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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

    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 α-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. From mechanical folding trajectories to intrinsic energy landscapes of biopolymers

    PubMed Central

    Hinczewski, Michael; Gebhardt, J. Christof M.; Rief, Matthias; Thirumalai, D.

    2013-01-01

    In single-molecule laser optical tweezer (LOT) pulling experiments, a protein or RNA is juxtaposed between DNA handles that are attached to beads in optical traps. The LOT generates folding trajectories under force in terms of time-dependent changes in the distance between the beads. How to construct the full intrinsic folding landscape (without the handles and beads) from the measured time series is a major unsolved problem. By using rigorous theoretical methods—which account for fluctuations of the DNA handles, rotation of the optical beads, variations in applied tension due to finite trap stiffness, as well as environmental noise and limited bandwidth of the apparatus—we provide a tractable method to derive intrinsic free-energy profiles. We validate the method by showing that the exactly calculable intrinsic free-energy profile for a generalized Rouse model, which mimics the two-state behavior in nucleic acid hairpins, can be accurately extracted from simulated time series in a LOT setup regardless of the stiffness of the handles. We next apply the approach to trajectories from coarse-grained LOT molecular simulations of a coiled-coil protein based on the GCN4 leucine zipper and obtain a free-energy landscape that is in quantitative agreement with simulations performed without the beads and handles. Finally, we extract the intrinsic free-energy landscape from experimental LOT measurements for the leucine zipper. PMID:23487746

  4. 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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26498066

  6. 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.

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

    PubMed

    Li, Chunhe; Wang, Erkang; Wang, Jin

    2012-05-21

    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.

  8. 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.

  9. Energy landscapes and persistent minima

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

    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.

  10. 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

  11. Topology of cyclo-octane energy landscape

    NASA Astrophysics Data System (ADS)

    Martin, Shawn; Thompson, Aidan; Coutsias, Evangelos A.; Watson, Jean-Paul

    2010-06-01

    Understanding energy landscapes is a major challenge in chemistry and biology. Although a wide variety of methods have been invented and applied to this problem, very little is understood about the actual mathematical structures underlying such landscapes. Perhaps the most general assumption is the idea that energy landscapes are low-dimensional manifolds embedded in high-dimensional Euclidean space. While this is a very mild assumption, we have discovered an example of an energy landscape which is nonmanifold, demonstrating previously unknown mathematical complexity. The example occurs in the energy landscape of cyclo-octane, which was found to have the structure of a reducible algebraic variety, composed of the union of a sphere and a Klein bottle, intersecting in two rings.

  12. 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.

  13. Energy landscapes and function of supramolecular systems

    PubMed Central

    Tantakitti, Faifan; Boekhoven, Job; Wang, Xin; Kazantsev, Roman; 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.

    2015-01-01

    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, function and energy landscape are linked, superseding the more traditional connection between molecular design and function. PMID:26779883

  14. 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.

  15. 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.

  16. 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.

  17. Efficient exploration of discrete energy landscapes

    NASA Astrophysics Data System (ADS)

    Mann, Martin; Klemm, Konstantin

    2011-01-01

    Many physical and chemical processes, such as folding of biopolymers, are best described as dynamics on large combinatorial energy landscapes. A concise approximate description of the dynamics is obtained by partitioning the microstates of the landscape into macrostates. Since most landscapes of interest are not tractable analytically, the probabilities of transitions between macrostates need to be extracted numerically from the microscopic ones, typically by full enumeration of the state space or approximations using the Arrhenius law. Here, we propose to approximate transition probabilities by a Markov chain Monte Carlo method. For landscapes of the number partitioning problem and an RNA switch molecule, we show that the method allows for accurate probability estimates with significantly reduced computational cost.

  18. Specificity and Affinity Quantification of Flexible Recognition from Underlying Energy Landscape Topography

    PubMed Central

    Chu, Xiakun; Wang, Jin

    2014-01-01

    Flexibility in biomolecular recognition is essential and critical for many cellular activities. Flexible recognition often leads to moderate affinity but high specificity, in contradiction with the conventional wisdom that high affinity and high specificity are coupled. Furthermore, quantitative understanding of the role of flexibility in biomolecular recognition is still challenging. Here, we meet the challenge by quantifying the intrinsic biomolecular recognition energy landscapes with and without flexibility through the underlying density of states. We quantified the thermodynamic intrinsic specificity by the topography of the intrinsic binding energy landscape and the kinetic specificity by association rate. We found that the thermodynamic and kinetic specificity are strongly correlated. Furthermore, we found that flexibility decreases binding affinity on one hand, but increases binding specificity on the other hand, and the decreasing or increasing proportion of affinity and specificity are strongly correlated with the degree of flexibility. This shows more (less) flexibility leads to weaker (stronger) coupling between affinity and specificity. Our work provides a theoretical foundation and quantitative explanation of the previous qualitative studies on the relationship among flexibility, affinity and specificity. In addition, we found that the folding energy landscapes are more funneled with binding, indicating that binding helps folding during the recognition. Finally, we demonstrated that the whole binding-folding energy landscapes can be integrated by the rigid binding and isolated folding energy landscapes under weak flexibility. Our results provide a novel way to quantify the affinity and specificity in flexible biomolecular recognition. PMID:25144525

  19. Local energy landscape in a simple liquid

    DOE PAGESBeta

    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

  20. 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.

  1. Local energy landscape in a simple liquid

    NASA Astrophysics Data System (ADS)

    Iwashita, T.; Egami, T.

    2014-11-01

    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. Fractal free energy landscapes in structural glasses.

    PubMed

    Charbonneau, Patrick; Kurchan, Jorge; Parisi, Giorgio; Urbani, Pierfrancesco; Zamponi, Francesco

    2014-01-01

    Glasses are amorphous solids whose constituent particles are caged by their neighbours and thus cannot flow. This sluggishness is often ascribed to the free energy landscape containing multiple minima (basins) separated by high barriers. Here we show, using theory and numerical simulation, that the landscape is much rougher than is classically assumed. Deep in the glass, it undergoes a 'roughness transition' to fractal basins, which brings about isostaticity and marginal stability on approaching jamming. Critical exponents for the basin width, the weak force distribution and the spatial spread of quasi-contacts near jamming can be analytically determined. Their value is found to be compatible with numerical observations. This advance incorporates the jamming transition of granular materials into the framework of glass theory. Because temperature and pressure control what features of the landscape are experienced, glass mechanics and transport are expected to reflect the features of the topology we discuss here. PMID:24759041

  3. 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.

  4. 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

  5. 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.

  6. Energy landscape of clathrate hydrates

    NASA Astrophysics Data System (ADS)

    Desmedt, A.; Bedouret, L.; Pefoute, E.; Pouvreau, M.; Say-Liang-Fat, S.; Alvarez, M.

    2012-11-01

    Clathrate hydrates are nanoporous crystalline materials made of a network of hydrogen-bonded water molecules (forming host cages) that is stabilized by the presence of foreign (generally hydrophobic) guest molecules. The natural existence of large quantities of hydrocarbon hydrates in deep oceans and permafrost is certainly at the origin of numerous applications in the broad areas of energy and environmental sciences and technologies (e.g. gas storage). At a fundamental level, their nanostructuration confers on these materials specific properties (e.g. their "glass-like" thermal conductivity) for which the host-guest interactions play a key role. These interactions occur on broad timescale and thus require the use of multi-technique approach in which neutron scattering brings unvaluable information. This work reviews the dynamical properties of clathrate hydrates, ranging from intramolecular vibrations to Brownian relaxations; it illustrates the contribution of neutron scattering in the understanding of the underlying factors governing chemical-physics properties specific to these nanoporous systems.

  7. 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

  8. Energy landscape in protein folding and unfolding.

    PubMed

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

    2016-03-22

    We use (1)H 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 295 < T < 365 K and following different trajectories along the protein energy 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.

  9. Energy landscapes of planar colloidal clusters

    NASA Astrophysics Data System (ADS)

    Morgan, John W. R.; Wales, David J.

    2014-08-01

    A short-ranged pairwise Morse potential is used to model colloidal clusters with planar morphologies. Potential and free energy global minima as well as rearrangement paths, obtained by basin-hopping global optimisation and discrete path sampling, are characterised. The potential and free energy landscapes are visualised using disconnectivity graphs. The short-ranged potential is found to favour close-packed structures, with the potential energy primarily controlled by the number of nearest neighbour contacts. In the case of quasi-degeneracy the free energy global minimum may differ from the potential energy global minimum. This difference is due to symmetry effects, which result in a higher entropy for structures with lower symmetry.

  10. Energy landscapes of planar colloidal clusters.

    PubMed

    Morgan, John W R; Wales, David J

    2014-09-21

    A short-ranged pairwise Morse potential is used to model colloidal clusters with planar morphologies. Potential and free energy global minima as well as rearrangement paths, obtained by basin-hopping global optimisation and discrete path sampling, are characterised. The potential and free energy landscapes are visualised using disconnectivity graphs. The short-ranged potential is found to favour close-packed structures, with the potential energy primarily controlled by the number of nearest neighbour contacts. In the case of quasi-degeneracy the free energy global minimum may differ from the potential energy global minimum. This difference is due to symmetry effects, which result in a higher entropy for structures with lower symmetry.

  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. Reconstructing Folding Energy Landscapes by Single-Molecule Force Spectroscopy

    PubMed Central

    Woodside, Michael T.; Block, Steven M.

    2015-01-01

    Folding may be described conceptually in terms of trajectories over a landscape of free energies corresponding to different molecular configurations. In practice, energy landscapes can be difficult to measure. Single-molecule force spectroscopy (SMFS), whereby structural changes are monitored in molecules subjected to controlled forces, has emerged as a powerful tool for probing energy landscapes. We summarize methods for reconstructing landscapes from force spectroscopy measurements under both equilibrium and nonequilibrium conditions. Other complementary, but technically less demanding, methods provide a model-dependent characterization of key features of the landscape. Once reconstructed, energy landscapes can be used to study critical folding parameters, such as the characteristic transition times required for structural changes and the effective diffusion coefficient setting the timescale for motions over the landscape. We also discuss issues that complicate measurement and interpretation, including the possibility of multiple states or pathways and the effects of projecting multiple dimensions onto a single coordinate. PMID:24895850

  13. Reconstructing folding energy landscapes by single-molecule force spectroscopy.

    PubMed

    Woodside, Michael T; Block, Steven M

    2014-01-01

    Folding may be described conceptually in terms of trajectories over a landscape of free energies corresponding to different molecular configurations. In practice, energy landscapes can be difficult to measure. Single-molecule force spectroscopy (SMFS), whereby structural changes are monitored in molecules subjected to controlled forces, has emerged as a powerful tool for probing energy landscapes. We summarize methods for reconstructing landscapes from force spectroscopy measurements under both equilibrium and nonequilibrium conditions. Other complementary, but technically less demanding, methods provide a model-dependent characterization of key features of the landscape. Once reconstructed, energy landscapes can be used to study critical folding parameters, such as the characteristic transition times required for structural changes and the effective diffusion coefficient setting the timescale for motions over the landscape. We also discuss issues that complicate measurement and interpretation, including the possibility of multiple states or pathways and the effects of projecting multiple dimensions onto a single coordinate.

  14. 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…

  15. Optimizing potential energy functions for maximal intrinsic hyperpolarizability

    SciTech Connect

    Zhou Juefei; Szafruga, Urszula B.; Kuzyk, Mark G.; Watkins, David S.

    2007-11-15

    We use numerical optimization to study the properties of (1) the class of one-dimensional potential energy functions and (2) systems of point nuclei in two dimensions that yield the largest intrinsic hyperpolarizabilities, which we find to be within 30% of the fundamental limit. In all cases, we use a one-electron model. It is found that a broad range of optimized potentials, each of very different character, yield the same intrinsic hyperpolarizability ceiling of 0.709. Furthermore, all optimized potential energy functions share common features such as (1) the value of the normalized transition dipole moment to the dominant state, which forces the hyperpolarizability to be dominated by only two excited states and (2) the energy ratio between the two dominant states. All optimized potentials are found to obey the three-level ansatz to within about 1%. Many of these potential energy functions may be implementable in multiple quantum well structures. The subset of potentials with undulations reaffirm that modulation of conjugation may be an approach for making better organic molecules, though there appear to be many others. Additionally, our results suggest that one-dimensional molecules may have larger diagonal intrinsic hyperpolarizability {beta}{sub xxx}{sup int} than higher-dimensional systems.

  16. Landscape Design and Nursery Operation for Energy Conservation.

    ERIC Educational Resources Information Center

    Bell, Richard C.; Glazener, Dennis

    Landforms, vegetation, water bodies, climate and solar radiation can be analyzed and used to design an energy-conserving landscape and horticulture operation. Accordingly, this course instructor's manual covers the use of the elements of the environment to make landscaping and nursery design and operation more energy-efficient. Five sections…

  17. Communication: Certifying the potential energy landscape

    NASA Astrophysics Data System (ADS)

    Mehta, Dhagash; Hauenstein, Jonathan D.; Wales, David J.

    2013-05-01

    It is highly desirable for numerical approximations to stationary points for a potential energy landscape to lie in the corresponding quadratic convergence basin. However, it is possible that an approximation may lie only in the linear convergence basin, or even in a chaotic region, and hence not converge to the actual stationary point when further optimization is attempted. Proving that a numerical approximation will quadratically converge to the associated stationary point is termed certification. Here, we apply Smale's α-theory to stationary points, providing a certification serving as a mathematical proof that the numerical approximation does indeed correspond to an actual stationary point, independent of the precision employed. As a practical example, employing recently developed certification algorithms, we show how the α-theory can be used to certify all the known minima and transition states of Lennard-Jones LJN atomic clusters for N = 7, …, 14.

  18. Certification and the potential energy landscape

    NASA Astrophysics Data System (ADS)

    Mehta, Dhagash; Hauenstein, Jonathan D.; Wales, David J.

    2014-06-01

    Typically, there is no guarantee that a numerical approximation obtained using standard nonlinear equation solvers is indeed an actual solution, meaning that it lies in the quadratic convergence basin. Instead, it may lie only in the linear convergence basin, or even in a chaotic region, and hence not converge to the corresponding stationary point when further optimization is attempted. In some cases, these non-solutions could be misleading. Proving that a numerical approximation will quadratically converge to a stationary point is termed certification. In this report, we provide details of how Smale's α-theory can be used to certify numerically obtained stationary points of a potential energy landscape, providing a mathematical proof that the numerical approximation does indeed correspond to an actual stationary point, independent of the precision employed.

  19. Certification and the potential energy landscape

    SciTech Connect

    Mehta, Dhagash; Hauenstein, Jonathan D.; Wales, David J.

    2014-06-14

    Typically, there is no guarantee that a numerical approximation obtained using standard nonlinear equation solvers is indeed an actual solution, meaning that it lies in the quadratic convergence basin. Instead, it may lie only in the linear convergence basin, or even in a chaotic region, and hence not converge to the corresponding stationary point when further optimization is attempted. In some cases, these non-solutions could be misleading. Proving that a numerical approximation will quadratically converge to a stationary point is termed certification. In this report, we provide details of how Smale's α-theory can be used to certify numerically obtained stationary points of a potential energy landscape, providing a mathematical proof that the numerical approximation does indeed correspond to an actual stationary point, independent of the precision employed.

  20. Energy landscape exploration of the folding processes of biological molecules

    NASA Astrophysics Data System (ADS)

    Engel, Megan Clare

    For decades, scientists from every discipline have struggled to understand the mechanism of biological self-assembly, which allows proteins and nucleic acids to fold reliably into functional three-dimensional structures. Such an understanding may hold the key to eliminating diseases such as Alzheimer's and Parkinson's and to effective protein engineering. The current best framework for describing biological folding processes is that of statistical mechanical energy landscape theory, and one of the most promising experimental techniques for exploring molecular energy landscapes is single molecule force spectroscopy (SMFS), in which molecules are mechanically denatured. Theoretical advances have enabled the extraction of complete energy landscape profiles from SMFS data. Here, SMFS experiments performed using laser optical tweezers are analyzed to yield the first ever full landscape profile for an RNA pseudoknot. Further, a promising novel landscape reconstruction technique is validated for the first time using experimental data from a DNA hairpin.

  1. 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.

  2. Potential energy landscapes of elemental and heterogeneous chalcogen clusters

    SciTech Connect

    Mauro, John C.; Loucks, Roger J.; Balakrishnan, Jitendra; Varshneya, Arun K.

    2006-02-15

    We describe the potential energy landscapes of elemental S{sub 8}, Se{sub 8}, and Te{sub 8} clusters using disconnectivity graphs. Inherent structures include both ring and chain configurations, with rings especially dominant in Se{sub 8}. We also map the potential energy landscapes of heterogeneous Se{sub n}(S,Te){sub 8-n} clusters, which offer insights into the structure of heterogeneous chalcogen glasses.

  3. Random versus Deterministic Descent in RNA Energy Landscape Analysis

    PubMed Central

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

    2016-01-01

    Identifying sets of metastable conformations is a major research topic in RNA energy landscape analysis, and recently several methods have been proposed for finding local minima in landscapes spawned by RNA secondary structures. An important and time-critical component of such methods is steepest, or gradient, descent in attraction basins of local minima. We analyse the speed-up achievable by randomised descent in attraction basins in the context of large sample sets where the size has an order of magnitude in the region of ~106. While the gain for each individual sample might be marginal, the overall run-time improvement can be significant. Moreover, for the two nongradient methods we analysed for partial energy landscapes induced by ten different RNA sequences, we obtained that the number of observed local minima is on average larger by 7.3% and 3.5%, respectively. The run-time improvement is approximately 16.6% and 6.8% on average over the ten partial energy landscapes. For the large sample size we selected for descent procedures, the coverage of local minima is very high up to energy values of the region where the samples were randomly selected from the partial energy landscapes; that is, the difference to the total set of local minima is mainly due to the upper area of the energy landscapes. PMID:27110241

  4. Random versus Deterministic Descent in RNA Energy Landscape Analysis.

    PubMed

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

    2016-01-01

    Identifying sets of metastable conformations is a major research topic in RNA energy landscape analysis, and recently several methods have been proposed for finding local minima in landscapes spawned by RNA secondary structures. An important and time-critical component of such methods is steepest, or gradient, descent in attraction basins of local minima. We analyse the speed-up achievable by randomised descent in attraction basins in the context of large sample sets where the size has an order of magnitude in the region of ~10(6). While the gain for each individual sample might be marginal, the overall run-time improvement can be significant. Moreover, for the two nongradient methods we analysed for partial energy landscapes induced by ten different RNA sequences, we obtained that the number of observed local minima is on average larger by 7.3% and 3.5%, respectively. The run-time improvement is approximately 16.6% and 6.8% on average over the ten partial energy landscapes. For the large sample size we selected for descent procedures, the coverage of local minima is very high up to energy values of the region where the samples were randomly selected from the partial energy landscapes; that is, the difference to the total set of local minima is mainly due to the upper area of the energy landscapes.

  5. 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.

  6. 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

  7. Intrinsic uncertainty on the nature of dark energy

    NASA Astrophysics Data System (ADS)

    Valkenburg, Wessel; Kunz, Martin; Marra, Valerio

    2013-12-01

    We argue that there is an intrinsic noise on measurements of the equation of state parameter w = p/ρ from large-scale structure around us. The presence of the large-scale structure leads to an ambiguity in the definition of the background universe and thus there is a maximal precision with which we can determine the equation of state of dark energy. To study the uncertainty due to local structure, we model density perturbations stemming from a standard inflationary power spectrum by means of the exact Lemaître-Tolman-Bondi solution of Einstein’s equation, and show that the usual distribution of matter inhomogeneities in a ΛCDM cosmology causes a variation of w - as inferred from distance measures - of several percent. As we observe only one universe, or equivalently because of the cosmic variance, this uncertainty is systematic in nature.

  8. Energy landscapes for a machine learning application to series data

    NASA Astrophysics Data System (ADS)

    Ballard, Andrew J.; Stevenson, Jacob D.; Das, Ritankar; Wales, David J.

    2016-03-01

    Methods developed to explore and characterise potential energy landscapes are applied to the corresponding landscapes obtained from optimisation of a cost function in machine learning. We consider neural network predictions for the outcome of local geometry optimisation in a triatomic cluster, where four distinct local minima exist. The accuracy of the predictions is compared for fits using data from single and multiple points in the series of atomic configurations resulting from local geometry optimisation and for alternative neural networks. The machine learning solution landscapes are visualised using disconnectivity graphs, and signatures in the effective heat capacity are analysed in terms of distributions of local minima and their properties.

  9. Energy landscapes for a machine learning application to series data.

    PubMed

    Ballard, Andrew J; Stevenson, Jacob D; Das, Ritankar; Wales, David J

    2016-03-28

    Methods developed to explore and characterise potential energy landscapes are applied to the corresponding landscapes obtained from optimisation of a cost function in machine learning. We consider neural network predictions for the outcome of local geometry optimisation in a triatomic cluster, where four distinct local minima exist. The accuracy of the predictions is compared for fits using data from single and multiple points in the series of atomic configurations resulting from local geometry optimisation and for alternative neural networks. The machine learning solution landscapes are visualised using disconnectivity graphs, and signatures in the effective heat capacity are analysed in terms of distributions of local minima and their properties.

  10. Can computed crystal energy landscapes help understand pharmaceutical solids?

    PubMed

    Price, Sarah L; Braun, Doris E; Reutzel-Edens, Susan M

    2016-06-01

    Computational crystal structure prediction (CSP) methods can now be applied to the smaller pharmaceutical molecules currently in drug development. We review the recent uses of computed crystal energy landscapes for pharmaceuticals, concentrating on examples where they have been used in collaboration with industrial-style experimental solid form screening. There is a strong complementarity in aiding experiment to find and characterise practically important solid forms and understanding the nature of the solid form landscape. PMID:27067116

  11. Conformational ensembles and sampled energy landscapes: Analysis and comparison.

    PubMed

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

    2015-06-15

    We present novel algorithms and software addressing four core problems in computational structural biology, namely analyzing a conformational ensemble, comparing two conformational ensembles, analyzing a sampled energy landscape, and comparing two sampled energy landscapes. Using recent developments in computational topology, graph theory, and combinatorial optimization, we make two notable contributions. First, we present a generic algorithm analyzing height fields. We then use this algorithm to perform density-based clustering of conformations, and to analyze a sampled energy landscape in terms of basins and transitions between them. In both cases, topological persistence is used to manage (geometric) frustration. Second, we introduce two algorithms to compare transition graphs. The first is the classical earth mover distance metric which depends only on local minimum energy configurations along with their statistical weights, while the second incorporates topological constraints inherent to conformational transitions. Illustrations are provided on a simplified protein model (BLN69), whose frustrated potential energy landscape has been thoroughly studied. The software implementing our tools is also made available, and should prove valuable wherever conformational ensembles and energy landscapes are used. PMID:25994596

  12. Conformational ensembles and sampled energy landscapes: Analysis and comparison.

    PubMed

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

    2015-06-15

    We present novel algorithms and software addressing four core problems in computational structural biology, namely analyzing a conformational ensemble, comparing two conformational ensembles, analyzing a sampled energy landscape, and comparing two sampled energy landscapes. Using recent developments in computational topology, graph theory, and combinatorial optimization, we make two notable contributions. First, we present a generic algorithm analyzing height fields. We then use this algorithm to perform density-based clustering of conformations, and to analyze a sampled energy landscape in terms of basins and transitions between them. In both cases, topological persistence is used to manage (geometric) frustration. Second, we introduce two algorithms to compare transition graphs. The first is the classical earth mover distance metric which depends only on local minimum energy configurations along with their statistical weights, while the second incorporates topological constraints inherent to conformational transitions. Illustrations are provided on a simplified protein model (BLN69), whose frustrated potential energy landscape has been thoroughly studied. The software implementing our tools is also made available, and should prove valuable wherever conformational ensembles and energy landscapes are used.

  13. Comparing the folding and misfolding energy landscapes of phosphoglycerate kinase.

    PubMed

    Agócs, Gergely; Szabó, Bence T; Köhler, Gottfried; Osváth, Szabolcs

    2012-06-20

    Partitioning of polypeptides between protein folding and amyloid formation is of outstanding pathophysiological importance. Using yeast phosphoglycerate kinase as model, here we identify the features of the energy landscape that decide the fate of the protein: folding or amyloidogenesis. Structure formation was initiated from the acid-unfolded state, and monitored by fluorescence from 10 ms to 20 days. Solvent conditions were gradually shifted between folding and amyloidogenesis, and the properties of the energy landscape governing structure formation were reconstructed. A gradual transition of the energy landscape between folding and amyloid formation was observed. In the early steps of both folding and misfolding, the protein searches through a hierarchically structured energy landscape to form a molten globule in a few seconds. Depending on the conditions, this intermediate either folds to the native state in a few minutes, or forms amyloid fibers in several days. As conditions are changed from folding to misfolding, the barrier separating the molten globule and native states increases, although the barrier to the amyloid does not change. In the meantime, the native state also becomes more unstable and the amyloid more stable. We conclude that the lower region of the energy landscape determines the final protein structure. PMID:22735533

  14. Inflation, dark matter, and dark energy in the string landscape.

    PubMed

    Liddle, Andrew R; Ureña-López, L Arturo

    2006-10-20

    We consider the conditions needed to unify the description of dark matter, dark energy, and inflation in the context of the string landscape. We find that incomplete decay of the inflaton field gives the possibility that a single field is responsible for all three phenomena. By contrast, unifying dark matter and dark energy into a single field, separate from the inflaton, appears rather difficult.

  15. Energy Landscapes for the Self-Assembly of Supramolecular Polyhedra

    NASA Astrophysics Data System (ADS)

    Russell, Emily R.; Menon, Govind

    2016-06-01

    We develop a mathematical model for the energy landscape of polyhedral supramolecular cages recently synthesized by self-assembly (Sun et al. in Science 328:1144-1147, 2010). Our model includes two essential features of the experiment: (1) geometry of the organic ligands and metallic ions; and (2) combinatorics. The molecular geometry is used to introduce an energy that favors square-planar vertices (modeling {Pd}^{2+} ions) and bent edges with one of two preferred opening angles (modeling boomerang-shaped ligands of two types). The combinatorics of the model involve two-colorings of edges of polyhedra with four-valent vertices. The set of such two-colorings, quotiented by the octahedral symmetry group, has a natural graph structure and is called the combinatorial configuration space. The energy landscape of our model is the energy of each state in the combinatorial configuration space. The challenge in the computation of the energy landscape is a combinatorial explosion in the number of two-colorings of edges. We describe sampling methods based on the symmetries of the configurations and connectivity of the configuration graph. When the two preferred opening angles encompass the geometrically ideal angle, the energy landscape exhibits a very low-energy minimum for the most symmetric configuration at equal mixing of the two angles, even when the average opening angle does not match the ideal angle.

  16. Quasi-combinatorial energy landscapes for nanoalloy structure optimisation.

    PubMed

    Schebarchov, D; Wales, D J

    2015-11-14

    We formulate nanoalloy structure prediction as a mixed-variable optimisation problem, where the homotops can be associated with an effective, quasi-combinatorial energy landscape in permutation space. We survey this effective landscape for a representative set of binary systems modelled by the Gupta potential. In segregating systems with small lattice mismatch, we find that homotops have a relatively straightforward landscape with few local optima - a scenario well-suited for local (combinatorial) optimisation techniques that scale quadratically with system size. Combining these techniques with multiple local-neighbourhood structures yields a search for multiminima, and we demonstrate that generalised basin-hopping with a metropolis acceptance criterion in the space of multiminima can then be effective for global optimisation of binary and ternary nanoalloys.

  17. 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.

  18. 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. PMID:27322823

  19. Free-energy landscape of a hyperstable RNA tetraloop.

    PubMed

    Miner, Jacob C; Chen, Alan A; García, Angel E

    2016-06-14

    We report the characterization of the energy landscape and the folding/unfolding thermodynamics of a hyperstable RNA tetraloop obtained through high-performance molecular dynamics simulations at microsecond timescales. Sampling of the configurational landscape is conducted using temperature replica exchange molecular dynamics over three isochores at high, ambient, and negative pressures to determine the thermodynamic stability and the free-energy landscape of the tetraloop. The simulations reveal reversible folding/unfolding transitions of the tetraloop into the canonical A-RNA conformation and the presence of two alternative configurations, including a left-handed Z-RNA conformation and a compact purine Triplet. Increasing hydrostatic pressure shows a stabilizing effect on the A-RNA conformation and a destabilization of the left-handed Z-RNA. Our results provide a comprehensive description of the folded free-energy landscape of a hyperstable RNA tetraloop and highlight the significant advances of all-atom molecular dynamics in describing the unbiased folding of a simple RNA secondary structure motif.

  20. Energy landscapes reveal the myopathic effects of tropomyosin mutations.

    PubMed

    Orzechowski, Marek; Fischer, Stefan; Moore, Jeffrey R; Lehman, William; Farman, Gerrie P

    2014-12-15

    Striated muscle contraction is regulated by an interaction network connecting the effects of troponin, Ca(2+), and myosin-heads to the azimuthal positioning of tropomyosin along thin filaments. Many missense mutations, located at the actin-tropomyosin interface, however, reset the regulatory switching mechanism either by weakening or strengthening residue-specific interactions, leading to hyper- or hypo-contractile pathologies. Here, we compute energy landscapes for the actin-tropomyosin interface and quantify contributions of single amino acid residues to actin-tropomyosin binding. The method is a useful tool to assess effects of actin and tropomyosin mutations, potentially relating initial stages of myopathy to alterations in thin filament stability and regulation. Landscapes for mutant filaments linked to hyper-contractility provide a simple picture that describes a decrease in actin-tropomyosin interaction energy. Destabilizing the blocked (relaxed)-state parallels previously noted enhanced Ca(2+)-sensitivity conferred by these mutants. Energy landscapes also identify post-translational modifications that can rescue regulatory imbalances. For example, cardiomyopathy-associated E62Q tropomyosin mutation weakens actin-tropomyosin interaction, but phosphorylation of neighboring S61 rescues the binding-deficit, results confirmed experimentally by in vitro motility assays. Unlike results on hyper-contractility-related mutants, landscapes for tropomyosin mutants tied to hypo-contractility do not present a straightforward picture. These mutations may affect other components of the regulatory network, e.g., troponin-tropomyosin signaling.

  1. Energy landscapes of resting-state brain networks.

    PubMed

    Watanabe, Takamitsu; Hirose, Satoshi; Wada, Hiroyuki; Imai, Yoshio; Machida, Toru; Shirouzu, Ichiro; Konishi, Seiki; Miyashita, Yasushi; Masuda, Naoki

    2014-01-01

    During rest, the human brain performs essential functions such as memory maintenance, which are associated with resting-state brain networks (RSNs) including the default-mode network (DMN) and frontoparietal network (FPN). Previous studies based on spiking-neuron network models and their reduced models, as well as those based on imaging data, suggest that resting-state network activity can be captured as attractor dynamics, i.e., dynamics of the brain state toward an attractive state and transitions between different attractors. Here, we analyze the energy landscapes of the RSNs by applying the maximum entropy model, or equivalently the Ising spin model, to human RSN data. We use the previously estimated parameter values to define the energy landscape, and the disconnectivity graph method to estimate the number of local energy minima (equivalent to attractors in attractor dynamics), the basin size, and hierarchical relationships among the different local minima. In both of the DMN and FPN, low-energy local minima tended to have large basins. A majority of the network states belonged to a basin of one of a few local minima. Therefore, a small number of local minima constituted the backbone of each RSN. In the DMN, the energy landscape consisted of two groups of low-energy local minima that are separated by a relatively high energy barrier. Within each group, the activity patterns of the local minima were similar, and different minima were connected by relatively low energy barriers. In the FPN, all dominant local minima were separated by relatively low energy barriers such that they formed a single coarse-grained global minimum. Our results indicate that multistable attractor dynamics may underlie the DMN, but not the FPN, and assist memory maintenance with different memory states.

  2. 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}.

  3. In Search of Energy Landscape for Network Glasses

    SciTech Connect

    R Golovchak; A Kovalskiy; O Shpotyuk; H Jain

    2011-12-31

    Quick scanning extended x-ray absorption fine-structure spectroscopy is used to obtain in situ structural information on the real-time response of network glasses at the nanoscale level of atomic organization to the temperature ramp through the glass transition range. The results testify nonlinear, real-time temperature response indicative of nanoscale dynamic heterogeneity in disordered systems with intermediate fragility, related to the intermetabasin transitions within potential energy/enthalpy landscape.

  4. 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.

  5. 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.

  6. The heterogeneous energy landscape expression of KWW relaxation

    PubMed Central

    Wu, J. H.; Jia, Q.

    2016-01-01

    Here we show a heterogeneous energy landscape approach to describing the Kohlrausch-Williams-Watts (KWW) relaxation function. For a homogeneous dynamic process, the distribution of free energy landscape is first proposed, revealing the significance of rugged fluctuations. In view of the heterogeneous relaxation given in two dynamic phases and the transmission coefficient in a rate process, we obtain a general characteristic relaxation time distribution equation for the KWW function in a closed, analytic form. Analyses of numerical computation show excellent accuracy, both in time and frequency domains, in the convergent performance of the heterogeneous energy landscape expression and shunning the catastrophic truncations reported in the previous work. The stretched exponential β, closely associated to temperature and apparent correlation with one dynamic phase, reveals a threshold value of 1/2 defining different behavior of the probability density functions. Our work may contribute, for example, to in-depth comprehension of the dynamic mechanism of glass transition, which cannot be provided by existing approaches. PMID:26879824

  7. 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.

  8. Potential Energy Landscape and Robustness of a Gene Regulatory Network: Toggle Switch

    PubMed Central

    Kim, Keun-Young; Wang, Jin

    2007-01-01

    Finding a multidimensional potential landscape is the key for addressing important global issues, such as the robustness of cellular networks. We have uncovered the underlying potential energy landscape of a simple gene regulatory network: a toggle switch. This was realized by explicitly constructing the steady state probability of the gene switch in the protein concentration space in the presence of the intrinsic statistical fluctuations due to the small number of proteins in the cell. We explored the global phase space for the system. We found that the protein synthesis rate and the unbinding rate of proteins to the gene were small relative to the protein degradation rate; the gene switch is monostable with only one stable basin of attraction. When both the protein synthesis rate and the unbinding rate of proteins to the gene are large compared with the protein degradation rate, two global basins of attraction emerge for a toggle switch. These basins correspond to the biologically stable functional states. The potential energy barrier between the two basins determines the time scale of conversion from one to the other. We found as the protein synthesis rate and protein unbinding rate to the gene relative to the protein degradation rate became larger, the potential energy barrier became larger. This also corresponded to systems with less noise or the fluctuations on the protein numbers. It leads to the robustness of the biological basins of the gene switches. The technique used here is general and can be applied to explore the potential energy landscape of the gene networks. PMID:17397255

  9. 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.

  10. Accelerated weight histogram method for exploring free energy landscapes

    NASA Astrophysics Data System (ADS)

    Lindahl, V.; Lidmar, J.; Hess, B.

    2014-07-01

    Calculating free energies is an important and notoriously difficult task for molecular simulations. The rapid increase in computational power has made it possible to probe increasingly complex systems, yet extracting accurate free energies from these simulations remains a major challenge. Fully exploring the free energy landscape of, say, a biological macromolecule typically requires sampling large conformational changes and slow transitions. Often, the only feasible way to study such a system is to simulate it using an enhanced sampling method. The accelerated weight histogram (AWH) method is a new, efficient extended ensemble sampling technique which adaptively biases the simulation to promote exploration of the free energy landscape. The AWH method uses a probability weight histogram which allows for efficient free energy updates and results in an easy discretization procedure. A major advantage of the method is its general formulation, making it a powerful platform for developing further extensions and analyzing its relation to already existing methods. Here, we demonstrate its efficiency and general applicability by calculating the potential of mean force along a reaction coordinate for both a single dimension and multiple dimensions. We make use of a non-uniform, free energy dependent target distribution in reaction coordinate space so that computational efforts are not wasted on physically irrelevant regions. We present numerical results for molecular dynamics simulations of lithium acetate in solution and chignolin, a 10-residue long peptide that folds into a β-hairpin. We further present practical guidelines for setting up and running an AWH simulation.

  11. Correlated energy landscape model for finite, random heteropolymers

    NASA Astrophysics Data System (ADS)

    Plotkin, Steven S.; Wang, Jin; Wolynes, Peter G.

    1996-06-01

    In this paper, we study the role of correlations in the energy landscape of a finite random heteropolymer by developing the mapping onto the generalized random energy model (GREM) proposed by Derrida and Gardner [J. Phys. C 19, 2253 (1986)] in the context of spin glasses. After obtaining the joint distribution for energies of pairs of configurations, and by calculating the entropy of the polymer subject to weak and strong topological constraints, the model yields thermodynamic quantities such as ground-state energy, entropy per thermodynamic basin, and glass transition temperature as functions of the polymer length and packing density. These are found to be very close to the uncorrelated landscape or random energy model (REM) estimates. A tricritical point is obtained where behavior of the order parameter q changes from first order with a discrete jump at the transition, to second-order continuous. While the thermodynamic quantities obtained from the free energy are close to the REM values, the Levinthal entropy describing the number of basins which must be searched at the glass transition is significantly modified by correlations.

  12. Accelerated weight histogram method for exploring free energy landscapes

    SciTech Connect

    Lindahl, V.; Lidmar, J.; Hess, B.

    2014-07-28

    Calculating free energies is an important and notoriously difficult task for molecular simulations. The rapid increase in computational power has made it possible to probe increasingly complex systems, yet extracting accurate free energies from these simulations remains a major challenge. Fully exploring the free energy landscape of, say, a biological macromolecule typically requires sampling large conformational changes and slow transitions. Often, the only feasible way to study such a system is to simulate it using an enhanced sampling method. The accelerated weight histogram (AWH) method is a new, efficient extended ensemble sampling technique which adaptively biases the simulation to promote exploration of the free energy landscape. The AWH method uses a probability weight histogram which allows for efficient free energy updates and results in an easy discretization procedure. A major advantage of the method is its general formulation, making it a powerful platform for developing further extensions and analyzing its relation to already existing methods. Here, we demonstrate its efficiency and general applicability by calculating the potential of mean force along a reaction coordinate for both a single dimension and multiple dimensions. We make use of a non-uniform, free energy dependent target distribution in reaction coordinate space so that computational efforts are not wasted on physically irrelevant regions. We present numerical results for molecular dynamics simulations of lithium acetate in solution and chignolin, a 10-residue long peptide that folds into a β-hairpin. We further present practical guidelines for setting up and running an AWH simulation.

  13. 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

  14. 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.

  15. 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.

  16. Energy landscapes of quantum Lennard-Jones solids.

    PubMed

    Chakravarty, Charusita

    2011-06-30

    To generalize inherent structure analysis to understand structural changes in quantum liquids and solids, differences between classical (V(x)) and quantum-corrected (U(qeff)(x)) energy landscapes are estimated as a function of the de Boer parameter (Λ). Path integral simulations of quantum Lennard-Jones solids are performed at zero pressure and a dimensionless reduced temperature of 0.123, corresponding to an absolute temperature of 4.2K. At constant temperature and pressure, Λ is increased from the classical limit of zero to Λ = 0.28, corresponding to para-H(2). Increasing quantum delocalization effects result in a continuous decrease in density and local order but without a transition to a disordered, liquid state. The inherent structure landscape of bulk systems is strongly dependent on density with the energy and stability of crystalline minima decreasing relative to that of amorphous packing minima as the system is stretched. For Λ ≈ 0.23, the volume fluctuations in quantum solids are sufficient to result in sampling of disordered minima while for Λ = 0.28, the underlying classical inherent structures are completely disordered, indicating that the topography of U(qeff)(x) and V(x) are qualitatively different for such values of Λ. To assess the nature of the quantum-corrected energy landscape, effective pair potentials are defined by u(qeff)(r) = -kT ln g(r) using the pair correlation function (g(r)) of the quantum system in the neighborhood of the first peak. Our results show that as Λ increases, the pair potentials become increasingly softer, shallower, and of increasing range with a shifting of the potential minimum to larger distances. For example, the reduction of the entropy of fusion and melting temperatures of quantum solids with increasing Λ are analogous to the changes in thermodynamics of melting seen in classical solids with increasing range and softness of interactions. The energy landscapes associated with such coarse-grained potentials

  17. Energy landscapes of quantum Lennard-Jones solids.

    PubMed

    Chakravarty, Charusita

    2011-06-30

    To generalize inherent structure analysis to understand structural changes in quantum liquids and solids, differences between classical (V(x)) and quantum-corrected (U(qeff)(x)) energy landscapes are estimated as a function of the de Boer parameter (Λ). Path integral simulations of quantum Lennard-Jones solids are performed at zero pressure and a dimensionless reduced temperature of 0.123, corresponding to an absolute temperature of 4.2K. At constant temperature and pressure, Λ is increased from the classical limit of zero to Λ = 0.28, corresponding to para-H(2). Increasing quantum delocalization effects result in a continuous decrease in density and local order but without a transition to a disordered, liquid state. The inherent structure landscape of bulk systems is strongly dependent on density with the energy and stability of crystalline minima decreasing relative to that of amorphous packing minima as the system is stretched. For Λ ≈ 0.23, the volume fluctuations in quantum solids are sufficient to result in sampling of disordered minima while for Λ = 0.28, the underlying classical inherent structures are completely disordered, indicating that the topography of U(qeff)(x) and V(x) are qualitatively different for such values of Λ. To assess the nature of the quantum-corrected energy landscape, effective pair potentials are defined by u(qeff)(r) = -kT ln g(r) using the pair correlation function (g(r)) of the quantum system in the neighborhood of the first peak. Our results show that as Λ increases, the pair potentials become increasingly softer, shallower, and of increasing range with a shifting of the potential minimum to larger distances. For example, the reduction of the entropy of fusion and melting temperatures of quantum solids with increasing Λ are analogous to the changes in thermodynamics of melting seen in classical solids with increasing range and softness of interactions. The energy landscapes associated with such coarse-grained potentials

  18. Energy landscapes and global thermodynamics for alanine peptides

    NASA Astrophysics Data System (ADS)

    Somani, Sandeep; Wales, David J.

    2013-09-01

    We compare different approaches for computing the thermodynamics of biomolecular systems. Techniques based on parallel replicas evolving via molecular dynamics or Monte Carlo simulations produce overlapping histograms for the densities of states. In contrast, energy landscape methods employ a superposition partition function constructed from local minima of the potential energy surface. The latter approach is particularly powerful for systems exhibiting broken ergodicity, and it is usually implemented using a harmonic normal mode approximation, which has not been extensively tested for biomolecules. The present contribution compares these alternative approaches for small alanine peptides modelled using the CHARMM and AMBER force fields. Densities of states produced from canonical sampling using multiple temperature replicas provide accurate reference data to evaluate the effect of the harmonic normal mode approximation in the superposition calculations. This benchmarking lays foundations for the application of energy landscape methods to larger biomolecules. It will also provide well characterised model systems for developing enhanced sampling methods, and for the treatment of anharmonicity corresponding to individual local minima.

  19. The Energy Landscape Analysis of Cancer Mutations in Protein Kinases

    PubMed Central

    Dixit, Anshuman; Verkhivker, Gennady M.

    2011-01-01

    The growing interest in quantifying the molecular basis of protein kinase activation and allosteric regulation by cancer mutations has fueled computational studies of allosteric signaling in protein kinases. In the present study, we combined computer simulations and the energy landscape analysis of protein kinases to characterize the interplay between oncogenic mutations and locally frustrated sites as important catalysts of allostetric kinase activation. While structurally rigid kinase core constitutes a minimally frustrated hub of the catalytic domain, locally frustrated residue clusters, whose interaction networks are not energetically optimized, are prone to dynamic modulation and could enable allosteric conformational transitions. The results of this study have shown that the energy landscape effect of oncogenic mutations may be allosteric eliciting global changes in the spatial distribution of highly frustrated residues. We have found that mutation-induced allosteric signaling may involve a dynamic coupling between structurally rigid (minimally frustrated) and plastic (locally frustrated) clusters of residues. The presented study has demonstrated that activation cancer mutations may affect the thermodynamic equilibrium between kinase states by allosterically altering the distribution of locally frustrated sites and increasing the local frustration in the inactive form, while eliminating locally frustrated sites and restoring structural rigidity of the active form. The energy landsape analysis of protein kinases and the proposed role of locally frustrated sites in activation mechanisms may have useful implications for bioinformatics-based screening and detection of functional sites critical for allosteric regulation in complex biomolecular systems. PMID:21998754

  20. 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

  1. 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

  2. Protein energy landscapes determined by five-dimensional crystallography.

    PubMed

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

    2013-12-01

    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.

  3. 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.

  4. Computer simulations of glasses: the potential energy landscape

    NASA Astrophysics Data System (ADS)

    Raza, Zamaan; Alling, Björn; Abrikosov, Igor A.

    2015-07-01

    We review the current state of research on glasses, discussing the theoretical background and computational models employed to describe them. This article focuses on the use of the potential energy landscape (PEL) paradigm to account for the phenomenology of glassy systems, and the way in which it can be applied in simulations and the interpretation of their results. This article provides a broad overview of the rich phenomenology of glasses, followed by a summary of the theoretical frameworks developed to describe this phenomonology. We discuss the background of the PEL in detail, the onerous task of how to generate computer models of glasses, various methods of analysing numerical simulations, and the literature on the most commonly used model systems. Finally, we tackle the problem of how to distinguish a good glass former from a good crystal former from an analysis of the PEL. In summarising the state of the potential energy landscape picture, we develop the foundations for new theoretical methods that allow the ab initio prediction of the glass-forming ability of new materials by analysis of the PEL.

  5. 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

  6. Randomized tree construction algorithm to explore energy landscapes.

    PubMed

    Jaillet, Léonard; Corcho, Francesc J; Pérez, Juan-Jesús; Cortés, Juan

    2011-12-01

    In this work, a new method for exploring conformational energy landscapes is described. The method, called transition-rapidly exploring random tree (T-RRT), combines ideas from statistical physics and robot path planning algorithms. A search tree is constructed on the conformational space starting from a given state. The tree expansion is driven by a double strategy: on the one hand, it is naturally biased toward yet unexplored regions of the space; on the other, a Monte Carlo-like transition test guides the expansion toward energetically favorable regions. The balance between these two strategies is automatically achieved due to a self-tuning mechanism. The method is able to efficiently find both energy minima and transition paths between them. As a proof of concept, the method is applied to two academic benchmarks and the alanine dipeptide.

  7. Randomized tree construction algorithm to explore energy landscapes.

    PubMed

    Jaillet, Léonard; Corcho, Francesc J; Pérez, Juan-Jesús; Cortés, Juan

    2011-12-01

    In this work, a new method for exploring conformational energy landscapes is described. The method, called transition-rapidly exploring random tree (T-RRT), combines ideas from statistical physics and robot path planning algorithms. A search tree is constructed on the conformational space starting from a given state. The tree expansion is driven by a double strategy: on the one hand, it is naturally biased toward yet unexplored regions of the space; on the other, a Monte Carlo-like transition test guides the expansion toward energetically favorable regions. The balance between these two strategies is automatically achieved due to a self-tuning mechanism. The method is able to efficiently find both energy minima and transition paths between them. As a proof of concept, the method is applied to two academic benchmarks and the alanine dipeptide. PMID:21919017

  8. Energy landscapes and catalysis in nitric-oxide synthase.

    PubMed

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

    2014-04-25

    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.

  9. 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

  10. Comparison of Quantum Mechanics and Molecular Mechanics Dimerization Energy Landscapes for Pairs of Ring-Containing Amino Acids in Proteins

    SciTech Connect

    Morozov, Alexandre V.; Misura M. S., Kira; Tsemekhman, Kiril; Baker, David

    2004-06-17

    A promising approach to developing improved potential functions for modeling macromolecular interactions consists of combining protein structural analysis, quantum mechanical calculations on small molecule models, and molecular mechanics potential decomposition. Here we apply this approach to the interactions of pairs of ring-containing amino acids in proteins. We find reasonable qualitative agreement between molecular mechanics and quantum chemistry calculations, both over one-dimensional projections of the binding free energy landscape for amino acid homodimers and over a set of homodimers and heterodimers from experimentally observed protein crystal structures. The molecular mechanics landscapes are a sum of charge-charge and Lennard-Jones contributions; short-range quantum mechanical effects such as charge transfer appear not to be significant in ring side chain interactions. We also find a reasonable degree of correlation between the molecular mechanics energy landscapes and the distributions of dimer geometries observed in protein structures, suggesting that the intrinsic dimer interaction energies do contribute to packing of side chains in proteins rather than being overwhelmed by the numerous interactions with other protein atoms and solvent. These results demonstrate that interactions involving aromatic residues and proline can be fairly well modeled using current molecular mechanics force fields, but there is still room for improvement, particularly for interactions involving proline and tyrosine.

  11. Energy-band structure and intrinsic coherent properties in two weakly linked Bose-Einstein condensates

    NASA Astrophysics Data System (ADS)

    Li, Wei-Dong; Zhang, Yunbo; Liang, J.-Q.

    2003-06-01

    The energy-band structure and energy splitting due to quantum tunneling in two weakly linked Bose-Einstein condensates were calculated by using the instanton method. The intrinsic coherent properties of Bose-Josephson junction (BJJ) were investigated in terms of energy splitting. For EC/EJ≪1, the energy splitting is small and the system is globally phase coherent. In the opposite limit, EC/EJ≫1, the energy splitting is large and the system becomes phase dissipated. Our results suggest that one should investigate the coherence phenomena of BJJ in proper condition such as EC/EJ˜1.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. The Complex Energy Landscape of the Protein IscU.

    PubMed

    Bothe, Jameson R; Tonelli, Marco; Ali, Ibrahim K; Dai, Ziqi; Frederick, Ronnie O; Westler, William M; Markley, John L

    2015-09-01

    IscU, the scaffold protein for iron-sulfur (Fe-S) cluster biosynthesis in Escherichia coli, traverses a complex energy landscape during Fe-S cluster synthesis and transfer. Our previous studies showed that IscU populates two interconverting conformational states: one structured (S) and one largely disordered (D). Both states appear to be functionally important because proteins involved in the assembly or transfer of Fe-S clusters have been shown to interact preferentially with either the S or D state of IscU. To characterize the complex structure-energy landscape of IscU, we employed NMR spectroscopy, small-angle x-ray scattering (SAXS), and differential scanning calorimetry. Results obtained for IscU at pH 8.0 show that its S state is maximally populated at 25°C and that heating or cooling converts the protein toward the D state. Results from NMR and DSC indicate that both the heat- and cold-induced S→D transitions are cooperative and two-state. Low-resolution structural information from NMR and SAXS suggests that the structures of the cold-induced and heat-induced D states are similar. Both states exhibit similar (1)H-(15)N HSQC spectra and the same pattern of peptidyl-prolyl peptide bond configurations by NMR, and both appear to be similarly expanded compared with the S state based on analysis of SAXS data. Whereas in other proteins the cold-denatured states have been found to be slightly more compact than the heat-denatured states, these two states occupy similar volumes in IscU.

  19. Mapping the Topography of a Protein Energy Landscape.

    PubMed

    Hutton, Richard D; Wilkinson, James; Faccin, Mauro; Sivertsson, Elin M; Pelizzola, Alessandro; Lowe, Alan R; Bruscolini, Pierpaolo; Itzhaki, Laura S

    2015-11-25

    Protein energy landscapes are highly complex, yet the vast majority of states within them tend to be invisible to experimentalists. Here, using site-directed mutagenesis and exploiting the simplicity of tandem-repeat protein structures, we delineate a network of these states and the routes between them. We show that our target, gankyrin, a 226-residue 7-ankyrin-repeat protein, can access two alternative (un)folding pathways. We resolve intermediates as well as transition states, constituting a comprehensive series of snapshots that map early and late stages of the two pathways and show both to be polarized such that the repeat array progressively unravels from one end of the molecule or the other. Strikingly, we find that the protein folds via one pathway but unfolds via a different one. The origins of this behavior can be rationalized using the numerical results of a simple statistical mechanics model that allows us to visualize the equilibrium behavior as well as single-molecule folding/unfolding trajectories, thereby filling in the gaps that are not accessible to direct experimental observation. Our study highlights the complexity of repeat-protein folding arising from their symmetrical structures; at the same time, however, this structural simplicity enables us to dissect the complexity and thereby map the precise topography of the energy landscape in full breadth and remarkable detail. That we can recapitulate the key features of the folding mechanism by computational analysis of the native structure alone will help toward the ultimate goal of designed amino-acid sequences with made-to-measure folding mechanisms-the Holy Grail of protein folding. PMID:26561984

  20. The Complex Energy Landscape of the Protein IscU

    PubMed Central

    Bothe, Jameson R.; Tonelli, Marco; Ali, Ibrahim K.; Dai, Ziqi; Frederick, Ronnie O.; Westler, William M.; Markley, John L.

    2015-01-01

    IscU, the scaffold protein for iron-sulfur (Fe-S) cluster biosynthesis in Escherichia coli, traverses a complex energy landscape during Fe-S cluster synthesis and transfer. Our previous studies showed that IscU populates two interconverting conformational states: one structured (S) and one largely disordered (D). Both states appear to be functionally important because proteins involved in the assembly or transfer of Fe-S clusters have been shown to interact preferentially with either the S or D state of IscU. To characterize the complex structure-energy landscape of IscU, we employed NMR spectroscopy, small-angle x-ray scattering (SAXS), and differential scanning calorimetry. Results obtained for IscU at pH 8.0 show that its S state is maximally populated at 25°C and that heating or cooling converts the protein toward the D state. Results from NMR and DSC indicate that both the heat- and cold-induced S→D transitions are cooperative and two-state. Low-resolution structural information from NMR and SAXS suggests that the structures of the cold-induced and heat-induced D states are similar. Both states exhibit similar 1H-15N HSQC spectra and the same pattern of peptidyl-prolyl peptide bond configurations by NMR, and both appear to be similarly expanded compared with the S state based on analysis of SAXS data. Whereas in other proteins the cold-denatured states have been found to be slightly more compact than the heat-denatured states, these two states occupy similar volumes in IscU. PMID:26331259

  1. Characterization of the potential energy landscape of an antiplasticized polymer

    NASA Astrophysics Data System (ADS)

    Riggleman, Robert A.; Douglas, Jack F.; de Pablo, Juan J.

    2007-07-01

    The nature of the individual transitions on the potential energy landscape (PEL) associated with particle motion are directly examined for model fragile glass-forming polymer melts, and the results are compared to those of an antiplasticized polymer system. In previous work, we established that the addition of antiplasticizer reduces the fragility of glass formation so that the antiplasticized material is a stronger glass former. In the present work, we find that the antiplasticizing molecules reduce the energy barriers for relaxation compared to the pure polymer, implying that the antiplasticized system has smaller barriers to overcome in order to explore its configuration space. We examine the cooperativity of segmental motion in these bulk fluids and find that more extensive stringlike collective motion enables the system to overcome larger potential energy barriers, in qualitative agreement with both the Stillinger-Weber and Adam-Gibbs views of glass formation. Notably, the stringlike collective motion identified by our PEL analysis corresponds to incremental displacements that occur within larger-scale stringlike particle displacement processes associated with PEL metabasin transitions that mediate structural relaxation. These “substrings” nonetheless seem to exhibit changes in relative size with antiplasticization similar to those observed in “superstrings” that arise at elevated temperatures. We also study the effects of confinement on the energy barriers in each system. Film confinement makes the energy barriers substantially smaller in the pure polymer, while it has little effect on the energy barriers in the antiplasticized system. This observation is qualitatively consistent with our previous studies of stringlike motion in these fluids at higher temperatures and with recent experimental measurements by Torkelson and co-workers.

  2. Relaxation of backbone bond geometry improves protein energy landscape modeling.

    PubMed

    Conway, Patrick; Tyka, Michael D; DiMaio, Frank; Konerding, David E; Baker, David

    2014-01-01

    A key issue in macromolecular structure modeling is the granularity of the molecular representation. A fine-grained representation can approximate the actual structure more accurately, but may require many more degrees of freedom than a coarse-grained representation and hence make conformational search more challenging. We investigate this tradeoff between the accuracy and the size of protein conformational search space for two frequently used representations: one with fixed bond angles and lengths and one that has full flexibility. We performed large-scale explorations of the energy landscapes of 82 protein domains under each model, and find that the introduction of bond angle flexibility significantly increases the average energy gap between native and non-native structures. We also find that incorporating bonded geometry flexibility improves low resolution X-ray crystallographic refinement. These results suggest that backbone bond angle relaxation makes an important contribution to native structure energetics, that current energy functions are sufficiently accurate to capture the energetic gain associated with subtle deformations from chain ideality, and more speculatively, that backbone geometry distortions occur late in protein folding to optimize packing in the native state.

  3. 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).

  4. Reconstructing folding energy landscapes from splitting probability analysis of single-molecule trajectories

    PubMed Central

    Manuel, Ajay P.; Lambert, John; Woodside, Michael T.

    2015-01-01

    Structural self-assembly in biopolymers, such as proteins and nucleic acids, involves a diffusive search for the minimum-energy state in a conformational free-energy landscape. The likelihood of folding proceeding to completion, as a function of the reaction coordinate used to monitor the transition, can be described by the splitting probability, pfold(x). Pfold encodes information about the underlying energy landscape, and it is often used to judge the quality of the reaction coordinate. Here, we show how pfold can be used to reconstruct energy landscapes from single-molecule folding trajectories, using force spectroscopy measurements of single DNA hairpins. Calculating pfold(x) directly from trajectories of the molecular extension measured for hairpins fluctuating in equilibrium between folded and unfolded states, we inverted the result expected from diffusion over a 1D energy landscape to obtain the implied landscape profile. The results agreed well with the landscapes reconstructed by established methods, but, remarkably, without the need to deconvolve instrumental effects on the landscape, such as tether compliance. The same approach was also applied to hairpins with multistate folding pathways. The relative insensitivity of the method to the instrumental compliance was confirmed by simulations of folding measured with different tether stiffnesses. This work confirms that the molecular extension is a good reaction coordinate for these measurements, and validates a powerful yet simple method for reconstructing landscapes from single-molecule trajectories. PMID:26039984

  5. 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…

  6. Saddles on the potential energy landscape of a Lennard-Jones liquid

    NASA Astrophysics Data System (ADS)

    Broderix, Kurt; Bhattacharya, Kamal K.; Cavagna, Andrea; Zippelius, Annette; Giardina, Irene

    2001-02-01

    By means of molecular dynamics simulations, we study the stationary points of the potential energy in a Lennard-Jones liquid, giving a purely geometric characterization of the energy landscape of the system. We find a linear relation between the degree of instability of the stationary points and their potential energy, and we locate the energy where the instability vanishes. This threshold energy marks the border between saddle-dominated and minima-dominated regions of the energy landscape. The temperature where the potential energy of the Stillinger-Weber minima becomes equal to the threshold energy turns out to be very close to the mode-coupling transition temperature Tc.

  7. Formation energies of intrinsic point defects in monoclinic VO2 studied by first-principles calculations

    NASA Astrophysics Data System (ADS)

    Cui, Yuanyuan; Liu, Bin; Chen, Lanli; Luo, Hongjie; Gao, Yanfeng

    2016-10-01

    VO2 is an attractive candidate for intelligent windows and thermal sensors. There are challenges for developing VO2-based devices, since the properties of monoclinic VO2 are very sensitive to its intrinsic point defects. In this work, the formation energies of the intrinsic point defects in monoclinic VO2 were studied through the first-principles calculations. Vacancies, interstitials, as well as antisites at various charge states were taken into consideration, and the finite-size supercell correction scheme was adopted as the charge correction scheme. Our calculation results show that the oxygen interstitial and oxygen vacancy are the most abundant intrinsic defects in the oxygen rich and oxygen deficient condition, respectively, indicating a consistency with the experimental results. The calculation results suggest that the oxygen interstitial or oxygen vacancy is correlated with the charge localization, which can introduce holes or electrons as free carriers and subsequently narrow the band gap of monoclinic VO2. These calculations and interpretations concerning the intrinsic point defects would be helpful for developing VO2-based devices through defect modifications.

  8. Construction of energy landscapes can clarify the movement and distribution of foraging animals

    PubMed Central

    Wilson, Rory P.; Quintana, Flavio; Hobson, Victoria J.

    2012-01-01

    Variation in the physical characteristics of the environment should impact the movement energetics of animals. Although cognizance of this may help interpret movement ecology, determination of the landscape-dependent energy expenditure of wild animals is problematic. We used accelerometers in animal-attached tags to derive energy expenditure in 54 free-living imperial cormorants Phalacrocorax atriceps and construct an energy landscape of the area around a breeding colony. Examination of the space use of a further 74 birds over 4 years showed that foraging areas selected varied considerably in distance from the colony and water depth, but were characterized by minimal power requirements compared with other areas in the available landscape. This accords with classic optimal foraging concepts, which state that animals should maximize net energy gain by minimizing costs where possible and show how deriving energy landscapes can help understand how and why animals distribute themselves in space. PMID:21900327

  9. Construction of energy landscapes can clarify the movement and distribution of foraging animals.

    PubMed

    Wilson, Rory P; Quintana, Flavio; Hobson, Victoria J

    2012-03-01

    Variation in the physical characteristics of the environment should impact the movement energetics of animals. Although cognizance of this may help interpret movement ecology, determination of the landscape-dependent energy expenditure of wild animals is problematic. We used accelerometers in animal-attached tags to derive energy expenditure in 54 free-living imperial cormorants Phalacrocorax atriceps and construct an energy landscape of the area around a breeding colony. Examination of the space use of a further 74 birds over 4 years showed that foraging areas selected varied considerably in distance from the colony and water depth, but were characterized by minimal power requirements compared with other areas in the available landscape. This accords with classic optimal foraging concepts, which state that animals should maximize net energy gain by minimizing costs where possible and show how deriving energy landscapes can help understand how and why animals distribute themselves in space. PMID:21900327

  10. The Energy Balance of the Winter Boreal Landscape.

    NASA Astrophysics Data System (ADS)

    Harding, R. J.; Pomeroy, J. W.

    1996-11-01

    During the winter of 1993/94 a study to quantify the winter energy balance of the main cover types of the boreal landscape took place. The study was based on the southern edge of boreal forest in Canada. Measurements were made over a mature jack pine stand and a frozen lake. Shortwave albedos of 12% to 14% over the jack pine and 20% to 88% on the frozen lake (both depending on snow cover) were measured. There were correspondingly large contrasts in the total radiation inputs and the turbulent heat fluxes. The mean net all-wave radiation input was large and positive into the forest and negative over the lake. The sensible heat fluxes were of the same sign as the radiative inputs with positive values over the forest peaking at +200 W m2 and failing to 100 W m2 over the lake. The evaporation from the forest depended on whether the there was snow on the canopy. When the canopy was snow-free, the evaporation was low, about 50% of net radiation but, when there was snow on the canopy, the evaporation was large, 4 mm over a 36-hour period. The results of these experiments are being used to design much-improved descriptions of boreal forest within the next generation of climate, models.

  11. Elementary excitation and energy landscape in simple liquids

    NASA Astrophysics Data System (ADS)

    Egami, T.

    2014-06-01

    The nature of excitations in liquids has been a subject of debate for a long time. In liquids, phonons are extremely short-lived and marginalized. Instead, recent research results indicate that local topological or configurational excitations (anankeons) are the elementary excitations in high temperature metallic liquids. Local topological excitations are those which locally alter the atomic connectivity network by cutting or forming atomic bonds, and are directly tied to the atomistic origin of viscosity in the liquid. The local potential energy landscape (PEL) of anankeons represents the probability weighted projection of the global PEL to a single atom. The original PEL is an insightful concept, but is highly multi-dimensional and difficult to characterize or even to visualize. A description in terms of the local PEL for anankeons appears to offer a simpler and more effective approach toward this complex problem. At the base of these advances, is the recognition that atomic discreteness and the topology of atomic connectivity are the most crucial features of the structure in liquids, which current nonlinear continuum theories cannot fully capture. These discoveries could open the way to the explanation of various complex phenomena in liquids, such as atomic transport, fragility, and the glass transition, in terms of these excitations.

  12. Energy and diffusivity landscapes, colloidal forces and assembly

    NASA Astrophysics Data System (ADS)

    Beltran Villegas, Daniel Jose

    Understanding dynamics of concentrated colloidal systems in the presence of different interactions and external fields provides a basis to predict the temporal evolution of colloidal microstructures in diverse phenomena including suspension rheology and colloidal crystallization. However, a microscopic theory of concentrated colloidal dynamics does not yet exist that rigorously includes both statistical mechanical and fluid mechanical contributions. In this dissertation a comprehensive analysis of colloidal dynamics is implemented to accomplish two goals: 1) the analysis of microscopy experiments to determine conservative and dissipative colloidal forces and 2) the dynamic modeling of colloidal assembly. Both goals are accomplished by means of analyzing the Smoluchowski equation (SE) to describe the dynamic evolution of colloidal systems. Conservative and dissipative forces are extracted from a SE analysis of measured particle excursions normal to an underlying substrate from Total Internal Reflection Microscopy (TIRM) data. An initial test of the analysis via simulated experiments is done, followed by the measurement of depletion induced interactions and hydrodynamic contributions due to adsorbing and non-adsorbing polymer brushes. This is the first time theories regarding both conservative and dissipative forces are validated by means of a non-intrusive experimental methodology. The development of models for colloidal assembly starts with the construction of free energy landscapes (FEL), from Monte Carlo equilibrium simulations, and analyzing their features in terms of order parameters. Dynamics are characterized by order-parameter based SE models that accurately capture the dynamic evolution of initially disordered colloidal fluid configurations into colloidal crystals. After identifying appropriate order parameters to monitor colloidal crystallization, we first show that umbrella sampling methods in conjunction with Monte Carlo simulations produce the same FEL

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

    PubMed

    Zhang, Bin; Wolynes, Peter G

    2016-06-17

    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.

  14. Acousto-optically generated potential energy landscapes: potential mapping using colloids under flow.

    PubMed

    Juniper, Michael P N; Besseling, Rut; Aarts, Dirk G A L; Dullens, Roel P A

    2012-12-17

    Optical potential energy landscapes created using acousto-optical deflectors are characterized via solvent-driven colloidal particles. The full potential energy of both single optical traps and complex landscapes composed of multiple overlapping traps are determined using a simple force balance argument. The potential of a single trap is shown to be well described by a Gaussian trap with stiffness found to be consistent with those obtained by a thermal equilibrium method. We also obtain directly the depth of the well, which (as with stiffness) varies with laser power. Finally, various complex systems ranging from double-well potentials to random landscapes are generated from individually controlled optical traps. Predictions of these landscapes as a sum of single Gaussian wells are shown to be a good description of experimental results, offering the potential for fully controlled design of optical landscapes, constructed from single optical traps.

  15. 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.

  16. 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.

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

    PubMed

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

    2015-01-01

    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.

  18. 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

  19. 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.

  20. Quantifying the Energy Landscape Statistics in Proteins - a Relaxation Mode Analysis

    NASA Astrophysics Data System (ADS)

    Cai, Zhikun; Zhang, Yang

    Energy landscape, the hypersurface in the configurational space, has been a useful concept in describing complex processes that occur over a very long time scale, such as the multistep slow relaxations of supercooled liquids and folding of polypeptide chains into structured proteins. Despite extensive simulation studies, its experimental characterization still remains a challenge. To address this challenge, we developed a relaxation mode analysis (RMA) for liquids under a framework analogous to the normal mode analysis for solids. Using RMA, important statistics of the activation barriers of the energy landscape becomes accessible from experimentally measurable two-point correlation functions, e.g. using quasi-elastic and inelastic scattering experiments. We observed a prominent coarsening effect of the energy landscape. The results were further confirmed by direct sampling of the energy landscape using a metadynamics-like adaptive autonomous basin climbing computation. We first demonstrate RMA in a supercooled liquid when dynamical cooperativity emerges in the landscape-influenced regime. Then we show this framework reveals encouraging energy landscape statistics when applied to proteins.

  1. The intrinsic energy of the gating isomerization of a neuromuscular acetylcholine receptor channel.

    PubMed

    Nayak, Tapan K; Purohit, Prasad G; Auerbach, Anthony

    2012-05-01

    Nicotinic acetylcholine receptor (AChR) channels at neuromuscular synapses rarely open in the absence of agonists, but many different mutations increase the unliganded gating equilibrium constant (E0) to generate AChRs that are active constitutively. We measured E0 for two different sets of mutant combinations and by extrapolation estimated E0 for wild-type AChRs. The estimates were 7.6 and 7.8×10(-7) in adult-type mouse AChRs (-100 mV at 23°C). The values are in excellent agreement with one obtained previously by using a completely different method (6.5×10(-7), from monoliganded gating). E0 decreases with depolarization to the same extent as does the diliganded gating equilibrium constant, e-fold with ∼60 mV. We estimate that at -100 mV the intrinsic energy of the unliganded gating isomerization is +8.4 kcal/mol (35 kJ/mol), and that in the absence of a membrane potential, the intrinsic chemical energy of this global conformational change is +9.4 kcal/mol (39 kJ/mol). Na+ and K+ in the extracellular solution have no measureable effect on E0, which suggests that unliganded gating occurs with only water occupying the transmitter binding sites. The results are discussed with regard to the energy changes in receptor activation and the competitive antagonism of ions in agonist binding.

  2. 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.

  3. 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.

  4. 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.

  5. Potential energy landscape of the two-dimensional XY model: Higher-index stationary points

    NASA Astrophysics Data System (ADS)

    Mehta, D.; Hughes, C.; Kastner, M.; Wales, D. J.

    2014-06-01

    The application of numerical techniques to the study of energy landscapes of large systems relies on sufficient sampling of the stationary points. Since the number of stationary points is believed to grow exponentially with system size, we can only sample a small fraction. We investigate the interplay between this restricted sample size and the physical features of the potential energy landscape for the two-dimensional XY model in the absence of disorder with up to N = 100 spins. Using an eigenvector-following technique, we numerically compute stationary points with a given Hessian index I for all possible values of I. We investigate the number of stationary points, their energy and index distributions, and other related quantities, with particular focus on the scaling with N. The results are used to test a number of conjectures and approximate analytic results for the general properties of energy landscapes.

  6. Exploring the energy landscapes of flexible molecular loops using higher-dimensional continuation.

    PubMed

    Porta, Josep M; Jaillet, Léonard

    2013-01-30

    The conformational space of a flexible molecular loop includes the set of conformations fulfilling the geometric loop-closure constraints and its energy landscape can be seen as a scalar field defined on this implicit set. Higher-dimensional continuation tools, recently developed in dynamical systems and also applied to robotics, provide efficient algorithms to trace out implicitly defined sets. This article describes these tools and applies them to obtain full descriptions of the energy landscapes of short molecular loops that, otherwise, can only be partially explored, mainly via sampling. Moreover, to deal with larger loops, this article exploits the higher-dimensional continuation tools to find local minima and minimum energy transition paths between them, without deviating from the loop-closure constraints. The proposed techniques are applied to previously studied molecules revealing the intricate structure of their energy landscapes.

  7. Exploring the energy landscapes of flexible molecular loops using higher-dimensional continuation.

    PubMed

    Porta, Josep M; Jaillet, Léonard

    2013-01-30

    The conformational space of a flexible molecular loop includes the set of conformations fulfilling the geometric loop-closure constraints and its energy landscape can be seen as a scalar field defined on this implicit set. Higher-dimensional continuation tools, recently developed in dynamical systems and also applied to robotics, provide efficient algorithms to trace out implicitly defined sets. This article describes these tools and applies them to obtain full descriptions of the energy landscapes of short molecular loops that, otherwise, can only be partially explored, mainly via sampling. Moreover, to deal with larger loops, this article exploits the higher-dimensional continuation tools to find local minima and minimum energy transition paths between them, without deviating from the loop-closure constraints. The proposed techniques are applied to previously studied molecules revealing the intricate structure of their energy landscapes. PMID:23015474

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

    PubMed

    Dee, Derek R; Woodside, Michael T

    2016-05-01

    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. PMID:27191683

  9. 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.

  10. Parallel pathways and free-energy landscapes for enzymatic hydride transfer probed by hydrostatic pressure.

    PubMed

    Pudney, Christopher R; McGrory, Tom; Lafite, Pierre; Pang, Jiayun; Hay, Sam; Leys, David; Sutcliffe, Michael J; Scrutton, Nigel S

    2009-05-25

    Mutation of an active-site residue in morphinone reductase leads to a conformationally rich landscape that enhances the rate of hydride transfer from NADH to FMN at standard pressure (1 bar). Increasing the pressure causes interconversion between different conformational substates in the mutant enzyme. While high pressure reduces the donor-acceptor distance in the wild-type enzyme, increased conformational freedom "dampens" its effect in the mutant.We show that hydride transfer from NADH to FMN catalysed by the N189A mutant of morphinone reductase occurs along parallel "chemical" pathways in a conformationally rich free-energy landscape. We have developed experimental kinetic and spectroscopic tools by using hydrostatic pressure to explore this free-energy landscape. The crystal structure of the N189A mutant enzyme in complex with the unreactive coenzyme analogue NADH(4) indicates that the nicotinamide moiety of the analogue is conformationally less restrained than the corresponding structure of the wild-type NADH(4) complex. This increased degree of conformational freedom in the N189A enzyme gives rise to the concept of multiple reactive configurations (MRCs), and we show that the relative population of these states across the free-energy landscape can be perturbed experimentally as a function of pressure. Specifically, the amplitudes of individual kinetic phases that were observed in stopped-flow studies of the hydride transfer reaction are sensitive to pressure; this indicates that pressure drives an altered distribution across the energy landscape. We show by absorbance spectroscopy that the loss of charge-transfer character of the enzyme-coenzyme complex is attributed to the altered population of MRCs on the landscape. The existence of a conformationally rich landscape in the N189A mutant is supported by molecular dynamics simulations at low and high pressure. The work provides firm experimental and computational support for the existence of parallel pathways

  11. 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

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

    SciTech Connect

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

    2014-07-14

    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 BaF{sub 2} (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 (V{sub X}) 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 BaF{sub 2} 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)).

  13. 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)).

  14. Potential energy landscapes for the 2D XY model: Minima, transition states, and pathways

    NASA Astrophysics Data System (ADS)

    Mehta, Dhagash; Hughes, Ciaran; Schröck, Mario; Wales, David J.

    2013-11-01

    We describe a numerical study of the potential energy landscape for the two-dimensional XY model (with no disorder), considering up to 100 spins and central processing unit and graphics processing unit implementations of local optimization, focusing on minima and saddles of index one (transition states). We examine both periodic and anti-periodic boundary conditions, and show that the number of stationary points located increases exponentially with increasing lattice size. The corresponding disconnectivity graphs exhibit funneled landscapes; the global minima are readily located because they exhibit relatively large basins of attraction compared to the higher energy minima as the lattice size increases.

  15. Landau-type expansion for the energy landscape of the designed heteropolymer

    NASA Astrophysics Data System (ADS)

    Grosberg, Alexander; Pande, Vijay; Tanaka, Toyoichi

    1997-03-01

    The concept of evolutional optimization of heteropolymer sequences is used to construct the phenomenological theory describing folding/unfoolding kinetics of the polymers with designed sequences. The relevant energy landscape is described in terms of Landau expansion over the powers of the overlap parameter of the current and the native conformations. It is shown that only linear term is sequence (mutation) dependent, the rest being determined by the underlying conformational geometry. The theory os free of the assumptions of the uncorrelated energy landscape type. We demonstrate the power of the theory by comparing data to the simulations and experiments.

  16. Connecting the kinetics and energy landscape of tRNA translocation on the ribosome.

    PubMed

    Whitford, Paul C; Blanchard, Scott C; Cate, Jamie H D; Sanbonmatsu, Karissa Y

    2013-01-01

    Functional rearrangements in biomolecular assemblies result from diffusion across an underlying energy landscape. While bulk kinetic measurements rely on discrete state-like approximations to the energy landscape, single-molecule methods can project the free energy onto specific coordinates. With measures of the diffusion, one may establish a quantitative bridge between state-like kinetic measurements and the continuous energy landscape. We used an all-atom molecular dynamics simulation of the 70S ribosome (2.1 million atoms; 1.3 microseconds) to provide this bridge for specific conformational events associated with the process of tRNA translocation. Starting from a pre-translocation configuration, we identified sets of residues that collectively undergo rotary rearrangements implicated in ribosome function. Estimates of the diffusion coefficients along these collective coordinates for translocation were then used to interconvert between experimental rates and measures of the energy landscape. This analysis, in conjunction with previously reported experimental rates of translocation, provides an upper-bound estimate of the free-energy barriers associated with translocation. While this analysis was performed for a particular kinetic scheme of translocation, the quantitative framework is general and may be applied to energetic and kinetic descriptions that include any number of intermediates and transition states.

  17. Dynamics of a molecular glass former: Energy landscapes for diffusion in ortho-terphenyl

    NASA Astrophysics Data System (ADS)

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

    2016-07-01

    Relaxation times and transport processes of many glass-forming supercooled liquids exhibit a super-Arrhenius temperature dependence. We examine this phenomenon by computer simulation of the Lewis-Wahnström model for ortho-terphenyl. We propose a microscopic definition for a single-molecule cage-breaking transition and show that, when correlation behaviour is taken into account, these rearrangements are sufficient to reproduce the correct translational diffusion constants over an intermediate temperature range in the supercooled regime. We show that super-Arrhenius behaviour can be attributed to increasing negative correlation in particle movement at lower temperatures and relate this to the cage-breaking description. Finally, we sample the potential energy landscape of the model and show that it displays hierarchical ordering. Substructures in the landscape, which may correspond to metabasins, have boundaries defined by cage-breaking transitions. The cage-breaking formulation provides a direct link between the potential energy landscape and macroscopic diffusion behaviour.

  18. 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.

  19. 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

  20. 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.

  1. 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. PMID:26186565

  2. 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.

  3. 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.

  4. 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

  5. Characterizing Energy Landscapes of Peptides Using a Combination of Stochastic Algorithms.

    PubMed

    Devaurs, Didier; Molloy, Kevin; Vaisset, Marc; Shehu, Amarda; Siméon, Thierry; Cortés, Juan

    2015-07-01

    Obtaining accurate representations of energy landscapes of biomolecules such as proteins and peptides is central to the study of their physicochemical properties and biological functions. Peptides are particularly interesting, as they exploit structural flexibility to modulate their biological function. Despite their small size, peptide modeling remains challenging due to the complexity of the energy landscape of such highly-flexible dynamic systems. Currently, only stochastic sampling-based methods can efficiently explore the conformational space of a peptide. In this paper, we suggest to combine two such methods to obtain a full characterization of energy landscapes of small yet flexible peptides. First, we propose a simplified version of the classical Basin Hopping algorithm to reveal low-energy regions in the landscape, and thus to identify the corresponding meta-stable structural states of a peptide. Then, we present several variants of a robotics-inspired algorithm, the Transition-based Rapidly-exploring Random Tree, to quickly determine transition path ensembles, as well as transition probabilities between meta-stable states. We demonstrate this combined approach on met-enkephalin.

  6. 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. PMID:27288028

  7. 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

  8. 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

  9. Fluctuating systems under cyclic perturbations: Relation between energy dissipation and intrinsic relaxation processes.

    PubMed

    Camerin, Fabrizio; Frezzato, Diego

    2016-08-01

    This study focuses on fluctuating classical systems in contact with a thermal bath, and whose configurational energetics undergoes cyclic transformations due to interaction with external perturbing agents. Under the assumptions that the configurational dynamics is a stochastic Markov process in the overdamped regime and that the nonequilibrium configurational distribution remains close to the underlying equilibrium one, we derived an analytic approximation of the average dissipated energy per cycle in the asymptotic limit (i.e., after many cycles of perturbation). The energy dissipation is then readily translated into average entropy production, per cycle, in the environment. The accuracy of the approximation was tested by comparing the outcomes with the exact values obtained by stochastic simulations of a model case: a "particle on a ring" that fluctuates in a bistable potential perturbed in two different ways. As pointed out in previous studies on the stochastic resonance phenomenon, the dependence of the average dissipation on the perturbation period may unveil the inner spectrum of the system's fluctuation rates. In this respect, the analytical approximation presented here makes it possible to unveil the connection between average dissipation, intrinsic rates and modes of fluctuation of the system at the unperturbed equilibrium, and features of the perturbation itself (namely, the period of the cycle and the projections of the energy perturbation over the system's modes). The possibilities of employing the analytical results as a guide to devising and rationalizing a sort of "spectroscopic calorimetry" experiment, and of employing them in strategies aiming to optimize the system's features on the basis of a target average dissipation, are briefly discussed. PMID:27627256

  10. Fluctuating systems under cyclic perturbations: Relation between energy dissipation and intrinsic relaxation processes

    NASA Astrophysics Data System (ADS)

    Camerin, Fabrizio; Frezzato, Diego

    2016-08-01

    This study focuses on fluctuating classical systems in contact with a thermal bath, and whose configurational energetics undergoes cyclic transformations due to interaction with external perturbing agents. Under the assumptions that the configurational dynamics is a stochastic Markov process in the overdamped regime and that the nonequilibrium configurational distribution remains close to the underlying equilibrium one, we derived an analytic approximation of the average dissipated energy per cycle in the asymptotic limit (i.e., after many cycles of perturbation). The energy dissipation is then readily translated into average entropy production, per cycle, in the environment. The accuracy of the approximation was tested by comparing the outcomes with the exact values obtained by stochastic simulations of a model case: a "particle on a ring" that fluctuates in a bistable potential perturbed in two different ways. As pointed out in previous studies on the stochastic resonance phenomenon, the dependence of the average dissipation on the perturbation period may unveil the inner spectrum of the system's fluctuation rates. In this respect, the analytical approximation presented here makes it possible to unveil the connection between average dissipation, intrinsic rates and modes of fluctuation of the system at the unperturbed equilibrium, and features of the perturbation itself (namely, the period of the cycle and the projections of the energy perturbation over the system's modes). The possibilities of employing the analytical results as a guide to devising and rationalizing a sort of "spectroscopic calorimetry" experiment, and of employing them in strategies aiming to optimize the system's features on the basis of a target average dissipation, are briefly discussed.

  11. Statistical mechanical modeling of RNA folding: from free energy landscape to tertiary structural prediction

    PubMed Central

    CAO, Song; CHEN, Shi-Jie

    2016-01-01

    In spite of the success of computational methods for predicting RNA secondary structure, the problem of predicting RNA tertiary structure folding remains. Low-resolution structural models show promise as they allow for rigorous statistical mechanical computation for the conformational entropies, free energies, and the coarse-grained structures of tertiary folds. Molecular dynamics refinement of coarse-grained structures leads to all-atom 3D structures. Modeling based on statistical mechanics principles also has the unique advantage of predicting the full free energy landscape, including local minima and the global free energy minimum. The energy landscapes combined with the 3D structures form the basis for quantitative predictions of RNA functions. In this chapter, we present an overview of statistical mechanical models for RNA folding and then focus on a recently developed RNA statistical mechanical model -- the Vfold model. The main emphasis is placed on the physics underpinning the models, the computational strategies, and the connections to RNA biology. PMID:27293312

  12. 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.

  13. 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.

  14. The histone H3 N-terminal tail: a computational analysis of the free energy landscape and kinetics.

    PubMed

    Zheng, Yuqing; Cui, Qiang

    2015-05-28

    Histone tails are the short peptide protrusions outside of the nucleosome core particle and they play a critical role in regulating chromatin dynamics and gene activity. A histone H3 N-terminal tail, like other histone tails, can be covalently modified on different residues to activate or repress gene expression. Previous studies have indicated that, despite its intrinsically disordered nature, the histone H3 N-terminal tail has regions of notable secondary structural propensities. To further understand the structure-dynamics-function relationship in this system, we have carried out 75.6 μs long implicit solvent simulations and 29.3 μs long explicit solvent simulations. The extensive samplings allow us to better characterize not only the underlying free energy landscape but also kinetic properties through Markov state models (MSM). Dihedral principal component analysis (dPCA) and locally scaled diffusion map (LSDMap) analysis yield consistent results that indicate an overall flat free energy surface with several shallow basins that correspond to conformations with a high α-helical propensity in two regions of the peptide. Kinetic information extracted from Markov state models reveals rapid transitions between different metastable states with mean first passage times spanning from several hundreds of nanoseconds to hundreds of microseconds. These findings shed light on how the dynamical nature of the histone H3 N-terminal tail is related to its function. The complementary nature of dPCA, LSDMap and MSM for the analysis of biomolecules is also discussed.

  15. Ensemble-based characterization of unbound and bound states on protein energy landscape

    PubMed Central

    Ruvinsky, Anatoly M; Kirys, Tatsiana; Tuzikov, Alexander V; Vakser, Ilya A

    2013-01-01

    Physicochemical description of numerous cell processes is fundamentally based on the energy landscapes of protein molecules involved. Although the whole energy landscape is difficult to reconstruct, increased attention to particular targets has provided enough structures for mapping functionally important subspaces associated with the unbound and bound protein structures. The subspace mapping produces a discrete representation of the landscape, further called energy spectrum. We compiled and characterized ensembles of bound and unbound conformations of six small proteins and explored their spectra in implicit solvent. First, the analysis of the unbound-to-bound changes points to conformational selection as the binding mechanism for four proteins. Second, results show that bound and unbound spectra often significantly overlap. Moreover, the larger the overlap the smaller the root mean square deviation (RMSD) between the bound and unbound conformational ensembles. Third, the center of the unbound spectrum has a higher energy than the center of the corresponding bound spectrum of the dimeric and multimeric states for most of the proteins. This suggests that the unbound states often have larger entropy than the bound states. Fourth, the exhaustively long minimization, making small intrarotamer adjustments (all-atom RMSD ≤ 0.7 Å), dramatically reduces the distance between the centers of the bound and unbound spectra as well as the spectra extent. It condenses unbound and bound energy levels into a thin layer at the bottom of the energy landscape with the energy spacing that varies between 0.8–4.6 and 3.5–10.5 kcal/mol for the unbound and bound states correspondingly. Finally, the analysis of protein energy fluctuations showed that protein vibrations itself can excite the interstate transitions, including the unbound-to-bound ones. PMID:23526684

  16. Towards the free energy landscape for catalysis in mammalian nitric oxide synthases.

    PubMed

    Leferink, Nicole G H; Hay, Sam; Rigby, Stephen E J; Scrutton, Nigel S

    2015-08-01

    The general requirement for conformational sampling in biological electron transfer reactions catalysed by multi-domain redox systems has been emphasized in recent years. Crucially, we lack insight into the extent of the conformational space explored and the nature of the energy landscapes associated with these reactions. The nitric oxide synthases (NOS) produce the signalling molecule NO through a series of complex electron transfer reactions. There is accumulating evidence that protein domain dynamics and calmodulin binding are implicated in regulating electron flow from NADPH, through the FAD and FMN cofactors, to the haem oxygenase domain, where NO is generated. Simple models based on static crystal structures of the isolated reductase domain have suggested a role for large-scale motions of the FMN-binding domain in shuttling electrons from the reductase domain to the oxygenase domain. However, detailed insight into the higher-order domain architecture and dynamic structural transitions in NOS enzymes during enzyme turnover is lacking. In this review, we discuss the recent advances made towards mapping the catalytic free energy landscapes of NOS enzymes through integration of both structural techniques (e.g. cryo-electron microscopy) and biophysical techniques (e.g. pulsed-electron paramagnetic resonance). The general picture that emerges from these experiments is that NOS enzymes exist in an equilibrium of conformations, comprising a 'rugged' or 'frustrated' energy landscape, with a key regulatory role for calmodulin in driving vectorial electron transfer by altering the conformational equilibrium. A detailed understanding of these landscapes may provide new opportunities for discovery of isoform-specific inhibitors that bind at the dynamic interfaces of these multi-dimensional energy landscapes.

  17. 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.

  18. 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.

  19. Minimal cooling speed for glass transition in a simple solvable energy landscape model

    NASA Astrophysics Data System (ADS)

    Toledo-Marín, J. Quetzalcóatl; Castillo, Isaac Pérez; Naumis, Gerardo G.

    2016-06-01

    The minimal cooling speed required to form a glass is obtained for a simple solvable energy landscape model. The model, made from a two-level system modified to include the topology of the energy landscape, is able to capture either a glass transition or a crystallization depending on the cooling rate. In this setup, the minimal cooling speed to achieve glass formation is then found to be related with the crystallization relaxation time, energy barrier and with the thermal history. In particular, we obtain that the thermal history encodes small fluctuations around the equilibrium population which are exponentially amplified near the glass transition, which mathematically corresponds to the boundary layer of the master equation. The change in the glass transition temperature is also found as a function of the cooling rate. Finally, to verify our analytical results, a kinetic Monte Carlo simulation was implemented.

  20. Statistical mechanics of a correlated energy landscape model for protein folding funnels

    NASA Astrophysics Data System (ADS)

    Plotkin, Steven S.; Wang, Jin; Wolynes, Peter G.

    1997-02-01

    In heteropolymers, energetic correlations exist due to polymeric constraints and the locality of interactions. Pair correlations in conjunction with the a priori specification of the existence of a particularly low energy state provide a method of introducing the aspect of minimal frustration to the energy landscapes of random heteropolymers. The resulting funneled landscape exhibits both a phase transition from a molten globule to a folded state, and the heteropolymeric glass transition in the globular state. We model the folding transition in the self-averaging regime, which together with a simple theory of collapse allows us to depict folding as a double-well free energy surface in terms of suitable reaction coordinates. Observed trends in barrier positions and heights with protein sequence length and thermodynamic conditions are discussed within the context of the model. We also discuss the new physics which arises from the introduction of explicitly cooperative many-body interactions, as might arise from sidechain packing and nonadditive hydrophobic forces.

  1. 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.

  2. 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.

  3. 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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26130159

  5. Graph-theoretical identification of dissociation pathways on free energy landscapes of biomolecular interaction.

    PubMed

    Wang, Ling; Stumm, Boris; Helms, Volkhard

    2010-03-01

    Biomolecular association and dissociation reactions take place on complicated interaction free energy landscapes that are still very hard to characterize computationally. For large enough distances, though, it often suffices to consider the six relative translational and rotational degrees of freedom of the two particles treated as rigid bodies. Here, we computed the six-dimensional free energy surface of a dimer of water-soluble alpha-helices by scanning these six degrees of freedom in about one million grid points. In each point, the relative free energy difference was computed as the sum of the polar and nonpolar solvation free energies of the helix dimer and of the intermolecular coulombic interaction energy. The Dijkstra graph algorithm was then applied to search for the lowest cost dissociation pathways based on a weighted, directed graph, where the vertices represent the grid points, the edges connect the grid points and their neighbors, and the weights are the reaction costs between adjacent pairs of grid points. As an example, the configuration of the bound state was chosen as the source node, and the eight corners of the translational cube were chosen as the destination nodes. With the strong electrostatic interaction of the two helices giving rise to a clearly funnel-shaped energy landscape, the eight lowest-energy cost pathways coming from different orientations converge into a well-defined pathway for association. We believe that the methodology presented here will prove useful for identifying low-energy association and dissociation pathways in future studies of complicated free energy landscapes for biomolecular interaction. PMID:19603501

  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. 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.

  8. Energy landscapes of ion clusters in isotropic quadrupolar and octupolar traps

    NASA Astrophysics Data System (ADS)

    Calvo, F.; Yurtsever, E.; Wales, D. J.

    2012-01-01

    The energy landscapes of ion clouds confined in isotropic quadrupolar and octupolar traps are characterized for several representative cluster sizes. All clusters exhibit stable multishell structures that belong to separate funnels. Quadrupolar confinement leads to more homogeneous clusters and denser distributions of isomers than octupolar confinement. Statistical analysis of the transition states indicates that the barriers associated with intrashell motion are lower but more asymmetric and more cooperative compared to intershell motion. The relaxation between low-energy funnels with different arrangements of shells mostly exhibits Arrhenius kinetics, with a weak variation of the activation energy at higher temperatures.

  9. Energy landscapes of ion clusters in isotropic quadrupolar and octupolar traps.

    PubMed

    Calvo, F; Yurtsever, E; Wales, D J

    2012-01-14

    The energy landscapes of ion clouds confined in isotropic quadrupolar and octupolar traps are characterized for several representative cluster sizes. All clusters exhibit stable multishell structures that belong to separate funnels. Quadrupolar confinement leads to more homogeneous clusters and denser distributions of isomers than octupolar confinement. Statistical analysis of the transition states indicates that the barriers associated with intrashell motion are lower but more asymmetric and more cooperative compared to intershell motion. The relaxation between low-energy funnels with different arrangements of shells mostly exhibits Arrhenius kinetics, with a weak variation of the activation energy at higher temperatures.

  10. 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

  11. 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. PMID:27003702

  12. Free energy landscape of receptor-mediated cell adhesion

    NASA Astrophysics Data System (ADS)

    Yang, Tianyi; Zaman, Muhammad H.

    2007-01-01

    Receptor-mediated cell adhesion plays a critical role in cell migration, proliferation, signaling, and survival. A number of diseases, including cancer, show a strong correlation between integrin activation and metastasis. A better understanding of cell adhesion is highly desirable for not only therapeutic but also a number of tissue engineering applications. While a number of computational models and experimental studies have addressed the issue of cell adhesion to surfaces, no model or theory has adequately addressed cell adhesion at the molecular level. In this paper, the authors present a thermodynamic model that addresses receptor-mediated cell adhesion at the molecular level. By incorporating the entropic, conformational, solvation, and long- and short-range interactive components of receptors and the extracellular matrix molecules, they are able to predict adhesive free energy as a function of a number of key variables such as surface coverage, interaction distance, molecule size, and solvent conditions. Their method allows them to compute the free energy of adhesion in a multicomponent system where they can simultaneously study adhesion receptors and ligands of different sizes, chemical identities, and conformational properties. The authors' results not only provide a fundamental understanding of adhesion at the molecular level but also suggest possible strategies for designing novel biomaterials.

  13. 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

  14. 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

  15. Noise-induced transitions in rugged energy landscapes

    NASA Astrophysics Data System (ADS)

    Duncan, A. B.; Kalliadasis, S.; Pavliotis, G. A.; Pradas, M.

    2016-09-01

    We consider the problem of an overdamped Brownian particle moving in multiscale potential with N +1 characteristic length scales: the macroscale and N separated microscales. We show that the coarse-grained dynamics is given by an overdamped Langevin equation with respect to the free energy and with a space-dependent diffusion tensor, the calculation of which requires the solution of N fully coupled Poisson equations. We study in detail the structure of the bifurcation diagram for one-dimensional problems, and we show that the multiscale structure in the potential leads to hysteresis effects and to noise-induced transitions. Furthermore, we obtain an explicit formula for the effective diffusion coefficient for a self-similar separable potential, and we investigate the limit of infinitely many small scales.

  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. 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

  18. Free-energy landscape of mechanically unfolded model proteins: Extended Jarzinsky versus inherent structure reconstruction

    NASA Astrophysics Data System (ADS)

    Luccioli, Stefano; Imparato, Alberto; Torcini, Alessandro

    2008-09-01

    The equilibrium free-energy landscape of off-lattice model heteropolymers as a function of an internal coordinate, namely the end-to-end distance, is reconstructed from out-of-equilibrium steered molecular dynamics data. This task is accomplished via two independent methods: By employing an extended version of the Jarzynski equality and the inherent structure formalism. A comparison of the free energies estimated with these two schemes with equilibrium results obtained via the umbrella sampling technique reveals a good quantitative agreement among all the approaches in a range of temperatures around the “folding transition” for the two examined sequences. In particular, for the sequence with good foldability properties, the mechanically induced structural transitions can be related to thermodynamical aspects of folding. Moreover, for the same sequence the knowledge of the landscape profile allows for a good estimation of the lifetimes of the native configuration for temperatures ranging from the folding to the collapse temperature. For the random sequence, mechanical and thermal unfolding appear to follow different paths along the landscape.

  19. 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.

  20. 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.

  1. Free-energy landscapes of granular clusters grown by magnetic interaction.

    PubMed

    González-Gutiérrez, Jorge; Carrillo-Estrada, J L; Carvente, O; Ruiz-Suárez, J C

    2014-05-01

    We experimentally study the aggregation of small clusters made of non-Brownian dipolar beads in a vibro-fluidized system. The particles are paramagnetic spheres that add around a fixed magnetic seed inside a granular gas of glass beads. We observe that under appropriate physical conditions symmetric and asymmetric cluster configurations are created and, as the number of particles increases, the aggregation time obeys a power law. We use an ensemble statistics to evaluate the free-energies and entropies landscapes of the granular clusters. The correspondence between such landscapes shows that, even if the system is of macroscopic scale and not in strict equilibrium, our approach to understand the relationship between the cluster structures and the interactions that create them is reliable.

  2. 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

  3. 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. PMID:25575309

  4. 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

  5. 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.

  6. Picosecond fluctuating protein energy landscape mapped by pressure temperature molecular dynamics simulation.

    SciTech Connect

    Meinhold, Lars; Smith, Jeremy C; Kitao, Akio; Zewail, Ahmed H.

    2007-10-01

    Microscopic statistical pressure fluctuations can, in principle, lead to corresponding fluctuations in the shape of a protein energy landscape. To examine this, nanosecond molecular dynamics simulations of lysozyme are performed covering a range of temperatures and pressures. The well known dynamical transition with temperature is found to be pressure-independent, indicating that the effective energy barriers separating conformational substates are not significantly influenced by pressure. In contrast, vibrations within substates stiffen with pressure, due to increased curvature of the local harmonic potential in which the atoms vibrate. The application of pressure is also shown to selectively increase the damping of the anharmonic, low-frequency collective modes in the protein, leaving the more local modes relatively unaffected. The critical damping frequency, i.e., the frequency at which energy is most efficiently dissipated, increases linearly with pressure. The results suggest that an invariant description of protein energy landscapes should be subsumed by a fluctuating picture and that this may have repercussions in, for example, mechanisms of energy dissipation accompanying functional, structural, and chemical relaxation.

  7. Picosecond Fluctuating Protein Energy Landscape Mapped by Pressure-Temperature Molecular Dynamics Simulation

    SciTech Connect

    Meinhold, Lars; Smith, Jeremy C; Kitao, Akio; Zewail, Ahmed H.

    2007-08-01

    Microscopic statistical pressure fluctuations can, in principle, lead to corresponding fluctuations in the shape of a protein energy landscape. To examine this, nanosecond molecular dynamics simulations of lysozyme are performed covering a range of temperatures and pressures. The well known dynamical transition with temperature is found to be pressure-independent, indicating that the effective energy barriers separating conformational substates are not significantly influenced by pressure. In contrast, vibrations within substates stiffen with pressure, due to increased curvature of the local harmonic potential in which the atoms vibrate. The application of pressure is also shown to selectively increase the damping of the anharmonic, low-frequency collective modes in the protein, leaving the more local modes relatively unaffected. The critical damping frequency, i.e., the frequency at which energy is most efficiently dissipated, increases linearly with pressure. The results suggest that an invariant description of protein energy landscapes should be subsumed by a fluctuating picture and that this may have repercussions in, for example, mechanisms of energy dissipation accompanying functional, structural, and chemical relaxation.

  8. Free energy landscapes of electron transfer system in dipolar environment below and above the rotational freezing temperature

    SciTech Connect

    Suzuki, Yohichi; Tanimura, Yoshitaka

    2007-02-07

    Electron transfer reaction in a polar solvent is modeled by a solute dipole surrounded by dipolar molecules with simple rotational dynamics posted on the three-dimensional distorted lattice sites. The interaction energy between the solute and solvent dipoles as a reaction coordinate is adopted and free energy landscapes are calculated by generating all possible states for a 26 dipolar system and by employing Wang-Landau sampling algorithm for a 92 dipolar system. For temperatures higher than the energy scale of dipole-dipole interactions, the free energy landscapes for the small reaction coordinate region have quadratic shape as predicted by Marcus [Rev. Mod. Phys. 65, 599 (1993)] whereas for the large reaction coordinate region, the landscapes exhibit a nonquadratic shape. When the temperature drops, small notched structures appear on the free energy profiles because of the frustrated interactions among dipoles. The formation of notched structure is analyzed with statistical approach and it is shown that the amplitude of notched structure depend upon the segment size of the reaction coordinate and is characterized by the interaction energy among the dipoles. Using simulated free energy landscapes, the authors calculate the reaction rates as a function of the energy gap for various temperatures. At high temperature, the reactions rates follow a bell shaped (inverted parabolic) energy gap law in the small energy gap regions, while it becomes steeper than the parabolic shape in a large energy gap regions due to the nonquadratic shape of the free energy landscape. The peak position of parabola also changes as the function of temperature. At low temperature, the profile of the reaction rates is no longer smooth because of the many local minima of the free energy landscape.

  9. 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.

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

    PubMed

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

    2016-04-01

    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.

  11. Ageing first passage time density in continuous time random walks and quenched energy landscapes

    NASA Astrophysics Data System (ADS)

    Krüsemann, Henning; Godec, Aljaž; Metzler, Ralf

    2015-07-01

    We study the first passage dynamics of an ageing stochastic process in the continuous time random walk (CTRW) framework. In such CTRW processes the test particle performs a random walk, in which successive steps are separated by random waiting times distributed in terms of the waiting time probability density function \\psi (t)≃ {t}-1-α (0≤slant α ≤slant 2). An ageing stochastic process is defined by the explicit dependence of its dynamic quantities on the ageing time ta, the time elapsed between its preparation and the start of the observation. Subdiffusive ageing CTRWs with 0\\lt α \\lt 1 describe systems such as charge carriers in amorphous semiconducters, tracer dispersion in geological and biological systems, or the dynamics of blinking quantum dots. We derive the exact forms of the first passage time density for an ageing subdiffusive CTRW in the semi-infinite, confined, and biased case, finding different scaling regimes for weakly, intermediately, and strongly aged systems: these regimes, with different scaling laws, are also found when the scaling exponent is in the range 1\\lt α \\lt 2, for sufficiently long ta. We compare our results with the ageing motion of a test particle in a quenched energy landscape. We test our theoretical results in the quenched landscape against simulations: only when the bias is strong enough, the correlations from returning to previously visited sites become insignificant and the results approach the ageing CTRW results. With small bias or without bias, the ageing effects disappear and a change in the exponent compared to the case of a completely annealed landscape can be found, reflecting the build-up of correlations in the quenched landscape.

  12. 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.

  13. Electrostatics, structure prediction, and the energy landscapes for protein folding and binding.

    PubMed

    Tsai, Min-Yeh; Zheng, Weihua; Balamurugan, D; Schafer, Nicholas P; Kim, Bobby L; Cheung, Margaret S; Wolynes, Peter G

    2016-01-01

    While being long in range and therefore weakly specific, electrostatic interactions are able to modulate the stability and folding landscapes of some proteins. The relevance of electrostatic forces for steering the docking of proteins to each other is widely acknowledged, however, the role of electrostatics in establishing specifically funneled landscapes and their relevance for protein structure prediction are still not clear. By introducing Debye-Hückel potentials that mimic long-range electrostatic forces into the Associative memory, Water mediated, Structure, and Energy Model (AWSEM), a transferable protein model capable of predicting tertiary structures, we assess the effects of electrostatics on the landscapes of thirteen monomeric proteins and four dimers. For the monomers, we find that adding electrostatic interactions does not improve structure prediction. Simulations of ribosomal protein S6 show, however, that folding stability depends monotonically on electrostatic strength. The trend in predicted melting temperatures of the S6 variants agrees with experimental observations. Electrostatic effects can play a range of roles in binding. The binding of the protein complex KIX-pKID is largely assisted by electrostatic interactions, which provide direct charge-charge stabilization of the native state and contribute to the funneling of the binding landscape. In contrast, for several other proteins, including the DNA-binding protein FIS, electrostatics causes frustration in the DNA-binding region, which favors its binding with DNA but not with its protein partner. This study highlights the importance of long-range electrostatics in functional responses to problems where proteins interact with their charged partners, such as DNA, RNA, as well as membranes.

  14. Monte Carlo method for computing density of states and quench probability of potential energy and enthalpy landscapes.

    PubMed

    Mauro, John C; Loucks, Roger J; Balakrishnan, Jitendra; Raghavan, Srikanth

    2007-05-21

    The thermodynamics and kinetics of a many-body system can be described in terms of a potential energy landscape in multidimensional configuration space. The partition function of such a landscape can be written in terms of a density of states, which can be computed using a variety of Monte Carlo techniques. In this paper, a new self-consistent Monte Carlo method for computing density of states is described that uses importance sampling and a multiplicative update factor to achieve rapid convergence. The technique is then applied to compute the equilibrium quench probability of the various inherent structures (minima) in the landscape. The quench probability depends on both the potential energy of the inherent structure and the volume of its corresponding basin in configuration space. Finally, the methodology is extended to the isothermal-isobaric ensemble in order to compute inherent structure quench probabilities in an enthalpy landscape.

  15. 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.

  16. 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.

  17. History Dependent Phenomena in the Transverse Ising Ferro-Glass: the Free Energy Landscape

    SciTech Connect

    KAO,YING-JER; GREST,GARY S.; LEVIN,K.; ROSENBAUM,T.F.; AEPPLI,G.

    2000-11-08

    In this paper the authors investigate the relationship between glassy and ferromagnetic phases in disordered Ising ferromagnets in the presence of transverse magnetic fields, {Lambda}. Iterative mean field simulations probe the free energy landscape and suggest the existence of a glass transition line in the {Lambda}, temperature T plane well within the ferromagnetic phase. New experimental field-cooled and zero-field-cooled data on LiHo{sub x} Y{sub 1{minus}x}F{sub 4} provide support for our theoretical picture.

  18. How Adequate are One- and Two-Dimensional Free Energy Landscapes for Protein Folding Dynamics?

    PubMed Central

    Maisuradze, Gia G.; Liwo, Adam; Scheraga, Harold A.

    2009-01-01

    The molecular dynamics trajectories of protein folding or unfolding, generated with the coarse-grained united-residue force field for the B domain of staphylococcal protein A, were analyzed by principal component analysis (PCA). The folding or unfolding process was examined by using free-energy landscapes (FELs) in PC space. By introducing a novel multidimensional FEL, it was shown that the low-dimensional FELs are not always sufficient for the description of folding or unfolding processes. Similarities between the topographies of FELs along low- and high-indexed principal components were observed. PMID:19658975

  19. 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. PMID:23140088

  20. Investigating protein conformational energy landscapes and atomic resolution dynamics from NMR dipolar couplings: a review.

    PubMed

    Salmon, Loïc; Blackledge, Martin

    2015-12-01

    Nuclear magnetic resonance spectroscopy is exquisitely sensitive to protein dynamics. In particular inter-nuclear dipolar couplings, that become measurable in solution when the protein is dissolved in a dilute liquid crystalline solution, report on all conformations sampled up to millisecond timescales. As such they provide the opportunity to describe the Boltzmann distribution present in solution at atomic resolution, and thereby to map the conformational energy landscape in unprecedented detail. The development of analytical methods and approaches based on numerical simulation and their application to numerous biologically important systems is presented. PMID:26517337

  1. Free-energy landscape of alcohol driven coacervation transition in aqueous gelatin solutions

    NASA Astrophysics Data System (ADS)

    Gupta, Amarnath; Reena, Bohidar, H. B.

    2006-08-01

    Liquid-liquid phase separation of a homogeneous polyampholyte (gelatin) solution into a dense polymer-rich coacervate and the dilute supernatant phase is discussed through free-energy landscape formalism. We have evaluated the free energy and entropy of the system as it undergoes the phenomenon of simple coacervation, driven by the addition of a nonsolvent. Electrophoretic mobility (μ) and turbidity measurements were performed on 0.01% and 0.05%(w/v) aqueous gelatin solutions that were driven towards coacervation by the addition of ethanol. The mobility of the polyampholyte molecules, which was typically μ ≈0.38±0.02μm/scm/V in water, gradually reduced for the soluble intermolecular complexes to a plateau value of μ ≈0.11±0.01μm/scm/V as the ethanol volume fraction equaled φns≈0.47±0.03, which coincided with the first appearance of coacervate droplets (coacervation transition) observed from turbidity measurements, a behavior found to be invariant of gelatin concentration. These results were used as input to the theoretical model to explicitly construct the free-energy landscape for a single gelatin chain and the global system comprising the polymer-rich coacervate and the dilute supernatant phase.

  2. Free energy landscapes and volumes of coexisting phases for a colloidal dispersion

    NASA Astrophysics Data System (ADS)

    Lang, Trinh Hoa; Wang, G. F.; Lai, S. K.

    2010-01-01

    Treating the repulsive part of a pairwise potential by the hard-sphere form and its attractive part by the effective depletion potential form, we calculate using this model potential the colloidal domains of phase separation. Differing from the usual recipe of applying the thermodynamic conditions of equal pressure and equal chemical potential where the branches of coexisting phases are the ultimate target, we employ the free energy density minimization approach [G. F. Wang and S. K. Lai, Phys. Rev. E 70, 051402 (2004)] to crosshatch the domains of equilibrium phases, which consist of the gas, liquid, and solid homogeneous phases as well as the coexistence of these phases. This numerical procedure is attractive since it yields naturally the colloidal volume of space occupied by each of the coexisting phases. In this work, we first examine the change in structures of the fluid and solid free energy density landscapes with the effective polymer concentration. We show by explicit illustration the link between the free energy density landscapes and the development of both the metastable and stable coexisting phases. Then, attention is paid to the spatial volumes predicted at the triple point. It is found here that the volumes of spaces of the three coexisting phases at the triple point vary one dimensionally, whereas for the two coexisting phases, they are uniquely determined.

  3. 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.

  4. Energy budget components, ammonia concentration and flux measurements on an agricultural landscape near Bjerringbro, Denmark

    NASA Astrophysics Data System (ADS)

    Pogány, Andrea; Weidinger, Tamás.; Bienkowski, Jerzy; Bordás, Árpád.; Bozóki, Zoltán.; Eredics, Attila; Hensen, Arjan; Janku, Krzysztof; Kiss, Győző; Kraai, Aline; Istenes, Zoltán.; Mohácsi, Árpád.; Szabó, Gábor; Schelde, Kirsten; Theobald, Mark

    2010-05-01

    As a part of the NitroEurope common field experiment, energy budget components and ammonia concentrations were measured by various methods on an agricultural field near Bjerringbro, Denmark in April 2009. Several sources of ammonia (pig farms, nearby fertilized fields) were present in the landscape and the field itself was also fertilized with pig slurry during the campaign. Turbulent fluxes were calculated using micrometeorological measurement data (standard meteorological parameters, radiation and surface energy budget components) as well as three different methods: (i) the gradient, (ii) the Bowen ratio and (iii) the eddy covariance method using 15 min average time. Results obtained using different methodologies for flux calculations and local effects on energy budget closure were compared. Instrumentation used for measuring ammonia concentrations included two wet-chemical (AMANDA) instruments and two photoacoustic instruments (a mid-IR CO2 laser based Nitolux and a self-developed near-IR diode laser based WaSul instrument). The WaSul instrument was operated in gradient configuration, which also enables the calculation of ammonia fluxes. The instruments were placed at different points of the field to gain more information on the spatial concentration distribution. Ammonia concentration data measured by the different instruments and wind speed and direction data were used to estimate the location of ammonia sources within the landscape. After fertilization of the field ammonia emission fluxes were calculated from the gradient data.

  5. Quantitative analysis of the publishing landscape in high-energy physics

    NASA Astrophysics Data System (ADS)

    Mele, Salvatore; Dallman, David; Vigen, Jens; Yeomans, Joanne

    2006-12-01

    World-wide collaboration in high-energy physics (HEP) is a tradition which dates back several decades, with scientific publications mostly coauthored by scientists from different countries. This coauthorship phenomenon makes it difficult to identify precisely the ``share'' of each country in HEP scientific production. One year's worth of HEP scientific articles published in peer-reviewed journals is analysed and their authors are uniquely assigned to countries. This method allows the first correct estimation on a pro rata basis of the share of HEP scientific publishing among several countries and institutions. The results provide an interesting insight into the geographical collaborative patterns of the HEP community. The HEP publishing landscape is further analysed to provide information on the journals favoured by the HEP community and on the geographical variation of their author bases. These results provide quantitative input to the ongoing debate on the possible transition of HEP publishing to an Open Access model. Foreword. This paper reports the results of a recent detailed study of the publishing landscape in high energy physics. We thought that because of its direct relevance to the high energy physics community, this important quantitative input to the debate on the transition to Open Access naturally finds its place in our journal. Marc Henneaux, JHEP Scientific Director

  6. 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

  7. 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.

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

    DOE PAGESBeta

    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

  9. 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.

  10. 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

  11. 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

  12. Monte Carlo Modeling of Spectral Diffusion Employing Multiwell Protein Energy Landscapes: Application to Pigment-Protein Complexes Involved in Photosynthesis.

    PubMed

    Najafi, Mehdi; Zazubovich, Valter

    2015-06-25

    We are reporting development and initial applications of the light-induced and thermally induced spectral diffusion modeling software, covering nonphotochemical spectral hole burning (NPHB), hole recovery, and single-molecule spectroscopy and involving random generation of the multiwell protein energy landscapes. The model includes tunneling and activated barrier-hopping in both ground and excited states of a protein-chromophore system. Evolution of such a system is predicted by solving the system of rate equations. Using the barrier parameters from the range typical for the energy landscapes of the pigment-protein complexes involved in photosynthesis, we (a) show that realistic cooling of the sample must result in proteins quite far from thermodynamic equilibrium, (b) demonstrate hole evolution in the cases of burning, fixed-temperature recovery and thermocycling that mostly agrees with the experiment and modeling based on the NPHB master equation, and (c) explore the effects of different protein energy landscapes on the antihole shape. Introducing the multiwell energy landscapes and starting the hole burning experiments in realistic nonequilibrium conditions are not sufficient to explain all experimental observations even qualitatively. Therefore, for instance, one is required to invoke the modified NPHB mechanism where a complex interplay of several small conformational changes is poising the energy landscape of the pigment-protein system for downhill tunneling.

  13. Evolution under Drug Pressure Remodels the Folding Free-Energy Landscape of Mature HIV-1 Protease.

    PubMed

    Louis, John M; Roche, Julien

    2016-07-01

    Using high-pressure NMR spectroscopy and differential scanning calorimetry, we investigate the folding landscape of the mature HIV-1 protease homodimer. The cooperativity of unfolding was measured in the absence or presence of a symmetric active site inhibitor for the optimized wild type protease (PR), its inactive variant PRD25N, and an extremely multidrug-resistant mutant, PR20. The individual fit of the pressure denaturation profiles gives rise to first order, ∆GNMR, and second order, ∆VNMR (the derivative of ∆GNMR with pressure); apparent thermodynamic parameters for each amide proton considered. Heterogeneity in the apparent ∆VNMR values reflects departure from an ideal cooperative unfolding transition. The narrow to broad distribution of ∆VNMR spanning the extremes from inhibitor-free PR20D25N to PR-DMP323 complex, and distinctively for PRD25N-DMP323 complex, indicated large variations in folding cooperativity. Consistent with this data, the shape of thermal unfolding transitions varies from asymmetric for PR to nearly symmetric for PR20, as dimer-inhibitor ternary complexes. Lack of structural cooperativity was observed between regions located close to the active site, including the hinge and tip of the glycine-rich flaps, and the rest of the protein. These results strongly suggest that inhibitor binding drastically decreases the cooperativity of unfolding by trapping the closed flap conformation in a deep energy minimum. To evade this conformational trap, PR20 evolves exhibiting a smoother folding landscape with nearly an ideal two-state (cooperative) unfolding transition. This study highlights the malleability of retroviral protease folding pathways by illustrating how the selection of mutations under drug pressure remodels the free-energy landscape as a primary mechanism. PMID:27170547

  14. Evolution under Drug Pressure Remodels the Folding Free-Energy Landscape of Mature HIV-1 Protease.

    PubMed

    Louis, John M; Roche, Julien

    2016-07-01

    Using high-pressure NMR spectroscopy and differential scanning calorimetry, we investigate the folding landscape of the mature HIV-1 protease homodimer. The cooperativity of unfolding was measured in the absence or presence of a symmetric active site inhibitor for the optimized wild type protease (PR), its inactive variant PRD25N, and an extremely multidrug-resistant mutant, PR20. The individual fit of the pressure denaturation profiles gives rise to first order, ∆GNMR, and second order, ∆VNMR (the derivative of ∆GNMR with pressure); apparent thermodynamic parameters for each amide proton considered. Heterogeneity in the apparent ∆VNMR values reflects departure from an ideal cooperative unfolding transition. The narrow to broad distribution of ∆VNMR spanning the extremes from inhibitor-free PR20D25N to PR-DMP323 complex, and distinctively for PRD25N-DMP323 complex, indicated large variations in folding cooperativity. Consistent with this data, the shape of thermal unfolding transitions varies from asymmetric for PR to nearly symmetric for PR20, as dimer-inhibitor ternary complexes. Lack of structural cooperativity was observed between regions located close to the active site, including the hinge and tip of the glycine-rich flaps, and the rest of the protein. These results strongly suggest that inhibitor binding drastically decreases the cooperativity of unfolding by trapping the closed flap conformation in a deep energy minimum. To evade this conformational trap, PR20 evolves exhibiting a smoother folding landscape with nearly an ideal two-state (cooperative) unfolding transition. This study highlights the malleability of retroviral protease folding pathways by illustrating how the selection of mutations under drug pressure remodels the free-energy landscape as a primary mechanism.

  15. Effects of oncogenic mutations on the conformational free-energy landscape of EGFR kinase

    PubMed Central

    Sutto, Ludovico; Gervasio, Francesco Luigi

    2013-01-01

    Activating mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase are frequently found in many cancers. It has been suggested that changes in the equilibrium between its active and inactive conformations are linked to its oncogenic potential. Here, we quantify the effects of some of the most common single (L858R and T790M) and double (T790M-L858R) oncogenic mutations on the conformational free-energy landscape of the EGFR kinase domain by using massive molecular dynamics simulations together with parallel tempering, metadynamics, and one of the best force-fields available. Whereas the wild-type EGFR catalytic domain monomer is mostly found in an inactive conformation, our results show a clear shift toward the active conformation for all of the mutants. The L858R mutation stabilizes the active conformation at the expense of the inactive conformation and rigidifies the αC-helix. The T790M gatekeeper mutant favors activation by stabilizing a hydrophobic cluster. Finally, T790M with L858R shows a significant positive epistasis effect. This combination not only stabilizes the active conformation, but in nontrivial ways changes the free-energy landscape lowering the transition barriers. PMID:23754386

  16. Glasses and Liquids Low on the Energy Landscape Prepared by Physical Vapor Deposition

    NASA Astrophysics Data System (ADS)

    Dalal, Shakeel; Fakhraai, Zahra; Ediger, Mark

    2014-03-01

    The lower portions of the potential energy landscape for glass-forming materials such as polymers and small molecules were historically inaccessible by experiments. Physical vapor deposition is uniquely able to prepare materials in this portion of the energy landscape, with the properties of the deposited material primarily modulated by the substrate temperature. Here we report on high-throughput experiments which utilize a temperature gradient stage to enable rapid screening of vapor-deposited organic glasses. Using ellipsometry, we characterize a 100 K range of substrate temperatures in a single experiment, allowing us to rapidly determine the density, kinetic stability, fictive temperature and molecular orientation of these glasses. Their properties fall into three temperature regimes. At substrate temperatures as low as 0.97Tg, we prepare materials which are equivalent to the supercooled liquid produced by cooling the melt. Below 0.9Tg (1.16TK) the properties of materials are kinetically controlled and highly tunable. At intermediate substrate temperatures we are able to produce materials whose bulk properties match those expected for the equilibrium supercooled liquid, down to 1.16TK, but are structurally anisotropic.

  17. Funneling and frustration in the energy landscapes of some designed and simplified proteins

    NASA Astrophysics Data System (ADS)

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

    2013-09-01

    We explore the similarities and differences between the energy landscapes of proteins that have been selected by nature and those of some proteins designed by humans. Natural proteins have evolved to function as well as fold, and this is a source of energetic frustration. The sequence of Top7, on the other hand, was designed with architecture alone in mind using only native state stability as the optimization criterion. Its topology had not previously been observed in nature. Experimental studies show that the folding kinetics of Top7 is more complex than the kinetics of folding of otherwise comparable naturally occurring proteins. In this paper, we use structure prediction tools, frustration analysis, and free energy profiles to illustrate the folding landscapes of Top7 and two other proteins designed by Takada. We use both perfectly funneled (structure-based) and predictive (transferable) models to gain insight into the role of topological versus energetic frustration in these systems and show how they differ from those found for natural proteins. We also study how robust the folding of these designs would be to the simplification of the sequences using fewer amino acid types. Simplification using a five amino acid type code results in comparable quality of structure prediction to the full sequence in some cases, while the two-letter simplification scheme dramatically reduces the quality of structure prediction.

  18. Crushing runtimes in adiabatic quantum computation with Energy Landscape Manipulation (ELM): Application to Quantum Factoring

    NASA Astrophysics Data System (ADS)

    Dattani, Nike; Tanburn, Richard; Lunt, Oliver

    We introduce two methods for speeding up adiabatic quantum computations by increasing the energy between the ground and first excited states. Our methods are even more general. They can be used to shift a Hamiltonian's density of states away from the ground state, so that fewer states occupy the low-lying energies near the minimum, hence allowing for faster adiabatic passages to find the ground state with less risk of getting caught in an undesired low-lying excited state during the passage. Even more generally, our methods can be used to transform a discrete optimization problem into a new one whose unique minimum still encodes the desired answer, but with the objective function's values forming a different landscape. Aspects of the landscape such as the objective function's range, or the values of certain coefficients, or how many different inputs lead to a given output value, can be decreased *or* increased. One of the many examples for which these methods are useful is in finding the ground state of a Hamiltonian using NMR. We apply our methods to an AQC algorithm for integer factorization, and the first method reduces the maximum runtime in our example by up to 754%, and the second method reduces the maximum runtime of another example by up to 250%.

  19. 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.

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

    PubMed

    Bello-Rivas, Juan M; Elber, Ron

    2016-03-01

    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.

  1. 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.

  2. Chiral effects on helicity studied via the energy landscape of short (d, l)-alanine peptides

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

    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.

  3. Metadynamics as a tool for exploring free energy landscapes of chemical reactions.

    PubMed

    Ensing, Bernd; De Vivo, Marco; Liu, Zhiwei; Moore, Preston; Klein, Michael L

    2006-02-01

    The metadynamics or hills method is a relatively new molecular dynamics technique aimed to enhance the sampling of separated regions in phase space and map out the underlying free energy landscape as a function of a small number of order parameters or collective variables. The high efficiency allows for the application of metadynamics in combination with first principles dynamics methods, in particular with Car-Parrinello molecular dynamics, to study processes in which changes in the electronic structure play a dominant role, such as chemical reactions. The option to choose several independent collective variables is important to tackle complex and concerted transformations that lack an obvious a priori choice for a single reaction coordinate. In this Account, we discuss the role of metadynamics in the search of transition states, local minima, reaction paths, free energy profiles, and reaction coordinates among a growing list of alternative methods. PMID:16489726

  4. 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.

  5. Intrinsic Chevrolets at the SSC

    SciTech Connect

    Brodsky, S.J.; Collins, J.C.; Ellis, S.D.; Gunion, J.F.; Mueller, A.H.

    1984-01-01

    The possibility of the production at high energy of heavy quarks, supersymmetric particles and other large mass colored systems via the intrinsic twist-six components in the proton wave function is discussed. While the existing data do not rule out the possible relevance of intrinsic charm production at present energies, the extrapolation of such intrinsic contributions to very high masses and energies suggests that they will not play an important role at the SSC.

  6. 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

  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. 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

  9. 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. PMID:26714673

  10. 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.

  11. 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

  12. 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.

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

    NASA Astrophysics Data System (ADS)

    Wales, D. J.

    2015-04-01

    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

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

    2015-07-01

    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.

  15. Free Energy Landscape of Rim-Pore Expansion in Membrane Fusion

    PubMed Central

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

    2014-01-01

    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. PMID:25418297

  16. 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

  17. Energy landscapes, structural topologies and rearrangement mechanisms in clusters of dipolar particles

    NASA Astrophysics Data System (ADS)

    Farrell, James D.; Lines, Christabel; Shepherd, James J.; Chakrabarti, Dwaipayan; Miller, Mark A.; Wales, David J.

    Clusters of spherical particles with isotropic attraction favour compact structures that maximise the number of energetically optimal nearest-neighbour interactions. In contrast, dipolar interactions lead to the formation of chains with a low coordination number. When both isotropic and dipolar interactions are present, the competition between them can lead to intricate knot, link and coil structures. Here, we investigate how these structures may self-organise and interconvert in clusters bound by the Stockmayer potential (Lennard-Jones plus point dipole). We map out the low-lying region of the energy landscape using disconnectivity graphs to follow how it evolves as the strength of the dipolar interactions increases. From comprehensive surveys of isomerisation pathways, we identify a number of rearrangement mechanisms that allow the topology of chain-like structures to interconvert.

  18. Free energy landscape of activation in a signaling protein at atomic resolution

    PubMed Central

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

    2015-01-01

    The interconversion between inactive and active protein states, traditionally described by two static structures, is at the heart of signaling. 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 NMR, and discover unexpected features underlying efficient signaling. 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. PMID:26073309

  19. Exploring the free energy and conformational landscape of tRNA at high temperature and pressure.

    PubMed

    Schuabb, Caroline; Berghaus, Melanie; Rosin, Christopher; Winter, Roland

    2015-01-12

    A combined temperature- and pressure-dependent study was employed to reveal the conformational and free-energy landscape of phenylalanine transfer RNA (tRNA(Phe) ), a known model for RNA function, to elucidate the features that are essential in determining its stability. These studies also help explore its structural properties under extreme environmental conditions, such as low/high temperatures and high pressures. To this end, fluorescence and FTIR spectroscopies, calorimetric and small-angle scattering measurements were carried out at different ion concentrations over a wide range of temperatures and pressures up to several hundred MPa. Compared with the pronounced temperature effect, the pressure-dependent structural changes of tRNA(Phe) are small. A maximum of only 15 % unpaired bases is observed upon pressurization up to 1 GPa. RNA unfolding differs not only from protein unfolding, but also from DNA melting. Its pressure stability seems to be similar to that of noncanonical DNA structures. PMID:25393611

  20. Navigating Membrane Protein Structure, Dynamics, and Energy Landscapes Using Spin Labeling and EPR Spectroscopy.

    PubMed

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

    2015-01-01

    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 toward generating high quality data.

  1. Imaging G protein–coupled receptors while quantifying their ligand-binding free-energy landscape

    PubMed Central

    Zhang, Cheng; Spoerri, Patrizia M; Coughlin, Shaun R; Kobilka, Brian K; Müller, Daniel J

    2016-01-01

    Imaging native membrane receptors and testing how they interact with ligands is of fundamental interest in the life sciences but has proven remarkably difficult to accomplish. Here, we introduce an approach that uses force-distance curve–based atomic force microscopy to simultaneously image single native G protein–coupled receptors in membranes and quantify their dynamic binding strength to native and synthetic ligands. We measured kinetic and thermodynamic parameters for individual protease-activated receptor-1 (PAR1) molecules in the absence and presence of antagonists, and these measurements enabled us to describe PAR1’s ligand-binding free-energy landscape with high accuracy. Our nanoscopic method opens an avenue to directly image and characterize ligand binding of native membrane receptors. PMID:26167642

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. DNA denaturation bubbles: Free-energy landscape and nucleation/closure rates

    NASA Astrophysics Data System (ADS)

    Sicard, François; Destainville, Nicolas; Manghi, Manoel

    2015-01-01

    The issue of the nucleation and slow closure mechanisms of non-superhelical stress-induced denaturation bubbles in DNA is tackled using coarse-grained MetaDynamics and Brownian simulations. A minimal mesoscopic model is used where the double helix is made of two interacting bead-spring rotating strands with a prescribed torsional modulus in the duplex state. We demonstrate that timescales for the nucleation (respectively, closure) of an approximately 10 base-pair bubble, in agreement with experiments, are associated with the crossing of a free-energy barrier of 22 kBT (respectively, 13 kBT) at room temperature T. MetaDynamics allows us to reconstruct accurately the free-energy landscape, to show that the free-energy barriers come from the difference in torsional energy between the bubble and duplex states, and thus to highlight the limiting step, a collective twisting, that controls the nucleation/closure mechanism, and to access opening time scales on the millisecond range. Contrary to small breathing bubbles, those more than 4 base-pair bubbles are of biological relevance, for example, when a pre-existing state of denaturation is required by specific DNA-binding proteins.

  7. Energy landscape paving with local search for global optimization of the BLN off-lattice model

    NASA Astrophysics Data System (ADS)

    Liu, Jingfa; Huang, Weibo; Liu, Wenjie; Song, Beibei; Sun, Yuanyuan; Chen, Mao

    2014-02-01

    The optimization problem for finding the global minimum energy structure is one of the main problems of protein structure prediction and is known to be an NP-hard problem in computational molecular biology. The low-energy conformational search problem in the hydrophobic-hydrophilic-neutral (BLN) off-lattice model is studied. We convert the problem into an unconstrained optimization problem by introducing the penalty function. By putting forward a new updating mechanism of the histogram function in the energy landscape paving (ELP) method and incorporating heuristic conformation update strategies into the ELP method, we obtain an improved ELP (IELP) method. Subsequently, by combining the IELP method with the local search (LS) based on the gradient descent method, we propose a hybrid algorithm, denoted by IELP-LS, for the conformational search of the off-lattice BLN model. Simulation results indicate that IELP-LS can find lower-energy states than other methods in the literature, showing that the proposed method is an effective tool for global optimization in the BLN off-lattice protein model.

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

    PubMed

    Nguyen, Duc; Mallek, Justin; Cloud, Andrew N; Abelson, John R; Girolami, Gregory S; 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-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.

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

    PubMed

    Nguyen, Duc; Mallek, Justin; Cloud, Andrew N; Abelson, John R; Girolami, Gregory S; 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-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. PMID:25429948

  10. 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.

  11. Rugged Energy Landscapes in Multiphase Porous Media Flow: A Discrete-Domain Description

    NASA Astrophysics Data System (ADS)

    Cueto-Felgueroso, L.; Juanes, R.

    2015-12-01

    Immiscible displacements in porous media involve a complex sequence of pore-scale events, from the smooth, reversible displacement of interfaces to abrupt interfacial reconfigurations and rapid pore invasion cascades. Discontinuous changes in pressure or saturation have been referred to as Haines jumps, and they emerge as a key mechanism to understand the origin of hysteresis in porous media flow. Hysteresis persists at the many-pore scale: when multiple cycles of drainage and imbibition of a porous sample are conducted, a dense hysteresis diagram emerges. The interpretation of hysteresis as a consequence of irreversible transitions and multistability is at the heart of early hysteresis models, and in recent experiments, and points to an inherently non-equilibrium behavior. For a given volume fraction of fluids occupying the pore space, many stable configurations are possible, due to the tortuous network of nonuniform pores and throats that compose the porous medium, and to complex wetting and capillary transitions. Multistability indicates that porous media systems exhibit rugged energy landscapes, where the system may remain pinned at local energy minima for long times. We address the question of developing a zero-dimensional model that inherits the path-dependence and `'bursty'' behavior of immiscible displacements, and propose a discrete-domain model that captures the role of metastability and local equilibria in the origin of hysteresis. We describe the porous medium and fluid system as a discrete set of weakly connected, multistable compartments, charaterized by a unique free energy function. This description does not depend explicitly on past saturations, turning points, or drainage/imbibition labels. The system behaves hysteretically, and we rationalize its behavior as sweeping a complex metastability diagram, with dissipation arising from discrete switches among metastable branches. The hysteretic behavior of the pressure-saturation curve is controlled by

  12. 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

  13. 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

    2016-03-01

    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(•-). PMID:26908223

  14. 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

  15. Uncertainty analysis of continuum scale ferroelectric energy landscapes using density functional theory

    NASA Astrophysics Data System (ADS)

    Oates, William S.; Miles, Paul; Leon, Lider; Smith, Ralph

    2016-04-01

    Density functional theory (DFT) provides exceptional predictions of material properties of ideal crystal structures such as elastic modulus and dielectric constants. This includes ferroelectric crystals where excellent predictions of spontaneous polarization, lattice strain, and elastic moduli have been predicted using DFT. Less analysis has focused on quantifying uncertainty of the energy landscape over a broad range of polarization states in ferroelectric materials. This is non-trivial because the degrees of freedom contained within a unit cell are reduced to a single vector order parameter which is normally polarization. For example, lead titanate contains five atoms and 15 degrees of freedom of atomic nuclei motion which contribute to the overall unit cell polarization. Bayesian statistics is used to identify the uncertainty and propagation of error of a continuum scale, Landau energy function for lead titanate. Uncertainty in different parameters is quantified and this uncertainty is propagated through the model to illustrate error propagation over the energy surface. Such results are shown to have an impact in integration of quantum simulations within a ferroelectric phase field continuum modeling framework.

  16. 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.

  17. Electrostatic optimization of the conformational energy landscape in a metamorphic protein.

    PubMed

    Tyler, Robert C; Wieting, Jamie C; Peterson, Francis C; Volkman, Brian F

    2012-11-13

    The equilibrium unfolding reaction of Ltn, a metamorphic C-class chemokine, was monitored by tryptophan fluorescence to determine unfolding free energies. Measurements revealed that addition of 150 mM NaCl stabilized the Ltn chemokine fold by approximately 1 kcal/mol. Specific mutations involving Arg23 and Arg43 also increased the stability by 1 kcal/mol, suggesting their involvement in chloride ion coordination. This interaction was confirmed by nuclear magnetic resonance (NMR) salt titration studies that revealed chemical shift perturbations localized to these residues and backbone amides within the proximal 40s loop. The effects of NaCl on the free energy landscape were further verified by ZZ-exchange NMR spectroscopy. Our results suggest that changes in the electrostatic environment modulate the Gibbs free energy of folding and alter the forward and reverse rates of interconversion. These results demonstrate how solution ions can promote metamorphic folding by adjusting the relative stabilities of two unrelated Ltn native-state structures.

  18. 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. PMID:26262876

  19. 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.

  20. 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. PMID:27208935

  1. 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. PMID:24156399

  2. 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.

  3. Water complexes of important air pollutants: geometries, complexation energies, concentrations, infrared spectra, and intrinsic reactivity.

    PubMed

    Galano, Annia; Narciso-Lopez, Marcela; Francisco-Marquez, Misaela

    2010-05-13

    Water complexes involving methanol, ethanol, formaldehyde, formic acid, acetone, ammonia, acetylene, ethylene, chloroethene, trichloroethene, 1,1,1-trichloroethane, hydroxyl radical, and hydroperoxyl radical have been studied. Enthalpies, entropies, and Gibbs free energies of association have been estimated, as well as the concentrations of the complexes under lower-troposphere conditions. The influence of the relative air humidity on the complexation processes has been analyzed. The association processes yielding water complexes of methanol, ethanol, formic acid, ammonia, acetone, hydroxyl radical, and hydroperoxyl radical were found to be more exothermic than that of the water dimer. General trends for the reactivity of the studied water complexes, compared to those of the corresponding free species, are proposed based on global reactivity indexes. The previously reported increased reactivity of the (*)OOH self-reaction, when there is water present, has been explained. The IR spectra of the complexes have been analyzed and compared with those of the free species. PMID:20394451

  4. The ruggedness of protein–protein energy landscape and the cutoff for 1/rn potentials

    PubMed Central

    Ruvinsky, Anatoly M.; Vakser, Ilya A.

    2009-01-01

    Motivation: Computational studies of the energetics of protein association are important for revealing the underlying fundamental principles and for designing better tools to model protein complexes. The interaction cutoff contribution to the ruggedness of protein–protein energy landscape is studied in terms of relative energy fluctuations for 1/rn potentials based on a simplistic model of a protein complex. This artificial ruggedness exists for short cutoffs and gradually disappears with the cutoff increase. Results: The critical values of the cutoff were calculated for each of 11 popular power-type potentials with n=0÷9, 12 and for two thresholds of 5% and 10%. The artificial ruggedness decreases to tolerable thresholds for cutoffs larger than the critical ones. The results showed that for both thresholds the critical cutoff is a non-monotonic function of the potential power n. The functions reach the maximum at n=3÷4 and then decrease with the increase of the potential power. The difference between two cutoffs for 5% and 10% artificial ruggedness becomes negligible for potentials decreasing faster than 1/r12. The analytical results obtained for the simple model of protein complexes agree with the analysis of artificial ruggedness in a dataset of 62 protein–protein complexes, with different parameterizations of soft Lennard–Jones potential and two types of protein representations: all-atom and coarse-grained. The results suggest that cutoffs larger than the critical ones can be recommended for protein–protein potentials. Contact: vakser@ku.edu PMID:19237445

  5. Region Graph Partition Function Expansion and Approximate Free Energy Landscapes: Theory and Some Numerical Results

    NASA Astrophysics Data System (ADS)

    Zhou, Haijun; Wang, Chuang

    2012-08-01

    Graphical models for finite-dimensional spin glasses and real-world combinatorial optimization and satisfaction problems usually have an abundant number of short loops. The cluster variation method and its extension, the region graph method, are theoretical approaches for treating the complicated short-loop-induced local correlations. For graphical models represented by non-redundant or redundant region graphs, approximate free energy landscapes are constructed in this paper through the mathematical framework of region graph partition function expansion. Several free energy functionals are obtained, each of which use a set of probability distribution functions or functionals as order parameters. These probability distribution function/functionals are required to satisfy the region graph belief-propagation equation or the region graph survey-propagation equation to ensure vanishing correction contributions of region subgraphs with dangling edges. As a simple application of the general theory, we perform region graph belief-propagation simulations on the square-lattice ferromagnetic Ising model and the Edwards-Anderson model. Considerable improvements over the conventional Bethe-Peierls approximation are achieved. Collective domains of different sizes in the disordered and frustrated square lattice are identified by the message-passing procedure. Such collective domains and the frustrations among them are responsible for the low-temperature glass-like dynamical behaviors of the system.

  6. Distinct dissociation kinetics between ion pairs: Solvent-coordinate free-energy landscape analysis.

    PubMed

    Yonetani, Yoshiteru

    2015-07-28

    Different ion pairs exhibit different dissociation kinetics; however, while the nature of this process is vital for understanding various molecular systems, the underlying mechanism remains unclear. In this study, to examine the origin of different kinetic rate constants for this process, molecular dynamics simulations were conducted for LiCl, NaCl, KCl, and CsCl in water. The results showed substantial differences in dissociation rate constant, following the trend kLiCl < kNaCl < kKCl < kCsCl. Analysis of the free-energy landscape with a solvent reaction coordinate and subsequent rate component analysis showed that the differences in these rate constants arose predominantly from the variation in solvent-state distribution between the ion pairs. The formation of a water-bridging configuration, in which the water molecule binds to an anion and a cation simultaneously, was identified as a key step in this process: water-bridge formation lowers the related dissociation free-energy barrier, thereby increasing the probability of ion-pair dissociation. Consequently, a higher probability of water-bridge formation leads to a higher ion-pair dissociation rate.

  7. Distinct dissociation kinetics between ion pairs: Solvent-coordinate free-energy landscape analysis

    NASA Astrophysics Data System (ADS)

    Yonetani, Yoshiteru

    2015-07-01

    Different ion pairs exhibit different dissociation kinetics; however, while the nature of this process is vital for understanding various molecular systems, the underlying mechanism remains unclear. In this study, to examine the origin of different kinetic rate constants for this process, molecular dynamics simulations were conducted for LiCl, NaCl, KCl, and CsCl in water. The results showed substantial differences in dissociation rate constant, following the trend kLiCl < kNaCl < kKCl < kCsCl. Analysis of the free-energy landscape with a solvent reaction coordinate and subsequent rate component analysis showed that the differences in these rate constants arose predominantly from the variation in solvent-state distribution between the ion pairs. The formation of a water-bridging configuration, in which the water molecule binds to an anion and a cation simultaneously, was identified as a key step in this process: water-bridge formation lowers the related dissociation free-energy barrier, thereby increasing the probability of ion-pair dissociation. Consequently, a higher probability of water-bridge formation leads to a higher ion-pair dissociation rate.

  8. Exploring the free-energy landscape of a short peptide using an average force

    NASA Astrophysics Data System (ADS)

    Chipot, Christophe; Hénin, Jérôme

    2005-12-01

    The reversible folding of deca-alanine is chosen as a test case for characterizing a method that uses an adaptive biasing force (ABF) to escape from the minima and overcome the barriers of the free-energy landscape. This approach relies on the continuous estimation of a biasing force that yields a Hamiltonian in which no average force is exerted along the ordering parameter ξ. Optimizing the parameters that control how the ABF is applied, the method is shown to be extremely effective when a nonequivocal ordering parameter can be defined to explore the folding pathway of the peptide. Starting from a β-turn motif and restraining ξ to a region of the conformational space that extends from the α-helical state to an ensemble of extended structures, the ABF scheme is successful in folding the peptide chain into a compact α helix. Sampling of this conformation is, however, marginal when the range of ξ values embraces arrangements of greater compactness, hence demonstrating the inherent limitations of free-energy methods when ambiguous ordering parameters are utilized.

  9. 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

  10. 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.

  11. Free-energy landscape and nucleation pathway of polymorphic minerals from solution in a Potts lattice-gas model.

    PubMed

    Okamoto, Atsushi; Kuwatani, Tatsu; Omori, Toshiaki; Hukushima, Koji

    2015-10-01

    Metastable minerals commonly form during reactions between water and rock. The nucleation mechanism of polymorphic phases from solution are explored here using a two-dimensional Potts model. The model system is composed of a solvent and three polymorphic solid phases. The local state and position of the solid phase are updated by Metropolis dynamics. Below the critical temperature, a large cluster of the least stable solid phase initially forms in the solution before transitioning into more-stable phases following the Ostwald step rule. The free-energy landscape as a function of the modal abundance of each solid phase clearly reveals that before cluster formation, the least stable phase has an energetic advantage because of its low interfacial energy with the solution, and after cluster formation, phase transformation occurs along the valley of the free-energy landscape, which contains several minima for the regions of three phases. Our results indicate that the solid-solid and solid-liquid interfacial energy contribute to the formation of the complex free-energy landscape and nucleation pathways following the Ostwald step rule. PMID:26565191

  12. 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.

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

    PubMed

    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. PMID:24329293

  14. 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.

  15. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2009-03-01

    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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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).

  4. 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

  5. Heuristic-based energy landscape paving for the circular packing problem with performance constraints of equilibrium

    NASA Astrophysics Data System (ADS)

    Liu, Jingfa; Jiang, Yucong; Li, Gang; Xue, Yu; Liu, Zhaoxia; Zhang, Zhen

    2015-08-01

    The optimal layout problem of circle group in a circular container with performance constraints of equilibrium belongs to a class of NP-hard problem. The key obstacle of solving this problem is the lack of an effective global optimization method. We convert the circular packing problem with performance constraints of equilibrium into the unconstrained optimization problem by using quasi-physical strategy and penalty function method. By putting forward a new updating mechanism of the histogram function in energy landscape paving (ELP) method and incorporating heuristic conformation update strategies into the ELP method, we obtain an improved ELP (IELP) method. Subsequently, by combining the IELP method and the local search (LS) procedure, we put forward a hybrid algorithm, denoted by IELP-LS, for the circular packing problem with performance constraints of equilibrium. We test three sets of benchmarks consisting of 21 representative instances from the current literature. The proposed algorithm breaks the records of all 10 instances in the first set, and achieves the same or even better results than other methods in literature for 10 out of 11 instances in the second and third sets. The computational results show that the proposed algorithm is an effective method for solving the circular packing problem with performance constraints of equilibrium.

  6. Connectivity in the potential energy landscape for binary Lennard-Jones systems

    NASA Astrophysics Data System (ADS)

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

    2009-05-01

    Connectivity in the potential energy landscape of a binary Lennard-Jones system can be characterized at the level of cage-breaking. We calculate the number of cage-breaking routes from a given local minimum and determine the branching probabilities at different temperatures, along with correlation factors that represent the repeated reversals of cage-breaking events. The number of reversals increases at lower temperatures and for more fragile systems, while the number of accessible connections decreases. We therefore associate changes in connectivity with super-Arrhenius behavior. Reversals in minimum-to-minimum transitions are common, but often correspond to "non-cage-breaking" processes. We demonstrate that the average waiting time within a minimum shows simple exponential behavior with decreasing temperature. To describe the long-term behavior of the system, we consider reversals and connectivity in terms of the "cage-breaking" processes that are pertinent to diffusion [V. K. de Souza and D. J. Wales, J. Chem. Phys. 129, 164507 (2008)]. These cage-breaking events can be modeled by a correlated random walk. Thus, a full correlation factor can be calculated using short simulations that extend up to two cage-breaking events.

  7. pH-Responsive Self-Assembly of Polysaccharide through a Rugged Energy Landscape.

    PubMed

    Morrow, Brian H; Payne, Gregory F; Shen, Jana

    2015-10-14

    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 the 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.

  8. 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

  9. 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.

  10. Luminous Landscapes.

    ERIC Educational Resources Information Center

    Okrent, Inez

    2000-01-01

    Describes an activity for third-grade students in which they learn about early American landscape painters, specifically Frederick Church, Thomas Moran, and Albert Bierstadt. Students create natural landscapes, using the basic elements of landscape compositions. Discusses the process. (CMK)

  11. 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

  12. Modulation of Intrinsically Disordered Protein Function by Post-translational Modifications.

    PubMed

    Bah, Alaji; Forman-Kay, Julie D

    2016-03-25

    Post-translational modifications (PTMs) produce significant changes in the structural properties of intrinsically disordered proteins (IDPs) by affecting their energy landscapes. PTMs can induce a range of effects, from local stabilization or destabilization of transient secondary structure to global disorder-to-order transitions, potentially driving complete state changes between intrinsically disordered and folded states or dispersed monomeric and phase-separated states. Here, we discuss diverse biological processes that are dependent on PTM regulation of IDPs. We also present recent tools for generating homogenously modified IDPs for studies of PTM-mediated IDP regulatory mechanisms. PMID:26851279

  13. 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

  14. 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.

  15. Can a continuum solvent model reproduce the free energy landscape of a β-hairpin folding in water?

    PubMed Central

    Zhou, Ruhong; Berne, Bruce J.

    2002-01-01

    The folding free energy landscape of the C-terminal β-hairpin of protein G is explored using the surface-generalized Born (SGB) implicit solvent model, and the results are compared with the landscape from an earlier study with explicit solvent model. The OPLSAA force field is used for the β-hairpin in both implicit and explicit solvent simulations, and the conformational space sampling is carried out with a highly parallel replica-exchange method. Surprisingly, we find from exhaustive conformation space sampling that the free energy landscape from the implicit solvent model is quite different from that of the explicit solvent model. In the implicit solvent model some nonnative states are heavily overweighted, and more importantly, the lowest free energy state is no longer the native β-strand structure. An overly strong salt-bridge effect between charged residues (E42, D46, D47, E56, and K50) is found to be responsible for this behavior in the implicit solvent model. Despite this, we find that the OPLSAA/SGB energies of all the nonnative structures are higher than that of the native structure; thus the OPLSAA/SGB energy is still a good scoring function for structure prediction for this β-hairpin. Furthermore, the β-hairpin population at 282 K is found to be less than 40% from the implicit solvent model, which is much smaller than the 72% from the explicit solvent model and ≈80% from experiment. On the other hand, both implicit and explicit solvent simulations with the OPLSAA force field exhibit no meaningful helical content during the folding process, which is in contrast to some very recent studies using other force fields. PMID:12242327

  16. Correlation between rate of folding, energy landscape, and topology in the folding of a model protein HP-36

    NASA Astrophysics Data System (ADS)

    Mukherjee, Arnab; Bagchi, Biman

    2003-03-01

    We explore the correlation between the energy landscape and topology in the folding of a model protein (chicken villin headpiece HP-36) by using a force-field which incorporates the effects of water through a hydropathy scale and the role of helical propensity of amino acids through a nonlocal harmonic potential. Each amino acid is represented by one side chain atom which is attached to the backbone Cα atom. Sizes and interactions of all the side chain residues are different and depend on the hydrophobicity of a particular amino acid, whereas helical propensities are incorporated in the interaction of Cα atoms. Simulations have been carried out by quenching from a fixed high temperature to two different low temperatures for many initial random configurations. The simulated structures resemble the real native state rather closely, with the root mean square deviation of the best structure being 4.5 Å. Moreover, the structure shows both the helices and bends at the appropriate positions of the model protein. The simplified model allows the study of energy landscape and also of the correlation between energy landscape with the dynamics of folding and topology. The initial part of folding is very fast, followed by two distinct slow stages, with the last stage being certainly the rate determining of the folding process. The initial fast dynamics is primarily due to hydrophobic collapse. The very slow last stage of folding is accompanied by a significant and sharp increase in the relative contact order parameter but relatively small decrease in energy. Analysis of the time dependence of the formation of the individual contact pairs show rich and complicated dynamics, where some contacts wait for a long time to form. This seems to suggest that the slow late stage folding is due to long range contact formation and also that the free energy barrier is entropic in origin. Results have been correlated with the theories of protein folding.

  17. 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.

  18. 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.

  19. 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.

  20. Colloids exposed to random potential energy landscapes: From particle number density to particle-potential and particle-particle interactions.

    PubMed

    Bewerunge, Jörg; Sengupta, Ankush; Capellmann, Ronja F; Platten, Florian; Sengupta, Surajit; Egelhaaf, Stefan U

    2016-07-28

    Colloidal particles were exposed to a random potential energy landscape that has been created optically via a speckle pattern. The mean particle density as well as the potential roughness, i.e., the disorder strength, were varied. The local probability density of the particles as well as its main characteristics were determined. For the first time, the disorder-averaged pair density correlation function g((1))(r) and an analogue of the Edwards-Anderson order parameter g((2))(r), which quantifies the correlation of the mean local density among disorder realisations, were measured experimentally and shown to be consistent with replica liquid state theory results.

  1. 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.

  2. TOPICAL REVIEW: Exploring the potential energy landscape of glass-forming systems: from inherent structures via metabasins to macroscopic transport

    NASA Astrophysics Data System (ADS)

    Heuer, Andreas

    2008-09-01

    In this review a systematic analysis of the potential energy landscape (PEL) of glass-forming systems is presented. Starting from the thermodynamics, the route towards the dynamics is elucidated. A key step in this endeavor is the concept of metabasins. The relevant energy scales of the PEL can be characterized. Based on the simulation results for some glass-forming systems one can formulate a relevant model system (ideal Gaussian glass-former) which can be treated analytically. The macroscopic transport can be related to the microscopic hopping processes, using either the strong relation between energy (thermodynamics) and waiting times (dynamics) or, alternatively, the concepts of the continuous-time random walk. The relation to the geometric properties of the PEL is stressed. The emergence of length scales within the PEL approach as well as the nature of finite-size effects is discussed. Furthermore, the PEL view is compared to other approaches describing the glass transition.

  3. The free energy landscape of pseudorotation in 3'-5' and 2'-5' linked nucleic acids.

    PubMed

    Li, Li; Szostak, Jack W

    2014-02-19

    The five-membered furanose ring is a central component of the chemical structure of biological nucleic acids. The conformations of the furanose ring can be analytically described using the concept of pseudorotation, and for RNA and DNA they are dominated by the C2'-endo and C3'-endo conformers. While the free energy difference between these two conformers can be inferred from NMR measurements, a free energy landscape of the complete pseudorotation cycle of nucleic acids in solution has remained elusive. Here, we describe a new free energy calculation method for molecular dynamics (MD) simulations using the two pseudorotation parameters directly as the collective variables. To validate our approach, we calculated the free energy surface of ribose pseudorotation in guanosine and 2'-deoxyguanosine. The calculated free energy landscape reveals not only the relative stability of the different pseudorotation conformers, but also the main transition path between the stable conformations. Applying this method to a standard A-form RNA duplex uncovered the expected minimum at the C3'-endo state. However, at a 2'-5' linkage, the minimum shifts to the C2'-endo conformation. The free energy of the C3'-endo conformation is 3 kcal/mol higher due to a weaker hydrogen bond and a reduced base stacking interaction. Unrestrained MD simulations suggest that the conversion from C3'-endo to C2'-endo and vice versa is on the nanosecond and microsecond time scale, respectively. These calculations suggest that 2'-5' linkages may enable folded RNAs to sample a wider spectrum of their pseudorotation conformations.

  4. Structure prediction of nanoclusters; a direct or a pre-screened search on the DFT energy landscape?

    PubMed

    Farrow, M R; Chow, Y; Woodley, S M

    2014-10-21

    The atomic structure of inorganic nanoclusters obtained via a search for low lying minima on energy landscapes, or hypersurfaces, is reported for inorganic binary compounds: zinc oxide (ZnO)n, magnesium oxide (MgO)n, cadmium selenide (CdSe)n, and potassium fluoride (KF)n, where n = 1-12 formula units. The computational cost of each search is dominated by the effort to evaluate each sample point on the energy landscape and the number of required sample points. The effect of changing the balance between these two factors on the success of the search is investigated. The choice of sample points will also affect the number of required data points and therefore the efficiency of the search. Monte Carlo based global optimisation routines (evolutionary and stochastic quenching algorithms) within a new software package, viz. Knowledge Led Master Code (KLMC), are employed to search both directly and after pre-screening on the DFT energy landscape. Pre-screening includes structural relaxation to minimise a cheaper energy function - based on interatomic potentials - and is found to improve significantly the search efficiency, and typically reduces the number of DFT calculations required to locate the local minima by more than an order of magnitude. Although the choice of functional form is important, the approach is robust to small changes to the interatomic potential parameters. The computational cost of initial DFT calculations of each structure is reduced by employing Gaussian smearing to the electronic energy levels. Larger (KF)n nanoclusters are predicted to form cuboid cuts from the rock-salt phase, but also share many structural motifs with (MgO)n for smaller clusters. The transition from 2D rings to 3D (bubble, or fullerene-like) structures occur at a larger cluster size for (ZnO)n and (CdSe)n. Differences between the HOMO and LUMO energies, for all the compounds apart from KF, are in the visible region of the optical spectrum (2-3 eV); KF lies deep in the UV region

  5. Structure prediction of nanoclusters; a direct or a pre-screened search on the DFT energy landscape?

    PubMed

    Farrow, M R; Chow, Y; Woodley, S M

    2014-10-21

    The atomic structure of inorganic nanoclusters obtained via a search for low lying minima on energy landscapes, or hypersurfaces, is reported for inorganic binary compounds: zinc oxide (ZnO)n, magnesium oxide (MgO)n, cadmium selenide (CdSe)n, and potassium fluoride (KF)n, where n = 1-12 formula units. The computational cost of each search is dominated by the effort to evaluate each sample point on the energy landscape and the number of required sample points. The effect of changing the balance between these two factors on the success of the search is investigated. The choice of sample points will also affect the number of required data points and therefore the efficiency of the search. Monte Carlo based global optimisation routines (evolutionary and stochastic quenching algorithms) within a new software package, viz. Knowledge Led Master Code (KLMC), are employed to search both directly and after pre-screening on the DFT energy landscape. Pre-screening includes structural relaxation to minimise a cheaper energy function - based on interatomic potentials - and is found to improve significantly the search efficiency, and typically reduces the number of DFT calculations required to locate the local minima by more than an order of magnitude. Although the choice of functional form is important, the approach is robust to small changes to the interatomic potential parameters. The computational cost of initial DFT calculations of each structure is reduced by employing Gaussian smearing to the electronic energy levels. Larger (KF)n nanoclusters are predicted to form cuboid cuts from the rock-salt phase, but also share many structural motifs with (MgO)n for smaller clusters. The transition from 2D rings to 3D (bubble, or fullerene-like) structures occur at a larger cluster size for (ZnO)n and (CdSe)n. Differences between the HOMO and LUMO energies, for all the compounds apart from KF, are in the visible region of the optical spectrum (2-3 eV); KF lies deep in the UV region

  6. 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.

  7. pH-dependent deformations of the energy landscape of avidin-like proteins investigated by single molecule force spectroscopy.

    PubMed

    Köhler, Melanie; Karner, Andreas; Leitner, Michael; Hytönen, Vesa P; Kulomaa, Markku; Hinterdorfer, Peter; Ebner, Andreas

    2014-08-18

    Avidin and avidin-like proteins are widely used in numerous techniques since the avidin-biotin interaction is known to be very robust and reliable. Within this study, we investigated this bond at the molecular level under harsh conditions ranging from very low to very high pH values. We compared avidin with streptavidin and a recently developed avidin-based mutant, chimeric avidin. To gain insights of the energy landscape of these interactions we used a single molecule approach and performed the Single Molecule Force Spectroscopy atomic force microscopy technique. There, the ligand (biotin) is covalently coupled to a sharp AFM tip via a distensible hetero-bi-functional crosslinker, whereas the receptor of interest is immobilized on the probe surface. Receptor-ligand complexes are formed and ruptured by repeatedly approaching and withdrawing the tip from the surface. Varying both pulling velocity and pH value, we could determine changes of the energy landscape of the complexes. Our results clearly demonstrate that avidin, streptavidin and chimeric avidin are stable over a wide pH range although we could identify differences at the outer pH range. Taking this into account, they can be used in a broad range of applications, like surface sensors at extreme pH values.

  8. 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

  9. Range effects of the Coulombic forces on structures, thermodynamic properties and potential energy landscapes: (KCl)32 and related systems

    NASA Astrophysics Data System (ADS)

    Wang, Chengju; Stephen Berry, R.; Jellinek, Julius

    2012-05-01

    By introducing two shielding parameters into the Coulombic part of the Coulomb plus Born-Mayer potential originally developed for (KCl)n systems, we study the effects of the range of the Coulombic interactions on the structures, thermodynamic properties and the potential energy landscapes of binary ionically bonded systems as illustrated by the case of n = 32. Our calculations show that shortening of the Coulomb interaction range leads to a decrease in the energy of the most stable structure, and the structure itself changes from the rocksalt cubic to a hollow cage type. The energy range, in which the heat capacity exhibits a negative value, gradually narrows and eventually disappears. The number of stationary points on the potential energy surface increases, and their energies get spread over a larger interval. The extent of the Coulombic interaction also affects the energy difference (gap) between the most stable structure and the structure that follows it. All these changes translate into changes in the melting behavior of the system. An analysis of the melting behavior as a function of the range of the Coulombic interaction is presented and correlated with the range-dependent changes in the topography of the underlying potential energy surface.

  10. Anisotropic reflectance is a major correction to energy-balance estimates of evapotranspiration in a semi-arid landscape

    NASA Astrophysics Data System (ADS)

    Mariotto, I.; Gutschick, V. P.; Clason, D. L.

    2009-12-01

    Modeling spatial variation of evapotranspiration (ET) over heterogeneous landscapes is a difficult task for hydrologists, agronomists, and meteorologists. The application of energy balance algorithms to remotely sensed imagery often fails in properly discriminating ET over spectrally diverse land covers for the complexity of modeling the surface roughness. Furthermore, the assumption of a horizontally homogeneous Lambertian surface reflecting energy equally in all directions affects the albedo and vegetation index calculations. The objective of this study is to improve the accuracy of the Surface Energy Balance Algorithm for Land (SEBAL) for estimating ET from ASTER datasets by analyzing the spatial variation of anisotropic reflectance and surface roughness among different plant species-dominated grasslands, shrublands, and dunelands in Southern New Mexico. The degree to which land cover surfaces are anisotropic is assessed by applying a wavelength-dependent non-Lambertian topographic transformation with the Minnaert function. Surface roughness is modeled using a land cover map in conjunction with the fractional vegetation cover derived from MSAVI. SEBAL with one or both modifications showed stronger agreement with the Eddy-Covariance measurements than the non-modified SEBAL. Furthermore, the former showed higher, intermediate, and lower ET values among grasslands, schrublands, and dunelands respectively, while the latter resulted in more homogeneous ET values among land covers and in overestimation of ET over dunelands and underestimation over grasslands. Multiple pairwise land covers comparisons of ET means showed higher potential of the corrected model in discriminating ET. This study suggests that some assumptions in SEBAL tend to inadvertently homogenize ET on these diverse landscapes.

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

    SciTech Connect

    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

  12. 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

  13. 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

  14. Volume Expansion Measurements in Metallic Liquids and Their Relation to Fragility and Glass Forming Ability: An Energy Landscape Interpretation

    NASA Astrophysics Data System (ADS)

    Bendert, J. C.; Gangopadhyay, A. K.; Mauro, N. A.; Kelton, K. F.

    2012-11-01

    Recent studies of Cu-Zr glasses have reported a rapid variation in the amorphous phase density near the optimal glass forming compositions, supporting the belief that the densest liquids are also the best glass formers. Here, we show that the measured densities of the Cu-Zr liquids at higher temperatures are not peaked sharply near these compositions, but the volume expansivities are. Theoretical studies have shown that the expansivity correlates with fragility near Tg; the experimental results presented here show that at high temperature they become anticorrelated. From energy landscape arguments, this indicates the existence of a crossover temperature for the expansivity-fragility correlation that scales inversely with the liquid fragility. These results lead to an improved understanding of the high temperature properties of liquids that form glasses and suggest a new method for identifying the best glass forming compositions within an alloy system from the properties of the equilibrium liquids.

  15. Volume expansion measurements in metallic liquids and their relation to fragility and glass forming ability: an energy landscape interpretation.

    PubMed

    Bendert, J C; Gangopadhyay, A K; Mauro, N A; Kelton, K F

    2012-11-01

    Recent studies of Cu-Zr glasses have reported a rapid variation in the amorphous phase density near the optimal glass forming compositions, supporting the belief that the densest liquids are also the best glass formers. Here, we show that the measured densities of the Cu-Zr liquids at higher temperatures are not peaked sharply near these compositions, but the volume expansivities are. Theoretical studies have shown that the expansivity correlates with fragility near T(g); the experimental results presented here show that at high temperature they become anticorrelated. From energy landscape arguments, this indicates the existence of a crossover temperature for the expansivity-fragility correlation that scales inversely with the liquid fragility. These results lead to an improved understanding of the high temperature properties of liquids that form glasses and suggest a new method for identifying the best glass forming compositions within an alloy system from the properties of the equilibrium liquids. PMID:23215298

  16. Energy landscape of the finite-size mean-field 2-spin spherical model and topology trivialization

    NASA Astrophysics Data System (ADS)

    Mehta, Dhagash; Hauenstein, Jonathan D.; Niemerg, Matthew; Simm, Nicholas J.; Stariolo, Daniel A.

    2015-02-01

    Motivated by the recently observed phenomenon of topology trivialization of potential energy landscapes (PELs) for several statistical mechanics models, we perform a numerical study of the finite-size 2-spin spherical model using both numerical polynomial homotopy continuation and a reformulation via non-Hermitian matrices. The continuation approach computes all of the complex stationary points of this model while the matrix approach computes the real stationary points. Using these methods, we compute the average number of stationary points while changing the topology of the PEL as well as the variance. Histograms of these stationary points are presented along with an analysis regarding the complex stationary points. This work connects topology trivialization to two different branches of mathematics: algebraic geometry and catastrophe theory, which is fertile ground for further interdisciplinary research.

  17. 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.

  18. Unusual biophysics of intrinsically disordered proteins.

    PubMed

    Uversky, Vladimir N

    2013-05-01

    Research of a past decade and a half leaves no doubt that complete understanding of protein functionality requires close consideration of the fact that many functional proteins do not have well-folded structures. These intrinsically disordered proteins (IDPs) and proteins with intrinsically disordered protein regions (IDPRs) are highly abundant in nature and play a number of crucial roles in a living cell. Their functions, which are typically associated with a wide range of intermolecular interactions where IDPs possess remarkable binding promiscuity, complement functional repertoire of ordered proteins. All this requires a close attention to the peculiarities of biophysics of these proteins. In this review, some key biophysical features of IDPs are covered. In addition to the peculiar sequence characteristics of IDPs these biophysical features include sequential, structural, and spatiotemporal heterogeneity of IDPs; their rough and relatively flat energy landscapes; their ability to undergo both induced folding and induced unfolding; the ability to interact specifically with structurally unrelated partners; the ability to gain different structures at binding to different partners; and the ability to keep essential amount of disorder even in the bound form. IDPs are also characterized by the "turned-out" response to the changes in their environment, where they gain some structure under conditions resulting in denaturation or even unfolding of ordered proteins. It is proposed that the heterogeneous spatiotemporal structure of IDPs/IDPRs can be described as a set of foldons, inducible foldons, semi-foldons, non-foldons, and unfoldons. They may lose their function when folded, and activation of some IDPs is associated with the awaking of the dormant disorder. It is possible that IDPs represent the "edge of chaos" systems which operate in a region between order and complete randomness or chaos, where the complexity is maximal. This article is part of a Special Issue

  19. Geometric intrinsic symmetries

    SciTech Connect

    Gozdz, A. Szulerecka, A.; Pedrak, A.

    2013-08-15

    The problem of geometric symmetries in the intrinsic frame of a many-body system (nucleus) is considered. An importance of symmetrization group notion is discussed. Ageneral structure of the intrinsic symmetry group structure is determined.

  20. 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.

  1. 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.

  2. 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.

  3. Using remote sensing energy balance and evapotranspiration to characterize montane landscape vegetation with focus on grass and pasture lands

    NASA Astrophysics Data System (ADS)

    Pôças, Isabel; Cunha, Mário; Pereira, Luís S.; Allen, Richard G.

    2013-04-01

    Water and energy balance interactions with vegetation in mountainous terrain are influenced by topographic effects, spatial variation in vegetation type and density, and water availability. This is the case for the mountainous areas of northern Portugal, where ancestral irrigated meadows (lameiros) are a main component of a complex vegetation mosaic. The widely used surface energy balance model METRIC was applied to four Landsat images to determine the spatial and temporal distribution of the energy balance terms in the identified land cover types (LCT). A discussion on the variability of evapotranspiration (ET) through the various vegetation types was supported by a comparison between the respective crop coefficients and those available in the literature corresponding to the LCT, which has shown the appropriateness of METRIC estimates of ET. METRIC products derived from images of May and June - NDVI, surface temperature, net radiation, soil heat flux, sensible heat flux, and ET - were used to characterize the LCTs, through application of principal component analysis. Three principal components explained the variance of observed variables and their varimax rotated loadings allowed a good explanation of the behaviour of the explanatory variables in association with the LCTs. Information gained contributes to improve the characterization of the study area and may further support conservation and management of these mountain landscapes.

  4. 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.

  5. 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

  6. Intrinsic structural defects in monolayer molybdenum disulfide

    SciTech Connect

    Zhou, Wu; Idrobo Tapia, Juan C

    2013-01-01

    Monolayer molybdenum disulfide (MoS2) is a two-dimensional direct band gap semiconductor with distinctive mechanical, electronic, optical and chemical properties that can be utilized for novel nanoelectronics and optoelectronics devices. The performance of these electronic devices strongly depends on the quality and defect morphology of the MoS2 layers. Yet, little is known about the atomic structure of defects present in monolayer MoS2 and their influences on the material properties. Here we provide a systematic study of various intrinsic structural defects, including point defects, grain boundaries, and edges, in chemical vapor phase grown monolayer MoS2 via direct atomic resolution imaging, and explore their energy landscape and electronic properties using first-principles calculations. We discover that one-dimensional metallic wires can be created via two different types of 60 grain boundaries consisting of distinct 4-fold ring chains. A new type of edge reconstruction, representing a transition state during growth, was also identified, providing insights into the material growth mechanism. The atomic scale study of structural defects presented here brings new opportunities to tailor the properties of MoS2 via controlled synthesis and defect engineering.

  7. 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).

  8. 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).

  9. Intrinsic anion oxidation potentials.

    PubMed

    Johansson, Patrik

    2006-11-01

    Anions of lithium battery salts have been investigated by electronic structure calculations with the objective to find a computational measure to correlate with the observed (in)stability of nonaqueous lithium battery electrolytes vs oxidation often encountered in practice. Accurate prediction of intrinsic anion oxidation potentials is here made possible by computing the vertical free energy difference between anion and neutral radical (Delta Gv) and further strengthened by an empirical correction using only the anion volume as a parameter. The 6-311+G(2df,p) basis set, the VSXC functional, and the C-PCM SCRF algorithm were used. The Delta Gv calculations can be performed using any standard computational chemistry software. PMID:17078600

  10. ''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

  11. Predominance of multielectron processes contributing to the intrinsic spectra of low-energy Auger transitions in copper and gold

    SciTech Connect

    Mukherjee, S. F.; Shastry, K.; Weiss, A. H.

    2011-10-15

    Positron-annihilation-induced Auger electron spectroscopy (PAES) was used to obtain Cu and Au Auger spectra that are free of primary-beam-induced backgrounds by impinging the positrons at an energy below the secondary-electron-emission threshold. The removal of the core electron via annihilation in the PAES process resulted in the elimination of postcollision effects. The spectra indicate that there is an intense low-energy tail (LET) associated with the Auger peak that extends all the way to 0 eV. The LET is interpreted as indicative of processes in which filling of the core hole by a valence electron results in the ejection of two or more valence electrons which share the energy of the conventional core-valence-valence Auger electron.

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

    PubMed

    Seki, Kazuhiko; Bagchi, Biman

    2015-11-21

    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. PMID:26590530

  13. 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

  14. Landscape Architecture.

    ERIC Educational Resources Information Center

    American School and University, 1985

    1985-01-01

    Members of the American Society of Landscape Architects shape open spaces on the campuses of Georgetown University, District of Columbia; the University of Missouri; Auraria Higher Education Center, Colorado; and the University of Michigan. (MLF)

  15. 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...

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

    PubMed Central

    Radak, Brian K.; Huang, Ming; Wong, Kin-Yiu

    2014-01-01

    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. PMID:24505217

  17. 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.

  18. 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.

  19. 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.

  20. Surveying a complex potential energy landscape: Overcoming broken ergodicity using basin-sampling

    NASA Astrophysics Data System (ADS)

    Wales, David J.

    2013-10-01

    A new basin-sampling scheme is introduced to obtain equilibrium thermodynamic properties by combining results from global optimisation and parallel tempering calculations. Regular minimisation is used to obtain a two-dimensional density of states. A model anharmonic form is optimised using a multihistogram approach for potential energy bins corresponding to local minima, connecting the results obtained for low and high temperatures. This procedure provides accurate densities of states and thermodynamic properties for benchmark atomic clusters exhibiting broken ergodicity. It can also be used to calculate the potential energy density of local minima for distinct permutation-inversion isomers and distinct structures.

  1. 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.

  2. 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.

  3. 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...

  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. 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.

  6. Emergent functionality of nucleobase radical cations in duplex DNA: prediction of reactivity using qualitative potential energy landscapes.

    PubMed

    Joseph, Joshy; Schuster, Gary B

    2006-05-10

    The one-electron oxidation of a series of DNA oligonucleotides was examined. Each oligomer contains a covalently linked anthraquinone (AQ) group. Irradiation of the AQ group with near-UV light results in a one-electron oxidation of the DNA that generates a radical cation (electron "hole"). The radical cation migrates through the DNA by a hopping mechanism and is trapped by reaction with water or molecular oxygen, which results in chemical reaction at particular nucleobases. This reaction is revealed as strand cleavage when the irradiated oligonucleotide is treated with piperidine. The specific oligomers examined reveal the existence of three categories of nucleobase sequences: charge shuttles, charge traps, and barriers to charge migration. The characterization of a sequence is not independent of the identity of other sequences in the oligonucleotide, and for this reason, the function of a particular sequence emerges from an analysis of the entire structure. Qualitative potential energy landscapes are introduced as a tool to assist in the rationalization and prediction of the reactions of nucleobases in oxidized DNA. PMID:16669676

  7. Low-coverage surface diffusion in complex periodic energy landscapes. II. Analytical solution for systems with asymmetric hops

    NASA Astrophysics Data System (ADS)

    Gosálvez, Miguel A.; Otrokov, Mikhail M.; Ferrando, Nestor; Ryabishchenkova, Anastasia G.; Ayuela, Andres; Echenique, Pedro M.; Chulkov, Evgueni V.

    2016-05-01

    This is part II in a series of two papers that introduce a general expression for the tracer diffusivity in complex, periodic energy landscapes with M distinct hop rates in one-, two-, and three-dimensional diluted systems (low coverage, single-tracer limit). While Part I [Gosálvez et al., Phys. Rev. B 93, 075429 (2016), 10.1103/PhysRevB.93.075429] focuses on the analysis of diffusion in systems where the end sites of the hops are located symmetrically with respect to the hop origins (symmetric hops), as encountered in many ideal surfaces and bulk materials, this report (Part II) presents a more general approach to determining the tracer diffusivity in systems where the end sites can be located asymmetrically with respect to the hop origins (asymmetric hops), as observed in reconstructed and/or chemically modified surfaces and/or bulk materials. The obtained diffusivity formulas for numerous systems are validated against kinetic Monte Carlo simulations and previously reported analytical expressions based on the continuous-time random walk (CTRW) method. The proposed method corrects some of the CTRW formulas and provides new expressions for difficult cases that have not been solved earlier. This demonstrates the ability of the proposed formalism to describe tracer diffusion.

  8. Utilizing Force Field Methods to Explore Potential Energy Landscapes of Flexible Biomolecules

    NASA Astrophysics Data System (ADS)

    Davis, Zachary S.; Carr, Joanne M.; Tan, Ivan Y. W.; Wales, David J.; Zwier, Timothy S.

    2012-06-01

    Spectroscopic studies of single conformations of flexible biomolecules are providing considerable new physical insight to their conformational preferences. Such studies are done against a backdrop of a full potential energy surface (PES) that has great complexity, often containing thousands of minima and an even greater number of transition states separating them. Often the relationship between experiment and the full PES is unclear. In this context, it would be extremely helpful to have predictions and summaries of the PES that enable comparisons from one molecule to the next, and of one molecule under different conditions. By utilizing the speed of force field calculations, the potential energy surface may be thoroughly explored, including both minima and transition states, in a computationally inexpensive manner. As minima and transition states are found, they are added to a disconnectivity graph, a summary of the entire potential energy surface in which the different minima are connected to one another by one or more transition states, which are grouped by energy. Disconnectivity graphs have been prepared for the flexible hexamide Z-(Gly)_5-NHMe (where the Z-cap is a benzocarboxy substituent), which has been studied experimentally in isolated form using single-conformation spectroscopy. Disconnectivity graphs of both the isolated and solvated molecule provide insight to the solvent-induced conformational differences. In addition, the peptide Ac-Phe-Ala-NHMe has been modeled using all α-amino acids, all β-amino acids, and all γ-amino acids. As the flexibility and complexity of the triamide increases, the disconnectivity graphs illuminate changes in the relationships between different conformational families as well as any changes in the height of the barriers between those families. These results will be compared to previous results from single-conformation spectroscopy on this series.

  9. Free energy landscapes of encounter complexes in protein-protein association.

    PubMed Central

    Camacho, C J; Weng, Z; Vajda, S; DeLisi, C

    1999-01-01

    We report the computer generation of a high-density map of the thermodynamic properties of the diffusion-accessible encounter conformations of four receptor-ligand protein pairs, and use it to study the electrostatic and desolvation components of the free energy of association. Encounter complex conformations are generated by sampling the translational/rotational space of the ligand around the receptor, both at 5-A and zero surface-to-surface separations. We find that partial desolvation is always an important effect, and it becomes dominant for complexes in which one of the reactants is neutral or weakly charged. The interaction provides a slowly varying attractive force over a small but significant region of the molecular surface. In complexes with no strong charge complementarity this region surrounds the binding site, and the orientation of the ligand in the encounter conformation with the lowest desolvation free energy is similar to the one observed in the fully formed complex. Complexes with strong opposite charges exhibit two types of behavior. In the first group, represented by barnase/barstar, electrostatics exerts strong orientational steering toward the binding site, and desolvation provides some added adhesion within the local region of low electrostatic energy. In the second group, represented by the complex of kallikrein and pancreatic trypsin inhibitor, the overall stability results from the rather nonspecific electrostatic attraction, whereas the affinity toward the binding region is determined by desolvation interactions. PMID:10049302

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

    PubMed

    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

  11. 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

  12. Dynamics and the free-energy landscape of proteins, explored with the Mössbauer effect and quasi-elastic neutron scattering.

    PubMed

    Frauenfelder, Hans; Young, Robert D; Fenimore, Paul W

    2013-10-24

    The Mössbauer effect and quasi-elastic neutron scattering (QENS) from hydrated proteins yield sharp elastic lines that are accompanied by broad wings. Conventionally, the elastic line and the broad wings are treated as separate phenomena. We show that there is no separation; the entire spectrum consists of Lorentzians with the natural line width. In protein crystals, the shifts of the individual lines from the elastic center above about 150 K are caused by beta fluctuations in the hydration shell. Vibrations cause shifts in the entire temperature range but are best seen below about 150 K. We construct a microscopic model for the dynamics that is based on a random walk of the proteins in their free-energy landscape. The model yields approximate values for the steps in the energy landscape. Remarkably, the quantum electrodynamic concept of gamma rays is needed to justify the model. PMID:23962200

  13. 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.

  14. Effect of salt bridges on the energy landscape of a model protein

    NASA Astrophysics Data System (ADS)

    Wales, David J.; Dewsbury, Peter E. J.

    2004-11-01

    The effect of introducing salt bridges (gatekeepers) into an off-lattice three-color, 46-bead model protein is investigated in terms of the effect on global optimization statistics. The global minima for all the gatekeepers that exhibited faster folding in previous molecular dynamics studies are located more rapidly than for the original potential, although the global minimum itself may change. Visualization of the underlying potential energy surface using disconnectivity graphs reveals that the gatekeepers exhibit structure intermediate between the original potential and a Gō model. Competition between low-lying minima and the global minimum is reduced in the gatekeepers compared to the original potential, and interconversion barriers are generally smaller.

  15. Analyzing the components of the free-energy landscape in a calcium selective ion channel by Widom's particle insertion method

    NASA Astrophysics Data System (ADS)

    Boda, Dezső; Giri, Janhavi; Henderson, Douglas; Eisenberg, Bob; Gillespie, Dirk

    2011-02-01

    The selectivity filter of the L-type calcium channel works as a Ca2 + binding site with a very large affinity for Ca2 + versus Na+. Ca2 + 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 (Ca2 +). 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 Ca2 + 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.

  16. Calculation of Free Energy Landscape in Multi-Dimensions with Hamiltonian-Exchange Umbrella Sampling on Petascale Supercomputer.

    PubMed

    Jiang, Wei; Luo, Yun; Maragliano, Luca; Roux, Benoît

    2012-11-13

    An extremely scalable computational strategy is described for calculations of the potential of mean force (PMF) in multidimensions on massively distributed supercomputers. The approach involves coupling thousands of umbrella sampling (US) simulation windows distributed to cover the space of order parameters with a Hamiltonian molecular dynamics replica-exchange (H-REMD) algorithm to enhance the sampling of each simulation. In the present application, US/H-REMD is carried out in a two-dimensional (2D) space and exchanges are attempted alternatively along the two axes corresponding to the two order parameters. The US/H-REMD strategy is implemented on the basis of parallel/parallel multiple copy protocol at the MPI level, and therefore can fully exploit computing power of large-scale supercomputers. Here the novel technique is illustrated using the leadership supercomputer IBM Blue Gene/P with an application to a typical biomolecular calculation of general interest, namely the binding of calcium ions to the small protein Calbindin D9k. The free energy landscape associated with two order parameters, the distance between the ion and its binding pocket and the root-mean-square deviation (rmsd) of the binding pocket relative the crystal structure, was calculated using the US/H-REMD method. The results are then used to estimate the absolute binding free energy of calcium ion to Calbindin D9k. The tests demonstrate that the 2D US/H-REMD scheme greatly accelerates the configurational sampling of the binding pocket, thereby improving the convergence of the potential of mean force calculation. PMID:26605623

  17. Calculation of Free Energy Landscape in Multi-Dimensions with Hamiltonian-Exchange Umbrella Sampling on Petascale Supercomputer.

    PubMed

    Jiang, Wei; Luo, Yun; Maragliano, Luca; Roux, Benoît

    2012-11-13

    An extremely scalable computational strategy is described for calculations of the potential of mean force (PMF) in multidimensions on massively distributed supercomputers. The approach involves coupling thousands of umbrella sampling (US) simulation windows distributed to cover the space of order parameters with a Hamiltonian molecular dynamics replica-exchange (H-REMD) algorithm to enhance the sampling of each simulation. In the present application, US/H-REMD is carried out in a two-dimensional (2D) space and exchanges are attempted alternatively along the two axes corresponding to the two order parameters. The US/H-REMD strategy is implemented on the basis of parallel/parallel multiple copy protocol at the MPI level, and therefore can fully exploit computing power of large-scale supercomputers. Here the novel technique is illustrated using the leadership supercomputer IBM Blue Gene/P with an application to a typical biomolecular calculation of general interest, namely the binding of calcium ions to the small protein Calbindin D9k. The free energy landscape associated with two order parameters, the distance between the ion and its binding pocket and the root-mean-square deviation (rmsd) of the binding pocket relative the crystal structure, was calculated using the US/H-REMD method. The results are then used to estimate the absolute binding free energy of calcium ion to Calbindin D9k. The tests demonstrate that the 2D US/H-REMD scheme greatly accelerates the configurational sampling of the binding pocket, thereby improving the convergence of the potential of mean force calculation.

  18. Intrinsic Analysis Training Manual.

    ERIC Educational Resources Information Center

    Gow, Doris T.

    This manual is for the training of linking agents between Education R&D and schools and for training teachers in the process of intrinsic analysis of curriculum materials. Intrinsic analysis means analysis of the instruction or process through examination of the materials, or artifacts, including teacher and student materials, developer's…

  19. Probing the energy landscape of activation gating of the bacterial potassium channel KcsA.

    PubMed

    Linder, Tobias; de Groot, Bert L; Stary-Weinzinger, Anna

    2013-01-01

    The bacterial potassium channel KcsA, which has been crystallized in several conformations, offers an ideal model to investigate activation gating of ion channels. In this study, essential dynamics simulations are applied to obtain insights into the transition pathways and the energy profile of KcsA pore gating. In agreement with previous hypotheses, our simulations reveal a two phasic activation gating process. In the first phase, local structural rearrangements in TM2 are observed leading to an intermediate channel conformation, followed by large structural rearrangements leading to full opening of KcsA. Conformational changes of a highly conserved phenylalanine, F114, at the bundle crossing region are crucial for the transition from a closed to an intermediate state. 3.9 µs umbrella sampling calculations reveal that there are two well-defined energy barriers dividing closed, intermediate, and open channel states. In agreement with mutational studies, the closed state was found to be energetically more favorable compared to the open state. Further, the simulations provide new insights into the dynamical coupling effects of F103 between the activation gate and the selectivity filter. Investigations on individual subunits support cooperativity of subunits during activation gating.

  20. 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.

  1. Exploring the free-energy landscapes of biological systems with steered molecular dynamics.

    PubMed

    Chen, L Y

    2011-04-01

    We perform steered molecular dynamics (SMD) simulations and use the Brownian dynamics fluctuation-dissipation-theorem (BD-FDT) to accurately compute the free-energy profiles for several biophysical processes of fundamental importance: hydration of methane and cations, binding of benzene to T4-lysozyme L99A mutant, and permeation of water through aquaglyceroporin. For each system, the center-of-mass of the small molecule (methane, ion, benzene, and water, respectively) is steered (pulled) at a given speed over a period of time, during which the system transitions from one macroscopic state/conformation (State A) to another one (State B). The mechanical work of pulling the system is measured during the process, sampling a forward pulling path. Then the reverse pulling is conducted to sample a reverse path from B back to A. Sampling a small number of forward and reverse paths, we are able to accurately compute the free-energy profiles for all the afore-listed systems that represent various important aspects of biological physics. The numerical results are in excellent agreement with the experimental data and/or other computational studies available in the literature.

  2. Biophysical approach for studying the MinD protein dynamics and energy landscape: a novel use of the spot tracking technique

    NASA Astrophysics Data System (ADS)

    Kanthang, P.; Ngamsaad, W.; Nuttavut, N.; Triampo, W.; Triampo, D.; Krittanai, C.

    2011-07-01

    The dynamics of MinD proteins have been acknowledged as playing a central role in accurate cell division. In our study, a spot tracking technique (STT) was applied to track motion and quantitatively characterize the dynamic behavior of MinD proteins on the level of particle cluster in Escherichia coli. We focused on the time and spatial distribution of MinD proteins. With the STT technique, the main quantitative results are twofold: (i) dynamic local and global pattern formations and (ii) energy landscape. The overall MinD cluster motion is governed by two dynamical time scales, namely the (slow) trapping time (~26 s) that appears at the cell poles, and the (fast) switching time (~1-2 s) which emerges between the cell poles. MinD cluster motion at the polar zones performs subdiffusion. The energy landscape is found to be two wells and one barrier. These energy landscape results are to relate with the memory effect of GFP-MinD cluster motion, measuring the PSD exponent approximately 1.57 (α ~ 0.57) corresponding to the estimated potential depth U0 ~ 1.75kBT.

  3. Exploring the potential energy landscape of the Thomson problem via Newton homotopies

    NASA Astrophysics Data System (ADS)

    Mehta, Dhagash; Chen, Tianran; Morgan, John W. R.; Wales, David J.

    2015-05-01

    Locating the stationary points of a real-valued multivariate potential energy function is an important problem in many areas of science. This task generally amounts to solving simultaneous nonlinear systems of equations. While there are several numerical methods that can find many or all stationary points, they each exhibit characteristic problems. Moreover, traditional methods tend to perform poorly near degenerate stationary points with additional zero Hessian eigenvalues. We propose an efficient and robust implementation of the Newton homotopy method, which is capable of quickly sampling a large number of stationary points of a wide range of indices, as well as degenerate stationary points. We demonstrate our approach by applying it to the Thomson problem. We also briefly discuss a possible connection between the present work and Smale's 7th problem.

  4. Quantifying Nonnative Interactions in the Protein-Folding Free-Energy Landscape.

    PubMed

    Mouro, Paulo Ricardo; de Godoi Contessoto, Vinícius; Chahine, Jorge; Junio de Oliveira, Ronaldo; Pereira Leite, Vitor Barbanti

    2016-07-26

    Protein folding is a central problem in biological physics. Energetic roughness is an important aspect that controls protein-folding stability and kinetics. The roughness is associated with conflicting interactions in the protein and is also known as frustration. Recent studies indicate that an addition of a small amount of energetic frustration may enhance folding speed for certain proteins. In this study, we have investigated the conditions under which frustration increases the folding rate. We used a Cα structure-based model to simulate a group of proteins. We found that the free-energy barrier at the transition state (ΔF) correlates with nonnative-contact variation (ΔA), and the simulated proteins are clustered according to their fold motifs. These findings are corroborated by the Clementi-Plotkin analytical model. As a consequence, the optimum frustration regime for protein folding can be predicted analytically. PMID:27463131

  5. 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.

  6. Combined inhibitor free-energy landscape and structural analysis reports on the mannosidase conformational coordinate.

    PubMed

    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

    2014-01-20

    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.

  7. 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.

  8. 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.

  9. 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.

  10. Ionic Strength Modulation of the Free Energy Landscape of Aβ40 Peptide Fibril Formation.

    PubMed

    Abelein, Axel; Jarvet, Jüri; Barth, Andreas; Gräslund, Astrid; Danielsson, Jens

    2016-06-01

    Protein misfolding and formation of cross-β structured amyloid fibrils are linked to many neurodegenerative disorders. Although recently developed quantitative approaches have started to reveal the molecular nature of self-assembly and fibril formation of proteins and peptides, it is yet unclear how these self-organization events are precisely modulated by microenvironmental factors, which are known to strongly affect the macroscopic aggregation properties. Here, we characterize the explicit effect of ionic strength on the microscopic aggregation rates of amyloid β peptide (Aβ40) self-association, implicated in Alzheimer's disease. We found that physiological ionic strength accelerates Aβ40 aggregation kinetics by promoting surface-catalyzed secondary nucleation reactions. This promoted catalytic effect can be assigned to shielding of electrostatic repulsion between monomers on the fibril surface or between the fibril surface itself and monomeric peptides. Furthermore, we observe the formation of two different β-structured states with similar but distinct spectroscopic features, which can be assigned to an off-pathway immature state (Fβ*) and a mature stable state (Fβ), where salt favors formation of the Fβ fibril morphology. Addition of salt to preformed Fβ* accelerates transition to Fβ, underlining the dynamic nature of Aβ40 fibrils in solution. On the basis of these results we suggest a model where salt decreases the free-energy barrier for Aβ40 folding to the Fβ state, favoring the buildup of the mature fibril morphology while omitting competing, energetically less favorable structural states. PMID:27171340

  11. 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.

  12. Deciphering the energy landscape of the interaction uranyl-DCP with antibodies using dynamic force spectroscopy.

    PubMed

    Teulon, Jean-Marie; Parot, Pierre; Odorico, Michael; Pellequer, Jean-Luc

    2008-11-15

    Previous studies on molecular recognition of uranyl-DCP (dicarboxy-phenanthroline chelator) compound by two distinct monoclonal antibodies (Mabs U04S and U08S) clearly showed the presence of a biphasic shape in Bell-Evans' plots and an accentuated difference in slopes at the high loading rates. To further explore the basis in the slope difference, we have performed complementary experiments using antibody PHE03S, raised against uranyl-DCP but, presenting a strong cross-reactivity toward the DCP chelator. This work allowed us to obtain a reallocation of the respective contributions of the metal ion itself and that of the chelator. Results led us to propose a 2D schematic model representing two energy barriers observed in the systems Mabs U04S- and U08S-[UO(2)-DCP] where the outer barrier characterizes the interaction between UO(2) and Mab whereas the inner barrier characterizes the interaction between DCP and Mab. Using dynamic force spectroscopy, it is thus possible to dissect molecular interactions during the unbinding between proteins and ligands.

  13. Free-energy landscape and characteristic forces for the initiation of DNA unzipping.

    PubMed

    Mentes, Ahmet; Florescu, Ana Maria; Brunk, Elizabeth; Wereszczynski, Jeff; Joyeux, Marc; Andricioaei, Ioan

    2015-04-01

    DNA unzipping, the separation of its double helix into single strands, is crucial in modulating a host of genetic processes. Although the large-scale separation of double-stranded DNA has been studied with a variety of theoretical and experimental techniques, the minute details of the very first steps of unzipping are still unclear. Here, we use atomistic molecular-dynamics simulations, coarse-grained simulations, and a statistical-mechanical model to study the initiation of DNA unzipping by an external force. Calculation of the potential of mean force profiles for the initial separation of the first few terminal basepairs in a DNA oligomer revealed that forces ranging between 130 and 230 pN are needed to disrupt the first basepair, and these values are an order of magnitude larger than those needed to disrupt basepairs in partially unzipped DNA. The force peak has an echo of ∼50 pN at the distance that unzips the second basepair. We show that the high peak needed to initiate unzipping derives from a free-energy basin that is distinct from the basins of subsequent basepairs because of entropic contributions, and we highlight the microscopic origin of the peak. To our knowledge, our results suggest a new window of exploration for single-molecule experiments. PMID:25863064

  14. 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.

  15. 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.

  16. 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.

  17. The Free Energy Landscape of GABA Binding to a Pentameric Ligand-Gated Ion Channel and Its Disruption by Mutations.

    PubMed

    Comitani, Federico; Limongelli, Vittorio; Molteni, Carla

    2016-07-12

    Pentameric ligand-gated ion channels (pLGICs) of the Cys-loop superfamily are important neuroreceptors that mediate fast synaptic transmission. They are activated by the binding of a neurotransmitter, but the details of this process are still not fully understood. As a prototypical pLGIC, here we choose the insect resistance to dieldrin (RDL) receptor involved in resistance to insecticides and investigate the binding of the neurotransmitter GABA to its extracellular domain at the atomistic level. We achieve this by means of μ-sec funnel-metadynamics simulations, which efficiently enhance the sampling of bound and unbound states by using a funnel-shaped restraining potential to limit the exploration in the solvent. We reveal the sequence of events in the binding process from the capture of GABA from the solvent to its pinning between the charged residues Arg111 and Glu204 in the binding pocket. We characterize the associated free energy landscapes in the wild-type RDL receptor and in two mutant forms, where the key residues Arg111 and Glu204 are mutated to Ala. Experimentally these mutations produce nonfunctional channels, which is reflected in the reduced ligand binding affinities due to the loss of essential interactions. We also analyze the dynamical behavior of the crucial loop C, whose opening allows the access of GABA to the binding site and closure locks the ligand into the protein. The RDL receptor shares structural and functional features with other pLGICs; hence, our work outlines a valuable protocol to study the binding of ligands to pLGICs beyond conventional docking and molecular dynamics techniques. PMID:27228114

  18. Learning Landscapes

    ERIC Educational Resources Information Center

    Noyes, Andrew

    2004-01-01

    This article explores the metaphor of learning landscapes, a tool developed in order to map children's experiences of, and attitudes to, learning (mathematics) before and after the transfer from primary to secondary school. Firstly, the continuing problems surrounding school transfer and why a re-examination of this is required are considered.…

  19. Multi-scale Characterization of the Energy Landscape of Proteins with Application to the C3d/Efb-C Complex

    PubMed Central

    Haspel, Nurit; Geisbrecht, Brian V.; Lambris, John; Kavraki, Lydia

    2009-01-01

    We present a novel multi-level methodology to explore and characterize the low energy landscape and the thermodynamics of proteins. Traditional conformational search methods typically explore only a small portion of the conformational space of proteins and are hard to apply to large proteins due to the large amount of calculations required. In our multi-scale approach, we first provide an initial characterization of the equilibrium state ensemble of a protein using an efficient computational conformational sampling method. We then enrich the obtained ensemble by performing short Molecular Dynamics (MD) simulations on selected conformations from the ensembles as starting points. To facilitate the analysis of the results we project the resulting conformations on a low-dimensional landscape to efficiently focus on important interactions and examine low energy regions. This methodology provides a more extensive sampling of the low energy landscape than an MD simulation starting from a single crystal structure as it explores multiple trajectories of the protein. This enables us to obtain a broader view of the dynamics of proteins and it can help in understanding complex binding, improving docking results and more. In this work we apply the methodology to provide an extensive characterization of the bound complexes of the C3d fragment of human Complement component C3 and one of its powerful bacterial inhibitors, the inhibitory domain of Staphylococcus aureus extra-cellular fibrinogen-binding domain (Efb-C) and two of its mutants. We characterize several important interactions along the binding interface and define low free energy regions in the three complexes. PMID:19899169

  20. 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.

  1. Utility of a Thermal-Based Two-Source Energy Balance Model for Estimating Surface Fluxes over a Wide Variety of Landscapes

    NASA Astrophysics Data System (ADS)

    Kustas, W. P.; Anderson, M. C.; Cammalleri, C.; Alfieri, J. G.; Semmens, K. A.; Prueger, J. H.; Hain, C.; Gao, F.; Kongoli, C.; Andreu, A.; Han, K.; Xia, T.

    2014-12-01

    Many landscapes are comprised of a variety of vegetation types with different canopy structure, rooting depth, physiological characteristics, soil/substrate conditions, etc. Even in agricultural regions, different management practices, including crop rotations, irrigation scheduling, planting density, seed varieties, tilling practices, and other factors result in complex patterns in vegetation growth stages, canopy cover, canopy architecture, cropping densities and understory soil/substrate properties. This variability at the canopy, field and landscape scale, makes it very challenging to reliably quantify spatially-distributed surface fluxes. This paper describes a robust but relatively simple thermal-based energy balance model that parameterizes the key soil/substrate and vegetation exchange processes affecting the radiative balance and turbulent energy transport with the overlying atmosphere. The thermal-based model, called the Two-Source Energy Balance (TSEB) model solves for the soil/substrate and canopy temperatures that achieves a balance in the radiation and turbulent heat flux exchange with the lower atmosphere for the soil/substrate and vegetation elements. The TSEB scheme permits interaction between soil/substrate and canopy elements which are both are coupled to the atmosphere via canopy-air temperature that is strongly correlated to the aerodynamic surface temperature. In doing so the TSEB modeling framework is applicable to a wide range in atmospheric and land cover conditions. An overview of applications of the TSEB modeling framework to a variety of landscapes will be presented that include both natural and agricultural ecosystems having a soil/substrate with standing water (flooded), snow covered and vegetated (canopy understory) requiring different levels of refinements to the TSEB formulations for these unique land cover conditions. In addition, examples using a modeling framework that allows the TSEB scheme to be applied at regional scales using

  2. 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.

  3. 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

  4. 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. PMID:15863622

  5. 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…

  6. Accidental inflation in the landscape

    SciTech Connect

    Blanco-Pillado, Jose J.; Metallinos, Konstantinos; Gomez-Reino, Marta E-mail: marta.gomez-reino.perez@cern.ch

    2013-02-01

    We study some aspects of fine tuning in inflationary scenarios within string theory flux compactifications and, in particular, in models of accidental inflation. We investigate the possibility that the apparent fine-tuning of the low energy parameters of the theory needed to have inflation can be generically obtained by scanning the values of the fluxes over the landscape. Furthermore, we find that the existence of a landscape of eternal inflation in this model provides us with a natural theory of initial conditions for the inflationary period in our vacuum. We demonstrate how these two effects work in a small corner of the landscape associated with the complex structure of the Calabi-Yau manifold P{sup 4}{sub [1,1,1,6,9]} by numerically investigating the flux vacua of a reduced moduli space. This allows us to obtain the distribution of observable parameters for inflation in this mini-landscape directly from the fluxes.

  7. Fluorescence resonance energy transfer studies on the proximity relationship between the intrinsic metal ion and substrate binding sites of Escherichia coli RNA polymerase.

    PubMed

    Wu, F Y; Tyagi, S C

    1987-09-25

    DNA-dependent RNA polymerase from Escherichia coli contains 2 mol of zinc/mol of holoenzyme (alpha 2 beta beta' sigma) with one zinc each in the beta and beta' subunits. A new method to substitute selectively the zinc in the beta subunit was developed by the inactivation of RNA polymerase with 0.25 M NaNO3, 1 M NaCl, 1 mM diaminocyclohexane tetraacetic acid, and 0.1 mM dithiothreitol followed by reconstitution with Co(II), Cd(II), or Cu(II). The hybrid Co-Zn, Cd-Zn, or Cu-Zn RNA polymerase thus obtained retains, respectively, 91, 88, and 50% enzyme activity of the reconstituted Zn-Zn RNA polymerase. Co-Zn RNA polymerase exhibits absorption maxima at 395 and 465 nm, and Cu-Zn RNA polymerase at 637 nm (epsilon = 815 M-1 cm-1). 1-Aminonaphthalene-5-sulfonic acid (AmNS) derivatives of ATP, UTP, and dinucleoside monophosphates (diNMPs), UpA or ApU, were synthesized with AmNS attached to NTP via a gamma-phosphoamidate bond or to diNMPs via a 5'-secondary amine linkage. Since the fluorescence emission maxima of (5'-AmNS)UpA, (gamma-AmNS)ATP, and (gamma-AmNS)UTP at 445, 464, and 464 nm, respectively, when excited at 340 nm, overlap the 465-nm absorption band of Co-Zn RNA polymerase, the spatial relationship between fluorescence substrate analogs and the intrinsic Co(II) in Co-Zn RNA polymerase was studied by fluorescence resonance energy transfer technique. The fluorescence of the initiator, (5'-AmNS)UpA, and elongator, (gamma-AmNS)UTP, of the RNA chain, was quenched 20.3 and 7.1%, by the addition of saturation concentration of Zn-Zn RNA polymerase, and 21.3 and 14.7%, respectively, by the addition of template, poly(dA-dT). The fluorescence of (5'-AmNS)UpA and (gamma-AmNS)UTP was quenched 81.8 and 80.6%, respectively, by the addition of the saturation concentration of Co-Zn RNA polymerase in the absence of template, and 82.7 and 82.9% in the presence of template. On the basis of respective Ro values of 21.3 and 21.9 A for the (5'-AmNS)UpA-Co and (gamma-AmNS)UTP-Co pairs

  8. 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

  9. Dynamical Collective Potential Energy Landscape: Its Impact on the Competition Between Fusion and Quasi-fission in a Heavy Fusing System

    SciTech Connect

    Diaz-Torres, Alexis

    2006-08-14

    A realistic microscopically-based quantum approach to the competition between fusion and quasi-fission in a heavy fusing system is applied to several reactions leading to 256No. Fusion and quasi-fission are described in terms of a diffusion process of nuclear shapes through a dynamical collective potential energy landscape which is initially diabatic and gradually becomes adiabatic. The microscopic ingredients of the theory are obtained with a realistic two-center shell model based on Woods-Saxon potentials. The results indicate that (i) the diabatic effects play a very important role in the onset of fusion hindrance for heavy systems, and (ii) very asymmetric reactions induced by closed shell nuclei seem to be the best suited to synthesize the heaviest compound nuclei.

  10. Energy-landscape-model analysis for irreversibility and its pulse-width dependence in cells subjected to a high-intensity ultrashort electric pulse

    NASA Astrophysics Data System (ADS)

    Joshi, R. P.; Hu, Q.; Schoenbach, K. H.; Beebe, S. J.

    2004-05-01

    We provide a simple, but physical analysis for cell irreversibility and apoptosis in response to an ultrashort (nanosecond), high-intensity electric pulse. Our approach is based on an energy landscape model for determining the temporal evolution of the configurational probability function p(q). The primary focus is on obtaining qualitative predictions of a pulse width dependence to apoptotic cell irreversibility that has been observed experimentally. The analysis couples a distributed electrical model for current flow with the Smoluchowski equation to provide self-consistent, time-dependent transmembrane voltages. The model captures the essence of the experimentally observed pulse-width dependence, and provides a possible physical picture that depends only on the electrical trigger. A number of interesting features are predicted.

  11. Energy-landscape-model analysis for irreversibility and its pulse-width dependence in cells subjected to a high-intensity ultrashort electric pulse.

    PubMed

    Joshi, R P; Hu, Q; Schoenbach, K H; Beebe, S J

    2004-05-01

    We provide a simple, but physical analysis for cell irreversibility and apoptosis in response to an ultrashort (nanosecond), high-intensity electric pulse. Our approach is based on an energy landscape model for determining the temporal evolution of the configurational probability function p(q). The primary focus is on obtaining qualitative predictions of a pulse width dependence to apoptotic cell irreversibility that has been observed experimentally. The analysis couples a distributed electrical model for current flow with the Smoluchowski equation to provide self-consistent, time-dependent transmembrane voltages. The model captures the essence of the experimentally observed pulse-width dependence, and provides a possible physical picture that depends only on the electrical trigger. A number of interesting features are predicted.

  12. Aspects of structural landscape of human islet amyloid polypeptide.

    PubMed

    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. PMID:25638009

  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. 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. Free Energy Landscapes for S-H Bonds in (Cp2Mo2S4)-Mo-star Complexes

    SciTech Connect

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

    2009-03-23

    Extensive thermochemical data have been determined for a series of complexes derived from Cp*Mo(μ S)2(μ SMe)(μ SH)MoCp* and Cp*Mo(μ S)2(μ SH)2MoCp*. These data include electrochemical potentials, pKa 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 FeCp2+/o for electrochemical potentials, 5 to 31 for pKa 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 wealth of thermochemical data are presented in free energy landscapes as a useful approach to visualizing and understanding the relative stabilities of all of the species under specified conditions. This work was supported by the U.S. Department of Energy's (DOE) Office of Basic Energy Sciences, Chemical Sciences program. The Pacific Northwest National Laboratory is operated by Battelle for DOE.

  17. 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.

  18. 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.

  19. Intrinsic Feature Motion Tracking

    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 timemore » 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.« less

  20. Atomistic Free Energy Model for Nucleic Acids: Simulations of Single-Stranded DNA and the Entropy Landscape of RNA Stem-Loop Structures.

    PubMed

    Mak, Chi H

    2015-11-25

    While single-stranded (ss) segments of DNAs and RNAs are ubiquitous in biology, details about their structures have only recently begun to emerge. To study ssDNA and RNAs, we have developed a new Monte Carlo (MC) simulation using a free energy model for nucleic acids that has the atomisitic accuracy to capture fine molecular details of the sugar-phosphate backbone. Formulated on the basis of a first-principle calculation of the conformational entropy of the nucleic acid chain, this free energy model correctly reproduced both the long and short length-scale structural properties of ssDNA and RNAs in a rigorous comparison against recent data from fluorescence resonance energy transfer, small-angle X-ray scattering, force spectroscopy and fluorescence correlation transport measurements on sequences up to ∼100 nucleotides long. With this new MC algorithm, we conducted a comprehensive investigation of the entropy landscape of small RNA stem-loop structures. From a simulated ensemble of ∼10(6) equilibrium conformations, the entropy for the initiation of different size RNA hairpin loops was computed and compared against thermodynamic measurements. Starting from seeded hairpin loops, constrained MC simulations were then used to estimate the entropic costs associated with propagation of the stem. The numerical results provide new direct molecular insights into thermodynaimc measurement from macroscopic calorimetry and melting experiments.

  1. 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

  2. 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...

  3. Multi-scaled explorations of binding-induced folding of intrinsically disordered protein inhibitor IA3 to its target enzyme.

    PubMed

    Wang, Jin; Wang, Yong; Chu, Xiakun; Hagen, Stephen J; Han, Wei; Wang, Erkang

    2011-04-01

    Biomolecular function is realized by recognition, and increasing evidence shows that recognition is determined not only by structure but also by flexibility and dynamics. We explored a biomolecular recognition process that involves a major conformational change - protein folding. In particular, we explore the binding-induced folding of IA3, an intrinsically disordered protein that blocks the active site cleft of the yeast aspartic proteinase saccharopepsin (YPrA) by folding its own N-terminal residues into an amphipathic alpha helix. We developed a multi-scaled approach that explores the underlying mechanism by combining structure-based molecular dynamics simulations at the residue level with a stochastic path method at the atomic level. Both the free energy profile and the associated kinetic paths reveal a common scheme whereby IA3 binds to its target enzyme prior to folding itself into a helix. This theoretical result is consistent with recent time-resolved experiments. Furthermore, exploration of the detailed trajectories reveals the important roles of non-native interactions in the initial binding that occurs prior to IA3 folding. In contrast to the common view that non-native interactions contribute only to the roughness of landscapes and impede binding, the non-native interactions here facilitate binding by reducing significantly the entropic search space in the landscape. The information gained from multi-scaled simulations of the folding of this intrinsically disordered protein in the presence of its binding target may prove useful in the design of novel inhibitors of aspartic proteinases.

  4. 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.

  5. 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.

  6. Impaired mitochondrial energy metabolism in Alzheimer's disease: Impact on pathogenesis via disturbed epigenetic regulation of chromatin landscape.

    PubMed

    Salminen, Antero; Haapasalo, Annakaisa; Kauppinen, Anu; Kaarniranta, Kai; Soininen, Hilkka; Hiltunen, Mikko

    2015-08-01

    The amyloid cascade hypothesis for the pathogenesis of Alzheimer's disease (AD) was proposed over twenty years ago. However, the mechanisms of neurodegeneration and synaptic loss have remained elusive delaying the effective drug discovery. Recent studies have revealed that amyloid-β peptides as well as phosphorylated and fragmented tau proteins accumulate within mitochondria. This process triggers mitochondrial fission (fragmentation) and disturbs Krebs cycle function e.g. by inhibiting the activity of 2-oxoglutarate dehydrogenase. Oxidative stress, hypoxia and calcium imbalance also disrupt the function of Krebs cycle in AD brains. Recent studies on epigenetic regulation have revealed that Krebs cycle intermediates control DNA and histone methylation as well as histone acetylation and thus they have fundamental roles in gene expression. DNA demethylases (TET1-3) and histone lysine demethylases (KDM2-7) are included in the family of 2-oxoglutarate-dependent oxygenases (2-OGDO). Interestingly, 2-oxoglutarate is the obligatory substrate of 2-OGDO enzymes, whereas succinate and fumarate are the inhibitors of these enzymes. Moreover, citrate can stimulate histone acetylation via acetyl-CoA production. Epigenetic studies have revealed that AD is associated with changes in DNA methylation and histone acetylation patterns. However, the epigenetic results of different studies are inconsistent but one possibility is that they represent both coordinated adaptive responses and uncontrolled stochastic changes, which provoke pathogenesis in affected neurons. Here, we will review the changes observed in mitochondrial dynamics and Krebs cycle function associated with AD, and then clarify the mechanisms through which mitochondrial metabolites can control the epigenetic landscape of chromatin and induce pathological changes in AD. PMID:26001589

  7. Impaired mitochondrial energy metabolism in Alzheimer's disease: Impact on pathogenesis via disturbed epigenetic regulation of chromatin landscape.

    PubMed

    Salminen, Antero; Haapasalo, Annakaisa; Kauppinen, Anu; Kaarniranta, Kai; Soininen, Hilkka; Hiltunen, Mikko

    2015-08-01

    The amyloid cascade hypothesis for the pathogenesis of Alzheimer's disease (AD) was proposed over twenty years ago. However, the mechanisms of neurodegeneration and synaptic loss have remained elusive delaying the effective drug discovery. Recent studies have revealed that amyloid-β peptides as well as phosphorylated and fragmented tau proteins accumulate within mitochondria. This process triggers mitochondrial fission (fragmentation) and disturbs Krebs cycle function e.g. by inhibiting the activity of 2-oxoglutarate dehydrogenase. Oxidative stress, hypoxia and calcium imbalance also disrupt the function of Krebs cycle in AD brains. Recent studies on epigenetic regulation have revealed that Krebs cycle intermediates control DNA and histone methylation as well as histone acetylation and thus they have fundamental roles in gene expression. DNA demethylases (TET1-3) and histone lysine demethylases (KDM2-7) are included in the family of 2-oxoglutarate-dependent oxygenases (2-OGDO). Interestingly, 2-oxoglutarate is the obligatory substrate of 2-OGDO enzymes, whereas succinate and fumarate are the inhibitors of these enzymes. Moreover, citrate can stimulate histone acetylation via acetyl-CoA production. Epigenetic studies have revealed that AD is associated with changes in DNA methylation and histone acetylation patterns. However, the epigenetic results of different studies are inconsistent but one possibility is that they represent both coordinated adaptive responses and uncontrolled stochastic changes, which provoke pathogenesis in affected neurons. Here, we will review the changes observed in mitochondrial dynamics and Krebs cycle function associated with AD, and then clarify the mechanisms through which mitochondrial metabolites can control the epigenetic landscape of chromatin and induce pathological changes in AD.

  8. 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

    2012-04-01

    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

  9. 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

  10. Preferential solvation dynamics in liquids: How geodesic pathways through the potential energy landscape reveal mechanistic details about solute relaxation in liquids

    NASA Astrophysics Data System (ADS)

    Nguyen, Crystal N.; Stratt, Richard M.

    2010-09-01

    It is not obvious that many-body phenomena as collective as solute energy relaxation in liquid solution should ever have identifiable molecular mechanisms, at least not in the sense of the well-defined sequence of molecular events one often attributes to chemical reactions. What can define such mechanisms, though, are the most efficient relaxation paths that solutions take through their potential energy landscapes. When liquid dynamics is dominated by slow diffusive processes, there are mathematically precise and computationally accessible routes to searching for such paths. We apply this observation to the dynamics of preferential solvation, the relaxation around a newly excited solute by a solvent composed of different components with different solvating abilities. The slow solvation seen experimentally in these mixtures stems from the dual needs to compress the solvent and to do solvent-solvent exchanges near the solute. By studying the geodesic (most efficient) paths for this combined process in a simple atomic liquid mixture, we show that the mechanism for preferential solvation features a reasonably sharp onset for slow diffusion, and that this diffusion involves a sequential, rather than concerted, series of solvent exchanges.

  11. The Campus Landscape.

    ERIC Educational Resources Information Center

    du Von, Jay

    1966-01-01

    All across the country, landscaping and site development are coming to the fore as essential and integral parts of university planning and development. This reprint concentrates on the function of landscape architecture, and briefly examines some of the major responsibilities of the landscape architect in planning a campus. Included are--(1)…

  12. Experimental quantum control landscapes: Inherent monotonicity and artificial structure

    SciTech Connect

    Roslund, Jonathan; Rabitz, Herschel

    2009-07-15

    Unconstrained searches over quantum control landscapes are theoretically predicted to generally exhibit trap-free monotonic behavior. This paper makes an explicit experimental demonstration of this intrinsic monotonicity for two controlled quantum systems: frequency unfiltered and filtered second-harmonic generation (SHG). For unfiltered SHG, the landscape is randomly sampled and interpolation of the data is found to be devoid of landscape traps up to the level of data noise. In the case of narrow-band-filtered SHG, trajectories are taken on the landscape to reveal a lack of traps. Although the filtered SHG landscape is trap free, it exhibits a rich local structure. A perturbation analysis around the top of these landscapes provides a basis to understand their topology. Despite the inherent trap-free nature of the landscapes, practical constraints placed on the controls can lead to the appearance of artificial structure arising from the resultant forced sampling of the landscape. This circumstance and the likely lack of knowledge about the detailed local landscape structure in most quantum control applications suggests that the a priori identification of globally successful (un)constrained curvilinear control variables may be a challenging task.

  13. 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.

  14. 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)

  15. 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. PMID:24631668

  16. Separating Scattering from Intrinsic Attenuation

    NASA Astrophysics Data System (ADS)

    van Wijk, K.; Scales, J. A.

    2003-12-01

    The subsurface appears disordered at all length-scales. Therefore, wave propatation at seismic or ultrasonic frequencies is subject to complicated scatterings. A pulse propagating in the subsurface loses energy at each scattering off an impedance contrast, but also decreases in amplitude as the impulse interacts with fluids in the rock. We call the latter non-elastic effect "intrinsic Q", while the former is "scattering Q". It is often the fluids in the rocks that are of interest, but conventional reflection and transmission of the incident pulse only cannot deceipher the individual components of Q due to scattering and fluid movement in the pore-space. We present an approach that can unravel these two mechanisms, allowing a separate estimate of absorption. This method treats the propagation of the average intensity in the framework of radiative transfer (RT); the arrival of (what is left of) the incident pulse is modeled as the coherent energy, whereas the later arriving multiply scattered events form the incoherent intensity. The coherent pulse decays exponentially due to a combination of scattering and absorption, and so does the incoherent intensity. However, multiple scattering can re-direct energy back to the receiver, supplying a gain-term at later times that makes up the incoherent intensity. Strictly speaking, one can invert for scattering and absorption from the intensity at late times only, often modeled with the late-time equivalent of RT, diffusion. However, we will show that fitting both early- and late-time signal with RT constrains absorption and scattering constants more rigorously. These ideas are illustrated by laboratory and sonic-logging measurements.

  17. Free Energy Landscape of Lipid Interactions with Regulatory Binding Sites on the Transmembrane Domain of the EGF Receptor.

    PubMed

    Hedger, George; Shorthouse, David; Koldsø, Heidi; Sansom, Mark S P

    2016-08-25

    Lipid molecules can bind to specific sites on integral membrane proteins, modulating their structure and function. We have undertaken coarse-grained simulations to calculate free energy profiles for glycolipids and phospholipids interacting with modulatory sites on the transmembrane helix dimer of the EGF receptor within a lipid bilayer environment. We identify lipid interaction sites at each end of the transmembrane domain and compute interaction free energy profiles for lipids with these sites. Interaction free energies ranged from ca. -40 to -4 kJ/mol for different lipid species. Those lipids (glycolipid GM3 and phosphoinositide PIP2) known to modulate EGFR function exhibit the strongest binding to interaction sites on the EGFR, and we are able to reproduce the preference for interaction with GM3 over other glycolipids suggested by experiment. Mutation of amino acid residues essential for EGFR function reduce the binding free energy of these key lipid species. The residues interacting with the lipids in the simulations are in agreement with those suggested by experimental (mutational) studies. This approach provides a generalizable tool for characterizing the interactions of lipids that bind to specific sites on integral membrane proteins.

  18. Free Energy Landscape of Lipid Interactions with Regulatory Binding Sites on the Transmembrane Domain of the EGF Receptor

    PubMed Central

    2016-01-01

    Lipid molecules can bind to specific sites on integral membrane proteins, modulating their structure and function. We have undertaken coarse-grained simulations to calculate free energy profiles for glycolipids and phospholipids interacting with modulatory sites on the transmembrane helix dimer of the EGF receptor within a lipid bilayer environment. We identify lipid interaction sites at each end of the transmembrane domain and compute interaction free energy profiles for lipids with these sites. Interaction free energies ranged from ca. −40 to −4 kJ/mol for different lipid species. Those lipids (glycolipid GM3 and phosphoinositide PIP2) known to modulate EGFR function exhibit the strongest binding to interaction sites on the EGFR, and we are able to reproduce the preference for interaction with GM3 over other glycolipids suggested by experiment. Mutation of amino acid residues essential for EGFR function reduce the binding free energy of these key lipid species. The residues interacting with the lipids in the simulations are in agreement with those suggested by experimental (mutational) studies. This approach provides a generalizable tool for characterizing the interactions of lipids that bind to specific sites on integral membrane proteins. PMID:27109430

  19. 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

  20. 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.

  1. Unfaulting mechanism of trapped self-interstitial atom clusters in bcc Fe: A kinetic study based on the potential energy landscape

    SciTech Connect

    Fan Yue; Kushima, Akihiro; Yildiz, Bilge

    2010-03-01

    We report on the complete unfaulting mechanism of a trapped self-interstitial atom cluster in the form of a nonparallel configuration (NPC), investigated using the autonomous basin climbing (ABC) method. A detailed set of transition state atomic trajectories in the unfaulting process from the trapped to the mobile glide <111> configuration and the corresponding potential energy landscape were identified. The breaking of the initial ring structure of the three trimers on (111) planes followed by the rotation of the <111> crowdion in the NPC are the main rate limiting processes of the unfaulting mechanism. The effective activation barrier in the transition from the NPC to the glide <111> configuration was calculated by combining the ABC and kinetic Monte Carlo methods and was further benchmarked against molecular dynamics (MD) simulations. The effective activation barrier was found as 0.82 eV; smaller than its previously reported value of 1.68 eV. The ABC method was confirmed to be more efficient than MD, especially for the defect structure evolution processes associated with high barriers and at low temperatures.

  2. Quantification of Canopy Structure and its Implication on Radiative Transfer, Carbon Dioxide and Energy Flux Densities in a Heterogeneous Oak-Grass Savanna Ecosystem at the Landscape Scale

    NASA Astrophysics Data System (ADS)

    Sonnentag, O.; Ryu, Y.; Vargas, R.; Baldocchi, D.

    2008-12-01

    Oak-grass savanna ecosystems are characterized by pronounced heterogeneity in canopy structure at the landscape scale. Due to this heterogeneity the accurate quantification of canopy structure still remains a major challenge. The objectives of this study are to quantify clumping index, leaf area index (LAI) and the leaf inclination angle distribution function (LIADF) to describe the canopy structure of an oak-grass savanna ecosystem in California, USA. This information is critical for utilizing a radiative transfer model to compute CO2 and energy flux densities. We used four established techniques (LAI-2000 Plant Canopy Analyzer, digital hemispherical photography, the Tracing Radiation and Architecture of Canopies (TRAC) instrument, and a robotics railroad radiometer) to measure clumping index and LAI within a 300 x 300 m plot centered at an eddy covariance (EC) tower. Leaf inclination angle distributions were assessed from digital photographs at multiple height intervals through analysis with a public domain image processing software. Preliminary analysis of the data showed that mean values for clumping index and LAI obtained from the various instruments are in good agreement, thus reducing the uncertainty inherent in the measurements. Our leaf angle measurements revealed the canopy to be predominantly erectophile at all height intervals, an ecological consequence of the fact that oak leaves must be erect to reduce thermal load.

  3. 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.

  4. 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

  5. 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.

  6. Intrinsic Negative Mass from Nonlinearity

    NASA Astrophysics Data System (ADS)

    Di Mei, F.; Caramazza, P.; Pierangeli, D.; Di Domenico, G.; Ilan, H.; Agranat, A. J.; Di Porto, P.; DelRe, E.

    2016-04-01

    We propose and provide experimental evidence of a mechanism able to support negative intrinsic effective mass. The idea is to use a shape-sensitive nonlinearity to change the sign of the mass in the leading linear propagation equation. Intrinsic negative-mass dynamics is reported for light beams in a ferroelectric crystal substrate, where the diffusive photorefractive nonlinearity leads to a negative-mass Schrödinger equation. The signature of inverted dynamics is the observation of beams repelled from strongly guiding integrated waveguides irrespective of wavelength and intensity and suggests shape-sensitive nonlinearity as a basic mechanism leading to intrinsic negative mass.

  7. 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.

  8. 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.

  9. Intrinsic Energy Cut-off in Diffusive Shock Acceleration: Possible Reason for Non-detection of TeV-protons in SNRs

    NASA Astrophysics Data System (ADS)

    Malkov, M. A.; Diamond, P. H.; Jones, T. W.

    2000-12-01

    The theory of shock acceleration predicts the maximum particle energy to be limited only by the acceleration time and the shock size. This led to optimistic estimates for the galactic cosmic ray energy achievable in the SNR shocks. The estimates imply that the accelerated particles, while making no strong impact on the shock structure (test particle approach) are still scattered by strong self-generated Alfven waves (turbulent boost) needed to accelerate particles quickly. These two assumptions are, however, in conflict when applied to SNRs of the age required for cosmic ray acceleration to the ``knee'' energy. We study the combined effect of acceleration nonlinearity (shock modification by acclerated particles) and the turbulent boost of acceleration on the maximum energy achievable by this mechanism in a given time. We show that the refraction to shorter wave lengths in the nonlinearly modified flow causes enhanced losses of particles in the momentum range pmax/R < p < pmax , where R > 1 is the nonlinear pre-compression of the flow and pmax is the absolute maximum momentum that could be reached in an unimpeded (linear, but turbulently boosted) acceleration process. The particle spectrum behaves as p{-σ }e-√ {p//line{p}} at p > p*= pmax/R as opposed to the conventional power-law p{-σ } at p < p* . Since R itself is proportional to /line{p} that characterizes the energy content of accelerated particlles (since σ < 4 and p* < /line{p} < pmax ) the observationally important spectral break p* should grow slower than √ {pmax} . Moreover, due to the lack of particles at pmax (and thus waves in resonance with them) caused by the spectral break at p*}=p{max/R , the pmax(t) itself should advance much slower than the estimates based on the Bohm diffusion would predict. These nonlinear mechanisms of momentum limitation may result in significant reduction of both the absolute maximum momentum pmax and the observationally more important spectral break p* .

  10. Free energy landscapes for the thermodynamic understanding of adsorption-induced deformations and structural transitions in porous materials

    NASA Astrophysics Data System (ADS)

    Bousquet, D.; Coudert, F.-X.; Boutin, A.

    2012-07-01

    Soft porous crystals are flexible metal-organic frameworks that respond to physical stimuli such as temperature, pressure, and gas adsorption by large changes in their structure and unit cell volume. While they have attracted a lot of interest, molecular simulation methods that directly couple adsorption and large structural deformations in an efficient manner are still lacking. We propose here a new Monte Carlo simulation method based on non-Boltzmann sampling in (guest loading, volume) space using the Wang-Landau algorithm, and show that it can be used to fully characterize the adsorption properties and the material's response to adsorption at thermodynamic equilibrium. We showcase this new method on a simple model of the MIL-53 family of breathing materials, demonstrating its potential and contrasting it with the pitfalls of direct, Boltzmann simulations. We furthermore propose an explanation for the hysteretic nature of adsorption in terms of free energy barriers between the two metastable host phases.

  11. 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.

  12. Nonequilibrium landscape theory of neural networks.

    PubMed

    Yan, Han; Zhao, Lei; Hu, Liang; Wang, Xidi; Wang, Erkang; Wang, Jin

    2013-11-01

    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.

  13. 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.

  14. 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.

  15. 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)

  16. Role of intrinsic width in fragment momentum distributions in heavy ion collisions.

    PubMed

    Tripathi, R K; Townsend, L W; Khan, F

    1994-04-01

    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 200A MeV to 2A 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 with correlations is presented.

  17. 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.

  18. 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.

  19. 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.

  20. Multi-ion free energy landscapes underscore the microscopic mechanism of ion selectivity in the KcsA channel

    PubMed Central

    Medovoy, David; Perozo, Eduardo; Roux, Benoît

    2016-01-01

    Potassium (K+) channels are transmembrane proteins that passively and selectively allow K+ ions to flow through them, after opening in response to an external stimulus. One of the most critical functional aspects of their function is their ability to remain very selective for K+ over Na+ while allowing high-throughput ion conduction at a rate close to the diffusion limit. Classically, it is assumed that the free energy difference between K+ and Na+ in the pore relative to the bulk solution is the critical quantity at the origin of selectivity. This is the thermodynamic view of ion selectivity. An alternative view assumes that kinetic factor play the dominant role. Recent results from a number of studies have also highlighted the great importance of the multi-ion single file on the selectivity of K+ channels. The data indicate that having multiple K+ ions bound simultaneously is required for selective K+ conduction, and that a reduction in the number of bound K+ ions destroys the multi-ion selectivity mechanism utilized by K+ channels. In the present study, multi-ion potential of mean force molecular dynamics computations are carried out to clarify the mechanism of ion selectivity in the KcsA channel. The computations show that the multi-ion character of the permeation process is a critical element for establishing the selective ion conductivity through K+-channels. PMID:26896693

  1. Intrinsic time in Wheeler-DeWitt conformal superspace

    NASA Astrophysics Data System (ADS)

    Pavlov, A. E.; Pervushin, V. N.

    In Geometrodynamics, the York's extrinsic time, constructed of the tensor of extrinsic curvature and the Misner's intrinsic time, built of the spatial metric tensor, coexist. In our paper, we prove the preference of selecting the internal time. To extract the intrinsic time, we generalize the Dirac's mapping of transition to conformal variables. In Friedmann cosmology, the many-fingered intrinsic time obtains a sense of a global time of the Universe. An accounting of metric scalar linear perturbations leads to adding some corrections not dominated to the effective energy density in the Hubble law. The metric vector and tensor perturbations do not influence the internal time in linear approximation.

  2. Extrinsic and Intrinsic Contributions to Plasmon Peaks in Solids

    NASA Astrophysics Data System (ADS)

    Alshehabi, Abbas; Kawai, Jun

    2016-01-01

    Intrinsic and extrinsic plasmons are defined and the contribution of each determined. It is shown that quantum interference between intrinsic and extrinsic satellites in X-ray photoelectron spectroscopy (XPS) as well as in Auger electron spectra (AES) does not occur for plasmon loss peaks higher than first order. Line widths in measured reflected electron energy loss spectra (EELS) are analysed by subtracting the Shirley background. Contrary to common understanding, extrinsic and intrinsic contributions by plasmon peaks can be experimentally distinguishable by comparison of line widths.

  3. The utility of a thermal-based two-source energy balance model for estimating surface energy fluxes over a snow-dominated landscape

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A thermal-based two- source energy balance (TSEB) model is modified to estimate surface energy fluxes over snow-dominated surfaces (TSEBs). Field measurements at two sites in a sagebrush and aspen forest ecosystem during the winter are used to evaluate the utility of TSEBs. Modifications include ...

  4. Landscape controls on long-term fluxes of water, energy and soil formation in a Mediterranean catchment

    NASA Astrophysics Data System (ADS)

    Román Sánchez, Andrea; Giráldez, Juan V.; Vanwalleghem, Tom

    2015-04-01

    compare for different topographical positions the importance of water and energy fluxes, erosion and soil formation and incorporate in a simple way their interactions quantitatively.

  5. 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

  6. 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.

  7. 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 Central

    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. PMID:26618408

  8. Landscape epidemiology of plant diseases.

    PubMed

    Plantegenest, Manuel; Le May, Christophe; Fabre, Frédéric

    2007-10-22

    Many agricultural landscapes are characterized by a high degree of heterogeneity and fragmentation. Landscape ecology focuses on the influence of habitat heterogeneity in space and time on ecological processes. Landscape epidemiology aims at applying concepts and approaches originating from landscape ecology to the study of pathogen dynamics at the landscape scale. However, despite the strong influence that the landscape properties may have on the spread of plant diseases, landscape epidemiology has still received little attention from plant pathologists. Some recent methodological and technological progress provides new and powerful tools to describe and analyse the spatial patterns of host-pathogen interactions. Here, we review some important topics in plant pathology that may benefit from a landscape perspective. These include the influence of: landscape composition on the global inoculum pressure; landscape heterogeneity on pathogen dynamics; landscape structure on pathogen dispersal; and landscape properties on the emergence of pathogens and on their evolution.

  9. Intrinsic Mean Square Displacement in Proteins

    NASA Astrophysics Data System (ADS)

    Vural, Derya; Glyde, Henry R.

    2012-02-01

    The dynamics of biological molecules is investigated in neutron scattering experiments, in molecular dynamics simulations, and using analytical theory. Specifically, the mean square displacement (MSD), exp, of hydrogen in proteins is determined from measurements of the incoherent elastic neutron scattering intensity (ENSI). The MSD, exp, is usually obtained from the dependence of the ENSI on the scattering wave vector Q. The MSD increases with increasing temperature reaching large values at room temperature. Large MSD is often associated with and used as an indicator of protein function. The observed MSD, however, depends on the energy resolution of the neutron spectrometer employed. We present a method, a first attempt, to extract the intrinsic MSD of hydrogen in protein from measurements, one that is independent of the instrument resolution. The method consists of a model of the ENSI that contains (1) the intrinsic MSD, (2) the instrument resolution width and (3) a parameter describing the motional processes that contribute to the MSD. Several examples of intrinsic MSDs in proteins obtained from fitting to data in the existing literature will be presented.

  10. Intrinsic mechanical behavior of femoral cortical bone in young, osteoporotic and bisphosphonate-treated individuals in low- and high energy fracture conditions

    DOE PAGESBeta

    Zimmermann, Elizabeth A.; Schaible, Eric; Gludovatz, Bernd; Schmidt, Felix N.; Riedel, Christoph; Krause, Matthias; Vettorazzi, Eik; Acevedo, Claire; Hahn, Michael; Püschel, Klaus; et al

    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

  11. Intrinsic mechanical behavior of femoral cortical bone in young, osteoporotic and bisphosphonate-treated individuals in low- and high energy fracture conditions.

    PubMed

    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. 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.

  12. 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

  13. Biochemical characterization of the novel rice kinesin K23 and its kinetic study using fluorescence resonance energy transfer between an intrinsic tryptophan residue and a fluorescent ATP analogue.

    PubMed

    Umezu, Nozomi; Hanzawa, Nobue; Yamada, Masafumi D; Kondo, Kazunori; Mitsui, Toshiaki; Maruta, Shinsaku

    2011-05-01

    We previously demonstrated that the rice kinesin K16, which belongs to the kinesin-7 subfamily, has unique enzymatic properties and atomic structure within key functional regions. In this study, we focused on a novel rice plant kinesin, K23, which also belongs to the kinesin-7 subfamily. The biochemical characterization of the K23 motor domain (K23MD) was studied and compared with the rice kinesin K16 and other related kinesins. K23 exhibits ∼45-fold (1.3 Pi mol(-1) site mol(-1) s(-1)) lower microtubule-dependent ATPase activity than conventional kinesins, whereas its affinity for microtubules is comparable with conventional kinesins. MgADP-free K23 is unstable compared with the unusually stable MgADP-free K16MD. The enzymatic properties of K23MD are somewhat different from those of K16. We used a fluorescent ATP analogue 2'(3')-O-(N'-methylanthraniloyl)-ATP (mant-ATP) for the kinetic characterization of K23. The fluorescence of mant-ATP was not significantly altered during its hydrolysis by K23. However, significant fluorescence resonance energy transfer (FRET) between mant-ATP and W21 in the motor domain was observed. The kinetic study using FRET revealed that K23 has unique kinetic characteristics when compared with other kinesins.

  14. 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.

  15. 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...

  16. 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

  17. 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...

  18. Decipher the mechanisms of protein conformational changes induced by nucleotide binding through free-energy landscape analysis: ATP binding to Hsp70.

    PubMed

    Nicolaï, Adrien; Delarue, Patrice; Senet, Patrick

    2013-01-01

    ATP regulates the function of many proteins in the cell by transducing its binding and hydrolysis energies into protein conformational changes by mechanisms which are challenging to identify at the atomic scale. Based on molecular dynamics (MD) simulations, a method is proposed to analyze the structural changes induced by ATP binding to a protein by computing the effective free-energy landscape (FEL) of a subset of its coordinates along its amino-acid sequence. The method is applied to characterize the mechanism by which the binding of ATP to the nucleotide-binding domain (NBD) of Hsp70 propagates a signal to its substrate-binding domain (SBD). Unbiased MD simulations were performed for Hsp70-DnaK chaperone in nucleotide-free, ADP-bound and ATP-bound states. The simulations revealed that the SBD does not interact with the NBD for DnaK in its nucleotide-free and ADP-bound states whereas the docking of the SBD was found in the ATP-bound state. The docked state induced by ATP binding found in MD is an intermediate state between the initial nucleotide-free and final ATP-bound states of Hsp70. The analysis of the FEL projected along the amino-acid sequence permitted to identify a subset of 27 protein internal coordinates corresponding to a network of 91 key residues involved in the conformational change induced by ATP binding. Among the 91 residues, 26 are identified for the first time, whereas the others were shown relevant for the allosteric communication of Hsp70 s in several experiments and bioinformatics analysis. The FEL analysis revealed also the origin of the ATP-induced structural modifications of the SBD recently measured by Electron Paramagnetic Resonance. The pathway between the nucleotide-free and the intermediate state of DnaK was extracted by applying principal component analysis to the subset of internal coordinates describing the transition. The methodology proposed is general and could be applied to analyze allosteric communication in other proteins.

  19. Decipher the Mechanisms of Protein Conformational Changes Induced by Nucleotide Binding through Free-Energy Landscape Analysis: ATP Binding to Hsp70

    PubMed Central

    Nicolaï, Adrien; Delarue, Patrice; Senet, Patrick

    2013-01-01

    ATP regulates the function of many proteins in the cell by transducing its binding and hydrolysis energies into protein conformational changes by mechanisms which are challenging to identify at the atomic scale. Based on molecular dynamics (MD) simulations, a method is proposed to analyze the structural changes induced by ATP binding to a protein by computing the effective free-energy landscape (FEL) of a subset of its coordinates along its amino-acid sequence. The method is applied to characterize the mechanism by which the binding of ATP to the nucleotide-binding domain (NBD) of Hsp70 propagates a signal to its substrate-binding domain (SBD). Unbiased MD simulations were performed for Hsp70-DnaK chaperone in nucleotide-free, ADP-bound and ATP-bound states. The simulations revealed that the SBD does not interact with the NBD for DnaK in its nucleotide-free and ADP-bound states whereas the docking of the SBD was found in the ATP-bound state. The docked state induced by ATP binding found in MD is an intermediate state between the initial nucleotide-free and final ATP-bound states of Hsp70. The analysis of the FEL projected along the amino-acid sequence permitted to identify a subset of 27 protein internal coordinates corresponding to a network of 91 key residues involved in the conformational change induced by ATP binding. Among the 91 residues, 26 are identified for the first time, whereas the others were shown relevant for the allosteric communication of Hsp70 s in several experiments and bioinformatics analysis. The FEL analysis revealed also the origin of the ATP-induced structural modifications of the SBD recently measured by Electron Paramagnetic Resonance. The pathway between the nucleotide-free and the intermediate state of DnaK was extracted by applying principal component analysis to the subset of internal coordinates describing the transition. The methodology proposed is general and could be applied to analyze allosteric communication in other proteins

  20. 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

  1. 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...

  2. 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.

  3. [Landscape and ecological genomics].

    PubMed

    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. PMID:25508669

  4. [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. PMID:25474890

  5. 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…

  6. 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.

  7. 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...

  8. Single temperature for Monte Carlo optimization on complex landscapes.

    PubMed

    Tolkunov, Denis; Morozov, Alexandre V

    2012-06-22

    We propose a new strategy for Monte Carlo (MC) optimization on rugged multidimensional landscapes. The strategy is based on querying the statistical properties of the landscape in order to find the temperature at which the mean first passage time across the current region of the landscape is minimized. Thus, in contrast to other algorithms such as simulated annealing, we explicitly match the temperature schedule to the statistics of landscape irregularities. In cases where these statistics are approximately the same over the entire landscape or where nonlocal moves couple distant parts of the landscape, a single-temperature MC scheme outperforms any other MC algorithm with the same move set. We also find that in strongly anisotropic Coulomb spin glass and traveling salesman problems, the only relevant statistics (which we use to assign a single MC temperature) are those of irregularities in low-energy funnels. Our results may explain why protein folding is efficient at constant temperature.

  9. 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

  10. Unraveling the intrinsic color of chlorophyll.

    PubMed

    Milne, Bruce F; Toker, Yoni; Rubio, Angel; Nielsen, Steen Brøndsted

    2015-02-01

    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.

  11. What is intrinsic atopic dermatitis?

    PubMed

    Roguedas-Contios, Anne-Marie; Misery, Laurent

    2011-12-01

    Many authors favor a distinction between the extrinsic and intrinsic forms of atopic dermatitis. In this review, the controversy is discussed and several definitions are presented. After reviewing many papers on this topic, it is our opinion that it is useful to separate the intrinsic and extrinsic forms of atopic dermatitis or atopic eczema and atopiform dermatitis because the pathophysiology appears to be different between them. However, these terms require concrete definition and clarification of the distinction between these two concepts. This debate is a new step in the history of atopic dermatitis. It is possible that a single patient could suffer from one form and then from another but genetic differences suggest that two types could really exist.

  12. Decoherence: Intrinsic, Extrinsic, and Environmental

    NASA Astrophysics Data System (ADS)

    Stamp, Philip

    2012-02-01

    Environmental decoherence times have been difficult to predict in solid-state systems. In spin systems, environmental decoherence is predicted to arise from nuclear spins, spin-phonon interactions, and long-range dipolar interactions [1]. Recent experiments have confirmed these predictions quantitatively in crystals of Fe8 molecules [2]. Coherent spin dynamics was observed over macroscopic volumes, with a decoherence Q-factor Qφ= 1.5 x10^6 (the upper predicted limit in this system being Qφ= 6 x10^7). Decoherence from dipolar interactions is particularly complex, and depends on the shape and the quantum state of the system. No extrinsic ``noise'' decoherence was observed. The generalization to quantum dot and superconducting qubit systems is also discussed. We then discuss searches for ``intrinsic'' decoherence [3,4], coming from non-linear corrections to quantum mechanics. Particular attention is paid to condensed matter tests of such intrinsic decoherence, in hybrid spin/optomechanical systems, and to ways of distinguishing intrinsic decoherence from environmental and extrinsic decoherence sources. [4pt] [1] Morello, A. Stamp, P. C. E. & Tupitsyn, Phys. Rev. Lett. 97, 207206 (2006).[0pt] [2] S. Takahashi et al., Nature 476, 76 (2011).[0pt] [3] Stamp, P. C. E., Stud. Hist. Phil. Mod. Phys. 37, 467 (2006). [0pt] [4] Stamp, P.C.E., Phil. Trans. Roy. Soc. A (to be published)

  13. Troponins, intrinsic disorder, and cardiomyopathy.

    PubMed

    Na, Insung; Kong, Min J; Straight, Shelby; Pinto, Jose R; Uversky, Vladimir N

    2016-08-01

    Cardiac troponin is a dynamic complex of troponin C, troponin I, and troponin T (TnC, TnI, and TnT, respectively) found in the myocyte thin filament where it plays an essential role in cardiac muscle contraction. Mutations in troponin subunits are found in inherited cardiomyopathies, such as hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). The highly dynamic nature of human cardiac troponin and presence of numerous flexible linkers in its subunits suggest that understanding of structural and functional properties of this important complex can benefit from the consideration of the protein intrinsic disorder phenomenon. We show here that mutations causing decrease in the disorder score in TnI and TnT are significantly more abundant in HCM and DCM than mutations leading to the increase in the disorder score. Identification and annotation of intrinsically disordered regions in each of the troponin subunits conducted in this study can help in better understanding of the roles of intrinsic disorder in regulation of interactomes and posttranslational modifications of these proteins. These observations suggest that disease-causing mutations leading to a decrease in the local flexibility of troponins can trigger a whole plethora of functional changes in the heart. PMID:27074551

  14. Intrinsic Patterns of Human Activity

    NASA Astrophysics Data System (ADS)

    Hu, Kun; Ivanov, Plamen Ch.; Chen, Zhi; Hilton, Michael; Stanley, H. Eugene; Shea, Steven

    2003-03-01

    Activity is one of the defining features of life. Control of human activity is complex, being influenced by many factors both extrinsic and intrinsic to the body. The most obvious extrinsic factors that affect activity are the daily schedule of planned events, such as work and recreation, as well as reactions to unforeseen or random events. These extrinsic factors may account for the apparently random fluctuations in human motion observed over short time scales. The most obvious intrinsic factors are the body clocks including the circadian pacemaker that influences our sleep/wake cycle and ultradian oscillators with shorter time scales [2, 3]. These intrinsic rhythms may account for the underlying regularity in average activity level over longer periods of up to 24 h. Here we ask if the known extrinsic and intrinsic factors fully account for all complex features observed in recordings of human activity. To this end, we measure activity over two weeks from forearm motion in subjects undergoing their regular daily routine. Utilizing concepts from statistical physics, we demonstrate that during wakefulness human activity possesses previously unrecognized complex dynamic patterns. These patterns of activity are characterized by robust fractal and nonlinear dynamics including a universal probability distribution and long-range power-law correlations that are stable over a wide range of time scales (from minutes to hours). Surprisingly, we find that these dynamic patterns are unaffected by changes in the average activity level that occur within individual subjects throughout the day and on different days of the week, and between subjects. Moreover, we find that these patterns persist when the same subjects undergo time-isolation laboratory experiments designed to account for the phase of the circadian pacemaker, and control the known extrinsic factors by restricting behaviors and manipulating scheduled events including the sleep/wake cycle. We attribute these newly

  15. 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

  16. Simulation of coupled folding and binding of an intrinsically disordered protein in explicit solvent with metadynamics.

    PubMed

    Han, Mengzhi; Xu, Ji; Ren, Ying; Li, Jinghai

    2016-07-01

    The C-terminal domain of measles virus nucleoprotein is an intrinsically disordered protein that could bind to the X domain (XD) of phosphoprotein P to exert its physiological function. Experiments reveal that the minimal binding unit is a 21-residue α-helical molecular recognition element (α-MoRE-MeV), which adopts a fully helical conformation upon binding to XD. Due to currently limited computing power, direct simulation of this coupled folding and binding process with atomic force field in explicit solvent cannot be achieved. In this work, two advanced sampling methods, metadynamics and parallel tempering, are combined to characterize the free energy surface of this process and investigate the underlying mechanism. Starting from an unbound and partially folded state of α-MoRE-MeV, multiple folding and binding events are observed during the simulation and the energy landscape was well estimated. The results demonstrate that the isolated α-MoRE-MeV resembles a molten globule and rapidly interconverts between random coil and multiple partially helical states in solution. The coupled folding and binding process occurs through the induced fit mechanism, with the residual helical conformations providing the initial binding sites. Upon binding, α-MoRE-MeV can easily fold into helical conformation without obvious energy barriers. Two mechanisms, namely, the system tending to adopt the structure in which the free energy of isolated α-MoRE-MeV is the minimum, and the binding energy of α-MoRE-MeV to its partner protein XD tending to the minimum, jointly dominate the coupled folding and binding process. With the advanced sampling approach, more IDP systems could be simulated and common mechanisms concerning the coupled folding and binding process could be investigated in the future. PMID:27423742

  17. Turbulent momentum transport and intrinsic rotation in tokamaks

    NASA Astrophysics Data System (ADS)

    Barnes, Michael

    2012-03-01

    A key physics issue for magnetic confinement fusion is the presence of high levels of turbulent particle and energy transport in magnetized plasmas. This transport is detrimental to fusion because it significantly lowers the plasma density and temperature, both of which must be kept high to increase fusion energy yield. Sheared flows have been shown to strongly reduce this plasma turbulent transport. Many current fusion experiments induce sheared flows by injecting beams of neutral particles, which make the plasma differentially rotate. However, this external momentum injection will be much less effective in the large, dense plasmas that may be required for a fusion reactor. A number of recent fusion experiments have measured significant differential rotation even without external momentum injection. This `intrinsic' rotation is a result of the rearrangement of momentum within the plasma. Since this rotation may determine the extent to which turbulent transport is suppressed, it is critical for the community to understand how momentum transport produces intrinsic rotation profiles. This is challenging, as intrinsic rotation exhibits a complex phenomenology that defies simple empirical scalings or heuristic models. This talk gives a brief overview of the intrinsic rotation phenomenology and elucidates features that any viable model for intrinsic rotation must contain. We propose a fully self-consistent, first-principles model for intrinsic rotation, which is based on an asymptotic expansion in the smallness of the turbulence fluctuation frequency relative to the ion Larmor frequency (known as gyrokinetics). Stringent conditions are placed on this model by a symmetry of the gyrokinetic equations. This model has been implemented in the gyrokinetic turbulence code GS2, from which we present simulation results on turbulent momentum transport. Various physical mechanisms that contribute to the momentum transport are studied to determine their dependences on key plasma

  18. 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. PMID:26858425

  19. 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

  20. From landscape to domain: Soils role in landscape classifications

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soil landscape classifications are designed to divide landscapes into units with significance for the provisioning and regulating of ecosystem services and the development of conservation plans for natural resources. More specifically, such classifications serve as the basis for stratifying manageme...

  1. Modeling animal landscapes.

    PubMed

    Porter, W P; Ostrowski, S; Williams, J B

    2010-01-01

    There is an increasing need to assess the effects of climate and land-use change on habitat quality, ideally from a mechanistic basis. The symposium "Molecules to Migration: Pressures of Life" at the Fourth International Conference in Africa for Comparative Physiology and Biochemistry, Maasai Mara National Reserve, Kenya, 2008, illustrated how the principles of biophysical ecology can capture the mechanistic links between organisms, climate, and other habitat features. These principles provide spatially explicit assessments of habitat quality from a physiological perspective (i.e., "animal landscapes") that can be validated independently of the data used to derive and parameterize them. The contents of this symposium showcased how the modeling of animal landscapes can be used to assess key issues in applied and theoretical ecology. The presentations included applications to amphibians, reptiles, birds, and mammals. The rare Arabian oryx on the Arabian Peninsula is used as an example for energetic calculations and their implications for behavior on the landscape. PMID:20670170

  2. 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...

  3. 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...

  4. Intrinsic Hysteresis Loops Calculation of BZT Thin Films

    NASA Astrophysics Data System (ADS)

    Hikam, M.; Adnan, S. R.

    2014-04-01

    The Landau Devonshire (LK) simulation is utilized to calculate the intrinsic hysteresis properties of Barium Zirconium Titanate (BZT) doped by Indium and Lanthanum. A Delphi program run on Windows platform is used to facilitate the calculation. The simulation is very useful to calculate and understand the Gibbs free energy and the relationship between spontaneous polarization and electric field.

  5. Nuclear Filtering of Intrinsic Charm

    SciTech Connect

    Kopeliovich, B. Z.; Potashnikova, I. K.; Schmidt, Ivan

    2010-11-12

    Nuclei are transparent for a heavy intrinsic charm (IC) component of the beam hadrons, what leads to an enhanced nuclear dependence of open charm production at large Feynman x{sub F}. Indeed, such an effect is supported by data from the SELEX experiment published recently [1]. Our calculations reproduce well the data, providing strong support for the presence of IC in hadrons in amount less than 1%. Moreover, we performed an analysis of nuclear effects in J/{Psi} production and found at large x{sub F} a similar, albeit weaker effect, which does not contradict data.

  6. A review of the intrinsic heavy quark content of the nucleon

    SciTech Connect

    Brodsky, S. J.; Kusina, A.; Lyonnet, F.; Schienbein, I.; Spiesberger, H.; Vogt, R.

    2015-04-29

    We present a review of the state of the art of our understanding of the intrinsic charm and bottom content of the nucleon. We discuss theoretical calculations, constraints from global analyses, and collider observables sensitive to the intrinsic heavy quark distributions. In addition, a particular emphasis is put on the potential of a high energy and high luminosity fixed target experiment using the LHC beams (AFTER@LHC) to search for intrinsic charm.

  7. A Review of the Intrinsic Heavy Quark Content of the Nucleon

    DOE PAGESBeta

    Brodsky, S. J.; Kusina, A.; Lyonnet, F.; Schienbein, I.; Spiesberger, H.; Vogt, R.

    2015-01-01

    We present a review of the state of the art of our understanding of the intrinsic charm and bottom content of the nucleon. We discuss theoretical calculations, constraints from global analyses, and collider observables sensitive to the intrinsic heavy quark distributions. A particular emphasis is put on the potential of a high energy and high luminosity fixed target experiment using the LHC beams (AFTER@LHC) to search for intrinsic charm.

  8. Sampling in landscape genomics.

    PubMed

    Manel, Stéphanie; Albert, Cécile H; Yoccoz, Nigel G

    2012-01-01

    Landscape genomics, based on the sampling of individuals genotyped for a large number of markers, may lead to the identification of regions of the genome correlated to selection pressures caused by the environment. In this chapter, we discuss sampling strategies to be used in a landscape genomics approach. We suggest that designs based on model-based stratification using the climatic and/or biological spaces are in general more efficient than designs based on the geographic space. More work is needed to identify designs that allow disentangling environmental selection pressures versus other processes such as range expansions or hierarchical population structure.

  9. Labyrinthine granular landscapes.

    PubMed

    Caps, H; Vandewalle, N

    2001-11-01

    We have numerically studied a model of granular landscape eroded by wind. We show the appearance of labyrinthic patterns when the wind orientation turns by 90 degrees. The occurrence of such structures is discussed. Moreover, we introduce the density n(k) of "defects" as the dynamic parameter governing the landscape evolution. A power-law behavior of n(k) is found as a function of time. In the case of wind variations, the exponent (drastically) shifts from two to one. The presence of two asymptotic values of n(k) implies the irreversibility of the labyrinthic formation process.

  10. Mapping the Dynamics Landscape of Conformational Transitions in Enzyme: The Adenylate Kinase Case

    PubMed Central

    Li, Dechang; Liu, Ming S.; Ji, Baohua

    2015-01-01

    Conformational transition describes the essential dynamics and mechanism of enzymes in pursuing their various functions. The fundamental and practical challenge to researchers is to quantitatively describe the roles of large-scale dynamic transitions for regulating the catalytic processes. In this study, we tackled this challenge by exploring the pathways and free energy landscape of conformational changes in adenylate kinase (AdK), a key ubiquitous enzyme for cellular energy homeostasis. Using explicit long-timescale (up to microseconds) molecular dynamics and bias-exchange metadynamics simulations, we determined at the atomistic level the intermediate conformational states and mapped the transition pathways of AdK in the presence and absence of ligands. There is clearly chronological operation of the functional domains of AdK. Specifically in the ligand-free AdK, there is no significant energy barrier in the free energy landscape separating the open and closed states. Instead there are multiple intermediate conformational states, which facilitate the rapid transitions of AdK. In the ligand-bound AdK, the closed conformation is energetically most favored with a large energy barrier to open it up, and the conformational population prefers to shift to the closed form coupled with transitions. The results suggest a perspective for a hybrid of conformational selection and induced fit operations of ligand binding to AdK. These observations, depicted in the most comprehensive and quantitative way to date, to our knowledge, emphasize the underlying intrinsic dynamics of AdK and reveal the sophisticated conformational transitions of AdK in fulfilling its enzymatic functions. The developed methodology can also apply to other proteins and biomolecular systems. PMID:26244746

  11. Pseudoknots in RNA folding landscapes

    PubMed Central

    Kucharík, Marcel; Hofacker, Ivo L.; Stadler, Peter F.; Qin, Jing

    2016-01-01

    Motivation: The function of an RNA molecule is not only linked to its native structure, which is usually taken to be the ground state of its folding landscape, but also in many cases crucially depends on the details of the folding pathways such as stable folding intermediates or the timing of the folding process itself. To model and understand these processes, it is necessary to go beyond ground state structures. The study of rugged RNA folding landscapes holds the key to answer these questions. Efficient coarse-graining methods are required to reduce the intractably vast energy landscapes into condensed representations such as barrier trees or basin hopping graphs (BHG) that convey an approximate but comprehensive picture of the folding kinetics. So far, exact and heuristic coarse-graining methods have been mostly restricted to the pseudoknot-free secondary structures. Pseudoknots, which are common motifs and have been repeatedly hypothesized to play an important role in guiding folding trajectories, were usually excluded. Results: We generalize the BHG framework to include pseudoknotted RNA structures and systematically study the differences in predicted folding behavior depending on whether pseudoknotted structures are allowed to occur as folding intermediates or not. We observe that RNAs with pseudoknotted ground state structures tend to have more pseudoknotted folding intermediates than RNAs with pseudoknot-free ground state structures. The occurrence and influence of pseudoknotted intermediates on the folding pathway, however, appear to depend very strongly on the individual RNAs so that no general rule can be inferred. Availability and implementation: The algorithms described here are implemented in C++ as standalone programs. Its source code and Supplemental material can be freely downloaded from http://www.tbi.univie.ac.at/bhg.html. Contact: qin@bioinf.uni-leipzig.de Supplementary information: Supplementary data are available at Bioinformatics online. PMID

  12. Gap-filling of flux measurements over a heterogeneous urban landscape

    NASA Astrophysics Data System (ADS)

    Menzer, O.; McFadden, J.

    2012-12-01

    A small, but growing, number of urban flux towers measure surface-atmospheric exchanges of energy, water, and greenhouse gases by the eddy covariance method. Imputation of gaps in these measurements caused by low turbulence conditions and system failures is essential for obtaining annual sums of CO2 exchange and evaporation. Yet most gap-filling methods were designed for natural measurement sites such as forests and grasslands. In the urban environment, however, the assumptions on which those approaches are based are violated and well known temperature or light response models are not applicable because of urban footprint heterogeneity and localized CO2 emissions. Observation-based methods of machine learning can reveal intrinsic mechanisms by using inputs such as wind direction, footprint size, and continuous traffic data, making gap-filling results more accurate. Here, we report preliminary gap-filling results using such empirical approaches for >3 years of flux measurements from the KUOM tall tower in a suburban neighborhood of Minneapolis, Minnesota, USA. We also ran one of the most common gap-filling methods that has been used for natural systems as a baseline or null model. We found that CO2 and water vapor fluxes from the urban landscape showed higher variability than those from a nearby turfgrass lawn, in which fluxes closely followed environmental drivers of light and temperature. Higher variability was found in NEE measurements as compared to LE, due to the relatively greater heterogeneity of sources and sinks that influenced CO2 exchange in the urban landscape.

  13. Measuring Intrinsic Curvature of Space with Electromagnetism

    NASA Astrophysics Data System (ADS)

    Mabin, Mason; Becker, Maria; Batelaan, Herman

    2016-10-01

    The concept of curved space is not readily observable in everyday life. The educational movie "Sphereland" attempts to illuminate the idea. The main character, a hexagon, has to go to great lengths to prove that her world is in fact curved. We present an experiment that demonstrates a new way to determine if a two-dimensional surface, the 2-sphere, is curved. The behavior of an electric field, placed on a spherical surface, is shown to be related to the intrinsic Gaussian curvature. This approach allows students to gain some understanding of Einstein's theory of general relativity, which relates the curvature of spacetime to the presence of mass and energy. Additionally, an opportunity is provided to investigate the dimensionality of Gauss's law.

  14. Thermal limit to the intrinsic emittance from metal photocathodes

    SciTech Connect

    Feng, Jun Nasiatka, J.; Wan, Weishi; Karkare, Siddharth; Padmore, Howard A.; Smedley, John

    2015-09-28

    Measurements of the intrinsic emittance and transverse momentum distributions obtained from a metal (antimony thin film) photocathode near and below the photoemission threshold are presented. Measurements show that the intrinsic emittance is limited by the lattice temperature of the cathode as the incident photon energy approaches the photoemission threshold. A theoretical model to calculate the transverse momentum distributions near this photoemission threshold is presented. An excellent match between the experimental measurements and the theoretical calculations is demonstrated. These measurements are relevant to low emittance electron sources for Free Electron Lasers and Ultrafast Electron Diffraction experiments.

  15. Theory of extrinsic and intrinsic heterojunctions in thermal equilibrium

    NASA Technical Reports Server (NTRS)

    Von Ross, O.

    1980-01-01

    A careful analysis of an abrupt heterojunction consisting of two distinct semiconductors either intrinsic or extrinsic is presented. The calculations apply to a one-dimensional, nondegenerate structure. Taking into account all appropriate boundary conditions, it is shown that the intrinsic Fermi level shows a discontinuity at the interface between the two materials which leads to a discontinuity of the valence band edge equal to the difference in the band gap energies of the two materials. The conduction band edge stays continuous however. This result is independent of possible charged interface states and in sharp contrast to the Anderson model. The reasons for this discrepancy are discussed.

  16. Landscape and Health: Connecting Psychology, Aesthetics, and Philosophy through the Concept of Affordance.

    PubMed

    Menatti, Laura; Casado da Rocha, Antonio

    2016-01-01

    In this paper we address a frontier topic in the humanities, namely how the cultural and natural construction that we call landscape affects well-being and health. Following an updated review of evidence-based literature in the fields of medicine, psychology, and architecture, we propose a new theoretical framework called "processual landscape," which is able to explain both the health-landscape and the medical agency-structure binomial pairs. We provide a twofold analysis of landscape, from both the cultural and naturalist points of view: in order to take into account its relationship with health, the definition of landscape as a cultural product needs to be broadened through naturalization, grounding it in the scientific domain. Landscape cannot be distinguished from the ecological environment. For this reason, we naturalize the idea of landscape through the notion of affordance and Gibson's ecological psychology. In doing so, we stress the role of agency in the theory of perception and the health-landscape relationship. Since it is the result of continuous and co-creational interaction between the cultural agent, the biological agent and the affordances offered to the landscape perceiver, the processual landscape is, in our opinion, the most comprehensive framework for explaining the health-landscape relationship. The consequences of our framework are not only theoretical, but ethical also: insofar as health is greatly affected by landscape, this construction represents something more than just part of our heritage or a place to be preserved for the aesthetic pleasure it provides. Rather, we can talk about the right to landscape as something intrinsically linked to the well-being of present and future generations. PMID:27199808

  17. Landscape and Health: Connecting Psychology, Aesthetics,