M.; Blumberger, Jochen; Rosso, Kevin M.

    2012-12-01

    The free energy profile for electron flow through the bacterial deca-heme cytochrome MtrF has been computed using thermodynamic integration and classical molecular dynamics. The extensive calculations on two versions of the structure help validate the method and results, because differences in the profiles can be related to differences in the charged amino acids local to specific heme groups. First estimates of reorganization free energies λ yield a range consistent with expectations for partially solvent exposed cofactors, and reveal an activation energy range surmountable for electron flow. Future work will aim at increasing the accuracy of λ with polarizable force field dynamics and quantum chemical energy gap calculations, as well as quantum chemical computation of electronic coupling matrix elements.

  20. Structures and free energy landscapes of the wild-type and A30P mutant-type α-synuclein proteins with dynamics.

    PubMed

    Wise-Scira, Olivia; Aloglu, Ahmet Kemal; Dunn, Aquila; Sakallioglu, Isin Tuna; Coskuner, Orkid

    2013-03-20

    The genetic missense A30P mutation of the wild-type α-synuclein protein results in the replacement of the 30th amino acid residue from alanine (Ala) to proline (Pro) and was initially found in the members of a German family who developed Parkinson's disease. Even though the structures of these proteins have been measured before, detailed understanding about the structures and their relationships with free energy landscapes is lacking, which is of interest to provide insights into the pathogenic mechanism of Parkinson's disease. We report the secondary and tertiary structures and conformational free energy landscapes of the wild-type and A30P mutant-type α-synuclein proteins in an aqueous solution environment via extensive parallel tempering molecular dynamics simulations along with thermodynamic calculations. In addition, we present the residual secondary structure component transition stabilities at the atomic level with dynamics in terms of free energy change calculations using a new strategy that we reported most recently. Our studies yield new interesting results; for instance, we find that the A30P mutation has local as well as long-range effects on the structural properties of the wild-type α-synuclein protein. The helical content at Ala18-Gly31 is less prominent in comparison to the wild-type α-synuclein protein. The β-sheet structure abundance decreases in the N-terminal region upon A30P mutation of the wild-type α-synuclein, whereas the NAC and C-terminal regions possess larger tendencies for β-sheet structure formation. Long-range intramolecular protein interactions are less abundant upon A30P mutation, especially between the NAC and C-terminal regions, which is linked to the less compact and less stable structures of the A30P mutant-type rather than the wild-type α-synuclein protein. Results including the usage of our new strategy for secondary structure transition stabilities show that the A30P mutant-type α-synuclein tendency toward

  1. Seasonal dynamics of the land surface energy balance of a boreal forest-peatland landscape affected by degrading permafrost in the Taiga Plains, Canada

    NASA Astrophysics Data System (ADS)

    Helbig, M.; Wischnewski, K.; Chasmer, L.; Quinton, W. L.; Kljun, N.; Detto, M.; Sonnentag, O.

    2014-12-01

    Northern boreal ecosystems along the southern limit of permafrost comprise a mosaic of forests with permafrost, and permafrost-free peatland and lake ecosystems. The proportion of permafrost-free areas has rapidly increased over the last decades due to increasingly warmer air temperatures. This change in land cover causes changes in vegetation composition and structure affecting land surface characteristics such as albedo and surface roughness with important implications for the land surface energy balance and thus regional climate. For example, a decrease in sensible heat flux potentially cools the atmosphere and thus constitutes a negative feedback to the climate system. Changes in latent heat fluxes alter regional water vapour dynamics and thus may affect precipitation patterns. To better understand the land surface energy balance under the influence of degrading permafrost, we measured sensible and latent heat fluxes with two eddy covariance systems, one at 15 m and one at 2 m above the ground surface, along with net radiation and soil heat flux at Scotty Creek, a watershed in the discontinuous permafrost zone in the southern part of the Northwest Territories, Canada. The flux footprint of the 15 m-eddy covariance system covers an area equally covered by black spruce forests and permafrost-free, treeless peatlands whereas the flux footprint of the adjacent 2 m-eddy covariance system covers a single bog within the footprint of the 15 m system. Peak sensible heat fluxes at the bog were up to 200 W m-2 smaller than the landscape-scale fluxes between April and July 2014. During the snow free period, peak latent heat fluxes at the wet bog were about 50 W m-2 higher than the landscape-scale fluxes. Albedo of the forest was generally smaller compared to the bog except for the immediate post-melt period when the bog was affected by widespread surface flooding. This difference in albedo leads to higher net radiation at the forest site, particularly during the snow cover

  2. Dimerization and conformation-related free energy landscapes of dye-tagged amyloid-β12-28 linked to FRET experiments.

    PubMed

    Kulesza, Alexander; Daly, Steven; Dugourd, Philippe

    2017-03-24

    We have investigated the free energy landscape of Aβ-peptide dimer models in connection to gas-phase FRET experiments. We use a FRET-related distance coordinate and one conformation-related coordinate per monomer for accelerated structural exploration with well-tempered metadynamics in solvent and in vacuo. The free energy profiles indicate that FRET under equilibrium conditions should be significantly affected by the de-solvation upon the transfer of ions to the gas-phase. In contrast, a change in the protonation state is found to be less impacting once de-solvated. Comparing F19P and WT alloforms, for which we measure different FRET efficiencies in the gas-phase, we predict only the relevant structural differences in the solution populations, not under gas-phase equilibrium conditions. This finding supports the hypothesis that the gas-phase action-FRET measurement after ESI operates under non-equilibrium conditions, with a memory of the solution conditions - even for the dimer of this relatively short peptide. The structural differences in solution are rationalized in terms of conformational propensities around residue 19, which show a transition to a poly-proline type of pattern upon mutation to F19P - a difference that gets lost in the gas-phase.

  3. Characterization of the polymer energy landscape in polymer:fullerene bulk heterojunctions with pure and mixed phases.

    PubMed

    Sweetnam, Sean; Graham, Kenneth R; Ngongang Ndjawa, Guy O; Heumüller, Thomas; Bartelt, Jonathan A; Burke, Timothy M; Li, Wentao; You, Wei; Amassian, Aram; McGehee, Michael D

    2014-10-08

    Theoretical and experimental studies suggest that energetic offsets between the charge transport energy levels in different morphological phases of polymer:fullerene bulk heterojunctions may improve charge separation and reduce recombination in polymer solar cells (PSCs). In this work, we use cyclic voltammetry, UV-vis absorption, and ultraviolet photoelectron spectroscopy to characterize hole energy levels in the polymer phases of polymer:fullerene bulk heterojunctions. We observe an energetic offset of up to 150 meV between amorphous and crystalline polymer due to bandgap widening associated primarily with changes in polymer conjugation length. We also observe an energetic offset of up to 350 meV associated with polymer:fullerene intermolecular interactions. The first effect has been widely observed, but the second effect is not always considered despite being larger in magnitude for some systems. These energy level shifts may play a major role in PSC performance and must be thoroughly characterized for a complete understanding of PSC function.

  4. Free energy landscape for glucose condensation and dehydration reactions in dimethyl sulfoxide and the effects of solvent.

    PubMed

    Qian, Xianghong; Liu, Dajiang

    2014-03-31

    The mechanisms and free energy surfaces (FES) for the initial critical steps during proton-catalyzed glucose condensation and dehydration reactions were elucidated in dimethyl sulfoxide (DMSO) using Car-Parrinello molecular dynamics (CPMD) coupled with metadynamics (MTD) simulations. Glucose condensation reaction is initiated by protonation of C1--OH whereas dehydration reaction is initiated by protonation of C2--OH. The mechanisms in DMSO are similar to those in aqueous solution. The DMSO molecules closest to the C1--OH or C2--OH on glucose are directly involved in the reactions and act as proton acceptors during the process. However, the energy barriers are strongly solvent dependent. Moreover, polarization from the long-range electrostatic interaction affects the mechanisms and energetics of glucose reactions. Experimental measurements conducted in various DMSO/Water mixtures also show that energy barriers are solvent dependent in agreement with our theoretical results.

  5. Time scales and mechanisms of relaxation in the energy landscape of polymer glass under deformation: direct atomistic modeling.

    PubMed

    Lyulin, Alexey V; Michels, M A J

    2007-08-24

    Molecular-dynamics simulation is used to explore the influence of thermal and mechanical history of typical glassy polymers on their deformation. Polymer stress-strain and energy-strain developments have been followed for different deformation velocities, also in closed extension-recompression loops. The latter simulate for the first time the experimentally observed mechanical rejuvenation and overaging of polymers, and energy partitioning reveals essential differences between mechanical and thermal rejuvenation. All results can be qualitatively interpreted by considering the ratios of the relevant time scales: for cooling down, for deformation, and for segmental relaxation.

  6. Proximity to Intrinsic Depolarizing Resonances with a Partial Siberian Snake

    NASA Astrophysics Data System (ADS)

    Crandell, D. A.; Alexeeva, L. V.; Anferov, V. A.; Blinov, B. B.; Chu, C. M.; Caussyn, D. D.; Courant, E. D.; Gladycheva, S. E.; Hu, S.; Krisch, A. D.; Nurushev, T. S.; Phelps, R. A.; Ratner, L. G.; Varzar, S. M.; Wong, V. K.; Derbenev, Ya. S.; Lee, S. Y.; Rinckel, T.; Schwandt, P.; Sperisen, F.; Stephenson, E. J.; von Przewoski, B.; Baiod, R.; Russell, A. D.; Ohmori, C.; Sato, H.

    1996-05-01

    Partial Siberian snakes are effective in overcoming imperfection depolarizing resonances, but they may also change the crossing energy for intrinsic depolarizing resonances. We experimentally investigated the effect of a partial Siberian snake near intrinsic depolarizing resonances with stored 140 MeV and 160 MeV polarized proton beams. Using various partial Siberian snake strengths up to 30%, depolarization was observed; this may be due to a change in the spin precession frequency which moves the energy of nearby intrinsic depolarizing resonances.

  7. Energy landscape of a GSTP1 polymorph linked with cytological function decay in response to chemical stressors.

    PubMed

    Basharat, Zarrin; Yasmin, Azra

    2017-04-20

    Gene polymorphisms lead to varied structure and functional properties. A single nucleotide polymorphism (SNP) i.e. Ile105Val (rs1695) in glutathione S-transferase P1 (GSTP1) gene influences cytological toxicity and modulates the risk to occupational diseases. Apart from this, cancer, neuropathy, NOx, SOx and ozone mediated respiratory function decline including lung inflammation, asthma, allergy etc., have been reported in people with this missense mutation. Here, the functional properties of rs1695 polymorph are revisited through a computational approach. Changes incurred by GSTP1 antioxidant protein as a result of alteration in its sequence, have been studied through docking followed by Poisson-Boltzmann electrostatic equation interpretation, grid and coulombic energy profile mapping for protein polymorphs with DelPhi. Molecular docking simulation of variant and wild type (WT) protein was carried out with eight FDA approved compounds that target GSTP1 for treatment of various diseases. This was to observe binding pattern variation upon mutation induction. Grid, reaction field and coulombic energy calculation of WT and mutated polymorph, complexed with and without these moieties was then attempted. Alteration in conformation and energy was observed in apo- and holo- form of GSTP1 and their ligand-bound complexes as a result of this mutation. This study is a demo of appraising gene-environment interaction based deleteriousness through molecular docking and dynamics simulation approach.

  8. Conformational landscape of the HIV-V3 hairpin loop from all-atom free-energy simulations

    NASA Astrophysics Data System (ADS)

    Verma, Abhinav; Wenzel, Wolfgang

    2008-03-01

    Small beta hairpins have many distinct biological functions, including their involvement in chemokine and viral receptor recognition. The relevance of structural similarities between different hairpin loops with near homologous sequences is not yet understood, calling for the development of methods for de novo hairpin structure prediction and simulation. De novo folding of beta strands is more difficult than that of helical proteins because of nonlocal hydrogen bonding patterns that connect amino acids that are distant in the amino acid sequence and there is a large variety of possible hydrogen bond patterns. Here we use a greedy version of the basin hopping technique with our free-energy forcefield PFF02 to reproducibly and predictively fold the hairpin structure of a HIV-V3 loop. We performed 20 independent basin hopping runs for 500cycles corresponding to 7.4×107 energy evaluations each. The lowest energy structure found in the simulation has a backbone root mean square deviation (bRMSD) of only 2.04Å to the native conformation. The lowest 9 out of the 20 simulations converged to conformations deviating less than 2.5Å bRMSD from native.

  9. PESP Landscaping Initiative

    EPA Pesticide Factsheets

    Landscaping practices can positively or negatively affect local environments and human health. The Landscaping Initiative seeks to enhance benefits of landscaping while reducing need for pesticides, fertilizers, etc., by working with partners.

  10. Enhancing the Simplified Surface Energy Balance (SSEB) approach for estimating landscape ET: Validation with the METRIC model

    USGS Publications Warehouse

    Senay, G.B.; Budde, M.E.; Verdin, J.P.

    2011-01-01

    Evapotranspiration (ET) can be derived from satellite data using surface energy balance principles. METRIC (Mapping EvapoTranspiration at high Resolution with Internalized Calibration) is one of the most widely used models available in the literature to estimate ET from satellite imagery. The Simplified Surface Energy Balance (SSEB) model is much easier and less expensive to implement. The main purpose of this research was to present an enhanced version of the Simplified Surface Energy Balance (SSEB) model and to evaluate its performance using the established METRIC model. In this study, SSEB and METRIC ET fractions were compared using 7 Landsat images acquired for south central Idaho during the 2003 growing season. The enhanced SSEB model compared well with the METRIC model output exhibiting an r2 improvement from 0.83 to 0.90 in less complex topography (elevation less than 2000m) and with an improvement of r2 from 0.27 to 0.38 in more complex (mountain) areas with elevation greater than 2000m. Independent evaluation showed that both models exhibited higher variation in complex topographic regions, although more with SSEB than with METRIC. The higher ET fraction variation in the complex mountainous regions highlighted the difficulty of capturing the radiation and heat transfer physics on steep slopes having variable aspect with the simple index model, and the need to conduct more research. However, the temporal consistency of the results suggests that the SSEB model can be used on a wide range of elevation (more successfully up 2000m) to detect anomalies in space and time for water resources management and monitoring such as for drought early warning systems in data scarce regions. SSEB has a potential for operational agro-hydrologic applications to estimate ET with inputs of surface temperature, NDVI, DEM and reference ET. ?? 2010.

  11. Enhancing the Simplified Surface Energy Balance (SSEB) Approach for Estimating Landscape ET: Validation with the METRIC model

    USGS Publications Warehouse

    Senay, Gabriel B.; Budde, Michael E.; Verdin, James P.

    2011-01-01

    Evapotranspiration (ET) can be derived from satellite data using surface energy balance principles. METRIC (Mapping EvapoTranspiration at high Resolution with Internalized Calibration) is one of the most widely used models available in the literature to estimate ET from satellite imagery. The Simplified Surface Energy Balance (SSEB) model is much easier and less expensive to implement. The main purpose of this research was to present an enhanced version of the Simplified Surface Energy Balance (SSEB) model and to evaluate its performance using the established METRIC model. In this study, SSEB and METRIC ET fractions were compared using 7 Landsat images acquired for south central Idaho during the 2003 growing season. The enhanced SSEB model compared well with the METRIC model output exhibiting an r2 improvement from 0.83 to 0.90 in less complex topography (elevation less than 2000 m) and with an improvement of r2 from 0.27 to 0.38 in more complex (mountain) areas with elevation greater than 2000 m. Independent evaluation showed that both models exhibited higher variation in complex topographic regions, although more with SSEB than with METRIC. The higher ET fraction variation in the complex mountainous regions highlighted the difficulty of capturing the radiation and heat transfer physics on steep slopes having variable aspect with the simple index model, and the need to conduct more research. However, the temporal consistency of the results suggests that the SSEB model can be used on a wide range of elevation (more successfully up 2000 m) to detect anomalies in space and time for water resources management and monitoring such as for drought early warning systems in data scarce regions. SSEB has a potential for operational agro-hydrologic applications to estimate ET with inputs of surface temperature, NDVI, DEM and reference ET.

  12. Navigating ligand protein binding free energy landscapes: universality and diversity of protein folding and molecular recognition mechanisms

    NASA Astrophysics Data System (ADS)

    Verkhivker, Gennady M.; Rejto, Paul A.; Bouzida, Djamal; Arthurs, Sandra; Colson, Anthony B.; Freer, Stephan T.; Gehlhaar, Daniel K.; Larson, Veda; Luty, Brock A.; Marrone, Tami; Rose, Peter W.

    2001-03-01

    Thermodynamic and kinetic aspects of ligand-protein binding are studied for the methotrexate-dihydrofolate reductase system from the binding free energy profile constructed as a function of the order parameter. Thermodynamic stability of the native complex and a cooperative transition to the unique native structure suggest the nucleation kinetic mechanism at the equilibrium transition temperature. Structural properties of the transition state ensemble and the ensemble of nucleation conformations are determined by kinetic simulations of the transmission coefficient and ligand-protein association pathways. Structural analysis of the transition states and the nucleation conformations reconciles different views on the nucleation mechanism in protein folding.

  13. Concerted or stepwise: how much do free-energy landscapes tell us about the mechanisms of elimination reactions?

    PubMed

    Duarte, Fernanda; Gronert, Scott; Kamerlin, Shina Caroline Lynn

    2014-02-07

    The base-catalyzed dehydration of benzene cis-1,2-dihydrodiols is driven by formation of an aromatic product as well as intermediates potentially stabilized by hyperaromaticity. Experiments exhibit surprising shifts in isotope effects, indicating an unusual mechanistic balance on the E2-E1cB continuum. In this study, both 1- and 2-dimensional free energy surfaces are generated for these compounds with various substituents, using density functional theory and a mixed implicit/explicit solvation model. The computational data help unravel hidden intermediates along the reaction coordinate and provide a novel conceptual framework for distinguishing between competing pathways in this and any other system with borderline reaction mechanisms.

  14. Reconstructing the free-energy landscape of Met-enkephalin using dihedral principal component analysis and well-tempered metadynamics

    NASA Astrophysics Data System (ADS)

    Sicard, François; Senet, Patrick

    2013-06-01

    Well-Tempered Metadynamics (WTmetaD) is an efficient method to enhance the reconstruction of the free-energy surface of proteins. WTmetaD guarantees a faster convergence in the long time limit in comparison with the standard metadynamics. It still suffers, however, from the same limitation, i.e., the non-trivial choice of pertinent collective variables (CVs). To circumvent this problem, we couple WTmetaD with a set of CVs generated from a dihedral Principal Component Analysis (dPCA) on the Ramachandran dihedral angles describing the backbone structure of the protein. The dPCA provides a generic method to extract relevant CVs built from internal coordinates, and does not depend on the alignment to an arbitrarily chosen reference structure as usual in Cartesian PCA. We illustrate the robustness of this method in the case of a reference model protein, the small and very diffusive Met-enkephalin pentapeptide. We propose a justification a posteriori of the considered number of CVs necessary to bias the metadynamics simulation in terms of the one-dimensional free-energy profiles associated with Ramachandran dihedral angles along the amino-acid sequence.

  15. Energy landscape of the reactions governing the Na+ deeply occluded state of the Na+/K+-ATPase in the giant axon of the Humboldt squid.

    PubMed

    Castillo, Juan P; De Giorgis, Daniela; Basilio, Daniel; Gadsby, David C; Rosenthal, Joshua J C; Latorre, Ramon; Holmgren, Miguel; Bezanilla, Francisco

    2011-12-20

    The Na(+)/K(+) pump is a nearly ubiquitous membrane protein in animal cells that uses the free energy of ATP hydrolysis to alternatively export 3Na(+) from the cell and import 2K(+) per cycle. This exchange of ions produces a steady-state outwardly directed current, which is proportional in magnitude to the turnover rate. Under certain ionic conditions, a sudden voltage jump generates temporally distinct transient currents mediated by the Na(+)/K(+) pump that represent the kinetics of extracellular Na(+) binding/release and Na(+) occlusion/deocclusion transitions. For many years, these events have escaped a proper thermodynamic treatment due to the relatively small electrical signal. Here, taking the advantages offered by the large diameter of the axons from the squid Dosidicus gigas, we have been able to separate the kinetic components of the transient currents in an extended temperature range and thus characterize the energetic landscape of the pump cycle and those transitions associated with the extracellular release of the first Na(+) from the deeply occluded state. Occlusion/deocclusion transition involves large changes in enthalpy and entropy as the ion is exposed to the external milieu for release. Binding/unbinding is substantially less costly, yet larger than predicted for the energetic cost of an ion diffusing through a permeation pathway, which suggests that ion binding/unbinding must involve amino acid side-chain rearrangements at the site.

  16. Energy landscape of the reactions governing the Na+ deeply occluded state of the Na+/K+-ATPase in the giant axon of the Humboldt squid

    PubMed Central

    Castillo, Juan P.; De Giorgis, Daniela; Basilio, Daniel; Gadsby, David C.; Rosenthal, Joshua J. C.; Latorre, Ramon; Holmgren, Miguel; Bezanilla, Francisco

    2011-01-01

    The Na+/K+ pump is a nearly ubiquitous membrane protein in animal cells that uses the free energy of ATP hydrolysis to alternatively export 3Na+ from the cell and import 2K+ per cycle. This exchange of ions produces a steady-state outwardly directed current, which is proportional in magnitude to the turnover rate. Under certain ionic conditions, a sudden voltage jump generates temporally distinct transient currents mediated by the Na+/K+ pump that represent the kinetics of extracellular Na+ binding/release and Na+ occlusion/deocclusion transitions. For many years, these events have escaped a proper thermodynamic treatment due to the relatively small electrical signal. Here, taking the advantages offered by the large diameter of the axons from the squid Dosidicus gigas, we have been able to separate the kinetic components of the transient currents in an extended temperature range and thus characterize the energetic landscape of the pump cycle and those transitions associated with the extracellular release of the first Na+ from the deeply occluded state. Occlusion/deocclusion transition involves large changes in enthalpy and entropy as the ion is exposed to the external milieu for release. Binding/unbinding is substantially less costly, yet larger than predicted for the energetic cost of an ion diffusing through a permeation pathway, which suggests that ion binding/unbinding must involve amino acid side-chain rearrangements at the site. PMID:22143771

  17. Predicting Intrinsic Motivation

    ERIC Educational Resources Information Center

    Martens, Rob; Kirschner, Paul A.

    2004-01-01

    Intrinsic motivation can be predicted from participants' perceptions of the social environment and the task environment (Ryan & Deci, 2000)in terms of control, relatedness and competence. To determine the degree of independence of these factors 251 students in higher vocational education (physiotherapy and hotel management) indicated the extent to…

  18. [Intrinsic cardiac ganglia].

    PubMed

    Birand, Ahmet

    2008-12-01

    Heart has been considered as the source and the seat of emotions, passion and love. But from the dawn of XIXth century, scientists have emphasized that the heart, though life depends on its ceaseless activity, is merely a electromechanical pump, pumping oxygenated blood. Nowadays, we all know that heart pumps blood commensurate with the needs of the body and this unending toil, and its regulation depends on the intrinsic properties of the myocardium, Frank-Starling Law and neurohumoral contribution. It has been understood, though not clearly enough, that these time-tensions may cause structural or functional cardiac impairments and arrhythmias are related to the autonomic nervous system. Less well known and less taken in account in daily cardiology practice is the fact that heart has an intrinsic cardiac nervous system, or "heart brain" consisting of complex ganglia, intrinsic cardiac ganglia containing afferent (receiving), local circuit (interneurons) and efferent (transmitting) sympathetic and parasympathetic neurons. This review enlightens structural and functional aspects of intrinsic cardiac ganglia as the very first step in the regulation of cardiac function. This issue is important for targets of pharmacological treatment and techniques of cardiac surgery interventions as repair of septal defects, valvular interventions and congenital corrections.

  19. Competition and Intrinsic Motivation.

    ERIC Educational Resources Information Center

    Tripathi, Kailas Nath

    1992-01-01

    Reports on a study of competition, motivation, and performance among 60 adolescents in India. Finds that direct competition with another person led to higher levels of immediate performance. Also finds that indirect competition against a pre-set standard resulted in greater intrinsic motivation. (CFR)

  20. Evaluating Intrinsic Goals.

    ERIC Educational Resources Information Center

    Silberman, Harry F.

    1984-01-01

    A social learning model focusing on intrinsic outcomes of vocational programs is proposed. It would assess technical skills and knowledge, communication skills and literacy, and personal skills and attitudes. Instruments should be devised to measure characteristics of the learning setting, learner involved activities, and nature of consequences of…

  1. Computing Free Energy Landscapes: Application to Ni-based Electrocatalysts with Pendant Amines for H2 Production and Oxidation

    SciTech Connect

    Chen, Shentan; Ho, Ming-Hsun; Bullock, R. Morris; DuBois, Daniel L.; Dupuis, Michel; Rousseau, Roger J.; Raugei, Simone

    2014-01-03

    A general strategy is reported for computational exploration of catalytic pathways of molecular catalysts. Our results are based on a set of linear free energy relationships derived from extensive electronic structure calculations that permit predicting the thermodynamics of intermediates, with accuracy comparable to experimental data. The approach is exemplified with the catalytic oxidation and production of H2 by [Ni(diphosphine)2]2+ electrocatalysts with pendant amines incorporated in the second coordination sphere of the metal center. The analysis focuses upon prediction of thermodynamic properties including reduction potentials, hydride donor abilities, and pKa values of both the protonated Ni center and pendant amine. It is shown that all of these chemical properties can be estimated from the knowledge of only the two redox potentials for the Ni(II)/Ni(I) and Ni(I)/Ni(0) couples of the non-protonated complex, and the pKa of the parent primary aminium ion. These three quantities are easily accessible either experimentally or theoretically. The proposed correlations reveal intimate details about the nature of the catalytic mechanism and its dependence on chemical structure and thermodynamic conditions such as applied external voltage and species concentration. This computational methodology is applied to exploration of possible catalytic pathways, identifying low and high-energy intermediates and, consequently, possibly avoiding bottlenecks associated with undesirable intermediates in the catalytic reactions. We discuss how to optimize some of the critical reaction steps in order to favor catalytically more efficient intermediates. The results of this study highlight the substantial interplay between the various parameters characterizing the catalytic activity, and form the basis needed to optimize the performance of this class of catalysts.

  2. New insight into the potential energy landscape and relaxation pathways of photoexcited aniline from CASSCF and XMCQDPT2 electronic structure calculations.

    PubMed

    Sala, Matthieu; Kirkby, Oliver M; Guérin, Stéphane; Fielding, Helen H

    2014-02-21

    There have been a number of recent experimental investigations of the nonadiabatic relaxation dynamics of aniline following excitation to the first three singlet excited states, 1(1)ππ*, 1(1)π3s/πσ* and 2(1)ππ*. Motivated by differences between the interpretations of experimental observations, we have employed CASSCF and XMCQDPT2 calculations to explore the potential energy landscape and relaxation pathways of photoexcited aniline. We find a new prefulvene-like MECI connecting the 1(1)ππ* state with the GS in which the carbon-atom carrying the amino group is distorted out-of-plane. This suggests that excitation above the 1(1)π3s/πσ* vertical excitation energy could be followed by electronic relaxation from the 1(1)ππ* state to the ground-electronic state through this MECI. We find a MECI connecting the 1(1)π3s/πσ* and 1(1)ππ* states close to the local minimum on 1(1)π3s/πσ* which suggests that photoexcitation to the 1(1)π3s/πσ* state could be followed by relaxation to the 1(1)ππ* state and to the dissociative component of the 1(1)π3s/πσ* state. We also find evidence for a new pathway from the 2(1)ππ* state to the ground electronic state that is likely to pass through a three-state conical intersection involving the 2(1)ππ*, 1(1)π3s/πσ* and 1(1)ππ* states.

  3. Potential energy landscape of the apparent first-order phase transition between low-density and high-density amorphous ice

    NASA Astrophysics Data System (ADS)

    Giovambattista, Nicolas; Sciortino, Francesco; Starr, Francis W.; Poole, Peter H.

    2016-12-01

    The potential energy landscape (PEL) formalism is a valuable approach within statistical mechanics to describe supercooled liquids and glasses. Here we use the PEL formalism and computer simulations to study the pressure-induced transformations between low-density amorphous ice (LDA) and high-density amorphous ice (HDA) at different temperatures. We employ the ST2 water model for which the LDA-HDA transformations are remarkably sharp, similar to what is observed in experiments, and reminiscent of a first-order phase transition. Our results are consistent with the view that LDA and HDA configurations are associated with two distinct regions (megabasins) of the PEL that are separated by a potential energy barrier. At higher temperature, we find that low-density liquid (LDL) configurations are located in the same megabasin as LDA, and that high-density liquid (HDL) configurations are located in the same megabasin as HDA. We show that the pressure-induced LDL-HDL and LDA-HDA transformations occur along paths that interconnect these two megabasins, but that the path followed by the liquid is different from the path followed by the amorphous solid. At higher pressure, we also study the liquid-to-ice-VII first-order phase transition, and find that the behavior of the PEL properties across this transition is qualitatively similar to the changes found during the LDA-HDA transformation. This similarity supports the interpretation that the LDA-HDA transformation is a first-order phase transition between out-of-equilibrium states. Finally, we compare the PEL properties explored during the LDA-HDA transformations in ST2 water with those reported previously for SPC/E water, for which the LDA-HDA transformations are rather smooth. This comparison illuminates the previous work showing that, at accessible computer times scales, a liquid-liquid phase transition occurs in the case of ST2 water, but not for SPC/E water.

  4. Potential energy landscape of the apparent first-order phase transition between low-density and high-density amorphous ice.

    PubMed

    Giovambattista, Nicolas; Sciortino, Francesco; Starr, Francis W; Poole, Peter H

    2016-12-14

    The potential energy landscape (PEL) formalism is a valuable approach within statistical mechanics to describe supercooled liquids and glasses. Here we use the PEL formalism and computer simulations to study the pressure-induced transformations between low-density amorphous ice (LDA) and high-density amorphous ice (HDA) at different temperatures. We employ the ST2 water model for which the LDA-HDA transformations are remarkably sharp, similar to what is observed in experiments, and reminiscent of a first-order phase transition. Our results are consistent with the view that LDA and HDA configurations are associated with two distinct regions (megabasins) of the PEL that are separated by a potential energy barrier. At higher temperature, we find that low-density liquid (LDL) configurations are located in the same megabasin as LDA, and that high-density liquid (HDL) configurations are located in the same megabasin as HDA. We show that the pressure-induced LDL-HDL and LDA-HDA transformations occur along paths that interconnect these two megabasins, but that the path followed by the liquid is different from the path followed by the amorphous solid. At higher pressure, we also study the liquid-to-ice-VII first-order phase transition, and find that the behavior of the PEL properties across this transition is qualitatively similar to the changes found during the LDA-HDA transformation. This similarity supports the interpretation that the LDA-HDA transformation is a first-order phase transition between out-of-equilibrium states. Finally, we compare the PEL properties explored during the LDA-HDA transformations in ST2 water with those reported previously for SPC/E water, for which the LDA-HDA transformations are rather smooth. This comparison illuminates the previous work showing that, at accessible computer times scales, a liquid-liquid phase transition occurs in the case of ST2 water, but not for SPC/E water.

  5. Potential Energy Landscape of the Electronic States of the GFP Chromophore in Different Protonation Forms: Electronic Transition Energies and Conical Intersections.

    PubMed

    Polyakov, I V; Grigorenko, B L; Epifanovsky, E M; Krylov, A I; Nemukhin, A V

    2010-08-10

    We present the results of quantum chemical calculations of the transition energies and conical intersection points for the two lowest singlet electronic states of the green fluorescent protein chromophore, 4'-hydroxybenzylidene-2,3-dimethylimidazolinone, in the vicinity of its cis conformation in the gas phase. Four protonation states of the chromophore, i.e., anionic, neutral, cationic, and zwitterionic, were considered. Energy differences were computed by the perturbatively corrected complete active space self-consistent field (CASSCF)-based approaches at the corresponding potential energy minima optimized by density functional theory and CASSCF (for the ground and excited states, respectively). We also report the EOM-CCSD and SOS-CIS(D) results for the excitation energies. The minimum energy S0/S1 conical intersection points were located using analytic state-specific CASSCF gradients. The results reproduce essential features of previous ab initio calculations of the anionic form of the chromophore and provide an extension for the neutral, cationic, and zwitterionic forms, which are important in the protein environment. The S1 PES of the anion is fairly flat, and the barrier separating the planar bright conformation from the dark twisted one as well as the conical intersection point with the S0 surface is very small (less than 2 kcal/mol). On the cationic surface, the barrier is considerably higher (∼13 kcal/mol). The PES of the S1 state of the zwitterionic form does not have a planar minimum in the Franck-Condon region. The S1 surface of the neutral form possesses a bright planar minimum; the energy barrier of about 9 kcal/mol separates it from the dark twisted conformation as well as from the conical intersection point leading to the cis-trans chromophore isomerization.

  6. Thermodynamics and kinetics of protein folding on the ribosome: Alteration in energy landscapes, denatured state, and transition state ensembles

    NASA Astrophysics Data System (ADS)

    O'Brien, Edward; Vendruscolo, Michele; Dobson, Christopher

    2010-03-01

    In vitro experiments examining cotranslational folding utilize ribosome-nascent chain complexes (RNCs) in which the nascent chain is stalled at different points of its biosynthesis on the ribosome. We investigate the thermodynamics, kinetics, and structural properties of RNCs containing five different globular and repeat proteins stalled at ten different nascent chain lengths using coarse grained replica exchange simulations. We find that when the proteins are stalled near the ribosome exit tunnel opening they exhibit altered folding coopserativity, quantified by the van't Hoff enthalpy criterion; a significantly altered denatured state ensemble, in terms of Rg and shape parameters (Rg tensor); and the appearance of partially folded intermediates during cotranslation, evidenced by the appearance of a third basin in the free energy profile. These trends are due in part to excluded volume (crowding) interactions between the ribosome and nascent chain. We perform in silico temperature-jump experiments on the RNCs and examine nascent chain folding kinetics and structural changes in the transition state ensemble at various stall lengths.

  7. Molecular dynamics and energy landscape of decanethiolates in self-assembled monolayers on Au(111) studied by scanning tunneling microscopy.

    PubMed

    Sotthewes, Kai; Wu, Hairong; Kumar, Avijit; Vancso, G Julius; Schön, Peter M; Zandvliet, Harold J W

    2013-03-19

    The energetics and dynamics of the various phases of decanethiolate self-assembled monolayers on Au(111) surfaces were studied with scanning tunneling microscopy. We have observed five different phases of the decanethiolate monolayer on Au(111): four ordered phases (β, δ, χ*, and φ) and one disordered phase (ε). We have determined the boundary free energies between the disordered and order phases by analyzing the thermally induced meandering of the domain boundaries. On the basis of these results, we are able to accurately predict the two-dimensional phase diagram of the decanethiolate/Au(111) system. The order-disorder phase transition of the χ* phase occurs at 295 K, followed by the order-disorder phase transition of the β phase at 325 K. Above temperatures of 325 K, only the densely packed φ and disordered ε phases remain. Our findings are in good agreement with the phase diagram of the decanethiolate/Au(111) system that was put forward by Poirier et al. [Langmuir 2001, 17 (4), 1176-1183].

  8. Isomers and Energy Landscapes of Perchlorate-Water Clusters and a Comparison to Pure Water and Sulfate-Water Clusters.

    PubMed

    Hey, John C; Smeeton, Lewis C; Oakley, Mark T; Johnston, Roy L

    2016-06-16

    Hydrated ions are crucially important in a wide array of environments, from biology to the atmosphere, and the presence and concentration of ions in a system can drastically alter its behavior. One way in which ions can affect systems is in their interactions with proteins. The Hofmeister series ranks ions by their ability to salt-out proteins, with kosmotropes, such as sulfate, increasing their stability and chaotropes, such as perchlorate, decreasing their stability. We study hydrated perchlorate clusters as they are strongly chaotropic and thus exhibit different properties than sulfate. In this study we simulate small hydrated perchlorate clusters using a basin-hopping geometry optimization search with empirical potentials. We compare topological features of these clusters to data from both computational and experimental studies of hydrated sulfate ions and draw some conclusions about ion effects in the Hofmeister series. We observe a patterning conferred to the water molecules within the cluster by the presence of the perchlorate ion and compare the magnitude of this effect to that observed in previous studies involving sulfate. We also investigate the influence of the overall ionic charge on the low-energy structures adopted by these clusters.

  9. An approach to assess NEE and C-costs associated with an energy-crop production at different erosion-induced transient states in a typical Northeastern Germany landscape using process-based agroecosystem modeling

    NASA Astrophysics Data System (ADS)

    Chatskikh, D.; Nendel, C.; Hagemann, U.; Specka, X.; Augustin, J.; Sommer, M.; Van Oost, K.

    2012-04-01

    Net Ecosystem Exchange (NEE) and C-costs associated with energy-crop production systems which are outside of NEE must be determined to suggest optimal mitigation options. In theory, NEE can be positive, if SOC is building up, neutral or balanced, with no change in SOC, or negative, if SOC is lost as a result of a soil degradation processes. Unclearness in complex multiscale interactions between different processes in the landscape in combination with a well-known wide range of uncertainties around NEE estimations makes these estimations for landscape scale scarce. In this study we used a process-based modeling to assess C-costs associated with soil erosion, assessing NEE at different erosion-induced transient states in the experiment settled Northeastern Germany (near Dedelow) in a representative section of younger landscape of hummocky ground moraine (CarboZALF-D). We used Monica, a soil-crop-atmosphere model, which is well-validated for various crops and soil in Germany. In the model, NEE (=-NEP) refer to NPP minus C losses in heterotrophic respiration, while NBE (=-NBP) refers to the change in SOC stocks after C losses due to regular (e.g. soil erosion) or occasional (e.g. harvest) disturbances. In this study we applied Monica to analyze relationships between past geomorphic processes, landscape position, crop growth and NEE. In this study we were interested in general trends and associated agroecosystem properties, rather than on magnitude of the fluxes. The results showed that past soil redistribution affected NEE at both positions, while the Monica-based scenarios in combination with data-based interpolations helped to interpret the NEE budgets. The model captured the magnitude of differences in the daily NEE values, but also the differences in an accumulated NEE fluxes between different erosion-induced transient states. Thus for both eroded and deposited positions NEE was negative. However absolute values of NEE were smaller for the deposited site compare to

  10. Estimation of water and energy fluxes over complex landscapes. Two Source Energy Balance modelling using very high resolution thermal and optical imagery in vineyards and wooded rangelands

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Modelling the water and energy balance at the land surface is a crucial task for many applications related to crop production, water resources management, climate change studies, weather forecasting, and natural hazards assessment. To improve the modelling of evapotranspiration (ET) over structurall...

  11. Potential Energy Surface-Based Automatic Deduction of Conformational Transition Networks and Its Application on Quantum Mechanical Landscapes of d-Glucose Conformers.

    PubMed

    Satoh, Hiroko; Oda, Tomohiro; Nakakoji, Kumiyo; Uno, Takeaki; Tanaka, Hiroaki; Iwata, Satoru; Ohno, Koichi

    2016-11-08

    This paper describes our approach that is built upon the potential energy surface (PES)-based conformational analysis. This approach automatically deduces a conformational transition network, called a conformational reaction route map (r-map), by using the Scaled Hypersphere Search of the Anharmonic Downward Distortion Following method (SHS-ADDF). The PES-based conformational search has been achieved by using large ADDF, which makes it possible to trace only low transition state (TS) barriers while restraining bond lengths and structures with high free energy. It automatically performs sampling the minima and TS structures by simply taking into account the mathematical feature of PES without requiring any a priori specification of variable internal coordinates. An obtained r-map is composed of equilibrium (EQ) conformers connected by reaction routes via TS conformers, where all of the reaction routes are already confirmed during the process of the deduction using the intrinsic reaction coordinate (IRC) method. The postcalculation analysis of the deduced r-map is interactively carried out using the RMapViewer software we have developed. This paper presents computational details of the PES-based conformational analysis and its application to d-glucose. The calculations have been performed for an isolated glucose molecule in the gas phase at the RHF/6-31G level. The obtained conformational r-map for α-d-glucose is composed of 201 EQ and 435 TS conformers and that for β-d-glucose is composed of 202 EQ and 371 TS conformers. For the postcalculation analysis of the conformational r-maps by using the RMapViewer software program we have found multiple minimum energy paths (MEPs) between global minima of (1)C4 and (4)C1 chair conformations. The analysis using RMapViewer allows us to confirm the thermodynamic and kinetic predominance of (4)C1 conformations; that is, the potential energy of the global minimum of (4)C1 is lower than that of (1)C4 (thermodynamic predominance

  12. A common landscape for membrane-active peptides

    PubMed Central

    Last, Nicholas B; Schlamadinger, Diana E; Miranker, Andrew D

    2013-01-01

    Three families of membrane-active peptides are commonly found in nature and are classified according to their initial apparent activity. Antimicrobial peptides are ancient components of the innate immune system and typically act by disruption of microbial membranes leading to cell death. Amyloid peptides contribute to the pathology of diverse diseases from Alzheimer's to type II diabetes. Preamyloid states of these peptides can act as toxins by binding to and permeabilizing cellular membranes. Cell-penetrating peptides are natural or engineered short sequences that can spontaneously translocate across a membrane. Despite these differences in classification, many similarities in sequence, structure, and activity suggest that peptides from all three classes act through a small, common set of physical principles. Namely, these peptides alter the Brownian properties of phospholipid bilayers, enhancing the sampling of intrinsic fluctuations that include membrane defects. A complete energy landscape for such systems can be described by the innate membrane properties, differential partition, and the associated kinetics of peptides dividing between surface and defect regions of the bilayer. The goal of this review is to argue that the activities of these membrane-active families of peptides simply represent different facets of what is a shared energy landscape. PMID:23649542

  13. Aspects of structural landscape of human islet amyloid polypeptide

    NASA Astrophysics Data System (ADS)

    He, Jianfeng; Dai, Jin; Li, Jing; Peng, Xubiao; Niemi, Antti J.

    2015-01-01

    The human islet amyloid polypeptide (hIAPP) co-operates with insulin to maintain glycemic balance. It also constitutes the amyloid plaques that aggregate in the pancreas of type-II diabetic patients. We have performed extensive in silico investigations to analyse the structural landscape of monomeric hIAPP, which is presumed to be intrinsically disordered. For this, we construct from first principles a highly predictive energy function that describes a monomeric hIAPP observed in a nuclear magnetic resonance experiment, as a local energy minimum. We subject our theoretical model of hIAPP to repeated heating and cooling simulations, back and forth between a high temperature regime where the conformation resembles a random walker and a low temperature limit where no thermal motions prevail. We find that the final low temperature conformations display a high level of degeneracy, in a manner which is fully in line with the presumed intrinsically disordered character of hIAPP. In particular, we identify an isolated family of α-helical conformations that might cause the transition to amyloidosis, by nucleation.

  14. Aspects of structural landscape of human islet amyloid polypeptide

    SciTech Connect

    He, Jianfeng Dai, Jin; Li, Jing; Peng, Xubiao; Niemi, Antti J.

    2015-01-28

    The human islet amyloid polypeptide (hIAPP) co-operates with insulin to maintain glycemic balance. It also constitutes the amyloid plaques that aggregate in the pancreas of type-II diabetic patients. We have performed extensive in silico investigations to analyse the structural landscape of monomeric hIAPP, which is presumed to be intrinsically disordered. For this, we construct from first principles a highly predictive energy function that describes a monomeric hIAPP observed in a nuclear magnetic resonance experiment, as a local energy minimum. We subject our theoretical model of hIAPP to repeated heating and cooling simulations, back and forth between a high temperature regime where the conformation resembles a random walker and a low temperature limit where no thermal motions prevail. We find that the final low temperature conformations display a high level of degeneracy, in a manner which is fully in line with the presumed intrinsically disordered character of hIAPP. In particular, we identify an isolated family of α-helical conformations that might cause the transition to amyloidosis, by nucleation.

  15. Estimating Evapotranspiration Over Agricultural Landscapes with Thermal Infrared Data: Towards the Comparison of Two Approaches Using Simple Energy Budget and Svat Modeling

    NASA Astrophysics Data System (ADS)

    Bigeard, G.; Coudert, B.; Jarlan, L.

    2011-12-01

    Evapotranspiration (ET) monitoring presents wide range of applications from agriculture and water resources management to meteorology. Several approaches have been developed to retrieve ET based on a joint use of remote sensing data and land surface modeling, in particular with a SVAT (Soil Vegetation Atmosphere Transfers) model or a SEB (Surface Energy Budget) model. The objective of our work is to estimate spatialized ET fluxes from Thermal Infra-Red (TIR) imagery. We will focus on simulating fluxes at low resolution with 2 methodologies: 1- Simulating with a SEB model directly at low resolution (landscape scale: 4km) with TIR forcing. 2- Aggregating high resolution (agricultural field scale) estimates from a SVAT model constrained by TIR data and forced by a spatialized database (landcover, LAI, vegetation height and meteorological forcing). By doing a sensitivity analysis and comparing both approaches we will point out mechanisms that govern scale switching, and how high resolution "informations" and aggregation scenarios impact low resolution estimates. Within this preliminary study, we compare in-situ potentialities of a SEB model (TSEB) versus a SVAT model (SEtHyS). TSEB (Two Sources Equation Balance) is a model of turbulent exchange (Norman & al. 1995) partitioning the available energy between soil and vegetation and driven directly via remote sensing TIR sensors. SEtHyS (French acronym for soil moisture monitoring) is a SVAT model (described by Coudert & al. 2006) which is physically based and has more inputs and parameters requirements. Besides fluxes, it outputs brightness temperatures which can be compared and constrained with TIR data. Models fluxes simulations are compared to in-situ Eddy-Correlation (EC) fluxes measurement stations. Models are then compared performing a sensitivity analysis on their inputs and parameters so as to characterize their capabilities and behaviors, and quantify error ranges that will be induced by spatialization over

  16. Mapping the Free Energy Landscape of PKA Inhibition and Activation: A Double-Conformational Selection Model for the Tandem cAMP-Binding Domains of PKA RIα.

    PubMed

    Akimoto, Madoka; McNicholl, Eric Tyler; Ramkissoon, Avinash; Moleschi, Kody; Taylor, Susan S; Melacini, Giuseppe

    2015-01-01

    Protein Kinase A (PKA) is the major receptor for the cyclic adenosine monophosphate (cAMP) secondary messenger in eukaryotes. cAMP binds to two tandem cAMP-binding domains (CBD-A and -B) within the regulatory subunit of PKA (R), unleashing the activity of the catalytic subunit (C). While CBD-A in RIα is required for PKA inhibition and activation, CBD-B functions as a "gatekeeper" domain that modulates the control exerted by CBD-A. Preliminary evidence suggests that CBD-B dynamics are critical for its gatekeeper function. To test this hypothesis, here we investigate by Nuclear Magnetic Resonance (NMR) the two-domain construct RIα (91-379) in its apo, cAMP2, and C-bound forms. Our comparative NMR analyses lead to a double conformational selection model in which each apo CBD dynamically samples both active and inactive states independently of the adjacent CBD within a nearly degenerate free energy landscape. Such degeneracy is critical to explain the sensitivity of CBD-B to weak interactions with C and its high affinity for cAMP. Binding of cAMP eliminates this degeneracy, as it selectively stabilizes the active conformation within each CBD and inter-CBD contacts, which require both cAMP and W260. The latter is contributed by CBD-B and mediates capping of the cAMP bound to CBD-A. The inter-CBD interface is dispensable for intra-CBD conformational selection, but is indispensable for full activation of PKA as it occludes C-subunit recognition sites within CBD-A. In addition, the two structurally homologous cAMP-bound CBDs exhibit marked differences in their residual dynamics profiles, supporting the notion that conservation of structure does not necessarily imply conservation of dynamics.

  17. THE LANDSCAPE OF THE NEUTRINO MECHANISM OF CORE-COLLAPSE SUPERNOVAE: NEUTRON STAR AND BLACK HOLE MASS FUNCTIONS, EXPLOSION ENERGIES, AND NICKEL YIELDS

    SciTech Connect

    Pejcha, Ondřej; Thompson, Todd A. E-mail: thompson@astronomy.ohio-state.edu

    2015-03-10

    If the neutrino luminosity from the proto-neutron star formed during a massive star core collapse exceeds a critical threshold, a supernova (SN) results. Using spherical quasi-static evolutionary sequences for hundreds of progenitors over a range of metallicities, we study how the explosion threshold maps onto observables, including the fraction of successful explosions, the neutron star (NS) and black hole (BH) mass functions, the explosion energies (E {sub SN}) and nickel yields (M {sub Ni}), and their mutual correlations. Successful explosions are intertwined with failures in a complex pattern that is not simply related to initial progenitor mass or compactness. We predict that progenitors with initial masses of 15 ± 1, 19 ± 1, and ∼21-26 M {sub ☉} are most likely to form BHs, that the BH formation probability is non-zero at solar-metallicity and increases significantly at low metallicity, and that low luminosity, low Ni-yield SNe come from progenitors close to success/failure interfaces. We qualitatively reproduce the observed E {sub SN}-M {sub Ni} correlation, we predict a correlation between the mean and width of the NS mass and E {sub SN} distributions, and that the means of the NS and BH mass distributions are correlated. We show that the observed mean NS mass of ≅ 1.33 M {sub ☉} implies that the successful explosion fraction is higher than 0.35. Overall, we show that the neutrino mechanism can in principle explain the observed properties of SNe and their compact objects. We argue that the rugged landscape of progenitors and outcomes mandates that SN theory should focus on reproducing the wide ranging distributions of observed SN properties.

  18. Do Geographically Isolated Wetlands Influence Landscape Functions?

    EPA Science Inventory

    Landscape functions such as flow generation, nutrient and sediment retention, and biodiversity support depend on the exchange of solutes, particles, energy, and organisms between elements in hydrological and habitat networks. Wetlands are important network elements, providing hyd...

  19. Exploring constrained quantum control landscapes

    NASA Astrophysics Data System (ADS)

    Moore, Katharine W.; Rabitz, Herschel

    2012-10-01

    The broad success of optimally controlling quantum systems with external fields has been attributed to the favorable topology of the underlying control landscape, where the landscape is the physical observable as a function of the controls. The control landscape can be shown to contain no suboptimal trapping extrema upon satisfaction of reasonable physical assumptions, but this topological analysis does not hold when significant constraints are placed on the control resources. This work employs simulations to explore the topology and features of the control landscape for pure-state population transfer with a constrained class of control fields. The fields are parameterized in terms of a set of uniformly spaced spectral frequencies, with the associated phases acting as the controls. This restricted family of fields provides a simple illustration for assessing the impact of constraints upon seeking optimal control. Optimization results reveal that the minimum number of phase controls necessary to assure a high yield in the target state has a special dependence on the number of accessible energy levels in the quantum system, revealed from an analysis of the first- and second-order variation of the yield with respect to the controls. When an insufficient number of controls and/or a weak control fluence are employed, trapping extrema and saddle points are observed on the landscape. When the control resources are sufficiently flexible, solutions producing the globally maximal yield are found to form connected "level sets" of continuously variable control fields that preserve the yield. These optimal yield level sets are found to shrink to isolated points on the top of the landscape as the control field fluence is decreased, and further reduction of the fluence turns these points into suboptimal trapping extrema on the landscape. Although constrained control fields can come in many forms beyond the cases explored here, the behavior found in this paper is illustrative of

  20. Landscape moderation of biodiversity patterns and processes - eight hypotheses.

    PubMed

    Tscharntke, Teja; Tylianakis, Jason M; Rand, Tatyana A; Didham, Raphael K; Fahrig, Lenore; Batáry, Péter; Bengtsson, Janne; Clough, Yann; Crist, Thomas O; Dormann, Carsten F; Ewers, Robert M; Fründ, Jochen; Holt, Robert D; Holzschuh, Andrea; Klein, Alexandra M; Kleijn, David; Kremen, Claire; Landis, Doug A; Laurance, William; Lindenmayer, David; Scherber, Christoph; Sodhi, Navjot; Steffan-Dewenter, Ingolf; Thies, Carsten; van der Putten, Wim H; Westphal, Catrin

    2012-08-01

    Understanding how landscape characteristics affect biodiversity patterns and ecological processes at local and landscape scales is critical for mitigating effects of global environmental change. In this review, we use knowledge gained from human-modified landscapes to suggest eight hypotheses, which we hope will encourage more systematic research on the role of landscape composition and configuration in determining the structure of ecological communities, ecosystem functioning and services. We organize the eight hypotheses under four overarching themes. Section A: 'landscape moderation of biodiversity patterns' includes (1) the landscape species pool hypothesis-the size of the landscape-wide species pool moderates local (alpha) biodiversity, and (2) the dominance of beta diversity hypothesis-landscape-moderated dissimilarity of local communities determines landscape-wide biodiversity and overrides negative local effects of habitat fragmentation on biodiversity. Section B: 'landscape moderation of population dynamics' includes (3) the cross-habitat spillover hypothesis-landscape-moderated spillover of energy, resources and organisms across habitats, including between managed and natural ecosystems, influences landscape-wide community structure and associated processes and (4) the landscape-moderated concentration and dilution hypothesis-spatial and temporal changes in landscape composition can cause transient concentration or dilution of populations with functional consequences. Section C: 'landscape moderation of functional trait selection' includes (5) the landscape-moderated functional trait selection hypothesis-landscape moderation of species trait selection shapes the functional role and trajectory of community assembly, and (6) the landscape-moderated insurance hypothesis-landscape complexity provides spatial and temporal insurance, i.e. high resilience and stability of ecological processes in changing environments. Section D: 'landscape constraints on

  1. Intrinsic excitations in doubly odd nuclei

    SciTech Connect

    Sood, P.C.

    1985-01-15

    A procedure is outlined for predicting the bandhead energies of the two-particle (intrinsic) states of odd-odd deformed nuclei based on a quantitative evaluation of the zero range n-p residual interaction energy. We present our results for 250Bk, where many such levels are experimentally known, and for 236Np and 246Am, where the information is very scarce and that too uncertain, to illustrate the effectiveness of this approach.

  2. Intrinsic optimization using stochastic nanomagnets

    NASA Astrophysics Data System (ADS)

    Sutton, Brian; Camsari, Kerem Yunus; Behin-Aein, Behtash; Datta, Supriyo

    2017-03-01

    This paper draws attention to a hardware system which can be engineered so that its intrinsic physics is described by the generalized Ising model and can encode the solution to many important NP-hard problems as its ground state. The basic constituents are stochastic nanomagnets which switch randomly between the ±1 Ising states and can be monitored continuously with standard electronics. Their mutual interactions can be short or long range, and their strengths can be reconfigured as needed to solve specific problems and to anneal the system at room temperature. The natural laws of statistical mechanics guide the network of stochastic nanomagnets at GHz speeds through the collective states with an emphasis on the low energy states that represent optimal solutions. As proof-of-concept, we present simulation results for standard NP-complete examples including a 16-city traveling salesman problem using experimentally benchmarked models for spin-transfer torque driven stochastic nanomagnets.

  3. Intrinsic optimization using stochastic nanomagnets

    PubMed Central

    Sutton, Brian; Camsari, Kerem Yunus; Behin-Aein, Behtash; Datta, Supriyo

    2017-01-01

    This paper draws attention to a hardware system which can be engineered so that its intrinsic physics is described by the generalized Ising model and can encode the solution to many important NP-hard problems as its ground state. The basic constituents are stochastic nanomagnets which switch randomly between the ±1 Ising states and can be monitored continuously with standard electronics. Their mutual interactions can be short or long range, and their strengths can be reconfigured as needed to solve specific problems and to anneal the system at room temperature. The natural laws of statistical mechanics guide the network of stochastic nanomagnets at GHz speeds through the collective states with an emphasis on the low energy states that represent optimal solutions. As proof-of-concept, we present simulation results for standard NP-complete examples including a 16-city traveling salesman problem using experimentally benchmarked models for spin-transfer torque driven stochastic nanomagnets. PMID:28295053

  4. Energy Landscapes of Folding Chromosomes

    NASA Astrophysics Data System (ADS)

    Zhang, Bin

    The genome, the blueprint of life, contains nearly all the information needed to build and maintain an entire organism. A comprehensive understanding of the genome is of paramount interest to human health and will advance progress in many areas, including life sciences, medicine, and biotechnology. The overarching goal of my research is to understand the structure-dynamics-function relationships of the human genome. In this talk, I will be presenting our efforts in moving towards that goal, with a particular emphasis on studying the three-dimensional organization, the structure of the genome with multi-scale approaches. Specifically, I will discuss the reconstruction of genome structures at both interphase and metaphase by making use of data from chromosome conformation capture experiments. Computationally modeling of chromatin fiber at atomistic level from first principles will also be presented as our effort for studying the genome structure from bottom up.

  5. Buildings Interoperability Landscape

    SciTech Connect

    Hardin, Dave; Stephan, Eric G.; Wang, Weimin; Corbin, Charles D.; Widergren, Steven E.

    2015-12-31

    Through its Building Technologies Office (BTO), the United States Department of Energy’s Office of Energy Efficiency and Renewable Energy (DOE-EERE) is sponsoring an effort to advance interoperability for the integration of intelligent buildings equipment and automation systems, understanding the importance of integration frameworks and product ecosystems to this cause. This is important to BTO’s mission to enhance energy efficiency and save energy for economic and environmental purposes. For connected buildings ecosystems of products and services from various manufacturers to flourish, the ICT aspects of the equipment need to integrate and operate simply and reliably. Within the concepts of interoperability lie the specification, development, and certification of equipment with standards-based interfaces that connect and work. Beyond this, a healthy community of stakeholders that contribute to and use interoperability work products must be developed. On May 1, 2014, the DOE convened a technical meeting to take stock of the current state of interoperability of connected equipment and systems in buildings. Several insights from that meeting helped facilitate a draft description of the landscape of interoperability for connected buildings, which focuses mainly on small and medium commercial buildings. This document revises the February 2015 landscape document to address reviewer comments, incorporate important insights from the Buildings Interoperability Vision technical meeting, and capture thoughts from that meeting about the topics to be addressed in a buildings interoperability vision. In particular, greater attention is paid to the state of information modeling in buildings and the great potential for near-term benefits in this area from progress and community alignment.

  6. Intrinsic mechanical behavior of femoral cortical bone in young, osteoporotic and bisphosphonate-treated individuals in low- and high energy fracture conditions

    PubMed Central

    Zimmermann, Elizabeth A.; Schaible, Eric; Gludovatz, Bernd; Schmidt, Felix N.; Riedel, Christoph; Krause, Matthias; Vettorazzi, Eik; Acevedo, Claire; Hahn, Michael; Püschel, Klaus; Tang, Simon; Amling, Michael; Ritchie, Robert O.; Busse, Björn

    2016-01-01

    Bisphosphonates are a common treatment to reduce osteoporotic fractures. This treatment induces osseous structural and compositional changes accompanied by positive effects on osteoblasts and osteocytes. Here, we test the hypothesis that restored osseous cell behavior, which resembles characteristics of younger, healthy cortical bone, leads to improved bone quality. Microarchitecture and mechanical properties of young, treatment-naïve osteoporosis, and bisphosphonate-treated cases were investigated in femoral cortices. Tissue strength was measured using three-point bending. Collagen fibril-level deformation was assessed in non-traumatic and traumatic fracture states using synchrotron small-angle x-ray scattering (SAXS) at low and high strain rates. The lower modulus, strength and fibril deformation measured at low strain rates reflects susceptibility for osteoporotic low-energy fragility fractures. Independent of age, disease and treatment status, SAXS revealed reduced fibril plasticity at high strain rates, characteristic of traumatic fracture. The significantly reduced mechanical integrity in osteoporosis may originate from porosity and alterations to the intra/extrafibrillar structure, while the fibril deformation under treatment indicates improved nano-scale characteristics. In conclusion, losses in strength and fibril deformation at low strain rates correlate with the occurrence of fragility fractures in osteoporosis, while improvements in structural and mechanical properties following bisphosphonate treatment may foster resistance to fracture during physiological strain rates. PMID:26879146

  7. Intrinsic mechanical behavior of femoral cortical bone in young, osteoporotic and bisphosphonate-treated individuals in low- and high energy fracture conditions

    SciTech Connect

    Zimmermann, Elizabeth A.; Schaible, Eric; Gludovatz, Bernd; Schmidt, Felix N.; Riedel, Christoph; Krause, Matthias; Vettorazzi, Eik; Acevedo, Claire; Hahn, Michael; Püschel, Klaus; Tang, Simon; Amling, Michael; Ritchie, Robert O.; Busse, Björn

    2016-02-16

    Bisphosphonates are a common treatment to reduce osteoporotic fractures. This treatment induces osseous structural and compositional changes accompanied by positive effects on osteoblasts and osteocytes. Here, we test the hypothesis that restored osseous cell behavior, which resembles characteristics of younger, healthy cortical bone, leads to improved bone quality. Microarchitecture and mechanical properties of young, treatment-naïve osteoporosis, and bisphosphonate-treated cases were investigated in femoral cortices. Tissue strength was measured using three-point bending. Collagen fibril-level deformation was assessed in non-traumatic and traumatic fracture states using synchrotron small-angle x-ray scattering (SAXS) at low and high strain rates. The lower modulus, strength and fibril deformation measured at low strain rates reflects susceptibility for osteoporotic low-energy fragility fractures. Independent of age, disease and treatment status, SAXS revealed reduced fibril plasticity at high strain rates, characteristic of traumatic fracture. We find the significantly reduced mechanical integrity in osteoporosis may originate from porosity and alterations to the intra/extrafibrillar structure, while the fibril deformation under treatment indicates improved nano-scale characteristics. In conclusion, losses in strength and fibril deformation at low strain rates correlate with the occurrence of fragility fractures in osteoporosis, while improvements in structural and mechanical properties following bisphosphonate treatment may foster resistance to fracture during physiological strain rates.

  8. Intrinsic mechanical behavior of femoral cortical bone in young, osteoporotic and bisphosphonate-treated individuals in low- and high energy fracture conditions

    DOE PAGES

    Zimmermann, Elizabeth A.; Schaible, Eric; Gludovatz, Bernd; ...

    2016-02-16

    Bisphosphonates are a common treatment to reduce osteoporotic fractures. This treatment induces osseous structural and compositional changes accompanied by positive effects on osteoblasts and osteocytes. Here, we test the hypothesis that restored osseous cell behavior, which resembles characteristics of younger, healthy cortical bone, leads to improved bone quality. Microarchitecture and mechanical properties of young, treatment-naïve osteoporosis, and bisphosphonate-treated cases were investigated in femoral cortices. Tissue strength was measured using three-point bending. Collagen fibril-level deformation was assessed in non-traumatic and traumatic fracture states using synchrotron small-angle x-ray scattering (SAXS) at low and high strain rates. The lower modulus, strength and fibrilmore » deformation measured at low strain rates reflects susceptibility for osteoporotic low-energy fragility fractures. Independent of age, disease and treatment status, SAXS revealed reduced fibril plasticity at high strain rates, characteristic of traumatic fracture. We find the significantly reduced mechanical integrity in osteoporosis may originate from porosity and alterations to the intra/extrafibrillar structure, while the fibril deformation under treatment indicates improved nano-scale characteristics. In conclusion, losses in strength and fibril deformation at low strain rates correlate with the occurrence of fragility fractures in osteoporosis, while improvements in structural and mechanical properties following bisphosphonate treatment may foster resistance to fracture during physiological strain rates.« less

  9. Intrinsic mechanical behavior of femoral cortical bone in young, osteoporotic and bisphosphonate-treated individuals in low- and high energy fracture conditions

    NASA Astrophysics Data System (ADS)

    Zimmermann, Elizabeth A.; Schaible, Eric; Gludovatz, Bernd; Schmidt, Felix N.; Riedel, Christoph; Krause, Matthias; Vettorazzi, Eik; Acevedo, Claire; Hahn, Michael; Püschel, Klaus; Tang, Simon; Amling, Michael; Ritchie, Robert O.; Busse, Björn

    2016-02-01

    Bisphosphonates are a common treatment to reduce osteoporotic fractures. This treatment induces osseous structural and compositional changes accompanied by positive effects on osteoblasts and osteocytes. Here, we test the hypothesis that restored osseous cell behavior, which resembles characteristics of younger, healthy cortical bone, leads to improved bone quality. Microarchitecture and mechanical properties of young, treatment-naïve osteoporosis, and bisphosphonate-treated cases were investigated in femoral cortices. Tissue strength was measured using three-point bending. Collagen fibril-level deformation was assessed in non-traumatic and traumatic fracture states using synchrotron small-angle x-ray scattering (SAXS) at low and high strain rates. The lower modulus, strength and fibril deformation measured at low strain rates reflects susceptibility for osteoporotic low-energy fragility fractures. Independent of age, disease and treatment status, SAXS revealed reduced fibril plasticity at high strain rates, characteristic of traumatic fracture. The significantly reduced mechanical integrity in osteoporosis may originate from porosity and alterations to the intra/extrafibrillar structure, while the fibril deformation under treatment indicates improved nano-scale characteristics. In conclusion, losses in strength and fibril deformation at low strain rates correlate with the occurrence of fragility fractures in osteoporosis, while improvements in structural and mechanical properties following bisphosphonate treatment may foster resistance to fracture during physiological strain rates.

  10. USING ENERGY AND EMERGY TO COUPLE GEOMORPHOLOGY AND HUMAN INFLUENCES INTO A WATERSHED/LANDSCAPE INDEX AND LINK THE INDEX TO DOWNSTREAM WATER AND HABITAT QUALITY

    EPA Science Inventory

    The Clean Water Act requires identification of all waters whose abiotic and biotic integrity have been compromised or impaired, but it is impossible to assess each water body in the nation. Although landscape studies attempting to find correlations between land use and water con...

  11. Intrinsic Feature Motion Tracking

    SciTech Connect

    Goddard, Jr., James S.

    2013-03-19

    Subject motion during 3D medical scanning can cause blurring and artifacts in the 3D images resulting in either rescans or poor diagnosis. Anesthesia or physical restraints may be used to eliminate motion but are undesirable and can affect results. This software measures the six degree of freedom 3D motion of the subject during the scan under a rigidity assumption using only the intrinsic features present on the subject area being monitored. This movement over time can then be used to correct the scan data removing the blur and artifacts. The software acquires images from external cameras or images stored on disk for processing. The images are from two or three calibrated cameras in a stereo arrangement. Algorithms extract and track the features over time and calculate position and orientation changes relative to an initial position. Output is the 3D position and orientation change measured at each image.

  12. Gaussian Intrinsic Entanglement

    NASA Astrophysics Data System (ADS)

    Mišta, Ladislav; Tatham, Richard

    2016-12-01

    We introduce a cryptographically motivated quantifier of entanglement in bipartite Gaussian systems called Gaussian intrinsic entanglement (GIE). The GIE is defined as the optimized mutual information of a Gaussian distribution of outcomes of measurements on parts of a system, conditioned on the outcomes of a measurement on a purifying subsystem. We show that GIE vanishes only on separable states and exhibits monotonicity under Gaussian local trace-preserving operations and classical communication. In the two-mode case, we compute GIE for all pure states as well as for several important classes of symmetric and asymmetric mixed states. Surprisingly, in all of these cases, GIE is equal to Gaussian Rényi-2 entanglement. As GIE is operationally associated with the secret-key agreement protocol and can be computed for several important classes of states, it offers a compromise between computable and physically meaningful entanglement quantifiers.

  13. Intrinsically variable stars

    NASA Technical Reports Server (NTRS)

    Bohm-Vitense, Erika; Querci, Monique

    1987-01-01

    The characteristics of intrinsically variable stars are examined, reviewing the results of observations obtained with the IUE satellite since its launch in 1978. Selected data on both medium-spectral-class pulsating stars (Delta Cep stars, W Vir stars, and related groups) and late-type variables (M, S, and C giants and supergiants) are presented in spectra, graphs, and tables and described in detail. Topics addressed include the calibration of the the period-luminosity relation, Cepheid distance determination, checking stellar evolution theory by the giant companions of Cepheids, Cepheid masses, the importance of the hydrogen convection zone in Cepheids, temperature and abundance estimates for Population II pulsating stars, mass loss in Population II Cepheids, SWP and LWP images of cold giants and supergiants, temporal variations in the UV lines of cold stars, C-rich cold stars, and cold stars with highly ionized emission lines.

  14. Profibus features intrinsic safety, interoperability

    SciTech Connect

    Bryant, M.

    1996-11-01

    The newest member of the Profibus (process fieldbus) family of interoperable field-bus protocols is {open_quotes}PA{close_quotes}, an intrinsically safe (IS) standard released more than a year ago. IS and non-IS plants using PA for process chemicals, energy production, and food manufacturing are coming online. PA was developed by vendor and user members of the Profibus standards community to meet the needs of customers in the process industries. PA complies with IEC 1158-2, which, among non-IS capabilities, specifies a low-speed, intrinsically safe fieldbus for automating explosive chemical manufacturing. PA thus provides all H1, or {open_quotes}hunk{close_quotes} 1, IS and non-IS services. Importantly, it also provides all H2, or {open_quotes}hunk{close_quotes} 2, services. As the newest segment of the site-proven system of fieldbus protocols, Profibus-PA defines by example the concepts of interoperability and interchangeability. It is a field instrument network that automatically interoperates with a large installed base of fieldbus nodes. As low-speed networks, PA and its competitor, Foundation fieldbus H1 comply with the same standard. They do the same job; auxiliary power to the application, with a data rate of 31.25 kbit/sec. Similarities include a function-block-based architecture and a device description language (DDL). They use the same physical layer for digital data transfer. A casual observer would find PA and H1 virtually the same. The key differences are in the protocol implementations. Although PA and H1 could be wired together, the messages delivered by one would make no sense to the other. At least not yet. PA protocols are capable of both IS and non-IS operations. This opens the door to a wide range of interoperable process-manufacturing requirements. 1 fig., 1 tab.

  15. Landscape Management: Field Supervisor.

    ERIC Educational Resources Information Center

    Newton, Deborah; Newton, Steve

    This module is the third volume in a series of instructional materials on landscape management. The materials are designed to help teachers train students in the job skills they will need in landscape occupations. The module contains six instructional units that cover the following topics: orientation; basic landscape design principles; irrigation…

  16. Intrinsic Studies of Materials.

    DTIC Science & Technology

    RELAXATION TIME , CRYSTAL LATTICES), (*RARE EARTH ELEMENTS, *ELECTRON TRANSITIONS), (*CRYSTAL DEFECTS, INTERACTIONS), EXCITATION, DOPING, LANTHANUM COMPOUNDS, PHONONS, ATOMIC ENERGY LEVELS, HOLMIUM, CHLORIDES, PRASEODYMIUM

  17. Metapopulation capacity of evolving fluvial landscapes

    NASA Astrophysics Data System (ADS)

    Bertuzzo, Enrico; Rodriguez-Iturbe, Ignacio; Rinaldo, Andrea

    2015-04-01

    The form of fluvial landscapes is known to attain stationary network configurations that settle in dynamically accessible minima of total energy dissipation by landscape-forming discharges. Recent studies have highlighted the role of the dendritic structure of river networks in controlling population dynamics of the species they host and large-scale biodiversity patterns. Here, we systematically investigate the relation between energy dissipation, the physical driver for the evolution of river networks, and the ecological dynamics of their embedded biota. To that end, we use the concept of metapopulation capacity, a measure to link landscape structures with the population dynamics they host. Technically, metapopulation capacity is the leading eigenvalue λM of an appropriate "landscape" matrix subsuming whether a given species is predicted to persist in the long run. λM can conveniently be used to rank different landscapes in terms of their capacity to support viable metapopulations. We study how λM changes in response to the evolving network configurations of spanning trees. Such sequence of configurations is theoretically known to relate network selection to general landscape evolution equations through imperfect searches for dynamically accessible states frustrated by the vagaries of Nature. Results show that the process shaping the metric and the topological properties of river networks, prescribed by physical constraints, leads to a progressive increase in the corresponding metapopulation capacity and therefore on the landscape capacity to support metapopulations—with implications on biodiversity in fluvial ecosystems.

  18. Qutrit teleportation under intrinsic decoherence

    NASA Astrophysics Data System (ADS)

    Jafarpour, Mojtaba; Naderi, Negar

    2016-08-01

    We study qutrit teleportation and its fidelity in the presence and absence of intrinsic decoherence through a qutrit channel. The channel consists of a Heisenberg chain with xyz interaction model and the intrinsic decoherence is implemented through the Milburn model. It is shown that while the fidelity diminishes due to intrinsic decoherence, it may be enhanced if the channel is initially in an entangled state. It is also observed that, for stronger intrinsic decoherence, the initial entanglement of the channel is more effective in enhancing of fidelity.

  19. Landscape genetics of plants.

    PubMed

    Holderegger, Rolf; Buehler, Dominique; Gugerli, Felix; Manel, Stéphanie

    2010-12-01

    Landscape genetics is the amalgamation of landscape ecology and population genetics to help with understanding microevolutionary processes such as gene flow and adaptation. In this review, we examine why landscape genetics of plants lags behind that of animals, both in number of studies and consideration of landscape elements. The classical landscape distance/resistance approach to study gene flow is challenging in plants, whereas boundary detection and the assessment of contemporary gene flow are more feasible. By contrast, the new field of landscape genetics of adaptive genetic variation, establishing the relationship between adaptive genomic regions and environmental factors in natural populations, is prominent in plant studies. Landscape genetics is ideally suited to study processes such as migration and adaptation under global change.

  20. Bioenergy in a Multifunctional Landscape

    ScienceCinema

    Watts, Chad; Negri, Cristina; Ssegane, Herbert

    2016-11-02

    How can our landscapes be managed most effectively to produce crops for food, feed, and bioenergy, while also protecting our water resources by preventing the loss of nutrients from the soil? Dr. Cristina Negri and her team at the U.S. Department of Energy’s Argonne National Laboratory are tackling this question at an agricultural research site located in Fairbury, Illinois.

  1. Intrinsic rotation in DIII-D

    SciTech Connect

    DeGrassie, J. S.; Rice, J. E.; Burrell, K. H.; Groebner, R. J.; Solomon, W. M.

    2007-05-15

    In the absence of any auxiliary torque input, the DIII-D plasma consists of nonzero toroidal angular momentum, in other words, it rotates. This effect is commonly observed in tokamaks, being referred to as intrinsic rotation. Measurements of intrinsic rotation profiles have been made in DIII-D [J. Luxon, Nucl. Fusion 42, 614 (2002)] H-mode discharges, with both Ohmic heating (OH) and electron cyclotron heating (ECH) in which there is no auxiliary torque. Recently, the H-mode data set has been extended with the newly configured DIII-D simultaneous co- and counter-directed neutral beam injection (NBI) capability resulting in control of the local torque deposition, where co and counter refer to the direction relative to the toroidal plasma current. Understanding intrinsic rotation is important for projection toward burning plasma performance where any NBI torque will be relatively small. The toroidal velocity is recognizably important regarding issues of stability and confinement. In DIII-D ECH H-modes the rotation profile is hollow, co-directed at large minor radius and depressed, or actually counter-directed, nearer the magnetic axis. This profile varies with the ECH power deposition profile to some extent. In contrast, OH H-modes have a relatively flat co-directed rotation profile. There is a scaling of the DIII-D intrinsic toroidal velocity with W/I{sub p}, as seen in intrinsic rotation in Alcator C-Mod [J. Rice, Nucl. Fusion 39, 1175 (1999)], where W is the total plasma thermal energy and I{sub p} is the magnitude of the toroidal plasma current. This common scaling resulted in a dimensionless similarity experiment between DIII-D and Alcator C-Mod on intrinsic rotation, obtaining a single spatial point match in the toroidal velocity normalized to the ion thermal velocity. The balanced NBI capability in DIII-D is a useful tool to push scaling studies to higher values of the plasma normalized energy, notwithstanding the details of torque deposition for co-NBI versus

  2. Intrinsic Angular Momentum of Light.

    ERIC Educational Resources Information Center

    Santarelli, Vincent

    1979-01-01

    Derives a familiar torque-angular momentum theorem for the electromagnetic field, and includes the intrinsic torques exerted by the fields on the polarized medium. This inclusion leads to the expressions for the intrinsic angular momentum carried by the radiation traveling through a charge-free medium. (Author/MA)

  3. The intrinsic resistance of bacteria.

    PubMed

    Gang, Zhang; Jie, Feng

    2016-10-20

    Antibiotic resistance is often considered to be a trait acquired by previously susceptible bacteria, on the basis of which can be attributed to the horizontal acquisition of new genes or the occurrence of spontaneous mutation. In addition to acquired resistance, bacteria have a trait of intrinsic resistance to different classes of antibiotics. An intrinsic resistance gene is involved in intrinsic resistance, and its presence in bacterial strains is independent of previous antibiotic exposure and is not caused by horizontal gene transfer. Recently, interest in intrinsic resistance genes has increased, because these gene products not only may provide attractive therapeutic targets for development of novel drugs that rejuvenate the activity of existing antibiotics, and but also might predict future emergence of resistant pathogens if they become mobilized. In the present review, we summarize the conventional examples of intrinsic resistance, including the impermeability of cellular envelopes, the activity of multidrug efflux pumps or lack of drug targets. We also demonstrate that transferases and enzymes involved in basic bacterial metabolic processes confer intrinsic resistance in Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. We present as well information on the cryptic intrinsic resistance genes that do not confer resistance to their native hosts but are capable of conferring resistance when their expression levels are increased and the activation of the cryptic genes. Finally, we discuss that intrinsic genes could be the origin of acquired resistance, especially in the genus Acinetobacter.

  4. Nonequilibrium landscape theory of neural networks.

    PubMed

    Yan, Han; Zhao, Lei; Hu, Liang; Wang, Xidi; Wang, Erkang; Wang, Jin

    2013-11-05

    The brain map project aims to map out the neuron connections of the human brain. Even with all of the wirings mapped out, the global and physical understandings of the function and behavior are still challenging. Hopfield quantified the learning and memory process of symmetrically connected neural networks globally through equilibrium energy. The energy basins of attractions represent memories, and the memory retrieval dynamics is determined by the energy gradient. However, the realistic neural networks are asymmetrically connected, and oscillations cannot emerge from symmetric neural networks. Here, we developed a nonequilibrium landscape-flux theory for realistic asymmetrically connected neural networks. We uncovered the underlying potential landscape and the associated Lyapunov function for quantifying the global stability and function. We found the dynamics and oscillations in human brains responsible for cognitive processes and physiological rhythm regulations are determined not only by the landscape gradient but also by the flux. We found that the flux is closely related to the degrees of the asymmetric connections in neural networks and is the origin of the neural oscillations. The neural oscillation landscape shows a closed-ring attractor topology. The landscape gradient attracts the network down to the ring. The flux is responsible for coherent oscillations on the ring. We suggest the flux may provide the driving force for associations among memories. We applied our theory to rapid-eye movement sleep cycle. We identified the key regulation factors for function through global sensitivity analysis of landscape topography against wirings, which are in good agreements with experiments.

  5. Energy Savers: Tips on Saving Money & Energy at Home

    SciTech Connect

    2011-12-01

    Provides consumers with home energy and money savings tips such as insulation, weatherization, heating, cooling, water heating, energy efficient windows, landscaping, lighting, and energy efficient appliances.

  6. Energy Savers: Tips on Saving Money & Energy at Home

    SciTech Connect

    2014-05-01

    Provides consumers with home energy and money savings tips such as insulation, weatherization, heating, cooling, water heating, energy efficient windows, landscaping, lighting, and energy efficient appliances.

  7. Dynamic Shade and Irradiance Simulation of Aquatic Landscapes and Watersheds

    EPA Science Inventory

    Penumbra is a landscape shade and irradiance simulation model that simulates how solar energy spatially and temporally interacts within dynamic ecosystems such as riparian zones, forests, and other terrain that cast topological shadows. Direct and indirect solar energy accumulate...

  8. Do geographically isolated wetlands influence landscape functions?

    USGS Publications Warehouse

    Cohen, Matthew J.; Creed, Irena F.; Alexander, Laurie C.; Basu, Nandita; Calhoun, Aram J. K.; Craft, Christopher; D’Amico, Ellen; DeKeyser, Edward S.; Fowler, Laurie; Golden, Heather E.; Jawitz, James W.; Kalla, Peter; Kirkman, L. Katherine; Lane, Charles R.; Lang, Megan; Leibowitz, Scott G.; Lewis, David Bruce; Marton, John; McLaughlin, Daniel L.; Mushet, David M.; Raanan-Kiperwas, Hadas; Rains, Mark C.; Smith, Lora; Walls, Susan C.

    2015-01-01

    Geographically isolated wetlands (GIWs), those surrounded by uplands, exchange materials, energy, and organisms with other elements in hydrological and habitat networks, contributing to landscape functions, such as flow generation, nutrient and sediment retention, and biodiversity support. GIWs constitute most of the wetlands in many North American landscapes, provide a disproportionately large fraction of wetland edges where many functions are enhanced, and form complexes with other water bodies to create spatial and temporal heterogeneity in the timing, flow paths, and magnitude of network connectivity. These attributes signal a critical role for GIWs in sustaining a portfolio of landscape functions, but legal protections remain weak despite preferential loss from many landscapes. GIWs lack persistent surface water connections, but this condition does not imply the absence of hydrological, biogeochemical, and biological exchanges with nearby and downstream waters. Although hydrological and biogeochemical connectivity is often episodic or slow (e.g., via groundwater), hydrologic continuity and limited evaporative solute enrichment suggest both flow generation and solute and sediment retention. Similarly, whereas biological connectivity usually requires overland dispersal, numerous organisms, including many rare or threatened species, use both GIWs and downstream waters at different times or life stages, suggesting that GIWs are critical elements of landscape habitat mosaics. Indeed, weaker hydrologic connectivity with downstream waters and constrained biological connectivity with other landscape elements are precisely what enhances some GIW functions and enables others. Based on analysis of wetland geography and synthesis of wetland functions, we argue that sustaining landscape functions requires conserving the entire continuum of wetland connectivity, including GIWs.

  9. Do geographically isolated wetlands influence landscape functions?

    PubMed

    Cohen, Matthew J; Creed, Irena F; Alexander, Laurie; Basu, Nandita B; Calhoun, Aram J K; Craft, Christopher; D'Amico, Ellen; DeKeyser, Edward; Fowler, Laurie; Golden, Heather E; Jawitz, James W; Kalla, Peter; Kirkman, L Katherine; Lane, Charles R; Lang, Megan; Leibowitz, Scott G; Lewis, David Bruce; Marton, John; McLaughlin, Daniel L; Mushet, David M; Raanan-Kiperwas, Hadas; Rains, Mark C; Smith, Lora; Walls, Susan C

    2016-02-23

    Geographically isolated wetlands (GIWs), those surrounded by uplands, exchange materials, energy, and organisms with other elements in hydrological and habitat networks, contributing to landscape functions, such as flow generation, nutrient and sediment retention, and biodiversity support. GIWs constitute most of the wetlands in many North American landscapes, provide a disproportionately large fraction of wetland edges where many functions are enhanced, and form complexes with other water bodies to create spatial and temporal heterogeneity in the timing, flow paths, and magnitude of network connectivity. These attributes signal a critical role for GIWs in sustaining a portfolio of landscape functions, but legal protections remain weak despite preferential loss from many landscapes. GIWs lack persistent surface water connections, but this condition does not imply the absence of hydrological, biogeochemical, and biological exchanges with nearby and downstream waters. Although hydrological and biogeochemical connectivity is often episodic or slow (e.g., via groundwater), hydrologic continuity and limited evaporative solute enrichment suggest both flow generation and solute and sediment retention. Similarly, whereas biological connectivity usually requires overland dispersal, numerous organisms, including many rare or threatened species, use both GIWs and downstream waters at different times or life stages, suggesting that GIWs are critical elements of landscape habitat mosaics. Indeed, weaker hydrologic connectivity with downstream waters and constrained biological connectivity with other landscape elements are precisely what enhances some GIW functions and enables others. Based on analysis of wetland geography and synthesis of wetland functions, we argue that sustaining landscape functions requires conserving the entire continuum of wetland connectivity, including GIWs.

  10. Another Paper Landscape?

    ERIC Educational Resources Information Center

    Radlak, Ted

    2001-01-01

    Describes the University of Toronto's extensive central campus revitalization plan to create lush landscapes that add to the school's image and attractiveness. Drawings and photographs are included. (GR)

  11. Role of intrinsic width in fragment momentum distributions in heavy ion collisions

    NASA Technical Reports Server (NTRS)

    Townsend, L. W.; Tripathi, R. K.; Khan, F.

    1994-01-01

    It is demonstrated that the intrinsic widths incorporating correlations in conjunction with dynamical contributions give better agreement with experiments for collisions in the energy range of 200 A MeV to 2.4 GeV than using only intrinsic widths without correlations. The sensitivity of the intrinsic width decreases with increasing projectile mass. A simple recipe for calculating intrinsic width correlations is presented.

  12. Intrinsic two-dimensional features as textons

    NASA Technical Reports Server (NTRS)

    Barth, E.; Zetzsche, C.; Rentschler, I.

    1998-01-01

    We suggest that intrinsic two-dimensional (i2D) features, computationally defined as the outputs of nonlinear operators that model the activity of end-stopped neurons, play a role in preattentive texture discrimination. We first show that for discriminable textures with identical power spectra the predictions of traditional models depend on the type of nonlinearity and fail for energy measures. We then argue that the concept of intrinsic dimensionality, and the existence of end-stopped neurons, can help us to understand the role of the nonlinearities. Furthermore, we show examples in which models without strong i2D selectivity fail to predict the correct ranking order of perceptual segregation. Our arguments regarding the importance of i2D features resemble the arguments of Julesz and co-workers regarding textons such as terminators and crossings. However, we provide a computational framework that identifies textons with the outputs of nonlinear operators that are selective to i2D features.

  13. Intrinsic emittance reduction in transmission mode photocathodes

    NASA Astrophysics Data System (ADS)

    Lee, Hyeri; Cultrera, Luca; Bazarov, Ivan

    2016-03-01

    High quantum efficiency (QE) and low emittance electron beams provided by multi-alkali photocathodes make them of great interest for next generation high brightness photoinjectors. Spicer's three-step model well describes the photoemission process; however, some photocathode characteristics such as their thickness have not yet been completely exploited to further improve the brightness of the generated electron beams. In this work, we report on the emittance and QE of a multi-alkali photocathode grown onto a glass substrate operated in transmission and reflection modes at different photon energies. We observed a 20% reduction in the intrinsic emittance from the reflection to the transmission mode operation. This observation can be explained by inelastic electron-phonon scattering during electrons' transit towards the cathode surface. Due to this effect, we predict that thicker photocathode layers will further reduce the intrinsic emittance of electron beams generated by photocathodes operated in transmission mode.

  14. Intrinsic Correlations for Flaring Blazars Detected by Fermi

    NASA Astrophysics Data System (ADS)

    Fan, J. H.; Yang, J. H.; Xiao, H. B.; Lin, C.; Constantin, D.; Luo, G. Y.; Pei, Z. Y.; Hao, J. M.; Mao, Y. W.

    2017-02-01

    Blazars are an extreme subclass of active galactic nuclei. Their rapid variability, luminous brightness, superluminal motion, and high and variable polarization are probably due to a beaming effect. However, this beaming factor (or Doppler factor) is very difficult to measure. Currently, a good way to estimate it is to use the timescale of their radio flares. In this Letter, we use multiwavelength data and Doppler factors reported in the literature for a sample of 86 flaring blazars detected by Fermi to compute their intrinsic multiwavelength data and intrinsic spectral energy distributions and investigate the correlations among observed and intrinsic data. Quite interestingly, intrinsic data show a positive correlation between luminosity and peak frequency, in contrast with the behavior of observed data, and a tighter correlation between γ-ray luminosity and the lower-energy ones. For flaring blazars detected by Fermi, we conclude that (1) observed emissions are strongly beamed; (2) the anti-correlation between luminosity and peak frequency from the observed data is an apparent result, the correlation between intrinsic data being positive; and (3) intrinsic γ-ray luminosity is strongly correlated with other intrinsic luminosities.

  15. Planetary Landscape Geography

    NASA Astrophysics Data System (ADS)

    Hargitai, H.

    INTRODUCTION Landscape is one of the most often used category in physical ge- ography. The term "landshap" was introduced by Dutch painters in the 15-16th cen- tury. [1] The elements that build up a landscape (or environment) on Earth consists of natural (biogenic and abiogenic - lithologic, atmospheric, hydrologic) and artificial (antropogenic) factors. Landscape is a complex system of these different elements. The same lithology makes different landscapes under different climatic conditions. If the same conditions are present, the same landscape type will appear. Landscapes build up a hierarchic system and cover the whole surface. On Earth, landscapes can be classified and qualified according to their characteristics: relief forms (morphology), and its potential economic value. Aesthetic and subjective parameters can also be considered. Using the data from landers and data from orbiters we can now classify planetary landscapes (these can be used as geologic mapping units as well). By looking at a unknown landscape, we can determine the processes that created it and its development history. This was the case in the Pathfinder/Sojourner panoramas. [2]. DISCUSSION Planetary landscape evolution. We can draw a raw landscape develop- ment history by adding the different landscape building elements to each other. This has a strong connection with the planet's thermal evolution (age of the planet or the present surface materials) and with orbital parameters (distance from the central star, orbit excentricity etc). This way we can build a complex system in which we use differ- ent evolutional stages of lithologic, atmospheric, hydrologic and biogenic conditions which determine the given - Solar System or exoplanetary - landscape. Landscape elements. "Simple" landscapes can be found on asteroids: no linear horizon is present (not differentiated body, only impact structures), no atmosphere (therefore no atmospheric scattering - black sky as part of the landscape) and no

  16. Development of a Digital Aquifer Permeability Map for the Pacific Southwest in Support of Hydrologic Landscape Classification: Methods

    EPA Science Inventory

    Researchers at the U.S. Environmental Protection Agency’s Western Ecology Division have been developing hydrologic landscape maps for selected U.S. states in an effort to create a method to identify the intrinsic watershed attributes of landscapes in regions with little dat...

  17. Monte Carlo simulations of the peptide recognition at the consensus binding site of the constant fragment of human immunoglobulin G: the energy landscape analysis of a hot spot at the intermolecular interface.

    PubMed

    Verkhivker, Gennady M; Bouzida, Djamal; Gehlhaar, Daniel K; Rejto, Paul A; Freer, Stephan T; Rose, Peter W

    2002-08-15

    Monte Carlo simulations of molecular recognition at the consensus binding site of the constant fragment (Fc) of human immunoglobulin G (Ig) protein have been performed to analyze structural and thermodynamic aspects of binding for the 13-residue cyclic peptide DCAWHLGELVWCT. The energy landscape analysis of a hot spot at the intermolecular interface using alanine scanning and equilibrium-simulated tempering dynamics with the simplified, knowledge-based energy function has enabled the role of the protein hot spot residues in providing the thermodynamic stability of the native structure to be determined. We have found that hydrophobic interactions between the peptide and the Met-252, Ile-253, His-433, and His-435 protein residues are critical to guarantee the thermodynamic stability of the crystallographic binding mode of the complex. Binding free energy calculations, using a molecular mechanics force field and a solvation energy model, combined with alanine scanning have been conducted to determine the energetic contribution of the protein hot spot residues in binding affinity. The conserved Asn-434, Ser-254, and Tyr-436 protein residues contribute significantly to the binding affinity of the peptide-protein complex, serving as an energetic hot spot at the intermolecular interface. The results suggest that evolutionary conserved hot spot protein residues at the intermolecular interface may be partitioned in fulfilling thermodynamic stability of the native binding mode and contributing to the binding affinity of the complex.

  18. Genomic Insights into Diffuse Intrinsic Pontine Glioma

    PubMed Central

    Lapin, Danielle H.; Tsoli, Maria; Ziegler, David S.

    2017-01-01

    Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive pediatric brainstem tumor with a peak incidence in middle childhood and a median survival of less than 1 year. The dismal prognosis associated with DIPG has been exacerbated by the failure of over 250 clinical trials to meaningfully improve survival compared with radiotherapy, the current standard of care. The traditional practice to not biopsy DIPG led to a scarcity in available tissue samples for laboratory analysis that till recently hindered therapeutic advances. Over the past few years, the acquisition of patient derived tumor samples through biopsy and autopsy protocols has led to distinct breakthroughs in the identification of key oncogenic drivers implicated in DIPG development. Aberrations have been discovered in critical genetic drivers including histone H3, ACVR1, TP53, PDGFRA, and Myc. Mutations, previously not identified in other malignancies, highlight DIPG as a distinct biological entity. Identification of novel markers has already greatly influenced the direction of preclinical investigations and offers the exciting possibility of establishing biologically targeted therapies. This review will outline the current knowledge of the genomic landscape related to DIPG, overview preclinical investigations, and reflect how biological advances have influenced the focus of clinical trials toward targeted therapies.

  19. [Landscape and ecological genomics].

    PubMed

    Tetushkin, E Ia

    2013-10-01

    Landscape genomics is the modern version of landscape genetics, a discipline that arose approximately 10 years ago as a combination of population genetics, landscape ecology, and spatial statistics. It studies the effects of environmental variables on gene flow and other microevolutionary processes that determine genetic connectivity and variations in populations. In contrast to population genetics, it operates at the level of individual specimens rather than at the level of population samples. Another important difference between landscape genetics and genomics and population genetics is that, in the former, the analysis of gene flow and local adaptations takes quantitative account of landforms and features of the matrix, i.e., hostile spaces that separate species habitats. Landscape genomics is a part of population ecogenomics, which, along with community genomics, is a major part of ecological genomics. One of the principal purposes of landscape genomics is the identification and differentiation of various genome-wide and locus-specific effects. The approaches and computation tools developed for combined analysis of genomic and landscape variables make it possible to detect adaptation-related genome fragments, which facilitates the planning of conservation efforts and the prediction of species' fate in response to expected changes in the environment.

  20. Quasispecies on Fitness Landscapes.

    PubMed

    Schuster, Peter

    2016-01-01

    Selection-mutation dynamics is studied as adaptation and neutral drift on abstract fitness landscapes. Various models of fitness landscapes are introduced and analyzed with respect to the stationary mutant distributions adopted by populations upon them. The concept of quasispecies is introduced, and the error threshold phenomenon is analyzed. Complex fitness landscapes with large scatter of fitness values are shown to sustain error thresholds. The phenomenological theory of the quasispecies introduced in 1971 by Eigen is compared to approximation-free numerical computations. The concept of strong quasispecies understood as mutant distributions, which are especially stable against changes in mutations rates, is presented. The role of fitness neutral genotypes in quasispecies is discussed.

  1. Ulnar intrinsic anatomy and dysfunction.

    PubMed

    Dell, Paul C; Sforzo, Christopher R

    2005-01-01

    Normal hand function is a balance between the extrinsic and intrinsic musculature. Although individually the intrinsics are small muscles in diameter, collectively they represent a large muscle that contributes approximately 50% of grip strength. Dysfunction of the intrinsics consequently leads to impaired grip and pinch strength as well recognized deformities. Low ulnar nerve palsy preserves ulnar innervated extrinsics resulting in sensory loss, digital clawing, thumb deformity, abduction of the small finger, and asynchronous finger motion. High ulnar nerve palsy is characterized by the above plus paralysis of the ulnar profundi and the flexor carpi ulnaris. Understanding the normal anatomy allows the clinician to identify the site of the lesion and plan appropriate surgical intervention. This article revisits the classic work of Richard J. Smith on ulnar nerve palsy with contemporary perspective.

  2. Enhancement Through Landscaping.

    ERIC Educational Resources Information Center

    Lindley, Charles

    1985-01-01

    Landscaping can make the school environment more attractive, thus encouraging students' intellectual, emotional, and physical development. Guidelines are offered for comprehensive site planning, tree and plant selection, and grounds maintenance. (MLF)

  3. Landscape evolution (A Review)

    PubMed Central

    Sharp, Robert P.

    1982-01-01

    Landscapes are created by exogenic and endogenic processes acting along the interface between the lithosphere and the atmosphere and hydrosphere. Various landforms result from the attack of weathering and erosion upon the highly heterogeneous lithospheric surface. Landscapes are dynamic, acutely sensitive to natural and artificial perturbation. Undisturbed, they can evolve through a succession of stages to a plain of low relief. Often, the progression of an erosion cycle is interrupted by tectonic or environmental changes; thus, many landscapes preserve vestiges of earlier cycles useful in reconstructing the recent history of Earth's surface. Landforms are bounded by slopes, so their evolution is best understood through study of slopes and the complex of factors controlling slope character and development. The substrate, biosphere, climatic environment, and erosive processes are principal factors. Creep of the disintegrated substrate and surface wash by water are preeminent. Some slopes attain a quasisteady form and recede parallel to themselves (backwearing); others become ever gentler with time (downwearing). The lovely convex/rectilinear/concave profile of many debris-mantled slopes reflects an interplay between creep and surface wash. Landscapes of greatest scenic attraction are usually those in which one or two genetic factors have strongly dominated or those perturbed by special events. Nature has been perturbing landscapes for billions of years, so mankind can learn about landscape perturbation from natural examples. Images

  4. Intrinsic Defects and H Doping in WO3

    PubMed Central

    Zhu, Jiajie; Vasilopoulou, Maria; Davazoglou, Dimitris; Kennou, Stella; Chroneos, Alexander; Schwingenschlögl, Udo

    2017-01-01

    WO3 is widely used as industrial catalyst. Intrinsic and/or extrinsic defects can tune the electronic properties and extend applications to gas sensors and optoelectonics. However, H doping is a challenge to WO3, the relevant mechanisms being hardly understood. In this context, we investigate intrinsic defects and H doping by density functional theory and experiments. Formation energies are calculated to determine the lowest energy defect states. O vacancies turn out to be stable in O-poor environment, in agreement with X-ray photoelectron spectroscopy, and O-H bond formation of H interstitial defects is predicted and confirmed by Fourier transform infrared spectroscopy. PMID:28098210

  5. Intrinsic Defects and H Doping in WO3

    NASA Astrophysics Data System (ADS)

    Zhu, Jiajie; Vasilopoulou, Maria; Davazoglou, Dimitris; Kennou, Stella; Chroneos, Alexander; Schwingenschlögl, Udo

    2017-01-01

    WO3 is widely used as industrial catalyst. Intrinsic and/or extrinsic defects can tune the electronic properties and extend applications to gas sensors and optoelectonics. However, H doping is a challenge to WO3, the relevant mechanisms being hardly understood. In this context, we investigate intrinsic defects and H doping by density functional theory and experiments. Formation energies are calculated to determine the lowest energy defect states. O vacancies turn out to be stable in O-poor environment, in agreement with X-ray photoelectron spectroscopy, and O-H bond formation of H interstitial defects is predicted and confirmed by Fourier transform infrared spectroscopy.

  6. Intrinsic Motivation in Physical Education

    ERIC Educational Resources Information Center

    Davies, Benjamin; Nambiar, Nathan; Hemphill, Caroline; Devietti, Elizabeth; Massengale, Alexandra; McCredie, Patrick

    2015-01-01

    This article describes ways in which educators can use Harter's perceived competence motivation theory, the achievement goal theory, and self-determination theory to develop students' intrinsic motivation to maintain physical fitness, as demonstrated by the Sound Body Sound Mind curriculum and proven effective by the 2013 University of…

  7. Individual Patterns in Intrinsic Motivation.

    ERIC Educational Resources Information Center

    Hom, Harry L., Jr.; Maxwell, Frederick R.

    The effects of extrinsic reward on students' intrinsic interest was investigated using a single-subject design in a behavior disorders classroom. Baseline measures of the interest level of five children (ages 9-11 years) were collected for academic and non-academic tasks. Assessment was then made of each subject's response hierarchy or level of…

  8. Unraveling the intrinsic color of chlorophyll.

    PubMed

    Milne, Bruce F; Toker, Yoni; Rubio, Angel; Nielsen, Steen Brøndsted

    2015-02-09

    The exact color of light absorbed by chlorophyll (Chl) pigments, the light-harvesters in photosynthesis, is tuned by the protein microenvironment, but without knowledge of the intrinsic color of Chl it remains unclear how large this effect is. Experimental first absorption energies of Chl a and b isolated in vacuo and tagged with quaternary ammonium cations are reported. The energies are largely insensitive to details of the tag structure, a finding supported by first-principles calculations using time-dependent density functional theory. Absorption is significantly blue-shifted compared to that of Chl-containing proteins (by 30-70 nm). A single red-shifting perturbation, such as axial ligation or the protein medium, is insufficient to account even for the smallest shift; the largest requires pigment-pigment interactions.

  9. Farming with Grass: Achieving Sustainable Mixed Agricultural Landscapes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Agriculture in grassland environments is facing multiple stresses from shifting demographics, declining and fragmented agricultural landscapes, declining environmental quality, variable and changing climate, volatile and increasing energy costs, marginal economic returns, and globalization. Grassla...

  10. Validation of Pacific Northwest hydrologic landscapes at the catchment scale

    EPA Science Inventory

    The interaction between the physical properties of a catchment (form) and climatic forcing of precipitation and energy control how water is partitioned, stored, and conveyed through a catchment (function). Hydrologic Landscapes (HLs) were previously developed across Oregon and de...

  11. Do geographically isolated wetlands influence landscape functions?

    PubMed Central

    Cohen, Matthew J.; Creed, Irena F.; Alexander, Laurie; Basu, Nandita B.; Calhoun, Aram J. K.; Craft, Christopher; D’Amico, Ellen; DeKeyser, Edward; Fowler, Laurie; Golden, Heather E.; Jawitz, James W.; Kalla, Peter; Kirkman, L. Katherine; Lane, Charles R.; Lang, Megan; Leibowitz, Scott G.; Lewis, David Bruce; Marton, John; McLaughlin, Daniel L.; Mushet, David M.; Raanan-Kiperwas, Hadas; Rains, Mark C.; Smith, Lora; Walls, Susan C.

    2016-01-01

    Geographically isolated wetlands (GIWs), those surrounded by uplands, exchange materials, energy, and organisms with other elements in hydrological and habitat networks, contributing to landscape functions, such as flow generation, nutrient and sediment retention, and biodiversity support. GIWs constitute most of the wetlands in many North American landscapes, provide a disproportionately large fraction of wetland edges where many functions are enhanced, and form complexes with other water bodies to create spatial and temporal heterogeneity in the timing, flow paths, and magnitude of network connectivity. These attributes signal a critical role for GIWs in sustaining a portfolio of landscape functions, but legal protections remain weak despite preferential loss from many landscapes. GIWs lack persistent surface water connections, but this condition does not imply the absence of hydrological, biogeochemical, and biological exchanges with nearby and downstream waters. Although hydrological and biogeochemical connectivity is often episodic or slow (e.g., via groundwater), hydrologic continuity and limited evaporative solute enrichment suggest both flow generation and solute and sediment retention. Similarly, whereas biological connectivity usually requires overland dispersal, numerous organisms, including many rare or threatened species, use both GIWs and downstream waters at different times or life stages, suggesting that GIWs are critical elements of landscape habitat mosaics. Indeed, weaker hydrologic connectivity with downstream waters and constrained biological connectivity with other landscape elements are precisely what enhances some GIW functions and enables others. Based on analysis of wetland geography and synthesis of wetland functions, we argue that sustaining landscape functions requires conserving the entire continuum of wetland connectivity, including GIWs. PMID:26858425

  12. Intrinsic randomness and intrinsic irreversibility in classical dynamical systems

    PubMed Central

    Courbage, M.; Prigogine, I.

    1983-01-01

    We continue our previous work on dynamic “intrinsically random” systems for which we can derive dissipative Markov processes through a one-to-one change of representation. For these systems, the unitary group of evolution can be transformed in this way into two distinct Markov processes leading to equilibrium for either t→ + ∞ or t→ - ∞. To lift the degeneracy, we first formulate the second principle as a selection rule that is meaningful in intrinsically random systems. For these systems, this excludes a set of unrealizable states. As a result of this exclusion, permitted initial conditions correspond to a set of states that is not invariant through velocity inversion. In this way, the time-reversal symmetry of dynamics is broken and these systems acquire a new feature we may call “intrinsic irreversibility.” The set of admitted initial conditions can be characterized by an entropy displaying the amount of information necessary for their preparation. The initial conditions selected by the second law correspond to a finite amount of information, while the initial conditions that are rejected correspond to an infinite amount of information and are therefore “impossible.” We believe that our formulation permits a microscopic formulation of the second law of thermodynamics for well-defined classes of dynamical systems. PMID:16578774

  13. Geomorpho-Landscapes

    NASA Astrophysics Data System (ADS)

    Farabollini, Piero; Lugeri, Francesca; Amadio, Vittorio

    2014-05-01

    Landscape is the object of human perceptions, being the image of spatial organization of elements and structures: mankind lives the first approach with the environment, viewing and feeling the landscape. Many definitions of landscape have been given over time: in this case we refer to the Landscape defined as the result of interaction among physical, biotic and anthropic phenomena acting in a different spatial-temporal scale (Foreman & Godron) Following an Aristotelic approach in studying nature, we can assert that " Shape is synthesis": so it is possible to read the land features as the expression of the endogenous and exogenous processes that mould earth surfaces; moreover, Landscape is the result of the interaction of natural and cultural components, and conditions the spatial-temporal development of a region. The study of the Landscape offers results useful in order to promote sustainable development, ecotourism, enhancement of natural and cultural heritage, popularization of the scientific knowledge. In Italy, a very important GIS-based tool to represent the territory is the "Carta della Natura" ("Map of Nature", presently coordinated by the ISPRA) that aims at assessing the state of the whole Italian territory, analyzing Landscape. The methodology follows a holistic approach, taking into consideration all the components of a landscape and then integrating the information. Each individual landscape, studied at different scales, shows distinctive elements: structural, which depend on physical form and specific spatial organization; functional, which depend on relationships created between biotic and abiotic elements, and dynamic, which depend on the successive evolution of the structure. The identification of the landscape units, recognized at different scales of analysis, allows an evaluation of the state of the land, referring to the dual risk/resource which characterizes the Italian country. An interesting opportunity is to discover those areas of unusual

  14. Transport and MHD simulations of intrinsic and pellet induced ELMs

    NASA Astrophysics Data System (ADS)

    Kim, Ki Min; Na, Yong-Su; Yi, Sumin; Kim, Hyunseok; Kim, Jin Yong

    2010-11-01

    Verification of ELM mechanism and demonstration of ELM control are important issues in current fusion researches targeting ITER and DEMO. This work investigates the physics and operational characteristics of intrinsic and pellet induced ELMs throughout transport simulations using 1.5 D transport codes (C1.5/ASTRA) and MHD simulations using M3D code. Transport simulations are focused on prediction of the global parameters such as ELM energy loss in the type-I ELMy H-mode discharges with and without pellet pace making to examine an applicability of pellet injection for ELM mitigation in KSTAR and ITER. On the other hand, MHD simulations are conducted to explore the physics of intrinsic and pellet induced ELMs by applying the artificial free energy sources of velocity stream and density perturbations on the marginally stable equilibrium, respectively. Similarities and differences of triggering phenomena between intrinsic and pellet induced ELMs are discussed from the MHD approach.

  15. Modeling high resolution space-time variations in energy demand/CO2 emissions of human inhabited landscapes in the United States under a changing climate

    NASA Astrophysics Data System (ADS)

    Godbole, A. V.; Gurney, K. R.

    2010-12-01

    With urban and exurban areas now accounting for more than 50% of the world's population, projected to increase 20% by 2050 (UN World Urbanization Prospects, 2009), urban-climate interactions are of renewed interest to the climate change scientific community (Karl et. al, 1988; Kalnay and Cai, 2003; Seto and Shepherd, 2009). Until recently, climate modeling efforts treated urban-human systems as independent of the earth system. With studies pointing to the disproportionately large influence of urban areas on their surrounding environment (Small et. al, 2010), modeling efforts have begun to explicitly account for urban processes in land models, like the CLM 4.0 urban layer, for example (Oleson.et. al, 2008, 2010). A significant portion of the urban energy demand comes from the space heating and cooling requirement of the residential and commercial sectors - as much as 51% (DOE, RECS 2005) and 11% (Belzer, D. 2006) respectively, in the United States. Thus, these sectors are both responsible for a significant fraction of fossil fuel CO2 emissions and will be influenced by a changing climate through changes in energy use and energy supply planning. This points to the possibility of interactive processes and feedbacks with the climate system. Space conditioning energy demand is strongly driven by external air temperature (Ruth, M. et.al, 2006) in addition to other socio-economic variables such as building characteristics (age of structure, activity cycle, weekend/weekday usage profile), occupant characteristics (age of householder, household income) and energy prices (Huang, 2006; Santin et. al, 2009; Isaac and van Vuuren, 2009). All of these variables vary both in space and time. Projections of climate change have begun to simulate changes in temperature at much higher resolution than in the past (Diffenbaugh et. al, 2005). Hence, in order to understand how climate change and variability will potentially impact energy use/emissions and energy planning, these two

  16. Landowner Attitudes and Perceptions of Impact from Wind and Natural Gas Development in Northern Pennsylvania: Implications for Energy Landscapes in Rural America

    NASA Astrophysics Data System (ADS)

    Jacquet, Jeffrey Bryan

    Energy developments such as industrial scale wind farms and unconventional natural gas drilling represent some of the largest and most controversial land use changes occurring in the United States today. A diverse array of academic disciplines have each sought to explain the social, psychological, and economic effects of siting large industrial facilities in rural areas, however the research has largely remained discipline-specific. This study measures resident attitudes and perceptions of impact from both wind and gas drilling occurring simultaneously in the Armenia Mountain Area of northern Pennsylvania. The results of a mail survey of landowners (n = 1028) in this study area reveal factors that explain landowner variation in attitudes and perception of impact, and describe new forms of participation in the planning and siting of these energy projects. Direction is provided for a new and synthetic theoretical understanding of how residents perceive these impacts and impacts from land use change. The work advances “risk of social and psychological disruption” as a key factor that may influence how residents respond to the prospect of large land use changes. Implications for the regulation and planning of these energy sources are offered, including a new understanding of how landowners participate in the planning and siting of large energy projects. Finally, the limitations of this work, as well as opportunities and implications for future research, are discussed.

  17. First-principles characterization of the energy landscape and optical spectra of green fluorescent protein along the A→I→B proton transfer route.

    PubMed

    Grigorenko, Bella L; Nemukhin, Alexander V; Polyakov, Igor V; Morozov, Dmitry I; Krylov, Anna I

    2013-08-07

    Structures and optical spectra of the green fluorescent protein (GFP) forms along the proton transfer route A→I→B are characterized by first-principles calculations. We show that in the ground electronic state the structure representing the wild-type (wt) GFP with the neutral chromophore (A-form) is lowest in energy, whereas the systems with the anionic chromophore (B- and I-forms) are about 1 kcal/mol higher. In the S65T mutant, the structures with the anionic chromophore are significantly lower in energy than the systems with the neutral chromophore. The role of the nearby amino acid residues in the chromophore-containing pocket is re-examined. Calculations reveal that the structural differences between the I- and B-forms (the former has a slightly red-shifted absorption relative to the latter) are based not on the Thr203 orientation, but on the Glu222 position. In the case of wt-GFP, the hydrogen bond between the chromophore and the His148 residue stabilizes the structures with the deprotonated phenolic ring in the I- and B-forms. In the S65T mutant, concerted contributions from the His148 and Thr203 residues are responsible for a considerable energy gap between the lowest energy structure of the B type with the anionic chromophore from other structures.

  18. Exploring the free-energy landscape of carbohydrate-protein complexes: development and validation of scoring functions considering the binding-site topology

    NASA Astrophysics Data System (ADS)

    Eid, Sameh; Saleh, Noureldin; Zalewski, Adam; Vedani, Angelo

    2014-12-01

    Carbohydrates play a key role in a variety of physiological and pathological processes and, hence, represent a rich source for the development of novel therapeutic agents. Being able to predict binding mode and binding affinity is an essential, yet lacking, aspect of the structure-based design of carbohydrate-based ligands. We assembled a diverse data set comprising 273 carbohydrate-protein crystal structures with known binding affinity and evaluated the prediction accuracy of a large collection of well-established scoring and free-energy functions, as well as combinations thereof. Unfortunately, the tested functions were not capable of reproducing binding affinities in the studied complexes. To simplify the complex free-energy surface of carbohydrate-protein systems, we classified the studied proteins according to the topology and solvent exposure of the carbohydrate-binding site into five distinct categories. A free-energy model based on the proposed classification scheme reproduced binding affinities in the carbohydrate data set with an r 2 of 0.71 and root-mean-squared-error of 1.25 kcal/mol ( N = 236). The improvement in model performance underlines the significance of the differences in the local micro-environments of carbohydrate-binding sites and demonstrates the usefulness of calibrating free-energy functions individually according to binding-site topology and solvent exposure.

  19. Pseudoknots in RNA fold