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Sample records for dynamics simulations reveal

  1. Peptide crystal simulations reveal hidden dynamics

    PubMed Central

    Janowski, Pawel A.; Cerutti, David S.; Holton, James; Case, David A.

    2013-01-01

    Molecular dynamics simulations of biomolecular crystals at atomic resolution have the potential to recover information on dynamics and heterogeneity hidden in the X-ray diffraction data. We present here 9.6 microseconds of dynamics in a small helical peptide crystal with 36 independent copies of the unit cell. The average simulation structure agrees with experiment to within 0.28 Å backbone and 0.42 Å all-atom rmsd; a model refined against the average simulation density agrees with the experimental structure to within 0.20 Å backbone and 0.33 Å all-atom rmsd. The R-factor between the experimental structure factors and those derived from this unrestrained simulation is 23% to 1.0 Å resolution. The B-factors for most heavy atoms agree well with experiment (Pearson correlation of 0.90), but B-factors obtained by refinement against the average simulation density underestimate the coordinate fluctuations in the underlying simulation where the simulation samples alternate conformations. A dynamic flow of water molecules through channels within the crystal lattice is observed, yet the average water density is in remarkable agreement with experiment. A minor population of unit cells is characterized by reduced water content, 310 helical propensity and a gauche(−) side-chain rotamer for one of the valine residues. Careful examination of the experimental data suggests that transitions of the helices are a simulation artifact, although there is indeed evidence for alternate valine conformers and variable water content. This study highlights the potential for crystal simulations to detect dynamics and heterogeneity in experimental diffraction data, as well as to validate computational chemistry methods. PMID:23631449

  2. Reveal protein dynamics by combining computer simulation and neutron scattering

    NASA Astrophysics Data System (ADS)

    Hong, Liang; Smith, Jeremy; CenterMolecular Biophysics Team

    2014-03-01

    Protein carries out most functions in living things on the earth through characteristic modulation of its three-dimensional structure over time. Understanding the microscopic nature of the protein internal motion and its connection to the function and structure of the biomolecule is a central topic in biophysics, and of great practical importance for drug design, study of diseases, and the development of renewable energy, etc. Under physiological conditions, protein exhibits a complex dynamics landscape, i.e., a variety of diffusive and conformational motions occur on similar time and length scales. This variety renders difficult the derivation of a simplified description of protein internal motions in terms of a small number of distinct, additive components. This difficulty is overcome by our work using a combined approach of Molecular Dynamics (MD) simulations and the Neutron Scattering experiments. Our approach enables distinct protein motions to be characterized separately, furnishing an in-depth understanding of the connection between protein structure, dynamics and function.

  3. Self-similar multiscale structure of lignin revealed by neutron scattering and molecular dynamics simulation

    SciTech Connect

    Petridis, Loukas; Pingali, Sai Venkatesh; Urban, Volker; Heller, William T; O'Neill, Hugh Michael; Foston, Marcus B; Ragauskas, Arthur J; Smith, Jeremy C

    2011-01-01

    Lignin, a major polymeric component of plant cell walls, forms aggregates in vivo and poses a barrier to cellulosic ethanol production. Here, neutron scattering experiments and molecular dynamics simulations reveal that lignin aggregates are characterized by a surface fractal dimension that is invariant under change of scale from 1 1000 A. The simulations also reveal extensive water penetration of the aggregates and heterogeneous chain dynamics corresponding to a rigid core with a fluid surface.

  4. Structure-based simulations reveal concerted dynamics of GPCR activation.

    PubMed

    Leioatts, Nicholas; Suresh, Pooja; Romo, Tod D; Grossfield, Alan

    2014-10-01

    G protein-coupled receptors (GPCRs) are a vital class of proteins that transduce biological signals across the cell membrane. However, their allosteric activation mechanism is not fully understood; crystal structures of active and inactive receptors have been reported, but the functional pathway between these two states remains elusive. Here, we use structure-based (Gō-like) models to simulate activation of two GPCRs, rhodopsin and the β₂ adrenergic receptor (β₂AR). We used data-derived reaction coordinates that capture the activation mechanism for both proteins, showing that activation proceeds through quantitatively different paths in the two systems. Both reaction coordinates are determined from the dominant concerted motions in the simulations so the technique is broadly applicable. There were two surprising results. First, the main structural changes in the simulations were distributed throughout the transmembrane bundle, and not localized to the obvious areas of interest, such as the intracellular portion of Helix 6. Second, the activation (and deactivation) paths were distinctly nonmonotonic, populating states that were not simply interpolations between the inactive and active structures. These transitions also suggest a functional explanation for β₂AR's basal activity: it can proceed through a more broadly defined path during the observed transitions. © 2014 Wiley Periodicals, Inc.

  5. Ligand Induced Conformational Changes of the Human Serotonin Transporter Revealed by Molecular Dynamics Simulations

    PubMed Central

    Grouleff, Julie; Schiøtt, Birgit

    2013-01-01

    The competitive inhibitor cocaine and the non-competitive inhibitor ibogaine induce different conformational states of the human serotonin transporter. It has been shown from accessibility experiments that cocaine mainly induces an outward-facing conformation, while the non-competitive inhibitor ibogaine, and its active metabolite noribogaine, have been proposed to induce an inward-facing conformation of the human serotonin transporter similar to what has been observed for the endogenous substrate, serotonin. The ligand induced conformational changes within the human serotonin transporter caused by these three different types of ligands, substrate, non-competitive and competitive inhibitors, are studied from multiple atomistic molecular dynamics simulations initiated from a homology model of the human serotonin transporter. The results reveal that diverse conformations of the human serotonin transporter are captured from the molecular dynamics simulations depending on the type of the ligand bound. The inward-facing conformation of the human serotonin transporter is reached with noribogaine bound, and this state resembles a previously identified inward-facing conformation of the human serotonin transporter obtained from molecular dynamics simulation with bound substrate, but also a recently published inward-facing conformation of a bacterial homolog, the leucine transporter from Aquifex Aoelicus. The differences observed in ligand induced behavior are found to originate from different interaction patterns between the ligands and the protein. Such atomic-level understanding of how an inhibitor can dictate the conformational response of a transporter by ligand binding may be of great importance for future drug design. PMID:23776432

  6. Revealing Atomic-Level Mechanisms of Protein Allostery with Molecular Dynamics Simulations.

    PubMed

    Hertig, Samuel; Latorraca, Naomi R; Dror, Ron O

    2016-06-01

    Molecular dynamics (MD) simulations have become a powerful and popular method for the study of protein allostery, the widespread phenomenon in which a stimulus at one site on a protein influences the properties of another site on the protein. By capturing the motions of a protein's constituent atoms, simulations can enable the discovery of allosteric binding sites and the determination of the mechanistic basis for allostery. These results can provide a foundation for applications including rational drug design and protein engineering. Here, we provide an introduction to the investigation of protein allostery using molecular dynamics simulation. We emphasize the importance of designing simulations that include appropriate perturbations to the molecular system, such as the addition or removal of ligands or the application of mechanical force. We also demonstrate how the bidirectional nature of allostery-the fact that the two sites involved influence one another in a symmetrical manner-can facilitate such investigations. Through a series of case studies, we illustrate how these concepts have been used to reveal the structural basis for allostery in several proteins and protein complexes of biological and pharmaceutical interest.

  7. Revealing Atomic-Level Mechanisms of Protein Allostery with Molecular Dynamics Simulations

    PubMed Central

    Hertig, Samuel

    2016-01-01

    Molecular dynamics (MD) simulations have become a powerful and popular method for the study of protein allostery, the widespread phenomenon in which a stimulus at one site on a protein influences the properties of another site on the protein. By capturing the motions of a protein’s constituent atoms, simulations can enable the discovery of allosteric binding sites and the determination of the mechanistic basis for allostery. These results can provide a foundation for applications including rational drug design and protein engineering. Here, we provide an introduction to the investigation of protein allostery using molecular dynamics simulation. We emphasize the importance of designing simulations that include appropriate perturbations to the molecular system, such as the addition or removal of ligands or the application of mechanical force. We also demonstrate how the bidirectional nature of allostery—the fact that the two sites involved influence one another in a symmetrical manner—can facilitate such investigations. Through a series of case studies, we illustrate how these concepts have been used to reveal the structural basis for allostery in several proteins and protein complexes of biological and pharmaceutical interest. PMID:27285999

  8. Specialized Dynamical Properties of Promiscuous Residues Revealed by Simulated Conformational Ensembles

    PubMed Central

    2013-01-01

    The ability to interact with different partners is one of the most important features in proteins. Proteins that bind a large number of partners (hubs) have been often associated with intrinsic disorder. However, many examples exist of hubs with an ordered structure, and evidence of a general mechanism promoting promiscuity in ordered proteins is still elusive. An intriguing hypothesis is that promiscuous binding sites have specific dynamical properties, distinct from the rest of the interface and pre-existing in the protein isolated state. Here, we present the first comprehensive study of the intrinsic dynamics of promiscuous residues in a large protein data set. Different computational methods, from coarse-grained elastic models to geometry-based sampling methods and to full-atom Molecular Dynamics simulations, were used to generate conformational ensembles for the isolated proteins. The flexibility and dynamic correlations of interface residues with a different degree of binding promiscuity were calculated and compared considering side chain and backbone motions, the latter both on a local and on a global scale. The study revealed that (a) promiscuous residues tend to be more flexible than nonpromiscuous ones, (b) this additional flexibility has a higher degree of organization, and (c) evolutionary conservation and binding promiscuity have opposite effects on intrinsic dynamics. Findings on simulated ensembles were also validated on ensembles of experimental structures extracted from the Protein Data Bank (PDB). Additionally, the low occurrence of single nucleotide polymorphisms observed for promiscuous residues indicated a tendency to preserve binding diversity at these positions. A case study on two ubiquitin-like proteins exemplifies how binding promiscuity in evolutionary related proteins can be modulated by the fine-tuning of the interface dynamics. The interplay between promiscuity and flexibility highlighted here can inspire new directions in protein

  9. Nanomechanical Behavior of Single Crystalline SiC Nanotubes Revealed by Molecular Dynamics Simulations

    SciTech Connect

    Wang, Zhiguo; Zu, Xiaotao T.; Gao, Fei; Weber, William J.

    2008-11-01

    Molecular dynamics simulations with Tersoff potentials were used to study the response of single crystalline SiC nanotubes under tensile, compressive, torsional, combined tension-torsional and combined compression-torsional strains. The simulation results reveal that the nanotubes deform through bond-stretching and breaking and exhibit brittle properties under uniaxial tensile strain, except for the thinnest nanotube at high temperatures, which fails in a ductile manner. Under uniaxial compressive strain, the SiC nanotubes buckle with two modes, i.e. shell buckling and column buckling, depending on the length of the nanotubes. Under torsional strain, the nanotubes buckle either collapse in the middle region into a dumbbell-like structure for thinner wall thicknesses or fail by bond breakage for the largest wall thickness. Both the tensile failure stress and buckling stress decrease under combined tension-torsional and combined compression-torsional strain, and they decrease with increasing torsional rate under combined loading.

  10. Structural signatures of DRD4 mutants revealed using molecular dynamics simulations: Implications for drug targeting.

    PubMed

    Jatana, Nidhi; Thukral, Lipi; Latha, N

    2016-01-01

    Human Dopamine Receptor D4 (DRD4) orchestrates several neurological functions and represents a target for many psychological disorders. Here, we examined two rare variants in DRD4; V194G and R237L, which elicit functional alterations leading to disruption of ligand binding and G protein coupling, respectively. Using atomistic molecular dynamics (MD) simulations, we provide in-depth analysis to reveal structural signatures of wild and mutant complexes with their bound agonist and antagonist ligands. We constructed intra-protein network graphs to discriminate the global conformational changes induced by mutations. The simulations also allowed us to elucidate the local side-chain dynamical variations in ligand-bound mutant receptors. The data suggest that the mutation in transmembrane V (V194G) drastically disrupts the organization of ligand binding site and causes disorder in the native helical arrangement. Interestingly, the R237L mutation leads to significant rewiring of side-chain contacts in the intracellular loop 3 (site of mutation) and also affects the distant transmembrane topology. Additionally, these mutations lead to compact ICL3 region compared to the wild type, indicating that the receptor would be inaccessible for G protein coupling. Our findings thus reveal unreported structural determinants of the mutated DRD4 receptor and provide a robust framework for design of effective novel drugs.

  11. Mechanically untying a protein slipknot: multiple pathways revealed by force spectroscopy and steered molecular dynamics simulations.

    PubMed

    He, Chengzhi; Genchev, Georgi Z; Lu, Hui; Li, Hongbin

    2012-06-27

    Protein structure is highly diverse when considering a wide range of protein types, helping to give rise to the multitude of functions that proteins perform. In particular, certain proteins are known to adopt a knotted or slipknotted fold. How such proteins undergo mechanical unfolding was investigated utilizing a combination of single molecule atomic force microscopy (AFM), protein engineering, and steered molecular dynamics (SMD) simulations to show the mechanical unfolding mechanism of the slipknotted protein AFV3-109. Our results reveal that the mechanical unfolding of AFV3-109 can proceed via multiple parallel unfolding pathways that all cause the protein slipknot to untie and the polypeptide chain to completely extend. These distinct unfolding pathways proceed via either a two- or three-state unfolding process involving the formation of a well-defined, stable intermediate state. SMD simulations predict the same contour length increments for different unfolding pathways as single molecule AFM results, thus providing a plausible molecular mechanism for the mechanical unfolding of AFV3-109. These SMD simulations also reveal that two-state unfolding is initiated from both the N- and C-termini, while three-state unfolding is initiated only from the C-terminus. In both pathways, the protein slipknot was untied during unfolding, and no tightened slipknot conformation was observed. Detailed analysis revealed that interactions between key structural elements lock the knotting loop in place, preventing it from shrinking and the formation of a tightened slipknot conformation. Our results demonstrate the bifurcation of the mechanical unfolding pathway of AFV3-109 and point to the generality of a kinetic partitioning mechanism for protein folding/unfolding.

  12. Mechanically Untying a Protein Slipknot: Multiple Pathways Revealed by Force Spectroscopy and Steered Molecular Dynamics Simulations

    PubMed Central

    He, Chengzhi; Genchev, Georgi Z.; Lu, Hui; Li, Hongbin

    2013-01-01

    Protein structure is highly diverse when considering a wide range of protein types, helping to give rise to the multitude of functions that proteins perform. In particular, certain proteins are known to adopt a knotted or slipknotted fold. How such proteins undergo mechanical unfolding was investigated utilizing a combination of single molecule atomic force microscopy (AFM), protein engineering and steered molecular dynamics (SMD) simulations to show the mechanical unfolding mechanism of the slipknotted protein AFV3-109. Our results reveal that the mechancial unfolding of AFV3-109 can proceed via multiple parallel unfolding pathways that all cause the protein slipknot to untie, and the polypeptide chain to completely extend. These distinct unfolding pathways proceed either via a two-state or three-state unfolding process involving the formation of a well-defined, stable intermediate state. SMD simulations predict the same contour length increments for different unfolding pathways as single molecule AFM results, thus provding a plausible molecular mechanism for the mechanical unfolding of AFV3-109. These SMD simulations also reveal that two-state unfolding is initiated from both the N- and C-termini, while three-state unfolding is initiated only from the C-terminus. In both pathways, the protein slipknot was untied during unfolding, and no tightened slipknot conformation observed. Detailed analysis revealed that interactions between key structural elements lock the knotting loop in place, preventing it from shrinking and the formation of a tightened slipknot conformation. Our results demonstrate the bifurcation of the mechancial unfolding pathway of AFV3-109, and point to the generality of a kinetic partitioning mechanism for protein folding/unfolding. PMID:22626004

  13. Mechanical properties of a complete microtubule revealed through molecular dynamics simulation.

    PubMed

    Wells, David B; Aksimentiev, Aleksei

    2010-07-21

    Microtubules (MTs) are the largest type of cellular filament, essential in processes ranging from mitosis and meiosis to flagellar motility. Many of the processes depend critically on the mechanical properties of the MT, but the elastic moduli, notably the Young's modulus, are not directly revealed in experiment, which instead measures either flexural rigidity or response to radial deformation. Molecular dynamics (MD) is a method that allows the mechanical properties of single biomolecules to be investigated through computation. Typically, MD requires an atomic resolution structure of the molecule, which is unavailable for many systems, including MTs. By combining structural information from cryo-electron microscopy and electron crystallography, we have constructed an all-atom model of a complete MT and used MD to determine its mechanical properties. The simulations revealed nonlinear axial stress-strain behavior featuring a pronounced softening under extension, a possible plastic deformation transition under radial compression, and a distinct asymmetry in response to the two senses of twist. This work demonstrates the possibility of combining different levels of structural information to produce all-atom models suitable for quantitative MD simulations, which extends the range of systems amenable to the MD method and should enable exciting advances in our microscopic knowledge of biology. Copyright (c) 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  14. Function of the hydration layer around an antifreeze protein revealed by atomistic molecular dynamics simulations

    SciTech Connect

    Nutt, David; Smith, Jeremy C

    2008-10-01

    Atomistic molecular dynamics simulations are used to investigate the mechanism by which the antifreeze protein from the spruce budworm, Choristoneura fumiferana, binds to ice. Comparison of structural and dynamic properties of the water around the three faces of the triangular prism-shaped protein in aqueous solution reveals that at low temperature the water structure is ordered and the dynamics slowed down around the ice-binding face of the protein, with a disordering effect observed around the other two faces. These results suggest a dual role for the solvation water around the protein. The preconfigured solvation shell around the ice-binding face is involved in the initial recognition and binding of the antifreeze protein to ice by lowering the barrier for binding and consolidation of the protein:ice interaction surface. Thus, the antifreeze protein can bind to the molecularly rough ice surface by becoming actively involved in the formation of its own binding site. Also, the disruption of water structure around the rest of the protein helps prevent the adsorbed protein becoming covered by further ice growth.

  15. Molecular dynamics simulation revealed binding of nucleotide inhibitors to ZIKV polymerase over 444 nanoseconds.

    PubMed

    Elfiky, Abdo A; Elshemey, Wael M

    2017-09-18

    In the year 2015, new Zika virus (ZIKV) broke out in Brazil and spread away in more than 80 countries. Scientists directed their efforts toward viral polymerase in attempt to find inhibitors that might interfere with its function. In this study, molecular dynamics simulation (MDS) was performed over 444 ns for a ZIKV polymerase model. Molecular docking (MD) was then performed every 10 ns during the MDS course to ensure the binding of small molecules to the polymerase over the entire time of the simulation. MD revealed the binding ability of four suggested guanosine inhibitors (GIs); (Guanosine substituted with OH and SH (phenyl) oxidanyl in the 2' carbon of the ribose ring). The GIs were compared to guanosine triphosphate (GTP) and five anti-hepatitis C virus drugs (either approved or under clinical trials). The mode of binding and the binding performance of GIs to ZIKV polymerase were found to be the same as GTP. Hence, these compounds were capable of competing GTP for the active site. Moreover, GIs bound to ZIKV active site more tightly compared to ribavirin, the wide-range antiviral drug. © 2017 Wiley Periodicals, Inc.

  16. Quantum Dynamics Simulations Reveal Vibronic Effects on the Optical Properties of [n]Cycloparaphenylenes.

    PubMed

    Reddy, V Sivaranjana; Camacho, Cristopher; Xia, Jianlong; Jasti, Ramesh; Irle, Stephan

    2014-09-09

    The size-dependent ultraviolet/visible photophysical property trends of [n]cycloparaphenylenes ([n]CPPs, n = 6, 8, and 10) are theoretically investigated using quantum dynamics simulations. For geometry optimizations on the ground- and excited-state Born-Oppenheimer potential energy surfaces (PESs), we employ density functional theory (DFT) and time-dependent DFT calculations. Harmonic normal-mode analyses are carried out for the electronic ground state at Franck-Condon geometries. A diabatic Hamiltonian, comprising four low-lying singlet excited electronic states and 26 vibrational degrees of freedom of CPP, is constructed within the linear vibronic coupling (VC) model to elucidate the absorption spectral features in the range of 300-500 nm. Quantum nuclear dynamics is simulated within the multiconfiguration time-dependent Hartree approach to calculate the vibronic structure of the excited electronic states. The symmetry-forbidden S0 → S1 transition appears in the longer wavelength region of the spectrum with weak intensity due to VC. It is found that the Jahn-Teller and pseudo-Jahn-Teller effects in the doubly degenerate S2 and S3 electronic states are essential in the quantitative interpretation of the experimental observation of a broad absorption peak around 340 nm. The vibronic mixing of the S1 state with higher electronic states is responsible for the efficient photoluminescence from the S1 state. The fluorescence properties are characterized on the basis of the stationary points of the excited-state PESs. The findings reveal that vibronic effects become important in determining the photophysical properties of CPPs with increased ring size.

  17. Molecular Dynamic Simulations Reveal the Structural Determinants of Fatty Acid Binding to Oxy-Myoglobin

    PubMed Central

    Chintapalli, Sree V.; Bhardwaj, Gaurav; Patel, Reema; Shah, Natasha; Patterson, Randen L.; van Rossum, Damian B.; Anishkin, Andriy; Adams, Sean H.

    2015-01-01

    The mechanism(s) by which fatty acids are sequestered and transported in muscle have not been fully elucidated. A potential key player in this process is the protein myoglobin (Mb). Indeed, there is a catalogue of empirical evidence supporting direct interaction of globins with fatty acid metabolites; however, the binding pocket and regulation of the interaction remains to be established. In this study, we employed a computational strategy to elucidate the structural determinants of fatty acids (palmitic & oleic acid) binding to Mb. Sequence analysis and docking simulations with a horse (Equus caballus) structural Mb reference reveals a fatty acid-binding site in the hydrophobic cleft near the heme region in Mb. Both palmitic acid and oleic acid attain a “U” shaped structure similar to their conformation in pockets of other fatty acid-binding proteins. Specifically, we found that the carboxyl head group of palmitic acid coordinates with the amino group of Lys45, whereas the carboxyl group of oleic acid coordinates with both the amino groups of Lys45 and Lys63. The alkyl tails of both fatty acids are supported by surrounding hydrophobic residues Leu29, Leu32, Phe33, Phe43, Phe46, Val67, Val68 and Ile107. In the saturated palmitic acid, the hydrophobic tail moves freely and occasionally penetrates deeper inside the hydrophobic cleft, making additional contacts with Val28, Leu69, Leu72 and Ile111. Our simulations reveal a dynamic and stable binding pocket in which the oxygen molecule and heme group in Mb are required for additional hydrophobic interactions. Taken together, these findings support a mechanism in which Mb acts as a muscle transporter for fatty acid when it is in the oxygenated state and releases fatty acid when Mb converts to deoxygenated state. PMID:26030763

  18. Unfolding mechanism of thrombin-binding aptamer revealed by molecular dynamics simulation and Markov State Model

    NASA Astrophysics Data System (ADS)

    Zeng, Xiaojun; Zhang, Liyun; Xiao, Xiuchan; Jiang, Yuanyuan; Guo, Yanzhi; Yu, Xinyan; Pu, Xuemei; Li, Menglong

    2016-04-01

    Thrombin-binding aptamer (TBA) with the sequence 5‧GGTTGGTGTGGTTGG3‧ could fold into G-quadruplex, which correlates with functionally important genomic regionsis. However, unfolding mechanism involved in the structural stability of G-quadruplex has not been satisfactorily elucidated on experiments so far. Herein, we studied the unfolding pathway of TBA by a combination of molecular dynamics simulation (MD) and Markov State Model (MSM). Our results revealed that the unfolding of TBA is not a simple two-state process but proceeds along multiple pathways with multistate intermediates. One high flux confirms some observations from NMR experiment. Another high flux exhibits a different and simpler unfolding pathway with less intermediates. Two important intermediate states were identified. One is similar to the G-triplex reported in the folding of G-quadruplex, but lack of H-bonding between guanines in the upper plane. More importantly, another intermediate state acting as a connector to link the folding region and the unfolding one, was the first time identified, which exhibits higher population and stability than the G-triplex-like intermediate. These results will provide valuable information for extending our understanding the folding landscape of G-quadruplex formation.

  19. Unfolding mechanism of thrombin-binding aptamer revealed by molecular dynamics simulation and Markov State Model

    PubMed Central

    Zeng, Xiaojun; Zhang, Liyun; Xiao, Xiuchan; Jiang, Yuanyuan; Guo, Yanzhi; Yu, Xinyan; Pu, Xuemei; Li, Menglong

    2016-01-01

    Thrombin-binding aptamer (TBA) with the sequence 5′GGTTGGTGTGGTTGG3′ could fold into G-quadruplex, which correlates with functionally important genomic regionsis. However, unfolding mechanism involved in the structural stability of G-quadruplex has not been satisfactorily elucidated on experiments so far. Herein, we studied the unfolding pathway of TBA by a combination of molecular dynamics simulation (MD) and Markov State Model (MSM). Our results revealed that the unfolding of TBA is not a simple two-state process but proceeds along multiple pathways with multistate intermediates. One high flux confirms some observations from NMR experiment. Another high flux exhibits a different and simpler unfolding pathway with less intermediates. Two important intermediate states were identified. One is similar to the G-triplex reported in the folding of G-quadruplex, but lack of H-bonding between guanines in the upper plane. More importantly, another intermediate state acting as a connector to link the folding region and the unfolding one, was the first time identified, which exhibits higher population and stability than the G-triplex-like intermediate. These results will provide valuable information for extending our understanding the folding landscape of G-quadruplex formation. PMID:27045335

  20. Using simulations and kinetic network models to reveal the dynamics and functions of riboswitches.

    PubMed

    Lin, Jong-Chin; Yoon, Jeseong; Hyeon, Changbong; Thirumalai, D

    2015-01-01

    Riboswitches, RNA elements found in the untranslated region, regulate gene expression by binding to target metaboloites with exquisite specificity. Binding of metabolites to the conserved aptamer domain allosterically alters the conformation in the downstream expression platform. The fate of gene expression is determined by the changes in the downstream RNA sequence. As the metabolite-dependent cotranscriptional folding and unfolding dynamics of riboswitches are the key determinant of gene expression, it is important to investigate both the thermodynamics and kinetics of riboswitches both in the presence and absence of metabolite. Single molecule force experiments that decipher the free energy landscape of riboswitches from their mechanical responses, theoretical and computational studies have recently shed light on the distinct mechanism of folding dynamics in different classes of riboswitches. Here, we first discuss the dynamics of water around riboswitch, highlighting that water dynamics can enhance the fluctuation of nucleic acid structure. To go beyond native state fluctuations, we used the Self-Organized Polymer model to predict the dynamics of add adenine riboswitch under mechanical forces. In addition to quantitatively predicting the folding landscape of add-riboswitch, our simulations also explain the difference in the dynamics between pbuE adenine- and add adenine-riboswitches. In order to probe the function in vivo, we use the folding landscape to propose a system level kinetic network model to quantitatively predict how gene expression is regulated for riboswitches that are under kinetic control.

  1. Using Simulations and Kinetic Network Models to Reveal the Dynamics and Functions of Riboswitches

    PubMed Central

    Lin, Jong-Chin; Yoon, Jeseong; Hyeon, Changbong; Thirumalai, D.

    2017-01-01

    Riboswitches, RNA elements found in the untranslated region, regulate gene expression by binding to target metaboloites with exquisite specificity. Binding of metabolites to the conserved aptamer domain allosterically alters the conformation in the downstream expression platform. The fate of gene expression is determined by the changes in the downstream RNA sequence. As the metabolite-dependent cotranscriptional folding and unfolding dynamics of riboswitches are the key determinant of gene expression, it is important to investigate both the thermodynamics and kinetics of riboswitches both in the presence and absence of metabolite. Single molecule force experiments that decipher the free energy landscape of riboswitches from their mechanical responses, theoretical and computational studies have recently shed light on the distinct mechanism of folding dynamics in different classes of riboswitches. Here, we first discuss the dynamics of water around riboswitch, highlighting that water dynamics can enhance the fluctuation of nucleic acid structure. To go beyond native state fluctuations, we used the Self-Organized Polymer model to predict the dynamics of add adenine riboswitch under mechanical forces. In addition to quantitatively predicting the folding landscape of add-riboswitch, our simulations also explain the difference in the dynamics between pbuE adenine- and add adenine-riboswitches. In order to probe the function in vivo, we use the folding landscape to propose a system level kinetic network model to quantitatively predict how gene expression is regulated for riboswitches that are under kinetic control. PMID:25726468

  2. Hydrated Electron Transfer to Nucleobases in Aqueous Solutions Revealed by Ab Initio Molecular Dynamics Simulations.

    PubMed

    Zhao, Jing; Wang, Mei; Fu, Aiyun; Yang, Hongfang; Bu, Yuxiang

    2015-08-03

    We present an ab initio molecular dynamics (AIMD) simulation study into the transfer dynamics of an excess electron from its cavity-shaped hydrated electron state to a hydrated nucleobase (NB)-bound state. In contrast to the traditional view that electron localization at NBs (G/A/C/T), which is the first step for electron-induced DNA damage, is related only to dry or prehydrated electrons, and a fully hydrated electron no longer transfers to NBs, our AIMD simulations indicate that a fully hydrated electron can still transfer to NBs. We monitored the transfer dynamics of fully hydrated electrons towards hydrated NBs in aqueous solutions by using AIMD simulations and found that due to solution-structure fluctuation and attraction of NBs, a fully hydrated electron can transfer to a NB gradually over time. Concurrently, the hydrated electron cavity gradually reorganizes, distorts, and even breaks. The transfer could be completed in about 120-200 fs in four aqueous NB solutions, depending on the electron-binding ability of hydrated NBs and the structural fluctuation of the solution. The transferring electron resides in the π*-type lowest unoccupied molecular orbital of the NB, which leads to a hydrated NB anion. Clearly, the observed transfer of hydrated electrons can be attributed to the strong electron-binding ability of hydrated NBs over the hydrated electron cavity, which is the driving force, and the transfer dynamics is structure-fluctuation controlled. This work provides new insights into the evolution dynamics of hydrated electrons and provides some helpful information for understanding the DNA-damage mechanism in solution.

  3. Molecular Dynamics Simulations Reveal the Mechanisms of Allosteric Activation of Hsp90 by Designed Ligands

    NASA Astrophysics Data System (ADS)

    Vettoretti, Gerolamo; Moroni, Elisabetta; Sattin, Sara; Tao, Jiahui; Agard, David A.; Bernardi, Anna; Colombo, Giorgio

    2016-04-01

    Controlling biochemical pathways through chemically designed modulators may provide novel opportunities to develop therapeutic drugs and chemical tools. The underlying challenge is to design new molecular entities able to act as allosteric chemical switches that selectively turn on/off functions by modulating the conformational dynamics of their target protein. We examine the origins of the stimulation of ATPase and closure kinetics in the molecular chaperone Hsp90 by allosteric modulators through atomistic molecular dynamics (MD) simulations and analysis of protein-ligand interactions. In particular, we focus on the cross-talk between allosteric ligands and protein conformations and its effect on the dynamic properties of the chaperone’s active state. We examine the impact of different allosteric modulators on the stability, structural and internal dynamics properties of Hsp90 closed state. A critical aspect of this study is the development of a quantitative model that correlates Hsp90 activation to the presence of a certain compound, making use of information on the dynamic adaptation of protein conformations to the presence of the ligand, which allows to capture conformational states relevant in the activation process. We discuss the implications of considering the conformational dialogue between allosteric ligands and protein conformations for the design of new functional modulators.

  4. Molecular Dynamics Simulations Reveal the Mechanisms of Allosteric Activation of Hsp90 by Designed Ligands

    PubMed Central

    Vettoretti, Gerolamo; Moroni, Elisabetta; Sattin, Sara; Tao, Jiahui; Agard, David A.; Bernardi, Anna; Colombo, Giorgio

    2016-01-01

    Controlling biochemical pathways through chemically designed modulators may provide novel opportunities to develop therapeutic drugs and chemical tools. The underlying challenge is to design new molecular entities able to act as allosteric chemical switches that selectively turn on/off functions by modulating the conformational dynamics of their target protein. We examine the origins of the stimulation of ATPase and closure kinetics in the molecular chaperone Hsp90 by allosteric modulators through atomistic molecular dynamics (MD) simulations and analysis of protein-ligand interactions. In particular, we focus on the cross-talk between allosteric ligands and protein conformations and its effect on the dynamic properties of the chaperone’s active state. We examine the impact of different allosteric modulators on the stability, structural and internal dynamics properties of Hsp90 closed state. A critical aspect of this study is the development of a quantitative model that correlates Hsp90 activation to the presence of a certain compound, making use of information on the dynamic adaptation of protein conformations to the presence of the ligand, which allows to capture conformational states relevant in the activation process. We discuss the implications of considering the conformational dialogue between allosteric ligands and protein conformations for the design of new functional modulators. PMID:27032695

  5. Effects of ionic strength on SAXS data for proteins revealed by molecular dynamics simulations.

    PubMed

    Oroguchi, Tomotaka; Ikeguchi, Mitsunori

    2011-01-14

    The combination of small-angle X-ray solution scattering (SAXS) experiments and molecular dynamics (MD) simulations is now becoming a powerful tool to study protein conformations in solution at an atomic resolution. In this study, we investigated effects of ionic strength on SAXS data theoretically by using MD simulations of hen egg white lysozyme at various NaCl concentrations from 0 to 1 M. The calculated SAXS excess intensities showed a significant dependence on ion concentration, which originates from the different solvent density distributions in the presence and absence of ions. The addition of ions induced a slow convergence of the SAXS data, and a ∼20 ns simulation is required to obtain convergence of the SAXS data with the presence of ions whereas only a 0.2 ns simulation is sufficient in the absence of ions. To circumvent the problem of the slow convergence in the presence of ions, we developed a novel method that reproduces the SAXS excess intensities with the presence of ions from short MD trajectories in pure water. By applying this method to SAXS data for the open and closed forms of transferrin at 1 M ion concentration, the correct form could be identified by simply using short MD simulations of the protein in pure water for 0.2 ns.

  6. Effects of ionic strength on SAXS data for proteins revealed by molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Oroguchi, Tomotaka; Ikeguchi, Mitsunori

    2011-01-01

    The combination of small-angle X-ray solution scattering (SAXS) experiments and molecular dynamics (MD) simulations is now becoming a powerful tool to study protein conformations in solution at an atomic resolution. In this study, we investigated effects of ionic strength on SAXS data theoretically by using MD simulations of hen egg white lysozyme at various NaCl concentrations from 0 to 1 M. The calculated SAXS excess intensities showed a significant dependence on ion concentration, which originates from the different solvent density distributions in the presence and absence of ions. The addition of ions induced a slow convergence of the SAXS data, and a ˜20 ns simulation is required to obtain convergence of the SAXS data with the presence of ions whereas only a 0.2 ns simulation is sufficient in the absence of ions. To circumvent the problem of the slow convergence in the presence of ions, we developed a novel method that reproduces the SAXS excess intensities with the presence of ions from short MD trajectories in pure water. By applying this method to SAXS data for the open and closed forms of transferrin at 1 M ion concentration, the correct form could be identified by simply using short MD simulations of the protein in pure water for 0.2 ns.

  7. Slow dynamics of a protein backbone in molecular dynamics simulation revealed by time-structure based independent component analysis

    SciTech Connect

    Naritomi, Yusuke; Fuchigami, Sotaro

    2013-12-07

    We recently proposed the method of time-structure based independent component analysis (tICA) to examine the slow dynamics involved in conformational fluctuations of a protein as estimated by molecular dynamics (MD) simulation [Y. Naritomi and S. Fuchigami, J. Chem. Phys. 134, 065101 (2011)]. Our previous study focused on domain motions of the protein and examined its dynamics by using rigid-body domain analysis and tICA. However, the protein changes its conformation not only through domain motions but also by various types of motions involving its backbone and side chains. Some of these motions might occur on a slow time scale: we hypothesize that if so, we could effectively detect and characterize them using tICA. In the present study, we investigated slow dynamics of the protein backbone using MD simulation and tICA. The selected target protein was lysine-, arginine-, ornithine-binding protein (LAO), which comprises two domains and undergoes large domain motions. MD simulation of LAO in explicit water was performed for 1 μs, and the obtained trajectory of C{sub α} atoms in the backbone was analyzed by tICA. This analysis successfully provided us with slow modes for LAO that represented either domain motions or local movements of the backbone. Further analysis elucidated the atomic details of the suggested local motions and confirmed that these motions truly occurred on the expected slow time scale.

  8. Slow dynamics of a protein backbone in molecular dynamics simulation revealed by time-structure based independent component analysis

    NASA Astrophysics Data System (ADS)

    Naritomi, Yusuke; Fuchigami, Sotaro

    2013-12-01

    We recently proposed the method of time-structure based independent component analysis (tICA) to examine the slow dynamics involved in conformational fluctuations of a protein as estimated by molecular dynamics (MD) simulation [Y. Naritomi and S. Fuchigami, J. Chem. Phys. 134, 065101 (2011)]. Our previous study focused on domain motions of the protein and examined its dynamics by using rigid-body domain analysis and tICA. However, the protein changes its conformation not only through domain motions but also by various types of motions involving its backbone and side chains. Some of these motions might occur on a slow time scale: we hypothesize that if so, we could effectively detect and characterize them using tICA. In the present study, we investigated slow dynamics of the protein backbone using MD simulation and tICA. The selected target protein was lysine-, arginine-, ornithine-binding protein (LAO), which comprises two domains and undergoes large domain motions. MD simulation of LAO in explicit water was performed for 1 μs, and the obtained trajectory of Cα atoms in the backbone was analyzed by tICA. This analysis successfully provided us with slow modes for LAO that represented either domain motions or local movements of the backbone. Further analysis elucidated the atomic details of the suggested local motions and confirmed that these motions truly occurred on the expected slow time scale.

  9. A Model of Lipid-Free Apolipoprotein A-I Revealed by Iterative Molecular Dynamics Simulation

    PubMed Central

    Zhang, Xing; Lei, Dongsheng; Zhang, Lei; Rames, Matthew; Zhang, Shengli

    2015-01-01

    Apolipoprotein A-I (apo A-I), the major protein component of high-density lipoprotein, has been proven inversely correlated to cardiovascular risk in past decades. The lipid-free state of apo A-I is the initial stage which binds to lipids forming high-density lipoprotein. Molecular models of lipid-free apo A-I have been reported by methods like X-ray crystallography and chemical cross-linking/mass spectrometry (CCL/MS). Through structural analysis we found that those current models had limited consistency with other experimental results, such as those from hydrogen exchange with mass spectrometry. Through molecular dynamics simulations, we also found those models could not reach a stable equilibrium state. Therefore, by integrating various experimental results, we proposed a new structural model for lipid-free apo A-I, which contains a bundled four-helix N-terminal domain (1–192) that forms a variable hydrophobic groove and a mobile short hairpin C-terminal domain (193–243). This model exhibits an equilibrium state through molecular dynamics simulation and is consistent with most of the experimental results known from CCL/MS on lysine pairs, fluorescence resonance energy transfer and hydrogen exchange. This solution-state lipid-free apo A-I model may elucidate the possible conformational transitions of apo A-I binding with lipids in high-density lipoprotein formation. PMID:25793886

  10. A model of lipid-free Apolipoprotein A-I revealed by iterative molecular dynamics simulation

    DOE PAGES

    Zhang, Xing; Lei, Dongsheng; Zhang, Lei; ...

    2015-03-20

    Apolipoprotein A-I (apo A-I), the major protein component of high-density lipoprotein, has been proven inversely correlated to cardiovascular risk in past decades. The lipid-free state of apo A-I is the initial stage which binds to lipids forming high-density lipoprotein. Molecular models of lipid-free apo A-I have been reported by methods like X-ray crystallography and chemical cross-linking/mass spectrometry (CCL/MS). Through structural analysis we found that those current models had limited consistency with other experimental results, such as those from hydrogen exchange with mass spectrometry. Through molecular dynamics simulations, we also found those models could not reach a stable equilibrium state. Therefore,more » by integrating various experimental results, we proposed a new structural model for lipidfree apo A-I, which contains a bundled four-helix N-terminal domain (1–192) that forms a variable hydrophobic groove and a mobile short hairpin C-terminal domain (193–243). This model exhibits an equilibrium state through molecular dynamics simulation and is consistent with most of the experimental results known from CCL/MS on lysine pairs, fluorescence resonance energy transfer and hydrogen exchange. This solution-state lipid-free apo A-I model may elucidate the possible conformational transitions of apo A-I binding with lipids in high-density lipoprotein formation.« less

  11. A model of lipid-free Apolipoprotein A-I revealed by iterative molecular dynamics simulation

    SciTech Connect

    Zhang, Xing; Lei, Dongsheng; Zhang, Lei; Rames, Matthew; Zhang, Shengli

    2015-03-20

    Apolipoprotein A-I (apo A-I), the major protein component of high-density lipoprotein, has been proven inversely correlated to cardiovascular risk in past decades. The lipid-free state of apo A-I is the initial stage which binds to lipids forming high-density lipoprotein. Molecular models of lipid-free apo A-I have been reported by methods like X-ray crystallography and chemical cross-linking/mass spectrometry (CCL/MS). Through structural analysis we found that those current models had limited consistency with other experimental results, such as those from hydrogen exchange with mass spectrometry. Through molecular dynamics simulations, we also found those models could not reach a stable equilibrium state. Therefore, by integrating various experimental results, we proposed a new structural model for lipidfree apo A-I, which contains a bundled four-helix N-terminal domain (1–192) that forms a variable hydrophobic groove and a mobile short hairpin C-terminal domain (193–243). This model exhibits an equilibrium state through molecular dynamics simulation and is consistent with most of the experimental results known from CCL/MS on lysine pairs, fluorescence resonance energy transfer and hydrogen exchange. This solution-state lipid-free apo A-I model may elucidate the possible conformational transitions of apo A-I binding with lipids in high-density lipoprotein formation.

  12. Nonequilibrium Chemical Effects in Single-Molecule SERS Revealed by Ab Initio Molecular Dynamics Simulations.

    PubMed

    Fischer, Sean A; Aprà, Edoardo; Govind, Niranjan; Hess, Wayne P; El-Khoury, Patrick Z

    2017-02-16

    Recent developments in nanophotonics have paved the way for achieving significant advances in the realm of single-molecule chemical detection, imaging, and dynamics. In particular, surface-enhanced Raman scattering (SERS) is a powerful analytical technique that is now routinely used to identify the chemical identity of single molecules. Understanding how nanoscale physical and chemical processes affect single-molecule SERS spectra and selection rules is a challenging task and is still actively debated. Herein, we explore underappreciated chemical phenomena in ultrasensitive SERS. We observe a fluctuating excited electronic state manifold, governed by the conformational dynamics of a molecule (4,4'-dimercaptostilbene, DMS) interacting with a metallic cluster (Ag20). This affects our simulated single-molecule SERS spectra; the time trajectories of a molecule interacting with its unique local environment dictates the relative intensities of the observable Raman-active vibrational states. Ab initio molecular dynamics of a model Ag20-DMS system are used to illustrate both concepts in light of recent experimental results.

  13. Molecular energetics in the capsomere of virus-like particle revealed by molecular dynamics simulations.

    PubMed

    Zhang, Lin; Tang, Ronghong; Bai, Shu; Connors, Natalie K; Lua, Linda H L; Chuan, Yap P; Middelberg, Anton P J; Sun, Yan

    2013-05-09

    Virus-like particles (VLPs) are highly organized nanoparticles that have great potential in vaccinology, gene therapy, drug delivery, and materials science. However, the application of VLPs is hindered by obstacles in their design and production due to low efficiency of self-assembly. In the present study, all-atom (AA) molecular dynamics (MD) simulations coupled with the molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) method are utilized to examine the molecular interactions in the capsomere of a murine polyomavirus (MPV) VLP. It is found that both low ionic strength and the intracapsomere disulfide bonds are favorable for maintaining a stable capsomere. Simulation results examining the effects of solution conditions on the stabilization of a capsomere were verified by calorimetry experiments. Simulation results of free energy decomposition indicate that hydrophobic interaction is favorable for the formation of a capsomere, whereas electrostatic interaction is unfavorable. With increasing ionic strength, the dominant interaction for the stabilization of a capsomere changes from hydrophobic to electrostatic. By comprehensive analyses, the key amino acid residues (hot spots) in VP1 protein aiding formation of a capsomere in different solution conditions have been identified. These results provide molecular insights into the stabilization of building blocks for VLP and are expected to have implications in their partitioning between the correct and off-pathway reactions in VLP assembly.

  14. ChromoShake: a chromosome dynamics simulator reveals that chromatin loops stiffen centromeric chromatin

    PubMed Central

    Lawrimore, Josh; Aicher, Joseph K.; Hahn, Patrick; Fulp, Alyona; Kompa, Ben; Vicci, Leandra; Falvo, Michael; Taylor, Russell M.; Bloom, Kerry

    2016-01-01

    ChromoShake is a three-dimensional simulator designed to find the thermodynamically favored states for given chromosome geometries. The simulator has been applied to a geometric model based on experimentally determined positions and fluctuations of DNA and the distribution of cohesin and condensin in the budding yeast centromere. Simulations of chromatin in differing initial configurations reveal novel principles for understanding the structure and function of a eukaryotic centromere. The entropic position of DNA loops mirrors their experimental position, consistent with their radial displacement from the spindle axis. The barrel-like distribution of cohesin complexes surrounding the central spindle in metaphase is a consequence of the size of the DNA loops within the pericentromere to which cohesin is bound. Linkage between DNA loops of different centromeres is requisite to recapitulate experimentally determined correlations in DNA motion. The consequences of radial loops and cohesin and condensin binding are to stiffen the DNA along the spindle axis, imparting an active function to the centromere in mitosis. PMID:26538024

  15. Membrane-induced conformational changes of kyotorphin revealed by molecular dynamics simulations.

    PubMed

    Machuqueiro, Miguel; Campos, Sara R R; Soares, Cláudio M; Baptista, António M

    2010-09-09

    The analgesic dipeptide kyotorphin (l-Tyr-l-Arg) was studied in the two most relevant protonation states at physiological pH, both in water and in a membrane model, using molecular dynamics simulations. Kyotorphin is found to exhibit a remarkable conformational freedom even when strongly interacting with the bilayer. Nevertheless, we observe a strong decrease in the population of the tyrosine's chi(1) torsion angle around 60 degrees that could be correlated with the dipeptide biological function. We employed a linear response approximation methodology to determine the N-terminus pK(a) values of kyotorphin and obtained 7.80 and 7.94 for aqueous and lipidic systems, respectively. Our results also indicate that the interaction of kyotorphin with a biological membrane model is consistent with the "membrane catalyst" hypothesis, and that even after the reduction of conformational freedom due to membrane insertion, this peptide fulfils most of the known constraints present in the opioid-like receptors.

  16. HDL surface lipids mediate CETP binding as revealed by electron microscopy and molecular dynamics simulation

    SciTech Connect

    Zhang, Meng; Charles, River; Tong, Huimin; Zhang, Lei; Patel, Mili; Wang, Francis; Rames, Matthew J.; Ren, Amy; Rye, Kerry-Anne; Qiu, Xiayang; Johns, Douglas G.; Charles, M. Arthur; Ren, Gang

    2015-03-04

    Cholesteryl ester transfer protein (CETP) mediates the transfer of cholesterol esters (CE) from atheroprotective high-density lipoproteins (HDL) to atherogenic low-density lipoproteins (LDL). CETP inhibition has been regarded as a promising strategy for increasing HDL levels and subsequently reducing the risk of cardiovascular diseases (CVD). Although the crystal structure of CETP is known, little is known regarding how CETP binds to HDL. Here, we investigated how various HDL-like particles interact with CETP by electron microscopy and molecular dynamics simulations. Results showed that CETP binds to HDL via hydrophobic interactions rather than protein-protein interactions. The HDL surface lipid curvature generates a hydrophobic environment, leading to CETP hydrophobic distal end interaction. This interaction is independent of other HDL components, such as apolipoproteins, cholesteryl esters and triglycerides. Thus, disrupting these hydrophobic interactions could be a new therapeutic strategy for attenuating the interaction of CETP with HDL.

  17. HDL surface lipids mediate CETP binding as revealed by electron microscopy and molecular dynamics simulation

    DOE PAGES

    Zhang, Meng; Charles, River; Tong, Huimin; ...

    2015-03-04

    Cholesteryl ester transfer protein (CETP) mediates the transfer of cholesterol esters (CE) from atheroprotective high-density lipoproteins (HDL) to atherogenic low-density lipoproteins (LDL). CETP inhibition has been regarded as a promising strategy for increasing HDL levels and subsequently reducing the risk of cardiovascular diseases (CVD). Although the crystal structure of CETP is known, little is known regarding how CETP binds to HDL. Here, we investigated how various HDL-like particles interact with CETP by electron microscopy and molecular dynamics simulations. Results showed that CETP binds to HDL via hydrophobic interactions rather than protein-protein interactions. The HDL surface lipid curvature generates a hydrophobicmore » environment, leading to CETP hydrophobic distal end interaction. This interaction is independent of other HDL components, such as apolipoproteins, cholesteryl esters and triglycerides. Thus, disrupting these hydrophobic interactions could be a new therapeutic strategy for attenuating the interaction of CETP with HDL.« less

  18. HDL surface lipids mediate CETP binding as revealed by electron microscopy and molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Zhang, Meng; Charles, River; Tong, Huimin; Zhang, Lei; Patel, Mili; Wang, Francis; Rames, Matthew J.; Ren, Amy; Rye, Kerry-Anne; Qiu, Xiayang; Johns, Douglas G.; Charles, M. Arthur; Ren, Gang

    2015-03-01

    Cholesteryl ester transfer protein (CETP) mediates the transfer of cholesterol esters (CE) from atheroprotective high-density lipoproteins (HDL) to atherogenic low-density lipoproteins (LDL). CETP inhibition has been regarded as a promising strategy for increasing HDL levels and subsequently reducing the risk of cardiovascular diseases (CVD). Although the crystal structure of CETP is known, little is known regarding how CETP binds to HDL. Here, we investigated how various HDL-like particles interact with CETP by electron microscopy and molecular dynamics simulations. Results showed that CETP binds to HDL via hydrophobic interactions rather than protein-protein interactions. The HDL surface lipid curvature generates a hydrophobic environment, leading to CETP hydrophobic distal end interaction. This interaction is independent of other HDL components, such as apolipoproteins, cholesteryl esters and triglycerides. Thus, disrupting these hydrophobic interactions could be a new therapeutic strategy for attenuating the interaction of CETP with HDL.

  19. Molecular Dynamics Simulation and Statistics Analysis Reveals the Defense Response Mechanism in Plants

    NASA Astrophysics Data System (ADS)

    Liu, Zhichao; Zhao, Yunjie; Zeng, Chen; Computational Biophysics Lab Team

    As the main protein of the bacterial flagella, flagellin plays an important role in perception and defense response. The newly discovered locus, FLS2, is ubiquitously expressed. FLS2 encodes a putative receptor kinase and shares many homologies with some plant resistance genes and even with some components of immune system of mammals and insects. In Arabidopsis, FLS2 perception is achieved by the recognition of epitope flg22, which induces FLS2 heteromerization with BAK1 and finally the plant immunity. Here we use both analytical methods such as Direct Coupling Analysis (DCA) and Molecular Dynamics (MD) Simulations to get a better understanding of the defense mechanism of FLS2. This may facilitate a redesign of flg22 or de-novo design for desired specificity and potency to extend the immune properties of FLS2 to other important crops and vegetables.

  20. Structural and functional insights into the conductive pili of Geobacter sulfurreducens revealed in molecular dynamics simulations.

    PubMed

    Feliciano, G T; Steidl, R J; Reguera, G

    2015-09-14

    Geobacter sulfurreducens (GS) electronically connects with extracellular electron acceptors using conductive protein filaments or pili. To gain insights into their role as biological nanowires, we investigated the structural dynamics of the GS pilus in solution via molecular dynamics simulations. In the model, all of the pilin's aromatics clustered as a right-handed helical band along the pilus, maintaining inter-aromatic distances and dimer configurations optimal for multistep hopping. The aromatics were interspersed within the regions of highest negative potential, which influenced the type and configuration of the aromatic contacts and the rates of electron transfer. Small foci of positive potential were also present but were neutralized within uncharged regions, thus minimizing charge trapping. Consistent with the model predictions, mutant strains with reduced aromatic contacts or negative potentials had defects in pili functions such as the reduction of Fe(III) oxides and electrodes. The results therefore support the notion of a pilus fiber evolved to function as an electronic conduit between the cell and extracellular electron acceptors.

  1. Preferential binding effects on protein structure and dynamics revealed by coarse-grained Monte Carlo simulation

    NASA Astrophysics Data System (ADS)

    Pandey, R. B.; Jacobs, D. J.; Farmer, B. L.

    2017-05-01

    The effect of preferential binding of solute molecules within an aqueous solution on the structure and dynamics of the histone H3.1 protein is examined by a coarse-grained Monte Carlo simulation. The knowledge-based residue-residue and hydropathy-index-based residue-solvent interactions are used as input to analyze a number of local and global physical quantities as a function of the residue-solvent interaction strength (f). Results from simulations that treat the aqueous solution as a homogeneous effective solvent medium are compared to when positional fluctuations of the solute molecules are explicitly considered. While the radius of gyration (Rg) of the protein exhibits a non-monotonic dependence on solvent interaction over a wide range of f within an effective medium, an abrupt collapse in Rg occurs in a narrow range of f when solute molecules rapidly bind to a preferential set of sites on the protein. The structure factor S(q) of the protein with wave vector (q) becomes oscillatory in the collapsed state, which reflects segmental correlations caused by spatial fluctuations in solute-protein binding. Spatial fluctuations in solute binding also modify the effective dimension (D) of the protein in fibrous (D ˜ 1.3), random-coil (D ˜ 1.75), and globular (D ˜ 3) conformational ensembles as the interaction strength increases, which differ from an effective medium with respect to the magnitude of D and the length scale.

  2. Molecular dynamics simulations reveal that water diffusion between graphene oxide layers is slow

    DOE PAGES

    Devanathan, Ram; Chase-Woods, Dylan; Shin, Yongsoon; ...

    2016-07-08

    Membranes made of stacked layers of graphene oxide (GO) hold the tantalizing promise of revolutionizing desalination and water filtration if selective transport of molecules can be controlled. We present the findings of a molecular dynamics simulation study of water intercalated between GO layers that have a C/O ratio of 4. We simulated a range of hydration levels from 1 wt.% to 23.3 wt.% water. The interlayer spacing increased upon hydration from 0.8 nm to 1.1 nm. We also synthesized GO membranes that showed an increase in spacing from about 0.7 nm to 0.8 nm and an increase in mass ofmore » about 14% on hydration. Water diffusion through GO layers is an order of magnitude slower than that in bulk water, because of strong hydrogen bonded interactions. Most of the water molecules are bound to OH groups even at the highest hydration level. We observed large water clusters that could span graphitic regions, oxidized regions and holes that have been experimentally observed in GO. As a result, slow interlayer diffusion can be consistent with experimentally observed water transport in GO if holes lead to a shorter path length than previously assumed and sorption serves as a key rate-limiting step.« less

  3. Molecular dynamics simulations reveal that water diffusion between graphene oxide layers is slow

    SciTech Connect

    Devanathan, Ram; Chase-Woods, Dylan; Shin, Yongsoon; Gotthold, David W.

    2016-07-08

    Membranes made of stacked layers of graphene oxide (GO) hold the tantalizing promise of revolutionizing desalination and water filtration if selective transport of molecules can be controlled. We present the findings of a molecular dynamics simulation study of water intercalated between GO layers that have a C/O ratio of 4. We simulated a range of hydration levels from 1 wt.% to 23.3 wt.% water. The interlayer spacing increased upon hydration from 0.8 nm to 1.1 nm. We also synthesized GO membranes that showed an increase in spacing from about 0.7 nm to 0.8 nm and an increase in mass of about 14% on hydration. Water diffusion through GO layers is an order of magnitude slower than that in bulk water, because of strong hydrogen bonded interactions. Most of the water molecules are bound to OH groups even at the highest hydration level. We observed large water clusters that could span graphitic regions, oxidized regions and holes that have been experimentally observed in GO. As a result, slow interlayer diffusion can be consistent with experimentally observed water transport in GO if holes lead to a shorter path length than previously assumed and sorption serves as a key rate-limiting step.

  4. Molecular Dynamics Simulations Reveal that Water Diffusion between Graphene Oxide Layers is Slow

    NASA Astrophysics Data System (ADS)

    Devanathan, Ram; Chase-Woods, Dylan; Shin, Yongsoon; Gotthold, David W.

    2016-07-01

    Membranes made of stacked layers of graphene oxide (GO) hold the tantalizing promise of revolutionizing desalination and water filtration if selective transport of molecules can be controlled. We present the findings of an integrated study that combines experiment and molecular dynamics simulation of water intercalated between GO layers. We simulated a range of hydration levels from 1 wt.% to 23.3 wt.% water. The interlayer spacing increased upon hydration from 0.8 nm to 1.1 nm. We also synthesized GO membranes that showed an increase in layer spacing from about 0.7 nm to 0.8 nm and an increase in mass of about 15% on hydration. Water diffusion through GO layers is an order of magnitude slower than that in bulk water, because of strong hydrogen bonded interactions. Most of the water molecules are bound to OH groups even at the highest hydration level. We observed large water clusters that could span graphitic regions, oxidized regions and holes that have been experimentally observed in GO. Slow interlayer diffusion can be consistent with experimentally observed water transport in GO if holes lead to a shorter path length than previously assumed and sorption serves as a key rate-limiting step.

  5. Molecular Dynamics Simulations Reveal that Water Diffusion between Graphene Oxide Layers is Slow

    PubMed Central

    Devanathan, Ram; Chase-Woods, Dylan; Shin, Yongsoon; Gotthold, David W.

    2016-01-01

    Membranes made of stacked layers of graphene oxide (GO) hold the tantalizing promise of revolutionizing desalination and water filtration if selective transport of molecules can be controlled. We present the findings of an integrated study that combines experiment and molecular dynamics simulation of water intercalated between GO layers. We simulated a range of hydration levels from 1 wt.% to 23.3 wt.% water. The interlayer spacing increased upon hydration from 0.8 nm to 1.1 nm. We also synthesized GO membranes that showed an increase in layer spacing from about 0.7 nm to 0.8 nm and an increase in mass of about 15% on hydration. Water diffusion through GO layers is an order of magnitude slower than that in bulk water, because of strong hydrogen bonded interactions. Most of the water molecules are bound to OH groups even at the highest hydration level. We observed large water clusters that could span graphitic regions, oxidized regions and holes that have been experimentally observed in GO. Slow interlayer diffusion can be consistent with experimentally observed water transport in GO if holes lead to a shorter path length than previously assumed and sorption serves as a key rate-limiting step. PMID:27388562

  6. Molecular dynamics simulations reveal the conformational dynamics of Arabidopsis thaliana BRI1 and BAK1 receptor-like kinases.

    PubMed

    Moffett, Alexander S; Bender, Kyle W; Huber, Steven C; Shukla, Diwakar

    2017-07-28

    The structural motifs responsible for activation and regulation of eukaryotic protein kinases in animals have been studied extensively in recent years, and a coherent picture of their activation mechanisms has begun to emerge. In contrast, non-animal eukaryotic protein kinases are not as well understood from a structural perspective, representing a large knowledge gap. To this end, we investigated the conformational dynamics of two key Arabidopsis thaliana receptor-like kinases, brassinosteroid-insensitive 1 (BRI1) and BRI1-associated kinase 1 (BAK1), through extensive molecular dynamics simulations of their fully phosphorylated kinase domains. Molecular dynamics simulations calculate the motion of each atom in a protein based on classical approximations of interatomic forces, giving researchers insight into protein function at unparalleled spatial and temporal resolutions. We found that in an otherwise "active" BAK1 the αC helix is highly disordered, a hallmark of deactivation, whereas the BRI1 αC helix is moderately disordered and displays swinging behavior similar to numerous animal kinases. An analysis of all known sequences in the A. thaliana kinome found that αC helix disorder may be a common feature of plant kinases. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Molecular Dynamics Simulation Reveals Unique Interplays Between a Tarantula Toxin and Lipid Membranes.

    PubMed

    Wu, Lei; Xie, Si-Si; Meng, Er; Li, Wen-Ying; Liu, Long; Zhang, Dong-Yi

    2017-06-01

    Tarantula toxins compose an important class of spider toxins that target ion channels, and some are known to interact with lipid membranes. In this study, we focus on a tarantula toxin, Jingzhaotoxin-III (JZTx-III) that specifically targets the cardiac voltage-gated sodium channel Na[Formula: see text]1.5 and is suspected to be able to interact with lipid membranes. Here, we use an all-atom model and long-term molecular dynamics simulations to investigate the interactions between JZTx-III and lipid membranes of different compositions. Trajectory analyses show that JZTx-III has no substantial interaction with the neutral 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipids, but binds to membranes containing negatively charged 1-palmitoyl-2-oleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (POPG). The most intriguing observations in our simulation are the different interactions between the toxin and the membrane in the mixed and pure POPG membrane systems. The POPC/POPG mixed membrane undergoes a phase transition to a rippled phase upon binding of the toxin, while the pure POPG membrane has no apparent change. Moreover, the binding of JZTx-III to both of the mixture and the pure POPG membrane systems induce small conformational changes. The sequence alignment shows that JZTx-III may not partition into the lipid bilayer due to the mutations of a C-terminal hydrophobic residue and some charged residues that affect toxin orientation. Taken together, JZTx-III and lipid membranes have unique effects on each other that may facilitate the specific binding of JZTx-III to Na[Formula: see text]1.5. This computational study also enriches our understanding of the potential complex interactions between spider toxins and lipid membranes.

  8. Mechanisms of crazing in glassy polymers revealed by molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Mahajan, Dhiraj K.; Hartmaier, Alexander

    2012-08-01

    Mechanisms leading to initiation of crazing type failure in a glassy polymer are not clearly understood. This is mainly due to the difficulty in characterizing the stress state and polymer configuration sufficiently locally at the craze initiation site. Using molecular dynamics simulations, we have now been able to access this information and have shown that the local heterogeneous deformation leads to craze initiation in glassy polymers. We found that zones of high plastic activity are constrained by their neighborhood and become unstable, initiating crazing from these sites. Furthermore, based on the constant flow stresses observed in the unstable zones, we conclude that microcavitation is the essential local deformation mode to trigger crazing in glassy polymers. Our results demonstrate the basic difference in the local deformation mode as well as the conditions that lead to either shear-yielding or crazing type failures in glassy polymers. We anticipate our paper to help in devising a new criterion for craze initiation that not only considers the stress state, but also considers local deformation heterogeneities that form the necessary condition for crazing in glassy polymers.

  9. Dissipative particle dynamics simulations reveal the pH-driven micellar transition pathway of monorhamnolipids.

    PubMed

    Xu, Jianchang; Wang, ZhiKun; Gao, Jianbang; Li, Chunling; Sun, Shuangqing; Hu, Songqing

    2017-11-15

    Dissipative particle dynamics (DPD) simulation has been used to study the effect of pH on the morphology transition of micelles assembled by monorhamnolipids (monoRLs). Results show that micellar structures and transition modes with increasing mass concentrations are multiform due to the changeable hydrophilicity of pH-responsive beads at different pH levels. Various chaotic multilayer aggregations of monoRLs are observed at low pH (pH<4.0) whereas well-ordered single-layer structures are obtained at high pH (pH>7.4). At medium pH region (4.0

  10. The biophysical properties of ethanolamine plasmalogens revealed by atomistic molecular dynamics simulations

    PubMed Central

    Rog, Tomasz; Koivuniemi, Artturi

    2016-01-01

    Given the importance of plasmalogens in cellular membranes and neurodegenerative diseases, a better understanding of how plasmalogens affect the lipid membrane properties is needed. Here we carried out molecular dynamics simulations to study a lipid membrane comprised of ethanolamine plasmalogens (PE–plasmalogens). We compared the results to the PE–diacyl counterpart and palmitoyl-oleyl-phosphatidylcholine (POPC) bilayers. Results show that PE–plasmalogens form more compressed, thicker, and rigid lipid bilayers in comparison with the PE–diacyl and POPC membranes. The results also point out that the vinyl–ether linkage increases the ordering of sn-1 chain substantially and the ordering of the sn-2 chain to a minor extent. Further, the vinyl–ether linkage changes the orientation of the lipid head group, but it does not cause changes in the head group and glycerol backbone tilt angles with respect to the bilayer normal. The vinyl–ether linkage also packs the proximal regions of the sn-1 and sn-2 chains more closely together which also decreases the distance between the rest of the sn-1 and sn-2 chains. PMID:26522077

  11. Molecular basis for polyol-induced protein stability revealed by molecular dynamics simulations.

    PubMed

    Liu, Fu-Feng; Ji, Luo; Zhang, Lin; Dong, Xiao-Yan; Sun, Yan

    2010-06-14

    Molecular dynamics simulations of chymotrypsin inhibitor 2 in different polyols (glycerol, xylitol, sorbitol, trehalose, and sucrose) at 363 K were performed to probe the molecular basis of the stabilizing effect, and the data in water, ethanol, and glycol were compared. It is found that protein protection by polyols is positively correlated with both the molecular volume and the fractional polar surface area, and the former contributes more significantly to the protein's stability. Polyol molecules have only a few direct hydrogen bonds with the protein, and the number of hydrogen bonds between a polyol and the protein is similar for different polyols. Thus, it is concluded that the direct interactions contribute little to the stabilizing effect. It is clarified that the preferential exclusion of the polyols is the origin of their protective effects, and it increases with increasing polyol size. Namely, there is preferential hydration on the protein surface (2 A), and polyol molecules cluster around the protein at a distance of about 4 A. The preferential exclusion of polyols leads to indirect interactions that prevent the protein from thermal unfolding. The water structure becomes more ordered with increasing the polyol size. So, the entropy of water in the first hydration shell decreases, and a larger extent of decrease is observed with increasing polyol size, leading to larger transfer free energy. The findings suggest that polyols protect the protein from thermal unfolding via indirect interactions. The work has thus elucidated the molecular mechanism of structural stability of the protein in polyol solutions.

  12. The structure of neuronal calcium sensor-1 in solution revealed by molecular dynamics simulations.

    PubMed

    Bellucci, Luca; Corni, Stefano; Di Felice, Rosa; Paci, Emanuele

    2013-01-01

    Neuronal calcium sensor-1 (NCS-1) is a protein able to trigger signal transduction processes by binding a large number of substrates and re-shaping its structure depending on the environmental conditions. The X-ray crystal structure of the unmyristoilated NCS-1 shows a large solvent-exposed hydrophobic crevice (HC); this HC is partially occupied by the C-terminal tail and thus elusive to the surrounding solvent. We studied the native state of NCS-1 by performing room temperature molecular dynamics (MD) simulations starting from the crystal and the solution structures. We observe relaxation to a state independent of the initial structure, in which the C-terminal tail occupies the HC. We suggest that the C-terminal tail shields the HC binding pocket and modulates the affinity of NCS-1 for its natural targets. By analyzing the topology and nature of the inter-residue potential energy, we provide a compelling description of the interaction network that determines the three-dimensional organization of NCS-1.

  13. Mechanisms of triggering H1 helix in prion proteins unfolding revealed by molecular dynamic simulation

    NASA Astrophysics Data System (ADS)

    Tseng, Chih-Yuan; Lee, H. C.

    2006-03-01

    In template-assistance model, normal Prion protein (PrP^C), the pathogen to cause several prion diseases such as Creutzfeldt-Jakob (CJD) in human, Bovine Spongiform Encephalopathy (BSE) in cow, and scrapie in sheep, converts to infectious prion (PrP^Sc) through a transient interaction with PrP^Sc. Furthermore, conventional studies showed S1-H1-S2 region in PrP^C to be the template of S1-S2 β-sheet in PrP^Sc, and Prion protein's conformational conversion may involve an unfolding of H1 and refolding into β-sheet. Here we prepare several mouse prion peptides that contain S1-H1-S2 region with specific different structures, which are corresponding to specific interactions, to investigate possible mechanisms to trigger H1 α-helix unfolding process via molecular dynamic simulation. Three properties, conformational transition, salt-bridge in H1, and hydrophobic solvent accessible surface (SAS) are analyzed. From these studies, we found the interaction that triggers H1 unfolding to be the one that causes dihedral angle at residue Asn^143 changes. Whereas interactions that cause S1 segment's conformational changes play a minor in this process. These studies offers an additional evidence for template-assistance model.

  14. Molecular basis for polyol-induced protein stability revealed by molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Liu, Fu-Feng; Ji, Luo; Zhang, Lin; Dong, Xiao-Yan; Sun, Yan

    2010-06-01

    Molecular dynamics simulations of chymotrypsin inhibitor 2 in different polyols (glycerol, xylitol, sorbitol, trehalose, and sucrose) at 363 K were performed to probe the molecular basis of the stabilizing effect, and the data in water, ethanol, and glycol were compared. It is found that protein protection by polyols is positively correlated with both the molecular volume and the fractional polar surface area, and the former contributes more significantly to the protein's stability. Polyol molecules have only a few direct hydrogen bonds with the protein, and the number of hydrogen bonds between a polyol and the protein is similar for different polyols. Thus, it is concluded that the direct interactions contribute little to the stabilizing effect. It is clarified that the preferential exclusion of the polyols is the origin of their protective effects, and it increases with increasing polyol size. Namely, there is preferential hydration on the protein surface (2 Å), and polyol molecules cluster around the protein at a distance of about 4 Å. The preferential exclusion of polyols leads to indirect interactions that prevent the protein from thermal unfolding. The water structure becomes more ordered with increasing the polyol size. So, the entropy of water in the first hydration shell decreases, and a larger extent of decrease is observed with increasing polyol size, leading to larger transfer free energy. The findings suggest that polyols protect the protein from thermal unfolding via indirect interactions. The work has thus elucidated the molecular mechanism of structural stability of the protein in polyol solutions.

  15. Gating motions in voltage-gated potassium channels revealed by coarse-grained molecular dynamics simulations.

    PubMed

    Treptow, Werner; Marrink, Siewert-J; Tarek, Mounir

    2008-03-20

    Voltage-gated potassium (Kv) channels are ubiquitous transmembrane proteins involved in electric signaling of excitable tissues. A fundamental property of these channels is the ability to open or close in response to changes in the membrane potential. To date, their structure-based activation mechanism remains unclear, and there is a large controversy on how these gates function at the molecular level, in particular, how movements of the voltage sensor domain are coupled to channel gating. So far, all mechanisms proposed for this coupling are based on the crystal structure of the open voltage-gated Kv1.2 channel and structural models of the closed form based on electrophysiology experiments. Here, we use coarse-grain (CG) molecular dynamics simulations that allow conformational changes from the open to the closed form of the channel (embedded in its membrane environment) to be followed. Despite the low specificity of the CG force field, the obtained closed structure satisfies several experimental constraints. The overall results suggest a gating mechanism in which a lateral displacement the S4-S5 linker leads to a closing of the gate. Only a small up-down movement of the S4 helices is noticed. Additionally, the study suggests a peculiar upward motion of the intracellular tetramerization domain of the channel, hence providing a molecular view on how this domain may further regulate conduction in Kv channels.

  16. Bending Vibration-Governed Solvation Dynamics of an Excess Electron in Liquid Acetonitrile Revealed by Ab Initio Molecular Dynamics Simulation.

    PubMed

    Liu, Jinxiang; Cukier, Robert I; Bu, Yuxiang

    2013-11-12

    We report an ab initio molecular dynamics simulation study of the solvation and dynamics of an excess electron in liquid acetonitrile (ACN). Four families of states are observed: a diffusely solvated state and three ACN core-localized states with monomer core, quasi-dimer (π*-Rydberg mode) core, and dual-core/dimer core (a coupled dual-core). These core localized states cannot be simply described as the corresponding anions because only a part of the excess electron resides in the core molecule(s). The quasi-dimer core state actually is a mixture that features cooperative excess electron capture by the π* and Rydberg orbitals of two ACNs. Well-defined dimer anion and solvated electron cavity were not observed in the 5-10 ps simulations, which may be attributed to slow dynamics of the formation of the dimer anion and difficulty of the formation of a cavity in such a fluxional medium. All of the above observed states have near-IR absorptions and thus can be regarded as the solvated electron states but with different structures, which can interpret the experimentally observed IR band. These states undergo continuous conversions via a combination of long-lasting breathing oscillation and core switching, characterized by highly cooperative oscillations of the electron cloud volume and vertical detachment energy. The quasi-dimer core and diffusely solvated states dominate the time evolution, with the monomer core and dual-core/dimer core states occurring occasionally during the breathing and core switching processes, respectively. All these oscillations and core switchings are governed by a combination of the electron-impacted bending vibration of the core ACN molecule(s) and thermal fluctuations.

  17. Three steps to gold: mechanism of protein adsorption revealed by Brownian and molecular dynamics simulations.

    PubMed

    Ozboyaci, M; Kokh, D B; Wade, R C

    2016-04-21

    The addition of three N-terminal histidines to β-lactamase inhibitor protein was shown experimentally to increase its binding potency to an Au(111) surface substantially but the binding mechanism was not resolved. Here, we propose a complete adsorption mechanism for this fusion protein by means of a multi-scale simulation approach and free energy calculations. We find that adsorption is a three-step process: (i) recognition of the surface predominantly by the histidine fusion peptide and formation of an encounter complex facilitated by a reduced dielectric screening of water in the interfacial region, (ii) adsorption of the protein on the surface and adoption of a specific binding orientation, and (iii) adaptation of the protein structure on the metal surface accompanied by induced fit. We anticipate that the mechanistic features of protein adsorption to an Au(111) surface revealed here can be extended to other inorganic surfaces and proteins and will therefore aid the design of specific protein-surface interactions.

  18. Revealing the toughening mechanism of graphene-polymer nanocomposite through molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Liu, Jun; Shen, Jianxiang; Zheng, Zijian; Wu, Youping; Zhang, Liqun

    2015-07-01

    By employing united atom molecular dynamics simulation, we have investigated the effects of polymer-graphene interaction {\\varepsilon }np, volume fraction of graphene φ , thermodynamics of polymer matrix (rubbery versus glassy), interfacial interaction in the case of the same dispersion state, shape of nanoparticles (NPs) such as {{{C}}}60, CNT and graphene at the same loading on the toughening efficiency of polymer nanocomposites. By beginning with the pure polymer, we observe that a plateau stress occurs at long chain length because entangled polymer chains in fibrils cannot become broken. We find that the work needed to dissipate during the failure increases with the increase of {\\varepsilon }np and φ , and the yield point in the stress-strain behavior occurs at a smaller strain for an attractive NPs filled system compared to the pure case, attributed to the more mechanically heterogeneous environment. The thermodynamics of the polymer matrix (below and above Tg) seems to have a significant effect on the toughening efficiency of graphene sheets. In the case of the same dispersion state, stronger interfacial interaction always induces long and highly orientated polymer fibrils along the deformation direction, with graphene sheets being encapsulated in these fiber-like bundles. By characterizing the interaction energy between polymer-polymer and polymer-graphene as a function of the strain, we find that the separation of polymer chains from the graphene sheets cease immediately after the yield point, followed by the continuous propagation of the cavities by excluding surrounded polymer chains and graphene sheets together. We also find that at the same attractive interfacial interaction and same loading, the toughening efficiency exhibits the following order: graphene > CNT > {{{C}}}60. Generally, the toughening mechanism of graphene sheets results from the formation of long and highly orientated polymer fibrils to prevent the occurrence of the rupture, which

  19. Beta-hairpin conformation of fibrillogenic peptides: structure and alpha-beta transition mechanism revealed by molecular dynamics simulations.

    PubMed

    Daidone, Isabella; Simona, Fabio; Roccatano, Danilo; Broglia, Ricardo A; Tiana, Guido; Colombo, Giorgio; Di Nola, Alfredo

    2004-10-01

    Understanding the conformational transitions that trigger the aggregation and amyloidogenesis of otherwise soluble peptides at atomic resolution is of fundamental relevance for the design of effective therapeutic agents against amyloid-related disorders. In the present study the transition from ideal alpha-helical to beta-hairpin conformations is revealed by long timescale molecular dynamics simulations in explicit water solvent, for two well-known amyloidogenic peptides: the H1 peptide from prion protein and the Abeta(12-28) fragment from the Abeta(1-42) peptide responsible for Alzheimer's disease. The simulations highlight the unfolding of alpha-helices, followed by the formation of bent conformations and a final convergence to ordered in register beta-hairpin conformations. The beta-hairpins observed, despite different sequences, exhibit a common dynamic behavior and the presence of a peculiar pattern of the hydrophobic side-chains, in particular in the region of the turns. These observations hint at a possible common aggregation mechanism for the onset of different amyloid diseases and a common mechanism in the transition to the beta-hairpin structures. Furthermore the simulations presented herein evidence the stabilization of the alpha-helical conformations induced by the presence of an organic fluorinated cosolvent. The results of MD simulation in 2,2,2-trifluoroethanol (TFE)/water mixture provide further evidence that the peptide coating effect of TFE molecules is responsible for the stabilization of the soluble helical conformation.

  20. Complete protein-protein association kinetics in atomic detail revealed by molecular dynamics simulations and Markov modelling

    NASA Astrophysics Data System (ADS)

    Plattner, Nuria; Doerr, Stefan; de Fabritiis, Gianni; Noé, Frank

    2017-10-01

    Protein-protein association is fundamental to many life processes. However, a microscopic model describing the structures and kinetics during association and dissociation is lacking on account of the long lifetimes of associated states, which have prevented efficient sampling by direct molecular dynamics (MD) simulations. Here we demonstrate protein-protein association and dissociation in atomistic resolution for the ribonuclease barnase and its inhibitor barstar by combining adaptive high-throughput MD simulations and hidden Markov modelling. The model reveals experimentally consistent intermediate structures, energetics and kinetics on timescales from microseconds to hours. A variety of flexibly attached intermediates and misbound states funnel down to a transition state and a native basin consisting of the loosely bound near-native state and the tightly bound crystallographic state. These results offer a deeper level of insight into macromolecular recognition and our approach opens the door for understanding and manipulating a wide range of macromolecular association processes.

  1. Molecular dynamics simulations of Ago silencing complexes reveal a large repertoire of admissible ‘seed-less’ targets

    PubMed Central

    Xia, Zhen; Clark, Peter; Huynh, Tien; Loher, Phillipe; Zhao, Yue; Chen, Huang-Wen; Rigoutsos, Isidore; Zhou, Ruhong

    2012-01-01

    To better understand the recognition mechanism of RISC and the repertoire of guide-target interactions we introduced G:U wobbles and mismatches at various positions of the microRNA (miRNA) ‘seed’ region and performed all-atom molecular dynamics simulations of the resulting Ago-miRNA:mRNA ternary complexes. Our simulations reveal that many modifications, including combinations of multiple G:U wobbles and mismatches in the seed region, are admissible and result in only minor structural fluctuations that do not affect overall complex stability. These results are further supported by analyses of HITS-CLIP data. Lastly, introduction of disruptive mutations revealed a bending motion of the PAZ domain along the L1/L2 ‘hinge’ and a subsequent opening of the nucleic-acid-binding channel. Our findings suggest that the spectrum of a miRNA's admissible targets is different from what is currently anticipated by the canonical seed-model. Moreover, they provide a likely explanation for the previously reported sequence-dependent regulation of unintended targeting by siRNAs. PMID:22888400

  2. Crystal Structures and Molecular Dynamics Simulations of Thermophilic Malate Dehydrogenase Reveal Critical Loop Motion for Co-Substrate Binding

    PubMed Central

    Luo, Huei-Ru; Wu, Szu-Pei; Hsu, Chun-Hua

    2013-01-01

    Malate dehydrogenase (MDH) catalyzes the conversion of oxaloacetate and malate by using the NAD/NADH coenzyme system. The system is used as a conjugate for enzyme immunoassays of a wide variety of compounds, such as illegal drugs, drugs used in therapeutic applications and hormones. We elucidated the biochemical and structural features of MDH from Thermus thermophilus (TtMDH) for use in various biotechnological applications. The biochemical characterization of recombinant TtMDH revealed greatly increased activity above 60°C and specific activity of about 2,600 U/mg with optimal temperature of 90°C. Analysis of crystal structures of apo and NAD-bound forms of TtMDH revealed a slight movement of the binding loop and few structural elements around the co-substrate binding packet in the presence of NAD. The overall structures did not change much and retained all related positions, which agrees with the CD analyses. Further molecular dynamics (MD) simulation at higher temperatures were used to reconstruct structures from the crystal structure of TtMDH. Interestingly, at the simulated structure of 353 K, a large change occurred around the active site such that with increasing temperature, a mobile loop was closed to co-substrate binding region. From biochemical characterization, structural comparison and MD simulations, the thermal-induced conformational change of the co-substrate binding loop of TtMDH may contribute to the essential movement of the enzyme for admitting NAD and may benefit the enzyme's activity. PMID:24386145

  3. Transient β-hairpin formation in α-synuclein monomer revealed by coarse-grained molecular dynamics simulation

    SciTech Connect

    Yu, Hang; Ma, Wen; Han, Wei; Schulten, Klaus

    2015-12-28

    Parkinson’s disease, originating from the intrinsically disordered peptide α-synuclein, is a common neurodegenerative disorder that affects more than 5% of the population above age 85. It remains unclear how α-synuclein monomers undergo conformational changes leading to aggregation and formation of fibrils characteristic for the disease. In the present study, we perform molecular dynamics simulations (over 180 μs in aggregated time) using a hybrid-resolution model, Proteins with Atomic details in Coarse-grained Environment (PACE), to characterize in atomic detail structural ensembles of wild type and mutant monomeric α-synuclein in aqueous solution. The simulations reproduce structural properties of α-synuclein characterized in experiments, such as secondary structure content, long-range contacts, chemical shifts, and {sup 3}J(H{sub N}H{sub C{sub α}})-coupling constants. Most notably, the simulations reveal that a short fragment encompassing region 38-53, adjacent to the non-amyloid-β component region, exhibits a high probability of forming a β-hairpin; this fragment, when isolated from the remainder of α-synuclein, fluctuates frequently into its β-hairpin conformation. Two disease-prone mutations, namely, A30P and A53T, significantly accelerate the formation of a β-hairpin in the stated fragment. We conclude that the formation of a β-hairpin in region 38-53 is a key event during α-synuclein aggregation. We predict further that the G47V mutation impedes the formation of a turn in the β-hairpin and slows down β-hairpin formation, thereby retarding α-synuclein aggregation.

  4. Transient β-hairpin formation in α-synuclein monomer revealed by coarse-grained molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Yu, Hang; Han, Wei; Ma, Wen; Schulten, Klaus

    2015-12-01

    Parkinson's disease, originating from the intrinsically disordered peptide α-synuclein, is a common neurodegenerative disorder that affects more than 5% of the population above age 85. It remains unclear how α-synuclein monomers undergo conformational changes leading to aggregation and formation of fibrils characteristic for the disease. In the present study, we perform molecular dynamics simulations (over 180 μs in aggregated time) using a hybrid-resolution model, Proteins with Atomic details in Coarse-grained Environment (PACE), to characterize in atomic detail structural ensembles of wild type and mutant monomeric α-synuclein in aqueous solution. The simulations reproduce structural properties of α-synuclein characterized in experiments, such as secondary structure content, long-range contacts, chemical shifts, and 3J(HNHCα)-coupling constants. Most notably, the simulations reveal that a short fragment encompassing region 38-53, adjacent to the non-amyloid-β component region, exhibits a high probability of forming a β-hairpin; this fragment, when isolated from the remainder of α-synuclein, fluctuates frequently into its β-hairpin conformation. Two disease-prone mutations, namely, A30P and A53T, significantly accelerate the formation of a β-hairpin in the stated fragment. We conclude that the formation of a β-hairpin in region 38-53 is a key event during α-synuclein aggregation. We predict further that the G47V mutation impedes the formation of a turn in the β-hairpin and slows down β-hairpin formation, thereby retarding α-synuclein aggregation.

  5. Energetic changes caused by antigenic module insertion in a virus-like particle revealed by experiment and molecular dynamics simulations.

    PubMed

    Zhang, Lin; Tang, Ronghong; Bai, Shu; Connors, Natalie K; Lua, Linda H L; Chuan, Yap P; Middelberg, Anton P J; Sun, Yan

    2014-01-01

    The success of recombinant virus-like particles (VLPs) for human papillomavirus and hepatitis B demonstrates the potential of VLPs as safe and efficacious vaccines. With new modular designs emerging, the effects of antigen module insertion on the self-assembly and structural integrity of VLPs should be clarified so as to better enabling improved design. Previous work has revealed insights into the molecular energetics of a VLP subunit, capsomere, comparing energetics within various solution conditions known to drive or inhibit self-assembly. In the present study, molecular dynamics (MD) simulations coupled with the molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) method were performed to examine the molecular interactions and energetics in a modular capsomere of a murine polyomavirus (MPV) VLP designed to protect against influenza. Insertion of an influenza antigenic module is found to lower the binding energy within the capsomere, and a more active state is observed in Assembly Buffer as compared with that in Stabilization Buffer, which has been experimentally validated through measurements using differential scanning calorimetry. Further in-depth analysis based on free-energy decomposition indicates that destabilized binding can be attributed to electrostatic interaction induced by the chosen antigen module. These results provide molecular insights into the conformational stability of capsomeres and their abilities to be exploited for antigen presentation, and are expected to be beneficial for the biomolecular engineering of VLP vaccines.

  6. Energetic Changes Caused by Antigenic Module Insertion in a Virus-Like Particle Revealed by Experiment and Molecular Dynamics Simulations

    PubMed Central

    Zhang, Lin; Tang, Ronghong; Bai, Shu; Connors, Natalie K.; Lua, Linda H. L.; Chuan, Yap P.; Middelberg, Anton P. J.; Sun, Yan

    2014-01-01

    The success of recombinant virus-like particles (VLPs) for human papillomavirus and hepatitis B demonstrates the potential of VLPs as safe and efficacious vaccines. With new modular designs emerging, the effects of antigen module insertion on the self-assembly and structural integrity of VLPs should be clarified so as to better enabling improved design. Previous work has revealed insights into the molecular energetics of a VLP subunit, capsomere, comparing energetics within various solution conditions known to drive or inhibit self-assembly. In the present study, molecular dynamics (MD) simulations coupled with the molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) method were performed to examine the molecular interactions and energetics in a modular capsomere of a murine polyomavirus (MPV) VLP designed to protect against influenza. Insertion of an influenza antigenic module is found to lower the binding energy within the capsomere, and a more active state is observed in Assembly Buffer as compared with that in Stabilization Buffer, which has been experimentally validated through measurements using differential scanning calorimetry. Further in-depth analysis based on free-energy decomposition indicates that destabilized binding can be attributed to electrostatic interaction induced by the chosen antigen module. These results provide molecular insights into the conformational stability of capsomeres and their abilities to be exploited for antigen presentation, and are expected to be beneficial for the biomolecular engineering of VLP vaccines. PMID:25215874

  7. Structural diversity of the soluble trimers of the human amylin(20-29) peptide revealed by molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Mo, Yuxiang; Lu, Yan; Wei, Guanghong; Derreumaux, Philippe

    2009-03-01

    The human islet amyloid polypeptide (hIAPP) or amylin is a 37-residue hormone found as amyloid deposits in pancreatic extracts of nearly all type 2 diabetes patients. The fragment 20-29 of sequence SNNFGAILSS (hIAPP20-29) has been shown to be responsible for the amyloidogenic propensities of the full length protein. Various polymorphic forms of hIAPP20-29 fibrils were described by using Fourier transform infrared (FTIR) and solid-state NMR experiments: unseeded hIAPP20-29 fibril with out-of-register antiparallel β-strands, and two forms of seeded hIAPP20-29 fibril, with in-register antiparallel or in-register parallel β-strands. As a first step toward understanding this polymorphism, we explore the equilibrium structures of the soluble hIAPP20-29 trimer, using multiple molecular dynamics (MD) simulations with the Optimized Potential for Efficient structure Prediction (OPEP) coarse-grained implicit solvent force field for a total length of 3.2 μs. Although, the trimer is found mainly random coil, consistent with the signal measured experimentally during the lag phase of hIAPP20-29 fibril formation, the central FGAIL residues have a relative high propensity to form interpeptide β-sheets and antiparallel β-strands are more probable than parallel β-strands. One MD-predicted out-of-register antiparallel three-stranded β-sheet matches exactly the FTIR-derived unseeded hIAPP20-29 fibril model. Our simulations, however, do not reveal any evidence of in-register parallel or in-register antiparallel β-sheets as reported for seeded hIAPP20-29 fibrils. All these results indicate that fibril polymorphism is partially encoded in a trimer.

  8. Structural diversity of the soluble trimers of the human amylin(20-29) peptide revealed by molecular dynamics simulations.

    PubMed

    Mo, Yuxiang; Lu, Yan; Wei, Guanghong; Derreumaux, Philippe

    2009-03-28

    The human islet amyloid polypeptide (hIAPP) or amylin is a 37-residue hormone found as amyloid deposits in pancreatic extracts of nearly all type 2 diabetes patients. The fragment 20-29 of sequence SNNFGAILSS (hIAPP20-29) has been shown to be responsible for the amyloidogenic propensities of the full length protein. Various polymorphic forms of hIAPP20-29 fibrils were described by using Fourier transform infrared (FTIR) and solid-state NMR experiments: unseeded hIAPP20-29 fibril with out-of-register antiparallel beta-strands, and two forms of seeded hIAPP20-29 fibril, with in-register antiparallel or in-register parallel beta-strands. As a first step toward understanding this polymorphism, we explore the equilibrium structures of the soluble hIAPP20-29 trimer, using multiple molecular dynamics (MD) simulations with the Optimized Potential for Efficient structure Prediction (OPEP) coarse-grained implicit solvent force field for a total length of 3.2 micros. Although, the trimer is found mainly random coil, consistent with the signal measured experimentally during the lag phase of hIAPP20-29 fibril formation, the central FGAIL residues have a relative high propensity to form interpeptide beta-sheets and antiparallel beta-strands are more probable than parallel beta-strands. One MD-predicted out-of-register antiparallel three-stranded beta-sheet matches exactly the FTIR-derived unseeded hIAPP20-29 fibril model. Our simulations, however, do not reveal any evidence of in-register parallel or in-register antiparallel beta-sheets as reported for seeded hIAPP20-29 fibrils. All these results indicate that fibril polymorphism is partially encoded in a trimer.

  9. Thermodynamic coupling between activation and inactivation gating in potassium channels revealed by free energy molecular dynamics simulations

    PubMed Central

    Pan, Albert C.; Cuello, Luis G.; Perozo, Eduardo

    2011-01-01

    The amount of ionic current flowing through K+ channels is determined by the interplay between two separate time-dependent processes: activation and inactivation gating. Activation is concerned with the stimulus-dependent opening of the main intracellular gate, whereas inactivation is a spontaneous conformational transition of the selectivity filter toward a nonconductive state occurring on a variety of timescales. A recent analysis of multiple x-ray structures of open and partially open KcsA channels revealed the mechanism by which movements of the inner activation gate, formed by the inner helices from the four subunits of the pore domain, bias the conformational changes at the selectivity filter toward a nonconductive inactivated state. This analysis highlighted the important role of Phe103, a residue located along the inner helix, near the hinge position associated with the opening of the intracellular gate. In the present study, we use free energy perturbation molecular dynamics simulations (FEP/MD) to quantitatively elucidate the thermodynamic basis for the coupling between the intracellular gate and the selectivity filter. The results of the FEP/MD calculations are in good agreement with experiments, and further analysis of the repulsive, van der Waals dispersive, and electrostatic free energy contributions reveals that the energetic basis underlying the absence of inactivation in the F103A mutation in KcsA is the absence of the unfavorable steric interaction occurring with the large Ile100 side chain in a neighboring subunit when the intracellular gate is open and the selectivity filter is in a conductive conformation. Macroscopic current analysis shows that the I100A mutant indeed relieves inactivation in KcsA, but to a lesser extent than the F103A mutant. PMID:22124115

  10. ``Cooperativity blockage'' in the mixed alkali effect as revealed by molecular-dynamics simulations of alkali metasilicate glass

    NASA Astrophysics Data System (ADS)

    Habasaki, Junko; Ngai, K. L.; Hiwatari, Yasuaki

    2004-07-01

    The relaxation dynamics of a complex interacting system can be drastically changed when mixing with another component having different dynamics. In this work, we elucidate the effect of the less mobile guest ions on the dynamics of the more mobile host ions in mixed alkali glasses by molecular-dynamics (MD) simulations. One MD simulation was carried out on lithium metasilicate glass with the guest ions created by freezing some randomly chosen lithium ions at their initial locations at 700 K. A remarkable slowing down of the dynamics of the majority mobile Li ions was observed both in the self-part of the density-density correlation function, Fs(k,t), and in the mean-squared displacements. On the other hand, there is no significant change in the structure. The motion of the Li ions in the unadulterated Li metasilicate glass is dynamically heterogeneous. In the present work, the fast and slow ions were divided into two groups. The number of fast ions, which shows faster dynamics (Lévy flight) facilitated by cooperative jumps, decreases considerably when small amount of Li ions are frozen. Consequently there is a large overall reduction of the mobility of the Li ions. The result is also in accordance with the experimental finding in mixed alkali silicate glasses that the most dramatic reduction of ionic conductivity occurs in the dilute foreign alkali limit. Similar suppression of the cooperative jumps is observed in the MD simulation data of mixed alkali system, LiKSiO3. Naturally, the effect found here is appropriately described as "cooperativity blockage." Slowing down of the motion of Li ions also was observed when a small number of oxygen atoms chosen at random were frozen. The effect is smaller than the case of freezing some the Li ions, but it is not negligible. The cooperativity blockage is also implemented by confining the Li metasilicate glass inside two parallel walls formed by freezing Li ions in the same metasilicate glass. Molecular-dynamics simulations

  11. Ab initio simulations reveal that reaction dynamics strongly affect product selectivity for the cracking of alkanes over H-MFI.

    PubMed

    Zimmerman, Paul M; Tranca, Diana C; Gomes, Joseph; Lambrecht, Daniel S; Head-Gordon, Martin; Bell, Alexis T

    2012-11-28

    Product selectivity of alkane cracking catalysis in the H-MFI zeolite is investigated using both static and dynamic first-principles quantum mechanics/molecular mechanics simulations. These simulations account for the electrostatic- and shape-selective interactions in the zeolite and provide enthalpic barriers that are closely comparable to experiment. Cracking transition states for n-pentane lead to a metastable intermediate (a local minimum with relatively small barriers to escape to deeper minima) where the proton is shared between two hydrocarbon fragments. The zeolite strongly stabilizes these carbocations compared to the gas phase, and the conversion of this intermediate to more stable species determines the product selectivity. Static reaction pathways on the potential energy surface starting from the metastable intermediate include a variety of possible conversions into more stable products. One-picosecond quasiclassical trajectory simulations performed at 773 K indicate that dynamic paths are substantially more diverse than the potential energy paths. Vibrational motion that is dynamically sampled after the cracking transition state causes spilling of the metastable intermediate into a variety of different products. A nearly 10-fold change in the branching ratio between C2/C3 cracking channels is found upon inclusion of post-transition-state dynamics, relative to static electronic structure calculations. Agreement with experiment is improved by the same factor. Because dynamical effects occur soon after passing through the rate-limiting transition state, it is the dynamics, and not only the potential energy barriers, that determine the catalytic selectivity. This study suggests that selectivity in zeolite catalysis is determined by high temperature pathways that differ significantly from 0 K potential surfaces.

  12. Ganglioside-Lipid and Ganglioside-Protein Interactions Revealed by Coarse-Grained and Atomistic Molecular Dynamics Simulations

    PubMed Central

    2016-01-01

    Gangliosides are glycolipids in which an oligosaccharide headgroup containing one or more sialic acids is connected to a ceramide. Gangliosides reside in the outer leaflet of the plasma membrane and play a crucial role in various physiological processes such as cell signal transduction and neuronal differentiation by modulating structures and functions of membrane proteins. Because the detailed behavior of gangliosides and protein-ganglioside interactions are poorly known, we investigated the interactions between the gangliosides GM1 and GM3 and the proteins aquaporin (AQP1) and WALP23 using equilibrium molecular dynamics simulations and potential of mean force calculations at both coarse-grained (CG) and atomistic levels. In atomistic simulations, on the basis of the GROMOS force field, ganglioside aggregation appears to be a result of the balance between hydrogen bond interactions and steric hindrance of the headgroups. GM3 clusters are slightly larger and more ordered than GM1 clusters due to the smaller headgroup of GM3. The different structures of GM1 and GM3 clusters from atomistic simulations are not observed at the CG level based on the Martini model, implying a difference in driving forces for ganglioside interactions in atomistic and CG simulations. For protein-ganglioside interactions, in the atomistic simulations, GM1 lipids bind to specific sites on the AQP1 surface, whereas they are depleted from WALP23. In the CG simulations, the ganglioside binding sites on the AQP1 surface are similar, but ganglioside aggregation and protein-ganglioside interactions are more prevalent than in the atomistic simulations. Using the polarizable Martini water model, results were closer to the atomistic simulations. Although experimental data for validation is lacking, we proposed modified Martini parameters for gangliosides to more closely mimic the sizes and structures of ganglioside clusters observed at the atomistic level. PMID:27610460

  13. Revealing the functionality of hypothetical protein KPN00728 from Klebsiella pneumoniae MGH78578: molecular dynamics simulation approaches

    PubMed Central

    2011-01-01

    Background Previously, the hypothetical protein, KPN00728 from Klebsiella pneumoniae MGH78578 was the Succinate dehydrogenase (SDH) chain C subunit via structural prediction and molecular docking simulation studies. However, due to limitation in docking simulation, an in-depth understanding of how SDH interaction occurs across the transmembrane of mitochondria could not be provided. Results In this present study, molecular dynamics (MD) simulation of KPN00728 and SDH chain D in a membrane was performed in order to gain a deeper insight into its molecular role as SDH. Structural stability was successfully obtained in the calculation for area per lipid, tail order parameter, thickness of lipid and secondary structural properties. Interestingly, water molecules were found to be highly possible in mediating the interaction between Ubiquinone (UQ) and SDH chain C via interaction with Ser27 and Arg31 residues as compared with earlier docking study. Polar residues such as Asp95 and Glu101 (KPN00728), Asp15 and Glu78 (SDH chain D) might have contributed in the creation of a polar environment which is essential for electron transport chain in Krebs cycle. Conclusions As a conclusion, a part from the structural stability comparability, the dynamic of the interacting residues and hydrogen bonding analysis had further proved that the interaction of KPN00728 as SDH is preserved and well agreed with our postulation earlier. PMID:22372825

  14. Relevant interactions of antimicrobial iron chelators and membrane models revealed by nuclear magnetic resonance and molecular dynamics simulations.

    PubMed

    Coimbra, João T S; Moniz, Tânia; Brás, Natércia F; Ivanova, Galya; Fernandes, Pedro A; Ramos, Maria J; Rangel, Maria

    2014-12-18

    The dynamics and interaction of 3-hydroxy-4-pyridinone fluorescent iron chelators, exhibiting antimicrobial properties, with biological membranes were evaluated through NMR and molecular dynamics simulations. Both NMR and MD simulation results support a strong interaction of the chelators with the lipid bilayers that seems to be strengthened for the rhodamine containing compounds, in particular for compounds that include ethyl groups and a thiourea link. For the latter type of compounds the interaction reaches the hydrophobic core of the lipid bilayer. The molecular docking and MD simulations performed for the potential interaction of the chelators with DC-SIGN receptors provide valuable information regarding the cellular uptake of these compounds since the results show that the fluorophore fragment of the molecular framework is essential for an efficient binding. Putting together our previous and present results, we put forward the hypothesis that all the studied fluorescent chelators have access to the cell, their uptake occurs through different pathways and their permeation properties correlate with a better access to the cell and its compartments and, consequently, with the chelators antimicrobial properties.

  15. Unique Aspects of the Structure and Dynamics of Elementary Iβ Cellulose Microfibrils Revealed by Computational Simulations1[OPEN

    PubMed Central

    Oehme, Daniel P.; Downton, Matthew T.; Doblin, Monika S.; Wagner, John; Gidley, Michael J.; Bacic, Antony

    2015-01-01

    The question of how many chains an elementary cellulose microfibril contains is critical to understanding the molecular mechanism(s) of cellulose biosynthesis and regulation. Given the hexagonal nature of the cellulose synthase rosette, it is assumed that the number of chains must be a multiple of six. We present molecular dynamics simulations on three different models of Iβ cellulose microfibrils, 18, 24, and 36 chains, to investigate their structure and dynamics in a hydrated environment. The 36-chain model stays in a conformational space that is very similar to the initial crystalline phase, while the 18- and 24-chain models sample a conformational space different from the crystalline structure yet similar to conformations observed in recent high-temperature molecular dynamics simulations. Major differences in the conformations sampled between the different models result from changes to the tilt of chains in different layers, specifically a second stage of tilt, increased rotation about the O2-C2 dihedral, and a greater sampling of non-TG exocyclic conformations, particularly the GG conformation in center layers and GT conformation in solvent-exposed exocyclic groups. With a reinterpretation of nuclear magnetic resonance data, specifically for contributions made to the C6 peak, data from the simulations suggest that the 18- and 24-chain structures are more viable models for an elementary cellulose microfibril, which also correlates with recent scattering and diffraction experimental data. These data inform biochemical and molecular studies that must explain how a six-particle cellulose synthase complex rosette synthesizes microfibrils likely comprised of either 18 or 24 chains. PMID:25786828

  16. Molecular dynamics simulation reveals how phosphorylation of tyrosine 26 of phosphoglycerate mutase 1 upregulates glycolysis and promotes tumor growth.

    PubMed

    Wang, Yan; Cai, Wen-Sheng; Chen, Luonan; Wang, Guanyu

    2017-02-14

    Phosphoglycerate mutase 1 (PGAM1) catalyzes the eighth step of glycolysis and is often found upregulated in cancer cells. To test the hypothesis that the phosphorylation of tyrosine 26 residue of PGAM1 greatly enhances its activity, we performed both conventional and steered molecular dynamics simulations on the binding and unbinding of PGAM1 to its substrates, with tyrosine 26 either phosphorylated or not. We analyzed the simulated data in terms of structural stability, hydrogen bond formation, binding free energy, etc. We found that tyrosine 26 phosphorylation enhances the binding of PGAM1 to its substrates through generating electrostatic environment and structural features that are advantageous to the binding. Our results may provide valuable insights into computer-aided design of drugs that specifically target cancer cells with PGAM1 tyrosine 26 phosphorylated.

  17. Ab initio molecular dynamics simulations reveal localization and time evolution dynamics of an excess electron in heterogeneous CO2-H2O systems.

    PubMed

    Liu, Ping; Zhao, Jing; Liu, Jinxiang; Zhang, Meng; Bu, Yuxiang

    2014-01-28

    In view of the important implications of excess electrons (EEs) interacting with CO2-H2O clusters in many fields, using ab initio molecular dynamics simulation technique, we reveal the structures and dynamics of an EE associated with its localization and subsequent time evolution in heterogeneous CO2-H2O mixed media. Our results indicate that although hydration can increase the electron-binding ability of a CO2 molecule, it only plays an assisting role. Instead, it is the bending vibrations that play the major role in localizing the EE. Due to enhanced attraction of CO2, an EE can stably reside in the empty, low-lying π(*) orbital of a CO2 molecule via a localization process arising from its initial binding state. The localization is completed within a few tens of femtoseconds. After EE trapping, the ∠OCO angle of the core CO2 (-) oscillates in the range of 127°∼142°, with an oscillation period of about 48 fs. The corresponding vertical detachment energy of the EE is about 4.0 eV, which indicates extreme stability of such a CO2-bound solvated EE in [CO2(H2O)n](-) systems. Interestingly, hydration occurs not only on the O atoms of the core CO2 (-) through formation of O⋯H-O H-bond(s), but also on the C atom, through formation of a C⋯H-O H-bond. In the latter binding mode, the EE cloud exhibits considerable penetration to the solvent water molecules, and its IR characteristic peak is relatively red-shifted compared with the former. Hydration on the C site can increase the EE distribution at the C atom and thus reduce the C⋯H distance in the C⋯H-O H-bonds, and vice versa. The number of water molecules associated with the CO2 (-) anion in the first hydration shell is about 4∼7. No dimer-core (C2O4 (-)) and core-switching were observed in the double CO2 aqueous media. This work provides molecular dynamics insights into the localization and time evolution dynamics of an EE in heterogeneous CO2-H2O media.

  18. Dynamic Structure of Bombolitin II Bound to Lipid Bilayers as Revealed by Solid-state NMR and Molecular-Dynamics Simulation

    PubMed Central

    Toraya, Shuichi; Javkhlantugs, Namsrai; Mishima, Daisuke; Nishimura, Katsuyuki; Ueda, Kazuyoshi; Naito, Akira

    2010-01-01

    Bombolitin II (BLT2) is one of the hemolytic heptadecapeptides originally isolated from the venom of a bumblebee. Structure and orientation of BLT2 bound to 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) membranes were determined by solid-state 31P and 13C NMR spectroscopy. 31P NMR spectra showed that BLT2-DPPC membranes were disrupted into small particles below the gel-to-liquid crystalline phase transition temperature (Tc) and fused to form a magnetically oriented vesicle system where the membrane surface is parallel to the magnetic fields above the Tc. 13C NMR spectra of site-specifically 13C-labeled BLT2 at the carbonyl carbons were observed and the chemical shift anisotropies were analyzed to determine the dynamic structure of BLT2 bound to the magnetically oriented vesicle system. It was revealed that the membrane-bound BLT2 adopted an α-helical structure, rotating around the membrane normal with the tilt angle of the helical axis at 33°. Interatomic distances obtained from rotational-echo double-resonance experiments further showed that BLT2 adopted a straight α-helical structure. Molecular dynamics simulation performed in the BLT2-DPPC membrane system showed that the BLT2 formed a straight α-helix and that the C-terminus was inserted into the membrane. The α-helical axis is tilted 30° to the membrane normal, which is almost the same as the value obtained from solid-state NMR. These results suggest that the membrane disruption induced by BLT2 is attributed to insertion of BLT2 into the lipid bilayers. PMID:21081076

  19. Atomistic mechanisms of huntingtin N-terminal fragment insertion on a phospholipid bilayer revealed by molecular dynamics simulations.

    PubMed

    Côté, Sébastien; Wei, Guanghong; Mousseau, Normand

    2014-07-01

    The huntingtin protein is characterized by a segment of consecutive glutamines (Q(N)) that is responsible for its fibrillation. As with other amyloid proteins, misfolding of huntingtin is related to Huntington's disease through pathways that can involve interactions with phospholipid membranes. Experimental results suggest that the N-terminal 17-amino-acid sequence (htt(NT)) positioned just before the Q(N) region is important for the binding of huntingtin to membranes. Through all-atom explicit solvent molecular dynamics simulations, we unveil the structure and dynamics of the htt(NT)Q(N) fragment on a phospholipid membrane at the atomic level. We observe that the insertion dynamics of this peptide can be described by four main steps-approach, reorganization, anchoring, and insertion-that are very diverse at the atomic level. On the membrane, the htt(NT) peptide forms a stable α-helix essentially parallel to the membrane with its nonpolar side-chains-mainly Leu-4, Leu-7, Phe-11 and Leu-14-positioned in the hydrophobic core of the membrane. Salt-bridges involving Glu-5, Glu-12, Lys-6, and Lys-15, as well as hydrogen bonds involving Thr-3 and Ser-13 with the phospholipids also stabilize the structure and orientation of the htt(NT) peptide. These observations do not significantly change upon adding the Q(N) region whose role is rather to provide, through its hydrogen bonds with the phospholipids' head group, a stable scaffold facilitating the partitioning of the htt(NT) region in the membrane. Moreover, by staying accessible to the solvent, the amyloidogenic Q(N) region could also play a key role for the oligomerization of htt(NT)Q(N) on phospholipid membranes. © 2014 Wiley Periodicals, Inc.

  20. The complex folding behavior of HIV-1-protease monomer revealed by optical-tweezer single-molecule experiments and molecular dynamics simulations.

    PubMed

    Caldarini, M; Sonar, P; Valpapuram, I; Tavella, D; Volonté, C; Pandini, V; Vanoni, M A; Aliverti, A; Broglia, R A; Tiana, G; Cecconi, C

    2014-12-01

    We have used optical tweezers and molecular dynamics simulations to investigate the unfolding and refolding process of a stable monomeric form of HIV-1-protease (PR). We have characterized the behavior under tension of the native state (N), and that of the ensemble of partially folded (PF) conformations the protein visits en route to N, which collectively act as a long-lived state controlling the slow kinetic phase of the folding process. Our results reveal a rich network of unfolding events, where the native state unfolds either in a two-state manner or by populating an intermediate state I, while the PF state unravels through a multitude of pathways, underscoring its structural heterogeneity. Refolding of mechanically denatured HIV-1-PR monomers is also a multiple-pathway process. Molecular dynamics simulations allowed us to gain insight into possible conformations the protein adopts along the unfolding pathways, and provide information regarding possible structural features of the PF state.

  1. NMR spectroscopy and molecular dynamics simulation of r(CCGCUGCGG)₂ reveal a dynamic UU internal loop found in myotonic dystrophy type 1.

    PubMed

    Parkesh, Raman; Fountain, Matthew; Disney, Matthew D

    2011-02-08

    The NMR structure of an RNA with a copy of the 5'CUG/3'GUC motif found in the triplet repeating disorder myotonic dystrophy type 1 (DM1) is disclosed. The lowest energy conformation of the UU pair is a single-hydrogen bond structure; however, the UU protons undergo exchange indicating structural dynamics. Molecular dynamics simulations show that the single hydrogen bond structure is the most populated one but the UU pair interconverts among zero, one, and two hydrogen bond pairs. These studies have implications for the recognition of the DM1 RNA by small molecules and proteins.

  2. Molecular basis for the Cu2+ binding-induced destabilization of beta2-microglobulin revealed by molecular dynamics simulation.

    PubMed

    Deng, Nan-Jie; Yan, Lisa; Singh, Deepak; Cieplak, Piotr

    2006-06-01

    According to experimental data, binding of the Cu(2+) ions destabilizes the native state of beta2-microglobulin (beta2m). The partial unfolding of the protein was generally considered an early step toward fibril formation in dialysis-related amyloidosis. Recent NMR studies have suggested that the destabilization of the protein might be achieved through increased flexibility upon Cu(2+) binding. However, the molecular mechanism of destabilization due to Cu(2+), its role in amyloid formation, and the relative contributions of different potential copper-binding sites remain unclear. To elucidate the effect of ion ligation at atomic detail, a series of molecular dynamics simulations were carried out on apo- and Cu(2+)-beta2m systems in explicit aqueous solutions, with varying numbers of bound ions. Simulations at elevated temperatures (360 K) provide detailed pictures for the process of Cu(2+)-binding-induced destabilization of the native structure at the nanosecond timescale, which are in agreement with experiments. Conformational transitions toward partially unfolded states were observed in protein solutions containing bound copper ions at His-31 and His-51, which is marked by an increase in the protein vibrational entropy, with TDeltaS(vibr) ranging from 30 to 69 kcal/mol. The binding of Cu(2+) perturbs the secondary structure and the hydrogen bonding pattern disrupts the native hydrophobic contacts in the neighboring segments, which include the beta-strand D2 and part of the beta-strand E, B, and C and results in greater exposure of the D-E loop and the B-C loop to the water environment. Analysis of the MD trajectories suggests that the changes in the hydrophobic environment near the copper-binding sites lower the barrier of conformational transition and stabilize the more disordered conformation. The results also indicate that the binding of Cu(2+) at His-13 has little effect on the conformational stability, whereas the copper-binding site His-31, and to a lesser

  3. Essential function of the N-termini tails of the proteasome for the gating mechanism revealed by molecular dynamics simulations.

    PubMed

    Ishida, Hisashi

    2014-09-01

    Proteasome is involved in the degradation of proteins. Proteasome activators bind to the proteasome core particle (CP) and facilitate opening a gate of the CP, where Tyr8 and Asp9 in the N-termini tails of the CP form the ordered open gate. In a double mutant (Tyr8Gly/Asp9Gly), the N-termini tails are disordered and the stabilized open-gate conformation cannot be formed. To understand the gating mechanism of the CP for the translocation of the substrate, four different molecular dynamics simulations were carried out: ordered- and Tyr8Gly/Asp9Gly disordered-gate models of the CP complexed with an ATP-independent PA26 and ordered- and disordered-gate models of the CP complexed with an ATP-dependent PAN-like activator. The free-energies of the translocation of a polypeptide substrate moving through the gate were estimated. In the ordered-gate models, the substrate in the activator was more stable than that in the CP. The conformational entropy of the N-termini tails of the CP was larger when the substrate was in the activator than in the CP. In the disordered-gate models, the substrate in the activator was more destabilized than in the ordered-gate models. The mutated N-termini tails became randomized and their increased conformational entropy could no longer increase further even when the substrate was in the activator, meaning the randomized N-termini tails had lost the ability to stabilize the substrate in the activator. Thus, it was concluded that the dynamics of the N-termini tails entropically play a key role in the translocation of the substrate. © 2014 Wiley Periodicals, Inc.

  4. A Wrench in the Works of Human Acetylcholinesterase: Soman Induced Conformational Changes Revealed by Molecular Dynamics Simulations

    PubMed Central

    Fattebert, Jean-Luc; Emigh, Aiyana

    2015-01-01

    Irreversible inactivation of human acetylcholinesterase (hAChE) by organophosphorous pesticides (OPs) and chemical weapon agents (CWA) has severe morbidity and mortality consequences. We present data from quantum mechanics/molecular mechanics (QM/MM) and 80 classical molecular dynamics (MD) simulations of the apo and soman-adducted forms of hAChE to investigate the effects on the dynamics and protein structure when the catalytic Serine 203 is phosphonylated. We find that the soman phosphonylation of the active site Ser203 follows a water assisted addition-elimination mechanism with the elimination of the fluoride ion being the highest energy barrier at 6.5 kcal/mole. We observe soman-dependent changes in backbone and sidechain motions compared to the apo form of the protein. These alterations restrict the soman-adducted hAChE to a structural state that is primed for the soman adduct to be cleaved and removed from the active site. The altered motions and resulting structures provide alternative pathways into and out of the hAChE active site. In the soman-adducted protein both side and back door pathways are viable for soman adduct access. Correlation analysis of the apo and soman adducted MD trajectories shows that the correlation of gorge entrance and back door motion is disrupted when hAChE is adducted. This supports the hypothesis that substrate and product can use two different pathways as entry and exit sites in the apo form of the protein. These alternative pathways have important implications for the rational design of medical countermeasures. PMID:25874456

  5. A wrench in the works of human acetylcholinesterase: Soman induced conformational changes revealed by molecular dynamics simulations

    DOE PAGES

    Bennion, Brian J.; Essiz, Sebnem G.; Lau, Edmond Y.; ...

    2015-04-13

    Irreversible inactivation of human acetylcholinesterase (hAChE) by organophosphorous pesticides (OPs) and chemical weapon agents (CWA) has severe morbidity and mortality consequences. We present data from quantum mechanics/molecular mechanics (QM/MM) and 80 classical molecular dynamics (MD) simulations of the apo and soman-adducted forms of hAChE to investigate the effects on the dynamics and protein structure when the catalytic Serine 203 is phosphonylated. We find that the soman phosphonylation of the active site Ser203 follows a water assisted addition-elimination mechanism with the elimination of the fluoride ion being the highest energy barrier at 6.5 kcal/mole. We observe soman-dependent changes in backbone andmore » sidechain motions compared to the apo form of the protein. These alterations restrict the soman-adducted hAChE to a structural state that is primed for the soman adduct to be cleaved and removed from the active site. The altered motions and resulting structures provide alternative pathways into and out of the hAChE active site. In the soman-adducted protein both side and back door pathways are viable for soman adduct access. Correlation analysis of the apo and soman adducted MD trajectories shows that the correlation of gorge entrance and back door motion is disrupted when hAChE is adducted. This supports the hypothesis that substrate and product can use two different pathways as entry and exit sites in the apo form of the protein. These alternative pathways have important implications for the rational design of medical countermeasures.« less

  6. A wrench in the works of human acetylcholinesterase: Soman induced conformational changes revealed by molecular dynamics simulations

    SciTech Connect

    Bennion, Brian J.; Essiz, Sebnem G.; Lau, Edmond Y.; Fattebert, Jean -Luc; Emigh, Aiyana; Lightstone, Felice C.; Salsbury , Jr, Freddie

    2015-04-13

    Irreversible inactivation of human acetylcholinesterase (hAChE) by organophosphorous pesticides (OPs) and chemical weapon agents (CWA) has severe morbidity and mortality consequences. We present data from quantum mechanics/molecular mechanics (QM/MM) and 80 classical molecular dynamics (MD) simulations of the apo and soman-adducted forms of hAChE to investigate the effects on the dynamics and protein structure when the catalytic Serine 203 is phosphonylated. We find that the soman phosphonylation of the active site Ser203 follows a water assisted addition-elimination mechanism with the elimination of the fluoride ion being the highest energy barrier at 6.5 kcal/mole. We observe soman-dependent changes in backbone and sidechain motions compared to the apo form of the protein. These alterations restrict the soman-adducted hAChE to a structural state that is primed for the soman adduct to be cleaved and removed from the active site. The altered motions and resulting structures provide alternative pathways into and out of the hAChE active site. In the soman-adducted protein both side and back door pathways are viable for soman adduct access. Correlation analysis of the apo and soman adducted MD trajectories shows that the correlation of gorge entrance and back door motion is disrupted when hAChE is adducted. This supports the hypothesis that substrate and product can use two different pathways as entry and exit sites in the apo form of the protein. These alternative pathways have important implications for the rational design of medical countermeasures.

  7. Molecular dynamics simulation reveals conformational switching of water-mediated uracil-cytosine base-pairs in an RNA duplex.

    PubMed

    Schneider, C; Brandl, M; Sühnel, J

    2001-01-26

    A 4 ns molecular dynamics simulation of an RNA duplex (r-GGACUUCGGUCC)(2 )in solution with Na+ and Cl- as counterions was performed. The X-ray structure of this duplex includes two water-mediated uracil-cytosine pairs. In contrast to the other base-pairs in the duplex the water-mediated pairs switch between different conformations. One conformation corresponds to the geometry of the water-mediated UC pairs in the duplex X-ray structure with water acting both as hydrogen-bond donor and acceptor. Another conformation is close to that of a water-mediated UC base-pair found in the X-ray structure of the 23 S rRNA sarcin/ricin domain. In this case the oxygen of the water molecule is linked to two-base donor sites. For a very short time also a direct UC base-pair and a further conformation that is similar to the one found in the RNA duplex structure but exhibits an increased H3(U)...N3(C) distance is observed. Water molecules with unusually long residence times are involved in the water-mediated conformations. These results indicate that the dynamic behaviour of the water-mediated UC base-pairs differs from that of the duplex Watson-Crick and non-canonical guanine-uracil pairs with two or three direct hydrogen bonds. The conformational variability and increased flexibility has to be taken into account when considering these base-pairs as RNA building blocks and as recognition motifs. Copyright 2001 Academic Press.

  8. Molecular Dynamics Simulation Reveals the Selective Binding of Human Leukocyte Antigen Alleles Associated with Behçet's Disease

    PubMed Central

    Kongkaew, Sirilak; Yotmanee, Pathumwadee; Rungrotmongkol, Thanyada; Kaiyawet, Nopporn; Meeprasert, Arthitaya; Kaburaki, Toshikatsu; Noguchi, Hiroshi; Takeuchi, Fujio; Kungwan, Nawee; Hannongbua, Supot

    2015-01-01

    Behçet’s disease (BD), a multi-organ inflammatory disorder, is associated with the presence of the human leukocyte antigen (HLA) HLA-B*51 allele in many ethnic groups. The possible antigen involvement of the major histocompatibility complex class I chain related gene A transmembrane (MICA-TM) nonapeptide (AAAAAIFVI) has been reported in BD symptomatic patients. This peptide has also been detected in HLA-A*26:01 positive patients. To investigate the link of BD with these two specific HLA alleles, molecular dynamics (MD) simulations were applied on the MICA-TM nonapeptide binding to the two BD-associated HLA alleles in comparison with the two non-BD-associated HLA alleles (B*35:01 and A*11:01). The MD simulations were applied on the four HLA/MICA-TM peptide complexes in aqueous solution. As a result, stabilization for the incoming MICA-TM was found to be predominantly contributed from van der Waals interactions. The P2/P3 residue close to the N-terminal and the P9 residue at the C-terminal of the MICA-TM nonapeptide served as the anchor for the peptide accommodated at the binding groove of the BD associated HLAs. The MM/PBSA free energy calculation predicted a stronger binding of the HLA/peptide complexes for the BD-associated HLA alleles than for the non-BD-associated ones, with a ranked binding strength of B*51:01 > B*35:01 and A*26:01 > A*11:01. Thus, the HLAs associated with BD pathogenesis expose the binding efficiency with the MICA-TM nonapeptide tighter than the non-associated HLA alleles. In addition, the residues 70, 73, 99, 146, 147 and 159 of the two BD-associated HLAs provided the conserved interaction for the MICA-TM peptide binding. PMID:26331842

  9. Multi-step formation of a hemifusion diaphragm for vesicle fusion revealed by all-atom molecular dynamics simulations.

    PubMed

    Tsai, Hui-Hsu Gavin; Chang, Che-Ming; Lee, Jian-Bin

    2014-06-01

    Membrane fusion is essential for intracellular trafficking and virus infection, but the molecular mechanisms underlying the fusion process remain poorly understood. In this study, we employed all-atom molecular dynamics simulations to investigate the membrane fusion mechanism using vesicle models which were pre-bound by inter-vesicle Ca(2+)-lipid clusters to approximate Ca(2+)-catalyzed fusion. Our results show that the formation of the hemifusion diaphragm for vesicle fusion is a multi-step event. This result contrasts with the assumptions made in most continuum models. The neighboring hemifused states are separated by an energy barrier on the energy landscape. The hemifusion diaphragm is much thinner than the planar lipid bilayers. The thinning of the hemifusion diaphragm during its formation results in the opening of a fusion pore for vesicle fusion. This work provides new insights into the formation of the hemifusion diaphragm and thus increases understanding of the molecular mechanism of membrane fusion. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Molecular dynamics simulation of water in cytochrome c oxidase reveals two water exit pathways and the mechanism of transport.

    PubMed

    Sugitani, Ryogo; Stuchebrukhov, Alexei A

    2009-09-01

    We have examined the network of connected internal cavities in cytochrome c oxidase along which water produced at the catalytic center is removed from the enzyme. Using combination of structural analysis, molecular dynamics simulations, and free energy calculations we have identified two exit pathways that connect the Mg2+ ion cavity to the outside of the enzyme. Each pathway has a well-defined bottleneck, which determines the overall rate of water traffic along the exit pathway, and a specific cooperative mechanism of passing it. One of the pathways is going via Arg438/439 (in bovine numbering) toward the CuA center, approaching closely its His204B ligand and Lys171B residue; and the other is going toward Asp364 and Thr294. Comparison of the pathways among different aa3-type enzymes shows that they are well conserved. Possible connections of the finding to redox-coupled proton pumping mechanism are discussed. We propose specific mutations near the bottlenecks of the exit pathways that can test some of our hypotheses.

  11. Structural Instability of the Prion Protein upon M205S/R Mutations Revealed by Molecular Dynamics Simulations

    PubMed Central

    Hirschberger, Thomas; Stork, Martina; Schropp, Bernhard; Winklhofer, Konstanze F.; Tatzelt, Jörg; Tavan, Paul

    2006-01-01

    The point mutations M205S and M205R have been demonstrated to severely disturb the folding and maturation process of the cellular prion protein (PrPC). These disturbances have been interpreted as consequences of mutation-induced structural changes in PrP, which are suggested to involve helix 1 and its attachment to helix 3, because the mutated residue M205 of helix 3 is located at the interface of these two helices. Furthermore, current models of the prion protein scrapie (PrPSc), which is the pathogenic isoform of PrPC in prion diseases, imply that helix 1 disappears during refolding of PrPC into PrPSc. Based on molecular-dynamics simulations of wild-type and mutant PrPC in aqueous solution, we show here that the native PrPC structure becomes strongly distorted within a few nanoseconds, once the point mutations M205S and M205R have been applied. In the case of M205R, this distortion is characterized by a motion of helix 1 away from the hydrophobic core into the aqueous environment and a subsequent structural decay. Together with experimental evidence on model peptides, this decay suggests that the hydrophobic attachment of helix 1 to helix 3 at M205 is required for its correct folding into its stable native structure. PMID:16513786

  12. Diffusion behavior of helium in titanium and the effect of grain boundaries revealed by molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Gui-Jun, Cheng; Bao-Qin, Fu; Qing, Hou; Xiao-Song, Zhou; Jun, Wang

    2016-07-01

    The microstructures of titanium (Ti), an attractive tritium (T) storage material, will affect the evolution process of the retained helium (He). Understanding the diffusion behavior of He at the atomic scale is crucial for the mechanism of material degradation. The novel diffusion behavior of He has been reported by molecular dynamics (MD) simulation for the bulk hcp-Ti system and the system with grain boundary (GB). It is observed that the diffusion of He in the bulk hcp-Ti is significantly anisotropic (the diffusion coefficient of the [0001] direction is higher than that of the basal plane), as represented by the different migration energies. Different from convention, the GB accelerates the diffusion of He in one direction but not in the other. It is observed that a twin boundary (TB) can serve as an effective trapped region for He. The TB accelerates diffusion of He in the direction perpendicular to the twinning direction (TD), while it decelerates the diffusion in the TD. This finding is attributable to the change of diffusion path caused by the distortion of the local favorable site for He and the change of its number in the TB region. Project supported by the National Natural Science Foundation of China (Grant No. 51501119), the Scientific Research Starting Foundation for Younger Teachers of Sichuan University, China (Grant No. 2015SCU11058), the National Magnetic Confinement Fusion Science Program of China (Grant No. 2013GB109002), and the Cooperative Research Project “Research of Diffusion Behaviour of He in Grain Boundary of HCP-Titanium”, China.

  13. Coarse-Grained Models Reveal Functional Dynamics – II. Molecular Dynamics Simulation at the Coarse-Grained Level – Theories and Biological Applications

    PubMed Central

    Chng, Choon-Peng; Yang, Lee-Wei

    2008-01-01

    Molecular dynamics (MD) simulation has remained the most indispensable tool in studying equilibrium/non-equilibrium conformational dynamics since its advent 30 years ago. With advances in spectroscopy accompanying solved biocomplexes in growing sizes, sampling their dynamics that occur at biologically interesting spatial/temporal scales becomes computationally intractable; this motivated the use of coarse-grained (CG) approaches. CG-MD models are used to study folding and conformational transitions in reduced resolution and can employ enlarged time steps due to the absence of some of the fastest motions in the system. The Boltzmann-Inversion technique, heavily used in parameterizing these models, provides a smoothed-out effective potential on which molecular conformation evolves at a faster pace thus stretching simulations into tens of microseconds. As a result, a complete catalytic cycle of HIV-1 protease or the assembly of lipid-protein mixtures could be investigated by CG-MD to gain biological insights. In this review, we survey the theories developed in recent years, which are categorized into Folding-based and Molecular-Mechanics-based. In addition, physical bases in the selection of CG beads/time-step, the choice of effective potentials, representation of solvent, and restoration of molecular representations back to their atomic details are systematically discussed. PMID:19812774

  14. Differential dynamics of the serotonin1A receptor in membrane bilayers of varying cholesterol content revealed by all atom molecular dynamics simulation.

    PubMed

    Patra, Swarna M; Chakraborty, Sudip; Shahane, Ganesh; Prasanna, Xavier; Sengupta, Durba; Maiti, Prabal K; Chattopadhyay, Amitabha

    2015-01-01

    The serotonin1A receptor belongs to the superfamily of G protein-coupled receptors (GPCRs) and is a potential drug target in neuropsychiatric disorders. The receptor has been shown to require membrane cholesterol for its organization, dynamics and function. Although recent work suggests a close interaction of cholesterol with the receptor, the structural integrity of the serotonin1A receptor in the presence of cholesterol has not been explored. In this work, we have carried out all atom molecular dynamics simulations, totaling to 3 μs, to analyze the effect of cholesterol on the structure and dynamics of the serotonin1A receptor. Our results show that the presence of physiologically relevant concentration of membrane cholesterol alters conformational dynamics of the serotonin1A receptor and, on an average lowers conformational fluctuations. Our results show that, in general, transmembrane helix VII is most affected by the absence of membrane cholesterol. These results are in overall agreement with experimental data showing enhancement of GPCR stability in the presence of membrane cholesterol. Our results constitute a molecular level understanding of GPCR-cholesterol interaction, and represent an important step in our overall understanding of GPCR function in health and disease.

  15. Structural dynamics and cation interactions of DNA quadruplex molecules containing mixed guanine/cytosine quartets revealed by large-scale MD simulations.

    PubMed

    Spacková, N; Berger, I; Sponer, J

    2001-04-11

    Large-scale molecular dynamics (MD) simulations have been utilized to study G-DNA quadruplex molecules containing mixed GCGC and all-guanine GGGG quartet layers. Incorporation of mixed GCGC quartets into G-DNA stems substantially enhances their sequence variability. The mixed quadruplexes form rigid assemblies that require integral monovalent cations for their stabilization. The interaction of cations with the all-guanine quartets is the leading contribution for the stability of the four-stranded assemblies, while the mixed quartets are rather tolerated within the structure. The simulations predict that two cations are preferred to stabilize a four-layer quadruplex stem composed of two GCGC and two all-guanine quartets. The distribution of cations in the structure is influenced by the position of the GCGC quartets within the quadruplex, the presence and arrangement of thymidine loops connecting the guanine/cytosine stretches forming the stems, and the cation type present (Na(+) or K(+)). The simulations identify multiple nanosecond-scale stable arrangements of the thymidine loops present in the molecules investigated. In these thymidine loops, several structured pockets are identified capable of temporarily coordinating cations. However, no stable association of cations to a loop has been observed. The simulations reveal several paths through the thymidine loop regions that can be followed by the cations when exchanging between the central ion channel in the quadruplex stem and the surrounding solvent. We have carried out 20 independent simulations while the length of simulations reaches a total of 90 ns, rendering this study one of the most extensive MD investigations carried out on nucleic acids so far. The trajectories provide a largely converged characterization of the structural dynamics of these four-stranded G-DNA molecules.

  16. The atomistic mechanism of hcp-to-bcc martensitic transformation in the Ti-Nb system revealed by molecular dynamics simulations.

    PubMed

    Li, Yang; Li, JiaHao; Liu, BaiXin

    2015-02-14

    Applying the constructed Ti-Nb potentials, molecular dynamics simulations were conducted to investigate the martensitic transformation of Ti100-xNbx alloys (x = 5, 10…25) from the α' phase (hcp) to the β phase (bcc). It is found that the transformation involved four phases, i.e. α', α'', fco (face-centered orthorhombic), and β phases. The structures of the obtained phases exhibit consistency with experimental data, verifying the validity of atomic simulations. The simulations not only revealed the processes of atomic displacements during the transformation, but also elucidated the underlying mechanism of the martensitic transformation at the atomic level. The martensitic transformation incorporates three types of coinstantaneous deformations i.e. slide, shear as well as extension, and the subsequent lattice constant relaxation. Furthermore, according to the proposed mechanism, the crystallographic correlation between the initial α' phase and the final β phase has been deduced. The simulation results provide a clear landscape on the martensitic transformation mechanism, facilitating our comprehensive understanding on the phase transition in the Ti-Nb system.

  17. New Insights into Active Site Conformation Dynamics of E. coli PNP Revealed by Combined H/D Exchange Approach and Molecular Dynamics Simulations.

    PubMed

    Kazazić, Saša; Bertoša, Branimir; Luić, Marija; Mikleušević, Goran; Tarnowski, Krzysztof; Dadlez, Michal; Narczyk, Marta; Bzowska, Agnieszka

    2016-01-01

    The biologically active form of purine nucleoside phosphorylase (PNP) from Escherichia coli (EC 2.4.2.1) is a homohexamer unit, assembled as a trimer of dimers. Upon binding of phosphate, neighboring monomers adopt different active site conformations, described as open and closed. To get insight into the functions of the two distinctive active site conformations, virtually inactive Arg24Ala mutant is complexed with phosphate; all active sites are found to be in the open conformation. To understand how the sites of neighboring monomers communicate with each other, we have combined H/D exchange (H/DX) experiments with molecular dynamics (MD) simulations. Both methods point to the mobility of the enzyme, associated with a few flexible regions situated at the surface and within the dimer interface. Although H/DX provides an average extent of deuterium uptake for all six hexamer active sites, it was able to indicate the dynamic mechanism of cross-talk between monomers, allostery. Using this technique, it was found that phosphate binding to the wild type (WT) causes arrest of the molecular motion in backbone fragments that are flexible in a ligand-free state. This was not the case for the Arg24Ala mutant. Upon nucleoside substrate/inhibitor binding, some release of the phosphate-induced arrest is observed for the WT, whereas the opposite effects occur for the Arg24Ala mutant. MD simulations confirmed that phosphate is bound tightly in the closed active sites of the WT; conversely, in the open conformation of the active site of the WT phosphate is bound loosely moving towards the exit of the active site. In Arg24Ala mutant binary complex Pi is bound loosely, too.

  18. Molecular Dynamics Simulations Reveal the Conformational Flexibility of Lipid II and Its Loose Association with the Defensin Plectasin in the Staphylococcus aureus Membrane.

    PubMed

    Witzke, Sarah; Petersen, Michael; Carpenter, Timothy S; Khalid, Syma

    2016-06-14

    Lipid II is critical for peptidoglycan synthesis, which is the main component of the bacterial cell wall. Lipid II is a relatively conserved and important part of the cell wall biosynthesis pathway and is targeted by antibiotics such as the lantibiotics, which achieve their function by disrupting the biosynthesis of the cell wall. Given the urgent need for development of novel antibiotics to counter the growing threat of bacterial infection resistance, it is imperative that a thorough molecular-level characterization of the molecules targeted by antibiotics be achieved. To this end, we present a molecular dynamics simulation study of the conformational dynamics of Lipid II within a detailed model of the Staphylococcus aureus cell membrane. We show that Lipid II is able to adopt a range of conformations, even within the packed lipidic environment of the membrane. Our simulations also reveal dimerization of Lipid II mediated by cations. In the presence of the defensin peptide plectasin, the conformational lability of Lipid II allows it to form loose complexes with the protein, via a number of different binding modes.

  19. Dynamical Mechanisms of Ozone Anomalies Formation as Revealed by Global-Scale and Regional Simulations with PlanetWRF and CAM modelling systems

    NASA Astrophysics Data System (ADS)

    Barodka, Siarhei; Krasouski, Alexander; Svetashev, Alexander; Turishev, Leonid; Zhuchkevich, Veronika

    2013-04-01

    parameterization scheme should allow for the possible radiative feedback on ozone dynamics. We perform global simulations with the PlanetWRF - WRFChem system and compare results with those obtained with the CAM system. Furthermore, to perform regional simulations on finer grids resolving mesoscale processes we use nested domains following spatial region of local ozone anomalies of interest. We perform studies of several cases of both negative (miniholes) and positive local ozone anomalies over the territory of Europe. Furthermore, we investigate the connection between ozone anomalies dynamics in the stratosphere and tropospheric weather phenomena. For that purpose we introduce perturbations to the initial conditions. First, we modify the variable fields on stratospheric model levels to see its possible impact on tropospheric phenomena. Independently, in a subsequent numerical experiment we introduce disturbances in surface and tropospheric variable fields in order to trace its influence on the stratospheric ozone dynamics. Intercomparison of modelling results is given, revealing interactions of the synoptic pressure formations with features of the stratospheric circulation. Apart from that, we analyze the role of vertical motions and ozone radiative heating on local anomalies formation. [1] Mangold A. et al - A model study of the January 2006 low total ozone episode over Western Europe and comparison with ozone sonde data // Atmospheric Chemistry and Physics, 9. - 2009. - pp. 6429-6451. [2] Semane N. et al - A very deep ozone minihole in the Northern Hemisphere stratosphere at mid-latitudes during the winter of 2000 // Tellus, 54A. - 2002. - pp. 382-389. [3] Liu C. et al - Dynamic formation of extreme ozone minimum events over the Tibetan Plateau during northern winters 1987-2001 // Journal of Geophysical Research, Vol. 115, D18311. - 2010.

  20. Molecular dynamics simulations on pars intercerebralis major peptide-C (PMP-C) reveal the role of glycosylation and disulfide bonds in its enhanced structural stability and function.

    PubMed

    Kaushik, Sandeep; Mohanty, Debasisa; Surolia, Avadhesha

    2012-01-01

    Fucosylation of Thr 9 in pars intercerebralis major peptide-C (PMP-C) enhances its structural stability and functional ability as a serine protease inhibitor. In order to understand the role of disulfide bonds and glycosylation on the structure and function of PMP-C, we have carried out multiple explicit solvent molecular dynamics (MD) simulations on fucosylated and non-fucosylated forms of PMP-C, both in the presence and absence of the disulfide bonds. Our simulations revealed that there were no significant structural changes in the native disulfide bonded forms of PMP-C due to fucosylation. On the other hand, the non-fucosylated form of PMP-C without disulfide bonds showed larger deviations from the starting structure than the fucosylated form. However, the structural deviations were restricted to the terminal regions while core β-sheet retained its hydrogen bonded structure even in absence of disulfide bonds as well as fucosylation. Interestingly, fucosylation of disulfide bonded native PMP-C led to a decreased thermal flexibility in the residue stretch 29-32 which is known to interact with the active site of the target proteases. Our analysis revealed that disulfide bonds covalently connect the residue stretch 29-32 to the central β-sheet of PMP-C and using a novel network of side chain interactions and disulfide bonds fucosylation at Thr 9 is altering the flexibility of the stretch 29-32 located at a distal site. Thus, our simulations explain for the first time, how presence of disulfide bonds between conserved cysteines and fucosylation enhance the function of PMP-C as a protease inhibitor.

  1. Factors affecting the interactions between beta-lactoglobulin and fatty acids as revealed in molecular dynamics simulations.

    PubMed

    Yi, Changhong; Wambo, Thierry O

    2015-09-21

    Beta-lactoglobulin (BLG), a bovine dairy protein, is a promiscuously interacting protein that can bind multiple hydrophobic ligands. Fatty acids (FAs), common hydrophobic molecules bound to BLG, are important sources of fuel for life because they yield large quantities of ATP when metabolized. The binding affinity increases with the length of the ligands, indicating the importance of the van der Waals (vdW) interactions between the hydrocarbon tail and the hydrophobic calyx of BLG. An exception to this rule is caprylic acid (OCA) which is two-carbon shorter but has a stronger binding affinity than capric acid. Theoretical calculations in the current literature are not accurate enough to shed light on the underlying physics of this exception. The computed affinity values are greater for longer fatty acids without respect for the caprylic exception and those values are generally several orders of magnitude away from the experimental data. In this work, we used hybrid steered molecular dynamics to accurately compute the binding free energies between BLG and the five saturated FAs of 8 to 16 carbon atoms. The computed binding free energies agree well with experimental data not only in rank but also in absolute values. We gained insights into the exceptional behavior of caprylic acid in the computed values of entropy and electrostatic interactions. We found that the electrostatic interaction between the carboxyl group of caprylic acid and the two amino groups of K60/69 in BLG is much stronger than the vdW force between the OCA's hydrophobic tail and the BLG calyx. This pulls OCA to the top of the beta barrel where it is easier to fluctuate, giving rise to greater entropy of OCA at the binding site.

  2. Sum Frequency Generation Spectroscopy and Molecular Dynamics Simulations Reveal a Rotationally Fluid Adsorption State of α-Pinene on Silica

    SciTech Connect

    Ho, Junming; Psciuk, Brian T.; Chase, Hilary M.; Rudshteyn, Benjamin; Upshur, Mary Alice; Fu, Li; Thomson, Regan J.; Wang, Hong-Fei; Geiger, Franz M.; Batista, Victor S.

    2016-06-16

    A rotationally fluid state of α-pinene at fused silica/vapor interfaces is revealed by computational and experimental vibrational sum frequency generation (SFG) studies. We report the first assignment of the vibrational modes in the notoriously congested C-H stretching region of α-pinene and identify its bridge methylene group on the four-membered ring ("βCH2") as the origin of its dominant spectral feature. We find that the spectra are perfused with Fermi resonances that need to be accounted for explicitly in the computation of vibrational spectra of strained hydrocarbons such α-pinene. The preferred orientations of α-pinene are consistent with optimization of van der Waals contacts with the silica surface that results in a bimodal distribution of highly fluxional orientations in which the βCH2 group points "towards" or "away from” the surface. The reported findings are particularly relevant to the exposure of α-pinene to primary oxidants in heterogeneous catalytic pathways that exploit α-pinene as a sustainable feedstock for fine chemicals and polymers.

  3. Molecular dynamics simulations.

    PubMed

    Lindahl, Erik

    2015-01-01

    Molecular dynamics has evolved from a niche method mainly applicable to model systems into a cornerstone in molecular biology. It provides us with a powerful toolbox that enables us to follow and understand structure and dynamics with extreme detail-literally on scales where individual atoms can be tracked. However, with great power comes great responsibility: Simulations will not magically provide valid results, but it requires a skilled researcher. This chapter introduces you to this, and makes you aware of some potential pitfalls. We focus on the two basic and most used methods; optimizing a structure with energy minimization and simulating motion with molecular dynamics. The statistical mechanics theory is covered briefly as well as limitations, for instance the lack of quantum effects and short timescales. As a practical example, we show each step of a simulation of a small protein, including examples of hardware and software, how to obtain a starting structure, immersing it in water, and choosing good simulation parameters. You will learn how to analyze simulations in terms of structure, fluctuations, geometrical features, and how to create ray-traced movies for presentations. With modern GPU acceleration, a desktop can perform μs-scale simulations of small proteins in a day-only 15 years ago this took months on the largest supercomputer in the world. As a final exercise, we show you how to set up, perform, and interpret such a folding simulation.

  4. Molecular simulations and Markov state modeling reveal the structural diversity and dynamics of a theophylline-binding RNA aptamer in its unbound state.

    PubMed

    Warfield, Becka M; Anderson, Peter C

    2017-01-01

    RNA aptamers are oligonucleotides that bind with high specificity and affinity to target ligands. In the absence of bound ligand, secondary structures of RNA aptamers are generally stable, but single-stranded and loop regions, including ligand binding sites, lack defined structures and exist as ensembles of conformations. For example, the well-characterized theophylline-binding aptamer forms a highly stable binding site when bound to theophylline, but the binding site is unstable and disordered when theophylline is absent. Experimental methods have not revealed at atomic resolution the conformations that the theophylline aptamer explores in its unbound state. Consequently, in the present study we applied 21 microseconds of molecular dynamics simulations to structurally characterize the ensemble of conformations that the aptamer adopts in the absence of theophylline. Moreover, we apply Markov state modeling to predict the kinetics of transitions between unbound conformational states. Our simulation results agree with experimental observations that the theophylline binding site is found in many distinct binding-incompetent states and show that these states lack a binding pocket that can accommodate theophylline. The binding-incompetent states interconvert with binding-competent states through structural rearrangement of the binding site on the nanosecond to microsecond timescale. Moreover, we have simulated the complete theophylline binding pathway. Our binding simulations supplement prior experimental observations of slow theophylline binding kinetics by showing that the binding site must undergo a large conformational rearrangement after the aptamer and theophylline form an initial complex, most notably, a major rearrangement of the C27 base from a buried to solvent-exposed orientation. Theophylline appears to bind by a combination of conformational selection and induced fit mechanisms. Finally, our modeling indicates that when Mg2+ ions are present the population

  5. Molecular simulations and Markov state modeling reveal the structural diversity and dynamics of a theophylline-binding RNA aptamer in its unbound state

    PubMed Central

    Warfield, Becka M.

    2017-01-01

    RNA aptamers are oligonucleotides that bind with high specificity and affinity to target ligands. In the absence of bound ligand, secondary structures of RNA aptamers are generally stable, but single-stranded and loop regions, including ligand binding sites, lack defined structures and exist as ensembles of conformations. For example, the well-characterized theophylline-binding aptamer forms a highly stable binding site when bound to theophylline, but the binding site is unstable and disordered when theophylline is absent. Experimental methods have not revealed at atomic resolution the conformations that the theophylline aptamer explores in its unbound state. Consequently, in the present study we applied 21 microseconds of molecular dynamics simulations to structurally characterize the ensemble of conformations that the aptamer adopts in the absence of theophylline. Moreover, we apply Markov state modeling to predict the kinetics of transitions between unbound conformational states. Our simulation results agree with experimental observations that the theophylline binding site is found in many distinct binding-incompetent states and show that these states lack a binding pocket that can accommodate theophylline. The binding-incompetent states interconvert with binding-competent states through structural rearrangement of the binding site on the nanosecond to microsecond timescale. Moreover, we have simulated the complete theophylline binding pathway. Our binding simulations supplement prior experimental observations of slow theophylline binding kinetics by showing that the binding site must undergo a large conformational rearrangement after the aptamer and theophylline form an initial complex, most notably, a major rearrangement of the C27 base from a buried to solvent-exposed orientation. Theophylline appears to bind by a combination of conformational selection and induced fit mechanisms. Finally, our modeling indicates that when Mg2+ ions are present the population

  6. Tether Dynamics Simulation

    NASA Technical Reports Server (NTRS)

    1987-01-01

    The proceedings of the conference are presented. The objective was to provide a forum for the discussion of the structure and status of existing computer programs which are used to simulate the dynamics of a variety of tether applications in space. A major topic was different simulation models and the process of validating them. Guidance on future work in these areas was obtained from a panel discussion; the panel was composed of resource and technical managers and dynamic analysts in the tether field. The conclusions of this panel are also presented.

  7. Dynamical Simulation of Probabilities

    NASA Technical Reports Server (NTRS)

    Zak, Michail

    1996-01-01

    It has been demonstrated that classical probabilities, and in particular, probabilistic Turing machine, can be simulated by combining chaos and non-Lipschitz dynamics, without utilization of any man-made devices(such as random number generators). Self-orgainizing properties of systems coupling simulated and calculated probabilities and their link to quantum computations are discussed. Special attention was focused upon coupled stochastic processes, defined in terms of conditional probabilities, for which joint probability does not exist. Simulations of quantum probabilities are also discussed.

  8. Dynamical Simulation of Probabilities

    NASA Technical Reports Server (NTRS)

    Zak, Michail

    1996-01-01

    It has been demonstrated that classical probabilities, and in particular, probabilistic Turing machine, can be simulated by combining chaos and non-Lipschitz dynamics, without utilization of any man-made devices(such as random number generators). Self-orgainizing properties of systems coupling simulated and calculated probabilities and their link to quantum computations are discussed. Special attention was focused upon coupled stochastic processes, defined in terms of conditional probabilities, for which joint probability does not exist. Simulations of quantum probabilities are also discussed.

  9. Molecular dynamics simulation reveals insights into the mechanism of unfolding by the A130T/V mutations within the MID1 zinc-binding Bbox1 domain.

    PubMed

    Zhao, Yunjie; Zeng, Chen; Massiah, Michael A

    2015-01-01

    The zinc-binding Bbox1 domain in protein MID1, a member of the TRIM family of proteins, facilitates the ubiquitination of the catalytic subunit of protein phosphatase 2A and alpha4, a protein regulator of PP2A. The natural mutation of residue A130 to a valine or threonine disrupts substrate recognition and catalysis. While NMR data revealed the A130T mutant Bbox1 domain failed to coordinate both structurally essential zinc ions and resulted in an unfolded structure, the unfolding mechanism is unknown. Principle component analysis revealed that residue A130 served as a hinge point between the structured β-strand-turn-β-strand (β-turn-β) and the lasso-like loop sub-structures that constitute loop1 of the ββα-RING fold that the Bbox1 domain adopts. Backbone RMSD data indicate significant flexibility and departure from the native structure within the first 5 ns of the molecular dynamics (MD) simulation for the A130V mutant (>6 Å) and after 30 ns for A130T mutant (>6 Å). Overall RMSF values were higher for the mutant structures and showed increased flexibility around residues 125 and 155, regions with zinc-coordinating residues. Simulated pKa values of the sulfhydryl group of C142 located near A130 suggested an increased in value to ~9.0, paralleling the increase in the apparent dielectric constants for the small cavity near residue A130. Protonation of the sulfhydryl group would disrupt zinc-coordination, directly contributing to unfolding of the Bbox1. Together, the increased motion of residues of loop 1, which contains four of the six zinc-binding cysteine residues, and the increased pKa of C142 could destabilize the structure of the zinc-coordinating residues and contribute to the unfolding.

  10. The temporal-spatial dynamics of feature maps during monocular deprivation revealed by chronic imaging and self-organization model simulation.

    PubMed

    Tong, Lei; Xie, Yang; Yu, Hongbo

    2016-12-17

    Experiments on the adult visual cortex of cats, ferrets and monkeys have revealed organized spatial relationships between multiple feature maps which can also be reproduced by the Kohonen and elastic net self-organization models. However, attempts to apply these models to simulate the temporal kinetics of monocular deprivation (MD) during the critical period, and their effects on the spatial arrangement of feature maps, have led to conflicting results. In this study, we performed MD and chronic imaging in the ferret visual cortex during the critical period of ocular dominance (OD) plasticity. We also used the Kohonen model to simulate the effects of MD on OD and orientation map development. Both the experiments and simulations demonstrated two general parameter-insensitive findings. Specifically, our first finding demonstrated that the OD index shift resulting from MD, and its subsequent recovery during binocular vision (BV), were both nonlinear, with a significantly stronger shift occurring during the initial period. Meanwhile, spatial reorganization of feature maps led to globally unchanged but locally shifted map patterns. In detail, we found that the periodicity of OD and orientation maps remained unchanged during, and after, deprivation. Relationships between OD and orientation maps remained similar but were significantly weakened due to OD border shifts. These results indicate that orthogonal gradient relationships between maps may be preset and are only mildly modifiable during the critical period. The Kohonen model was able to reproduce these experimental results, hence its role is further extended to the description of cortical feature map dynamics during development. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Secondary Water Pore Formation for Proton Transport in a ClC Exchanger Revealed by an Atomistic Molecular-Dynamics Simulation

    PubMed Central

    Ko, Youn Jo; Jo, Won Ho

    2010-01-01

    Abstract Several prokaryotic ClC proteins have been demonstrated to function as exchangers that transport both chloride ions and protons simultaneously in opposite directions. However, the path of the proton through the ClC exchanger, and how the protein brings about the coupled movement of both ions are still unknown. In this work, we use an atomistic molecular dynamics (MD) simulation to demonstrate that a previously unknown secondary water pore is formed inside an Escherichia coli ClC exchanger. The secondary water pore is bifurcated from the chloride ion pathway at E148. From the systematic simulations, we determined that the glutamate residue exposed to the intracellular solution, E203, plays an important role as a trigger for the formation of the secondary water pore, and that the highly conserved tyrosine residue Y445 functions as a barrier that separates the proton from the chloride ion pathways. Based on our simulation results, we conclude that protons in the ClC exchanger are conducted via a water network through the secondary water pore, and we propose a new mechanism for the coupled transport of chloride ions and protons. It has been reported that several members of ClC proteins are not just channels that simply transport chloride ions across lipid bilayers; rather, they are exchangers that transport both the chloride ion and proton in opposite directions. However, the ion transit pathways and the mechanism of the coupled movement of these two ions have not yet been unveiled. In this article, we report a new finding (to our knowledge) of a water pore inside a prokaryotic ClC protein as revealed by computer simulation. This water pore is bifurcated from the putative chloride ion, and water molecules inside the new pore connect two glutamate residues that are known to be key residues for proton transport. On the basis of our simulation results, we conclude that the water wire that is formed inside the newly found pore acts as a proton pathway, which

  12. Molecular dynamics simulations of apo, holo, and inactivator bound GABA-at reveal the role of active site residues in PLP dependent enzymes.

    PubMed

    Gökcan, Hatice; Monard, Gerald; Sungur Konuklar, F Aylin

    2016-07-01

    The pyridoxal 5-phosphate (PLP) cofactor is a significant organic molecule in medicinal chemistry. It is often found covalently bound to lysine residues in proteins to form PLP dependent enzymes. An example of this family of PLP dependent enzymes is γ-aminobutyric acid aminotransferase (GABA-AT) which is responsible for the degradation of the neurotransmitter GABA. Its inhibition or inactivation can be used to prevent the reduction of GABA concentration in brain which is the source of several neurological disorders. As a test case for PLP dependent enzymes, we have performed molecular dynamics simulations of GABA-AT to reveal the roles of the protein residues and its cofactor. Three different states have been considered: the apoenzyme, the holoenzyme, and the inactive state obtained after the suicide inhibition by vigabatrin. Different protonation states have also been considered for PLP and two key active site residues: Asp298 and His190. Together, 24 independent molecular dynamics trajectories have been simulated for a cumulative total of 2.88 µs. Our results indicate that, unlike in aqueous solution, the PLP pyridine moiety is protonated in GABA-AT. This is a consequence of a pKa shift triggered by a strong charge-charge interaction with an ionic "diad" formed by Asp298 and His190 that would help the activation of the first half-reaction of the catalytic mechanism in GABA-AT: the conversion of PLP to free pyridoxamine phosphate (PMP). In addition, our MD simulations exhibit additional strong hydrogen bond networks between the protein and PLP: the phosphate group is held in place by the donation of at least three hydrogen bonds while the carbonyl oxygen of the pyridine ring interacts with Gln301; Phe181 forms a π-π stacking interaction with the pyridine ring and works as a gate keeper with the assistance of Val300. All these interactions are hypothesized to help maintain free PMP in place inside the protein active site to facilitate the second half

  13. Molecular dynamics simulations.

    PubMed

    Lindahl, Erik R

    2008-01-01

    Molecular simulation is a very powerful toolbox in modern molecular modeling, and enables us to follow and understand structure and dynamics with extreme detail--literally on scales where motion of individual atoms can be tracked. This chapter focuses on the two most commonly used methods, namely, energy minimization and molecular dynamics, that, respectively, optimize structure and simulate the natural motion of biological macromolecules. The common theoretical framework based on statistical mechanics is covered briefly as well as limitations of the computational approach, for instance, the lack of quantum effects and limited timescales accessible. As a practical example, a full simulation of the protein lysozyme in water is described step by step, including examples of necessary hardware and software, how to obtain suitable starting molecular structures, immersing it in a solvent, choosing good simulation parameters, and energy minimization. The chapter also describes how to analyze the simulation in terms of potential energies, structural fluctuations, coordinate stability, geometrical features, and, finally, how to create beautiful ray-traced movies that can be used in presentations.

  14. Dynamic load simulator

    NASA Technical Reports Server (NTRS)

    Joncas, K. P.

    1972-01-01

    Concepts and techniques for identifying and simulating both the steady state and dynamic characteristics of electrical loads for use during integrated system test and evaluation are discussed. The investigations showed that it is feasible to design and develop interrogation and simulation equipment to perform the desired functions. During the evaluation, actual spacecraft loads were interrogated by stimulating the loads with their normal input voltage and measuring the resultant voltage and current time histories. Elements of the circuits were optimized by an iterative process of selecting element values and comparing the time-domain response of the model with those obtained from the real equipment during interrogation.

  15. Molecular dynamics simulation of human serum paraoxonase 1 in DPPC bilayer reveals a critical role of transmembrane helix H1 for HDL association.

    PubMed

    Patra, Mahesh Chandra; Rath, Surya Narayan; Pradhan, Sukanta Kumar; Maharana, Jitendra; De, Sachinandan

    2014-01-01

    Serum paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-bound mammalian enzyme exhibiting antiatherosclerotic activity. Despite years of research, an accurate model for the binding interaction between PON1 and HDL has not been established. However, it is reported that anchoring of PON1 to HDL is mainly governed by an N-terminal alpha helix H1 and another short helix H2. Here, we studied the molecular association of full-length human PON1 (huPON1) with a HDL-mimetic dipalmitoylphosphatidylcholine (DPPC) bilayer using homology modeling and molecular dynamics simulations. Our results indicate that H1 is the highly dynamic part of huPON1, showing clockwise rotation of up to 30° within the DPPC bilayer. However, without phospholipid molecules, H1 experiences helical distortions, illustrating an incompatible HDL-anchoring conformation. Snorkeling interactions of K3, R18, and R27 together with aromatic locks formed by Y187, Y190, W194, and W202 are highly essential for anchoring of huPON1 to HDL's surface. Molecular mechanics/Poisson-Boltzmann solvent-accessible surface area (MM/PBSA) binding free energy calculation revealed that H1 displays greater binding affinity towards lipid molecules compared with H2 and H3, suggesting that H1 is the most probable HDL-binding domain of PON1. Binding free energy decomposition showed that K3, R18, and R27 interact with polar headgroups of DPPC membrane through electrostatic interaction. Moreover, Y187, Y190, W194, and W202 interact with DPPC lipids mainly through van der Waals interaction. Taken together, these results show that the transmembrane helix H1 along with the interfacial positively charged and aromatic resides were crucial for PON1's association with HDL particle. The current study will be useful towards understanding the antiatherosclerotic and bioscavenging properties of this promiscuous enzyme.

  16. Data Systems Dynamic Simulator

    NASA Technical Reports Server (NTRS)

    Rouff, Christopher; Clark, Melana; Davenport, Bill; Message, Philip

    1993-01-01

    The Data System Dynamic Simulator (DSDS) is a discrete event simulation tool. It was developed for NASA for the specific purpose of evaluating candidate architectures for data systems of the Space Station era. DSDS provides three methods for meeting this requirement. First, the user has access to a library of standard pre-programmed elements. These elements represent tailorable components of NASA data systems and can be connected in any logical manner. Secondly, DSDS supports the development of additional elements. This allows the more sophisticated DSDS user the option of extending the standard element set. Thirdly, DSDS supports the use of data streams simulation. Data streams is the name given to a technique that ignores packet boundaries, but is sensitive to rate changes. Because rate changes are rare compared to packet arrivals in a typical NASA data system, data stream simulations require a fraction of the CPU run time. Additionally, the data stream technique is considerably more accurate than another commonly-used optimization technique.

  17. Homology modeling and molecular dynamics simulations of the active state of the nociceptin receptor reveal new insights into agonist binding and activation.

    PubMed

    Daga, Pankaj R; Zaveri, Nurulain T

    2012-08-01

    The opioid receptor-like receptor, also known as the nociceptin receptor (NOP), is a class A G protein-coupled receptor (GPCR) in the opioid receptor family. Although NOP shares a significant homology with the other opioid receptors, it does not bind known opioid ligands and has been shown to have a distinct mechanism of activation compared to the closely related opioid receptors mu, delta, and kappa. Previously reported homology models of the NOP receptor, based on the inactive-state GPCR crystal structures, give limited information on the activation and selectivity features of this fourth member of the opioid receptor family. We report here the first active-state homology model of the NOP receptor based on the opsin GPCR crystal structure. An inactive-state homology model of NOP was also built using a multiple template approach. Molecular dynamics simulation of the active-state NOP model and comparison to the inactive-state model suggest that NOP activation involves movements of transmembrane (TM)3 and TM6 and several activation microswitches, consistent with GPCR activation. Docking of the selective nonpeptidic NOP agonist ligand Ro 64-6198 into the active-state model reveals active-site residues in NOP that play a role in the high selectivity of this ligand for NOP over the other opioid receptors. Docking the shortest active fragment of endogenous agonist nociceptin/orphaninFQ (residues 1-13) shows that the NOP extracellular loop 2 (EL2) loop interacts with the positively charged residues (8-13) of N/OFQ. Both agonists show extensive polar interactions with residues at the extracellular end of the TM domain and EL2 loop, suggesting agonist-induced reorganization of polar networks, during receptor activation. Copyright © 2012 Wiley Periodicals, Inc.

  18. Look-ahead Dynamic Simulation

    SciTech Connect

    2015-10-20

    Look-ahead dynamic simulation software system incorporates the high performance parallel computing technologies, significantly reduces the solution time for each transient simulation case, and brings the dynamic simulation analysis into on-line applications to enable more transparency for better reliability and asset utilization. It takes the snapshot of the current power grid status, functions in parallel computing the system dynamic simulation, and outputs the transient response of the power system in real time.

  19. Sawfishes stealth revealed using computational fluid dynamics.

    PubMed

    Bradney, D R; Davidson, A; Evans, S P; Wueringer, B E; Morgan, D L; Clausen, P D

    2017-02-27

    Detailed computational fluid dynamics simulations for the rostrum of three species of sawfish (Pristidae) revealed that negligible turbulent flow is generated from all rostra during lateral swipe prey manipulation and swimming. These results suggest that sawfishes are effective stealth hunters that may not be detected by their teleost prey's lateral line sensory system during pursuits. Moreover, during lateral swipes, the rostra were found to induce little velocity into the surrounding fluid. Consistent with previous data of sawfish feeding behaviour, these data indicate that the rostrum is therefore unlikely to be used to stir up the bottom to uncover benthic prey. Whilst swimming with the rostrum inclined at a small angle to the horizontal, the coefficient of drag of the rostrum is relatively low and the coefficient of lift is zero.

  20. Steered molecular dynamics simulations of a bacterial type IV pilus reveal characteristics of an experimentally-observed, force-induced conformational transition

    NASA Astrophysics Data System (ADS)

    Baker, Joseph; Biais, Nicolas; Tama, Florence

    2011-10-01

    Type IV pili (T4P) are long, filamentous structures that emanate from the cellular surface of many infectious bacteria. They are built from a 158 amino acid long subunit called pilin. T4P can grow to many micrometers in length, and can withstand large tension forces. During the infection process, pili attach themselves to host cells, and therefore naturally find themselves under tension. We investigated the response of a T4 pilus to a pulling force using the method of steered molecular dynamics (SMD) simulation. Our simulations expose to the external environment an amino acid sequence initially hidden in the native filament, in agreement with experimental data. Therefore, our simulations might be probing the initial stage of the transition to a force-induced conformation of the T4 pilus. Additional exposed amino acid sequences that might be useful targets for drugs designed to mitigate bacterial infection were also predicted.

  1. Diffusion-Controlled Recrystallization of Water Sorbed into Poly(meth)acrylates Revealed by Variable-Temperature Mid-Infrared Spectroscopy and Molecular Dynamics Simulation.

    PubMed

    Yasoshima, Nobuhiro; Fukuoka, Mizuki; Kitano, Hiromi; Kagaya, Shigehiro; Ishiyama, Tatsuya; Gemmei-Ide, Makoto

    2017-05-18

    Recrystallization behaviors of water sorbed into four poly(meth)acrylates, poly(2-methoxyethyl acrylate), poly(tetrahydrofurfuryl acrylate), poly(methyl acrylate), and poly(methyl methacrylate), are investigated by variable-temperature mid-infrared (VT-MIR) spectroscopy and molecular dynamics (MD) simulation. VT-MIR spectra demonstrate that recrystallization temperatures of water sorbed into the polymers are positively correlated with their glass-transition temperatures reported previously. The present MD simulation shows that a lower-limit temperature of the diffusion for the sorbed water and the glass-transition temperatures of the polymers also have a positive correlation, indicating that the recrystallization is controlled by diffusion mechanism rather than reorientation mechanism. Detailed molecular processes of not only recrystallization during rewarming but also crystallization during cooling and hydrogen-bonding states of water in the polymers are systematically analyzed and discussed.

  2. Dispersion of Response Times Reveals Cognitive Dynamics

    PubMed Central

    Holden, John G.; Van Orden, Guy C.; Turvey, Michael T.

    2013-01-01

    Trial to trial variation in word pronunciation times exhibits 1/f scaling. One explanation is that human performances are consequent on multiplicative interactions among interdependent processes – interaction dominant dynamics. This article describes simulated distributions of pronunciation times in a further test for multiplicative interactions and interdependence. Individual participant distributions of ≈1100 word pronunciation times are successfully mimicked for each participant in combinations of lognormal and power law behavior. Successful hazard function simulations generalize these results to establish interaction dominant dynamics, in contrast with component dominant dynamics, as a likely mechanism for cognitive activity. PMID:19348544

  3. Eye Movements Reveal Dynamics of Task Control

    ERIC Educational Resources Information Center

    Mayr, Ulrich; Kuhns, David; Rieter, Miranda

    2013-01-01

    With the goal to determine the cognitive architecture that underlies flexible changes of control settings, we assessed within-trial and across-trial dynamics of attentional selection by tracking of eye movements in the context of a cued task-switching paradigm. Within-trial dynamics revealed a switch-induced, discrete delay in onset of…

  4. Eye Movements Reveal Dynamics of Task Control

    ERIC Educational Resources Information Center

    Mayr, Ulrich; Kuhns, David; Rieter, Miranda

    2013-01-01

    With the goal to determine the cognitive architecture that underlies flexible changes of control settings, we assessed within-trial and across-trial dynamics of attentional selection by tracking of eye movements in the context of a cued task-switching paradigm. Within-trial dynamics revealed a switch-induced, discrete delay in onset of…

  5. Molecular dynamics simulations reveal the allosteric effect of F1174C resistance mutation to ceritinib in ALK-associated lung cancer.

    PubMed

    Ni, Zhong; Wang, Xiting; Zhang, Tianchen; Jin, Rong Zhong

    2016-12-01

    Anaplastic lymphoma kinase (ALK) has become as an important target for the treatment of various human cancers, especially non-small-cell lung cancer. A mutation, F1174C, suited in the C-terminal helix αC of ALK and distal from the small-molecule inhibitor ceritinib bound to the ATP-binding site, causes the emergence of drug resistance to ceritinib. However, the detailed mechanism for the allosteric effect of F1174C resistance mutation to ceritinib remains unclear. Here, molecular dynamics (MD) simulations and binding free energy calculations [Molecular Mechanics/Generalized Born Surface Area (MM/GBSA)] were carried out to explore the advent of drug resistance mutation in ALK. MD simulations observed that the exquisite aromatic-aromatic network formed by residues F1098, F1174, F1245, and F1271 in the wild-type ALK-ceritinib complex was disrupted by the F1174C mutation. The resulting mutation allosterically affected the conformational dynamic of P-loop and caused the upward movement of the P-loop from the ATP-binding site, thereby weakening the interaction between ceritinib and the P-loop. The subsequent MM/GBSA binding free energy calculations and decomposition analysis of binding free energy validated this prediction. This study provides mechanistic insight into the allosteric effect of F1174C resistance mutation to ceritinib in ALK and is expected to contribute to design the next-generation of ALK inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Molecular Dynamics Simulations of the Bacterial UraA H+-Uracil Symporter in Lipid Bilayers Reveal a Closed State and a Selective Interaction with Cardiolipin

    PubMed Central

    Kalli, Antreas C.; Sansom, Mark S. P.; Reithmeier, Reinhart A. F.

    2015-01-01

    The Escherichia coli UraA H+-uracil symporter is a member of the nucleobase/ascorbate transporter (NAT) family of proteins, and is responsible for the proton-driven uptake of uracil. Multiscale molecular dynamics simulations of the UraA symporter in phospholipid bilayers consisting of: 1) 1-palmitoyl 2-oleoyl-phosphatidylcholine (POPC); 2) 1-palmitoyl 2-oleoyl-phosphatidylethanolamine (POPE); and 3) a mixture of 75% POPE, 20% 1-palmitoyl 2-oleoyl-phosphatidylglycerol (POPG); and 5% 1-palmitoyl 2-oleoyl-diphosphatidylglycerol/cardiolipin (CL) to mimic the lipid composition of the bacterial inner membrane, were performed using the MARTINI coarse-grained force field to self-assemble lipids around the crystal structure of this membrane transport protein, followed by atomistic simulations. The overall fold of the protein in lipid bilayers remained similar to the crystal structure in detergent on the timescale of our simulations. Simulations were performed in the absence of uracil, and resulted in a closed state of the transporter, due to relative movement of the gate and core domains. Anionic lipids, including POPG and especially CL, were found to associate with UraA, involving interactions between specific basic residues in loop regions and phosphate oxygens of the CL head group. In particular, three CL binding sites were identified on UraA: two in the inner leaflet and a single site in the outer leaflet. Mutation of basic residues in the binding sites resulted in the loss of CL binding in the simulations. CL may play a role as a “proton trap” that channels protons to and from this transporter within CL-enriched areas of the inner bacterial membrane. PMID:25729859

  7. ``Half-hydration'' at the air/water interface revealed by heterodyne-detected electronic sum frequency generation spectroscopy, polarization second harmonic generation, and molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Watanabe, Hidekazu; Yamaguchi, Shoichi; Sen, Sobhan; Morita, Akihiro; Tahara, Tahei

    2010-04-01

    A solute-solvent interaction at the air/water interface was investigated both experimentally and theoretically, by studying a prototypical surface-active polarity indicator molecule, coumarin 110 (C110), adsorbed at the air/water interface with heterodyne-detected electronic sum frequency generation (HD-ESFG) spectroscopy, polarization second harmonic generation (SHG), and a molecular dynamics (MD) simulation. The second-order nonlinear optical susceptibility (χ(2)) tensor elements of C110 at the air/water interface were determined experimentally by HD-ESFG and polarization SHG, and information on "intermediate" polarity sensed by C110 at the interface was obtained by HD-ESFG. An MD simulation and a time-dependent density functional theory calculation were used to theoretically evaluate the χ(2) tensor elements, which were in good agreement with the experimental results of HD-ESFG and polarization SHG. The microscopic "half-hydration" structure around C110 at the water surface was visualized on the basis of the MD simulation data, with which we can intuitively understand the microscopic origin of the surface activity of C110 and the intermediate polarity sensed by C110 at the air/water interface.

  8. The kinetics of molecular oxygen migration in the isolated α chains of human hemoglobin as revealed by molecular dynamics simulations and laser kinetic spectroscopy.

    PubMed

    Lepeshkevich, Sergei V; Biziuk, Sergey A; Lemeza, Alexander M; Dzhagarov, Boris M

    2011-10-01

    Bimolecular and germinate molecular oxygen (O(2)) rebinding to isolated α chains of human adult hemoglobin in solutions is analyzed. Multiple extended molecular dynamics (MD) simulations of the O(2) migration within the protein after dissociation are described. Computational modeling is exploited to identify hydrophobic pockets within the αchains and internal O(2) migration pathways associated with the experimentally observed ligand rebinding kinetics. To initiate dissociation, trajectories of the liganded protein are interrupted, the iron-dioxygen bond is broken, and the parameters of the iron-nitrogen bonds are simultaneously altered to produce a deoxyheme conformation. MD simulations provide 140 essentially independent trajectories (up to 25-ns long) of the O(2) migration in the protein. The time dependence of cavities occupancy, obtained by the MD simulations, and the kinetics of O(2) rebinding, measured by flash-photolysis techniques, allow us to obtain the kinetics of the entire O(2) migration process within the nanosecond time range and construct an explicit kinetic model of the O(2) migration and rebinding process. The amino acids that have the most pronounced effect on the ligand migration within the α chain matrix are predicted. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. A dissociative quantum mechanical/molecular mechanical molecular dynamics simulation and infrared experiments reveal characteristics of the strongly hydrolytic arsenic(III).

    PubMed

    Canaval, Lorenz R; Lutz, Oliver M D; Weiss, Alexander K H; Huck, Christian W; Hofer, Thomas S

    2014-11-17

    This work presents a hybrid ab initio quantum mechanical/molecular mechanical simulation at the RI-MP2 level of theory investigating the hydrolysis process of arsenic(III), ultimately leading to arsenous acid (H3AsO3). A newly implemented dissociative water model has been applied to treat the interactions in the classical region, which is capable of describing non-neutral water species such as hydroxide and oxonium ions. Three stages of hydrolysis have been observed during the simulation and besides profound dynamical considerations, detailed insights into structural changes and atomic partial charge shifts are presented. In particular, the geometrical properties of H-bonds involved in each of the three proton transfer events and subsequent proton hopping reactions are discussed. A Laguerre tessellation analysis has been employed to estimate the molecular volume of H3AsO3. Estimations of pKa values of the arsenic(III)-aquo-complexes have been obtained at the G4 and CBS-Q//B3 levels of theory using a thermodynamic cycle, whereas rate constants for the final hydrolysis step have been determined via reaction path optimization and transition state theory. Newly recorded Fourier transform infrared (FT-IR) spectroscopy measurements have been compared to power spectra obtained from the simulation data, confirming its quality. The simulation findings, as well as results from computational spectroscopic calculations utilizing the PT2-VSCF methodology, proved valuable for the interpretation of the experimental FT-IR data, elucidating the particularities of the strongly observed IR Raman noncoincidence effect.

  10. Remote manipulator dynamic simulation

    NASA Technical Reports Server (NTRS)

    Wild, E. C.; Donges, P. K.; Garand, W. A.

    1972-01-01

    A simulator to generate the real time visual scenes required to perform man in the loop investigations of remote manipulator application and design concepts for the space shuttle is described. The simulated remote manipulator consists of a computed display system that uses a digital computer, the electronic scene generator, an operator's station, and associated interface hardware. A description of the capabilities of the implemented simulation is presented. The mathematical models and programs developed for the simulation are included.

  11. Functional conformations of the L11–ribosomal RNA complex revealed by correlative analysis of cryo-EM and molecular dynamics simulations

    PubMed Central

    Li, Wen; Sengupta, Jayati; Rath, Bimal K.; Frank, Joachim

    2006-01-01

    The interaction between the GTPase-associated center (GAC) and the aminoacyl-tRNA·EF-Tu·GTP ternary complex is of crucial importance in the dynamic process of decoding and tRNA accommodation. The GAC includes protein L11 and helices 43–44 of 23S rRNA (referred to as L11–rRNA complex). In this study, a method of fitting based on a systematic comparison between cryo-electron microscopy (cryo-EM) density maps and structures obtained by molecular dynamics simulations has been developed. This method has led to the finding of atomic models of the GAC that fit the EM maps with much improved cross-correlation coefficients compared with the fitting of the X-ray structure. Two types of conformations of the L11–rRNA complex, produced by the simulations, match the cryo-EM maps representing the states either bound or unbound to the aa-tRNA·EF-Tu·GTP ternary complex. In the bound state, the N-terminal domain of L11 is extended from its position in the crystal structure, and the base of nucleotide A1067 in the 23S ribosomal RNA is flipped out. This position of the base allows the RNA to reach the elbow region of the aminoacyl-tRNA when the latter is bound in the A/T site. In the unbound state, the N-terminal domain of L11 is rotated only slightly, and A1067 of the RNA is flipped back into the less-solvent-exposed position, as in the crystal structure. By matching our experimental cryo-EM maps with much improved cross-correlation coefficients compared to the crystal structure, these two conformations prove to be strong candidates of the two functional states. PMID:16682558

  12. Computational diagnosis of protein conformational diseases: short molecular dynamics simulations reveal a fast unfolding of r-LDL mutants that cause familial hypercholesterolemia.

    PubMed

    Cuesta-López, S; Falo, F; Sancho, J

    2007-01-01

    The molecular basis of conformational diseases frequently resides in mutant proteins constituting a subset of the vast mutational space. While the subtleties of protein structure point to molecular dynamics (MD) techniques as promising tools for an efficient exploration of such a space, the average size of proteins and the time scale of unfolding events make this goal difficult with present computational capabilities. We show here, nevertheless, that an efficient approach is already feasible for modular proteins. Familial hypercholesterolemia (FH) is a conformational disease linked to mutations in the gene encoding the low density lipoprotein receptor. A high percentage of these mutations has been found in the seven small modular binding repeats of the receptor. Taking advantage of its small size, we have performed an in depth MD study of the fifth binding repeat. Fast unfolding dynamics have been observed in the absence of a structural bound calcium ion, which agrees with its reported essential role in the stability of the module. In addition, several mutations detected in FH patients have been analyzed, starting from the native conformation. Our results indicate that in contrast with the wild type protein and an innocuous control mutant, disease-related mutants experience, in short simulation times (2-8 ns), gross departures from the native state that lead to unfolded conformations and, in some cases, to binding site desorganization deriving in calcium release. Computational diagnosis of mutations leading to conformational diseases seems thus feasible, at least for small or modular pathogenic proteins.

  13. Revealing Origin of Decrease in Potency of Darunavir and Amprenavir against HIV-2 relative to HIV-1 Protease by Molecular Dynamics Simulations

    NASA Astrophysics Data System (ADS)

    Chen, Jianzhong; Liang, Zhiqiang; Wang, Wei; Yi, Changhong; Zhang, Shaolong; Zhang, Qinggang

    2014-11-01

    Clinical inhibitors Darunavir (DRV) and Amprenavir (APV) are less effective on HIV-2 protease (PR2) than on HIV-1 protease (PR1). To identify molecular basis associated with the lower inhibition, molecular dynamics (MD) simulations and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations were performed to investigate the effectiveness of the PR1 inhibitors DRV and APV against PR1/PR2. The rank of predicted binding free energies agrees with the experimental determined one. Moreover, our results show that two inhibitors bind less strongly to PR2 than to PR1, again in agreement with the experimental findings. The decrease in binding free energies for PR2 relative to PR1 is found to arise from the reduction of the van der Waals interactions induced by the structural adjustment of the triple mutant V32I, I47V and V82I. This result is further supported by the difference between the van der Waals interactions of inhibitors with each residue in PR2 and in PR1. The results from the principle component analysis suggest that inhibitor binding tends to make the flaps of PR2 close and the one of PR1 open. We expect that this study can theoretically provide significant guidance and dynamics information for the design of potent dual inhibitors targeting PR1/PR2.

  14. Effect of initial ion positions on the interactions of monovalent and divalent ions with a DNA duplex as revealed with atomistic molecular dynamics simulations.

    PubMed

    Robbins, Timothy J; Wang, Yongmei

    2013-01-01

    Monovalent (Na(+)) and divalent (Mg(2+)) ion distributions around the Dickerson-Drew dodecamer were studied by atomistic molecular dynamics (MD) simulations with AMBER molecular modeling software. Different initial placements of ions were tried and the resulting effects on the ion distributions around DNA were investigated. For monovalent ions, results were found to be nearly independent of initial cation coordinates. However, Mg(2+) ions demonstrated a strong initial coordinate dependent behavior. While some divalent ions initially placed near the DNA formed essentially permanent direct coordination complexes with electronegative DNA atoms, Mg(2+) ions initially placed further away from the duplex formed a full, nonexchanging, octahedral first solvation shell. These fully solvated cations were still capable of binding with DNA with events lasting up to 20 ns, and in comparison were bound much longer than Na(+) ions. Force field parameters were also investigated with modest and little differences arising from ion (ions94 and ions08) and nucleic acid description (ff99, ff99bsc0, and ff10), respectively. Based on known Mg(2+) ion solvation structure, we conclude that in most cases Mg(2+) ions retain their first solvation shell, making only solvent-mediated contacts with DNA duplex. The proper way to simulate Mg(2+) ions around DNA duplex, therefore, should begin with ions placed in the bulk water.

  15. Dispersion of Response Times Reveals Cognitive Dynamics

    ERIC Educational Resources Information Center

    Holden, John G.; Van Orden, Guy C.; Turvey, Michael T.

    2009-01-01

    Trial-to-trial variation in word-pronunciation times exhibits 1/f scaling. One explanation is that human performances are consequent on multiplicative interactions among interdependent processes-interaction dominant dynamics. This article describes simulated distributions of pronunciation times in a further test for multiplicative interactions and…

  16. Mechanism of Inhibition of Hsp90 Dimerization by Gyrase B Inhibitor Coumermycin A1 (C-A1) Revealed by Molecular Dynamics Simulations and Thermodynamic Calculations.

    PubMed

    Cele, Favourite N; Kumalo, Hezekiel; Soliman, Mahmoud E S

    2016-09-01

    Heat shock protein (Hsp) 90 an emerging and attracting target in the anti-HIV drug discovery process due to the key role it plays in the pathogenicity of HIV-1 virus. In this research study, long-range all-atom molecular dynamics simulations were engaged for the bound and the unbound proteins to enhance the understanding of the molecular mechanisms of the Hsp90 dimerization and inhibition. Results evidently showed that coumermycin A1 (C-A1), a recently discovered Hsp90 inhibitor, binds at the dimer's active site of the Hsp90 protein and leads to a substantial parting between dimeric opposed residues, which include Arg591.B, Lys594.A, Ser663.A, Thr653.B, Ala665.A, Thr649.B, Leu646.B and Asn669.A. Significant differences in magnitudes were observed in radius of gyration, root-mean-square deviation and root-mean-square fluctuation, which confirms a reasonably more flexible state in the apo conformation associated with it dimerization. In contrast, the bound conformer of Hsp90 showed less flexibility. This visibly highpoints the inhibition process resulting from the binding of the ligand. These findings were further validated by principal component analysis. We believe that the detailed dynamic analyses of Hsp90 presented in this study, would give an imperative insight and better understanding to the function and mechanisms of inhibition. Furthermore, information obtained from the binding mode of the inhibitor would be of great assistance in the design of more potent inhibitors against the HIV target Hsp90.

  17. Membrane negative curvature induced by a hybrid peptide from pediocin PA-1 and plantaricin 149 as revealed by atomistic molecular dynamics simulations.

    PubMed

    da Hora, G C A; Archilha, N L; Lopes, J L S; Müller, D M; Coutinho, K; Itri, R; Soares, T A

    2016-11-04

    Antimicrobial peptides (AMPs) are cationic peptides that kill bacteria with a broad spectrum of action, low toxicity to mammalian cells and exceptionally low rates of bacterial resistance. These features have led to considerable efforts in developing AMPs as an alternative antibacterial therapy. In vitro studies have shown that AMPs interfere with membrane bilayer integrity via several possible mechanisms, which are not entirely understood. We have performed the synthesis, membrane lysis measurements, and biophysical characterization of a novel hybrid peptide. These measurements show that PA-Pln149 does not form nanopores, but instead promotes membrane rupture. It causes fast rupture of the bacterial model membrane (POPG-rich) at concentrations 100-fold lower than that required for the disruption of mammalian model membranes (POPC-rich). Atomistic molecular dynamics (MD) simulations were performed for single and multiple copies of PA-Pln149 in the presence of mixed and pure POPC/POPG bilayers to investigate the concentration-dependent membrane disruption by the hybrid peptide. These simulations reproduced the experimental trend and provided a potential mechanism of action for PA-Pln149. It shows that the PA-Pln149 does not form nanopores, but instead promotes membrane destabilization through peptide aggregation and induction of membrane negative curvature with the collapse of the lamellar arrangement. The sequence of events depicted for PA-Pln149 may offer insights into the mechanism of action of AMPs previously shown to induce negative deformation of membrane curvature and often associated with peptide translocation via non-bilayer intermediate structures.

  18. Dynamic Power Grid Simulation

    SciTech Connect

    Top, Philip; Woodward, Carol; Smith, Steve; Banks, Lawrence; Kelley, Brian

    2015-09-14

    GridDyn is a part of power grid simulation toolkit. The code is designed using modern object oriented C++ methods utilizing C++11 and recent Boost libraries to ensure compatibility with multiple operating systems and environments.

  19. Molecular Mechanism and Energy Basis of Conformational Diversity of Antibody SPE7 Revealed by Molecular Dynamics Simulation and Principal Component Analysis

    PubMed Central

    Chen, Jianzhong; Wang, Jinan; Zhu, Weiliang

    2016-01-01

    More and more researchers are interested in and focused on how a limited repertoire of antibodies can bind and correspondingly protect against an almost limitless diversity of invading antigens. In this work, a series of 200-ns molecular dynamics (MD) simulations followed by principal component (PC) analysis and free energy calculations were performed to probe potential mechanism of conformational diversity of antibody SPE7. The results show that the motion direction of loops H3 and L3 is different relative to each other, implying that a big structural difference exists between these two loops. The calculated energy landscapes suggest that the changes in the backbone angles ψ and φ of H-Y101 and H-Y105 provide significant contributions to the conformational diversity of SPE7. The dihedral angle analyses based on MD trajectories show that the side-chain conformational changes of several key residues H-W33, H-Y105, L-Y34 and L-W93 around binding site of SPE7 play a key role in the conformational diversity of SPE7, which gives a reasonable explanation for potential mechanism of cross-reactivity of single antibody toward multiple antigens. PMID:27830740

  20. Molecular Mechanism and Energy Basis of Conformational Diversity of Antibody SPE7 Revealed by Molecular Dynamics Simulation and Principal Component Analysis

    NASA Astrophysics Data System (ADS)

    Chen, Jianzhong; Wang, Jinan; Zhu, Weiliang

    2016-11-01

    More and more researchers are interested in and focused on how a limited repertoire of antibodies can bind and correspondingly protect against an almost limitless diversity of invading antigens. In this work, a series of 200-ns molecular dynamics (MD) simulations followed by principal component (PC) analysis and free energy calculations were performed to probe potential mechanism of conformational diversity of antibody SPE7. The results show that the motion direction of loops H3 and L3 is different relative to each other, implying that a big structural difference exists between these two loops. The calculated energy landscapes suggest that the changes in the backbone angles ψ and φ of H-Y101 and H-Y105 provide significant contributions to the conformational diversity of SPE7. The dihedral angle analyses based on MD trajectories show that the side-chain conformational changes of several key residues H-W33, H-Y105, L-Y34 and L-W93 around binding site of SPE7 play a key role in the conformational diversity of SPE7, which gives a reasonable explanation for potential mechanism of cross-reactivity of single antibody toward multiple antigens.

  1. Structure and orientation of antibiotic peptide alamethicin in phospholipid bilayers as revealed by chemical shift oscillation analysis of solid state nuclear magnetic resonance and molecular dynamics simulation.

    PubMed

    Nagao, Takashi; Mishima, Daisuke; Javkhlantugs, Namsrai; Wang, Jun; Ishioka, Daisuke; Yokota, Kiyonobu; Norisada, Kazushi; Kawamura, Izuru; Ueda, Kazuyoshi; Naito, Akira

    2015-11-01

    The structure, topology and orientation of membrane-bound antibiotic alamethicin were studied using solid state nuclear magnetic resonance (NMR) spectroscopy. (13)C chemical shift interaction was observed in [1-(13)C]-labeled alamethicin. The isotropic chemical shift values indicated that alamethicin forms a helical structure in the entire region. The chemical shift anisotropy of the carbonyl carbon of isotopically labeled alamethicin was also analyzed with the assumption that alamethicin molecules rotate rapidly about the bilayer normal of the phospholipid bilayers. It is considered that the adjacent peptide planes form an angle of 100° or 120° when it forms α-helix or 310-helix, respectively. These properties lead to an oscillation of the chemical shift anisotropy with respect to the phase angle of the peptide plane. Anisotropic data were acquired for the 4 and 7 sites of the N- and C-termini, respectively. The results indicated that the helical axes for the N- and C-termini were tilted 17° and 32° to the bilayer normal, respectively. The chemical shift oscillation curves indicate that the N- and C-termini form the α-helix and 310-helix, respectively. The C-terminal 310-helix of alamethicin in the bilayer was experimentally observed and the unique bending structure of alamethicin was further confirmed by measuring the internuclear distances of [1-(13)C] and [(15)N] doubly-labeled alamethicin. Molecular dynamics simulation of alamethicin embedded into dimyristoyl phophatidylcholine (DMPC) bilayers indicates that the helical axes for α-helical N- and 310-helical C-termini are tilted 12° and 32° to the bilayer normal, respectively, which is in good agreement with the solid state NMR results. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Floating orbital molecular dynamics simulations.

    PubMed

    Perlt, Eva; Brüssel, Marc; Kirchner, Barbara

    2014-04-21

    We introduce an alternative ab initio molecular dynamics simulation as a unification of Hartree-Fock molecular dynamics and the floating orbital approach. The general scheme of the floating orbital molecular dynamics method is presented. Moreover, a simple but sophisticated guess for the orbital centers is provided to reduce the number of electronic structure optimization steps at each molecular dynamics step. The conservation of total energy and angular momentum is investigated in order to validate the floating orbital molecular dynamics approach with and without application of the initial guess. Finally, a water monomer and a water dimer are simulated, and the influence of the orbital floating on certain properties like the dipole moment is investigated.

  3. Modeling Molecular Dynamics from Simulations

    SciTech Connect

    Hinrichs, Nina Singhal

    2009-01-28

    Many important processes in biology occur at the molecular scale. A detailed understanding of these processes can lead to significant advances in the medical and life sciences. For example, many diseases are caused by protein aggregation or misfolding. One approach to studying these systems is to use physically-based computational simulations to model the interactions and movement of the molecules. While molecular simulations are computationally expensive, it is now possible to simulate many independent molecular dynamics trajectories in a parallel fashion by using super- or distributed- computing methods such as Folding@Home or Blue Gene. The analysis of these large, high-dimensional data sets presents new computational challenges. In this seminar, I will discuss a novel approach to analyzing large ensembles of molecular dynamics trajectories to generate a compact model of the dynamics. This model groups conformations into discrete states and describes the dynamics as Markovian, or history-independent, transitions between the states. I will discuss why the Markovian state model (MSM) is suitable for macromolecular dynamics, and how it can be used to answer many interesting and relevant questions about the molecular system. I will also discuss many of the computational and statistical challenges in building such a model, such as how to appropriately cluster conformations, determine the statistical reliability, and efficiently design new simulations.

  4. Molecular dynamics simulations of nanostructures

    NASA Astrophysics Data System (ADS)

    Yuan, Zaoshi

    This dissertation is focused on multimillion-atom molecular dynamics (MD) simulations of nanoscale materials. In the past decade, nanoscale materials have made significant commercial impacts, which will potentially lead to the next industrial revolution. The interest lies in the novel and promising features nanoscale materials exhibit due to their confined sizes. However, not all novel behaviors are understood or controllable. Many uncontrollable parameters, e.g. defects and dangling bonds, are known to hinder the performance of nanodevices. Solutions to these problems rely on our understanding of fundamental elements in nanoscience: isolated individual nanostructures and their assemblies. In this dissertation, we will address atomistic foundations of several problems of technological importance in nanoscience. Specifically, three basic problems are discussed: (1) embrittlement of nanocrystalline metal; (2) novel thermo-mechanical behaviors of nanowires (NWs); and (3) planar defect generation in NWs. With a scalable algorithm implemented on massively parallel computing platforms and various data mining methods, MD simulations can provide valuable insights into these problems. An essential role of sulfur segregation-induced amorphization of crystalline nickel was recently discovered experimentally, but the atomistic mechanism of the amorphization remains unexplained. Our MD simulations reveal that the large steric size of sulfur impurity causes strong sulfur-sulfur interaction mediated by lattice distortion, which leads to amorphization near the percolation threshold at the sulfur-sulfur network in nickel crystal. The generality of the mechanism due to the percolation of an impurity network is further confirmed by a model binary system. In our study of novel behaviors of semiconductor NWs, MD simulations construct a rich size-temperature `phase diagram' for the mechanical response of a zinc-oxide NW under tension. For smaller diameters and higher temperatures, novel

  5. Structural basis for the temperature-induced transition of D-amino acid oxidase from pig kidney revealed by molecular dynamic simulation and photo-induced electron transfer.

    PubMed

    Nueangaudom, Arthit; Lugsanangarm, Kiattisak; Pianwanit, Somsak; Kokpol, Sirirat; Nunthaboot, Nadtanet; Tanaka, Fumio

    2012-02-28

    The structural basis for the temperature-induced transition in the D-amino acid oxidase (DAAO) monomer from pig kidney was studied by means of molecular dynamic simulations (MDS). The center to center (Rc) distances between the isoalloxazine ring (Iso) and all aromatic amino acids (Trp and Tyr) were calculated at 10 °C and 30 °C. Rc was shortest in Tyr224 (0.82 and 0.88 nm at 10 and 30 °C, respectively), and then in Tyr228. Hydrogen bonding (H-bond) formed between the Iso N1 and Gly315 N (peptide), between the Iso N3H and Leu51 O (peptide) and between the Iso N5 and Ala49 N (peptide) at 10 °C, whilst no H-bond was formed at the Iso N1 and Iso N3H at 30 °C. The H-bond of Iso O4 with Leu51 N (peptide) at 10 °C switched to that with Ala49 N (peptide) at 30 °C. The reported fluorescence lifetimes (228 and 182 ps at 10 and 30 °C, respectively) of DAAO were analyzed with Kakitani and Mataga (KM) ET theory. The calculated fluorescence lifetimes displayed an excellent agreement with the observed lifetimes. The ET rate was fastest from Tyr224 to the excited Iso (Iso*) at 10 °C and from Tyr314 at 30 °C, despite the fact that the Rc was shortest between Iso and Tyr224 at both temperatures. This was explained by the electrostatic energy in the protein. The differences in the observed fluorescence lifetimes at 10 and 30 °C were ascribed to the differences in electron affinity of the Iso* at both temperatures, in which the free energies of the electron affinity of Iso* at 10 and 30 °C were -8.69 eV and -8.51 eV respectively. The other physical quantities related to ET did not differ appreciably at both temperatures. The electron affinities at both temperatures were calculated with a semi-empirical molecular orbital method (MO) of PM6. Mean calculated electron affinities over 100 snapshots with 0.1 ps intervals were -7.69 eV at 10 °C and -7.59 eV at 30 °C. The difference in the calculated electron affinities, -0.11 eV, was close to the observed difference in the

  6. Hydrophobic Interactions Are a Key to MDM2 Inhibition by Polyphenols as Revealed by Molecular Dynamics Simulations and MM/PBSA Free Energy Calculations

    PubMed Central

    Verma, Sharad; Grover, Sonam; Tyagi, Chetna; Goyal, Sukriti; Jamal, Salma; Singh, Aditi; Grover, Abhinav

    2016-01-01

    p53, a tumor suppressor protein, has been proven to regulate the cell cycle, apoptosis, and DNA repair to prevent malignant transformation. MDM2 regulates activity of p53 and inhibits its binding to DNA. In the present study, we elucidated the MDM2 inhibition potential of polyphenols (Apigenin, Fisetin, Galangin and Luteolin) by MD simulation and MM/PBSA free energy calculations. All polyphenols bind to hydrophobic groove of MDM2 and the binding was found to be stable throughout MD simulation. Luteolin showed the highest negative binding free energy value of -173.80 kJ/mol followed by Fisetin with value of -172.25 kJ/mol. It was found by free energy calculations, that hydrophobic interactions (vdW energy) have major contribution in binding free energy. PMID:26863418

  7. Dynamical simulation of gravothermal catastrophe.

    PubMed

    Klinko, Peter; Miller, Bruce N

    2004-01-16

    We investigate the dynamical evolution of gravothermal catastrophe in a model of a spherical cluster where, besides the energy and angular momentum, an additional integral of motion is also taken into account. Using dynamical simulation, we study a system of concentric, rotating, spherical shells employing a precise, event-driven, algorithm that permits the controlled exchange of internal angular momentum. Initially the system starts to relax to a locally stable state that is in good agreement with mean field predictions. This is followed by core collapse with the development of a core-halo structure and gravothermal oscillation.

  8. Accelerated dynamics simulations of nanotubes.

    SciTech Connect

    Uberuaga, B. P.; Stuart, S. J.; Voter, A. F.

    2002-01-01

    We report on the application of accelerated dynamics techniques to the study of carbon nanotubes. We have used the parallel replica method and temperature accelerated dynamics simulations are currently in progress. In the parallel replica study, we have stretched tubes at a rate significantly lower than that used in previous studies. In these preliminary results, we find that there are qualitative differences in the rupture of the nanotubes at different temperatures. We plan on extending this investigation to include nanotubes of various chiralities. We also plan on exploring unique geometries of nanotubes.

  9. Molecular dynamics simulation of pyridine

    NASA Astrophysics Data System (ADS)

    Trumpakaj, Zygmunt; Linde, Bogumił

    2015-04-01

    Molecular Dynamics (MD) simulations are used for the investigation of molecular motions in pyridine in the temperature range 20-480 K under normal pressure. The results obtained are analyzed within the frame of the Mori Zwanzig memory function formalism. An analytical approximation of the first memory function K(t) is applied to predict some dependences on temperature. Experimental results of the Rayleigh scattering of depolarized light from liquid pyridine are used as the main base for the comparison.

  10. Neutron Imaging Reveals Internal Plant Hydraulic Dynamics

    SciTech Connect

    Warren, Jeffrey; Bilheux, Hassina Z; Kang, Misun; Voisin, Sophie; Cheng, Chu-Lin; Horita, Jusuke; Perfect, Edmund

    2013-01-01

    Many terrestrial ecosystem processes are constrained by water availability and transport within the soil. Knowledge of plant water fluxes is thus critical for assessing mechanistic processes linked to biogeochemical cycles, yet resolution of root structure and xylem water transport dynamics has been a particularly daunting task for the ecologist. Through neutron imaging, we demonstrate the ability to non-invasively monitor individual root functionality and water fluxes within Zea mays L. (maize) and Panicum virgatum L. (switchgrass) seedlings growing in a sandy medium. Root structure and growth were readily imaged by neutron radiography and neutron computed tomography. Seedlings were irrigated with water or deuterium oxide and imaged through time as a growth lamp was cycled on to alter leaf demand for water. Sub-millimeter scale resolution reveals timing and magnitudes of root water uptake, redistribution within the roots, and root-shoot hydraulic linkages, relationships not well characterized by other techniques.

  11. Dynamic simulations of tissue welding

    SciTech Connect

    Maitland, D.J.; Eder, D.C.; London, R.A.; Glinsky, M.E.

    1996-02-01

    The exposure of human skin to near-infrared radiation is numerically simulated using coupled laser, thermal transport and mass transport numerical models. The computer model LATIS is applied in both one-dimensional and two-dimensional geometries. Zones within the skin model are comprised of a topical solder, epidermis, dermis, and fatty tissue. Each skin zone is assigned initial optical, thermal and water density properties consistent with values listed in the literature. The optical properties of each zone (i.e. scattering, absorption and anisotropy coefficients) are modeled as a kinetic function of the temperature. Finally, the water content in each zone is computed from water diffusion where water losses are accounted for by evaporative losses at the air-solder interface. The simulation results show that the inclusion of water transport and evaporative losses in the model are necessary to match experimental observations. Dynamic temperature and damage distributions are presented for the skin simulations.

  12. Molecular dynamics simulation of benzene

    NASA Astrophysics Data System (ADS)

    Trumpakaj, Zygmunt; Linde, Bogumił B. J.

    2016-03-01

    Intermolecular potentials and a few models of intermolecular interaction in liquid benzene are tested by Molecular Dynamics (MD) simulations. The repulsive part of the Lennard-Jones 12-6 (LJ 12-6) potential is too hard, which yields incorrect results. The exp-6 potential with a too hard repulsive term is also often used. Therefore, we took an expa-6 potential with a small Gaussian correction plus electrostatic interactions. This allows to modify the curvature of the potential. The MD simulations are carried out in the temperature range 280-352 K under normal pressure and at experimental density. The Rayleigh scattering of depolarized light is used for comparison. The results of MD simulations are comparable with the experimental values.

  13. Molecular dynamics simulations reveal the balance of forces governing the formation of a guanine tetrad—a common structural unit of G-quadruplex DNA

    PubMed Central

    Kogut, Mateusz; Kleist, Cyprian; Czub, Jacek

    2016-01-01

    G-quadruplexes (G4) are nucleic acid conformations of guanine-rich sequences, in which guanines are arranged in the square-planar G-tetrads, stacked on one another. G4 motifs form in vivo and are implicated in regulation of such processes as gene expression and chromosome maintenance. The structure and stability of various G4 topologies were determined experimentally; however, the driving forces for their formation are not fully understood at the molecular level. Here, we used all-atom molecular dynamics to probe the microscopic origin of the G4 motif stability. By computing the free energy profiles governing the dissociation of the 3′-terminal G-tetrad in the telomeric parallel-stranded G4, we examined the thermodynamic and kinetic stability of a single G-tetrad, as a common structural unit of G4 DNA. Our results indicate that the energetics of guanine association alone does not explain the overall stability of the G-tetrad and that interactions involving sugar–phosphate backbone, in particular, the constrained minimization of the phosphate–phosphate repulsion energy, are crucial in providing the observed enthalpic stabilization. This enthalpic gain is largely compensated by the unfavorable entropy change due to guanine association and optimization of the backbone topology. PMID:26980278

  14. Structural adaptation of cold-active RTX lipase from Pseudomonas sp. strain AMS8 revealed via homology and molecular dynamics simulation approaches.

    PubMed

    Mohamad Ali, Mohd Shukuri; Mohd Fuzi, Siti Farhanie; Ganasen, Menega; Abdul Rahman, Raja Noor Zaliha Raja; Basri, Mahiran; Salleh, Abu Bakar

    2013-01-01

    The psychrophilic enzyme is an interesting subject to study due to its special ability to adapt to extreme temperatures, unlike typical enzymes. Utilizing computer-aided software, the predicted structure and function of the enzyme lipase AMS8 (LipAMS8) (isolated from the psychrophilic Pseudomonas sp., obtained from the Antarctic soil) are studied. The enzyme shows significant sequence similarities with lipases from Pseudomonas sp. MIS38 and Serratia marcescens. These similarities aid in the prediction of the 3D molecular structure of the enzyme. In this study, 12 ns MD simulation is performed at different temperatures for structural flexibility and stability analysis. The results show that the enzyme is most stable at 0°C and 5°C. In terms of stability and flexibility, the catalytic domain (N-terminus) maintained its stability more than the noncatalytic domain (C-terminus), but the non-catalytic domain showed higher flexibility than the catalytic domain. The analysis of the structure and function of LipAMS8 provides new insights into the structural adaptation of this protein at low temperatures. The information obtained could be a useful tool for low temperature industrial applications and molecular engineering purposes, in the near future.

  15. Structural Adaptation of Cold-Active RTX Lipase from Pseudomonas sp. Strain AMS8 Revealed via Homology and Molecular Dynamics Simulation Approaches

    PubMed Central

    Mohamad Ali, Mohd. Shukuri; Mohd Fuzi, Siti Farhanie; Ganasen, Menega; Abdul Rahman, Raja Noor Zaliha Raja; Basri, Mahiran; Salleh, Abu Bakar

    2013-01-01

    The psychrophilic enzyme is an interesting subject to study due to its special ability to adapt to extreme temperatures, unlike typical enzymes. Utilizing computer-aided software, the predicted structure and function of the enzyme lipase AMS8 (LipAMS8) (isolated from the psychrophilic Pseudomonas sp., obtained from the Antarctic soil) are studied. The enzyme shows significant sequence similarities with lipases from Pseudomonas sp. MIS38 and Serratia marcescens. These similarities aid in the prediction of the 3D molecular structure of the enzyme. In this study, 12 ns MD simulation is performed at different temperatures for structural flexibility and stability analysis. The results show that the enzyme is most stable at 0°C and 5°C. In terms of stability and flexibility, the catalytic domain (N-terminus) maintained its stability more than the noncatalytic domain (C-terminus), but the non-catalytic domain showed higher flexibility than the catalytic domain. The analysis of the structure and function of LipAMS8 provides new insights into the structural adaptation of this protein at low temperatures. The information obtained could be a useful tool for low temperature industrial applications and molecular engineering purposes, in the near future. PMID:23738333

  16. Dynamic Multiscale Simulation of Polyelectrolyte Nanoassemblies

    DTIC Science & Technology

    2008-08-21

    REPORT Dynamic Multiscale Simulation of Polyelectrolyte Nanoassemblies 14. ABSTRACT 16. SECURITY CLASSIFICATION OF: The goal of this project is to...Std. Z39.18 - 31-May-2008 Dynamic Multiscale Simulation of Polyelectrolyte Nanoassemblies Report Title ABSTRACT The goal of this project is to...Total Number: Sub Contractors (DD882) Inventions (DD882) Final Progress Report Dynamic Multiscale Simulation of Polyelectrolyte Nanoassemblies

  17. Rotational Brownian Dynamics simulations of clathrin cage formation

    SciTech Connect

    Ilie, Ioana M.; Briels, Wim J.; Otter, Wouter K. den

    2014-08-14

    The self-assembly of nearly rigid proteins into ordered aggregates is well suited for modeling by the patchy particle approach. Patchy particles are traditionally simulated using Monte Carlo methods, to study the phase diagram, while Brownian Dynamics simulations would reveal insights into the assembly dynamics. However, Brownian Dynamics of rotating anisotropic particles gives rise to a number of complications not encountered in translational Brownian Dynamics. We thoroughly test the Rotational Brownian Dynamics scheme proposed by Naess and Elsgaeter [Macromol. Theory Simul. 13, 419 (2004); Naess and Elsgaeter Macromol. Theory Simul. 14, 300 (2005)], confirming its validity. We then apply the algorithm to simulate a patchy particle model of clathrin, a three-legged protein involved in vesicle production from lipid membranes during endocytosis. Using this algorithm we recover time scales for cage assembly comparable to those from experiments. We also briefly discuss the undulatory dynamics of the polyhedral cage.

  18. Rotational Brownian dynamics simulations of clathrin cage formation.

    PubMed

    Ilie, Ioana M; den Otter, Wouter K; Briels, Wim J

    2014-08-14

    The self-assembly of nearly rigid proteins into ordered aggregates is well suited for modeling by the patchy particle approach. Patchy particles are traditionally simulated using Monte Carlo methods, to study the phase diagram, while Brownian Dynamics simulations would reveal insights into the assembly dynamics. However, Brownian Dynamics of rotating anisotropic particles gives rise to a number of complications not encountered in translational Brownian Dynamics. We thoroughly test the Rotational Brownian Dynamics scheme proposed by Naess and Elsgaeter [Macromol. Theory Simul. 13, 419 (2004); Naess and Elsgaeter Macromol. Theory Simul. 14, 300 (2005)], confirming its validity. We then apply the algorithm to simulate a patchy particle model of clathrin, a three-legged protein involved in vesicle production from lipid membranes during endocytosis. Using this algorithm we recover time scales for cage assembly comparable to those from experiments. We also briefly discuss the undulatory dynamics of the polyhedral cage.

  19. Microsecond Molecular Dynamics Simulations of Lipid Mixing

    PubMed Central

    2015-01-01

    Molecular dynamics (MD) simulations of membranes are often hindered by the slow lateral diffusion of lipids and the limited time scale of MD. In order to study the dynamics of mixing and characterize the lateral distribution of lipids in converged mixtures, we report microsecond-long all-atom MD simulations performed on the special-purpose machine Anton. Two types of mixed bilayers, POPE:POPG (3:1) and POPC:cholesterol (2:1), as well as a pure POPC bilayer, were each simulated for up to 2 μs. These simulations show that POPE:POPG and POPC:cholesterol are each fully miscible at the simulated conditions, with the final states of the mixed bilayers similar to a random mixture. By simulating three POPE:POPG bilayers at different NaCl concentrations (0, 0.15, and 1 M), we also examined the effect of salt concentration on lipid mixing. While an increase in NaCl concentration is shown to affect the area per lipid, tail order, and lipid lateral diffusion, the final states of mixing remain unaltered, which is explained by the largely uniform increase in Na+ ions around POPE and POPG. Direct measurement of water permeation reveals that the POPE:POPG bilayer with 1 M NaCl has reduced water permeability compared with those at zero or low salt concentration. Our calculations provide a benchmark to estimate the convergence time scale of all-atom MD simulations of lipid mixing. Additionally, equilibrated structures of POPE:POPG and POPC:cholesterol, which are frequently used to mimic bacterial and mammalian membranes, respectively, can be used as starting points of simulations involving these membranes. PMID:25237736

  20. Detecting Allosteric Networks Using Molecular Dynamics Simulation.

    PubMed

    Bowerman, S; Wereszczynski, J

    2016-01-01

    Allosteric networks allow enzymes to transmit information and regulate their catalytic activities over vast distances. In principle, molecular dynamics (MD) simulations can be used to reveal the mechanisms that underlie this phenomenon; in practice, it can be difficult to discern allosteric signals from MD trajectories. Here, we describe how MD simulations can be analyzed to reveal correlated motions and allosteric networks, and provide an example of their use on the coagulation enzyme thrombin. Methods are discussed for calculating residue-pair correlations from atomic fluctuations and mutual information, which can be combined with contact information to identify allosteric networks and to dynamically cluster a system into highly correlated communities. In the case of thrombin, these methods show that binding of the antagonist hirugen significantly alters the enzyme's correlation landscape through a series of pathways between Exosite I and the catalytic core. Results suggest that hirugen binding curtails dynamic diversity and enforces stricter venues of influence, thus reducing the accessibility of thrombin to other molecules. © 2016 Elsevier Inc. All rights reserved.

  1. Molecular dynamics simulation in virus research

    PubMed Central

    Ode, Hirotaka; Nakashima, Masaaki; Kitamura, Shingo; Sugiura, Wataru; Sato, Hironori

    2012-01-01

    Virus replication in the host proceeds by chains of interactions between viral and host proteins. The interactions are deeply influenced by host immune molecules and anti-viral compounds, as well as by mutations in viral proteins. To understand how these interactions proceed mechanically and how they are influenced by mutations, one needs to know the structures and dynamics of the proteins. Molecular dynamics (MD) simulation is a powerful computational method for delineating motions of proteins at an atomic-scale via theoretical and empirical principles in physical chemistry. Recent advances in the hardware and software for biomolecular simulation have rapidly improved the precision and performance of this technique. Consequently, MD simulation is quickly extending the range of applications in biology, helping to reveal unique features of protein structures that would be hard to obtain by experimental methods alone. In this review, we summarize the recent advances in MD simulations in the study of virus–host interactions and evolution, and present future perspectives on this technique. PMID:22833741

  2. Stochastic heart-rate model can reveal pathologic cardiac dynamics

    NASA Astrophysics Data System (ADS)

    Kuusela, Tom

    2004-03-01

    A simple one-dimensional Langevin-type stochastic difference equation can simulate the heart-rate fluctuations in a time scale from minutes to hours. The model consists of a deterministic nonlinear part and a stochastic part typical of Gaussian noise, and both parts can be directly determined from measured heart-rate data. Data from healthy subjects typically exhibit the deterministic part with two or more stable fixed points. Studies of 15 congestive heart-failure subjects reveal that the deterministic part of pathologic heart dynamics has no clear stable fixed points. Direct simulations of the stochastic model for normal and pathologic cases can produce statistical parameters similar to those of real subjects. Results directly indicate that pathologic situations simplify the heart-rate control system.

  3. Neutron Imaging Reveals Internal Plant Hydraulic Dynamics

    NASA Astrophysics Data System (ADS)

    Warren, J.; Bilheux, H.; Kang, M.; Voisin, S.; Cheng, C.; Horita, J.; Perfect, E.

    2011-12-01

    In situ quantification of soil-plant water fluxes have not been fully successful due to a lack of non-destructive techniques capable of revealing roots or water fluxes at relevant spatial scales. Neutron imaging is a unique non-invasive tool that can assess sub-millimeter scale material properties and transport in situ, and which has been successfully applied to characterize soil and plant water status. Here, we have applied neutron radiography and tomography to quantify water transport through individual maize roots in response to internal plant demand. Zea mays seedlings were grown for 10 days in Flint silica sand within 2.6 cm diameter Al chambers. Using a reactor-based neutron source at Oak Ridge National Laboratory (HFIR), water fluxes were tracked through the maize soil-root systems by collecting consecutive neutron radiographs over a 12 h period following irrigation with D2O. D has a much lower neutron attenuation than H, thus D2O displacement of existing H2O within the plant vascular system, or influx of D2O into previously dry tissue or soil is readily tracked by changes in image intensity through time. Plant water release and uptake was regulated by periodically cycling on a high-intensity grow light. From each maize replicate, selected regions of interest (ROI) were delineated around individual roots, root free soil, stem and leaf segments. Changes in ROI were tracked through time to reveal patterns of water flux. The hydration of root and stem tissue cycled in response to illumination; root water content often increased during darkness, then decreased with illumination as water was transported from the root into the stem. Relative root-shoot hydration through time illustrates the balance between demand, storage capacity and uptake, which varies depending on root characteristics and its localized soil environment. The dynamic transport of water between soil, individual roots, stems and leaves was readily visualized and quantified illustrating the value

  4. An Integrated Crustal Dynamics Simulator

    NASA Astrophysics Data System (ADS)

    Xing, H. L.; Mora, P.

    2007-12-01

    Numerical modelling offers an outstanding opportunity to gain an understanding of the crustal dynamics and complex crustal system behaviour. This presentation provides our long-term and ongoing effort on finite element based computational model and software development to simulate the interacting fault system for earthquake forecasting. A R-minimum strategy based finite-element computational model and software tool, PANDAS, for modelling 3-dimensional nonlinear frictional contact behaviour between multiple deformable bodies with the arbitrarily-shaped contact element strategy has been developed by the authors, which builds up a virtual laboratory to simulate interacting fault systems including crustal boundary conditions and various nonlinearities (e.g. from frictional contact, materials, geometry and thermal coupling). It has been successfully applied to large scale computing of the complex nonlinear phenomena in the non-continuum media involving the nonlinear frictional instability, multiple material properties and complex geometries on supercomputers, such as the South Australia (SA) interacting fault system, South California fault model and Sumatra subduction model. It has been also extended and to simulate the hot fractured rock (HFR) geothermal reservoir system in collaboration of Geodynamics Ltd which is constructing the first geothermal reservoir system in Australia and to model the tsunami generation induced by earthquakes. Both are supported by Australian Research Council.

  5. Simulations of Dynamic Relativistic Magnetospheres

    NASA Astrophysics Data System (ADS)

    Parfrey, Kyle Patrick

    Neutron stars and black holes are generally surrounded by magnetospheres of highly conducting plasma in which the magnetic flux density is so high that hydrodynamic forces are irrelevant. In this vanishing-inertia—or ultra-relativistic—limit, magnetohydrodynamics becomes force-free electrodynamics, a system of equations comprising only the magnetic and electric fields, and in which the plasma response is effected by a nonlinear current density term. In this dissertation I describe a new pseudospectral simulation code, designed for studying the dynamic magnetospheres of compact objects. A detailed description of the code and several numerical test problems are given. I first apply the code to the aligned rotator problem, in which a star with a dipole magnetic field is set rotating about its magnetic axis. The solution evolves to a steady state, which is nearly ideal and dissipationless everywhere except in a current sheet, or magnetic field discontinuity, at the equator, into which electromagnetic energy flows and is dissipated. Magnetars are believed to have twisted magnetospheres, due to internal magnetic evolution which deforms the crust, dragging the footpoints of external magnetic field lines. This twisting may be able to explain both magnetars' persistent hard X-ray emission and their energetic bursts and flares. Using the new code, I simulate the evolution of relativistic magnetospheres subjected to slow twisting through large angles. The field lines expand outward, forming a strong current layer; eventually the configuration loses equilibrium and a dynamic rearrangement occurs, involving large-scale rapid magnetic reconnection and dissipation of the free energy of the twisted magnetic field. When the star is rotating, the magnetospheric twisting leads to a large increase in the stellar spin-down rate, which may take place on the long twisting timescale or in brief explosive events, depending on where the twisting is applied and the history of the system

  6. Dynamical simulations of sedimenting spheres

    SciTech Connect

    Ladd, A.J.C. )

    1993-02-01

    The sedimentation of monodisperse suspensions of rigid spheres has been studied by dynamical simulation; computational techniques are described and numerical results are reported. It has been found that there is a slow relaxation of the suspension microstructure during sedimentation, so that compared with the initial equilibrium distribution, there is an increased number of pairs of particles near contact; this leads to a 5%--10% increase in the average sedimentation velocity. Individual particle velocities fluctuate about the mean fall speed; these fluctuations are large and persist for long times. The resulting hydrodynamically induced dispersion of the particles can be characterized by strongly anisotropic diffusion coefficients; however, the dispersion process is non-Fickian at high solids concentrations.

  7. Planetary Interior Structure Revealed by Spin Dynamics

    NASA Astrophysics Data System (ADS)

    Margot, J.; Peale, S. J.; Jurgens, R. F.; Slade, M. A.; Holin, I. V.

    2002-12-01

    The spin state of a planet depends on the distribution of mass within the interior, gradual and discrete changes in its moments of inertia, dissipation mechanisms at the surface and below, and external torques. Detailed measurements of the spin dynamics can therefore reveal much about planetary interior structure, interactions at the core-mantle and atmosphere-surface boundaries, and mass redistribution events. Studies of the spin precession, polar wobble, and length of day variations have been used to determine Earth's moments of inertia and rigidity and to study the effects of atmospheric angular momentum changes, post-glacial rebound, and large earthquakes. In planetary investigations the spin measurements are particularly important because other means of constraining interior properties require in-situ or orbiting sensors (e.g. seismometers, magnetometers, and Doppler tracking of spacecraft). Here we describe the successful implementation of a new Earth-based radar technique (Holin, 1992) that provides spin state measurements with unprecedented accuracy. Our first observations were designed to characterize Mercury's core. Peale (1976) showed that the measurement of four quantities (the obliquity of the planet, the amplitude of its longitude librations, and the second-degree gravitational harmonics) are sufficient to determine the size and state of Mercury's core. The existence of a molten core would place strong constraints on the thermal and rotational histories of the planet, with profound implications for the composition and rotation state of the planet at the time of formation. A solid core would have a fundamental impact on theories of planetary magnetic field generation. We observed Mercury with the Goldstone radar and the Green Bank Telescope in May-June 2002. We illuminated the planet with a monochromatic signal, recorded the scattered power at the two antennas, and cross-correlated the echoes in the time domain. We obtained strong correlations which

  8. Revealing networks from dynamics: an introduction

    NASA Astrophysics Data System (ADS)

    Timme, Marc; Casadiego, Jose

    2014-08-01

    What can we learn from the collective dynamics of a complex network about its interaction topology? Taking the perspective from nonlinear dynamics, we briefly review recent progress on how to infer structural connectivity (direct interactions) from accessing the dynamics of the units. Potential applications range from interaction networks in physics, to chemical and metabolic reactions, protein and gene regulatory networks as well as neural circuits in biology and electric power grids or wireless sensor networks in engineering. Moreover, we briefly mention some standard ways of inferring effective or functional connectivity.

  9. Enabling Strain Hardening Simulations with Dislocation Dynamics

    SciTech Connect

    Arsenlis, A; Cai, W

    2006-12-20

    Numerical algorithms for discrete dislocation dynamics simulations are investigated for the purpose of enabling strain hardening simulations of single crystals on massively parallel computers. The algorithms investigated include the /(N) calculation of forces, the equations of motion, time integration, adaptive mesh refinement, the treatment of dislocation core reactions, and the dynamic distribution of work on parallel computers. A simulation integrating all of these algorithmic elements using the Parallel Dislocation Simulator (ParaDiS) code is performed to understand their behavior in concert, and evaluate the overall numerical performance of dislocation dynamics simulations and their ability to accumulate percents of plastic strain.

  10. Multiscale Molecular Dynamics Simulations of Polaritonic Chemistry.

    PubMed

    Luk, Hoi Ling; Feist, Johannes; Toppari, J Jussi; Groenhof, Gerrit

    2017-09-12

    When photoactive molecules interact strongly with confined light modes as found in plasmonic structures or optical cavities, new hybrid light-matter states can form, the so-called polaritons. These polaritons are coherent superpositions (in the quantum mechanical sense) of excitations of the molecules and of the cavity photon or surface plasmon. Recent experimental and theoretical works suggest that access to these polaritons in cavities could provide a totally new and attractive paradigm for controlling chemical reactions that falls in between traditional chemical catalysis and coherent laser control. However, designing cavity parameters to control chemistry requires a theoretical model with which the effect of the light-matter coupling on the molecular dynamics can be predicted accurately. Here we present a multiscale quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulation model for photoactive molecules that are strongly coupled to confined light in optical cavities or surface plasmons. Using this model we have performed simulations with up to 1600 Rhodamine molecules in a cavity. The results of these simulations reveal that the contributions of the molecules to the polariton are time-dependent due to thermal fluctuations that break symmetry. Furthermore, the simulations suggest that in addition to the cavity quality factor, also the Stokes shift and number of molecules control the lifetime of the polariton. Because large numbers of molecules interacting with confined light can now be simulated in atomic detail, we anticipate that our method will lead to a better understanding of the effects of strong coupling on chemical reactivity. Ultimately the method may even be used to systematically design cavities to control photochemistry.

  11. Dynamic Shade and Irradiance Simulation of Aquatic ...

    EPA Pesticide Factsheets

    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 accumulates across landscapes and is the main energy driver for increasing aquatic and landscape temperatures at both local and holistic scales. Landscape disturbances such as landuse change, clear cutting, and fire can cause significant variations in the resulting irradiance reaching particular locations. Penumbra can simulate solar angles and irradiance at definable temporal grains as low as one minute while simulating landscape shadowing up to an entire year. Landscapes can be represented at sub-meter resolutions with appropriate spatial data inputs, such as field data or elevation and surface object heights derived from light detection and ranging (LiDAR) data. This work describes Penumbra’s framework and methodology, external model integration capability, and appropriate model application for a variety of watershed restoration project types. First, an overview of Penumbra’s framework reveals what this model adds to the existing ecological modeling domain. Second, Penumbra’s stand-alone and integration modes are explained and demonstrated. Stand-alone modeling results are showcased within the 3-D visualization tool VISTAS (VISualizing Terrestrial-Aquatic Systems), which fluently summariz

  12. Organ Dynamics and Fluid Dynamics of the HH25 Chick Embryonic Cardiac Ventricle as Revealed by a Novel 4D High-Frequency Ultrasound Imaging Technique and Computational Flow Simulations.

    PubMed

    Ho, Sheldon; Tan, Germaine Xin Yi; Foo, Toon Jin; Phan-Thien, Nhan; Yap, Choon Hwai

    2017-07-25

    Past literature has provided evidence that a normal mechanical force environment of blood flow may guide normal development while an abnormal environment can lead to congenital malformations, thus warranting further studies on embryonic cardiovascular flow dynamics. In the current study, we developed a non-invasive 4D high-frequency ultrasound technique, and use it to analyze cardiovascular organ dynamics and flow dynamics. Three chick embryos at stage HH25 were scanned with high frequency ultrasound in cine-B-mode at multiple planes spaced at 0.05 mm. 4D images of the heart and nearby arteries were generated via temporal and spatial correlation coupled with quadratic mean ensemble averaging. Dynamic mesh CFD was performed to understand the flow dynamics in the ventricle of the 2 hearts. Our imaging technique has sufficiently high resolution to enable organ dynamics quantification and CFD. Fine structures such as the aortic arches and details such as the cyclic distension of the carotid arteries were captured. The outflow tract completely collapsed during ventricular diastole, possible serving the function of a valve to prevent regurgitation. CFD showed that ventricular wall shear stress (WSS) were in the range of 0.1-0.5 Pa, and that the left side of the common ventricle experienced lower WSS than the right side. The pressure gradient from the inlet to the outlet of the ventricle was positive over most of the cardiac cycle, and minimal regurgitation flow was observed, despite the absence of heart valves. We developed a new image-based CFD method to elucidate cardiac organ dynamics and flow dynamics of embryonic hearts. The embryonic heart appeared to be optimized to generate net forward flow despite the absence of valves, and the WSS environment appeared to be side-specific.

  13. Ananke: temporal clustering reveals ecological dynamics of microbial communities

    PubMed Central

    Rohwer, Robin R.; Perrie, Jonathan; McMahon, Katherine D.

    2017-01-01

    Taxonomic markers such as the 16S ribosomal RNA gene are widely used in microbial community analysis. A common first step in marker-gene analysis is grouping genes into clusters to reduce data sets to a more manageable size and potentially mitigate the effects of sequencing error. Instead of clustering based on sequence identity, marker-gene data sets collected over time can be clustered based on temporal correlation to reveal ecologically meaningful associations. We present Ananke, a free and open-source algorithm and software package that complements existing sequence-identity-based clustering approaches by clustering marker-gene data based on time-series profiles and provides interactive visualization of clusters, including highlighting of internal OTU inconsistencies. Ananke is able to cluster distinct temporal patterns from simulations of multiple ecological patterns, such as periodic seasonal dynamics and organism appearances/disappearances. We apply our algorithm to two longitudinal marker gene data sets: faecal communities from the human gut of an individual sampled over one year, and communities from a freshwater lake sampled over eleven years. Within the gut, the segregation of the bacterial community around a food-poisoning event was immediately clear. In the freshwater lake, we found that high sequence identity between marker genes does not guarantee similar temporal dynamics, and Ananke time-series clusters revealed patterns obscured by clustering based on sequence identity or taxonomy. Ananke is free and open-source software available at https://github.com/beiko-lab/ananke. PMID:28966891

  14. Deuterium reveals the dynamics of notch activation.

    PubMed

    Raphael, Kopan

    2011-04-13

    Notch activation requires unfolding of a juxtamembrane negative regulatory domain (NRR). Tiyanont et al. (2011) analyzed the dynamics of NRR unfolding in the presence of EGTA. As predicted from the crystal structure and deletion analyses, the lin-Notch repeats unfold first, facilitating access by ADAM proteases. Surprisingly, the heterodimerization domain remains stable.

  15. Using Dynamic Graphs to Reveal Student Reasoning

    ERIC Educational Resources Information Center

    Lassak, Marshall

    2009-01-01

    Using dynamic graphs, future secondary mathematics teachers were able to represent and communicate their understanding of a brief mathematical investigation in a way that a symbolic proof of the problem could not. Four different student work samples are discussed. (Contains 6 figures.)

  16. Modeling Nanocomposites for Molecular Dynamics (MD) Simulations

    DTIC Science & Technology

    2015-01-01

    Maximum 200 Words) The minimum energy configuration for Molecular Dynamics (MD) simulations is found for a carbon nanotube (CNT)/polymer... Carbon Nanotubes (CNTs), Molecular Dynamics Simulations 15. NUMBER OF PAGES 18 16. PRICE CODE 17. SECURITY CLASSIFICATION OF REPORT... Carbon Nanotubes ,” Macromolecules, Volume 39, Number 16, pp. 5194-5205, July 2006. 6. “VMD-Visual Molecular Dynamics ,” March 2014, http

  17. Molecular Dynamics Simulation of Supercritical Spray Phenomena

    DTIC Science & Technology

    2008-09-26

    Dynamics of the Rheological and Structural Properties of Linear and Branched Molecules. Simple Shear and Poiseuille Flows ; Instabilities and Slip...Michael Barrucco Publications: "Comparison of Wall Models for the Molecular Dynamics Simulation of Micro flows ," R. D. Branam and M. M...Performance 3. DATES COVERED (From - To) 1 Dec. 2003 - 31 May 2008 4. TITLE AND SUBTITLE Molecular Dynamics Simulation of Supercritical

  18. Novel methods for molecular dynamics simulations.

    PubMed

    Elber, R

    1996-04-01

    In the past year, significant progress was made in the development of molecular dynamics methods for the liquid phase and for biological macromolecules. Specifically, faster algorithms to pursue molecular dynamics simulations were introduced and advances were made in the design of new optimization algorithms guided by molecular dynamics protocols. A technique to calculate the quantum spectra of protein vibrations was introduced.

  19. Metrics for comparing dynamic earthquake rupture simulations

    USGS Publications Warehouse

    Barall, Michael; Harris, Ruth A.

    2014-01-01

    Earthquakes are complex events that involve a myriad of interactions among multiple geologic features and processes. One of the tools that is available to assist with their study is computer simulation, particularly dynamic rupture simulation. A dynamic rupture simulation is a numerical model of the physical processes that occur during an earthquake. Starting with the fault geometry, friction constitutive law, initial stress conditions, and assumptions about the condition and response of the near‐fault rocks, a dynamic earthquake rupture simulation calculates the evolution of fault slip and stress over time as part of the elastodynamic numerical solution (Ⓔ see the simulation description in the electronic supplement to this article). The complexity of the computations in a dynamic rupture simulation make it challenging to verify that the computer code is operating as intended, because there are no exact analytic solutions against which these codes’ results can be directly compared. One approach for checking if dynamic rupture computer codes are working satisfactorily is to compare each code’s results with the results of other dynamic rupture codes running the same earthquake simulation benchmark. To perform such a comparison consistently, it is necessary to have quantitative metrics. In this paper, we present a new method for quantitatively comparing the results of dynamic earthquake rupture computer simulation codes.

  20. AVHRR imagery reveals Antarctic ice dynamics

    NASA Technical Reports Server (NTRS)

    Bindschadler, Robert A.; Vornberger, Patricia L.

    1990-01-01

    A portion of AVHRR data taken on December 5, 1987 at 06:15 GMT over a part of Antarctica is used here to show that many of the most significant dynamic features of ice sheets can be identified by a careful examination of AVHRR imagery. The relatively low resolution of this instrument makes it ideal for obtaining a broad view of the ice sheets, while its wide swath allows coverage of areas beyond the reach of high-resolution imagers either currently in orbit or planned. An interpretation is given of the present data, which cover the area of ice streams that drain the interior of the West Antarctic ice sheet into the Ross Ice Shelf.

  1. AVHRR imagery reveals Antarctic ice dynamics

    SciTech Connect

    Bindschadler, R.A.; Vornberger, P.L. STX Corp., Lanham, MD )

    1990-06-01

    A portion of AVHRR data taken on December 5, 1987 at 06:15 GMT over a part of Antarctica is used here to show that many of the most significant dynamic features of ice sheets can be identified by a careful examination of AVHRR imagery. The relatively low resolution of this instrument makes it ideal for obtaining a broad view of the ice sheets, while its wide swath allows coverage of areas beyond the reach of high-resolution imagers either currently in orbit or planned. An interpretation is given of the present data, which cover the area of ice streams that drain the interior of the West Antarctic ice sheet into the Ross Ice Shelf. 21 refs.

  2. Human dynamics revealed through Web analytics.

    PubMed

    Gonçalves, Bruno; Ramasco, José J

    2008-08-01

    The increasing ubiquity of Internet access and the frequency with which people interact with it raise the possibility of using the Web to better observe, understand, and monitor several aspects of human social behavior. Web sites with large numbers of frequently returning users are ideal for this task. If these sites belong to companies or universities, their usage patterns can furnish information about the working habits of entire populations. In this work, we analyze the properly anonymized logs detailing the access history to Emory University's Web site. Emory is a medium-sized university located in Atlanta, Georgia. We find interesting structure in the activity patterns of the domain and study in a systematic way the main forces behind the dynamics of the traffic. In particular, we find that linear preferential linking, priority-based queuing, and the decay of interest for the contents of the pages are the essential ingredients to understand the way users navigate the Web.

  3. Human dynamics revealed through Web analytics

    NASA Astrophysics Data System (ADS)

    Gonçalves, Bruno; Ramasco, José J.

    2008-08-01

    The increasing ubiquity of Internet access and the frequency with which people interact with it raise the possibility of using the Web to better observe, understand, and monitor several aspects of human social behavior. Web sites with large numbers of frequently returning users are ideal for this task. If these sites belong to companies or universities, their usage patterns can furnish information about the working habits of entire populations. In this work, we analyze the properly anonymized logs detailing the access history to Emory University’s Web site. Emory is a medium-sized university located in Atlanta, Georgia. We find interesting structure in the activity patterns of the domain and study in a systematic way the main forces behind the dynamics of the traffic. In particular, we find that linear preferential linking, priority-based queuing, and the decay of interest for the contents of the pages are the essential ingredients to understand the way users navigate the Web.

  4. Mapping conformational dynamics of proteins using torsional dynamics simulations.

    PubMed

    Gangupomu, Vamshi K; Wagner, Jeffrey R; Park, In-Hee; Jain, Abhinandan; Vaidehi, Nagarajan

    2013-05-07

    All-atom molecular dynamics simulations are widely used to study the flexibility of protein conformations. However, enhanced sampling techniques are required for simulating protein dynamics that occur on the millisecond timescale. In this work, we show that torsional molecular dynamics simulations enhance protein conformational sampling by performing conformational search in the low-frequency torsional degrees of freedom. In this article, we use our recently developed torsional-dynamics method called Generalized Newton-Euler Inverse Mass Operator (GNEIMO) to study the conformational dynamics of four proteins. We investigate the use of the GNEIMO method in simulations of the conformationally flexible proteins fasciculin and calmodulin, as well as the less flexible crambin and bovine pancreatic trypsin inhibitor. For the latter two proteins, the GNEIMO simulations with an implicit-solvent model reproduced the average protein structural fluctuations and sample conformations similar to those from Cartesian simulations with explicit solvent. The application of GNEIMO with replica exchange to the study of fasciculin conformational dynamics produced sampling of two of this protein's experimentally established conformational substates. Conformational transition of calmodulin from the Ca(2+)-bound to the Ca(2+)-free conformation occurred readily with GNEIMO simulations. Moreover, the GNEIMO method generated an ensemble of conformations that satisfy about half of both short- and long-range interresidue distances obtained from NMR structures of holo to apo transitions in calmodulin. Although unconstrained all-atom Cartesian simulations have failed to sample transitions between the substates of fasciculin and calmodulin, GNEIMO simulations show the transitions in both systems. The relatively short simulation times required to capture these long-timescale conformational dynamics indicate that GNEIMO is a promising molecular-dynamics technique for studying domain motion in

  5. Mapping Conformational Dynamics of Proteins Using Torsional Dynamics Simulations

    PubMed Central

    Gangupomu, Vamshi K.; Wagner, Jeffrey R.; Park, In-Hee; Jain, Abhinandan; Vaidehi, Nagarajan

    2013-01-01

    All-atom molecular dynamics simulations are widely used to study the flexibility of protein conformations. However, enhanced sampling techniques are required for simulating protein dynamics that occur on the millisecond timescale. In this work, we show that torsional molecular dynamics simulations enhance protein conformational sampling by performing conformational search in the low-frequency torsional degrees of freedom. In this article, we use our recently developed torsional-dynamics method called Generalized Newton-Euler Inverse Mass Operator (GNEIMO) to study the conformational dynamics of four proteins. We investigate the use of the GNEIMO method in simulations of the conformationally flexible proteins fasciculin and calmodulin, as well as the less flexible crambin and bovine pancreatic trypsin inhibitor. For the latter two proteins, the GNEIMO simulations with an implicit-solvent model reproduced the average protein structural fluctuations and sample conformations similar to those from Cartesian simulations with explicit solvent. The application of GNEIMO with replica exchange to the study of fasciculin conformational dynamics produced sampling of two of this protein’s experimentally established conformational substates. Conformational transition of calmodulin from the Ca2+-bound to the Ca2+-free conformation occurred readily with GNEIMO simulations. Moreover, the GNEIMO method generated an ensemble of conformations that satisfy about half of both short- and long-range interresidue distances obtained from NMR structures of holo to apo transitions in calmodulin. Although unconstrained all-atom Cartesian simulations have failed to sample transitions between the substates of fasciculin and calmodulin, GNEIMO simulations show the transitions in both systems. The relatively short simulation times required to capture these long-timescale conformational dynamics indicate that GNEIMO is a promising molecular-dynamics technique for studying domain motion in

  6. Wigner flow reveals topological order in quantum phase space dynamics.

    PubMed

    Steuernagel, Ole; Kakofengitis, Dimitris; Ritter, Georg

    2013-01-18

    The behavior of classical mechanical systems is characterized by their phase portraits, the collections of their trajectories. Heisenberg's uncertainty principle precludes the existence of sharply defined trajectories, which is why traditionally only the time evolution of wave functions is studied in quantum dynamics. These studies are quite insensitive to the underlying structure of quantum phase space dynamics. We identify the flow that is the quantum analog of classical particle flow along phase portrait lines. It reveals hidden features of quantum dynamics and extra complexity. Being constrained by conserved flow winding numbers, it also reveals fundamental topological order in quantum dynamics that has so far gone unnoticed.

  7. Simulation Exercises in Population Dynamics.

    ERIC Educational Resources Information Center

    Falk, Laurence L.; Falk, Carol J.

    1986-01-01

    Describes a computer simulation providing population change profiles at 5-year intervals for 100 years, projecting natural rate of increase and total population, per capita gross national product, energy consumption, age-specific fertility rates, and survival ratios. Data sources for the simulation, sample printed output, and learning activities…

  8. Computational models of protein kinematics and dynamics: beyond simulation.

    PubMed

    Gipson, Bryant; Hsu, David; Kavraki, Lydia E; Latombe, Jean-Claude

    2012-01-01

    Physics-based simulation represents a powerful method for investigating the time-varying behavior of dynamic protein systems at high spatial and temporal resolution. Such simulations, however, can be prohibitively difficult or lengthy for large proteins or when probing the lower-resolution, long-timescale behaviors of proteins generally. Importantly, not all questions about a protein system require full space and time resolution to produce an informative answer. For instance, by avoiding the simulation of uncorrelated, high-frequency atomic movements, a larger, domain-level picture of protein dynamics can be revealed. The purpose of this review is to highlight the growing body of complementary work that goes beyond simulation. In particular, this review focuses on methods that address kinematics and dynamics, as well as those that address larger organizational questions and can quickly yield useful information about the long-timescale behavior of a protein.

  9. Computational Models of Protein Kinematics and Dynamics: Beyond Simulation

    PubMed Central

    Gipson, Bryant; Hsu, David; Kavraki, Lydia E.; Latombe, Jean-Claude

    2016-01-01

    Physics-based simulation represents a powerful method for investigating the time-varying behavior of dynamic protein systems at high spatial and temporal resolution. Such simulations, however, can be prohibitively difficult or lengthy for large proteins or when probing the lower-resolution, long-timescale behaviors of proteins generally. Importantly, not all questions about a protein system require full space and time resolution to produce an informative answer. For instance, by avoiding the simulation of uncorrelated, high-frequency atomic movements, a larger, domain-level picture of protein dynamics can be revealed. The purpose of this review is to highlight the growing body of complementary work that goes beyond simulation. In particular, this review focuses on methods that address kinematics and dynamics, as well as those that address larger organizational questions and can quickly yield useful information about the long-timescale behavior of a protein. PMID:22524225

  10. Simulating protein dynamics: Novel methods and applications

    NASA Astrophysics Data System (ADS)

    Vishal, V.

    This Ph.D dissertation describes several methodological advances in molecular dynamics (MD) simulations. Methods like Markov State Models can be used effectively in combination with distributed computing to obtain long time scale behavior from an ensemble of short simulations. Advanced computing architectures like Graphics Processors can be used to greatly extend the scope of MD. Applications of MD techniques to problems like Alzheimer's Disease and fundamental questions in protein dynamics are described.

  11. Discrete Molecular Dynamics Simulation of Biomolecules

    NASA Astrophysics Data System (ADS)

    Ding, Feng

    2011-10-01

    Discrete molecular dynamics (DMD) simulation of hard spheres was the first implementation of molecular dynamics (MD) in history. DMD simulations are computationally more efficient than continuous MD simulations due to simplified interaction potentials. However, also due to these simplified potentials, DMD has often been associated with coarse-grained modeling, and hence continuous MD has become the dominant approach used to study the internal dynamics of biomolecules. With the recent advances in DMD methodology, including the development of high-resolution models for biomolecules and approaches to increase DMD efficiency, DMD simulations are emerging as an important tool in the field of molecular modeling, including the study of protein folding, protein misfolding and aggregation, and protein engineering. Recently, DMD methodology has been applied to modeling RNA folding and protein-ligand recognition. With these improvements to DMD methodology and the continuous increase in available computational power, we expect a growing role of DMD simulations in our understanding of biology.

  12. The "Collisions Cube" Molecular Dynamics Simulator.

    ERIC Educational Resources Information Center

    Nash, John J.; Smith, Paul E.

    1995-01-01

    Describes a molecular dynamics simulator that employs ping-pong balls as the atoms or molecules and is suitable for either large lecture halls or small classrooms. Discusses its use in illustrating many of the fundamental concepts related to molecular motion and dynamics and providing a three-dimensional perspective of molecular motion. (JRH)

  13. Visualizing Structure and Dynamics of Disaccharide Simulations

    SciTech Connect

    Matthews, J. F.; Beckham, G. T.; Himmel, M. E.; Crowley, M. F.

    2012-01-01

    We examine the effect of several solvent models on the conformational properties and dynamics of disaccharides such as cellobiose and lactose. Significant variation in timescale for large scale conformational transformations are observed. Molecular dynamics simulation provides enough detail to enable insight through visualization of multidimensional data sets. We present a new way to visualize conformational space for disaccharides with Ramachandran plots.

  14. Strong Analog Classical Simulation of Coherent Quantum Dynamics

    NASA Astrophysics Data System (ADS)

    Wang, Dong-Sheng

    2017-02-01

    A strong analog classical simulation of general quantum evolution is proposed, which serves as a novel scheme in quantum computation and simulation. The scheme employs the approach of geometric quantum mechanics and quantum informational technique of quantum tomography, which applies broadly to cases of mixed states, nonunitary evolution, and infinite dimensional systems. The simulation provides an intriguing classical picture to probe quantum phenomena, namely, a coherent quantum dynamics can be viewed as a globally constrained classical Hamiltonian dynamics of a collection of coupled particles or strings. Efficiency analysis reveals a fundamental difference between the locality in real space and locality in Hilbert space, the latter enables efficient strong analog classical simulations. Examples are also studied to highlight the differences and gaps among various simulation methods. Funding support from NSERC of Canada and a research fellowship at Department of Physics and Astronomy, University of British Columbia are acknowledged

  15. Simulating Flexible-Spacecraft Dynamics and Control

    NASA Technical Reports Server (NTRS)

    Fedor, Joseph

    1987-01-01

    Versatile program applies to many types of spacecraft and dynamical problems. Flexible Spacecraft Dynamics and Control program (FSD) developed to aid in simulation of large class of flexible and rigid spacecraft. Extremely versatile and used in attitude dynamics and control analysis as well as in-orbit support of deployment and control of spacecraft. Applicable to inertially oriented spinning, Earth-oriented, or gravity-gradient-stabilized spacecraft. Written in FORTRAN 77.

  16. Molecular Dynamics Simulations of Simple Liquids

    ERIC Educational Resources Information Center

    Speer, Owner F.; Wengerter, Brian C.; Taylor, Ramona S.

    2004-01-01

    An experiment, in which students were given the opportunity to perform molecular dynamics simulations on a series of molecular liquids using the Amber suite of programs, is presented. They were introduced to both physical theories underlying classical mechanics simulations and to the atom-atom pair distribution function.

  17. Molecular Dynamics Simulations of Simple Liquids

    ERIC Educational Resources Information Center

    Speer, Owner F.; Wengerter, Brian C.; Taylor, Ramona S.

    2004-01-01

    An experiment, in which students were given the opportunity to perform molecular dynamics simulations on a series of molecular liquids using the Amber suite of programs, is presented. They were introduced to both physical theories underlying classical mechanics simulations and to the atom-atom pair distribution function.

  18. Observing dynamical SUSY breaking with lattice simulation

    SciTech Connect

    Kanamori, Issaku

    2008-11-23

    On the basis of the recently developed lattice formulation of supersymmetric theories which keeps a part of the supersymmetry, we propose a method of observing dynamical SUSY breaking with lattice simulation. We use Hamiltonian as an order parameter and measure the ground state energy as a zero temperature limit of the finite temperature simulation. Our method provides a way of obtaining a physical result from the lattice simulation for supersymmetric theories.

  19. Molecular dynamics simulations: advances and applications

    PubMed Central

    Hospital, Adam; Goñi, Josep Ramon; Orozco, Modesto; Gelpí, Josep L

    2015-01-01

    Molecular dynamics simulations have evolved into a mature technique that can be used effectively to understand macromolecular structure-to-function relationships. Present simulation times are close to biologically relevant ones. Information gathered about the dynamic properties of macromolecules is rich enough to shift the usual paradigm of structural bioinformatics from studying single structures to analyze conformational ensembles. Here, we describe the foundations of molecular dynamics and the improvements made in the direction of getting such ensemble. Specific application of the technique to three main issues (allosteric regulation, docking, and structure refinement) is discussed. PMID:26604800

  20. Dynamic Coupling among Protein Binding, Sliding, and DNA Bending Revealed by Molecular Dynamics.

    PubMed

    Tan, Cheng; Terakawa, Tsuyoshi; Takada, Shoji

    2016-07-13

    Protein binding to DNA changes the DNA's structure, and altered DNA structure can, in turn, modulate the dynamics of protein binding. This mutual dependency is poorly understood. Here we investigated dynamic couplings among protein binding to DNA, protein sliding on DNA, and DNA bending by applying a coarse-grained simulation method to the bacterial architectural protein HU and 14 other DNA-binding proteins. First, we verified our method by showing that the simulated HU exhibits a weak preference for A/T-rich regions of DNA and a much higher affinity for gapped and nicked DNA, consistent with biochemical experiments. The high affinity was attributed to a local DNA bend, but not the specific chemical moiety of the gap/nick. The long-time dynamic analysis revealed that HU sliding is associated with the movement of the local DNA bending site. Deciphering single sliding steps, we found the coupling between HU sliding and DNA bending is akin to neither induced-fit nor population-shift; instead they moved concomitantly. This is reminiscent of a cation transfer on DNA and can be viewed as a protein version of polaron-like sliding. Interestingly, on shorter time scales, HU paused when the DNA was highly bent at the bound position and escaped from pauses once the DNA spontaneously returned to a less bent structure. The HU sliding is largely regulated by DNA bending dynamics. With 14 other proteins, we explored the generality and versatility of the dynamic coupling and found that 6 of the 15 assayed proteins exhibit the polaron-like sliding.

  1. Revealing physical interaction networks from statistics of collective dynamics.

    PubMed

    Nitzan, Mor; Casadiego, Jose; Timme, Marc

    2017-02-01

    Revealing physical interactions in complex systems from observed collective dynamics constitutes a fundamental inverse problem in science. Current reconstruction methods require access to a system's model or dynamical data at a level of detail often not available. We exploit changes in invariant measures, in particular distributions of sampled states of the system in response to driving signals, and use compressed sensing to reveal physical interaction networks. Dynamical observations following driving suffice to infer physical connectivity even if they are temporally disordered, are acquired at large sampling intervals, and stem from different experiments. Testing various nonlinear dynamic processes emerging on artificial and real network topologies indicates high reconstruction quality for existence as well as type of interactions. These results advance our ability to reveal physical interaction networks in complex synthetic and natural systems.

  2. Revealing physical interaction networks from statistics of collective dynamics

    PubMed Central

    Nitzan, Mor; Casadiego, Jose; Timme, Marc

    2017-01-01

    Revealing physical interactions in complex systems from observed collective dynamics constitutes a fundamental inverse problem in science. Current reconstruction methods require access to a system’s model or dynamical data at a level of detail often not available. We exploit changes in invariant measures, in particular distributions of sampled states of the system in response to driving signals, and use compressed sensing to reveal physical interaction networks. Dynamical observations following driving suffice to infer physical connectivity even if they are temporally disordered, are acquired at large sampling intervals, and stem from different experiments. Testing various nonlinear dynamic processes emerging on artificial and real network topologies indicates high reconstruction quality for existence as well as type of interactions. These results advance our ability to reveal physical interaction networks in complex synthetic and natural systems. PMID:28246630

  3. Simulation of wetlands forest vegetation dynamics

    USGS Publications Warehouse

    Phipps, R.L.

    1979-01-01

    A computer program, SWAMP, was designed to simulate the effects of flood frequency and depth to water table on southern wetlands forest vegetation dynamics. By incorporating these hydrologic characteristics into the model, forest vegetation and vegetation dynamics can be simulated. The model, based on data from the White River National Wildlife Refuge near De Witt, Arkansas, "grows" individual trees on a 20 x 20-m plot taking into account effects on the tree growth of flooding, depth to water table, shade tolerance, overtopping and crowding, and probability of death and reproduction. A potential application of the model is illustrated with simulations of tree fruit production following flood-control implementation and lumbering. ?? 1979.

  4. Combining molecular dynamics with mesoscopic Green's function reaction dynamics simulations

    NASA Astrophysics Data System (ADS)

    Vijaykumar, Adithya; Bolhuis, Peter G.; ten Wolde, Pieter Rein

    2015-12-01

    In many reaction-diffusion processes, ranging from biochemical networks, catalysis, to complex self-assembly, the spatial distribution of the reactants and the stochastic character of their interactions are crucial for the macroscopic behavior. The recently developed mesoscopic Green's Function Reaction Dynamics (GFRD) method enables efficient simulation at the particle level provided the microscopic dynamics can be integrated out. Yet, many processes exhibit non-trivial microscopic dynamics that can qualitatively change the macroscopic behavior, calling for an atomistic, microscopic description. We propose a novel approach that combines GFRD for simulating the system at the mesoscopic scale where particles are far apart, with a microscopic technique such as Langevin dynamics or Molecular Dynamics (MD), for simulating the system at the microscopic scale where reactants are in close proximity. This scheme defines the regions where the particles are close together and simulated with high microscopic resolution and those where they are far apart and simulated with lower mesoscopic resolution, adaptively on the fly. The new multi-scale scheme, called MD-GFRD, is generic and can be used to efficiently simulate reaction-diffusion systems at the particle level.

  5. Computational plasticity algorithm for particle dynamics simulations

    NASA Astrophysics Data System (ADS)

    Krabbenhoft, K.; Lyamin, A. V.; Vignes, C.

    2017-03-01

    The problem of particle dynamics simulation is interpreted in the framework of computational plasticity leading to an algorithm which is mathematically indistinguishable from the common implicit scheme widely used in the finite element analysis of elastoplastic boundary value problems. This algorithm provides somewhat of a unification of two particle methods, the discrete element method and the contact dynamics method, which usually are thought of as being quite disparate. In particular, it is shown that the former appears as the special case where the time stepping is explicit while the use of implicit time stepping leads to the kind of schemes usually labelled contact dynamics methods. The framing of particle dynamics simulation within computational plasticity paves the way for new approaches similar (or identical) to those frequently employed in nonlinear finite element analysis. These include mixed implicit-explicit time stepping, dynamic relaxation and domain decomposition schemes.

  6. Spin dynamics simulations at AGS

    SciTech Connect

    Huang, H.; MacKay, W.W.; Meot, F.; Roser, T.

    2010-05-23

    To preserve proton polarization through acceleration, it is important to have a correct model of the process. It has been known that with the insertion of the two helical partial Siberian snakes in the Alternating Gradient Synchrotron (AGS), the MAD model of AGS can not deal with a field map with offset orbit. The stepwise ray-tracing code Zgoubi provides a tool to represent the real electromagnetic fields in the modeling of the optics and spin dynamics for the AGS. Numerical experiments of resonance crossing, including spin dynamics in presence of the snakes and Q-jump, have been performed in AGS lattice models, using Zgoubi. This contribution reports on various results so obtained.

  7. Substrate Channel in Nitrogenase Revealed by a Molecular Dynamics Approach

    SciTech Connect

    Smith, Dayle; Danyal, Karamatullah; Raugei, Simone; Seefeldt, Lance C.

    2014-03-22

    Mo-dependent nitrogenase catalyzes the biological reduction of N2 to 2NH3 at the FeMo-cofactor buried deep inside the MoFe protein. Access of substrates, such as N2, to the active site is likely restricted by the surrounding protein, requiring substrate channels that lead from the surface to the active site. Earlier studies on crystallographic structures of the MoFe protein have suggested three putative substrate channels. Here, we have utilized sub-microsecond atomistic molecular dynamics simulations to allow the nitrogenase MoFe protein to explore its conformational space in an aqueous solution at physiological ionic strength, revealing a putative substrate channel not previously reported. The viability of the proposed channel was tested by examining the free energy of passage of N2 from the surface through the channel to FeMo-cofactor, with discovery of a very low energy barrier. These studies point to a viable substrate channel in nitrogenase that appears during thermal motions of the protein in an aqueous environment that approaches a face of FeMo-cofactor earlier implicated in substrate binding.

  8. Dynamic simulation of particle sedimentation

    NASA Astrophysics Data System (ADS)

    Zhang, Zhongzhen; Prosperetti, Andrea

    2004-11-01

    The sedimentation of 1024 spheres has been simulated via a recently developed method:Physalis Method. Particles are initially randomly distributed and periodic boundary conditions are assumed. The time evolution of the particle spatial distribution is studied by meassuering the structure factor. Properties of particles velocity distribution, e.g. variance, time autocorrelation, have been studied. The effects of particle rotation and collision are discussed.

  9. The data system dynamic simulation /DSDS/

    NASA Technical Reports Server (NTRS)

    Hooper, J. W.; Piner, J. R.

    1978-01-01

    The paper describes the development by NASA of the data system dynamic simulation (DSDS) which provides a data system simulation capability for a broad range of programs, with the capability to model and simulate all or any portion of an end-to-end data system to multiple levels of fidelity. Versatility is achieved by specifying parameters which define the performance characteristics of data system components, and by specifying control and data paths in a data system. DSDS helps reduce overall simulation cost and the time required for obtaining a data systems analysis, and helps provide both early realistic representations of data systems and the flexibility to study design changes and operating strategies.

  10. Multibody dynamic simulation of knee contact mechanics

    PubMed Central

    Bei, Yanhong; Fregly, Benjamin J.

    2006-01-01

    Multibody dynamic musculoskeletal models capable of predicting muscle forces and joint contact pressures simultaneously would be valuable for studying clinical issues related to knee joint degeneration and restoration. Current three-dimensional multi-body knee models are either quasi-static with deformable contact or dynamic with rigid contact. This study proposes a computationally efficient methodology for combining multibody dynamic simulation methods with a deformable contact knee model. The methodology requires preparation of the articular surface geometry, development of efficient methods to calculate distances between contact surfaces, implementation of an efficient contact solver that accounts for the unique characteristics of human joints, and specification of an application programming interface for integration with any multibody dynamic simulation environment. The current implementation accommodates natural or artificial tibiofemoral joint models, small or large strain contact models, and linear or nonlinear material models. Applications are presented for static analysis (via dynamic simulation) of a natural knee model created from MRI and CT data and dynamic simulation of an artificial knee model produced from manufacturer’s CAD data. Small and large strain natural knee static analyses required 1 min of CPU time and predicted similar contact conditions except for peak pressure, which was higher for the large strain model. Linear and nonlinear artificial knee dynamic simulations required 10 min of CPU time and predicted similar contact force and torque but different contact pressures, which were lower for the nonlinear model due to increased contact area. This methodology provides an important step toward the realization of dynamic musculoskeletal models that can predict in vivo knee joint motion and loading simultaneously. PMID:15564115

  11. Perspective: chemical dynamics simulations of non-statistical reaction dynamics.

    PubMed

    Ma, Xinyou; Hase, William L

    2017-04-28

    Non-statistical chemical dynamics are exemplified by disagreements with the transition state (TS), RRKM and phase space theories of chemical kinetics and dynamics. The intrinsic reaction coordinate (IRC) is often used for the former two theories, and non-statistical dynamics arising from non-IRC dynamics are often important. In this perspective, non-statistical dynamics are discussed for chemical reactions, with results primarily obtained from chemical dynamics simulations and to a lesser extent from experiment. The non-statistical dynamical properties discussed are: post-TS dynamics, including potential energy surface bifurcations, product energy partitioning in unimolecular dissociation and avoiding exit-channel potential energy minima; non-RRKM unimolecular decomposition; non-IRC dynamics; direct mechanisms for bimolecular reactions with pre- and/or post-reaction potential energy minima; non-TS theory barrier recrossings; and roaming dynamics.This article is part of the themed issue 'Theoretical and computational studies of non-equilibrium and non-statistical dynamics in the gas phase, in the condensed phase and at interfaces'. © 2017 The Author(s).

  12. Dynamic centrifugal compressor model for system simulation

    NASA Astrophysics Data System (ADS)

    Jiang, Wei; Khan, Jamil; Dougal, Roger A.

    A dynamic model of a centrifugal compressor capable of system simulation in the virtual test bed (VTB) computational environment is presented. The model is based on first principles, i.e. the dynamic performance including the losses is determined from the compressor geometry and not from the experimentally determined characteristic performance curves. In this study, the compressor losses, such as incidence and friction losses, etc., are mathematically modeled for developing compressor characteristics. For easy implementation in the VTB platform, the non-linear governing equations are discretized in resistive companion (RC) form. The developed simulation model can be applied to virtually any centrifugal compressor. By interfacing with a composite system, such as a Brayton cycle gas turbine, or a fuel cell, the compressor dynamic performance can be evaluated. The surge line for the compressor can also be determined from the simulation results. Furthermore, the model presented here provides a valuable tool for evaluating the system performance as a function of various operating parameters.

  13. Dynamic procedure for filtered gyrokinetic simulations

    SciTech Connect

    Morel, P.; Banon Navarro, A.; Albrecht-Marc, M.; Carati, D.; Merz, F.; Goerler, T.; Jenko, F.

    2012-01-15

    Large eddy simulations (LES) of gyrokinetic plasma turbulence are investigated as interesting candidates to decrease the computational cost. A dynamic procedure is implemented in the gene code, allowing for dynamic optimization of the free parameters of the LES models (setting the amplitudes of dissipative terms). Employing such LES methods, one recovers the free energy and heat flux spectra obtained from highly resolved direct numerical simulations. Systematic comparisons are performed for different values of the temperature gradient and magnetic shear, parameters which are of prime importance in ion temperature gradient driven turbulence. Moreover, the degree of anisotropy of the problem, which can vary with parameters, can be adapted dynamically by the method that shows gyrokinetic large eddy simulation to be a serious candidate to reduce numerical cost of gyrokinetic solvers.

  14. Molecular dynamics simulations of substitutional diffusion

    DOE PAGES

    Zhou, Xiaowang; Jones, Reese E.; Gruber, Jacob

    2016-12-18

    In atomistic simulations, diffusion energy barriers are usually calculated for each atomic jump path using a nudged elastic band method. Practical materials often involve thousands of distinct atomic jump paths that are not known a priori. Hence, it is often preferred to determine an overall diffusion energy barrier and an overall pre-exponential factor from the Arrhenius equation constructed through molecular dynamics simulations of mean square displacement of the diffusion species at different temperatures. This approach has been well established for interstitial diffusion, but not for substitutional diffusion at the same confidence. Using In 0.1 Ga 0.9 N as an example,more » we have identified conditions where molecular dynamics simulations can be used to calculate highly converged Arrhenius plots for substitutional alloys. As a result, this may enable many complex diffusion problems to be easily and reliably studied in the future using molecular dynamics, provided that moderate computing resources are available.« less

  15. Molecular dynamics simulations of substitutional diffusion

    SciTech Connect

    Zhou, Xiaowang; Jones, Reese E.; Gruber, Jacob

    2016-12-18

    In atomistic simulations, diffusion energy barriers are usually calculated for each atomic jump path using a nudged elastic band method. Practical materials often involve thousands of distinct atomic jump paths that are not known a priori. Hence, it is often preferred to determine an overall diffusion energy barrier and an overall pre-exponential factor from the Arrhenius equation constructed through molecular dynamics simulations of mean square displacement of the diffusion species at different temperatures. This approach has been well established for interstitial diffusion, but not for substitutional diffusion at the same confidence. Using In 0.1 Ga 0.9 N as an example, we have identified conditions where molecular dynamics simulations can be used to calculate highly converged Arrhenius plots for substitutional alloys. As a result, this may enable many complex diffusion problems to be easily and reliably studied in the future using molecular dynamics, provided that moderate computing resources are available.

  16. Dynamic modeling and simulation of planetary rovers

    NASA Technical Reports Server (NTRS)

    Lindemann, Randel A.

    1992-01-01

    This paper documents a preliminary study into the dynamic modeling and computer simulation of wheeled surface vehicles. The research centered on the feasibility of using commercially available multibody dynamics codes running on engineering workstations to perform the analysis. The results indicated that physically representative vehicle mechanics can be modeled and simulated in state-of-the-art Computer Aided Engineering environments, but at excessive cost in modeling and computation time. The results lead to the recommendation for the development of an efficient rover mobility-specific software system. This system would be used for vehicle design and simulation in planetary environments; controls prototyping, design, and testing; as well as local navigation simulation and expectation planning.

  17. Choice of timestep in molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Fincham, David

    1986-06-01

    In molecular dynamics computer simulation of liquids it is important to use as large a timestep as possible in order to sample phase space rapidly and save on computer expense. The effect of the resulting algorithm errors in the trajectories of the molecules is not well understood. An empirical investigation into this question is reported. Several simulations differing only in the timestep used are compared. It is found that much larger timesteps than usual can be employed without producing significant errors in observed thermodynamic, structural or dynamic properties.

  18. Massively-Parallel Dislocation Dynamics Simulations

    SciTech Connect

    Cai, W; Bulatov, V V; Pierce, T G; Hiratani, M; Rhee, M; Bartelt, M; Tang, M

    2003-06-18

    Prediction of the plastic strength of single crystals based on the collective dynamics of dislocations has been a challenge for computational materials science for a number of years. The difficulty lies in the inability of the existing dislocation dynamics (DD) codes to handle a sufficiently large number of dislocation lines, in order to be statistically representative and to reproduce experimentally observed microstructures. A new massively-parallel DD code is developed that is capable of modeling million-dislocation systems by employing thousands of processors. We discuss the general aspects of this code that make such large scale simulations possible, as well as a few initial simulation results.

  19. Dynamic Fracture Simulations of Explosively Loaded Cylinders

    SciTech Connect

    Arthur, Carly W.; Goto, D. M.

    2015-11-30

    This report documents the modeling results of high explosive experiments investigating dynamic fracture of steel (AerMet® 100 alloy) cylinders. The experiments were conducted at Lawrence Livermore National Laboratory (LLNL) during 2007 to 2008 [10]. A principal objective of this study was to gain an understanding of dynamic material failure through the analysis of hydrodynamic computer code simulations. Two-dimensional and three-dimensional computational cylinder models were analyzed using the ALE3D multi-physics computer code.

  20. Dynamics modeling and simulation of flexible airships

    NASA Astrophysics Data System (ADS)

    Li, Yuwen

    The resurgence of airships has created a need for dynamics models and simulation capabilities of these lighter-than-air vehicles. The focus of this thesis is a theoretical framework that integrates the flight dynamics, structural dynamics, aerostatics and aerodynamics of flexible airships. The study begins with a dynamics model based on a rigid-body assumption. A comprehensive computation of aerodynamic effects is presented, where the aerodynamic forces and moments are categorized into various terms based on different physical effects. A series of prediction approaches for different aerodynamic effects are unified and applied to airships. The numerical results of aerodynamic derivatives and the simulated responses to control surface deflection inputs are verified by comparing to existing wind-tunnel and flight test data. With the validated aerodynamics and rigid-body modeling, the equations of motion of an elastic airship are derived by the Lagrangian formulation. The airship is modeled as a free-free Euler-Bernoulli beam and the bending deformations are represented by shape functions chosen as the free-free normal modes. In order to capture the coupling between the aerodynamic forces and the structural elasticity, local velocity on the deformed vehicle is used in the computation of aerodynamic forces. Finally, with the inertial, gravity, aerostatic and control forces incorporated, the dynamics model of a flexible airship is represented by a single set of nonlinear ordinary differential equations. The proposed model is implemented as a dynamics simulation program to analyze the dynamics characteristics of the Skyship-500 airship. Simulation results are presented to demonstrate the influence of structural deformation on the aerodynamic forces and the dynamics behavior of the airship. The nonlinear equations of motion are linearized numerically for the purpose of frequency domain analysis and for aeroelastic stability analysis. The results from the latter for the

  1. Dynamic simulation recalls condensate piping event

    SciTech Connect

    Farrell, R.J.; Reneberg, K.O. ); Moy, H.C. )

    1994-05-01

    This article describes how experience gained from simulating and reconstructing a condensate piping event will be used by Consolidated Edison to analyze control system problems. A cooperative effort by Con Edison and the Chemical Engineering Department at Polytechnic University used modular modeling system to investigate the probable cause of a Con Edison condensate piping event. Con Edison commissioned the work to serve as a case study for the more general problem of control systems analysis using dynamic simulation and MMS.

  2. Distortion and flow of nematics simulated by dissipative particle dynamics.

    PubMed

    Zhao, Tongyang; Wang, Xiaogong

    2014-05-14

    In this study, we simulated distortion and flow of nematics by dissipative particle dynamics (DPD). The nematics were modeled by a binary mixture that contained rigid rods composed of DPD particles as mesogenic units and normal DPD particles as solvent. Elastic distortions were investigated by monitoring director orientation in space under influences of boundary anchoring and external fields. Static distortion demonstrated by the simulation is consistent with the prediction of Frank elastic theory. Spatial distortion profile of the director was examined to obtain static elastic constants. Rotational motions of the director under influence of the external field were simulated to understand the dynamic process. The rules revealed by the simulation are in a good agreement with those obtained from dynamical experiments and classical theories for nematics. Three Miesowicz viscosities were obtained by using external fields to hold the orientation of the rods in shear flows. The simulation showed that the Miesowicz viscosities have the order of ηc > ηa > ηb and the rotational viscosity γ1 is about two orders larger than the Miesowicz viscosity ηb. The DPD simulation correctly reproduced the non-monotonic concentration dependence of viscosity, which is a unique property of lyotropic nematic fluids. By comparing simulation results with classical theories for nematics and experiments, the DPD nematic fluids are proved to be a valid model to investigate the distortion and flow of lyotropic nematics.

  3. Insights from molecular dynamics simulations for computational protein design.

    PubMed

    Childers, Matthew Carter; Daggett, Valerie

    2017-02-01

    A grand challenge in the field of structural biology is to design and engineer proteins that exhibit targeted functions. Although much success on this front has been achieved, design success rates remain low, an ever-present reminder of our limited understanding of the relationship between amino acid sequences and the structures they adopt. In addition to experimental techniques and rational design strategies, computational methods have been employed to aid in the design and engineering of proteins. Molecular dynamics (MD) is one such method that simulates the motions of proteins according to classical dynamics. Here, we review how insights into protein dynamics derived from MD simulations have influenced the design of proteins. One of the greatest strengths of MD is its capacity to reveal information beyond what is available in the static structures deposited in the Protein Data Bank. In this regard simulations can be used to directly guide protein design by providing atomistic details of the dynamic molecular interactions contributing to protein stability and function. MD simulations can also be used as a virtual screening tool to rank, select, identify, and assess potential designs. MD is uniquely poised to inform protein design efforts where the application requires realistic models of protein dynamics and atomic level descriptions of the relationship between dynamics and function. Here, we review cases where MD simulations was used to modulate protein stability and protein function by providing information regarding the conformation(s), conformational transitions, interactions, and dynamics that govern stability and function. In addition, we discuss cases where conformations from protein folding/unfolding simulations have been exploited for protein design, yielding novel outcomes that could not be obtained from static structures.

  4. Numerical simulation of interplanetary dynamics

    NASA Astrophysics Data System (ADS)

    Wu, Chin-Chun

    This dissertation discusses investigations into the physics of the propagation of solar generated disturbances in the interplanetary medium. The motivation to initiate this study was two-fold: (1) understanding the fundamental physics of the nonlinear interactions of solar generated MHD shocks and non-homogeneous interplanetary medium, and (2) understanding the physics of solar generated disturbance effects on the Earth's environment, (i.e. the solar connection to the geomagnetic storm). In order to achieve these goals, the authors employed two numerical models to encompass these studies. In the first part, a one-dimensional MHD code with adaptive grids is used to study the evolution of interplanetary slow shocks (ISS), the interaction of a forward slow shock with a reverse slow shock, and the interaction of a fast shock with a slow shock. Results show that the slow shocks can be generated by a decreasing density, velocity or temperature perturbation or by a pressure pulse by following a forward fast shock and that slow shocks can propagate over 1 AU; results also show that the ISS never evolves into fast shocks. Interestingly, it is also found that an ISS could be 'eaten up' by an interplanetary fast shock (IFS) catching up from behind. This could be a reason that the slow shock has been difficult to observe near 1 AU. In addition, a forward slow shock could be dissipated by following a strong forward fast shock (Mach number greater than 1.7). In the second part, a fully three-dimensional (3D), time-dependent, MHD interplanetary global model (3D IGM) is used to study the relationship between different forms of solar activity and transient variations of the north-south component, Bx, of the interplanetary magnetic field, IMF, at 1 AU. One form of solar activity, the flare, is simulated by using a pressure pulse at different locations near the solar surface and observing the simulated IMF evolution of Btheta (= -Bx) at 1 AU. Results show that, for a given pressure

  5. Charge-dependent conformations and dynamics of pamam dendrimers revealed by neutron scattering and molecular dynamics

    NASA Astrophysics Data System (ADS)

    Wu, Bin

    spatial instrumental scales, understanding experimental results involves extensive and difficult data analysis based on liquid theory and condensed matter physics. Therefore, a model that successfully describes the inter- and intra-dendrimer correlations is crucial in obtaining and delivering reliable information. On the other hand, making meaningful comparisons between molecular dynamics and neutron scattering is a fundamental challenge to link simulations and experiments at the nano-scale. This challenge stems from our approach to utilize MD simulation to explain the underlying mechanism of experimental observation. The SANS measurements were conducted on a series of SANS spectrometers including the Extended Q-Range Small-Angle Neutron Scattering Diffractometer (EQ-SANS) and the General-Purpose Small-Angle Neutron Scattering Diffractometer (GP-SANS) at the Oak Ridge National Laboratory (ORNL), and NG7 Small Angle Neutron Scattering Spectrometer at National Institute of Standards (NIST) and Technology in U.S.A., large dynamic range small-angle diffractometer D22 at Institut Laue-Langevin (ILL) in France, and 40m-SANS Spectrometer at Korea Atomic Energy Research Institute (KAERI) in Korea. On the other hand, the Amber molecular dynamics simulation package is utilized to carry out the computational study. In this dissertation, the following observations have been revealed. The previously developed theoretical model for polyelectrolyte dendrimers are adopted to analyze SANS measurements and superb model fitting quality is found. Coupling with advanced contrast variation small angle neutron scattering (CVSANS) data analysis scheme reported recently, the intra-dendrimer hydration and hydrocarbon components distributions are revealed experimentally. The results indeed indicate that the maximum density is located in the molecular center rather than periphery, which is consistent to previous SANS studies and the back-folding picture of PAMAM dendrimers. According to this picture

  6. Molecular dynamic simulations of ocular tablet dissolution.

    PubMed

    Ru, Qian; Fadda, Hala M; Li, Chung; Paul, Daniel; Khaw, Peng T; Brocchini, Steve; Zloh, Mire

    2013-11-25

    Small tablets for implantation into the subconjunctival space in the eye are being developed to inhibit scarring after glaucoma filtration surgery (GFS). There is a need to evaluate drug dissolution at the molecular level to determine how the chemical structure of the active may correlate with dissolution in the nonsink conditions of the conjunctival space. We conducted molecular dynamics simulations to study the dissolution process of tablets derived from two drugs that can inhibit fibrosis after GFS, 5-fluorouracil (5-FU) and the matrix metalloprotease inhibitor (MMPi), ilomastat. The dissolution was simulated in the presence of simple point charge (SPC) water molecules, and the liquid turnover of the aqueous humor in the subconjunctival space was simulated by removal of the dissolved drug molecules at regular intervals and replacement by new water molecules. At the end of the simulation, the total molecular solvent accessible surface area of 5-FU tablets increased by 60 times more than that of ilomastat as a result of tablet swelling and release of molecules into solution. The tablet dissolution pattern shown in our molecular dynamic simulations tends to correlate with experimental release profiles. This work indicates that a series of molecular dynamic simulations can be used to predict the influence of the molecular properties of a drug on its dissolution profile and could be useful during preformulation where sufficient amounts of the drug are not always available to perform dissolution studies.

  7. Quantum Simulation for Open-System Dynamics

    NASA Astrophysics Data System (ADS)

    Wang, Dong-Sheng; de Oliveira, Marcos Cesar; Berry, Dominic; Sanders, Barry

    2013-03-01

    Simulations are essential for predicting and explaining properties of physical and mathematical systems yet so far have been restricted to classical and closed quantum systems. Although forays have been made into open-system quantum simulation, the strict algorithmic aspect has not been explored yet is necessary to account fully for resource consumption to deliver bounded-error answers to computational questions. An open-system quantum simulator would encompass classical and closed-system simulation and also solve outstanding problems concerning, e.g. dynamical phase transitions in non-equilibrium systems, establishing long-range order via dissipation, verifying the simulatability of open-system dynamics on a quantum Turing machine. We construct an efficient autonomous algorithm for designing an efficient quantum circuit to simulate many-body open-system dynamics described by a local Hamiltonian plus decoherence due to separate baths for each particle. The execution time and number of gates for the quantum simulator both scale polynomially with the system size. DSW funded by USARO. MCO funded by AITF and Brazilian agencies CNPq and FAPESP through Instituto Nacional de Ciencia e Tecnologia-Informacao Quantica (INCT-IQ). DWB funded by ARC Future Fellowship (FT100100761). BCS funded by AITF, CIFAR, NSERC and USARO.

  8. The [Lys(-2)-Arg(-1)-des(17-21)]-endothelin-1 peptide retains the specific Arg(-1)-Asp8 salt bridge but reveals discrepancies between NMR data and molecular dynamics simulations.

    PubMed

    Kaas, Quentin; Aumelas, André; Kubo, Shigeru; Chino, Naoyoshi; Kobayashi, Yuji; Chiche, Laurent

    2002-09-17

    The [des(17-21)]-endothelin-1 (CSH-ET) and [Lys(-)(2)-Arg(-)(1)-des(17-21)]-endothelin-1 (KR-CSH-ET) peptides, designed by removing the five-residue hydrophobic tail from the endothelin-1 (ET-1) and [Lys(-)(2)-Arg(-)(1)]-endothelin-1 (KR-ET-1) peptides, respectively, were synthesized. Previous studies on KR-ET-1 showed that, in contrast to ET-1, this engineered compound displays a pH-dependent conformational change related to the formation of a stabilizing salt bridge between the Arg(-)(1) and Asp(8) side chains. CD and NMR spectra indicate that CSH-ET and KR-CSH-ET display conformational behavior similar to those of ET-1 and KR-ET-1, respectively. The short salt bridge-stabilized KR-CSH-ET peptide therefore appears to be an attractive elementary scaffold for drug design. The solution structure of the salt-bridged form of KR-CSH-ET was determined by NMR at pH 4.5 and is very similar to the corresponding form of the parent KR-ET-1 peptide. Molecular dynamics simulations of the salt-bridged form of KR-CSH-ET were performed using both the GB/SA implicit solvation scheme or an explicit solvation and the particle-mesh Ewald method for long-range electrostatic calculation. Unexpectedly, the Arg(-)(1)-Asp(8) salt bridge does not display in the simulation the stability that could be expected from the experimental data. The cooperative involvement of a cation-pi interaction in formation of the salt bridge has been hypothesized. Difficulties in accurately simulating cation-pi interactions might be responsible for the lack of stability in the simulation. At this time, however, no definitive explanation for the observed discrepancy between experiments and simulations is available, and further experimental studies appear to be necessary to fully understand in atomic detail the pH-dependent conformational change observed in the KR-ET-1 series.

  9. Airborne Simulation of Launch Vehicle Dynamics

    NASA Technical Reports Server (NTRS)

    Miller, Christopher J.; Orr, Jeb S.; Hanson, Curtis E.; Gilligan, Eric T.

    2015-01-01

    In this paper we present a technique for approximating the short-period dynamics of an exploration-class launch vehicle during flight test with a high-performance surrogate aircraft in relatively benign endoatmospheric flight conditions. The surrogate vehicle relies upon a nonlinear dynamic inversion scheme with proportional-integral feedback to drive a subset of the aircraft states into coincidence with the states of a time-varying reference model that simulates the unstable rigid body dynamics, servodynamics, and parasitic elastic and sloshing dynamics of the launch vehicle. The surrogate aircraft flies a constant pitch rate trajectory to approximate the boost phase gravity turn ascent, and the aircraft's closed-loop bandwidth is sufficient to simulate the launch vehicle's fundamental lateral bending and sloshing modes by exciting the rigid body dynamics of the aircraft. A novel control allocation scheme is employed to utilize the aircraft's relatively fast control effectors in inducing various failure modes for the purposes of evaluating control system performance. Sufficient dynamic similarity is achieved such that the control system under evaluation is configured for the full-scale vehicle with no changes to its parameters, and pilot-control system interaction studies can be performed to characterize the effects of guidance takeover during boost. High-fidelity simulation and flight-test results are presented that demonstrate the efficacy of the design in simulating the Space Launch System (SLS) launch vehicle dynamics using the National Aeronautics and Space Administration (NASA) Armstrong Flight Research Center Fullscale Advanced Systems Testbed (FAST), a modified F/A-18 airplane (McDonnell Douglas, now The Boeing Company, Chicago, Illinois), over a range of scenarios designed to stress the SLS's Adaptive Augmenting Control (AAC) algorithm.

  10. Airborne Simulation of Launch Vehicle Dynamics

    NASA Technical Reports Server (NTRS)

    Gilligan, Eric T.; Miller, Christopher J.; Hanson, Curtis E.; Orr, Jeb S.

    2014-01-01

    In this paper we present a technique for approximating the short-period dynamics of an exploration-class launch vehicle during flight test with a high-performance surrogate aircraft in relatively benign endoatmospheric flight conditions. The surrogate vehicle relies upon a nonlinear dynamic inversion scheme with proportional-integral feedback to drive a subset of the aircraft states into coincidence with the states of a time-varying reference model that simulates the unstable rigid body dynamics, servodynamics, and parasitic elastic and sloshing dynamics of the launch vehicle. The surrogate aircraft flies a constant pitch rate trajectory to approximate the boost phase gravity-turn ascent, and the aircraft's closed-loop bandwidth is sufficient to simulate the launch vehicle's fundamental lateral bending and sloshing modes by exciting the rigid body dynamics of the aircraft. A novel control allocation scheme is employed to utilize the aircraft's relatively fast control effectors in inducing various failure modes for the purposes of evaluating control system performance. Sufficient dynamic similarity is achieved such that the control system under evaluation is optimized for the full-scale vehicle with no changes to its parameters, and pilot-control system interaction studies can be performed to characterize the effects of guidance takeover during boost. High-fidelity simulation and flight test results are presented that demonstrate the efficacy of the design in simulating the Space Launch System (SLS) launch vehicle dynamics using NASA Dryden Flight Research Center's Full-scale Advanced Systems Testbed (FAST), a modified F/A-18 airplane, over a range of scenarios designed to stress the SLS's adaptive augmenting control (AAC) algorithm.

  11. Revealing the Effects of Cognitive Education Programmes through Dynamic Assessment

    ERIC Educational Resources Information Center

    Tzuriel, David

    2011-01-01

    The major objective of this paper is to demonstrate the effectiveness of dynamic assessment (DA) in revealing outcomes of cognitive education programmes. Three programmes based on "mediated learning experience" theory are reviewed: "Feuerstein's Instrumental Enrichment", "Bright Start", and "Peer Mediation with…

  12. Multiscale model approach for magnetization dynamics simulations

    NASA Astrophysics Data System (ADS)

    De Lucia, Andrea; Krüger, Benjamin; Tretiakov, Oleg A.; Kläui, Mathias

    2016-11-01

    Simulations of magnetization dynamics in a multiscale environment enable the rapid evaluation of the Landau-Lifshitz-Gilbert equation in a mesoscopic sample with nanoscopic accuracy in areas where such accuracy is required. We have developed a multiscale magnetization dynamics simulation approach that can be applied to large systems with spin structures that vary locally on small length scales. To implement this, the conventional micromagnetic simulation framework has been expanded to include a multiscale solving routine. The software selectively simulates different regions of a ferromagnetic sample according to the spin structures located within in order to employ a suitable discretization and use either a micromagnetic or an atomistic model. To demonstrate the validity of the multiscale approach, we simulate the spin wave transmission across the regions simulated with the two different models and different discretizations. We find that the interface between the regions is fully transparent for spin waves with frequency lower than a certain threshold set by the coarse scale micromagnetic model with no noticeable attenuation due to the interface between the models. As a comparison to exact analytical theory, we show that in a system with a Dzyaloshinskii-Moriya interaction leading to spin spirals, the simulated multiscale result is in good quantitative agreement with the analytical calculation.

  13. Simulating Dynamic Equilibria: A Class Experiment

    NASA Astrophysics Data System (ADS)

    Harrison, John A.; Buckley, Paul D.

    2000-08-01

    A first-order reversible reaction is simulated on an overhead projector using small coins or discs. A simulation is carried out in which initially there are 24 discs representing reactant A and none representing reactant B. At the end of each minute half of the reactant A discs get converted to reactant B, and one quarter of the reactant B discs get converted to reactant A discs. Equilibrium is established with 8 A discs and 16 B discs, and no further net change is observed as the simulation continues. Another simulation beginning with 48 A discs and 0 B discs leads at equilibrium to 16 A discs and 32 B discs. These results illustrate how dynamic equilibria are established and allow the introduction of the concept of an equilibrium constant. Le Châtelier's principle is illustrated by further simulations.

  14. Dynamic simulation of a reverse Brayton refrigerator

    SciTech Connect

    Peng, N.; Xiong, L. Y.; Dong, B.; Liu, L. Q.; Lei, L. L.; Tang, J. C.

    2014-01-29

    A test refrigerator based on the modified Reverse Brayton cycle has been developed in the Chinese Academy of Sciences recently. To study the behaviors of this test refrigerator, a dynamic simulation has been carried out. The numerical model comprises the typical components of the test refrigerator: compressor, valves, heat exchangers, expander and heater. This simulator is based on the oriented-object approach and each component is represented by a set of differential and algebraic equations. The control system of the test refrigerator is also simulated, which can be used to optimize the control strategies. This paper describes all the models and shows the simulation results. Comparisons between simulation results and experimental data are also presented. Experimental validation on the test refrigerator gives satisfactory results.

  15. Digital simulation of stiff linear dynamic systems.

    NASA Technical Reports Server (NTRS)

    Holland, L. D.; Walsh, J. R., Jr.; Kerr, J. H.

    1972-01-01

    A method is derived for digital computer simulation of linear time-invariant systems when the insignificant eigenvalues involved in such systems are eliminated by an ALSAP root removal technique. The method is applied to a thirteenth-order dynamic system representing a passive RLC network.

  16. Dynamics Simulation of Langmuir-Blodgett Films

    DTIC Science & Technology

    1990-04-01

    of water. During the dynamics simulation, theposition of the water molecules are frozen. A 1515 edge effect as shown in Fig. 4: the tilts for...temperature, I.e. 300K, by gradually assigning random understand. The strong edge effect makes it necessary to iintroduce periodic boundaries In future

  17. Molecular dynamics simulations of magnetized dusty plasmas

    NASA Astrophysics Data System (ADS)

    Piel, Alexander; Reichstein, Torben; Wilms, Jochen

    2012-10-01

    The combination of the electric field that confines a dust cloud with a static magnetic field generally leads to a rotation of the dust cloud. In weak magnetic fields, the Hall component of the ion flow exerts a drag force that sets the dust in rotation. We have performed detailed molecular-dynamics simulations of the dynamics of torus-shaped dust clouds in anodic plasmas. The stationary flow [1] is characterized by a shell structure in the laminar dust flow and by the spontaneous formation of a shear-flow around a stationary vortex. Here we present new results on dynamic phenomena, among them fluctuations due to a Kelvin-Helmholtz instability in the shear-flow. The simulations are compared with experimental results. [4pt] [1] T. Reichstein, A. Piel, Phys. Plasmas 18, 083705 (2011)

  18. Simulations reveal increased fluctuations in estrogen receptor-alpha conformation upon antagonist binding.

    PubMed

    Ng, Ho Leung

    2016-09-01

    Molecular dynamics (MD) simulations have been used to model dynamic fluctuations in the structure of estrogen receptor-alpha (ER-α) upon binding to the natural agonist 17β-estradiol (E2) and to the active metabolite of the breast cancer drug and antagonist, 4-hydroxytamoxifen (OHT). We present the most extensive MD simulations to date of ER-α, with over 1μs of combined simulations for the monomer and dimer forms. Simulations reveal that the antagonist-bound complex includes significant fluctuations while the agonist-bound complex is tightly restrained. OHT increases dynamic disorder in the loops located to either side of the tail H12 helix; H12 has been associated with the activation status of ER-α. We also report that fluctuations near H12 lead to greater conformational variation in the binding mode of the ethylamine tail of OHT. Both the agonist and antagonist conformations are stable throughout the 240ns simulations, supporting the hypothesis that there are no transitions between these two states or into intermediate states. The stable position of H12 in the OHT-bound conformation suggests that OHT stabilizes a well-defined antagonist conformational ensemble rather than merely blocking the agonist-driven activation of ER-α. Simultaneously, the increased dynamic properties of the OHT-bound complex is a potential source of binding entropy.

  19. Simulation of NMR data reveals that proteins' local structures are stabilized by electronic polarization.

    PubMed

    Tong, Yan; Ji, Chang G; Mei, Ye; Zhang, John Z H

    2009-06-24

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

  20. Test of a flexible spacecraft dynamics simulator

    NASA Technical Reports Server (NTRS)

    Dichmann, Donald; Sedlak, Joseph

    1998-01-01

    There are a number of approaches one can take to modeling the dynamics of a flexible body. While one can attempt to capture the full dynamical behavior subject to disturbances from actuators and environmental torques, such a detailed description often is unnecessary. Simplification is possible either by limiting the amplitude of motion to permit linearization of the dynamics equations or by restricting the types of allowed motion. In this work, we study the nonlinear dynamics of bending deformations of wire booms on spinning spacecraft. The theory allows for large amplitude excursions from equilibrium while enforcing constraints on the dynamics to prohibit those modes that are physically less relevant or are expected to damp out fast. These constraints explicitly remove the acoustic modes (i.e., longitudinal sound waves and shear waves) while allowing for arbitrary bending and twisting, motions which typically are of lower frequency. As a test case, a spin axis reorientation maneuver by the Polar Plasma Laboratory (POLAR) spacecraft has been simulated. POLAR was chosen as a representative spacecraft because it has flexible wire antennas that extend to a length of 65 meters. Bending deformations in these antennas could be quite large and have a significant effect on the attitude dynamics of the spacecraft body. Summary results from the simulation are presented along, with a comparison with POLAR flight data.

  1. GROSS- GAMMA RAY OBSERVATORY ATTITUDE DYNAMICS SIMULATOR

    NASA Technical Reports Server (NTRS)

    Garrick, J.

    1994-01-01

    The Gamma Ray Observatory (GRO) spacecraft will constitute a major advance in gamma ray astronomy by offering the first opportunity for comprehensive observations in the range of 0.1 to 30,000 megaelectronvolts (MeV). The Gamma Ray Observatory Attitude Dynamics Simulator, GROSS, is designed to simulate this mission. The GRO Dynamics Simulator consists of three separate programs: the Standalone Profile Program; the Simulator Program, which contains the Simulation Control Input/Output (SCIO) Subsystem, the Truth Model (TM) Subsystem, and the Onboard Computer (OBC) Subsystem; and the Postprocessor Program. The Standalone Profile Program models the environment of the spacecraft and generates a profile data set for use by the simulator. This data set contains items such as individual external torques; GRO spacecraft, Tracking and Data Relay Satellite (TDRS), and solar and lunar ephemerides; and star data. The Standalone Profile Program is run before a simulation. The SCIO subsystem is the executive driver for the simulator. It accepts user input, initializes parameters, controls simulation, and generates output data files and simulation status display. The TM subsystem models the spacecraft dynamics, sensors, and actuators. It accepts ephemerides, star data, and environmental torques from the Standalone Profile Program. With these and actuator commands from the OBC subsystem, the TM subsystem propagates the current state of the spacecraft and generates sensor data for use by the OBC and SCIO subsystems. The OBC subsystem uses sensor data from the TM subsystem, a Kalman filter (for attitude determination), and control laws to compute actuator commands to the TM subsystem. The OBC subsystem also provides output data to the SCIO subsystem for output to the analysts. The Postprocessor Program is run after simulation is completed. It generates printer and CRT plots and tabular reports of the simulated data at the direction of the user. GROSS is written in FORTRAN 77 and

  2. GROSS- GAMMA RAY OBSERVATORY ATTITUDE DYNAMICS SIMULATOR

    NASA Technical Reports Server (NTRS)

    Garrick, J.

    1994-01-01

    The Gamma Ray Observatory (GRO) spacecraft will constitute a major advance in gamma ray astronomy by offering the first opportunity for comprehensive observations in the range of 0.1 to 30,000 megaelectronvolts (MeV). The Gamma Ray Observatory Attitude Dynamics Simulator, GROSS, is designed to simulate this mission. The GRO Dynamics Simulator consists of three separate programs: the Standalone Profile Program; the Simulator Program, which contains the Simulation Control Input/Output (SCIO) Subsystem, the Truth Model (TM) Subsystem, and the Onboard Computer (OBC) Subsystem; and the Postprocessor Program. The Standalone Profile Program models the environment of the spacecraft and generates a profile data set for use by the simulator. This data set contains items such as individual external torques; GRO spacecraft, Tracking and Data Relay Satellite (TDRS), and solar and lunar ephemerides; and star data. The Standalone Profile Program is run before a simulation. The SCIO subsystem is the executive driver for the simulator. It accepts user input, initializes parameters, controls simulation, and generates output data files and simulation status display. The TM subsystem models the spacecraft dynamics, sensors, and actuators. It accepts ephemerides, star data, and environmental torques from the Standalone Profile Program. With these and actuator commands from the OBC subsystem, the TM subsystem propagates the current state of the spacecraft and generates sensor data for use by the OBC and SCIO subsystems. The OBC subsystem uses sensor data from the TM subsystem, a Kalman filter (for attitude determination), and control laws to compute actuator commands to the TM subsystem. The OBC subsystem also provides output data to the SCIO subsystem for output to the analysts. The Postprocessor Program is run after simulation is completed. It generates printer and CRT plots and tabular reports of the simulated data at the direction of the user. GROSS is written in FORTRAN 77 and

  3. Accelerated molecular dynamics simulations of protein folding.

    PubMed

    Miao, Yinglong; Feixas, Ferran; Eun, Changsun; McCammon, J Andrew

    2015-07-30

    Folding of four fast-folding proteins, including chignolin, Trp-cage, villin headpiece and WW domain, was simulated via accelerated molecular dynamics (aMD). In comparison with hundred-of-microsecond timescale conventional molecular dynamics (cMD) simulations performed on the Anton supercomputer, aMD captured complete folding of the four proteins in significantly shorter simulation time. The folded protein conformations were found within 0.2-2.1 Å of the native NMR or X-ray crystal structures. Free energy profiles calculated through improved reweighting of the aMD simulations using cumulant expansion to the second-order are in good agreement with those obtained from cMD simulations. This allows us to identify distinct conformational states (e.g., unfolded and intermediate) other than the native structure and the protein folding energy barriers. Detailed analysis of protein secondary structures and local key residue interactions provided important insights into the protein folding pathways. Furthermore, the selections of force fields and aMD simulation parameters are discussed in detail. Our work shows usefulness and accuracy of aMD in studying protein folding, providing basic references in using aMD in future protein-folding studies. © 2015 Wiley Periodicals, Inc.

  4. Mesoscopic Simulation Methods for Polymer Dynamics

    NASA Astrophysics Data System (ADS)

    Larson, Ronald

    2015-03-01

    We assess the accuracy and efficiency of mesoscopic simulation methods, namely Brownian Dynamics (BD), Stochastic Rotation Dynamics (SRD) and Dissipative Particle Dynamics (DPD), for polymers in solution at equilibrium and in flows in microfluidic geometries. Both SRD and DPD use solvent ``particles'' to carry momentum, and so account automatically for hydrodynamic interactions both within isolated polymer coils, and with other polymer molecules and with nearby solid boundaries. We assess quantitatively the effects of artificial particle inertia and fluid compressibility and show that they can be made small with appropriate choice of simulation parameters. We then use these methods to study flow-induced migration of polymer chains produced by: 1) hydrodynamic interactions, 2) streamline curvature or stress-gradients, and 3) convection of wall depletion zones. We show that huge concentration gradients can be produced by these mechanisms in microfluidic geometries that can be exploited for separation of polymers by size in periodic contraction-expansion geometries. We also assess the range of conditions for which BD, SRD or DPD is preferable for mesoscopic simulations. Finally, we show how such methods can be used to simulate quantitatively the swimming of micro-organisms such as E. coli. In collaboration with Lei Jiang and Tongyang Zhao, University of Michigan, Ann Arbor, MI.

  5. The fractional-nonlinear robotic manipulator: Modeling and dynamic simulations

    NASA Astrophysics Data System (ADS)

    David, S. A.; Balthazar, J. M.; Julio, B. H. S.; Oliveira, C.

    2012-11-01

    In this paper, we applied the Riemann-Liouville approach and the fractional Euler-Lagrange equations in order to obtain the fractional-order nonlinear dynamics equations of a two link robotic manipulator. The aformentioned equations have been simulated for several cases involving: integer and non-integer order analysis, with and without external forcing acting and some different initial conditions. The fractional nonlinear governing equations of motion are coupled and the time evolution of the angular positions and the phase diagrams have been plotted to visualize the effect of fractional order approach. The new contribution of this work arises from the fact that the dynamics equations of a two link robotic manipulator have been modeled with the fractional Euler-Lagrange dynamics approach. The results reveal that the fractional-nonlinear robotic manipulator can exhibit different and curious behavior from those obtained with the standard dynamical system and can be useful for a better understanding and control of such nonlinear systems.

  6. Dynamical fingerprints for probing individual relaxation processes in biomolecular dynamics with simulations and kinetic experiments

    SciTech Connect

    Noe, F; Diadone, Isabella; Lollmann, Marc; Sauer, Marcus; Chondera, John D; Smith, Jeremy C

    2011-01-01

    There is a gap between kinetic experiment and simulation in their views of the dynamics of complex biomolecular systems. Whereas experiments typically reveal only a few readily discernible exponential relaxations, simulations often indicate complex multistate behavior. Here, a theoretical framework is presented that reconciles these two approaches. The central concept is dynamical fingerprints which contain peaks at the time scales of the dynamical processes involved with amplitudes determined by the experimental observable. Fingerprints can be generated from both experimental and simulation data, and their comparison by matching peaks permits assignment of structural changes present in the simulation to experimentally observed relaxation processes. The approach is applied here to a test case interpreting single molecule fluorescence correlation spectroscopy experiments on a set of fluorescent peptides with molecular dynamics simulations. The peptides exhibit complex kinetics shown to be consistent with the apparent simplicity of the experimental data. Moreover, the fingerprint approach can be used to design new experiments with site-specific labels that optimally probe specific dynamical processes in the molecule under investigation.

  7. Dynamic Multicore Processing for Pandemic Influenza Simulation

    PubMed Central

    Eriksson, Henrik; Timpka, Toomas; Spreco, Armin; Dahlström, Örjan; Strömgren, Magnus; Holm, Einar

    2016-01-01

    Pandemic simulation is a useful tool for analyzing outbreaks and exploring the impact of variations in disease, population, and intervention models. Unfortunately, this type of simulation can be quite time-consuming especially for large models and significant outbreaks, which makes it difficult to run the simulations interactively and to use simulation for decision support during ongoing outbreaks. Improved run-time performance enables new applications of pandemic simulations, and can potentially allow decision makers to explore different scenarios and intervention effects. Parallelization of infection-probability calculations and multicore architectures can take advantage of modern processors to achieve significant run-time performance improvements. However, because of the varying computational load during each simulation run, which originates from the changing number of infectious persons during the outbreak, it is not useful to us the same multicore setup during the simulation run. The best performance can be achieved by dynamically changing the use of the available processor cores to balance the overhead of multithreading with the performance gains of parallelization. PMID:28269849

  8. Topological structure dynamics revealing collective evolution in active nematics.

    PubMed

    Shi, Xia-qing; Ma, Yu-qiang

    2013-01-01

    Topological defects frequently emerge in active matter like bacterial colonies, cytoskeleton extracts on substrates, self-propelled granular or colloidal layers and so on, but their dynamical properties and the relations to large-scale organization and fluctuations in these active systems are seldom touched. Here we reveal, through a simple model for active nematics using self-driven hard elliptic rods, that the excitation, annihilation and transportation of topological defects differ markedly from those in non-active media. These dynamical processes exhibit strong irreversibility in active nematics in the absence of detailed balance. Moreover, topological defects are the key factors in organizing large-scale dynamic structures and collective flows, resulting in multi-spatial temporal effects. These findings allow us to control the self-organization of active matter through topological structures.

  9. Lipid Clustering Correlates with Membrane Curvature as Revealed by Molecular Simulations of Complex Lipid Bilayers

    PubMed Central

    Koldsø, Heidi; Shorthouse, David; Hélie, Jean; Sansom, Mark S. P.

    2014-01-01

    Cell membranes are complex multicomponent systems, which are highly heterogeneous in the lipid distribution and composition. To date, most molecular simulations have focussed on relatively simple lipid compositions, helping to inform our understanding of in vitro experimental studies. Here we describe on simulations of complex asymmetric plasma membrane model, which contains seven different lipids species including the glycolipid GM3 in the outer leaflet and the anionic lipid, phosphatidylinositol 4,5-bisphophate (PIP2), in the inner leaflet. Plasma membrane models consisting of 1500 lipids and resembling the in vivo composition were constructed and simulations were run for 5 µs. In these simulations the most striking feature was the formation of nano-clusters of GM3 within the outer leaflet. In simulations of protein interactions within a plasma membrane model, GM3, PIP2, and cholesterol all formed favorable interactions with the model α-helical protein. A larger scale simulation of a model plasma membrane containing 6000 lipid molecules revealed correlations between curvature of the bilayer surface and clustering of lipid molecules. In particular, the concave (when viewed from the extracellular side) regions of the bilayer surface were locally enriched in GM3. In summary, these simulations explore the nanoscale dynamics of model bilayers which mimic the in vivo lipid composition of mammalian plasma membranes, revealing emergent nanoscale membrane organization which may be coupled both to fluctuations in local membrane geometry and to interactions with proteins. PMID:25340788

  10. Lipid clustering correlates with membrane curvature as revealed by molecular simulations of complex lipid bilayers.

    PubMed

    Koldsø, Heidi; Shorthouse, David; Hélie, Jean; Sansom, Mark S P

    2014-10-01

    Cell membranes are complex multicomponent systems, which are highly heterogeneous in the lipid distribution and composition. To date, most molecular simulations have focussed on relatively simple lipid compositions, helping to inform our understanding of in vitro experimental studies. Here we describe on simulations of complex asymmetric plasma membrane model, which contains seven different lipids species including the glycolipid GM3 in the outer leaflet and the anionic lipid, phosphatidylinositol 4,5-bisphophate (PIP2), in the inner leaflet. Plasma membrane models consisting of 1500 lipids and resembling the in vivo composition were constructed and simulations were run for 5 µs. In these simulations the most striking feature was the formation of nano-clusters of GM3 within the outer leaflet. In simulations of protein interactions within a plasma membrane model, GM3, PIP2, and cholesterol all formed favorable interactions with the model α-helical protein. A larger scale simulation of a model plasma membrane containing 6000 lipid molecules revealed correlations between curvature of the bilayer surface and clustering of lipid molecules. In particular, the concave (when viewed from the extracellular side) regions of the bilayer surface were locally enriched in GM3. In summary, these simulations explore the nanoscale dynamics of model bilayers which mimic the in vivo lipid composition of mammalian plasma membranes, revealing emergent nanoscale membrane organization which may be coupled both to fluctuations in local membrane geometry and to interactions with proteins.

  11. Kinetic dynamics simulation of the detached plasma

    NASA Astrophysics Data System (ADS)

    Pianpanit, Theerasarn; Ishiguro, Seiji; Hasegawa, Hiroki

    2015-11-01

    The detached plasma has been proposed to reduce the heat flux to the divertor. Fluid code has been widely used to investigate the detached plasma but the cooling of plasma, trapped particle effects, and other kinetic dynamics in the detached plasma has not been well understood. Particle-in-Cell (PIC) simulation with the Monte Carlo collisions and the cumulative scattering angle coulomb collision are carried out to study dynamical kinetic behavior of the plasma. The constant pressure and temperature of neutral gas box in front of the divertor target model has been used in the simulation. The results show the decrease in electron temperature in front of the divertor plate strongly relate to the Coulomb collision frequency.

  12. Brownian dynamics simulations of amelogenin microribbons formation

    NASA Astrophysics Data System (ADS)

    Li, Wei; Perez Lopez, Anthony; Liu, Ya; Chakrabarti, Amit; Gunton, James

    2011-03-01

    Recent advances in chemical particle synthesis have emphasized the fundamental role of surface colloidal heterogeneities and their detailed chemical composition, which is particularly significant for an important subclass of colloidal systems, namely, proteins. Recently, the process of self-assembly of amelogenin monomers with a hydrophobic/hydrophilic bipolar nature into ordered ribbon structures has been studied experimentally. In this work, we study this dynamical process by means of a Brownian dynamic simulation of a simple model which represents the bipolar character of the globular amelogenin molecule and the hydrophilic C-terminal tail. We monitor the kinetics of self-assembly through a study of the structure factor. We also calculate the phase diagram of the model using Gibbs ensemble Monte Carlo simulation and thermodynamic perturbation theory. This work is supported by grants from the NSF and Mathers Foundation.

  13. Fluctuation power spectra reveal dynamical heterogeneity of peptides

    NASA Astrophysics Data System (ADS)

    Khatri, Bhavin; Yew, Zu Thur; Krivov, Sergei; McLeish, Tom; Paci, Emanuele

    2010-07-01

    Characterizing the conformational properties and dynamics of biopolymers and their relation to biological activity and function is an ongoing challenge. Single molecule techniques have provided a rich experimental window on these properties, yet they have often relied on simple one-dimensional projections of a multidimensional free energy landscape for a practical interpretation of the results. Here, we study three short peptides with different structural propensity (α helical, β hairpin, and random coil) in the presence (or absence) of a force applied to their ends using Langevin dynamics simulation and an all-atom model with implicit solvation. Each peptide produces fluctuation power spectra with a characteristic dynamic fingerprint consistent with persistent structural motifs of helices, hairpins, and random coils. The spectra for helix formation shows two well-defined relaxation modes, corresponding to local relaxation and cooperative coil to uncoil interconversion. In contrast, both the hairpin and random coil are polymerlike, showing a broad and continuous range of relaxation modes giving characteristic power laws of ω-5/4 and ω-3/2, respectively; the -5/4 power law for hairpins is robust and has not been previously observed. Langevin dynamics simulations of diffusers on a potential of mean force derived from the atomistic simulations fail to reproduce the fingerprints of each peptide motif in the power spectral density, demonstrating explicitly that such information is lacking in such one-dimensional projections. Our results demonstrate the yet unexploited potential of single molecule fluctuation spectroscopy to probe more fine scaled properties of proteins and biological macromolecules and how low dimensional projections may cause the loss of relevant information.

  14. Hydration dynamics in water clusters via quantum molecular dynamics simulations

    SciTech Connect

    Turi, László

    2014-05-28

    We have investigated the hydration dynamics in size selected water clusters with n = 66, 104, 200, 500, and 1000 water molecules using molecular dynamics simulations. To study the most fundamental aspects of relaxation phenomena in clusters, we choose one of the simplest, still realistic, quantum mechanically treated test solute, an excess electron. The project focuses on the time evolution of the clusters following two processes, electron attachment to neutral equilibrated water clusters and electron detachment from an equilibrated water cluster anion. The relaxation dynamics is significantly different in the two processes, most notably restoring the equilibrium final state is less effective after electron attachment. Nevertheless, in both scenarios only minor cluster size dependence is observed. Significantly different relaxation patterns characterize electron detachment for interior and surface state clusters, interior state clusters relaxing significantly faster. This observation may indicate a potential way to distinguish surface state and interior state water cluster anion isomers experimentally. A comparison of equilibrium and non-equilibrium trajectories suggests that linear response theory breaks down for electron attachment at 200 K, but the results converge to reasonable agreement at higher temperatures. Relaxation following electron detachment clearly belongs to the linear regime. Cluster relaxation was also investigated using two different computational models, one preferring cavity type interior states for the excess electron in bulk water, while the other simulating non-cavity structure. While the cavity model predicts appearance of several different hydrated electron isomers in agreement with experiment, the non-cavity model locates only cluster anions with interior excess electron distribution. The present simulations show that surface isomers computed with the cavity predicting potential show similar dynamical behavior to the interior clusters of

  15. Simulation of counterflow pedestrian dynamics using spheropolygons.

    PubMed

    Alonso-Marroquín, Fernando; Busch, Jonathan; Chiew, Coraline; Lozano, Celia; Ramírez-Gómez, Álvaro

    2014-12-01

    Pedestrian dynamic models are typically designed for comfortable walking or slightly congested conditions and typically use a single disk or combination of three disks for the shape of a pedestrian. Under crowd conditions, a more accurate pedestrian shape has advantages over the traditional single or three-disks model. We developed a method for simulating pedestrian dynamics in a large dense crowd of spheropolygons adapted to the cross section of the chest and arms of a pedestrian. Our numerical model calculates pedestrian motion from Newton's second law, taking into account viscoelastic contact forces, contact friction, and ground-reaction forces. Ground-reaction torque was taken to arise solely from the pedestrians' orientation toward their preferred destination. Simulations of counterflow pedestrians dynamics in corridors were used to gain insight into a tragic incident at the Madrid Arena pavilion in Spain, where five girls were crushed to death. The incident took place at a Halloween Celebration in 2012, in a long, densely crowded hallway used as entrance and exit at the same time. Our simulations reconstruct the mechanism of clogging in the hallway. The hypothetical case of a total evacuation order was also investigated. The results highlights the importance of the pedestrians' density and the effect of counterflow in the onset of avalanches and clogging and provides an estimation of the number of injuries based on a calculation of the contact-force network between the pedestrians.

  16. Simulation of counterflow pedestrian dynamics using spheropolygons

    NASA Astrophysics Data System (ADS)

    Alonso-Marroquín, Fernando; Busch, Jonathan; Chiew, Coraline; Lozano, Celia; Ramírez-Gómez, Álvaro

    2014-12-01

    Pedestrian dynamic models are typically designed for comfortable walking or slightly congested conditions and typically use a single disk or combination of three disks for the shape of a pedestrian. Under crowd conditions, a more accurate pedestrian shape has advantages over the traditional single or three-disks model. We developed a method for simulating pedestrian dynamics in a large dense crowd of spheropolygons adapted to the cross section of the chest and arms of a pedestrian. Our numerical model calculates pedestrian motion from Newton's second law, taking into account viscoelastic contact forces, contact friction, and ground-reaction forces. Ground-reaction torque was taken to arise solely from the pedestrians' orientation toward their preferred destination. Simulations of counterflow pedestrians dynamics in corridors were used to gain insight into a tragic incident at the Madrid Arena pavilion in Spain, where five girls were crushed to death. The incident took place at a Halloween Celebration in 2012, in a long, densely crowded hallway used as entrance and exit at the same time. Our simulations reconstruct the mechanism of clogging in the hallway. The hypothetical case of a total evacuation order was also investigated. The results highlights the importance of the pedestrians' density and the effect of counterflow in the onset of avalanches and clogging and provides an estimation of the number of injuries based on a calculation of the contact-force network between the pedestrians.

  17. IGCC Dynamic Simulator and Training Center

    SciTech Connect

    Zitney, S.E.; Erbes, M.R.

    2006-10-01

    Integrated Gasification Combined Cycle (IGCC) is emerging as the technology of choice for providing clean, low-cost electricity for the next generation of coal-fired power plants and will play a central role in the development of high-efficiency, zero-emissions power plants such as FutureGen. Several major utilities and developers recently announced plans to build IGCC plants and other major utilities are evaluating IGCC’s suitability for base-load capacity additions. This recent surge of attention to IGCC power generation is creating a growing demand for experience with the analysis, operation, and control of commercial-scale IGCC plants. To meet this need, the National Energy Technology Laboratory (NETL) has launched a project to develop a generic, full-scope, IGCC dynamic plant simulator for use in establishing a state-of-the-art simulator training center at West Virginia University’s (WVU) National Research Center for Coal and Energy (NRCCE). The IGCC Dynamic Simulator & Training (DS&T) Center will be established under the auspices of the Collaboratory for Process & Dynamic Systems Modeling (“Collaboratory”) organized between NETL, WVU, the University of Pittsburgh, and Carnegie Mellon University.

  18. Integrated computer simulation on FIR FEL dynamics

    SciTech Connect

    Furukawa, H.; Kuruma, S.; Imasaki, K.

    1995-12-31

    An integrated computer simulation code has been developed to analyze the RF-Linac FEL dynamics. First, the simulation code on the electron beam acceleration and transport processes in RF-Linac: (LUNA) has been developed to analyze the characteristics of the electron beam in RF-Linac and to optimize the parameters of RF-Linac. Second, a space-time dependent 3D FEL simulation code (Shipout) has been developed. The RF-Linac FEL total simulations have been performed by using the electron beam data from LUNA in Shipout. The number of particles using in a RF-Linac FEL total simulation is approximately 1000. The CPU time for the simulation of 1 round trip is about 1.5 minutes. At ILT/ILE, Osaka, a 8.5MeV RF-Linac with a photo-cathode RF-gun is used for FEL oscillation experiments. By using 2 cm wiggler, the FEL oscillation in the wavelength approximately 46 {mu}m are investigated. By the simulations using LUNA with the parameters of an ILT/ILE experiment, the pulse shape and the energy spectra of the electron beam at the end of the linac are estimated. The pulse shape of the electron beam at the end of the linac has sharp rise-up and it slowly decays as a function of time. By the RF-linac FEL total simulations with the parameters of an ILT/ILE experiment, the dependencies of the start up of the FEL oscillations on the pulse shape of the electron beam at the end of the linac are estimated. The coherent spontaneous emission effects and the quick start up of FEL oscillations have been observed by the RF-Linac FEL total simulations.

  19. Adaptive wavelet simulation of global ocean dynamics

    NASA Astrophysics Data System (ADS)

    Kevlahan, N. K.-R.; Dubos, T.; Aechtner, M.

    2015-07-01

    In order to easily enforce solid-wall boundary conditions in the presence of complex coastlines, we propose a new mass and energy conserving Brinkman penalization for the rotating shallow water equations. This penalization does not lead to higher wave speeds in the solid region. The error estimates for the penalization are derived analytically and verified numerically for linearized one dimensional equations. The penalization is implemented in a conservative dynamically adaptive wavelet method for the rotating shallow water equations on the sphere with bathymetry and coastline data from NOAA's ETOPO1 database. This code could form the dynamical core for a future global ocean model. The potential of the dynamically adaptive ocean model is illustrated by using it to simulate the 2004 Indonesian tsunami and wind-driven gyres.

  20. Brownian dynamics simulation of electrostatically interacting proteins

    NASA Astrophysics Data System (ADS)

    Ermakova, E.; Krushelnitsky, A. G.; Fedotov, V. D.

    Brownian dynamics simulation software has been developed to study the dynamics of proteins as a whole in solution. The proteins were modelled as spheres with point dipoles embedded in the centre of sphere. A set of Brownian dynamics simulations at different values of the dipole moments, protein concentration and translational diffusion coefficient was performed to investigate the influence of interprotein electrostatic interactions on dynamic protein behaviour in solution. It was shown that these interactions led to the slowing down of protein rotation and a complex non-exponential shape of the rotational correlation function. Analysis of the correlation functions was performed within the frame of the model of electrostatic interprotein interactions advanced earlier on the basis of NMR and dielectric spectroscopy data. This model assumes that, due to electrostatic interactions, protein Brownian rotation becomes anisotropic. The lifetime of this anisotropy is controlled mainly by translational diffusion of proteins. Thus, the correlation function can be decomposed into two components corresponding to anisotropic Brownian rotation and an isotropic motion of an external electric field vector produced by the surrounding proteins.

  1. Simulating stochastic dynamics using large time steps.

    PubMed

    Corradini, O; Faccioli, P; Orland, H

    2009-12-01

    We present an approach to investigate the long-time stochastic dynamics of multidimensional classical systems, in contact with a heat bath. When the potential energy landscape is rugged, the kinetics displays a decoupling of short- and long-time scales and both molecular dynamics or Monte Carlo (MC) simulations are generally inefficient. Using a field theoretic approach, we perform analytically the average over the short-time stochastic fluctuations. This way, we obtain an effective theory, which generates the same long-time dynamics of the original theory, but has a lower time-resolution power. Such an approach is used to develop an improved version of the MC algorithm, which is particularly suitable to investigate the dynamics of rare conformational transitions. In the specific case of molecular systems at room temperature, we show that elementary integration time steps used to simulate the effective theory can be chosen a factor approximately 100 larger than those used in the original theory. Our results are illustrated and tested on a simple system, characterized by a rugged energy landscape.

  2. Molecular Dynamics Simulations of Network Glasses

    NASA Astrophysics Data System (ADS)

    Drabold, David A.

    The following sections are included: * Introduction and Background * History and use of MD * The role of the potential * Scope of the method * Use of a priori information * Appraising a model * MD Method * Equations of motion * Energy minimization and equilibration * Deeper or global minima * Simulated annealing * Genetic algorithms * Activation-relaxation technique * Alternate dynamics * Modeling infinite systems: Periodic boundary conditions * The Interatomic Interactions * Overview * Empirical classical potentials * Potentials from electronic structure * The tight-binding method * Approximate methods based on tight-binding * First principles * Local basis: "ab initio tight binding" * Plane-waves: Car-Parrinello methods * Efficient ab initio methods for large systems * The need for locality of electron states in real space * Avoiding explicit orthogonalization * Connecting Simulation to Experiment * Structure * Network dynamics * Computing the harmonic modes * Dynamical autocorrelation functions * Dynamical structure factor * Electronic structure * Density of states * Thermal modulation of the electron states * Transport * Applications * g-GeSe2 * g-GexSe1-x glasses * Amorphous carbon surface * Where to Get Codes to Get Started * Acknowledgments * References

  3. NMR reveals a dynamic allosteric pathway in thrombin

    PubMed Central

    Handley, Lindsey D.; Fuglestad, Brian; Stearns, Kyle; Tonelli, Marco; Fenwick, R. Bryn; Markwick, Phineus R. L.; Komives, Elizabeth A.

    2017-01-01

    Although serine proteases are found ubiquitously in both eukaryotes and prokaryotes, and they comprise the largest of all of the peptidase families, their dynamic motions remain obscure. The backbone dynamics of the coagulation serine protease, apo-thrombin (S195M-thrombin), were compared to the substrate-bound form (PPACK-thrombin). R1, R2, 15N-{1H}NOEs, and relaxation dispersion NMR experiments were measured to capture motions across the ps to ms timescale. The ps-ns motions were not significantly altered upon substrate binding. The relaxation dispersion data revealed that apo-thrombin is highly dynamic, with μs-ms motions throughout the molecule. The region around the N-terminus of the heavy chain, the Na+-binding loop, and the 170 s loop, all of which are implicated in allosteric coupling between effector binding sites and the active site, were dynamic primarily in the apo-form. Most of the loops surrounding the active site become more ordered upon PPACK-binding, but residues in the N-terminal part of the heavy chain, the γ-loop, and anion-binding exosite 1, the main allosteric binding site, retain μs-ms motions. These residues form a dynamic allosteric pathway connecting the active site to the main allosteric site that remains in the substrate-bound form. PMID:28059082

  4. Dynamic adaptive chemistry for turbulent flame simulations

    NASA Astrophysics Data System (ADS)

    Yang, Hongtao; Ren, Zhuyin; Lu, Tianfeng; Goldin, Graham M.

    2013-02-01

    The use of large chemical mechanisms in flame simulations is computationally expensive due to the large number of chemical species and the wide range of chemical time scales involved. This study investigates the use of dynamic adaptive chemistry (DAC) for efficient chemistry calculations in turbulent flame simulations. DAC is achieved through the directed relation graph (DRG) method, which is invoked for each computational fluid dynamics cell/particle to obtain a small skeletal mechanism that is valid for the local thermochemical condition. Consequently, during reaction fractional steps, one needs to solve a smaller set of ordinary differential equations governing chemical kinetics. Test calculations are performed in a partially-stirred reactor (PaSR) involving both methane/air premixed and non-premixed combustion with chemistry described by the 53-species GRI-Mech 3.0 mechanism and the 129-species USC-Mech II mechanism augmented with recently updated NO x pathways, respectively. Results show that, in the DAC approach, the DRG reduction threshold effectively controls the incurred errors in the predicted temperature and species concentrations. The computational saving achieved by DAC increases with the size of chemical kinetic mechanisms. For the PaSR simulations, DAC achieves a speedup factor of up to three for GRI-Mech 3.0 and up to six for USC-Mech II in simulation time, while at the same time maintaining good accuracy in temperature and species concentration predictions.

  5. MDLab: a molecular dynamics simulation prototyping environment.

    PubMed

    Cickovski, Trevor; Chatterjee, Santanu; Wenger, Jacob; Sweet, Christopher R; Izaguirre, Jesús A

    2010-05-01

    Molecular dynamics (MD) simulation involves solving Newton's equations of motion for a system of atoms, by calculating forces and updating atomic positions and velocities over a timestep Deltat. Despite the large amount of computing power currently available, the timescale of MD simulations is limited by both the small timestep required for propagation, and the expensive algorithm for computing pairwise forces. These issues are currently addressed through the development of efficient simulation methods, some of which make acceptable approximations and as a result can afford larger timesteps. We present MDLab, a development environment for MD simulations built with Python which facilitates prototyping, testing, and debugging of these methods. MDLab provides constructs which allow the development of propagators, force calculators, and high level sampling protocols that run several instances of molecular dynamics. For computationally demanding sampling protocols which require testing on large biomolecules, MDL includes an interface to the OpenMM libraries of Friedrichs et al. which execute on graphical processing units (GPUs) and achieve considerable speedup over execution on the CPU. As an example of an interesting high level method developed in MDLab, we present a parallel implementation of the On-The-Fly string method of Maragliano and Vanden-Eijnden. MDLab is available at http://mdlab.sourceforge.net. Copyright 2009 Wiley Periodicals, Inc.

  6. Nanodrop contact angles from molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Ravipati, Srikanth; Aymard, Benjamin; Yatsyshin, Petr; Galindo, Amparo; Kalliadasis, Serafim

    2016-11-01

    The contact angle between three phases being in thermodynamic equilibrium is highly sensitive to the nature of the intermolecular forces as well as to various fluctuation effects. Determining the Young contact angle of a sessile drop sitting on a substrate from molecular dynamics (MD) simulations is a highly non-trivial task. Most commonly employed methods for finding droplet contact angles from MD simulation data either require large numbers of particles or are system-dependent. We propose a systematic geometry based methodology for extracting the contact angle from simulated sessile droplets by analysing an appropriately coarse-grained density field. To demonstrate the method, we consider Lennard-Jones (LJ) and SPC/E water nanodroplets of different sizes sitting on planar LJ walls. Our results are in good agreement with Young contact angle values computed employing test-area perturbation method.

  7. Dynamic simulator for PEFC propulsion plant

    SciTech Connect

    Hiraide, Masataka; Kaneda, Eiichi; Sato, Takao

    1996-12-31

    This report covers part of a joint study on a PEFC propulsion system for surface ships, summarized in a presentation to this Seminar, entitled {open_quote}Study on a Polymer Electrolyte Fuel Cell (PEFC) Propulsion System for Surface Ships{close_quotes}, and which envisages application to a 1,500 DWT cargo vessel. The work presented here focuses on a simulation study on PEFC propulsion plant performance, and particularly on the system response to changes in load. Using a dynamic simulator composed of system components including fuel cell, various simulations were executed, to examine the performance of the system as a whole and of the individual system components under quick and large load changes such as occasioned by maneuvering operations and by racing when the propeller emerges above water in heavy sea.

  8. Classical Molecular Dynamics Simulation of Nuclear Fuel

    SciTech Connect

    Devanathan, Ram; Krack, Matthias; Bertolus, Marjorie

    2015-10-10

    Molecular dynamics simulation is well suited to study primary damage production by irradiation, defect interactions with fission gas atoms, gas bubble nucleation, grain boundary effects on defect and gas bubble evolution in nuclear fuel, and the resulting changes in thermo-mechanical properties. In these simulations, the forces on the ions are dictated by interaction potentials generated by fitting properties of interest to experimental data. The results obtained from the present generation of potentials are qualitatively similar, but quantitatively different. There is a need to refine existing potentials to provide a better representation of the performance of polycrystalline fuel under a variety of operating conditions, and to develop models that are equipped to handle deviations from stoichiometry. In addition to providing insights into fundamental mechanisms governing the behaviour of nuclear fuel, MD simulations can also provide parameters that can be used as inputs for mesoscale models.

  9. Molecular-dynamics simulations of lead clusters

    NASA Astrophysics Data System (ADS)

    Hendy, S. C.; Hall, B. D.

    2001-08-01

    Molecular-dynamics simulations of nanometer-sized lead clusters have been performed using the Lim-Ong-Ercolessi glue potential [Surf. Sci. 269/270, 1109 (1992)]. The binding energies of clusters forming crystalline (fcc), decahedron and icosahedron structures are compared, showing that fcc cuboctahedra are the most energetically favored of these polyhedral model structures. However, simulations of the freezing of liquid droplets produced a characteristic form of surface-reconstructed ``shaved'' icosahedron, in which atoms are absent at the edges and apexes of the polyhedron. This arrangement is energetically favored for 600-4000 atom clusters. Larger clusters favor crystalline structures. Indeed, simulated freezing of a 6525-atom liquid droplet produced an imperfect fcc Wulff particle, containing a number of parallel stacking faults. The effects of temperature on the preferred structure of crystalline clusters below the melting point have been considered. The implications of these results for the interpretation of experimental data is discussed.

  10. A Fault Evolution Model Including the Rupture Dynamic Simulation

    NASA Astrophysics Data System (ADS)

    Wu, Y.; Chen, X.

    2011-12-01

    We perform a preliminary numerical simulation of seismicity and stress evolution along a strike-slip fault in a 3D elastic half space. Following work of Ben-Zion (1996), the fault geometry is devised as a vertical plane which is about 70 km long and 17 km wide, comparable to the size of San Andreas Fault around Parkfield. The loading mechanism is described by "backslip" method. The fault failure is governed by a static/kinetic friction law, and induced stress transfer is calculated with Okada's static solution. In order to track the rupture propagation in detail, we allow induced stress to propagate through the medium at the shear wave velocity by introducing a distance-dependent time delay to responses to stress changes. Current simulation indicates small to moderate earthquakes following the Gutenberg-Richter law and quasi-periodical characteristic large earthquakes, which are consistent with previous work by others. Next we will consider introducing a more realistic friction law, namely, the laboratory-derived rate- and state- dependent law, which can simulate more realistic and complicated sliding behavior such as the stable and unstable slip, the aseismic sliding and the slip nucleation process. In addition, the long duration of aftershocks is expected to be reproduced due to this time-dependent friction law, which is not available in current seismicity simulation. The other difference from previous work is that we are trying to include the dynamic ruptures in this study. Most previous study on seismicity simulation is based on the static solution when dealing with failure induced stress changes. However, studies of numerical simulation of rupture dynamics have revealed lots of important details which are missing in the quasi-static/quasi- dynamic simulation. For example, dynamic simulations indicate that the slip on the ground surface becomes larger if the dynamic rupture process reaches the free surface. The concentration of stress on the propagating crack

  11. Dynamic processes in biological membrane mimics revealed by quasielastic neutron scattering.

    PubMed

    Lautner, Lisa; Pluhackova, Kristyna; Barth, Nicolai K H; Seydel, Tilo; Lohstroh, Wiebke; Böckmann, Rainer A; Unruh, Tobias

    2017-08-01

    Neutron scattering is a powerful tool to study relaxation processes in biological membrane mimics in space and time. Combining different inelastic and quasielastic neutron scattering techniques, a large dynamic range can be covered: from atomic to mesoscopic lengths and from femto- to some hundreds of nanoseconds in time. This allows studies on e.g. the diffusion of lipids, the membrane undulation motions, the dispersion of sound waves in membranes as well as the mutual interactions of membrane constituents such as lipids, proteins, and additives. In particular, neutron scattering provides a quite direct experimental approach to the inter-atomic and inter-molecular potentials on length and time scales which are perfectly accessible by molecular dynamics (MD) simulations. Neutron scattering experiments may thus substantially support the further refinement of biomolecular force fields for MD simulations by supplying structural and dynamical information with high spatial and temporal resolution. In turn, MD simulations support the interpretation of neutron scattering data. The combination of both, neutron scattering experiments and MD simulations, yields an unprecedented insight into the molecular interactions governing the structure and dynamics of biological membranes. This review provides an overview of the molecular dynamics in biological membrane mimics as revealed by neutron scattering. It focuses on the latest findings such as the fundamental molecular mechanism of lateral lipid diffusion as well as the influence of additives and proteins on the short-time dynamics of lipids. Special emphasis is placed on the comparison of recent neutron scattering and MD simulation data with respect to molecular membrane dynamics on the pico- to nanosecond time scale. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Dynamic regulation of phenylalanine hydroxylase by simulated redox manipulation.

    PubMed

    Fuchs, Julian E; Huber, Roland G; von Grafenstein, Susanne; Wallnoefer, Hannes G; Spitzer, Gudrun M; Fuchs, Dietmar; Liedl, Klaus R

    2012-01-01

    Recent clinical studies revealed increased phenylalanine levels and phenylalanine to tyrosine ratios in patients suffering from infection, inflammation and general immune activity. These data implicated down-regulation of activity of phenylalanine hydroxylase by oxidative stress upon in vivo immune activation. Though the structural damage of oxidative stress is expected to be comparably small, a structural rationale for this experimental finding was lacking. Hence, we investigated the impact of side chain oxidation at two vicinal cysteine residues on local conformational flexibility in the protein by comparative molecular dynamics simulations. Analysis of backbone dynamics revealed a highly flexible loop region (Tyr138-loop) in proximity to the active center of phenylalanine hydroxylase. We observed elevated loop dynamics in connection with a loop movement towards the active site in the oxidized state, thereby partially blocking access for the substrate phenylalanine. These findings were confirmed by extensive replica exchange molecular dynamics simulations and serve as a first structural explanation for decreased enzyme turnover in situations of oxidative stress.

  13. Dynamic simulation of regulatory networks using SQUAD

    PubMed Central

    Di Cara, Alessandro; Garg, Abhishek; De Micheli, Giovanni; Xenarios, Ioannis; Mendoza, Luis

    2007-01-01

    Background The ambition of most molecular biologists is the understanding of the intricate network of molecular interactions that control biological systems. As scientists uncover the components and the connectivity of these networks, it becomes possible to study their dynamical behavior as a whole and discover what is the specific role of each of their components. Since the behavior of a network is by no means intuitive, it becomes necessary to use computational models to understand its behavior and to be able to make predictions about it. Unfortunately, most current computational models describe small networks due to the scarcity of kinetic data available. To overcome this problem, we previously published a methodology to convert a signaling network into a dynamical system, even in the total absence of kinetic information. In this paper we present a software implementation of such methodology. Results We developed SQUAD, a software for the dynamic simulation of signaling networks using the standardized qualitative dynamical systems approach. SQUAD converts the network into a discrete dynamical system, and it uses a binary decision diagram algorithm to identify all the steady states of the system. Then, the software creates a continuous dynamical system and localizes its steady states which are located near the steady states of the discrete system. The software permits to make simulations on the continuous system, allowing for the modification of several parameters. Importantly, SQUAD includes a framework for perturbing networks in a manner similar to what is performed in experimental laboratory protocols, for example by activating receptors or knocking out molecular components. Using this software we have been able to successfully reproduce the behavior of the regulatory network implicated in T-helper cell differentiation. Conclusion The simulation of regulatory networks aims at predicting the behavior of a whole system when subject to stimuli, such as drugs, or

  14. Molecular Dynamics Simulation of Nitrobenzene Dioxygenase Using AMBER Force Field

    PubMed Central

    2015-01-01

    Molecular dynamics simulation of the oxygenase component of nitrobenzene dioxygenase (NBDO) system, a member of the naphthalene family of Rieske nonheme iron dioxygenases, has been carried out using the AMBER force field combined with a new set of parameters for the description of the mononuclear nonheme iron center and iron–sulfur Rieske cluster. Simulation results provide information on the structure and dynamics of nitrobenzene dioxygenase in an aqueous environment and shed light on specific interactions that occur in its catalytic center. The results suggest that the architecture of the active site is stabilized by key hydrogen bonds, and Asn258 positions the substrate for oxidation. Analysis of protein–water interactions reveal the presence of a network of solvent molecules at the entrance to the active site, which could be of potential catalytic importance. PMID:24955078

  15. Molecular dynamics simulation of radiation damage cascades in diamond

    SciTech Connect

    Buchan, J. T.; Robinson, M.; Christie, H. J.; Roach, D. L.; Ross, D. K.; Marks, N. A.

    2015-06-28

    Radiation damage cascades in diamond are studied by molecular dynamics simulations employing the Environment Dependent Interaction Potential for carbon. Primary knock-on atom (PKA) energies up to 2.5 keV are considered and a uniformly distributed set of 25 initial PKA directions provide robust statistics. The simulations reveal the atomistic origins of radiation-resistance in diamond and provide a comprehensive computational analysis of cascade evolution and dynamics. As for the case of graphite, the atomic trajectories are found to have a fractal-like character, thermal spikes are absent and only isolated point defects are generated. Quantitative analysis shows that the instantaneous maximum kinetic energy decays exponentially with time, and that the timescale of the ballistic phase has a power-law dependence on PKA energy. Defect recombination is efficient and independent of PKA energy, with only 50% of displacements resulting in defects, superior to graphite where the same quantity is nearly 75%.

  16. A review of the analytical simulation of aircraft crash dynamics

    NASA Technical Reports Server (NTRS)

    Fasanella, Edwin L.; Carden, Huey D.; Boitnott, Richard L.; Hayduk, Robert J.

    1990-01-01

    A large number of full scale tests of general aviation aircraft, helicopters, and one unique air-to-ground controlled impact of a transport aircraft were performed. Additionally, research was also conducted on seat dynamic performance, load-limiting seats, load limiting subfloor designs, and emergency-locator-transmitters (ELTs). Computer programs were developed to provide designers with methods for predicting accelerations, velocities, and displacements of collapsing structure and for estimating the human response to crash loads. The results of full scale aircraft and component tests were used to verify and guide the development of analytical simulation tools and to demonstrate impact load attenuating concepts. Analytical simulation of metal and composite aircraft crash dynamics are addressed. Finite element models are examined to determine their degree of corroboration by experimental data and to reveal deficiencies requiring further development.

  17. INCORPORATING DYNAMIC 3D SIMULATION INTO PRA

    SciTech Connect

    Steven R Prescott; Curtis Smith

    2011-07-01

    provide superior results and insights. We also couple the state model with the dynamic 3D simulation analysis representing events (such as flooding) to determine which (if any) components fail. Not only does the simulation take into account any failed items from the state model, but any failures caused by the simulation are incorporated back into the state model and factored into the overall results. Using this method we incorporate accurate 3D simulation results, eliminate static-based PRA issues, and have time ordered failure information.

  18. Computer simulations reveal motor properties generating stable antiparallel microtubule interactions.

    PubMed

    Nédélec, François

    2002-09-16

    An aster of microtubules is a set of flexible polar filaments with dynamic plus ends that irradiate from a common location at which the minus ends of the filaments are found. Processive soluble oligomeric motor complexes can bind simultaneously to two microtubules, and thus exert forces between two asters. Using computer simulations, I have explored systematically the possible steady-state regimes reached by two asters under the action of various kinds of oligomeric motors. As expected, motor complexes can induce the asters to fuse, for example when the complexes consist only of minus end-directed motors, or to fully separate, when the motors are plus end directed. More surprisingly, complexes made of two motors of opposite directionalities can also lead to antiparallel interactions between overlapping microtubules that are stable and sustained, like those seen in mitotic spindle structures. This suggests that such heterocomplexes could have a significant biological role, if they exist in the cell.

  19. Dynamic changes in network synchrony reveal resting-state functional networks

    NASA Astrophysics Data System (ADS)

    Vuksanović, Vesna; Hövel, Philipp

    2015-02-01

    Experimental functional magnetic resonance imaging studies have shown that spontaneous brain activity, i.e., in the absence of any external input, exhibit complex spatial and temporal patterns of co-activity between segregated brain regions. These so-called large-scale resting-state functional connectivity networks represent dynamically organized neural assemblies interacting with each other in a complex way. It has been suggested that looking at the dynamical properties of complex patterns of brain functional co-activity may reveal neural mechanisms underlying the dynamic changes in functional interactions. Here, we examine how global network dynamics is shaped by different network configurations, derived from realistic brain functional interactions. We focus on two main dynamics measures: synchrony and variations in synchrony. Neural activity and the inferred hemodynamic response of the network nodes are simulated using a system of 90 FitzHugh-Nagumo neural models subject to system noise and time-delayed interactions. These models are embedded into the topology of the complex brain functional interactions, whose architecture is additionally reduced to its main structural pathways. In the simulated functional networks, patterns of correlated regional activity clearly arise from dynamical properties that maximize synchrony and variations in synchrony. Our results on the fast changes of the level of the network synchrony also show how flexible changes in the large-scale network dynamics could be.

  20. The Fermi-Pasta-Ulam problem: Simulation and modern dynamics

    SciTech Connect

    Weissert, T.P.

    1992-01-01

    In 1952, Enrico Fermi, John Pasta and Stanislaw Ulam (FPU) simulated the loaded string model, perturbed with small, nonlinear interaction terms. Because Poincare's theorem guarantees the non-existence of a complete set of integrals for three-body problem, they expected to see the diffusion of energy from its single-mode initial condition to all other modes of the string. But for every combination of initial conditions, the energy remained bounded within the lowest few modes. No theoretical explanation existed for this failure of the underlying hypothesis that erogidicity follows from the lack of a complete set of integrals of the motion in a Hamiltonian model. The author traces the history of this problem from the FPU simulation to the point that a consensus was reached concerning its solution twenty years later. During this period, the simulation of nonlinearly-perturbed integral models became the methodology for a new era in dynamics. Through the use of simulation, dynamicists discovered deterministic chaos, in which the exponential separation of pair orbits generate randomness in deterministic macroscopic systems, and a new kind of structure-related to the KAM theorem-that provides limited order in the absence of analytic integrals of the motions. The author maps the set of conceptually-related journal articles into a chronological inference topology that tracks the understanding of this problem of dynamics. Simulating non-integrable models on a digital computer requires the discretization of time and space. These approximations affect what the simulation can reveal about the model, and the model about reality. Simulations play the role of experiments on mathematical models. A discussion is presented of the issues that emerge with the use of simulation as a heuristic device and the groundwork is laid for an epistemology of simulation.

  1. Molecular dynamics simulation of fractal aggregate diffusion

    NASA Astrophysics Data System (ADS)

    Pranami, Gaurav; Lamm, Monica H.; Vigil, R. Dennis

    2010-11-01

    The diffusion of fractal aggregates constructed with the method by Thouy and Jullien [J. Phys. A 27, 2953 (1994)10.1088/0305-4470/27/9/012] comprised of Np spherical primary particles was studied as a function of the aggregate mass and fractal dimension using molecular dynamics simulations. It is shown that finite-size effects have a strong impact on the apparent value of the diffusion coefficient (D) , but these can be corrected by carrying out simulations using different simulation box sizes. Specifically, the diffusion coefficient is inversely proportional to the length of a cubic simulation box, and the constant of proportionality appears to be independent of the aggregate mass and fractal dimension. Using this result, it is possible to compute infinite dilution diffusion coefficients (Do) for aggregates of arbitrary size and fractal dimension, and it was found that Do∝Np-1/df , as is often assumed by investigators simulating Brownian aggregation of fractal aggregates. The ratio of hydrodynamic radius to radius of gyration is computed and shown to be independent of mass for aggregates of fixed fractal dimension, thus enabling an estimate of the diffusion coefficient for a fractal aggregate based on its radius of gyration.

  2. An Acrobatic Substrate Metamorphosis Reveals a Requirement for Substrate Conformational Dynamics in Trypsin Proteolysis

    DOE PAGES

    Kayode, Olumide; Wang, Ruiying; Pendlebury, Devon F.; ...

    2016-11-03

    The molecular basis of enzyme catalytic power and specificity derives from dynamic interactions between enzyme and substrate during catalysis. While considerable effort has been devoted to understanding how conformational dynamics within enzymes affect catalysis, the role of conformational dynamics within protein substrates has not been addressed. Here in this paper, we examine the importance of substrate dynamics in the cleavage of Kunitz-BPTI protease inhibitors by mesotrypsin, finding that the varied conformational dynamics of structurally similar substrates can profoundly impact the rate of catalysis. A 1.4 Å crystal structure of a mesotrypsin-product complex formed with a rapidly cleaved substrate reveals amore » dramatic conformational change in the substrate upon proteolysis. Using long all-atom molecular dynamics simulations of acyl-enzyme intermediates with proteolysis rates spanning three orders of magnitude, we identify global and local dynamic features of substrates on the ns-μs timescale that correlate with enzymatic rates and explain differential susceptibility to proteolysis. By integrating multiple enhanced sampling methods for molecular dynamics, we model a viable conformational pathway between substratelike and product-like states, linking substrate dynamics on the ns-μs timescale with large collective substrate motions on the much slower timescale of catalysis. Our findings implicate substrate flexibility as a critical determinant of catalysis.« less

  3. An Acrobatic Substrate Metamorphosis Reveals a Requirement for Substrate Conformational Dynamics in Trypsin Proteolysis

    SciTech Connect

    Kayode, Olumide; Wang, Ruiying; Pendlebury, Devon F.; Cohen, Itay; Henin, Rachel D.; Hockla, Alexandra; Soares, Alexei S.; Papo, Niv; Caulfield, Thomas R.; Radisky, Evette S.

    2016-11-03

    The molecular basis of enzyme catalytic power and specificity derives from dynamic interactions between enzyme and substrate during catalysis. While considerable effort has been devoted to understanding how conformational dynamics within enzymes affect catalysis, the role of conformational dynamics within protein substrates has not been addressed. Here in this paper, we examine the importance of substrate dynamics in the cleavage of Kunitz-BPTI protease inhibitors by mesotrypsin, finding that the varied conformational dynamics of structurally similar substrates can profoundly impact the rate of catalysis. A 1.4 Å crystal structure of a mesotrypsin-product complex formed with a rapidly cleaved substrate reveals a dramatic conformational change in the substrate upon proteolysis. Using long all-atom molecular dynamics simulations of acyl-enzyme intermediates with proteolysis rates spanning three orders of magnitude, we identify global and local dynamic features of substrates on the ns-μs timescale that correlate with enzymatic rates and explain differential susceptibility to proteolysis. By integrating multiple enhanced sampling methods for molecular dynamics, we model a viable conformational pathway between substratelike and product-like states, linking substrate dynamics on the ns-μs timescale with large collective substrate motions on the much slower timescale of catalysis. Our findings implicate substrate flexibility as a critical determinant of catalysis.

  4. Revealing the properties of plant defensins through dynamics.

    PubMed

    Valente, Ana Paula; de Paula, Viviane Silva; Almeida, Fabio C L

    2013-09-13

    Defensins are potent, ancient natural antibiotics that are present in organisms ranging from lower organisms to humans. Although the structures of several defensins have been well characterized, the dynamics of only a few have been studied. This review discusses the diverse dynamics of two plant defensins for which the structure and dynamics have been characterized, both in the free state and in the presence of target membranes. Multiple motions are observed in loops and in secondary structure elements and may be related to twisting or breathing of the α-helix and β-sheet. This complex behavior is altered in the presence of an interface and is responsive to the presence of the putative target. The stages of membrane recognition and disruption can be mapped over a large time scale range, demonstrating that defensins in solution exist as an ensemble of different conformations, a subset of which is selected upon membrane binding. Therefore, studies on the dynamics have revealed that defensins interact with membranes through a mechanism of conformational selection.

  5. Monoamine transporters: insights from molecular dynamics simulations

    PubMed Central

    Grouleff, Julie; Ladefoged, Lucy Kate; Koldsø, Heidi; Schiøtt, Birgit

    2015-01-01

    The human monoamine transporters (MATs) facilitate the reuptake of the neurotransmitters serotonin, dopamine, and norepinephrine from the synaptic cleft. Imbalance in monoaminergic neurotransmission is linked to various diseases including major depression, attention deficit hyperactivity disorder, schizophrenia, and Parkinson’s disease. Inhibition of the MATs is thus an important strategy for treatment of such diseases. The MATs are sodium-coupled transport proteins belonging to the neurotransmitter/Na+ symporter (NSS) family, and the publication of the first high-resolution structure of a NSS family member, the bacterial leucine transporter LeuT, in 2005, proved to be a major stepping stone for understanding this family of transporters. Structural data allows for the use of computational methods to study the MATs, which in turn has led to a number of important discoveries. The process of substrate translocation across the membrane is an intrinsically dynamic process. Molecular dynamics simulations, which can provide atomistic details of molecular motion on ns to ms timescales, are therefore well-suited for studying transport processes. In this review, we outline how molecular dynamics simulations have provided insight into the large scale motions associated with transport of the neurotransmitters, as well as the presence of external and internal gates, the coupling between ion and substrate transport, and differences in the conformational changes induced by substrates and inhibitors. PMID:26528185

  6. Brownian Dynamics Simulation of Protein Solutions: Structural and Dynamical Properties

    PubMed Central

    Mereghetti, Paolo; Gabdoulline, Razif R.; Wade, Rebecca C.

    2010-01-01

    The study of solutions of biomacromolecules provides an important basis for understanding the behavior of many fundamental cellular processes, such as protein folding, self-assembly, biochemical reactions, and signal transduction. Here, we describe a Brownian dynamics simulation procedure and its validation for the study of the dynamic and structural properties of protein solutions. In the model used, the proteins are treated as atomically detailed rigid bodies moving in a continuum solvent. The protein-protein interaction forces are described by the sum of electrostatic interaction, electrostatic desolvation, nonpolar desolvation, and soft-core repulsion terms. The linearized Poisson-Boltzmann equation is solved to compute electrostatic terms. Simulations of homogeneous solutions of three different proteins with varying concentrations, pH, and ionic strength were performed. The results were compared to experimental data and theoretical values in terms of long-time self-diffusion coefficients, second virial coefficients, and structure factors. The results agree with the experimental trends and, in many cases, experimental values are reproduced quantitatively. There are no parameters specific to certain protein types in the interaction model, and hence the model should be applicable to the simulation of the behavior of mixtures of macromolecules in cell-like crowded environments. PMID:21112303

  7. High-frequency microrheology reveals cytoskeleton dynamics in living cells

    NASA Astrophysics Data System (ADS)

    Rigato, Annafrancesca; Miyagi, Atsushi; Scheuring, Simon; Rico, Felix

    2017-08-01

    Living cells are viscoelastic materials, dominated by an elastic response on timescales longer than a millisecond. On shorter timescales, the dynamics of individual cytoskeleton filaments are expected to emerge, but active microrheology measurements on cells accessing this regime are scarce. Here, we develop high-frequency microrheology experiments to probe the viscoelastic response of living cells from 1 Hz to 100 kHz. We report the viscoelasticity of different cell types under cytoskeletal drug treatments. On previously inaccessible short timescales, cells exhibit rich viscoelastic responses that depend on the state of the cytoskeleton. Benign and malignant cancer cells revealed remarkably different scaling laws at high frequencies, providing a unique mechanical fingerprint. Microrheology over a wide dynamic range--up to the frequency characterizing the molecular components--provides a mechanistic understanding of cell mechanics.

  8. Ultrafast cooling reveals microsecond-scale biomolecular dynamics.

    PubMed

    Polinkovsky, Mark E; Gambin, Yann; Banerjee, Priya R; Erickstad, Michael J; Groisman, Alex; Deniz, Ashok A

    2014-12-17

    The temperature-jump technique, in which the sample is rapidly heated by a powerful laser pulse, has been widely used to probe the fast dynamics of folding of proteins and nucleic acids. However, the existing temperature-jump setups tend to involve sophisticated and expensive instrumentation, while providing only modest temperature changes of ~10-15 °C, and the temperature changes are only rapid for heating, but not cooling. Here we present a setup comprising a thermally conductive sapphire substrate with light-absorptive nano-coating, a microfluidic device and a rapidly switched moderate-power infrared laser with the laser beam focused on the nano-coating, enabling heating and cooling of aqueous solutions by ~50 °C on a 1-μs time scale. The setup is used to probe folding and unfolding dynamics of DNA hairpins after direct and inverse temperature jumps, revealing low-pass filter behaviour during periodic temperature variations.

  9. Molecular Dynamics Simulation of Iron — A Review

    NASA Astrophysics Data System (ADS)

    Chui, C. P.; Liu, Wenqing; Xu, Yongbing; Zhou, Yan

    2015-12-01

    Molecular dynamics (MD) is a technique of atomistic simulation which has facilitated scientific discovery of interactions among particles since its advent in the late 1950s. Its merit lies in incorporating statistical mechanics to allow for examination of varying atomic configurations at finite temperatures. Its contributions to materials science from modeling pure metal properties to designing nanowires is also remarkable. This review paper focuses on the progress of MD in understanding the behavior of iron — in pure metal form, in alloys, and in composite nanomaterials. It also discusses the interatomic potentials and the integration algorithms used for simulating iron in the literature. Furthermore, it reveals the current progress of MD in simulating iron by exhibiting some results in the literature. Finally, the review paper briefly mentions the development of the hardware and software tools for such large-scale computations.

  10. Molecular dynamics simulation of short-wavelength collective dynamics of phospholipid membranes

    NASA Astrophysics Data System (ADS)

    Conti Nibali, Valeria; D'Angelo, Giovanna; Tarek, Mounir

    2014-05-01

    We investigated the short-wavelength longitudinal and transverse collective dynamics of the fluid and gel phases of phospholipid bilayers by means of molecular dynamics simulation. Similarly to a crystal, the spectrum of collective excitations in a bilayer consists of longitudinal and transverse acoustic modes, though modified by disorder. Beside acoustic modes, a series of broad dispersionless excitations are revealed. The dispersion curves of the observed excitations may be represented in a pseudo-Brillouin zone scheme centered around the spatial correlation peak of the acyl chains. The study provides evidence for a resonant interaction between the lowest frequency optical phonon and the longitudinal acoustic mode.

  11. Allosteric dynamics of SAMHD1 studied by molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Patra, K. K.; Bhattacharya, A.; Bhattacharya, S.

    2016-10-01

    SAMHD1 is a human cellular enzyme that blocks HIV-1 infection in myeloid cells and non-cycling CD4+T cells. The enzyme is an allosterically regulated triphosphohydrolase that modulates the level of cellular dNTP. The virus restriction is attributed to the lowering of the pool of dNTP in the cell to a point where reverse-transcription is impaired. Mutations in SAMHD1 are also implicated in Aicardi-Goutieres syndrome. A mechanistic understanding of the allosteric activation of the enzyme is still elusive. We have performed molecular dynamics simulations to examine the allosteric site dynamics of the protein and to examine the connection between the stability of the tetrameric complex and the Allosite occupancy.

  12. Dynamic transitions in molecular dynamics simulations of supercooled silicon

    NASA Astrophysics Data System (ADS)

    Mei, Xiaojun; Eapen, Jacob

    2013-04-01

    Two dynamic transitions or crossovers, one at a low temperature (T* ≈ 1006 K) and the other at a high temperature (T0 ≈ 1384 K), are shown to emerge in supercooled liquid silicon using molecular dynamics simulations. The high-temperature transition (T0) marks the decoupling of stress, density, and energy relaxation mechanisms. At the low-temperature transition (T*), depending on the cooling rate, supercooled silicon can either undergo a high-density-liquid to low-density-liquid (HDL-LDL) phase transition or experience an HDL-HDL crossover. Dynamically heterogeneous domains that emerge with supercooling become prominent across the HDL-HDL transition at 1006 K, with well-separated mobile and immobile regions. Interestingly, across the HDL-LDL transition, the most mobile atoms form large prominent aggregates while the least mobile atoms get spatially dispersed akin to that in a crystalline state. The attendant partial return to spatial uniformity with the HDL-LDL phase transition indicates a dynamic mechanism for relieving the frustration in supercooled states.

  13. Dynamical simulation of dipolar Janus colloids: Dynamical properties

    NASA Astrophysics Data System (ADS)

    Hagy, Matthew C.; Hernandez, Rigoberto

    2013-05-01

    The dynamical properties of dipolar Janus particles are studied through simulation using our previously-developed detailed pointwise (PW) model and an isotropically coarse-grained (CG) model [M. C. Hagy and R. Hernandez, J. Chem. Phys. 137, 044505 (2012), 10.1063/1.4737432]. The CG model is found to have accelerated dynamics relative to the PW model over a range of conditions for which both models have near identical static equilibrium properties. Physically, this suggests dipolar Janus particles have slower transport properties (such as diffusion) in comparison to isotropically attractive particles. Time rescaling and damping with Langevin friction are explored to map the dynamics of the CG model to that of the PW model. Both methods map the diffusion constant successfully and improve the velocity autocorrelation function and the mean squared displacement of the CG model. Neither method improves the distribution of reversible bond durations f(tb) observed in the CG model, which is found to lack the longer duration reversible bonds observed in the PW model. We attribute these differences in f(tb) to changes in the energetics of multiple rearrangement mechanisms. This suggests a need for new methods that map the coarse-grained dynamics of such systems to the true time scale.

  14. Mobility Laws in Dislocation Dynamics Simulations

    SciTech Connect

    Cai, W; Bulatov, V V

    2003-10-21

    Prediction of the plastic deformation behavior of single crystals based on the collective dynamics of dislocations has been a challenge for computational materials science for a number of years. The difficulty lies in the inability of existing dislocation dynamics (DD) codes to handle a sufficiently large number of dislocation lines, to establish a statistically representative model of crystal plasticity. A new massively-parallel DD code is developed that is capable of modeling million-dislocation systems by employing thousands of processors. We discuss an important ingredient of this code--the mobility laws dictating the behavior of individual dislocations. They are materials input for DD simulations and are constructed based on the understanding of dislocation motion at the atomistic level.

  15. Molecular dynamics simulation of aluminium melting

    NASA Astrophysics Data System (ADS)

    Novak, Jakob

    2016-06-01

    Solid-liquid phase transition has been simulated by the molecular dynamics method, using isobaric-isoenthalpic ensemble. For interatomic potential, glue potential has been selected. The original algorithm for bookkeeping of the information on neighbouring relationships of the atoms has been developed and used in this research. Time consumption for calculation of interatomic forces has been reduced from o(N2) to o(N) by the use of this algorithm. Calculations show that phase transition from solid to liquid occurs between 1,000 K and 1,300 K. The simulated temperature of phase transition is higher than the experimental value due to the absence of crystal defects. If constant heat flux is supplied, temperature decreases during melting because the superheated state becomes unstable. During the cooling process, no significant changes of the observed variables were detected due to the high cooling rate, which prevents crystallisation.

  16. Molecular Dynamics Simulations of Hypervelocity Impacts

    NASA Astrophysics Data System (ADS)

    Owens, Eli T.; Bachlechner, Martina E.

    2007-03-01

    Outer space silicon solar cells are exposed to impacts with micro meteors that can destroy the surface leading to device failure. A protective coating of silicon nitride will protect against such failure. Large-scale molecular dynamics simulations are used to study how silicon/silicon nitride fails due to hypervelocity impacts. Three impactors made of silicon nitride are studied. Their cross-sectional areas, relative to the target, are as follows: the same as the target, half of the target, and a quarter of the target. Impactor speeds from 5 to 11 km/second yield several modes of failure, such as deformation of the target by the impactor and delimitation of the silicon nitride from the silicon at the interface. These simulations will give a much clearer picture of how solar cells composed of a silicon/silicon nitride interface will respond to impacts in outer space. This will ultimately lead to improved devices with longer life spans.

  17. Isotropic MD simulations of dynamic brittle fracture

    SciTech Connect

    Espanol, P.; Rubio, M.A.; Zuniga, I.

    1996-12-01

    The authors present results obtained by molecular dynamics simulations on the propagation of fast cracks in triangular 2D lattices. Their aim is to simulate Mode 1 fracture of brittle isotropic materials. They propose a force law that respects the isotropy of the material. The code yields the correct imposed sound c{sub {parallel}}, shear c{sub {perpendicular}} and surface V{sub R} wave speeds. Different notch lengths are systematically studied. They observed that initially the cracks are linear and always branch at a particular critical velocity c* {approx} 0.8V{sub R} and that this occurs when the crack tip reaches the position of a front emitted from the initial crack tip and propagating at a speed c = 0.68V{sub R}.

  18. Cloud-based simulations on Google Exacycle reveal ligand-modulation of GPCR activation pathways

    PubMed Central

    Bowman, Gregory R.; Konerding, David E.; Belov, Dan; Altman, Russ B.; Pande, Vijay S.

    2014-01-01

    Simulations can provide tremendous insight into atomistic details of biological mechanisms, but micro- to milliseconds timescales are historically only accessible on dedicated supercomputers. We demonstrate that cloud computing is a viable alternative, bringing long-timescale processes within reach of a broader community. We used Google's Exacycle cloud computing platform to simulate 2 milliseconds of dynamics of the β2 adrenergic receptor — a major drug target G protein-coupled receptor (GPCR). Markov state models aggregate independent simulations into a single statistical model that is validated by previous computational and experimental results. Moreover, our models provide an atomistic description of the activation of a GPCR, revealing multiple activation pathways. Agonists and inverse agonists interact differentially with these pathways, with profound implications for drug design PMID:24345941

  19. Cloud-based simulations on Google Exacycle reveal ligand modulation of GPCR activation pathways

    NASA Astrophysics Data System (ADS)

    Kohlhoff, Kai J.; Shukla, Diwakar; Lawrenz, Morgan; Bowman, Gregory R.; Konerding, David E.; Belov, Dan; Altman, Russ B.; Pande, Vijay S.

    2014-01-01

    Simulations can provide tremendous insight into the atomistic details of biological mechanisms, but micro- to millisecond timescales are historically only accessible on dedicated supercomputers. We demonstrate that cloud computing is a viable alternative that brings long-timescale processes within reach of a broader community. We used Google's Exacycle cloud-computing platform to simulate two milliseconds of dynamics of a major drug target, the G-protein-coupled receptor β2AR. Markov state models aggregate independent simulations into a single statistical model that is validated by previous computational and experimental results. Moreover, our models provide an atomistic description of the activation of a G-protein-coupled receptor and reveal multiple activation pathways. Agonists and inverse agonists interact differentially with these pathways, with profound implications for drug design.

  20. Molecular Dynamics Simulations of Interface Failure

    NASA Astrophysics Data System (ADS)

    Bachlechner, Martina E.; Cao, Deng; Leonard, Robert H.; Owens, Eli T.; Swan, Wm. Trevor, III; Ducatman, Samuel C.

    2007-03-01

    The mechanical integrity of silicon/silicon nitride interfaces is of great importance in their applications in micro electronics and solar cells. Large-scale molecular dynamics simulations are an excellent tool to study mechanical and structural failure of interfaces subjected to externally applied stresses and strains. When pulling the system parallel to the interface, cracks in silicon nitride and slip and pit formation in silicon are typical failure mechanisms. Hypervelocity impact perpendicular to the interface plane leads to structural transformation and delamination at the interface. Influence of system temperature, strain rate, impact velocity, and system size on type and characteristics of failure will be discussed.

  1. Parallel beam dynamics simulation of linear accelerators

    SciTech Connect

    Qiang, Ji; Ryne, Robert D.

    2002-01-31

    In this paper we describe parallel particle-in-cell methods for the large scale simulation of beam dynamics in linear accelerators. These techniques have been implemented in the IMPACT (Integrated Map and Particle Accelerator Tracking) code. IMPACT is being used to study the behavior of intense charged particle beams and as a tool for the design of next-generation linear accelerators. As examples, we present applications of the code to the study of emittance exchange in high intensity beams and to the study of beam transport in a proposed accelerator for the development of accelerator-driven waste transmutation technologies.

  2. Dynamic Deployment Simulations of Inflatable Space Structures

    NASA Technical Reports Server (NTRS)

    Wang, John T.

    2005-01-01

    The feasibility of using Control Volume (CV) method and the Arbitrary Lagrangian Eulerian (ALE) method in LSDYNA to simulate the dynamic deployment of inflatable space structures is investigated. The CV and ALE methods were used to predict the inflation deployments of three folded tube configurations. The CV method was found to be a simple and computationally efficient method that may be adequate for modeling slow inflation deployment sine the inertia of the inflation gas can be neglected. The ALE method was found to be very computationally intensive since it involves the solving of three conservative equations of fluid as well as dealing with complex fluid structure interactions.

  3. Molecular dynamics simulations of dense plasmas

    SciTech Connect

    Collins, L.A.; Kress, J.D.; Kwon, I.; Lynch, D.L.; Troullier, N.

    1993-12-31

    We have performed quantum molecular dynamics simulations of hot, dense plasmas of hydrogen over a range of temperatures(0.1-5eV) and densities(0.0625-5g/cc). We determine the forces quantum mechanically from density functional, extended Huckel, and tight binding techniques and move the nuclei according to the classical equations of motion. We determine pair-correlation functions, diffusion coefficients, and electrical conductivities. We find that many-body effects predominate in this regime. We begin to obtain agreement with the OCP and Thomas-Fermi models only at the higher temperatures and densities.

  4. Osmosis : a molecular dynamics computer simulation study

    NASA Astrophysics Data System (ADS)

    Lion, Thomas

    Osmosis is a phenomenon of critical importance in a variety of processes ranging from the transport of ions across cell membranes and the regulation of blood salt levels by the kidneys to the desalination of water and the production of clean energy using potential osmotic power plants. However, despite its importance and over one hundred years of study, there is an ongoing confusion concerning the nature of the microscopic dynamics of the solvent particles in their transfer across the membrane. In this thesis the microscopic dynamical processes underlying osmotic pressure and concentration gradients are investigated using molecular dynamics (MD) simulations. I first present a new derivation for the local pressure that can be used for determining osmotic pressure gradients. Using this result, the steady-state osmotic pressure is studied in a minimal model for an osmotic system and the steady-state density gradients are explained using a simple mechanistic hopping model for the solvent particles. The simulation setup is then modified, allowing us to explore the timescales involved in the relaxation dynamics of the system in the period preceding the steady state. Further consideration is also given to the relative roles of diffusive and non-diffusive solvent transport in this period. Finally, in a novel modification to the classic osmosis experiment, the solute particles are driven out-of-equilibrium by the input of energy. The effect of this modification on the osmotic pressure and the osmotic ow is studied and we find that active solute particles can cause reverse osmosis to occur. The possibility of defining a new "osmotic effective temperature" is also considered and compared to the results of diffusive and kinetic temperatures..

  5. Memory in motion: movement dynamics reveal memory strength.

    PubMed

    Papesh, Megan H; Goldinger, Stephen D

    2012-10-01

    Recognition memory is typically examined as a discrete end-state, describable by static variables, such as accuracy, response time, and confidence. In the present study, we combined real-time mouse-tracking with subsequent, overt confidence estimates to examine the dynamic nature of memory decisions. By examining participants' streaming x-, y- mouse coordinates during recognition decisions, we observed that movement trajectories revealed underlying response confidence. More confident decisions were associated with shorter decision times and more linear response trajectories. Less confident decisions were made slowly, with increased trajectory curvature. Statistical indices of curvature and decision times, including area-under-the-curve and time to maximum deviation, suggested that memory strength relates to response dynamics. Whether participants were correct or incorrect, old responses showed a stronger correspondence between mouse trajectories and confidence, relative to new responses. We suggest that people subjectively experience a correspondence between feelings of memory and feelings of confidence; that subjective experience reveals itself in real-time decision processes, as suggested by sequential sampling models of recognition decisions.

  6. Molecular dynamics simulation of bicrystalline metal surface treatment

    SciTech Connect

    Nikonov, A. Yu.

    2015-10-27

    The paper reports the molecular dynamics simulation results on the behavior of a copper crystallite in local frictional contact. The crystallite has a perfect defect-free structure and contains a high-angle grain boundary of type Σ5. The influence of the initial structure on the specimen behavior under loading was analyzed. It is shown that nanoblocks are formed in the subsurface layer. The atomic mechanism of nanofragmentation was studied. A detailed analysis of atomic displacements in the blocks showed that the displacements are rotational. Calculations revealed that the misorientation angle of formed nanoblocks along different directions does not exceed 2 degrees.

  7. Brownian dynamics simulation of restricted rotational diffusion.

    PubMed Central

    Martínez, M C; García de la Torre, J

    1987-01-01

    The restricted rotational diffusion of an axially symmetric particle is simulated by the Brownian dynamics technique. In addition to the wobbling-in-a-cone model, several continuous potentials are considered. The particle studied is particularly simple: a sphere anchored to a point fixed in space. However, presenting the results in a convenient, reduced form, they are valid for any axially symmetric particle. From simulated rotational trajectories, we calculate (P2(cos alpha] as a function of t, where alpha is the angle between two orientations separated by time t and P2 is the second Legendre polynomial. This correlation function is closely related to time-resolved electro-optic and spectroscopic properties. Simulated results for the cone model are in excellent agreement with the quasiexact results of Lipari and Szabo (1981, J. Chem. Phys., 75:2971-2976). Thus we confirm the good performance of the simulation technique and the validity of our working conditions. Novel results are presented for continuous restricting potentials, V(theta). The (P2) results for V = 1/2K theta 2 and V = Q(1 - cos theta) are practically the same if K and Q are chosen so tht the long-time (P2) values coincide. Thus, the quadratic potential seems to be a good representation of any monotonically increasing potential. However, for an uniaxial potential such as V = Csin2 theta, the decay is appreciably faster. The (P2) decays simulated for the continuous potentials are analyzed by the monoexponential version of the cone model. We found that such an analysis produces an overestimation of the true rotational diffusion coefficient of approximately 15% only, although for uniaxial potentials the error may be larger. PMID:3663834

  8. Massively Parallel Reactive and Quantum Molecular Dynamics Simulations

    NASA Astrophysics Data System (ADS)

    Vashishta, Priya

    2015-03-01

    In this talk I will discuss two simulations: Cavitation bubbles readily occur in fluids subjected to rapid changes in pressure. We use billion-atom reactive molecular dynamics simulations on a 163,840-processor BlueGene/P supercomputer to investigate chemical and mechanical damages caused by shock-induced collapse of nanobubbles in water near silica surface. Collapse of an empty nanobubble generates high-speed nanojet, resulting in the formation of a pit on the surface. The gas-filled bubbles undergo partial collapse and consequently the damage on the silica surface is mitigated. Quantum molecular dynamics (QMD) simulations are performed on 786,432-processor Blue Gene/Q to study on-demand production of hydrogen gas from water using Al nanoclusters. QMD simulations reveal rapid hydrogen production from water by an Al nanocluster. We find a low activation-barrier mechanism, in which a pair of Lewis acid and base sites on the Aln surface preferentially catalyzes hydrogen production. I will also discuss on-demand production of hydrogen gas from water using and LiAl alloy particles. Research reported in this lecture was carried in collaboration with Rajiv Kalia, Aiichiro Nakano and Ken-ichi Nomura from the University of Southern California, and Fuyuki Shimojo and Kohei Shimamura from Kumamoto University, Japan.

  9. Brownian Dynamics Simulations of Ion Transport through the VDAC

    PubMed Central

    Lee, Kyu Il; Rui, Huan; Pastor, Richard W.; Im, Wonpil

    2011-01-01

    It is important to gain a physical understanding of ion transport through the voltage-dependent anion channel (VDAC) because this channel provides primary permeation pathways for metabolites and electrolytes between the cytosol and mitochondria. We performed grand canonical Monte Carlo/Brownian dynamics (GCMC/BD) simulations to explore the ion transport properties of human VDAC isoform 1 (hVDAC1; PDB:2K4T) embedded in an implicit membrane. When the MD-derived, space-dependent diffusion constant was used in the GCMC/BD simulations, the current-voltage characteristics and ion number profiles inside the pore showed excellent agreement with those calculated from all-atom molecular-dynamics (MD) simulations, thereby validating the GCMC/BD approach. Of the 20 NMR models of hVDAC1 currently available, the third one (NMR03) best reproduces both experimental single-channel conductance and ion selectivity (i.e., the reversal potential). In addition, detailed analyses of the ion trajectories, one-dimensional multi-ion potential of mean force, and protein charge distribution reveal that electrostatic interactions play an important role in the channel structure and ion transport relationship. Finally, the GCMC/BD simulations of various mutants based on NMR03 show good agreement with experimental ion selectivity. The difference in ion selectivity between the wild-type and the mutants is the result of altered potential of mean force profiles that are dominated by the electrostatic interactions. PMID:21281575

  10. How to identify dislocations in molecular dynamics simulations?

    NASA Astrophysics Data System (ADS)

    Li, Duo; Wang, FengChao; Yang, ZhenYu; Zhao, YaPu

    2014-12-01

    Dislocations are of great importance in revealing the underlying mechanisms of deformed solid crystals. With the development of computational facilities and technologies, the observations of dislocations at atomic level through numerical simulations are permitted. Molecular dynamics (MD) simulation suggests itself as a powerful tool for understanding and visualizing the creation of dislocations as well as the evolution of crystal defects. However, the numerical results from the large-scale MD simulations are not very illuminating by themselves and there exist various techniques for analyzing dislocations and the deformed crystal structures. Thus, it is a big challenge for the beginners in this community to choose a proper method to start their investigations. In this review, we summarized and discussed up to twelve existing structure characterization methods in MD simulations of deformed crystal solids. A comprehensive comparison was made between the advantages and disadvantages of these typical techniques. We also examined some of the recent advances in the dynamics of dislocations related to the hydraulic fracturing. It was found that the dislocation emission has a significant effect on the propagation and bifurcation of the crack tip in the hydraulic fracturing.

  11. The Dynamics of Miscible Interfaces: Simulations

    NASA Technical Reports Server (NTRS)

    Meiburg, Eckart

    2005-01-01

    This research project focuses on the dynamics of interfacial regions between miscible fluids. While much attention has focused on immiscible interfaces in the past, miscible interfaces have been explored to a much lesser degree, so that there are many open questions regarding their dynamics at this time. Among the more pressing issues is the role that nonconventional stresses can play in such interfacial regions. Such stresses are typically not accounted for in efforts to model the dynamics of miscible flows. Our research aims to clarify under which circumstances these stresses do have to be taken into account, and what quantitative approaches are most suitable in this regard. In order to address these issues, we have focused on conducting linear stability analyses and nonlinear simulations for capillary tube and Hele-Shaw flows, and to compare the results with corresponding experiments performed in the labs of our co-investigators Prof. Maxworthy at USC, and Dr. Balasubramaniam at NASA. Over the duration of the project we have, among other things, focused on the effects of variable diffusion coefficients in such flows, and specifically on their influence in the growth of instabilities. Furthermore, our three-dimensional spectral element simulations have made good progress, so that we have come to a point where we can conduct more detailed comparisons with experimental observations. We are currently focusing our efforts on reproducing the tip-splitting instability observed by Maxworthy. Finally, we have discovered a new core-annular flow instability in the Stokes flow regime during the last year. This represents a significant finding, as this instability does not have an immiscible counterpart.

  12. Photodynamics of oxybenzone sunscreen: Nonadiabatic dynamics simulations.

    PubMed

    Li, Chun-Xiang; Guo, Wei-Wei; Xie, Bin-Bin; Cui, Ganglong

    2016-08-21

    Herein we have used combined static electronic structure calculations and "on-the-fly" global-switching trajectory surface-hopping dynamics simulations to explore the photochemical mechanism of oxybenzone sunscreen. We have first employed the multi-configurational CASSCF method to optimize minima, conical intersections, and minimum-energy reaction paths related to excited-state intramolecular proton transfer (ESIPT) and excited-state decays in the (1)ππ(∗), (1)nπ(∗), and S0 states (energies are refined at the higher MS-CASPT2 level). According to the mapped potential energy profiles, we have identified two ultrafast excited-state deactivation pathways for the initially populated (1)ππ(∗) system. The first is the diabatic ESIPT process along the (1)ππ(∗) potential energy profile. The generated (1)ππ(∗) keto species then decays to the S0 state via the keto (1)ππ(∗)/gs conical intersection. The second is internal conversion to the dark (1)nπ(∗) state near the (1)ππ(∗) /(1)nπ(∗) crossing point in the course of the diabatic (1)ππ(∗) ESIPT process. Our following dynamics simulations have shown that the ESIPT and (1)ππ(∗) → S0 internal conversion times are 104 and 286 fs, respectively. Finally, our present work demonstrates that in addition to the ESIPT process and the (1)ππ(∗) → S0 internal conversion in the keto region, the (1)ππ(∗) → (1)nπ(∗) internal conversion in the enol region plays as well an important role for the excited-state relaxation dynamics of oxybenzone.

  13. Photodynamics of oxybenzone sunscreen: Nonadiabatic dynamics simulations

    NASA Astrophysics Data System (ADS)

    Li, Chun-Xiang; Guo, Wei-Wei; Xie, Bin-Bin; Cui, Ganglong

    2016-08-01

    Herein we have used combined static electronic structure calculations and "on-the-fly" global-switching trajectory surface-hopping dynamics simulations to explore the photochemical mechanism of oxybenzone sunscreen. We have first employed the multi-configurational CASSCF method to optimize minima, conical intersections, and minimum-energy reaction paths related to excited-state intramolecular proton transfer (ESIPT) and excited-state decays in the 1ππ∗, 1nπ∗, and S0 states (energies are refined at the higher MS-CASPT2 level). According to the mapped potential energy profiles, we have identified two ultrafast excited-state deactivation pathways for the initially populated 1ππ∗ system. The first is the diabatic ESIPT process along the 1ππ∗ potential energy profile. The generated 1ππ∗ keto species then decays to the S0 state via the keto 1ππ∗/gs conical intersection. The second is internal conversion to the dark 1nπ∗ state near the 1ππ∗ /1nπ∗ crossing point in the course of the diabatic 1ππ∗ ESIPT process. Our following dynamics simulations have shown that the ESIPT and 1ππ∗ → S0 internal conversion times are 104 and 286 fs, respectively. Finally, our present work demonstrates that in addition to the ESIPT process and the 1ππ∗ → S0 internal conversion in the keto region, the 1ππ∗ → 1nπ∗ internal conversion in the enol region plays as well an important role for the excited-state relaxation dynamics of oxybenzone.

  14. Dynamical simulations of vesicle growth and division

    NASA Astrophysics Data System (ADS)

    Ruiz-Herrero, Teresa; Mahadevan, L.

    2015-03-01

    Prebiotic cells constitute a beautiful and intriguing example of self-replicating vesicles. How these cells managed to grow and divide without sophisticated machinery is still an open question. The properties of these primitive vesicles can shed light on the ways modern cells have evolved by exploiting those characteristics to develop their replication mechanisms. The equilibrium configurations of elastic shells are well understood, however the dynamical behavior during growth still lacks of a deep theoretical understanding. To study vesicle growth from a general perspective, we have developed a minimal generic model where vesicles are represented by a 2D spring network and characterized by a minimum set of magnitudes: growth rate, permeability, bending stiffness, viscosity and temperature. We have performed hybrid molecuar dynamic simulations as a function of a reduced set of dimensionless parameters. Three main outcomes were observed: vesicles that grow without division, vesicles that divide symmetrically, and vesicles that act as generators of daughter vesicles. The type of outcome depends on the system parameters and specifically on its dynamics via two timescales. Furthermore, we found sets of parameters where the system shows size homeostasis. TRH was supported by Ramon Areces Foundation.

  15. Molecular dynamics simulations of xDNA.

    PubMed

    Varghese, Mathew K; Thomas, Renjith; Unnikrishnan, N V; Sudarsanakumar, C

    2009-05-01

    xDNA is a modified DNA, which contains natural as well as expanded bases. Expanded bases are generated by the addition of a benzene spacer to the natural bases. A set of AMBER force-field parameters were derived for the expanded bases and the structural dynamics of the xDNA decamer (xT5' G xT A xC xG C xA xG T3').(xA5' C T xG C G xT A xC A3') was explored using a 22 ns molecular dynamics simulation in explicit solvent. During the simulation, the duplex retained its Watson-Crick base-pairing and double helical structure, with deviations from the starting B-form geometry towards A-form; the deviations are mainly in the backbone torsion angles and in the helical parameters. The sugar pucker of the residues were distributed among a variety of modes; C2' endo, C1' exo, O4' endo, C4' exo, C2' exo, and C3' endo. The enhanced stacking interactions on account of the modification in the bases could help to retain the duplex nature of the helix with minor deviations from the ideal geometry. In our simulation, the xDNA showed a reduced minor groove width and an enlarged major groove width in comparison with the NMR structure. Both the grooves are larger than that of standard B-DNA, but major groove width is larger than that of A-DNA with almost equal minor groove width. The enlarged groove widths and the possibility of additional hydration in the grooves makes xDNA a potential molecule for various applications. Copyright (c) 2009 Wiley Periodicals, Inc.

  16. Quantum molecular dynamics simulations of dense matter

    SciTech Connect

    Collins, L.; Kress, J.; Troullier, N.; Lenosky, T.; Kwon, I.

    1997-12-31

    The authors have developed a quantum molecular dynamics (QMD) simulation method for investigating the properties of dense matter in a variety of environments. The technique treats a periodically-replicated reference cell containing N atoms in which the nuclei move according to the classical equations-of-motion. The interatomic forces are generated from the quantum mechanical interactions of the (between?) electrons and nuclei. To generate these forces, the authors employ several methods of varying sophistication from the tight-binding (TB) to elaborate density functional (DF) schemes. In the latter case, lengthy simulations on the order of 200 atoms are routinely performed, while for the TB, which requires no self-consistency, upwards to 1000 atoms are systematically treated. The QMD method has been applied to a variety cases: (1) fluid/plasma Hydrogen from liquid density to 20 times volume-compressed for temperatures of a thousand to a million degrees Kelvin; (2) isotopic hydrogenic mixtures, (3) liquid metals (Li, Na, K); (4) impurities such as Argon in dense hydrogen plasmas; and (5) metal/insulator transitions in rare gas systems (Ar,Kr) under high compressions. The advent of parallel versions of the methods, especially for fast eigensolvers, presage LDA simulations in the range of 500--1000 atoms and TB runs for tens of thousands of particles. This leap should allow treatment of shock chemistry as well as large-scale mixtures of species in highly transient environments.

  17. Molecular Dynamics Simulation of a RNA Aptasensor.

    PubMed

    Ruan, Min; Seydou, Mahamadou; Noel, Vincent; Piro, Benoit; Maurel, François; Barbault, Florent

    2017-04-14

    Single-stranded RNA aptamers have emerged as novel biosensor tools. However, the immobilization procedure of the aptamer onto a surface generally induces a loss of affinity. To understand this molecular process, we conducted a complete simulation study for the Flavin mononucleotide aptamer for which experimental data are available. Several molecular dynamics simulations (MD) of the Flavin in complex with its RNA aptamer were conducted in solution, linked with six thymidines (T6) and, finally, immobilized on an hexanol-thiol-functionalized gold surface. First, we demonstrated that our MD computations were able to reproduce the experimental solution structure and to provide a meaningful estimation of the Flavin free energy of binding. We also demonstrated that the T6 linkage, by itself, does not generate a perturbation of the Flavin recognition process. From the simulation of the complete biosensor system, we observed that the aptamer stays oriented parallel to the surface at a distance around 36 Å avoiding, this way, interaction with the surface. We evidenced a structural reorganization of the Flavin aptamer binding mode related to the loss of affinity and induced by an anisotropic distribution of sodium cationic densities. This means that ionic diffusion is different between the surface and the aptamer than above this last one. We suggest that these findings might be extrapolated to other nucleic acids systems for the future design of biosensors with higher efficiency and selectivity.

  18. Brownian dynamics simulation of DNA condensation.

    PubMed Central

    Sottas, P E; Larquet, E; Stasiak, A; Dubochet, J

    1999-01-01

    DNA condensation observed in vitro with the addition of polyvalent counterions is due to intermolecular attractive forces. We introduce a quantitative model of these forces in a Brownian dynamics simulation in addition to a standard mean-field Poisson-Boltzmann repulsion. The comparison of a theoretical value of the effective diameter calculated from the second virial coefficient in cylindrical geometry with some experimental results allows a quantitative evaluation of the one-parameter attractive potential. We show afterward that with a sufficient concentration of divalent salt (typically approximately 20 mM MgCl(2)), supercoiled DNA adopts a collapsed form where opposing segments of interwound regions present zones of lateral contact. However, under the same conditions the same plasmid without torsional stress does not collapse. The condensed molecules present coexisting open and collapsed plectonemic regions. Furthermore, simulations show that circular DNA in 50% methanol solutions with 20 mM MgCl(2) aggregates without the requirement of torsional energy. This confirms known experimental results. Finally, a simulated DNA molecule confined in a box of variable size also presents some local collapsed zones in 20 mM MgCl(2) above a critical concentration of the DNA. Conformational entropy reduction obtained either by supercoiling or by confinement seems thus to play a crucial role in all forms of condensation of DNA. PMID:10512808

  19. Digital system for structural dynamics simulation

    NASA Technical Reports Server (NTRS)

    Krauter, A. I.; Lagace, L. J.; Wojnar, M. K.; Glor, C.

    1982-01-01

    State-of-the-art digital hardware and software for the simulation of complex structural dynamic interactions, such as those which occur in rotating structures (engine systems). System were incorporated in a designed to use an array of processors in which the computation for each physical subelement or functional subsystem would be assigned to a single specific processor in the simulator. These node processors are microprogrammed bit-slice microcomputers which function autonomously and can communicate with each other and a central control minicomputer over parallel digital lines. Inter-processor nearest neighbor communications busses pass the constants which represent physical constraints and boundary conditions. The node processors are connected to the six nearest neighbor node processors to simulate the actual physical interface of real substructures. Computer generated finite element mesh and force models can be developed with the aid of the central control minicomputer. The control computer also oversees the animation of a graphics display system, disk-based mass storage along with the individual processing elements.

  20. Dynamics simulations for engineering macromolecular interactions.

    PubMed

    Robinson-Mosher, Avi; Shinar, Tamar; Silver, Pamela A; Way, Jeffrey

    2013-06-01

    The predictable engineering of well-behaved transcriptional circuits is a central goal of synthetic biology. The artificial attachment of promoters to transcription factor genes usually results in noisy or chaotic behaviors, and such systems are unlikely to be useful in practical applications. Natural transcriptional regulation relies extensively on protein-protein interactions to insure tightly controlled behavior, but such tight control has been elusive in engineered systems. To help engineer protein-protein interactions, we have developed a molecular dynamics simulation framework that simplifies features of proteins moving by constrained Brownian motion, with the goal of performing long simulations. The behavior of a simulated protein system is determined by summation of forces that include a Brownian force, a drag force, excluded volume constraints, relative position constraints, and binding constraints that relate to experimentally determined on-rates and off-rates for chosen protein elements in a system. Proteins are abstracted as spheres. Binding surfaces are defined radially within a protein. Peptide linkers are abstracted as small protein-like spheres with rigid connections. To address whether our framework could generate useful predictions, we simulated the behavior of an engineered fusion protein consisting of two 20,000 Da proteins attached by flexible glycine/serine-type linkers. The two protein elements remained closely associated, as if constrained by a random walk in three dimensions of the peptide linker, as opposed to showing a distribution of distances expected if movement were dominated by Brownian motion of the protein domains only. We also simulated the behavior of fluorescent proteins tethered by a linker of varying length, compared the predicted Förster resonance energy transfer with previous experimental observations, and obtained a good correspondence. Finally, we simulated the binding behavior of a fusion of two ligands that could

  1. Dynamics simulations for engineering macromolecular interactions

    NASA Astrophysics Data System (ADS)

    Robinson-Mosher, Avi; Shinar, Tamar; Silver, Pamela A.; Way, Jeffrey

    2013-06-01

    The predictable engineering of well-behaved transcriptional circuits is a central goal of synthetic biology. The artificial attachment of promoters to transcription factor genes usually results in noisy or chaotic behaviors, and such systems are unlikely to be useful in practical applications. Natural transcriptional regulation relies extensively on protein-protein interactions to insure tightly controlled behavior, but such tight control has been elusive in engineered systems. To help engineer protein-protein interactions, we have developed a molecular dynamics simulation framework that simplifies features of proteins moving by constrained Brownian motion, with the goal of performing long simulations. The behavior of a simulated protein system is determined by summation of forces that include a Brownian force, a drag force, excluded volume constraints, relative position constraints, and binding constraints that relate to experimentally determined on-rates and off-rates for chosen protein elements in a system. Proteins are abstracted as spheres. Binding surfaces are defined radially within a protein. Peptide linkers are abstracted as small protein-like spheres with rigid connections. To address whether our framework could generate useful predictions, we simulated the behavior of an engineered fusion protein consisting of two 20 000 Da proteins attached by flexible glycine/serine-type linkers. The two protein elements remained closely associated, as if constrained by a random walk in three dimensions of the peptide linker, as opposed to showing a distribution of distances expected if movement were dominated by Brownian motion of the protein domains only. We also simulated the behavior of fluorescent proteins tethered by a linker of varying length, compared the predicted Förster resonance energy transfer with previous experimental observations, and obtained a good correspondence. Finally, we simulated the binding behavior of a fusion of two ligands that could

  2. Origin of Granular Capillarity Revealed by Particle-Based Simulations.

    PubMed

    Fan, Fengxian; Parteli, Eric J R; Pöschel, Thorsten

    2017-05-26

    When a thin tube is dipped into water, the water will ascend to a certain height, against the action of gravity. While this effect, termed capillarity, is well known, recent experiments have shown that agitated granular matter reveals a similar behavior. Namely, when a vertical tube is inserted into a container filled with granular material and is then set into vertical vibration, the particles rise up along the tube. In the present Letter, we investigate the effect of granular capillarity by means of numerical simulations and show that the effect is caused by convection of the granular material in the container. Moreover, we identify two regimes of behavior for the capillary height H_{c}^{∞} depending on the tube-to-particle-diameter ratio, D/d. For large D/d, a scaling of H_{c}^{∞} with the inverse of the tube diameter, which is reminiscent of liquids, is observed. However, when D/d decreases down to values smaller than a few particle sizes, a uniquely granular behavior is observed where H_{c}^{∞} increases linearly with the tube diameter.

  3. Origin of Granular Capillarity Revealed by Particle-Based Simulations

    NASA Astrophysics Data System (ADS)

    Fan, Fengxian; Parteli, Eric J. R.; Pöschel, Thorsten

    2017-05-01

    When a thin tube is dipped into water, the water will ascend to a certain height, against the action of gravity. While this effect, termed capillarity, is well known, recent experiments have shown that agitated granular matter reveals a similar behavior. Namely, when a vertical tube is inserted into a container filled with granular material and is then set into vertical vibration, the particles rise up along the tube. In the present Letter, we investigate the effect of granular capillarity by means of numerical simulations and show that the effect is caused by convection of the granular material in the container. Moreover, we identify two regimes of behavior for the capillary height Hc∞ depending on the tube-to-particle-diameter ratio, D /d . For large D /d , a scaling of Hc∞ with the inverse of the tube diameter, which is reminiscent of liquids, is observed. However, when D /d decreases down to values smaller than a few particle sizes, a uniquely granular behavior is observed where Hc∞ increases linearly with the tube diameter.

  4. Genomic analysis of regulatory network dynamics reveals large topological changes

    NASA Astrophysics Data System (ADS)

    Luscombe, Nicholas M.; Madan Babu, M.; Yu, Haiyuan; Snyder, Michael; Teichmann, Sarah A.; Gerstein, Mark

    2004-09-01

    Network analysis has been applied widely, providing a unifying language to describe disparate systems ranging from social interactions to power grids. It has recently been used in molecular biology, but so far the resulting networks have only been analysed statically. Here we present the dynamics of a biological network on a genomic scale, by integrating transcriptional regulatory information and gene-expression data for multiple conditions in Saccharomyces cerevisiae. We develop an approach for the statistical analysis of network dynamics, called SANDY, combining well-known global topological measures, local motifs and newly derived statistics. We uncover large changes in underlying network architecture that are unexpected given current viewpoints and random simulations. In response to diverse stimuli, transcription factors alter their interactions to varying degrees, thereby rewiring the network. A few transcription factors serve as permanent hubs, but most act transiently only during certain conditions. By studying sub-network structures, we show that environmental responses facilitate fast signal propagation (for example, with short regulatory cascades), whereas the cell cycle and sporulation direct temporal progression through multiple stages (for example, with highly inter-connected transcription factors). Indeed, to drive the latter processes forward, phase-specific transcription factors inter-regulate serially, and ubiquitously active transcription factors layer above them in a two-tiered hierarchy. We anticipate that many of the concepts presented here-particularly the large-scale topological changes and hub transience-will apply to other biological networks, including complex sub-systems in higher eukaryotes.

  5. Genomic analysis of regulatory network dynamics reveals large topological changes.

    PubMed

    Luscombe, Nicholas M; Babu, M Madan; Yu, Haiyuan; Snyder, Michael; Teichmann, Sarah A; Gerstein, Mark

    2004-09-16

    Network analysis has been applied widely, providing a unifying language to describe disparate systems ranging from social interactions to power grids. It has recently been used in molecular biology, but so far the resulting networks have only been analysed statically. Here we present the dynamics of a biological network on a genomic scale, by integrating transcriptional regulatory information and gene-expression data for multiple conditions in Saccharomyces cerevisiae. We develop an approach for the statistical analysis of network dynamics, called SANDY, combining well-known global topological measures, local motifs and newly derived statistics. We uncover large changes in underlying network architecture that are unexpected given current viewpoints and random simulations. In response to diverse stimuli, transcription factors alter their interactions to varying degrees, thereby rewiring the network. A few transcription factors serve as permanent hubs, but most act transiently only during certain conditions. By studying sub-network structures, we show that environmental responses facilitate fast signal propagation (for example, with short regulatory cascades), whereas the cell cycle and sporulation direct temporal progression through multiple stages (for example, with highly inter-connected transcription factors). Indeed, to drive the latter processes forward, phase-specific transcription factors inter-regulate serially, and ubiquitously active transcription factors layer above them in a two-tiered hierarchy. We anticipate that many of the concepts presented here--particularly the large-scale topological changes and hub transience--will apply to other biological networks, including complex sub-systems in higher eukaryotes.

  6. On sequential dynamical systems and simulation

    SciTech Connect

    Barrett, C.L.; Mortveit, H.S.; Reidys, C.M.

    1999-06-01

    The generic structure of computer simulations motivates a new class of discrete dynamical systems that captures this structure in a mathematically precise way. This class of systems consists of (1) a loopfree graph {Upsilon} with vertex set {l_brace}1,2,{hor_ellipsis},n{r_brace} where each vertex has a binary state, (2) a vertex labeled set of functions (F{sub i,{Upsilon}}:F{sub 2}{sup n} {r_arrow} F{sub 2}{sup n}){sub i} and (3) a permutation {pi} {element_of} S{sub n}. The function F{sub i,{Upsilon}} updates the state of vertex i as a function of the states of vertex i and its {Upsilon}-neighbors and leaves the states of all other vertices fixed. The permutation {pi} represents the update ordering, i.e., the order in which the functions F{sub i,{Upsilon}} are applied. By composing the functions F{sub i,{Upsilon}} in the order given by {pi} one obtains the dynamical system (equation given in paper) which the authors refer to as a sequential dynamical system, or SDS for short. The authors will present bounds for the number of functionally different systems and for the number of nonisomorphic digraphs {Gamma}[F{sub {Upsilon}},{pi}] that can be obtained by varying the update order and applications of these to specific graphs and graph classes. This will be done using both combinatorial/algebraic techniques and probabilistic techniques. Finally the authors give results on dynamical system properties for some special systems.

  7. Indole Localization in an Explicit Bilayer Revealed via Molecular Dynamics

    NASA Astrophysics Data System (ADS)

    Norman, Kristen

    2005-11-01

    It is well known that the amino-acid tryptophan is particularly stable in the interfacial region of biological membranes, and this preference is a property of the tryptophan side-chain. Analogues of this side-chain, such as indole, strongly localize in the interfacial region, especially near the glycerol moiety of the lipids in the bilayer. Using molecular dynamics calculations, we determine the potential of mean force (PMF) for indoles in the bilayer. We compare the calculated PMF for indole with that of benzene to show that exclusion from the center of the lipid bilayer does not occur in all aromatics, but is strong in indoles. We find three minima in the PMF. Indole is most stabilized near the glycerol moiety. A weaker binding location is found near the choline groups of the lipid molecules. An even weaker binding side is found near the center of the lipid hydrocarbon core. Comparisions between uncharged, weakly charged, and highly charged indoles demonstrate that the exclusion is caused by the charge distribution on the indole rather than the ``lipo-phobic'' effect. High temperature simulations are used to determine the relative contribution of enthalpy and entropy to indole localization. The orientation of indole is found to be largely charge independent and is a strong function of depth within the bilayer. We find good agreement between simulated SCD order parameters for indole and experimentally determined order parameters.

  8. REVEAL: An Extensible Reduced Order Model Builder for Simulation and Modeling

    SciTech Connect

    Agarwal, Khushbu; Sharma, Poorva; Ma, Jinliang; Lo, Chaomei; Gorton, Ian; Liu, Yan

    2013-04-30

    Many science domains need to build computationally efficient and accurate representations of high fidelity, computationally expensive simulations. These computationally efficient versions are known as reduced-order models. This paper presents the design and implementation of a novel reduced-order model (ROM) builder, the REVEAL toolset. This toolset generates ROMs based on science- and engineering-domain specific simulations executed on high performance computing (HPC) platforms. The toolset encompasses a range of sampling and regression methods that can be used to generate a ROM, automatically quantifies the ROM accuracy, and provides support for an iterative approach to improve ROM accuracy. REVEAL is designed to be extensible in order to utilize the core functionality with any simulator that has published input and output formats. It also defines programmatic interfaces to include new sampling and regression techniques so that users can ‘mix and match’ mathematical techniques to best suit the characteristics of their model. In this paper, we describe the architecture of REVEAL and demonstrate its usage with a computational fluid dynamics model used in carbon capture.

  9. Coupled nucleotide covariations reveal dynamic RNA interaction patterns.

    PubMed Central

    Gultyaev, A P; Franch, T; Gerdes, K

    2000-01-01

    Evolutionarily conserved structures in related RNA molecules contain coordinated variations (covariations) of paired nucleotides. Analysis of covariations is a very powerful approach to deduce phylogenetically conserved (i.e., functional) conformations, including tertiary interactions. Here we discuss conserved RNA folding pathways that are revealed by covariation patterns. In such pathways, structural requirements for alternative pairings cause some nucleotides to covary with two different partners. Such "coupled" covariations between three or more nucleotides were found in various types of RNAs. The analysis of coupled covariations can unravel important features of RNA folding dynamics and improve phylogeny reconstruction in some cases. Importantly, it is necessary to distinguish between multiple covariations determined by mutually exclusive structures and those determined by tertiary contacts. PMID:11105748

  10. More Dynamical Properties Revealed from a 3D Lorenz-like System

    NASA Astrophysics Data System (ADS)

    Wang, Haijun; Li, Xianyi

    After a 3D Lorenz-like system has been revisited, more rich hidden dynamics that was not found previously is clearly revealed. Some more precise mathematical work, such as for the complete distribution and the local stability and bifurcation of its equilibrium points, the existence of singularly degenerate heteroclinic cycles as well as homoclinic and heteroclinic orbits, and the dynamics at infinity, is carried out in this paper. In particular, another possible new mechanism behind the creation of chaotic attractors is presented. Based on this mechanism, some different structure types of chaotic attractors are numerically found in the case of small b > 0. All theoretical results obtained are further illustrated by numerical simulations. What we formulate in this paper is to not only show those dynamical properties hiding in this system, but also (more mainly) present a kind of way and means — both "locally" and "globally" and both "finitely" and "infinitely" — to comprehensively explore a given system.

  11. Indole Localization in Lipid Membranes Revealed by Molecular Simulation

    PubMed Central

    Norman, Kristen E.; Nymeyer, Hugh

    2006-01-01

    It is commonly known that the amino acid residue tryptophan and its side-chain analogs, e.g., indole, are strongly attracted to the interfacial region of lipid bilayers. Phenylalanine and its side-chain analogs, e.g., benzene, do not localize in the interface but are distributed throughout the lipid bilayer. We use molecular dynamics to investigate the details of indole and benzene localization and orientation within a POPC bilayer and the factors that lead to their different properties. We identify three sites in the bilayer at which indole is localized: 1), a site in the interface near the glycerol moiety; 2), a weakly bound site in the interface near the choline moiety; and 3), a weakly bound site in the center of the bilayer's hydrocarbon core. Benzene is localized in the same three positions, but the most stable position is the hydrocarbon core followed by the site near the glycerol moiety. Transfer of indole from water to the hydrocarbon core shows a classic hydrophobic effect. In contrast, interfacial binding is strongly enthalpy driven. We use several different sets of partial charges to investigate the factors that contribute to indole's and benzene's orientational and spatial distribution. Our simulations show that a number of electrostatic interactions appear to contribute to localization, including hydrogen bonding to the lipid carbonyl groups, cation-π interactions, interactions between the indole dipole and the lipid bilayer's strong interfacial electric field, and nonspecific electrostatic stabilization due to a mismatch in the variation of the nonpolar forces and local dielectric with position in the bilayer. PMID:16815896

  12. The benefits of dynamic simulation to the Mensa development project

    SciTech Connect

    Lamey, M.F.; Lang, P.; Rainey, M.; Turner, S.; Wasden, F.

    1998-12-31

    Deep water production and sub sea tiebacks have presented new operational challenges for production operators. Shell Deepwater Development Inc. recent developed a dynamic simulation of its record setting Mensa gas field sub sea development. The project has set world records for water depth and pipeline length. The model revealed several transient conditions that were not readily apparent from earlier work and/or development tools. Changes to the start up plan and normal operating guidelines resulted. The model was also used to train operating personnel in the dynamic response of the system, which is significantly different from conventional offshore systems. A data collection plan was developed and implemented to compare actual vs. predicted operating conditions. Results and recommendation for future developments are presented.

  13. Structural dynamics of the box C/D RNA kink-turn and its complex with proteins: the role of the A-minor 0 interaction, long-residency water bridges, and structural ion-binding sites revealed by molecular simulations.

    PubMed

    Spacková, Nad'a; Réblová, Kamila; Sponer, Jirí

    2010-08-19

    Kink-turns (K-turns) are recurrent elbow-like RNA motifs that participate in protein-assisted RNA folding and contribute to RNA dynamics. We carried out a set of molecular dynamics (MD) simulations using parm99 and parmbsc0 force fields to investigate structural dynamics of the box C/D RNA and its complexes with two proteins: native archaeal L7ae protein and human 15.5 kDa protein, originally bound to very similar structure of U4 snRNA. The box C/D RNA forms K-turn with A-minor 0 tertiary interaction between its canonical (C) and noncanonical (NC) stems. The local K-turn architecture is thus different from the previously studied ribosomal K-turns 38 and 42 having A-minor I interaction. The simulations reveal visible structural dynamics of this tertiary interaction involving altogether six substates which substantially contribute to the elbow-like flexibility of the K-turn. The interaction can even temporarily shift to the A-minor I type pattern; however, this is associated with distortion of the G/A base pair in the NC-stem of the K-turn. The simulations show reduction of the K-turn flexibility upon protein binding. The protein interacts with the apex of the K-turn and with the NC-stem. The protein-RNA interface includes long-residency hydration sites. We have also found long-residency hydration sites and major ion-binding sites associated with the K-turn itself. The overall topology of the K-turn remains stable in all simulations. However, in simulations of free K-turn, we observed instability of the key C16(O2')-A7(N1) H-bond, which is a signature interaction of K-turns and which was visibly more stable in simulations of K-turns possessing A-minor I interaction. It may reflect either some imbalance of the force field or it may be a correct indication of early stages of unfolding since this K-turn requires protein binding for its stabilization. Interestingly, the 16(O2')-7(N1) H- bond is usually not fully lost since it is replaced by a water bridge with a tightly

  14. Molecular Dynamics Simulations of Homogeneous Crystallization in Polymer Melt

    NASA Astrophysics Data System (ADS)

    Kong, Bin

    2015-03-01

    Molecular mechanisms of homogeneous nucleation and crystal growth from the melt of polyethylene-like polymer were investigated by molecular dynamics simulations. The crystallinity was determined by using the site order parameter method (SOP), which described local order degree around an atom. Snapshots of the simulations showed evolution of the nucleation and the crystal growth through SOP images clearly. The isothermal crystallization kinetics was determined at different temperatures. The rate of crystallization, Kc, and the Avrami exponents, n, were determined as a function of temperature. The forming of nucleis was traced to reveal that the nucleis were formed with more ordered cores and less ordered shells. A detailed statistical analysis of the MD snapshots and trajectories suggested conformations of the polymer chains changed smoothly from random coil to chain folded lamella in the crystallization processes.

  15. Circulating protein synthesis rates reveal skeletal muscle proteome dynamics

    PubMed Central

    Shankaran, Mahalakshmi; King, Chelsea L.; Angel, Thomas E.; Holmes, William E.; Li, Kelvin W.; Colangelo, Marc; Price, John C.; Turner, Scott M.; Bell, Christopher; Hamilton, Karyn L.; Miller, Benjamin F.; Hellerstein, Marc K.

    2015-01-01

    Here, we have described and validated a strategy for monitoring skeletal muscle protein synthesis rates in rodents and humans over days or weeks from blood samples. We based this approach on label incorporation into proteins that are synthesized specifically in skeletal muscle and escape into the circulation. Heavy water labeling combined with sensitive tandem mass spectrometric analysis allowed integrated synthesis rates of proteins in muscle tissue across the proteome to be measured over several weeks. Fractional synthesis rate (FSR) of plasma creatine kinase M-type (CK-M) and carbonic anhydrase 3 (CA-3) in the blood, more than 90% of which is derived from skeletal muscle, correlated closely with FSR of CK-M, CA-3, and other proteins of various ontologies in skeletal muscle tissue in both rodents and humans. Protein synthesis rates across the muscle proteome generally changed in a coordinate manner in response to a sprint interval exercise training regimen in humans and to denervation or clenbuterol treatment in rodents. FSR of plasma CK-M and CA-3 revealed changes and interindividual differences in muscle tissue proteome dynamics. In human subjects, sprint interval training primarily stimulated synthesis of structural and glycolytic proteins. Together, our results indicate that this approach provides a virtual biopsy, sensitively revealing individualized changes in proteome-wide synthesis rates in skeletal muscle without a muscle biopsy. Accordingly, this approach has potential applications for the diagnosis, management, and treatment of muscle disorders. PMID:26657858

  16. CADS:Cantera Aerosol Dynamics Simulator.

    SciTech Connect

    Moffat, Harry K.

    2007-07-01

    This manual describes a library for aerosol kinetics and transport, called CADS (Cantera Aerosol Dynamics Simulator), which employs a section-based approach for describing the particle size distributions. CADS is based upon Cantera, a set of C++ libraries and applications that handles gas phase species transport and reactions. The method uses a discontinuous Galerkin formulation to represent the particle distributions within each section and to solve for changes to the aerosol particle distributions due to condensation, coagulation, and nucleation processes. CADS conserves particles, elements, and total enthalpy up to numerical round-off error, in all of its formulations. Both 0-D time dependent and 1-D steady state applications (an opposing-flow flame application) have been developed with CADS, with the initial emphasis on developing fundamental mechanisms for soot formation within fires. This report also describes the 0-D application, TDcads, which models a time-dependent perfectly stirred reactor.

  17. Protein Dynamics from NMR and Computer Simulation

    NASA Astrophysics Data System (ADS)

    Wu, Qiong; Kravchenko, Olga; Kemple, Marvin; Likic, Vladimir; Klimtchuk, Elena; Prendergast, Franklyn

    2002-03-01

    Proteins exhibit internal motions from the millisecond to sub-nanosecond time scale. The challenge is to relate these internal motions to biological function. A strategy to address this aim is to apply a combination of several techniques including high-resolution NMR, computer simulation of molecular dynamics (MD), molecular graphics, and finally molecular biology, the latter to generate appropriate samples. Two difficulties that arise are: (1) the time scale which is most directly biologically relevant (ms to μs) is not readily accessible by these techniques and (2) the techniques focus on local and not collective motions. We will outline methods using ^13C-NMR to help alleviate the second problem, as applied to intestinal fatty acid binding protein, a relatively small intracellular protein believed to be involved in fatty acid transport and metabolism. This work is supported in part by PHS Grant GM34847 (FGP) and by a fellowship from the American Heart Association (QW).

  18. Mathematical simulation of Earth system dynamics

    NASA Astrophysics Data System (ADS)

    Dymnikov, V. P.; Lykosov, V. N.; Volodin, E. M.

    2015-05-01

    The mathematical simulation of the Earth system, the dynamics of which depends on physical, chemical, biological, and other processes and which requires interdisciplinary approaches to studying this problem, is considered. The term "the Earth system" extends the concept "the climatic system," since additional geospheres (lithosphere, heliosphere, etc.) are taken into account and a wider range of physical, chemical, biological, and social interactions is described. The present-day level of climate modeling is discussed, and some data obtained at the Institute of Numerical Mathematics, Russian Academy of Sciences (INM RAS), are presented for this purpose. The prospects for further development of climate models toward the creation of the Earth system models based on a seamless approach, according to which a unified model is used to make short-term (several days) and long-term (climatic) prediction, are considered.

  19. Simulating the dynamics of complex plasmas.

    PubMed

    Schwabe, M; Graves, D B

    2013-08-01

    Complex plasmas are low-temperature plasmas that contain micrometer-size particles in addition to the neutral gas particles and the ions and electrons that make up the plasma. The microparticles interact strongly and display a wealth of collective effects. Here we report on linked numerical simulations that reproduce many of the experimental results of complex plasmas. We model a capacitively coupled plasma with a fluid code written for the commercial package comsol. The output of this model is used to calculate forces on microparticles. The microparticles are modeled using the molecular dynamics package lammps, which we extended to include the forces from the plasma. Using this method, we are able to reproduce void formation, the separation of particles of different sizes into layers, lane formation, vortex formation, and other effects.

  20. Euclidean lattice simulation for dynamical supersymmetry breaking

    SciTech Connect

    Kanamori, Issaku; Suzuki, Hiroshi; Sugino, Fumihiko

    2008-05-01

    The global supersymmetry is spontaneously broken if and only if the ground-state energy is strictly positive. We propose to use this fact to observe the spontaneous supersymmetry breaking in Euclidean lattice simulations. For lattice formulations that possess a manifest fermionic symmetry, there exists a natural choice of a Hamiltonian operator that is consistent with a topological property of the Witten index. We confirm validity of our idea in models of the supersymmetric quantum mechanics. We then examine a possibility of a dynamical supersymmetry breaking in the two-dimensional N=(2,2) super Yang-Mills theory with the gauge group SU(2), for which the Witten index is unknown. Differently from a recent conjectural claim, our numerical result tempts us to conclude that supersymmetry is not spontaneously broken in this system.

  1. Simulating dynamical features of escape panic

    NASA Astrophysics Data System (ADS)

    Helbing, Dirk; Farkas, Illés; Vicsek, Tamás

    2000-09-01

    One of the most disastrous forms of collective human behaviour is the kind of crowd stampede induced by panic, often leading to fatalities as people are crushed or trampled. Sometimes this behaviour is triggered in life-threatening situations such as fires in crowded buildings; at other times, stampedes can arise during the rush for seats or seemingly without cause. Although engineers are finding ways to alleviate the scale of such disasters, their frequency seems to be increasing with the number and size of mass events. But systematic studies of panic behaviour and quantitative theories capable of predicting such crowd dynamics are rare. Here we use a model of pedestrian behaviour to investigate the mechanisms of (and preconditions for) panic and jamming by uncoordinated motion in crowds. Our simulations suggest practical ways to prevent dangerous crowd pressures. Moreover, we find an optimal strategy for escape from a smoke-filled room, involving a mixture of individualistic behaviour and collective `herding' instinct.

  2. Magnetotail dynamics: MHD simulations of driven and spontaneous dynamic changes

    SciTech Connect

    Birn, J.; Schindler, K.; Hesse, M.

    1994-05-01

    The dynamic evolution of the magnetotail during growth phase and expansion phase of a substorm is studied through threedimensional time-dependent MHD simulations. To model growth phase effects, an external electric field with an equatorward inflow is applied at the boundaries over a finite time period. This leads to the formation of a thin current sheet with greatly enhanced current density in the near tail, embedded in the wider plasma/current sheet, which becomes diminished in strength. A faster, spontaneous current sheet formation occurs when entropy conservation is released in an isobaric model, while the ideal MHD constraint persists. This may be a suitable model for the late, explosive part of the growth phase. The transition to the substorm expansive phase is modeled by an increase in anomalous resistivity, using either uniform resistivity or a current density dependent resistivity which is turned on when the current density exceeds a certain threshold. In both cases the violation of ideal MHD leads to resistive instability and the formation of a near-Earth neutral line, fast flow, and plasmoid ejection, together with the dipolarization and current reduction in the region further earthward. The spontaneous increase in total region 1 type field-aligned currents associated with the disruptions of the thin current sheets is less significant than that found in earlier simulations of the disruption of a wider current sheet, whereas the driven increase in the region 1 type current is substantial. The results demonstrate that the same dynamic process which appears spontaneous in the behavior of some quantities might be interpreted as entirely driven from the observation of others.

  3. Fiber lubrication: A molecular dynamics simulation study

    NASA Astrophysics Data System (ADS)

    Liu, Hongyi

    Molecular and mesoscopic level description of friction and lubrication remains a challenge because of difficulties in the phenomenological understanding of to the behaviors of solid-liquid interfaces during sliding. Fortunately, there is the computational simulation approach opens an opportunity to predict and analyze interfacial phenomena, which were studied with molecular dynamics (MD) and mesoscopic dynamics (MesoDyn) simulations. Polypropylene (PP) and cellulose are two of most common polymers in textile fibers. Confined amorphous surface layers of PP and cellulose were built successfully with xenon crystals which were used to compact the polymers. The physical and surface properties of the PP and cellulose surface layers were investigated by MD simulations, including the density, cohesive energy, volumetric thermal expansion, and contact angle with water. The topology method was employed to predict the properties of poly(alkylene glycol) (PAG) diblock copolymers and Pluronic triblock copolymers used as lubricants on surfaces. Density, zero shear viscosity, shear module, cohesive energy and solubility parameter were predicted with each block copolymer. Molecular dynamics simulations were used to study the interaction energy per unit contact area of block copolymer melts with PP and cellulose surfaces. The interaction energy is defined as the ratio of interfacial interaction energy to the contact area. Both poly(proplene oxide) (PPO) and poly(ethylene oxide) (PEO) segments provided a lipophilic character to both PP and cellulose surfaces. The PPO/PEO ratio and the molecular weight were found to impact the interaction energy on both PP and cellulose surfaces. In aqueous solutions, the interaction energy is complicated due to the presence of water and the cross interactions between the multiple molecular components. The polymer-water-surface (PWS) calculation method was proposed to calculate such complex systems. In a contrast with a vacuum condition, the presence

  4. In silico FRET from simulated dye dynamics

    NASA Astrophysics Data System (ADS)

    Hoefling, Martin; Grubmüller, Helmut

    2013-03-01

    Single molecule fluorescence resonance energy transfer (smFRET) experiments probe molecular distances on the nanometer scale. In such experiments, distances are recorded from FRET transfer efficiencies via the Förster formula, E=1/(1+(). The energy transfer however also depends on the mutual orientation of the two dyes used as distance reporter. Since this information is typically inaccessible in FRET experiments, one has to rely on approximations, which reduce the accuracy of these distance measurements. A common approximation is an isotropic and uncorrelated dye orientation distribution. To assess the impact of such approximations, we present the algorithms and implementation of a computational toolkit for the simulation of smFRET on the basis of molecular dynamics (MD) trajectory ensembles. In this study, the dye orientation dynamics, which are used to determine dynamic FRET efficiencies, are extracted from MD simulations. In a subsequent step, photons and bursts are generated using a Monte Carlo algorithm. The application of the developed toolkit on a poly-proline system demonstrated good agreement between smFRET simulations and experimental results and therefore confirms our computational method. Furthermore, it enabled the identification of the structural basis of measured heterogeneity. The presented computational toolkit is written in Python, available as open-source, applicable to arbitrary systems and can easily be extended and adapted to further problems. Catalogue identifier: AENV_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AENV_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: GPLv3, the bundled SIMD friendly Mersenne twister implementation [1] is provided under the SFMT-License. No. of lines in distributed program, including test data, etc.: 317880 No. of bytes in distributed program, including test data, etc.: 54774217 Distribution format: tar.gz Programming language

  5. Coarse-grained protein molecular dynamics simulations.

    PubMed

    Derreumaux, Philippe; Mousseau, Normand

    2007-01-14

    A limiting factor in biological science is the time-scale gap between experimental and computational trajectories. At this point, all-atom explicit solvent molecular dynamics (MD) are clearly too expensive to explore long-range protein motions and extract accurate thermodynamics of proteins in isolated or multimeric forms. To reach the appropriate time scale, we must then resort to coarse graining. Here we couple the coarse-grained OPEP model, which has already been used with activated methods, to MD simulations. Two test cases are studied: the stability of three proteins around their experimental structures and the aggregation mechanisms of the Alzheimer's Abeta16-22 peptides. We find that coarse-grained isolated proteins are stable at room temperature within 50 ns time scale. Based on two 220 ns trajectories starting from disordered chains, we find that four Abeta16-22 peptides can form a three-stranded beta sheet. We also demonstrate that the reptation move of one chain over the others, first observed using the activation-relaxation technique, is a kinetically important mechanism during aggregation. These results show that MD-OPEP is a particularly appropriate tool to study qualitatively the dynamics of long biological processes and the thermodynamics of molecular assemblies.

  6. Coarse-grained protein molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Derreumaux, Philippe; Mousseau, Normand

    2007-01-01

    A limiting factor in biological science is the time-scale gap between experimental and computational trajectories. At this point, all-atom explicit solvent molecular dynamics (MD) are clearly too expensive to explore long-range protein motions and extract accurate thermodynamics of proteins in isolated or multimeric forms. To reach the appropriate time scale, we must then resort to coarse graining. Here we couple the coarse-grained OPEP model, which has already been used with activated methods, to MD simulations. Two test cases are studied: the stability of three proteins around their experimental structures and the aggregation mechanisms of the Alzheimer's Aβ16-22 peptides. We find that coarse-grained isolated proteins are stable at room temperature within 50ns time scale. Based on two 220ns trajectories starting from disordered chains, we find that four Aβ16-22 peptides can form a three-stranded β sheet. We also demonstrate that the reptation move of one chain over the others, first observed using the activation-relaxation technique, is a kinetically important mechanism during aggregation. These results show that MD-OPEP is a particularly appropriate tool to study qualitatively the dynamics of long biological processes and the thermodynamics of molecular assemblies.

  7. Molecular Dynamics Simulations of Ferroelectric Phase Transitions

    NASA Astrophysics Data System (ADS)

    Yu, Rici; Krakauer, Henry

    1997-03-01

    Based on an analysis of the wavevector dependence of the lattice instabilities in KNbO_3, we proposed a real-space chain-like instability and a scenario of sequential freezing out or onset of coherence of these instabilities, which qualitatively explains the sequence of observed temperature-dependent ferroelectric phases.(R. Yu and H. Krakauer, Phys. Rev. Lett. 74), 4067 (1995). We suggested that this chain-like instability should also be found in BaTiO_3, and this has been subsequently confirmed by Ghosez et al.(P. Ghosez et al.), Proc. 4th Williamsburg Workshop on First-Principles Calculations for Ferroelectrics, to be published We will present molecular dynamics simulations on BaTiO_3, using effective Hamiltonians constructed from first-principles calculations,(W. Zhong, D. Vanderbilt, and K. M. Rabe, Phys. Rev. Lett. 73), 1861 (1994). that reproduce the essential features of diffuse x-ray scattering measurements in the cubic, tetragonal, orthorhombic, and rhombohedral phases. The good agreement supports the interpretation of real-space chain-formation. Simulations for KNbO3 may also be reported.

  8. Molecular dynamics simulations of microscale fluid transport

    SciTech Connect

    Wong, C.C.; Lopez, A.R.; Stevens, M.J.; Plimpton, S.J.

    1998-02-01

    Recent advances in micro-science and technology, like Micro-Electro-Mechanical Systems (MEMS), have generated a group of unique liquid flow problems that involve characteristic length scales of a Micron. Also, in manufacturing processes such as coatings, current continuum models are unable to predict microscale physical phenomena that appear in these non-equilibrium systems. It is suspected that in these systems, molecular-level processes can control the interfacial energy and viscoelastic properties at the liquid/solid boundary. A massively parallel molecular dynamics (MD) code has been developed to better understand microscale transport mechanisms, fluid-structure interactions, and scale effects in micro-domains. Specifically, this MD code has been used to analyze liquid channel flow problems for a variety of channel widths, e.g. 0.005-0.05 microns. This report presents results from MD simulations of Poiseuille flow and Couette flow problems and addresses both scaling and modeling issues. For Poiseuille flow, the numerical predictions are compared with existing data to investigate the variation of the friction factor with channel width. For Couette flow, the numerical predictions are used to determine the degree of slip at the liquid/solid boundary. Finally, the results also indicate that shear direction with respect to the wall lattice orientation can be very important. Simulation results of microscale Couette flow and microscale Poiseuille flow for two different surface structures and two different shear directions will be presented.

  9. Numerical simulation of tulip flame dynamics

    SciTech Connect

    Cloutman, L.D.

    1991-11-30

    A finite difference reactive flow hydrodynamics program based on the full Navier-Stokes equations was used to simulate the combustion process in a homogeneous-charge, constant-volume combustion bomb in which an oddly shaped flame, known as a tulip flame'' in the literature, occurred. The tulip flame'' was readily reproduced in the numerical simulations, producing good agreement with the experimental flame shapes and positions at various times. The calculations provide sufficient detail about the dynamics of the experiment to provide some insight into the physical mechanisms responsible for the peculiar flame shape. Several factors seem to contribute to the tulip formation. The most important process is the baroclinic production of vorticity by the flame front, and this rate of production appears to be dramatically increased by the nonaxial flow generated when the initial semicircular flame front burns out along the sides of the chamber. The vorticity produces a pair of vortices behind the flame that advects the flame into the tulip shape. Boundary layer effects contribute to the details of the flame shape next to the walls of the chamber, but are otherwise not important. 24 refs.

  10. Numerical simulation of tulip flame dynamics

    SciTech Connect

    Cloutman, L.D.

    1991-11-30

    A finite difference reactive flow hydrodynamics program based on the full Navier-Stokes equations was used to simulate the combustion process in a homogeneous-charge, constant-volume combustion bomb in which an oddly shaped flame, known as a ``tulip flame`` in the literature, occurred. The ``tulip flame`` was readily reproduced in the numerical simulations, producing good agreement with the experimental flame shapes and positions at various times. The calculations provide sufficient detail about the dynamics of the experiment to provide some insight into the physical mechanisms responsible for the peculiar flame shape. Several factors seem to contribute to the tulip formation. The most important process is the baroclinic production of vorticity by the flame front, and this rate of production appears to be dramatically increased by the nonaxial flow generated when the initial semicircular flame front burns out along the sides of the chamber. The vorticity produces a pair of vortices behind the flame that advects the flame into the tulip shape. Boundary layer effects contribute to the details of the flame shape next to the walls of the chamber, but are otherwise not important. 24 refs.

  11. Dynamical simulation of tether in orbit deployment

    NASA Astrophysics Data System (ADS)

    Smirnov, N. N.; Demyanov, Yu. A.; Zvyaguin, A. V.; Malashin, A. A.; Luzhin, A. A.

    2010-08-01

    The paper is aimed at studying the peculiarities of dynamical behavior of tether in its deployment in low Earth orbit during YES2 experiment in Foton-M3 mission, and performing flight data analysis with account of these effects. The analysis in the first part of the paper uses as input a pre-provided tension profile for the mission (resulting from a simulation to be independently validated). With this input it then performs an open-loop simulation which explains the sensitivity to the initial parameters. For the actual flight design a feedback mechanism and algorithm was used in order to control the deployment speed along a nominal profile, minimizing sensitivity to conditions such as initial velocity and endmass value. The paper provides solutions accounting for final velocities of wave propagation in tether, which is especially important for such stages of the deployment as sharp changing of the velocity direction and intensive braking. Moreover the YES2 data is used to validate the theoretical derivations.

  12. PACO: PArticle COunting Method To Enforce Concentrations in Dynamic Simulations.

    PubMed

    Berti, Claudio; Furini, Simone; Gillespie, Dirk

    2016-03-08

    We present PACO, a computationally efficient method for concentration boundary conditions in nonequilibrium particle simulations. Because it requires only particle counting, its computational effort is significantly smaller than other methods. PACO enables Brownian dynamics simulations of micromolar electrolytes (3 orders of magnitude lower than previously simulated). PACO for Brownian dynamics is integrated in the BROWNIES package (www.phys.rush.edu/BROWNIES). We also introduce a molecular dynamics PACO implementation that allows for very accurate control of concentration gradients.

  13. Molecular dynamics simulations of cavitation bubble collapse and sonoluminescence

    NASA Astrophysics Data System (ADS)

    Schanz, Daniel; Metten, Burkhard; Kurz, Thomas; Lauterborn, Werner

    2012-11-01

    The dynamics of the medium within a collapsing and rebounding cavitation bubble is investigated by means of molecular dynamics (MD) simulations adopting a hard sphere model for the species inside the bubble. The dynamics of the surrounding liquid (water) is modelled using a Rayleigh-Plesset (RP)-type equation coupled to the bubble interior by the gas pressure at the wall obtained from the MD calculations. Water vapour and vapour chemistry are included in the RP-MD model as well as mass and energy transfer through the bubble wall. The calculations reveal the evolution of temperature, density and pressure within a bubble at conditions typical of single-bubble sonoluminescence and predict how the particle numbers and densities of different vapour dissociation and reaction products in the bubble develop in space and time. Among the parameters varied are the sound pressure amplitude of a sonoluminescence bubble in water, the noble gas mixture in the bubble and the accommodation coefficients for mass and energy exchange through the bubble wall. Simulation particle numbers up to 10 million are used; most calculations, however, are performed with one million particles to save computer run time. Validation of the MD code was done by comparing MD results with solutions obtained by continuum mechanics calculations for the Euler equations.

  14. Frontiers in molecular dynamics simulations of DNA.

    PubMed

    Pérez, Alberto; Luque, F Javier; Orozco, Modesto

    2012-02-21

    It has been known for decades that DNA is extremely flexible and polymorphic, but our knowledge of its accessible conformational space remains limited. Structural data, primarily from X-ray diffraction studies, is sparse in comparison to the manifold configurations possible, and direct experimental examinations of DNA's flexibility still suffer from many limitations. In the face of these shortcomings, molecular dynamics (MD) is now an essential tool in the study of DNA. It affords detailed structural and dynamical insights, which explains its recent transition from a small number of highly specialized laboratories to a large variety of groups dealing with challenging biological problems. MD is now making an irreversible journey to the mainstream of research in biology, with the attendant opportunities and challenges. But given the speed with which MD studies of DNA have spread, the roots remain somewhat shallow: in many cases, there is a lack of deep knowledge about the foundations, strengths, and limits of the technique. In this Account, we discuss how MD has become the most important source of structural and flexibility data on DNA, focusing on advances since 2007 of atomistic MD in the description of DNA under near-physiological conditions and highlighting the possibilities and shortcomings of the technique. The evolution in the field over the past four years is a prelude to the ongoing revolution. The technique has gained in robustness and predictive power, which when coupled with the spectacular improvements in software and hardware has enabled the tackling of systems of increasing complexity. Simulation times of microseconds have now been achieved, with even longer times when specialized hardware is used. As a result, we have seen the first real-time simulation of large conformational transitions, including folding and unfolding of short DNA duplexes. Noteworthy advances have also been made in the study of DNA-ligand interactions, and we predict that a global

  15. Thermostat for nonequilibrium multiparticle-collision-dynamics simulations

    NASA Astrophysics Data System (ADS)

    Huang, Chien-Cheng; Varghese, Anoop; Gompper, Gerhard; Winkler, Roland G.

    2015-01-01

    Multiparticle collision dynamics (MPC), a particle-based mesoscale simulation technique for complex fluid, is widely employed in nonequilibrium simulations of soft matter systems. To maintain a defined thermodynamic state, thermalization of the fluid is often required for certain MPC variants. We investigate the influence of three thermostats on the nonequilibrium properties of a MPC fluid under shear or in Poiseuille flow. In all cases, the local velocities are scaled by a factor, which is either determined via a local simple scaling approach (LSS), a Monte Carlo-like procedure (MCS), or by the Maxwell-Boltzmann distribution of kinetic energy (MBS). We find that the various scaling schemes leave the flow profile unchanged and maintain the local temperature well. The fluid viscosities extracted from the various simulations are in close agreement. Moreover, the numerically determined viscosities are in remarkably good agreement with the respective theoretically predicted values. At equilibrium, the calculation of the dynamic structure factor reveals that the MBS method closely resembles an isothermal ensemble, whereas the MCS procedure exhibits signatures of an adiabatic system at larger collision-time steps. Since the velocity distribution of the LSS approach is non-Gaussian, we recommend to apply the MBS thermostat, which has been shown to produce the correct velocity distribution even under nonequilibrium conditions.

  16. The Dynamics of Miscible Interfaces: Simulations

    NASA Technical Reports Server (NTRS)

    Meiburg, Eckart

    2002-01-01

    The goal of this experimental/computational investigation (joint with Prof Maxworthy at USC) has been to study the dynamics of miscible interfaces, both from a scientific and a practical point of view, and to prepare a related experiment to be flown on the International Space Station. In order to address these effects, we have focused experimental and computational investigations on miscible displacements in cylindrical capillary tubes, as well as in Hele-Shaw cells. Regarding the flow in a capillary tube, the question was addressed as to whether Korteweg stresses and/or divergence effects can potentially account for discrepancies observed between conventional Stokes flow simulations and experiments for miscible flows in capillary tubes. An estimate of the vorticity and streamfunction fields induced by the Kortewegs stresses was derived, which shows these stresses to result in the formation of a vortex ring structure near the tip of the concentration front. Through this mechanism the propagation velocity of the concentration front is reduced, in agreement with the experimental observations. Divergence effects, on the other hand, were seen to be very small, and they have a negligible influence on the tip velocity. As a result, it can be concluded that they are not responsible for the discrepancies between experiments and conventional Stokes simulations. A further part of our investigation focussed on the development of high-accuracy three-dimensional spectral element simulation techniques for miscible flows in capillary tubes, including the effects of variable density and viscosity. Towards this end, the conservation equations are treated in cylindrical coordinates.

  17. Consequence modeling using the fire dynamics simulator.

    PubMed

    Ryder, Noah L; Sutula, Jason A; Schemel, Christopher F; Hamer, Andrew J; Van Brunt, Vincent

    2004-11-11

    The use of Computational Fluid Dynamics (CFD) and in particular Large Eddy Simulation (LES) codes to model fires provides an efficient tool for the prediction of large-scale effects that include plume characteristics, combustion product dispersion, and heat effects to adjacent objects. This paper illustrates the strengths of the Fire Dynamics Simulator (FDS), an LES code developed by the National Institute of Standards and Technology (NIST), through several small and large-scale validation runs and process safety applications. The paper presents two fire experiments--a small room fire and a large (15 m diameter) pool fire. The model results are compared to experimental data and demonstrate good agreement between the models and data. The validation work is then extended to demonstrate applicability to process safety concerns by detailing a model of a tank farm fire and a model of the ignition of a gaseous fuel in a confined space. In this simulation, a room was filled with propane, given time to disperse, and was then ignited. The model yields accurate results of the dispersion of the gas throughout the space. This information can be used to determine flammability and explosive limits in a space and can be used in subsequent models to determine the pressure and temperature waves that would result from an explosion. The model dispersion results were compared to an experiment performed by Factory Mutual. Using the above examples, this paper will demonstrate that FDS is ideally suited to build realistic models of process geometries in which large scale explosion and fire failure risks can be evaluated with several distinct advantages over more traditional CFD codes. Namely transient solutions to fire and explosion growth can be produced with less sophisticated hardware (lower cost) than needed for traditional CFD codes (PC type computer verses UNIX workstation) and can be solved for longer time histories (on the order of hundreds of seconds of computed time) with

  18. 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...

  19. 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...

  20. Dynamics of solutes with hydrodynamic interactions: comparison between Brownian dynamics and stochastic rotation dynamics simulations.

    PubMed

    Batôt, G; Dahirel, V; Mériguet, G; Louis, A A; Jardat, M

    2013-10-01

    The dynamics of particles in solution or suspension is influenced by thermal fluctuations and hydrodynamic interactions. Several mesoscale methods exist to account for these solvent-induced effects such as Brownian dynamics with hydrodynamic interactions and hybrid molecular dynamics-stochastic rotation dynamics methods. Here we compare two ways of coupling solutes to the solvent with stochastic rotation dynamics (SRD) to Brownian dynamics with and without explicit hydrodynamic interactions. In the first SRD scheme [SRD with collisional coupling (CC)] the solutes participate in the collisional step with the solvent and in the second scheme [SRD with central force coupling (CFC)] the solutes interact through direct forces with the solvent, generating slip boundary conditions. We compare the transport coefficients of neutral and charged solutes in a model system obtained by these simulation schemes. Brownian dynamics without hydrodynamic interactions is used as a reference to quantify the influence of hydrodynamics on the transport coefficients as modeled by the different methods. We show that, in the dilute range, the SRD CFC method provides results similar to those of Brownian dynamics with hydrodynamic interactions for the diffusion coefficients and for the electrical conductivity. The SRD CC scheme predicts diffusion coefficients close to those obtained by Brownian dynamic simulations without hydrodynamic interactions, but accounts for part of the influence of hydrodynamics on the electrical conductivity.

  1. Rigid Residue Scan Simulations Systematically Reveal Residue Entropic Roles in Protein Allostery.

    PubMed

    Kalescky, Robert; Zhou, Hongyu; Liu, Jin; Tao, Peng

    2016-04-01

    Intra-protein information is transmitted over distances via allosteric processes. This ubiquitous protein process allows for protein function changes due to ligand binding events. Understanding protein allostery is essential to understanding protein functions. In this study, allostery in the second PDZ domain (PDZ2) in the human PTP1E protein is examined as model system to advance a recently developed rigid residue scan method combining with configurational entropy calculation and principal component analysis. The contributions from individual residues to whole-protein dynamics and allostery were systematically assessed via rigid body simulations of both unbound and ligand-bound states of the protein. The entropic contributions of individual residues to whole-protein dynamics were evaluated based on covariance-based correlation analysis of all simulations. The changes of overall protein entropy when individual residues being held rigid support that the rigidity/flexibility equilibrium in protein structure is governed by the La Châtelier's principle of chemical equilibrium. Key residues of PDZ2 allostery were identified with good agreement with NMR studies of the same protein bound to the same peptide. On the other hand, the change of entropic contribution from each residue upon perturbation revealed intrinsic differences among all the residues. The quasi-harmonic and principal component analyses of simulations without rigid residue perturbation showed a coherent allosteric mode from unbound and bound states, respectively. The projection of simulations with rigid residue perturbation onto coherent allosteric modes demonstrated the intrinsic shifting of ensemble distributions supporting the population-shift theory of protein allostery. Overall, the study presented here provides a robust and systematic approach to estimate the contribution of individual residue internal motion to overall protein dynamics and allostery.

  2. Rigid Residue Scan Simulations Systematically Reveal Residue Entropic Roles in Protein Allostery

    PubMed Central

    Liu, Jin

    2016-01-01

    Intra-protein information is transmitted over distances via allosteric processes. This ubiquitous protein process allows for protein function changes due to ligand binding events. Understanding protein allostery is essential to understanding protein functions. In this study, allostery in the second PDZ domain (PDZ2) in the human PTP1E protein is examined as model system to advance a recently developed rigid residue scan method combining with configurational entropy calculation and principal component analysis. The contributions from individual residues to whole-protein dynamics and allostery were systematically assessed via rigid body simulations of both unbound and ligand-bound states of the protein. The entropic contributions of individual residues to whole-protein dynamics were evaluated based on covariance-based correlation analysis of all simulations. The changes of overall protein entropy when individual residues being held rigid support that the rigidity/flexibility equilibrium in protein structure is governed by the La Châtelier’s principle of chemical equilibrium. Key residues of PDZ2 allostery were identified with good agreement with NMR studies of the same protein bound to the same peptide. On the other hand, the change of entropic contribution from each residue upon perturbation revealed intrinsic differences among all the residues. The quasi-harmonic and principal component analyses of simulations without rigid residue perturbation showed a coherent allosteric mode from unbound and bound states, respectively. The projection of simulations with rigid residue perturbation onto coherent allosteric modes demonstrated the intrinsic shifting of ensemble distributions supporting the population-shift theory of protein allostery. Overall, the study presented here provides a robust and systematic approach to estimate the contribution of individual residue internal motion to overall protein dynamics and allostery. PMID:27115535

  3. Resting state networks in empirical and simulated dynamic functional connectivity.

    PubMed

    Glomb, Katharina; Ponce-Alvarez, Adrián; Gilson, Matthieu; Ritter, Petra; Deco, Gustavo

    2017-08-03

    , control networks, and somatomotor network. Second, we simulate data with our stationary mean field model whose nodes are connected according to results from DTI and fiber tracking. In this model, all spatio-temporal structure is due to noisy fluctuations around the average FC. We analyze the simulated data in the same way as the empirical data in order to determine whether stationary dynamics can explain the emergence of distinct FC patterns (RSNs) which have their own time courses. We find that this is the case for all four networks using the spatio-temporal information revealed by tensor decomposition if nodes in the simulation are connected according to model-based effective connectivity. Furthermore, we find that these results require only a small part of the FC values, namely the highest values that occur across time and ROI pair. Our findings show that stationary dynamics can account for the emergence of RSNs. We provide an innovative method that does not make strong assumptions about the underlying data and is generally applicable to resting state or task data from different subject populations. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Brownian dynamics simulation of peptides with the University of Houston Brownian Dynamics (UHBD) program.

    PubMed

    Shen, Tongye; Wong, Chung F

    2015-01-01

    This chapter provides the background theory and a practical protocol for performing Brownian dynamics simulation of peptides. Brownian dynamics simulation represents a complementary approach to Monte Carlo and molecular dynamics methods. Unlike Monte Carlo methods, it could provide dynamical information in a timescale longer than the momentum relaxation time. On the other hand, it is faster than molecular dynamics by approximating the solvent by a continuum and by operating in the over-damped limit. This chapter introduces the use of the University of Houston Brownian Dynamics (UHBD) program [1, 2] to perform Brownian dynamics simulation on peptides.

  5. High-Throughput Simulations Reveal Membrane-Mediated Effects of Alcohols on MscL Gating

    PubMed Central

    2017-01-01

    The mechanosensitive channels of large conductance (MscL) are bacterial membrane proteins that serve as last resort emergency release valves in case of severe osmotic downshock. Sensing bilayer tension, MscL channels are sensitive to changes in the bilayer environment and are, therefore, an ideal test case for exploring membrane protein coupling. Here, we use high-throughput coarse-grained molecular dynamics simulations to characterize MscL gating kinetics in different bilayer environments under the influence of alcohols. We performed over five hundred simulations to obtain sufficient statistics to reveal the subtle effects of changes in the membrane environment on MscL gating. MscL opening times were found to increase with the addition of the straight-chain alcohols ethanol, octanol, and to some extent dodecanol but not with hexadecanol. Increasing concentration of octanol increased the impeding effect, but only up to 10–20 mol %. Our in silico predictions were experimentally confirmed using reconstituted MscL in a liposomal fluorescent efflux assay. Our combined data reveal that the effect of alcohols on MscL gating arises not through specific binding sites but through a combination of the alcohol-induced changes to a number of bilayer properties and their alteration of the MscL–bilayer interface. Our work provides a key example of how extensive molecular simulations can be used to predict the functional modification of membrane proteins by subtle changes in their bilayer environment. PMID:28122455

  6. High-throughput simulations reveal membrane-mediated effects of alcohols on MscL gating

    DOE PAGES

    Melo, Manuel N.; Arnarez, Clement; Sikkema, Hendrik; ...

    2017-01-26

    The mechanosensitive channels of large conductance (MscL) are bacterial membrane proteins that serve as last resort emergency release valves in case of severe osmotic downshock. Sensing bilayer tension, MscL channels are sensitive to changes in the bilayer environment and are, therefore, an ideal test case for exploring membrane protein coupling. Here, we use high-throughput coarse-grained molecular dynamics simulations to characterize MscL gating kinetics in different bilayer environments under the influence of alcohols. We performed over five hundred simulations to obtain sufficient statistics to reveal the subtle effects of changes in the membrane environment on MscL gating. MscL opening times weremore » found to increase with the addition of the straight-chain alcohols ethanol, octanol, and to some extent dodecanol but not with hexadecanol. Increasing concentration of octanol increased the impeding effect, but only up to 10–20 mol %. Our in silico predictions were experimentally confirmed using reconstituted MscL in a liposomal fluorescent efflux assay. Our combined data reveal that the effect of alcohols on MscL gating arises not through specific binding sites but through a combination of the alcohol-induced changes to a number of bilayer properties and their alteration of the MscL–bilayer interface. Finally, our work provides a key example of how extensive molecular simulations can be used to predict the functional modification of membrane proteins by subtle changes in their bilayer environment.« less

  7. Simulation of chemical isomerization reaction dynamics on a NMR quantum simulator.

    PubMed

    Lu, Dawei; Xu, Nanyang; Xu, Ruixue; Chen, Hongwei; Gong, Jiangbin; Peng, Xinhua; Du, Jiangfeng

    2011-07-08

    Quantum simulation can beat current classical computers with minimally a few tens of qubits. Here we report an experimental demonstration that a small nuclear-magnetic-resonance quantum simulator is already able to simulate the dynamics of a prototype laser-driven isomerization reaction using engineered quantum control pulses. The experimental results agree well with classical simulations. We conclude that the quantum simulation of chemical reaction dynamics not computable on current classical computers is feasible in the near future.

  8. High frequency dynamic engine simulation. [TF-30 engine

    NASA Technical Reports Server (NTRS)

    Schuerman, J. A.; Fischer, K. E.; Mclaughlin, P. W.

    1977-01-01

    A digital computer simulation of a mixed flow, twin spool turbofan engine was assembled to evaluate and improve the dynamic characteristics of the engine simulation to disturbance frequencies of at least 100 Hz. One dimensional forms of the dynamic mass, momentum and energy equations were used to model the engine. A TF30 engine was simulated so that dynamic characteristics could be evaluated against results obtained from testing of the TF30 engine at the NASA Lewis Research Center. Dynamic characteristics of the engine simulation were improved by modifying the compression system model. Modifications to the compression system model were established by investigating the influence of size and number of finite dynamic elements. Based on the results of this program, high frequency engine simulations using finite dynamic elements can be assembled so that the engine dynamic configuration is optimum with respect to dynamic characteristics and computer execution time. Resizing of the compression systems finite elements improved the dynamic characteristics of the engine simulation but showed that additional refinements are required to obtain close agreement simulation and actual engine dynamic characteristics.

  9. In situ structure and dynamics of DNA origami determined through molecular dynamics simulations

    PubMed Central

    Yoo, Jejoong; Aksimentiev, Aleksei

    2013-01-01

    The DNA origami method permits folding of long single-stranded DNA into complex 3D structures with subnanometer precision. Transmission electron microscopy, atomic force microscopy, and recently cryo-EM tomography have been used to characterize the properties of such DNA origami objects, however their microscopic structures and dynamics have remained unknown. Here, we report the results of all-atom molecular dynamics simulations that characterized the structural and mechanical properties of DNA origami objects in unprecedented microscopic detail. When simulated in an aqueous environment, the structures of DNA origami objects depart from their idealized targets as a result of steric, electrostatic, and solvent-mediated forces. Whereas the global structural features of such relaxed conformations conform to the target designs, local deformations are abundant and vary in magnitude along the structures. In contrast to their free-solution conformation, the Holliday junctions in the DNA origami structures adopt a left-handed antiparallel conformation. We find the DNA origami structures undergo considerable temporal fluctuations on both local and global scales. Analysis of such structural fluctuations reveals the local mechanical properties of the DNA origami objects. The lattice type of the structures considerably affects global mechanical properties such as bending rigidity. Our study demonstrates the potential of all-atom molecular dynamics simulations to play a considerable role in future development of the DNA origami field by providing accurate, quantitative assessment of local and global structural and mechanical properties of DNA origami objects. PMID:24277840

  10. In situ structure and dynamics of DNA origami determined through molecular dynamics simulations.

    PubMed

    Yoo, Jejoong; Aksimentiev, Aleksei

    2013-12-10

    The DNA origami method permits folding of long single-stranded DNA into complex 3D structures with subnanometer precision. Transmission electron microscopy, atomic force microscopy, and recently cryo-EM tomography have been used to characterize the properties of such DNA origami objects, however their microscopic structures and dynamics have remained unknown. Here, we report the results of all-atom molecular dynamics simulations that characterized the structural and mechanical properties of DNA origami objects in unprecedented microscopic detail. When simulated in an aqueous environment, the structures of DNA origami objects depart from their idealized targets as a result of steric, electrostatic, and solvent-mediated forces. Whereas the global structural features of such relaxed conformations conform to the target designs, local deformations are abundant and vary in magnitude along the structures. In contrast to their free-solution conformation, the Holliday junctions in the DNA origami structures adopt a left-handed antiparallel conformation. We find the DNA origami structures undergo considerable temporal fluctuations on both local and global scales. Analysis of such structural fluctuations reveals the local mechanical properties of the DNA origami objects. The lattice type of the structures considerably affects global mechanical properties such as bending rigidity. Our study demonstrates the potential of all-atom molecular dynamics simulations to play a considerable role in future development of the DNA origami field by providing accurate, quantitative assessment of local and global structural and mechanical properties of DNA origami objects.

  11. Temporal dynamics of reward processing revealed by magnetoencephalography.

    PubMed

    Doñamayor, Nuria; Marco-Pallarés, Josep; Heldmann, Marcus; Schoenfeld, M Ariel; Münte, Thomas F

    2011-12-01

    Monetary gains and losses in gambling situations are associated with a distinct electroencephalographic signature: in the event-related potentials (ERPs), a mediofrontal feedback-related negativity (FRN) is seen for losses, whereas oscillatory activity shows a burst of in the θ-range for losses and in the β-range for gains. We used whole-head magnetoencephalography to pinpoint the magnetic counterparts of these effects in young healthy adults and explore their evolution over time. On each trial, participants bet on one of two visually presented numbers (25 or 5) by button-press. Both numbers changed color: if the chosen number turned green (red), it indicated a gain (loss) of the corresponding sum in Euro cent. For losses, we found the magnetic correlate of the FRN extending between 230 and 465 ms. Source localization with low-resolution electromagnetic tomography indicated a first generator in posterior cingulate cortex with subsequent activity in the anterior cingulate cortex. Importantly, this effect was sensitive to the magnitude of the monetary loss (25 cent > 5 cent). Later activation was also found in the right insula. Time-frequency analysis revealed a number of oscillatory components in the theta, alpha, and high-beta/low-gamma bands associated to gains, and in the high-beta band, associated to the magnitude of the loss. All together, these effects provide a more fine-grained picture of the temporal dynamics of the processing of monetary rewards and losses in the brain.

  12. Cytoplasmic dynamics reveals two modes of nucleoid-dependent mobility.

    PubMed

    Stylianidou, Stella; Kuwada, Nathan J; Wiggins, Paul A

    2014-12-02

    It has been proposed that forces resulting from the physical exclusion of macromolecules from the bacterial nucleoid play a central role in organizing the bacterial cell, yet this proposal has not been quantitatively tested. To investigate this hypothesis, we mapped the generic motion of large protein complexes in the bacterial cytoplasm through quantitative analysis of thousands of complete cell-cycle trajectories of fluorescently tagged ectopic MS2-mRNA complexes. We find the motion of these complexes in the cytoplasm is strongly dependent on their spatial position along the long axis of the cell, and that their dynamics are consistent with a quantitative model that requires only nucleoid exclusion and membrane confinement. This analysis also reveals that the nucleoid increases the mobility of MS2-mRNA complexes, resulting in a fourfold increase in diffusion coefficients between regions of the lowest and highest nucleoid density. These data provide strong quantitative support for two modes of nucleoid action: the widely accepted mechanism of nucleoid exclusion in organizing the cell and a newly proposed mode, in which the nucleoid facilitates rapid motion throughout the cytoplasm.

  13. Accurate Langevin approaches to simulate Markovian channel dynamics

    NASA Astrophysics Data System (ADS)

    Huang, Yandong; Rüdiger, Sten; Shuai, Jianwei

    2015-12-01

    The stochasticity of ion-channels dynamic is significant for physiological processes on neuronal cell membranes. Microscopic simulations of the ion-channel gating with Markov chains can be considered to be an accurate standard. However, such Markovian simulations are computationally demanding for membrane areas of physiologically relevant sizes, which makes the noise-approximating or Langevin equation methods advantageous in many cases. In this review, we discuss the Langevin-like approaches, including the channel-based and simplified subunit-based stochastic differential equations proposed by Fox and Lu, and the effective Langevin approaches in which colored noise is added to deterministic differential equations. In the framework of Fox and Lu’s classical models, several variants of numerical algorithms, which have been recently developed to improve accuracy as well as efficiency, are also discussed. Through the comparison of different simulation algorithms of ion-channel noise with the standard Markovian simulation, we aim to reveal the extent to which the existing Langevin-like methods approximate results using Markovian methods. Open questions for future studies are also discussed.

  14. Nanoscale deicing by molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Xiao, Senbo; He, Jianying; Zhang, Zhiliang

    2016-07-01

    Deicing is important to human activities in low-temperature circumstances, and is critical for combating the damage caused by excessive accumulation of ice. The aim of creating anti-icing materials, surfaces and applications relies on the understanding of fundamental nanoscale ice adhesion mechanics. Here in this study, we employ all-atom modeling and molecular dynamics simulation to investigate ice adhesion. We apply force to detach and shear nano-sized ice cubes for probing the determinants of atomistic adhesion mechanics, and at the same time investigate the mechanical effect of a sandwiched aqueous water layer between ice and substrates. We observe that high interfacial energy restricts ice mobility and increases both ice detaching and shearing stresses. We quantify up to a 60% decrease in ice adhesion strength by an aqueous water layer, and provide atomistic details that support previous experimental studies. Our results contribute quantitative comparison of nanoscale adhesion strength of ice on hydrophobic and hydrophilic surfaces, and supply for the first time theoretical references for understanding the mechanics at the atomistic origins of macroscale ice adhesion.Deicing is important to human activities in low-temperature circumstances, and is critical for combating the damage caused by excessive accumulation of ice. The aim of creating anti-icing materials, surfaces and applications relies on the understanding of fundamental nanoscale ice adhesion mechanics. Here in this study, we employ all-atom modeling and molecular dynamics simulation to investigate ice adhesion. We apply force to detach and shear nano-sized ice cubes for probing the determinants of atomistic adhesion mechanics, and at the same time investigate the mechanical effect of a sandwiched aqueous water layer between ice and substrates. We observe that high interfacial energy restricts ice mobility and increases both ice detaching and shearing stresses. We quantify up to a 60% decrease in ice

  15. Nonlinear Resonance Artifacts in Molecular Dynamics Simulations

    NASA Astrophysics Data System (ADS)

    Schlick, Tamar; Mandziuk, Margaret; Skeel, Robert D.; Srinivas, K.

    1998-02-01

    The intriguing phenomenon of resonance, a pronounced integrator-induced corruption of a system's dynamics, is examined for simple molecular systems subject to the classical equations of motion. This source of timestep limitation is not well appreciated in general, and certainly analyses of resonance patterns have been few in connection to biomolecular dynamics. Yet resonances are present in the commonly used Verlet integrator, in symplectic implicit schemes, and also limit the scope of current multiple-timestep methods that are formulated as symplectic and reversible. The only general remedy to date has been to reduce the timestep. For this purpose, we derive method-dependent timestep thresholds (e.g., Tables 1 and 2) that serve as useful guidelines in practice for biomolecular simulations. We also devise closely related symplectic implicit schemes for which the limitation on the discretization stepsize is much less severe. Specifically, we design methods to remove third-order, or both the third- and fourth-order, resonances. These severe low-order resonances can lead to instability or very large energies. Our tests on two simple molecular problems (Morse and Lennard-Jones potentials), as well as a 22-atom molecule, N-acetylalanyl-N '-methylamide, confirm this prediction; our methods can delay resonances so that they occur only at larger timesteps (EW method) or are essentially removed (LIM2 method). Although stable for large timesteps by this approach, trajectories show large energy fluctuations, perhaps due to the coupling with other factors that induce instability in complex nonlinear systems. Thus, the methods developed here may be more useful for conformational sampling of biomolecular structures. The analysis presented here for the blocked alanine model emphasizes that one-dimensional analysis of resonances can be applied to a more complex, multimode system to analyze resonance behavior, but that resonance due to frequency coupling is more complex to pinpoint

  16. Molecular dynamics simulations of glycoclusters and glycodendrimers.

    PubMed

    von der Lieth, Claus W; Frank, Martin; Lindhorst, Thisbe K

    2002-05-01

    Protein-carbohydrate recognition plays a crucial role in a wide range of biological processes, required both for normal physiological functions and the onset of disease. Nature uses multivalency in carbohydrate-protein interactions as a strategy to overcome the low affinity found for singular binding of an individual saccharide epitope to a single carbohydrate recognition domain of a lectin. To mimic the complex multi-branched oligosaccharides found in glycoconjugates, which form the structural basis of multivalent carbohydrate-protein interactions, so-called glycoclusters and glycodendrimers have been designed to serve as high-affinity ligands of the respective receptor proteins. To allow a rational design of glycodendrimer-type molecules with regard to the receptor structures involved in carbohydrate recognition, a deeper knowledge of the dynamics of such molecules is desirable. Most glycodendrimers have to be considered highly flexible molecules with their conformational preferences most difficult to elucidate by experimental methods. Longtime molecular dynamics (MD) simulations with inclusion of explicit solvent molecules are suited to explore the conformational space accessible to glycodendrimers. Here, a detailed geometric and conformational analysis of 15 glycodendrimers and glycoclusters has been accomplished, which differ with regard to their core moieties, spacer characteristics and the type of terminal carbohydrate units. It is shown that the accessible conformational space depends strongly on the structural features of the core and spacer moieties and even on the type of terminating sugars. The obtained knowledge about possible spatial distributions of the sugar epitopes exposed on the investigated hyperbranched neoglycoconjugates is detailed for all examples and forms important information for the interpretation and prediction of affinity data, which can be deduced from biological testing of these multivalent neoglycoconjugates.

  17. Molecular Dynamics Simulation of Disordered Zircon

    SciTech Connect

    Devanathan, Ram; Corrales, Louis R.; Weber, William J.; Chartier, Alain; Meis, Constantin

    2004-02-27

    The melting of zircon and the amorphous state produced by quenching from the melt were simulated by molecular dynamics using a new partial charge model combined with the Ziegler-Biersack-Littmark potential. The model has been established for the description of the crystalline and aperiodic structures of zircon in order to be used for the simulation of displacement cascades. It provides an excellent fit to the structure, and accounts with convenient precision the mechanical and thermodynamic properties of zircon. The calculated melting temperature is about 2100 K. The activation energy for self-diffusion of ions in the liquid state was determined to be 190-200 kJ/mole. Melt quenching was employed to produce two different disordered states with distinct densities and structures. In the high density disordered state, the zircon structure is intact but the bond angle distributions are broader, 4% of the Si units are polymerized, and the volume swelling is about 8%. In the low density amorphous state, the Zr and Si coordination numbers are lower, and the Zr-O and Si-O bond lengths are shorter than corresponding values for the crystal. In addition, a highly polymerized Si network, with average connectivity of two, is observed in the low density amorphous state. These features have all been experimentally observed in natural metamict zircon. The present findings, when considered in light of experimental radiation effects studies, suggest that the swelling in zircon arises initially from disorder in the zircon crystal, and at high doses the disordered crystal is unable to accommodate the volume expansion and transforms to the amorphous state.

  18. Conformational Dynamics of Mechanically Compliant DNA Nanostructures from Coarse-Grained Molecular Dynamics Simulations.

    PubMed

    Shi, Ze; Castro, Carlos E; Arya, Gaurav

    2017-05-23

    Structural DNA nanotechnology, the assembly of rigid 3D structures of complex yet precise geometries, has recently been used to design dynamic, mechanically compliant nanostructures with tunable equilibrium conformations and conformational distributions. Here we use coarse-grained molecular dynamics simulations to provide insights into the conformational dynamics of a set of mechanically compliant DNA nanostructures-DNA hinges that use single-stranded DNA "springs" to tune the equilibrium conformation of a layered double-stranded DNA "joint" connecting two stiff "arms" constructed from DNA helix bundles. The simulations reproduce the experimentally measured equilibrium angles between hinge arms for a range of hinge designs. The hinges are found to be structurally stable, except for some fraying of the open ends of the DNA helices comprising the hinge arms and some loss of base-pairing interactions in the joint regions coinciding with the crossover junctions, especially in hinges designed to exhibit a small bending angle that exhibit large local stresses resulting in strong kinks in their joints. Principal component analysis reveals that while the hinge dynamics are dominated by bending motion, some twisting and sliding of hinge arms relative to each other also exists. Forced deformation of the hinges reveals distinct bending mechanisms for hinges with short, inextensible springs versus those with longer, more extensible springs. Lastly, we introduce an approach for rapidly predicting equilibrium hinge angles from individual force-deformation behaviors of its single- and double-stranded DNA components. Taken together, these results demonstrate that coarse-grained modeling is a promising approach for designing, predicting, and studying the dynamics of compliant DNA nanostructures, where conformational fluctuations become important, multiple deformation mechanisms exist, and continuum approaches may not yield accurate properties.

  19. Dynamics and energetics of permeation through aquaporins. What do we learn from molecular dynamics simulations?

    PubMed

    Hub, Jochen S; Grubmüller, Helmut; de Groot, Bert L

    2009-01-01

    Aquaporins (AQPs) are a family of integral membrane proteins, which facilitate the rapid and yet highly selective flux of water and other small solutes across biological membranes. Molecular dynamics (MD) simulations contributed substantially to the understanding of the molecular mechanisms that underlie this remarkable efficiency and selectivity of aquaporin channels. This chapter reviews the current state of MD simulations of aquaporins and related aquaglyceroporins as well as the insights these simulations have provided. The mechanism of water permeation through AQPs and methods to determine channel permeabilities from simulations are described. Protons are strictly excluded from AQPs by a large electrostatic barrier and not by an interruption of the Grotthuss mechanism inside the pore. Both the protein's electric field and desolvation effects contribute to this barrier. Permeation of apolar gas molecules such as CO(2) through AQPs is accompanied by a large energetic barrier and thus can only be expected in membranes with a low intrinsic gas permeability. Additionally, the insights from simulations into the mechanism of glycerol permeation through the glycerol facilitator GlpF from E. coli are summarized. Finally, MD simulations are discussed that revealed that the aro-matic/arginine constriction region is generally the filter for uncharged solutes, and that AQP selectivity is controlled by a hydrophobic effect and steric restraints.

  20. Molecular dynamics simulation of biomembranes in aqueous solution

    NASA Astrophysics Data System (ADS)

    Bostick, David Lee

    In recent years, the developments in classical molecular dynamics simulation have allowed for an atomistic depiction of mesoscopic biological systems. With the awareness of such developments, the natural strive of the scientific community has been to increase the size of such simulated systems [70]. Nonetheless, the subtleties in the properties of biomembranes require an unusually thoughtful approach [70, 203]. In this work, a hierarchical approach is taken, with respect to system complexity, in the classical molecular dynamics simulation of biomembrane systems in aqueous solution. A progression of simulation studies is presented that begins with the analysis of the interfacial properties of neat bilayers composed of zwitterionic (phosphatidylcholine) lipids in both pure water and in electrolyte. We move on to study mixed bilayers containing zwitterionic (phosphatidylcholine) and acidic (phosphatidylserine) lipids with counterions immersed in electrolyte. Yet another layer of complexity is added to the problem by studying hydrated bilayers containing phosphatidylcholine lipids and cholesterol. Finally, we address the semipermeable nature of biomembranes by studying two membrane-channel systems. We start with a simple model membrane-channel consisting of a six-helix alamethicin bundle embedded in a hydrated phosphatidylcholine bilayer. The knowledge gained from this study is then carried over to the simulation of a large membrane-embedded prokaryotic ClC Cl-/H + antiporter, utilizing a free-energetic analysis to reveal the role of protons in the Cl- transport mechanism. Throughout the progression, methods are developed and used in the analysis of interfacial aqueous solution structure, ion-membrane binding, lipid structural properties, inter-lipid hydrogen bonded complexation, and electrostatics at the membrane interface. The developments reveal the layered nature of water near the rugged, molecularscale aqueous solution/membrane interface and its electrostatic

  1. Non-equilibrium dynamics in disordered materials: Ab initio molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Ohmura, Satoshi; Nagaya, Kiyonobu; Shimojo, Fuyuki; Yao, Makoto

    2015-08-01

    The dynamic properties of liquid B2O3 under pressure and highly-charged bromophenol molecule are studied by using molecular dynamics (MD) simulations based on density functional theory (DFT). Diffusion properties of covalent liquids under high pressure are very interesting in the sense that they show unexpected pressure dependence. It is found from our simulation that the magnitude relation of diffusion coefficients for boron and oxygen in liquid B2O3 shows the anomalous pressure dependence. The simulation clarified the microscopic origin of the anomalous diffusion properties. Our simulation also reveals the dissociation mechanism in the coulomb explosion of the highly-charged bromophenol molecule. When the charge state n is 6, hydrogen atom in the hydroxyl group dissociates at times shorter than 20 fs while all hydrogen atoms dissociate when n is 8. After the hydrogen dissociation, the carbon ring breaks at about 100 fs. There is also a difference on the mechanism of the ring breaking depending on charge states, in which the ring breaks with expanding (n = 6) or shrink (n = 8).

  2. Non-equilibrium dynamics in disordered materials: Ab initio molecular dynamics simulations

    SciTech Connect

    Ohmura, Satoshi; Nagaya, Kiyonobu; Yao, Makoto; Shimojo, Fuyuki

    2015-08-17

    The dynamic properties of liquid B{sub 2}O{sub 3} under pressure and highly-charged bromophenol molecule are studied by using molecular dynamics (MD) simulations based on density functional theory (DFT). Diffusion properties of covalent liquids under high pressure are very interesting in the sense that they show unexpected pressure dependence. It is found from our simulation that the magnitude relation of diffusion coefficients for boron and oxygen in liquid B{sub 2}O{sub 3} shows the anomalous pressure dependence. The simulation clarified the microscopic origin of the anomalous diffusion properties. Our simulation also reveals the dissociation mechanism in the coulomb explosion of the highly-charged bromophenol molecule. When the charge state n is 6, hydrogen atom in the hydroxyl group dissociates at times shorter than 20 fs while all hydrogen atoms dissociate when n is 8. After the hydrogen dissociation, the carbon ring breaks at about 100 fs. There is also a difference on the mechanism of the ring breaking depending on charge states, in which the ring breaks with expanding (n = 6) or shrink (n = 8)

  3. Paddling mechanism for the substrate translocation by AAA+ motor revealed by multiscale molecular simulations

    PubMed Central

    Koga, Nobuyasu; Kameda, Tomoshi; Okazaki, Kei-ichi; Takada, Shoji

    2009-01-01

    Hexameric ring-shaped AAA+ molecular motors have a key function of active translocation of a macromolecular chain through the central pore. By performing multiscale molecular dynamics (MD) simulations, we revealed that HslU, a AAA+ motor in a bacterial homologue of eukaryotic proteasome, translocates its substrate polypeptide via paddling mechanism during ATP-driven cyclic conformational changes. First, fully atomistic MD simulations showed that the HslU pore grips the threaded signal peptide by the highly conserved Tyr-91 and Val-92 firmly in the closed form and loosely in the open form of the HslU. The grip depended on the substrate sequence. These features were fed into a coarse-grained MD, and conformational transitions of HslU upon ATP cycles were simulated. The simulations exhibited stochastic unidirectional translocation of a polypeptide. This unidirectional translocation is attributed to paddling motions of Tyr-91s between the open and the closed forms: downward motions of Tyr-91s with gripping the substrate and upward motions with slipping on it. The paddling motions were caused by the difference between the characteristic time scales of the pore-radius change and the up-down displacements of Tyr-91s. Computational experiments on mutations at the pore and the substrate were in accord with several experiments. PMID:19828442

  4. Revealing the morphological architecture of a shape memory polyurethane by simulation

    NASA Astrophysics Data System (ADS)

    Hu, Jinlian; Zhang, Cuili; Ji, Fenglong; Li, Xun; Han, Jianping; Wu, You

    2016-07-01

    The lack of specific knowledge of the network structure in shape memory polymers (SMPs) has prevented us from gaining an in-depth understanding of their mechanisms and limited the potential for materials innovation. This paper firstly reveals the unit-cell nanoscale morphological architecture of SMPs by simulation. The phase separated architecture of a segmented shape memory polyurethane (SMPU) with a 30 wt% hard segment content (HSC, 4,4’-diphenylmethane diisocyanate (MDI) and 1,4-butanediol (BDO)) showing good shape memory properties was investigated by dissipative particle dynamics (DPD) simulations. A linked-spherical netpoint-frame phase of MDI, a matrix-switch phase of polycaprolactone (PCL) and a connected-spider-like interphase for BDO were obtained for this SMPU. The BDO interphase can reinforce the MDI network. Based on these simulation results, a three-dimensional (3D) overall morphological architectural model of the SMPU can be established. This theoretical study has verified, enriched and integrated two existing schematic models: one being the morphological model deduced from experiments and the other the frame model for SMPs reported before. It can serve as a theoretical guide for smart polymeric materials design. This method for the simulation of polymer structure at the nanoscale can be extended to many areas such as photonic crystals where nanoscale self-assembly plays a vital role.

  5. Revealing the morphological architecture of a shape memory polyurethane by simulation.

    PubMed

    Hu, Jinlian; Zhang, Cuili; Ji, Fenglong; Li, Xun; Han, Jianping; Wu, You

    2016-07-04

    The lack of specific knowledge of the network structure in shape memory polymers (SMPs) has prevented us from gaining an in-depth understanding of their mechanisms and limited the potential for materials innovation. This paper firstly reveals the unit-cell nanoscale morphological architecture of SMPs by simulation. The phase separated architecture of a segmented shape memory polyurethane (SMPU) with a 30 wt% hard segment content (HSC, 4,4'-diphenylmethane diisocyanate (MDI) and 1,4-butanediol (BDO)) showing good shape memory properties was investigated by dissipative particle dynamics (DPD) simulations. A linked-spherical netpoint-frame phase of MDI, a matrix-switch phase of polycaprolactone (PCL) and a connected-spider-like interphase for BDO were obtained for this SMPU. The BDO interphase can reinforce the MDI network. Based on these simulation results, a three-dimensional (3D) overall morphological architectural model of the SMPU can be established. This theoretical study has verified, enriched and integrated two existing schematic models: one being the morphological model deduced from experiments and the other the frame model for SMPs reported before. It can serve as a theoretical guide for smart polymeric materials design. This method for the simulation of polymer structure at the nanoscale can be extended to many areas such as photonic crystals where nanoscale self-assembly plays a vital role.

  6. Revealing the morphological architecture of a shape memory polyurethane by simulation

    PubMed Central

    Hu, Jinlian; Zhang, Cuili; Ji, Fenglong; Li, Xun; Han, Jianping; Wu, You

    2016-01-01

    The lack of specific knowledge of the network structure in shape memory polymers (SMPs) has prevented us from gaining an in-depth understanding of their mechanisms and limited the potential for materials innovation. This paper firstly reveals the unit-cell nanoscale morphological architecture of SMPs by simulation. The phase separated architecture of a segmented shape memory polyurethane (SMPU) with a 30 wt% hard segment content (HSC, 4,4’-diphenylmethane diisocyanate (MDI) and 1,4-butanediol (BDO)) showing good shape memory properties was investigated by dissipative particle dynamics (DPD) simulations. A linked-spherical netpoint-frame phase of MDI, a matrix-switch phase of polycaprolactone (PCL) and a connected-spider-like interphase for BDO were obtained for this SMPU. The BDO interphase can reinforce the MDI network. Based on these simulation results, a three-dimensional (3D) overall morphological architectural model of the SMPU can be established. This theoretical study has verified, enriched and integrated two existing schematic models: one being the morphological model deduced from experiments and the other the frame model for SMPs reported before. It can serve as a theoretical guide for smart polymeric materials design. This method for the simulation of polymer structure at the nanoscale can be extended to many areas such as photonic crystals where nanoscale self-assembly plays a vital role. PMID:27373495

  7. Expansion techniques for collisionless stellar dynamical simulations

    SciTech Connect

    Meiron, Yohai; Li, Baile; Holley-Bockelmann, Kelly; Spurzem, Rainer

    2014-09-10

    We present graphics processing unit (GPU) implementations of two fast force calculation methods based on series expansions of the Poisson equation. One method is the self-consistent field (SCF) method, which is a Fourier-like expansion of the density field in some basis set; the other method is the multipole expansion (MEX) method, which is a Taylor-like expansion of the Green's function. MEX, which has been advocated in the past, has not gained as much popularity as SCF. Both are particle-field methods and optimized for collisionless galactic dynamics, but while SCF is a 'pure' expansion, MEX is an expansion in just the angular part; thus, MEX is capable of capturing radial structure easily, while SCF needs a large number of radial terms. We show that despite the expansion bias, these methods are more accurate than direct techniques for the same number of particles. The performance of our GPU code, which we call ETICS, is profiled and compared to a CPU implementation. On the tested GPU hardware, a full force calculation for one million particles took ∼0.1 s (depending on expansion cutoff), making simulations with as many as 10{sup 8} particles fast for a comparatively small number of nodes.

  8. Molecular Dynamics Simulations of Coulomb Explosion

    SciTech Connect

    Bringa, E M

    2002-05-17

    A swift ion creates a track of electronic excitations in the target material. A net repulsion inside the track can cause a ''Coulomb Explosion'', which can lead to damage and sputtering of the material. Here we report results from molecular-dynamics (MD) simulations of Coulomb explosion for a cylindrical track as a function of charge density and neutralization/quenching time, {tau}. Screening by the free electrons is accounted for using a screened Coulomb potential for the interaction among charges. The yield exhibits a prompt component from the track core and a component, which dominates at higher excitation density, from the heated region produced. For the cases studied, the number of atoms ejected per incident ion, i.e. the sputtering yield Y, is quadratic with charge density along the track as suggested by simple models. Y({tau} = 0.2 Debye periods) is nearly 20% of the yield when there is no neutralization ({tau} {yields} {infinity}). The connections between ''Coulomb explosions'', thermal spikes and measurements of electronic sputtering are discussed.

  9. Annual Report 1999 Environmental Dynamics and Simulation

    SciTech Connect

    NS Foster-Mills

    2000-06-28

    This annual report describes selected 1999 research accomplishments for the Environmental Dynamics and Simulation (ED and S) directorate, one of six research organizations in the William R. Wiley Environmental Molecular Sciences Laboratory (EMSL). These accomplishments are representative of the different lines of research underway in the ED and S directorate. EMSL is one of US Department of Energy's (DOE) national scientific user facilities and is the centerpiece of DOE's commitment to providing world-class experimental, theoretical, and computational capabilities for solving the nation's environmental problems. Capabilities in the EMSL include over 100 major instrument systems for use by the resident research staff, their collaborators, and users of the EMSL. These capabilities are used to address the fundamental science that will be the basis for finding solutions to national environmental issues such as cleaning up contamianted areas at DOE sites across the country and developing green technologies that will reduce or eliminate future pollution production. The capabilities are also used to further the understanding of global climate change and environmental issues relevant to energy production and use and health effects resulting from exposure to contaminated environments.

  10. Dynamical simulation of an abrasive wear process

    NASA Astrophysics Data System (ADS)

    Elalem, Khaled; Li, D. Y.

    1999-05-01

    A dynamic computer model was developed to simulate wear behavior of materials on micro-scales. In this model, a material system is discretized and mapped onto a lattice or grid. Each lattice site represents a small volume of the material. During a wear process, a lattice site may move under the influence of external force and the interaction between the site and its adjacent sites. The site-site interaction is a function of mechanical properties of the material such as the elastic modulus, yield strength, work hardening and the fracture strain. Newton's law of motion is used to determine the movement of lattice sites during a wear process. The strain between a pair of sites is recoverable if it is within the elastic deformation range; otherwise plastic deformation takes place. A bond between two adjacent sites is broken when its strain exceeds a critical value. A site or a cluster of sites is worn away if all bonds connecting the site or the cluster to its nearest neighbors are broken. The model well describes the strain distribution in a contact region, in consistence with a finite element analysis. This model was applied to several metallic materials abraded under the ASTM G65 abrasion condition, and the results were compared to experimental observations. Good agreement between the modeling and the experiment was found.

  11. Application of control theory to dynamic systems simulation

    NASA Technical Reports Server (NTRS)

    Auslander, D. M.; Spear, R. C.; Young, G. E.

    1982-01-01

    The application of control theory is applied to dynamic systems simulation. Theory and methodology applicable to controlled ecological life support systems are considered. Spatial effects on system stability, design of control systems with uncertain parameters, and an interactive computing language (PARASOL-II) designed for dynamic system simulation, report quality graphics, data acquisition, and simple real time control are discussed.

  12. Dynamic Simulation over Long Time Periods with 100% Solar Generation.

    SciTech Connect

    Concepcion, Ricky James; Elliott, Ryan Thomas

    2015-12-01

    This project aimed to identify the path forward for dynamic simulation tools to accommodate these needs by characterizing the properties of power systems (with high PV penetration), analyzing how these properties affect dynamic simulation software, and offering solutions for potential problems.

  13. Photodissociation dynamics of phenol: multistate trajectory simulations including tunneling.

    PubMed

    Xu, Xuefei; Zheng, Jingjing; Yang, Ke R; Truhlar, Donald G

    2014-11-19

    We report multistate trajectory simulations, including coherence, decoherence, and multidimensional tunneling, of phenol photodissociation dynamics. The calculations are based on full-dimensional anchor-points reactive potential surfaces and state couplings fit to electronic structure calculations including dynamical correlation with an augmented correlation-consistent polarized valence double-ζ basis set. The calculations successfully reproduce the experimentally observed bimodal character of the total kinetic energy release spectra and confirm the interpretation of the most recent experiments that the photodissociation process is dominated by tunneling. Analysis of the trajectories uncovers an unexpected dissociation pathway for one quantum excitation of the O-H stretching mode of the S1 state, namely, tunneling in a coherent mixture of states starting in a smaller ROH (∼0.9-1.0 Å) region than has previously been invoked. The simulations also show that most trajectories do not pass close to the S1-S2 conical intersection (they have a minimum gap greater than 0.6 eV), they provide statistics on the out-of-plane angles at the locations of the minimum energy adiabatic gap, and they reveal information about which vibrational modes are most highly activated in the products.

  14. Bilayer deformation by the Kv channel voltage sensor domain revealed by self-assembly simulations.

    PubMed

    Bond, Peter J; Sansom, Mark S P

    2007-02-20

    Coarse-grained molecular dynamics simulations are used to explore the interaction with a phospholipid bilayer of the voltage sensor (VS) domain and the S4 helix from the archaebacterial voltage-gated potassium (Kv) channel KvAP. Multiple 2-mus self-assembly simulations reveal that the isolated S4 helix may adopt either interfacial or transmembrane (TM) locations with approximately equal probability. In the TM state, the insertion of the voltage-sensing region of S4 is facilitated via local bilayer deformation that, combined with side chain "snorkeling," enables its Arg side chains to interact with lipid headgroups and water. Multiple 0.2-mus self-assembly simulations of the VS domain are also performed, along with simulations of MscL and KcsA, to permit comparison with more "canonical" integral membrane protein structures. All three stably adopt a TM orientation within a bilayer. For MscL and KcsA, there is no significant bilayer deformation. In contrast, for the VS, there is considerable local deformation, which is again primarily due to the lipid-exposed S4. It is shown that for both the VS and isolated S4 helix, the positively charged side chains of S4 are accommodated within the membrane through a combination of stabilizing interactions with lipid glycerol and headgroup regions, water, and anionic side chains. Our results support the possibility that bilayer deformation around key gating charge residues in Kv channels may result in "focusing" of the electrostatic field, and indicate that, when considering competing models of voltage-sensing, it is essential to consider the dynamics and structure of not only the protein but also of the local lipid environment.

  15. Controlled multibody dynamics simulation for large space structures

    NASA Technical Reports Server (NTRS)

    Housner, J. M.; Wu, S. C.; Chang, C. W.

    1989-01-01

    Multibody dynamics discipline, and dynamic simulation in control structure interaction (CSI) design are discussed. The use, capabilities, and architecture of the Large Angle Transient Dynamics (LATDYN) code as a simulation tool are explained. A generic joint body with various types of hinge connections; finite element and element coordinate systems; results of a flexible beam spin-up on a plane; mini-mast deployment; space crane and robotic slewing manipulations; a potential CSI test article; and multibody benchmark experiments are also described.

  16. Hydrotropic Solubilization by Urea Derivatives: A Molecular Dynamics Simulation Study

    PubMed Central

    Cui, Yong

    2013-01-01

    Hydrotropy is a phenomenon where the presence of a large quantity of one solute enhances the solubility of another solute. The mechanism of this phenomenon remains a topic of debate. This study employed molecular dynamics simulation to investigate the hydrotropic mechanism of a series of urea derivatives, that is, urea (UR), methylurea (MU), ethylurea (EU), and butylurea (BU). A poorly water-soluble compound, nifedipine (NF), was used as the model solute that was solubilized. Structural, dynamic, and energetic changes upon equilibration were analyzed to supply insights to the solubilization mechanism. The study demonstrated that NF and urea derivatives underwent significant nonstoichiometric molecular aggregation in the aqueous solution, a result consistent with the self-aggregation of urea derivatives under the same conditions. The analysis of hydrogen bonding and energy changes revealed that the aggregation was driven by the partial restoration of normal water structure. The energetic data also suggested that the promoted solubilization of NF is favored in the presence of urea derivatives. While the solutes aggregated to a varying degree, the systems were still in single-phase liquid state as attested by their active dynamics. PMID:26555993

  17. Swimming patterns and dynamics of simulated Escherichia coli bacteria.

    PubMed

    Zonia, Laura; Bray, Dennis

    2009-11-06

    A spatially and temporally realistic simulation of Escherichia coli chemotaxis was used to investigate the swimming patterns of wild-type and mutant bacteria within a rectangular arena in response to chemoattractant gradients. Swimming dynamics were analysed during long time series with phase-space trajectories, power spectra and estimations of fractal dimensions (FDs). Cell movement displayed complex trajectories in the phase space owing to interaction of multiple attractors that captured runs and tumbles. Deletion of enzymes responsible for adaptation (CheR and CheB) restricted the pattern of bacterial swimming in the absence of a gradient. In the presence of a gradient, there was a strong increase in trajectories arising from runs and attenuation of those arising from tumbles. Similar dynamics were observed for mutants lacking CheY, which are unable to tumble. The deletion of CheR, CheB and CheY also caused significant shifts in chemotaxis spectral frequencies. Rescaled range analysis and estimation of FD suggest that wild-type bacteria display characteristics of fractional Brownian motion with positive correlation between past and future events. These results reveal an underlying order in bacterial swimming dynamics, which enables a chemotactic search strategy conforming to a fractal walk.

  18. Cold-active enzymes studied by comparative molecular dynamics simulation.

    PubMed

    Spiwok, Vojtech; Lipovová, Petra; Skálová, Tereza; Dusková, Jarmila; Dohnálek, Jan; Hasek, Jindrich; Russell, Nicholas J; Králová, Blanka

    2007-04-01

    Enzymes from cold-adapted species are significantly more active at low temperatures, even those close to zero Celsius, but the rationale of this adaptation is complex and relatively poorly understood. It is commonly stated that there is a relationship between the flexibility of an enzyme and its catalytic activity at low temperature. This paper gives the results of a study using molecular dynamics simulations performed for five pairs of enzymes, each pair comprising a cold-active enzyme plus its mesophilic or thermophilic counterpart. The enzyme pairs included alpha-amylase, citrate synthase, malate dehydrogenase, alkaline protease and xylanase. Numerous sites with elevated flexibility were observed in all enzymes; however, differences in flexibilities were not striking. Nevertheless, amino acid residues common in both enzymes of a pair (not present in insertions of a structure alignment) are generally more flexible in the cold-active enzymes. The further application of principle component analysis to the protein dynamics revealed that there are differences in the rate and/or extent of opening and closing of the active sites. The results indicate that protein dynamics play an important role in catalytic processes where structural rearrangements, such as those required for active site access by substrate, are involved. They also support the notion that cold adaptation may have evolved by selective changes in regions of enzyme structure rather than in global change to the whole protein.

  19. Swimming patterns and dynamics of simulated Escherichia coli bacteria

    PubMed Central

    Zonia, Laura; Bray, Dennis

    2009-01-01

    A spatially and temporally realistic simulation of Escherichia coli chemotaxis was used to investigate the swimming patterns of wild-type and mutant bacteria within a rectangular arena in response to chemoattractant gradients. Swimming dynamics were analysed during long time series with phase-space trajectories, power spectra and estimations of fractal dimensions (FDs). Cell movement displayed complex trajectories in the phase space owing to interaction of multiple attractors that captured runs and tumbles. Deletion of enzymes responsible for adaptation (CheR and CheB) restricted the pattern of bacterial swimming in the absence of a gradient. In the presence of a gradient, there was a strong increase in trajectories arising from runs and attenuation of those arising from tumbles. Similar dynamics were observed for mutants lacking CheY, which are unable to tumble. The deletion of CheR, CheB and CheY also caused significant shifts in chemotaxis spectral frequencies. Rescaled range analysis and estimation of FD suggest that wild-type bacteria display characteristics of fractional Brownian motion with positive correlation between past and future events. These results reveal an underlying order in bacterial swimming dynamics, which enables a chemotactic search strategy conforming to a fractal walk. PMID:19324687

  20. A Simulation Program for Dynamic Infrared (IR) Spectra

    ERIC Educational Resources Information Center

    Zoerb, Matthew C.; Harris, Charles B.

    2013-01-01

    A free program for the simulation of dynamic infrared (IR) spectra is presented. The program simulates the spectrum of two exchanging IR peaks based on simple input parameters. Larger systems can be simulated with minor modifications. The program is available as an executable program for PCs or can be run in MATLAB on any operating system. Source…

  1. A Simulation Program for Dynamic Infrared (IR) Spectra

    ERIC Educational Resources Information Center

    Zoerb, Matthew C.; Harris, Charles B.

    2013-01-01

    A free program for the simulation of dynamic infrared (IR) spectra is presented. The program simulates the spectrum of two exchanging IR peaks based on simple input parameters. Larger systems can be simulated with minor modifications. The program is available as an executable program for PCs or can be run in MATLAB on any operating system. Source…

  2. Allosteric Mechanism of Calmodulin Revealed by Targeted Molecular Dynamics Simulation

    NASA Astrophysics Data System (ADS)

    Liang, Qian-Yun; Pang, Chun-Li; Li, Jun-Wei; Zhang, Su-Hua; Liu, Hui; Zhan, Yong; An, Hai-Long

    2017-06-01

    Not Available Supported by the Natural Science Fund for Distinguished Young Scholars of Hebei Province under Grant Nos C2015202340 and C2013202244, the Fund for Outstanding Talents of Hebei Province under Grant No C201400305, the National Natural Science Fund of China under Grant Nos 11247010, 11175055, 11475053, 11347017, 31600594, 31400711 and 11647121, the Fund for the Science and Technology Program of Higher Education Institutions of Hebei Province under Grant No QN2016113, the Scientific Innovation Grant for Excellent Young Scientists of Hebei University of Technology under Grant No 2015010, and the Natural Science Foundation of Hebei Province under Grant No C2017202208.

  3. Eye Movements Reveal the Dynamic Simulation of Speed in Language

    ERIC Educational Resources Information Center

    Speed, Laura J.; Vigliocco, Gabriella

    2014-01-01

    This study investigates how speed of motion is processed in language. In three eye-tracking experiments, participants were presented with visual scenes and spoken sentences describing fast or slow events (e.g., "The lion ambled/dashed to the balloon"). Results showed that looking time to relevant objects in the visual scene was affected…

  4. Eye Movements Reveal the Dynamic Simulation of Speed in Language

    ERIC Educational Resources Information Center

    Speed, Laura J.; Vigliocco, Gabriella

    2014-01-01

    This study investigates how speed of motion is processed in language. In three eye-tracking experiments, participants were presented with visual scenes and spoken sentences describing fast or slow events (e.g., "The lion ambled/dashed to the balloon"). Results showed that looking time to relevant objects in the visual scene was affected…

  5. Molecular dynamics simulations of oxidized and reduced Clostridium beijerinckii flavodoxin.

    PubMed Central

    Leenders, R; van Gunsteren, W F; Berendsen, H J; Visser, A J

    1994-01-01

    Molecular dynamics simulations of oxidized and reduced Clostridium beijerinckii flavodoxin in water have been performed in a sphere of 1.4-nm radius surrounded by a restrained shell of 0.8 nm. The flavin binding site, comprising the active site of the flavodoxin, was in the center of the sphere. No explicit information about protein-bound water molecules was included. An analysis is made of the motional characteristics of residues located in the active site. Positional fluctuations, hydrogen bonding patterns, dihedral angle transitions, solvent behavior, and time-dependent correlations are examined. The 375-ps trajectories show that both oxidized and reduced protein-bound flavins are immobilized within the protein matrix, in agreement with earlier obtained time-resolved fluorescence anisotropy data. The calculated time-correlated behavior of the tryptophan residues reveals significant picosecond mobility of the tryptophan side chain located close to the reduced isoalloxazine part of the flavin. PMID:8011895

  6. Diffusion and structure in silica liquid: a molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Hung, P. K.; Hong, N. V.; Vinh, L. T.

    2007-11-01

    Diffusion and structure in liquid silica under pressure have been investigated by a molecular dynamics model of 999 atoms with the inter-atomic potentials of van Beest, Kramer and van Santen. The simulation reveals that silica liquid is composed of the species SiO4, SiO5 and SiO6 with a fraction dependent on pressure. The density as well as volume of voids can be expressed as a linear function of the fraction of those species. Low-density liquid is mainly constructed of SiO4 and has a large number of O- and Si-voids and a large void tube. This tube contains most O-voids and is spread over the whole system. The anomalous diffusion behavior is observed and discussed.

  7. Relationship between nanocrystalline and amorphous microstructures by molecular dynamics simulation

    SciTech Connect

    Keblinski, P.; Phillpot, S.R.; Wolf, D.; Gleiter, H.

    1996-08-01

    A recent molecular dynamics simulation method for growth of fully dense nanocrystalline materials crystallized from melt was used with the Stillinger-Weber three-body potential to synthesize nanocrystalline Si with a grain size up to 75{Angstrom}. Structures of the highly constrained grain boundaries (GBs), triple lines, and point grain junctions were found to be highly disordered and similar to the structure of amorphous Si. These and earlier results for fcc metals suggest that a nanocrystalline microstructure may be viewed as a two-phase system, namely an ordered crystalline phase in the grain interiors connected by an amorphous, intergranular, glue-like phase. Analysis of the structures of bicrystalline GBs in the same materials reveals the presence of an amorphous intergranular equilibrium phase only in the high-energy but not the low-energy GBs, suggesting that only high-energy boundaries are present in nanocrystalline microstructures.

  8. Molecular dynamics simulation of graphene bombardment with Si ion

    NASA Astrophysics Data System (ADS)

    Qin, Xin-Mao; Gao, Ting-Hong; Yan, Wan-Jun; Guo, Xiao-Tian; Xie, Quan

    2014-03-01

    Molecular dynamics simulations with Tersoff-Ziegler-Biersack-Littmark (Tersoff-ZBL) potential and adaptive intermolecular reactive empirical bond order (AIREBO) potential are performed to study the effect of irradiated graphene with silicon ion at several positions and energy levels of 0.1-1000 eV. The simulations reveal four processes: absorption, replacement, transmission and damage. At energies below 110 eV, the dominant process is absorption. For atom in group (a), the process that takes place is replacement, in which the silicon ion removes one carbon atom and occupies the place of the eliminated atom at the incident energy of 72-370 eV. Transmission is present at energies above 100 eV for atom in group (d). Damage is a very important process in current bombardment, and there are four types of defects: single vacancy, replacement-single vacancy, double vacancy and nanopore. The simulations provide a fundamental understanding of the silicon bombardment of graphene, and the parameters required to develop graphene-based devices by controlling defect formation.

  9. Dynamical diffraction simulations in FePt--I.

    PubMed

    Torres, Karen L; Vanfleet, Richard R; Thompson, Gregory B

    2011-06-01

    A series of multislice simulations to quantify the effect of various degrees of order, composition, and thickness on the electron diffracted intensities were performed using the L1₀ FePt system as the case study. The dynamical diffraction studies were done in both a convergent electron beam diffraction and selected area electron diffraction condition. The L1₀ symmetry demonstrated some peculiar challenges in the simulation, in particular between the {111} plane normal and the <111> direction, which are not equivalent because of tetragonality. A hybrid weighting function atom of Fe-Pt was constructed to account for S < 1 or nonequiatomic compositions. This statistical approach reduced the complexity of constructing a crystal with the probability that a particular atom was at a particular lattice site for a given order parameter and composition. Considerations of accelerating voltage, convergent angle, and thermal effects are discussed. The simulations revealed significant differences in intensity ratios between films of various compositions but equivalent unit cell numbers and degree of order.

  10. Dynamic Evaluation of Two Decades of CMAQ Simulations ...

    EPA Pesticide Factsheets

    This presentation focuses on the dynamic evaluation of the CMAQ model over the continental United States using multi-decadal simulations for the period from 1990 to 2010 to examine how well the changes in observed ozone air quality induced by variations in meteorology and/or emissions are simulated by the model. We applied spectral decomposition of the ozone time-series using the KZ filter to assess the variations in the strengths of synoptic (weather-induced variations) and baseline (long-term variation) forcings, embedded in the simulated and observed concentrations. The results reveal that CMAQ captured the year-to-year variability (more so in the later years than the earlier years) and the synoptic forcing in accordance with what the observations are showing. The National Exposure Research Laboratory (NERL) Computational Exposure Division (CED) develops and evaluates data, decision-support tools, and models to be applied to media-specific or receptor-specific problem areas. CED uses modeling-based approaches to characterize exposures, evaluate fate and transport, and support environmental diagnostics/forensics with input from multiple data sources. It also develops media- and receptor-specific models, process models, and decision support tools for use both within and outside of EPA.

  11. Simulations reveal the role of composition into the atomic-level flexibility of bioactive glass cements.

    PubMed

    Tian, Kun Viviana; Chass, Gregory A; Di Tommaso, Devis

    2016-01-14

    Bioactive glass ionomer cements (GICs), the reaction product of a fluoro-alumino-silicate glass and polyacrylic acid, have been in effective use in dentistry for over 40 years and more recently in orthopaedics and medical implantation. Their desirable properties have affirmed GIC's place in the medical materials community, yet are limited to non-load bearing applications due to the brittle nature of the hardened composite cement, thought to arise from the glass component and the interfaces it forms. Towards helping resolve the fundamental bases of the mechanical shortcomings of GICs, we report the 1st ever computational models of a GIC-relevant component. Ab initio molecular dynamics simulations were employed to generate and characterise three fluoro-alumino-silicate glasses of differing compositions with focus on resolving the atomic scale structural and dynamic contributions of aluminium, phosphorous and fluorine. Analyses of the glasses revealed rising F-content leading to the expansion of the glass network, compression of Al-F bonding, angular constraint at Al-pivots, localisation of alumino-phosphates and increased fluorine diffusion. Together, these changes to the structure, speciation and dynamics with raised fluorine content impart an overall rigidifying effect on the glass network, and suggest a predisposition to atomic-level inflexibility, which could manifest in the ionomer cements they form.

  12. Molecular dynamics simulation of liquid water confined inside graphite channels: dielectric and dynamical properties.

    PubMed

    Martí, J; Nagy, G; Guàrdia, E; Gordillo, M C

    2006-11-30

    Electric and dielectric properties and microscopic dynamics of liquid water confined between graphite slabs are analyzed by means of molecular dynamics simulations for several graphite-graphite separations at ambient conditions. The electric potential across the interface shows oscillations due to water layering, and the overall potential drop is about -0.28 V. The total dielectric constant is larger than the corresponding value for the bulklike internal region of the system. This is mainly due to the preferential orientations of water nearest the graphite walls. Estimation of the capacitance of the system is reported, indicating large variations for the different adsorption layers. The main trend observed concerning water diffusion is 2-fold: on one hand, the overall diffusion of water is markedly smaller for the closest graphite-graphite separations, and on the other hand, water molecules diffuse in interfaces slightly slower than those in the bulklike internal areas. Molecular reorientational times are generally larger than those corresponding to those of unconstrained bulk water. The analysis of spectral densities revealed significant spectral shifts, compared to the bands in unconstrained water, in different frequency regions, and associated to confinement effects. These findings are important because of the scarce information available from experimental, theoretical, and computer simulation research into the dielectric and dynamical properties of confined water.

  13. Dynamics of the Wulong landslide revealed by broadband seismic records

    NASA Astrophysics Data System (ADS)

    Li, Zhengyuan; Huang, Xinghui; Xu, Qiang; Yu, Dan; Fan, Junyi; Qiao, Xuejun

    2017-02-01

    The catastrophic Wulong landslide occurred at 14:51 (Beijing time, UTC+8) on 5 June 2009, in Wulong Prefecture, Southwest China. This rockslide occurred in a complex topographic environment. Seismic signals generated by this event were recorded by the seismic network deployed in the surrounding area, and long-period signals were extracted from 8 broadband seismic stations within 250 km to obtain source time functions by inversion. The location of this event was simultaneously acquired using a stepwise refined grid search approach, with an error of 2.2 km. The estimated source time functions reveal that, according to the movement parameters, this landslide could be divided into three stages with different movement directions, velocities, and increasing inertial forces. The sliding mass moved northward, northeastward and northward in the three stages, with average velocities of 6.5, 20.3, and 13.8 m/s, respectively. The maximum movement velocity of the mass reached 35 m/s before the end of the second stage. The basal friction coefficients were relatively small in the first stage and gradually increasing; large in the second stage, accompanied by the largest variability; and oscillating and gradually decreasing to a stable value, in the third stage. Analysis shows that the movement characteristics of these three stages are consistent with the topography of the sliding zone, corresponding to the northward initiation, eastward sliding after being stopped by the west wall, and northward debris flowing after collision with the east slope of the Tiejianggou valley. The maximum movement velocity of the sliding mass results from the largest height difference of the west slope of the Tiejianggou valley. The basal friction coefficients of the three stages represent the thin weak layer in the source zone, the dramatically varying topography of the west slope of the Tiejianggou valley, and characteristics of the debris flow along the Tiejianggou valley. Based on the above

  14. 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

  15. Cape buffalo mitogenomics reveals a Holocene shift in the African human-megafauna dynamics.

    PubMed

    Heller, Rasmus; Brüniche-Olsen, Anna; Siegismund, Hans R

    2012-08-01

    Africa is unique among the continents in having maintained an extraordinarily diverse and prolific megafauna spanning the Pleistocene-Holocene epochs. Little is known about the historical dynamics of this community and even less about the reasons for its unique persistence to modern times. We sequenced complete mitochondrial genomes from 43 Cape buffalo (Syncerus caffer caffer) to infer the demographic history of this large mammal. A combination of Bayesian skyline plots, simulations and Approximate Bayesian Computation (ABC) were used to distinguish population size dynamics from the confounding effect of population structure and identify the most probable demographic scenario. Our analyses revealed a late Pleistocene expansion phase concurrent with the human expansion between 80 000 and 10 000 years ago, refuting an adverse ecological effect of Palaeolithic humans on this quarry species, but also showed that the buffalo subsequently declined during the Holocene. The distinct two-phased dynamic inferred here suggests that a major ecological transition occurred in the Holocene. The timing of this transition coincides with the onset of drier conditions throughout tropical Africa following the Holocene Optimum (∼9000-5000 years ago), but also with the explosive growth in human population size associated with the transition from the Palaeolithic to the Neolithic cultural stage. We evaluate each of these possible causal factors and their potential impact on the African megafauna, providing the first systematic assessment of megafauna dynamics on the only continent where large mammals remain abundant.

  16. Animated molecular dynamics simulations of hydrated caesium-smectite interlayers

    PubMed Central

    Sutton, Rebecca; Sposito, Garrison

    2002-01-01

    Computer animation of center of mass coordinates obtained from 800 ps molecular dynamics simulations of Cs-smectite hydrates (1/3 and 2/3 water monolayers) provided information concerning the structure and dynamics of the interlayer region that could not be obtained through traditional simulation analysis methods. Cs+ formed inner sphere complexes with the mineral surface, and could be seen to jump from one attracting location near a layer charge site to the next, while water molecules were observed to migrate from the hydration shell of one ion to that of another. Neighboring ions maintained a partial hydration shell by sharing water molecules, such that a single water molecule hydrated two ions simultaneously for hundreds of picoseconds. Cs-montmorillonite hydrates featured the largest extent of this sharing interaction, because interlayer ions were able to inhabit positions near surface cavities as well as at their edges, close to oxygen triads. The greater positional freedom of Cs+ within the montmorillonite interlayer, a result of structural hydroxyl orientation and low tetrahedral charge, promoted the optimization of distances between cations and water molecules required for water sharing. Preference of Cs+ for locations near oxygen triads was observed within interlayer beidellite and hectorite. Water molecules also could be seen to interact directly with the mineral surface, entering its surface cavities to approach attracting charge sites and structural hydroxyls. With increasing water content, water molecules exhibited increased frequency and duration of both cavity habitation and water sharing interactions. Competition between Cs+ and water molecules for surface sites was evident. These important cooperative and competitive features of interlayer molecular behavior were uniquely revealed by animation of an otherwise highly complex simulation output.

  17. Laser altimetry reveals complex pattern of Greenland Ice Sheet dynamics.

    PubMed

    Csatho, Beata M; Schenk, Anton F; van der Veen, Cornelis J; Babonis, Gregory; Duncan, Kyle; Rezvanbehbahani, Soroush; van den Broeke, Michiel R; Simonsen, Sebastian B; Nagarajan, Sudhagar; van Angelen, Jan H

    2014-12-30

    We present a new record of ice thickness change, reconstructed at nearly 100,000 sites on the Greenland Ice Sheet (GrIS) from laser altimetry measurements spanning the period 1993-2012, partitioned into changes due to surface mass balance (SMB) and ice dynamics. We estimate a mean annual GrIS mass loss of 243 ± 18 Gt ⋅ y(-1), equivalent to 0.68 mm ⋅ y(-1) sea level rise (SLR) for 2003-2009. Dynamic thinning contributed 48%, with the largest rates occurring in 2004-2006, followed by a gradual decrease balanced by accelerating SMB loss. The spatial pattern of dynamic mass loss changed over this time as dynamic thinning rapidly decreased in southeast Greenland but slowly increased in the southwest, north, and northeast regions. Most outlet glaciers have been thinning during the last two decades, interrupted by episodes of decreasing thinning or even thickening. Dynamics of the major outlet glaciers dominated the mass loss from larger drainage basins, and simultaneous changes over distances up to 500 km are detected, indicating climate control. However, the intricate spatiotemporal pattern of dynamic thickness change suggests that, regardless of the forcing responsible for initial glacier acceleration and thinning, the response of individual glaciers is modulated by local conditions. Recent projections of dynamic contributions from the entire GrIS to SLR have been based on the extrapolation of four major outlet glaciers. Considering the observed complexity, we question how well these four glaciers represent all of Greenland's outlet glaciers.

  18. Nanomaterials under extreme environments: A study of structural and dynamic properties using reactive molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Shekhar, Adarsh

    Nanotechnology is becoming increasingly important with the continuing advances in experimental techniques. As researchers around the world are trying to expand the current understanding of the behavior of materials at the atomistic scale, the limited resolution of equipment, both in terms of time and space, act as roadblocks to a comprehensive study. Numerical methods, in general and molecular dynamics, in particular act as able compliment to the experiments in our quest for understanding material behavior. In this research work, large scale molecular dynamics simulations to gain insight into the mechano-chemical behavior under extreme conditions of a variety of systems with many real world applications. The body of this work is divided into three parts, each covering a particular system: 1) Aggregates of aluminum nanoparticles are good solid fuel due to high flame propagation rates. Multi-million atom molecular dynamics simulations reveal the mechanism underlying higher reaction rate in a chain of aluminum nanoparticles as compared to an isolated nanoparticle. This is due to the penetration of hot atoms from reacting nanoparticles to an adjacent, unreacted nanoparticle, which brings in external heat and initiates exothermic oxidation reactions. 2) Cavitation bubbles readily occur in fluids subjected to rapid changes in pressure. We use billion-atom reactive molecular dynamics simulations on a 163,840-processor BlueGene/P supercomputer to investigate chemical and mechanical damages caused by shock-induced collapse of nanobubbles in water near amorphous silica. Collapse of an empty nanobubble generates high-speed nanojet, resulting in the formation of a pit on the surface. The pit contains a large number of silanol groups and its volume is found to be directly proportional to the volume of the nanobubble. The gas-filled bubbles undergo partial collapse and consequently the damage on the silica surface is mitigated. 3) The structure and dynamics of water confined in

  19. Partial structure factors reveal atomic dynamics in metallic alloy melts

    NASA Astrophysics Data System (ADS)

    Nowak, B.; Holland-Moritz, D.; Yang, F.; Voigtmann, Th.; Kordel, T.; Hansen, T. C.; Meyer, A.

    2017-07-01

    We investigate the dynamical decoupling of the diffusion coefficients of the different components in a metallic alloy melt, using a combination of neutron diffraction, isotopic substitution, and electrostatic levitation in Zr-Ni melts. We show that excess Ni atoms can diffuse more freely in a background of saturated chemical interaction, causing their dynamics to become much faster and thus decoupled than anticipated from the interparticle interactions. Based on the mode-coupling theory of the glass transition, the averaged structure as given by the partial static structure factors is able to explain the observed dynamical behavior.

  20. Mechanics of severing for large microtubule complexes revealed by coarse-grained simulations

    NASA Astrophysics Data System (ADS)

    Theisen, Kelly E.; Desai, Neha J.; Volski, Allison M.; Dima, Ruxandra I.

    2013-09-01

    We investigate the mechanical behavior of microtubule (MT) protofilaments under the action of bending forces, ramped up linearly in time, to provide insight into the severing of MTs by microtubule associated proteins (MAPs). We used the self-organized polymer model which employs a coarse-grained description of the protein chain and ran Brownian dynamics simulations accelerated on graphics processing units that allow us to follow the dynamics of a MT system on experimental timescales. Our study focused on the role played in the MT depolymerization dynamics by the inter-tubulin contacts a protofilament experiences when embedded in the MT lattice, and the number of binding sites of MAPs on MTs. We found that proteins inducing breaking of MTs must have at least three attachment points on any tubulin dimer from an isolated protofilament. In contrast, two points of contact would suffice when dimers are located in an intact MT lattice, in accord with experimental findings on MT severing proteins. Our results show that confinement of a protofilament in the MT lattice leads to a drastic reduction in the energy required for the removal of tubulin dimers, due to the drastic reduction in entropy. We further showed that there are differences in the energetic requirements based on the location of the dimer to be removed by severing. Comparing the energy of tubulin dimers removal revealed by our simulations with the amount of energy resulting from one ATP hydrolysis, which is the source of energy for all MAPs, we provided strong evidence for the experimental finding that severing proteins do not bind uniformly along the MT wall.

  1. Simulating fiction: individual differences in literature comprehension revealed with FMRI.

    PubMed

    Nijhof, Annabel D; Willems, Roel M

    2015-01-01

    When we read literary fiction, we are transported to fictional places, and we feel and think along with the characters. Despite the importance of narrative in adult life and during development, the neurocognitive mechanisms underlying fiction comprehension are unclear. We used functional magnetic resonance imaging (fMRI) to investigate how individuals differently employ neural networks important for understanding others' beliefs and intentions (mentalizing), and for sensori-motor simulation while listening to excerpts from literary novels. Localizer tasks were used to localize both the cortical motor network and the mentalizing network in participants after they listened to excerpts from literary novels. Results show that participants who had high activation in anterior medial prefrontal cortex (aMPFC; part of the mentalizing network) when listening to mentalizing content of literary fiction, had lower motor cortex activity when they listened to action-related content of the story, and vice versa. This qualifies how people differ in their engagement with fiction: some people are mostly drawn into a story by mentalizing about the thoughts and beliefs of others, whereas others engage in literature by simulating more concrete events such as actions. This study provides on-line neural evidence for the existence of qualitatively different styles of moving into literary worlds, and adds to a growing body of literature showing the potential to study narrative comprehension with neuroimaging methods.

  2. Multimillion atom molecular dynamics simulations of glasses and ceramic materials

    NASA Astrophysics Data System (ADS)

    Vashishta, Priya; Kalia, Rajiv K.; Nakano, Aiichiro

    1999-11-01

    Molecular dynamics simulations are a powerful tool for studying physical and chemical phenomena in materials. In these lectures we shall review the molecular dynamics method and its implementation on parallel computer architectures. Using the molecular dynamics method we will study a number of materials in different ranges of density, temperature, and uniaxial strain. These include structural correlations in silica glass under pressure, crack propagation in silicon nitride films, sintering of silicon nitride nanoclusters, consolidation of nanophase materials, and dynamic fracture. Multimillion atom simulations of oxidation of aluminum nanoclusters and nanoindentation in silicon nitride will also be discussed.

  3. Glycan flexibility: insights into nanosecond dynamics from a microsecond molecular dynamics simulation explaining an unusual nuclear Overhauser effect.

    PubMed

    Landström, Jens; Widmalm, Göran

    2010-01-26

    An atomistic all-atom molecular dynamics simulation of the trisaccharide beta-D-ManpNAc-(1-->4)[alpha-D-Glcp-(1-->3)]-alpha-L-Rhap-OMe with explicit solvent molecules has been carried out. The trisaccharide represents a model for the branching region of the O-chain polysaccharide of a strain from Aeromonas salmonicida. The extensive MD simulations having a 1-micros duration revealed a conformational dynamics process on the nanosecond time scale, that is, a 'time window' not extensively investigated for carbohydrates to date. The results obtained from the MD simulation underscore the predictive power of molecular simulations in studies of biomolecular systems and also explain an unusual nuclear Overhauser effect originating from conformational exchange. 2009 Elsevier Ltd. All rights reserved.

  4. Protein dynamics and enzyme catalysis: insights from simulations.

    PubMed

    McGeagh, John D; Ranaghan, Kara E; Mulholland, Adrian J

    2011-08-01

    The role of protein dynamics in enzyme catalysis is one of the most active and controversial areas in enzymology today. Some researchers claim that protein dynamics are at the heart of enzyme catalytic efficiency, while others state that dynamics make no significant contribution to catalysis. What is the biochemist - or student - to make of the ferocious arguments in this area? Protein dynamics are complex and fascinating, as molecular dynamics simulations and experiments have shown. The essential question is: do these complex motions have functional significance? In particular, how do they affect or relate to chemical reactions within enzymes, and how are chemical and conformational changes coupled together? Biomolecular simulations can analyse enzyme reactions and dynamics in atomic detail, beyond that achievable in experiments: accurate atomistic modelling has an essential part to play in clarifying these issues. This article is part of a Special Issue entitled: Protein Dynamics: Experimental and Computational Approaches.

  5. Dynamics modeling and simulation of autonomous underwater vehicles with appendages

    NASA Astrophysics Data System (ADS)

    Su, Yumin; Zhao, Jinxin; Cao, Jian; Zhang, Guocheng

    2013-03-01

    To provide a simulation system platform for designing and debugging a small autonomous underwater vehicle's (AUV) motion controller, a six-degree of freedom (6-DOF) dynamic model for AUV controlled by thruster and fins with appendages is examined. Based on the dynamic model, a simulation system for the AUV's motion is established. The different kinds of typical motions are simulated to analyze the motion performance and the maneuverability of the AUV. In order to evaluate the influences of appendages on the motion performance of the AUV, simulations of the AUV with and without appendages are performed and compared. The results demonstrate the AUV has good maneuverability with and without appendages.

  6. Laser altimetry reveals complex pattern of Greenland Ice Sheet dynamics

    PubMed Central

    Csatho, Beata M.; Schenk, Anton F.; van der Veen, Cornelis J.; Babonis, Gregory; Duncan, Kyle; Rezvanbehbahani, Soroush; van den Broeke, Michiel R.; Simonsen, Sebastian B.; Nagarajan, Sudhagar; van Angelen, Jan H.

    2014-01-01

    We present a new record of ice thickness change, reconstructed at nearly 100,000 sites on the Greenland Ice Sheet (GrIS) from laser altimetry measurements spanning the period 1993–2012, partitioned into changes due to surface mass balance (SMB) and ice dynamics. We estimate a mean annual GrIS mass loss of 243 ± 18 Gt⋅y−1, equivalent to 0.68 mm⋅y−1 sea level rise (SLR) for 2003–2009. Dynamic thinning contributed 48%, with the largest rates occurring in 2004–2006, followed by a gradual decrease balanced by accelerating SMB loss. The spatial pattern of dynamic mass loss changed over this time as dynamic thinning rapidly decreased in southeast Greenland but slowly increased in the southwest, north, and northeast regions. Most outlet glaciers have been thinning during the last two decades, interrupted by episodes of decreasing thinning or even thickening. Dynamics of the major outlet glaciers dominated the mass loss from larger drainage basins, and simultaneous changes over distances up to 500 km are detected, indicating climate control. However, the intricate spatiotemporal pattern of dynamic thickness change suggests that, regardless of the forcing responsible for initial glacier acceleration and thinning, the response of individual glaciers is modulated by local conditions. Recent projections of dynamic contributions from the entire GrIS to SLR have been based on the extrapolation of four major outlet glaciers. Considering the observed complexity, we question how well these four glaciers represent all of Greenland’s outlet glaciers. PMID:25512537

  7. Molecular dynamics simulations of granular compaction: The single granule case

    NASA Astrophysics Data System (ADS)

    Sanchez-Castillo, Francisco X.; Anwar, Jamshed; Heyes, David M.

    2003-03-01

    We have carried out nonequilibrium molecular dynamics simulations of the compaction of a single three-dimensional granule composed of over 1000 Lennard-Jones (LJ) particles. The granule was contained within an orthorhombic box with repulsive walls and deformed by a vertically moving top wall. The compaction cycle adopted was intended to mimic the procedure employed in industrial tabletting processes, by compressing the granule during the downward movement of the top wall (compaction) followed by an upward movement of the top wall (decompaction). We have explored the effects of different compression rates on the deformation, microstructure, and the final integrity of the granule. Although the simulations are formally atomistic, we believe a mesoscopic significance can be attached to the results that makes them relevant to the larger scale compaction involved in industrially relevant processes. The cluster representation of the granule allows for significant deformation during the process, and the simulations reproduce a number of well-known effects found in the pharmaceutical tabletting and other literature. Rapid compaction resulted in an essentially elastic response and even break up of the formed tablet during the decompaction stage, an effect known as lamination. Slower compaction speeds, which enabled greater internal rearrangement of the LJ particles through plastic deformation, produced a more structurally uniform tablet at the end of the cycle. For the faster compaction speed the top wall moved away faster than the compacted material could recover, giving rise to misleadingly low values of the apparent elastic response of the material as measured by the force from the material on the top wall. We believe this could be an important issue when interpreting experimental data. These simulations were able to capture the transition between the fast and slow compaction rate regimes and reveal some rudiments of the lamination problem that plagues the industrial

  8. Comparisons of Kinematics and Dynamics Simulation Software Tools

    NASA Technical Reports Server (NTRS)

    Shiue, Yeu-Sheng Paul

    2002-01-01

    Kinematic and dynamic analyses for moving bodies are essential to system engineers and designers in the process of design and validations. 3D visualization and motion simulation plus finite element analysis (FEA) give engineers a better way to present ideas and results. Marshall Space Flight Center (MSFC) system engineering researchers are currently using IGRIP from DELMIA Inc. as a kinematic simulation tool for discrete bodies motion simulations. Although IGRIP is an excellent tool for kinematic simulation with some dynamic analysis capabilities in robotic control, explorations of other alternatives with more powerful dynamic analysis and FEA capabilities are necessary. Kinematics analysis will only examine the displacement, velocity, and acceleration of the mechanism without considering effects from masses of components. With dynamic analysis and FEA, effects such as the forces or torques at the joint due to mass and inertia of components can be identified. With keen market competition, ALGOR Mechanical Event Simulation (MES), MSC visualNastran 4D, Unigraphics Motion+, and Pro/MECHANICA were chosen for explorations. In this study, comparisons between software tools were presented in terms of following categories: graphical user interface (GUI), import capability, tutorial availability, ease of use, kinematic simulation capability, dynamic simulation capability, FEA capability, graphical output, technical support, and cost. Propulsion Test Article (PTA) with Fastrac engine model exported from IGRIP and an office chair mechanism were used as examples for simulations.

  9. Comparisons of Kinematics and Dynamics Simulation Software Tools

    NASA Technical Reports Server (NTRS)

    Shiue, Yeu-Sheng Paul

    2002-01-01

    Kinematic and dynamic analyses for moving bodies are essential to system engineers and designers in the process of design and validations. 3D visualization and motion simulation plus finite element analysis (FEA) give engineers a better way to present ideas and results. Marshall Space Flight Center (MSFC) system engineering researchers are currently using IGRIP from DELMIA Inc. as a kinematic simulation tool for discrete bodies motion simulations. Although IGRIP is an excellent tool for kinematic simulation with some dynamic analysis capabilities in robotic control, explorations of other alternatives with more powerful dynamic analysis and FEA capabilities are necessary. Kinematics analysis will only examine the displacement, velocity, and acceleration of the mechanism without considering effects from masses of components. With dynamic analysis and FEA, effects such as the forces or torques at the joint due to mass and inertia of components can be identified. With keen market competition, ALGOR Mechanical Event Simulation (MES), MSC visualNastran 4D, Unigraphics Motion+, and Pro/MECHANICA were chosen for explorations. In this study, comparisons between software tools were presented in terms of following categories: graphical user interface (GUI), import capability, tutorial availability, ease of use, kinematic simulation capability, dynamic simulation capability, FEA capability, graphical output, technical support, and cost. Propulsion Test Article (PTA) with Fastrac engine model exported from IGRIP and an office chair mechanism were used as examples for simulations.

  10. Mosquito population dynamics from cellular automata-based simulation

    NASA Astrophysics Data System (ADS)

    Syafarina, Inna; Sadikin, Rifki; Nuraini, Nuning

    2016-02-01

    In this paper we present an innovative model for simulating mosquito-vector population dynamics. The simulation consist of two stages: demography and dispersal dynamics. For demography simulation, we follow the existing model for modeling a mosquito life cycles. Moreover, we use cellular automata-based model for simulating dispersal of the vector. In simulation, each individual vector is able to move to other grid based on a random walk. Our model is also capable to represent immunity factor for each grid. We simulate the model to evaluate its correctness. Based on the simulations, we can conclude that our model is correct. However, our model need to be improved to find a realistic parameters to match real data.

  11. Dynamic control of protein conformation transition in chromatographic separation based on hydrophobic interactions: molecular dynamics simulation.

    PubMed

    Zhang, Lin; Lu, Diannan; Liu, Zheng

    2009-03-20

    Conformational transitions of a protein in hydrophobic interaction based chromatography, including hydrophobic interaction chromatography (HIC) and reversed-phase liquid chromatography (RPLC), and their impact on the separation process and performance were probed by molecular dynamics simulation of a 46-bead beta-barrel coarse-grained model protein in a confined pore, which represents the porous adsorbent. The transition of the adsorbed protein from the native conformation to an unfolded one occurred as a result of strong hydrophobic interactions with the pore surface, which reduced the formation of protein aggregates. The conformational transition was also displayed in the simulation once an elution buffer characterized by weaker hydrophobicity was introduced to strip protein from pore surface. The discharged proteins that underwent conformational transition were prone to aggregation; thus, an unsatisfactory yield of the native protein was obtained. An orthogonal experiment revealed that in addition to the strengths of the protein-protein and protein-adsorbent hydrophobic interactions, the elution time required to reduce the above-mentioned interactions also determined the yield of native protein by HIC and RPLC. Stepwise elution, characterized by sequential reduction of the hydrophobic interactions between the protein and adsorbent, was presented as a dynamic strategy for tuning conformational transitions to favor the native conformation and reduce the formation of protein aggregates during the elution process. The yield of the native protein obtained by this dynamic operation strategy was higher than that obtained by steady-state elution. The simulation study qualitatively reproduced the experimental observations and provided molecular insight that would be helpful for designing and optimizing HIC and RPLC separation of proteins.

  12. Physical Properties of GaN Nanotubes as Revealed by Computer Simulation

    SciTech Connect

    Wang, Zhiguo; Gao, Fei; Zu, Xiaotao; Weber, William J.

    2008-07-25

    Single-crystalline wurtzite GaN nanotubes have been synthesized recently with proposed applications in nanoscale electronics, optoelectronics and the biochemical-sensing field. Molecular dynamics methods with a Stillinger-Weber potential are used to investigate the melting behavior, thermal conductivity and mechanical properties of these wurtzite-type single crystalline GaN nanotubes. Four major topical areas are summarized in this chapter. (1) The melting temperature of the GaN nanotubes increases with the thickness of the nanotubes to a saturation value, which is close to the melting temperature of bulk GaN. The simulations result reveal that the nanotubes begin to melt at the surface, and then the melting rapidly extends to the interior of the nanotubes as the temperature increases. (2) The thermal conductivity of nanotubes is smaller than that of the bulk GaN single crystal. The thermal conductivity is also found to decrease with temperature and increase with increasing wall thickness of the nanotubes. The change of phonon spectrum and surface inelastic scattering may account for the reduction of thermal conductivity in the nanotubes, while thermal softening and high frequency phonon interactions at high temperatures may provide an explanation for its decrease with increasing temperature. (3) At low temperatures, the simulation results show that the nanotubes exhibit brittle properties; whereas at high temperatures, they behave as ductile materials. The brittle to ductile transition temperature generally increases with increasing wall thickness of the nanotubes and increasing strain rate. (4) The simulation temperature, tube length and strain rate affect the buckling behavior of GaN nanotubes. The critical stress decreases with the increase of simulation temperature and tube length. The dependence of buckling on tube length is consistent with the analysis of equivalent continuum structures using Euler buckling theory.

  13. Simulating Hamiltonian Dynamics with a Truncated Taylor Series

    NASA Astrophysics Data System (ADS)

    Somma, Rolando

    2015-03-01

    One of the main motivations for quantum computers is their ability to efficiently simulate the dynamics of quantum systems. Since the mid-1990s, many algorithms have been developed to simulate Hamiltonian dynamics on a quantum computer, with applications to problems such as simulating spin models and quantum chemistry. While it is now well known that quantum computers can efficiently simulate Hamiltonian dynamics, ongoing work has improved the performance and expanded the scope of such simulations. In this talk, I will describe a very simple and efficient algorithm for simulating Hamiltonian dynamics on a quantum computer by approximating the truncated Taylor series of the evolution operator. This algorithm can simulate the time evolution of a wide variety of physical systems. The cost of this algorithm depends only logarithmically on the inverse of the desired precision, and can be shown to be optimal. Such a cost also represents an exponential improvement over known methods for Hamiltonian simulation based on, e.g., Trotter-Suzuki approximations. Roughly speaking, doubling the number of digits of accuracy of the simulation only doubles the complexity. The new algorithm and its analysis are highly simplified due to a technique for implementing linear combinations of unitary operations to directly apply the truncated Taylor series. This is joint work with Dominic Berry, Andrew Childs, Richard Cleve, and Robin Kothari.

  14. Dynamics of water confined in lyotropic liquid crystals: Molecular dynamics simulations of the dynamic structure factor

    NASA Astrophysics Data System (ADS)

    Mantha, Sriteja; Yethiraj, Arun

    2016-02-01

    The properties of water under confinement are of practical and fundamental interest. In this work, we study the properties of water in the self-assembled lyotropic phases of Gemini surfactants with a focus on testing the standard analysis of quasi-elastic neutron scattering (QENS) experiments. In QENS experiments, the dynamic structure factor is measured and fit to models to extract the translational diffusion constant, DT, and rotational relaxation time, τR. We test this procedure by using simulation results for the dynamic structure factor, extracting the dynamic parameters from the fit as is typically done in experiments, and comparing the values to those directly measured in the simulations. We find that the de-coupling approximation, where the intermediate scattering function is assumed to be a product of translational and rotational contributions, is quite accurate. The jump-diffusion and isotropic rotation models, however, are not accurate when the degree of confinement is high. In particular, the exponential approximations for the intermediate scattering function fail for highly confined water and the values of DT and τR can differ from the measured value by as much as a factor of two. Other models have more fit parameters, however, and with the range of energies and wave-vectors accessible to QENS, the typical analysis appears to be the best choice. In the most confined lamellar phase, the dynamics are sufficiently slow that QENS does not access a large enough time scale.

  15. Dynamics of water confined in lyotropic liquid crystals: Molecular dynamics simulations of the dynamic structure factor.

    PubMed

    Mantha, Sriteja; Yethiraj, Arun

    2016-02-28

    The properties of water under confinement are of practical and fundamental interest. In this work, we study the properties of water in the self-assembled lyotropic phases of Gemini surfactants with a focus on testing the standard analysis of quasi-elastic neutron scattering (QENS) experiments. In QENS experiments, the dynamic structure factor is measured and fit to models to extract the translational diffusion constant, D(T), and rotational relaxation time, τ(R). We test this procedure by using simulation results for the dynamic structure factor, extracting the dynamic parameters from the fit as is typically done in experiments, and comparing the values to those directly measured in the simulations. We find that the de-coupling approximation, where the intermediate scattering function is assumed to be a product of translational and rotational contributions, is quite accurate. The jump-diffusion and isotropic rotation models, however, are not accurate when the degree of confinement is high. In particular, the exponential approximations for the intermediate scattering function fail for highly confined water and the values of D(T) and τ(R) can differ from the measured value by as much as a factor of two. Other models have more fit parameters, however, and with the range of energies and wave-vectors accessible to QENS, the typical analysis appears to be the best choice. In the most confined lamellar phase, the dynamics are sufficiently slow that QENS does not access a large enough time scale.

  16. Structure and Dynamics of Four-way DNA Junctions Dynamics Revealed by Single-Molecule AFM

    NASA Astrophysics Data System (ADS)

    Lyubchenko, Yuri

    2004-03-01

    For-way DNA junctions (Holliday junctions) are critical intermediates for homologous, site-specific recombination, DNA repair and replication. A wealth of structural information is available for immobile four-way junctions. However, these data cannot give the answer on the mechanism of branch migration, the major property of the Holliday junction. Two models for the mechanism of branch migration were suggested. According to the early model of Alberts-Meselson-Sigal, exchanging DNA strands around the junction remain parallel during branch migration. Kinetic studies of branch migration suggest an alternative model in which the junction adopts an extended conformation. We tested these models using a Holliday junction undergoing branch migration. Note that it was the first time when the dynamics of the four-way DNA junction capable of branch migration had been analyzed. We applied time-lapse atomic force microscopy (single molecule dynamics AFM) to image directly loosely bound DNA at liquid-surface interface. These experiments show that mobile Holliday junctions adopt an unfolded conformation during branch migration. This conformation of the junction remains unchanged until strand separation. The data obtained support the model for branch migration having the extended conformation of the Holliday junction. The analysis of the Holliday junctions dynamics at conditions limiting branch migration revealed a broad movement of the arms suggesting that the range of mobility of these junctions is much wider than detected before. Further applications of the time-lapse AFM approach in attempt to resolve the subpopulations of the junctions conformers and the prospects for analyses of dynamics of complex biological systems will be discussed.

  17. A fast recursive algorithm for molecular dynamics simulation

    NASA Technical Reports Server (NTRS)

    Jain, A.; Vaidehi, N.; Rodriguez, G.

    1993-01-01

    The present recursive algorithm for solving molecular systems' dynamical equations of motion employs internal variable models that reduce such simulations' computation time by an order of magnitude, relative to Cartesian models. Extensive use is made of spatial operator methods recently developed for analysis and simulation of the dynamics of multibody systems. A factor-of-450 speedup over the conventional O(N-cubed) algorithm is demonstrated for the case of a polypeptide molecule with 400 residues.

  18. Simulation of Codman's paradox reveals a general law of motion.

    PubMed

    Cheng, Pei Lai

    2006-01-01

    Codman's paradox refers to a specific pattern of motion at the shoulder joint. It asked how a mysterious axial rotation about the longitudinal axis of the arm occurred during two or three sequential arm rotations that did not involve rotation about the long-axis. The objective of this paper was to find how the mysterious axial rotation occurred in the Codman's paradox. First, Codman's paradox and Codman's rotation were defined in general situations that involved arm rotations about orthogonal axes starting from the neutral attitude as well as rotations about non-orthogonal axes and starting from non-neutral attitudes. Then a general law of motion was proposed to answer the question of the Codman's paradox, which is stated as when the long-axis of the arm performs a closed-loop motion by three sequential rotations defined as Codman's rotation, it produces an equivalent axial rotation angle about the long-axis. The equivalent axial rotation angle equals the angle of swing-the second rotation in the three sequential long-axis rotations. Validity of the proposed law of motion is demonstrated by computer simulation of various Codman's rotations. Clinical relevance of the proposed law of motion is also discussed in the paper.

  19. Electrostatic mechanism of nucleosomal array folding revealed by computer simulation

    NASA Astrophysics Data System (ADS)

    Sun, Jian; Zhang, Qing; Schlick, Tamar

    2005-06-01

    Although numerous experiments indicate that the chromatin fiber displays salt-dependent conformations, the associated molecular mechanism remains unclear. Here, we apply an irregular Discrete Surface Charge Optimization (DiSCO) model of the nucleosome with all histone tails incorporated to describe by Monte Carlo simulations salt-dependent rearrangements of a nucleosomal array with 12 nucleosomes. The ensemble of nucleosomal array conformations display salt-dependent condensation in good agreement with hydrodynamic measurements and suggest that the array adopts highly irregular 3D zig-zag conformations at high (physiological) salt concentrations and transitions into the extended "beads-on-a-string" conformation at low salt. Energy analyses indicate that the repulsion among linker DNA leads to this extended form, whereas internucleosome attraction drives the folding at high salt. The balance between these two contributions determines the salt-dependent condensation. Importantly, the internucleosome and linker DNA-nucleosome attractions require histone tails; we find that the H3 tails, in particular, are crucial for stabilizing the moderately folded fiber at physiological monovalent salt. chromatin modeling | irregular 3D zig-zag | Discrete Surface Charge Optimization model

  20. Electrostatic mechanism of nucleosomal array folding revealed by computer simulation

    PubMed Central

    Sun, Jian; Zhang, Qing; Schlick, Tamar

    2005-01-01

    Although numerous experiments indicate that the chromatin fiber displays salt-dependent conformations, the associated molecular mechanism remains unclear. Here, we apply an irregular Discrete Surface Charge Optimization (DiSCO) model of the nucleosome with all histone tails incorporated to describe by Monte Carlo simulations salt-dependent rearrangements of a nucleosomal array with 12 nucleosomes. The ensemble of nucleosomal array conformations display salt-dependent condensation in good agreement with hydrodynamic measurements and suggest that the array adopts highly irregular 3D zig-zag conformations at high (physiological) salt concentrations and transitions into the extended “beads-on-a-string” conformation at low salt. Energy analyses indicate that the repulsion among linker DNA leads to this extended form, whereas internucleosome attraction drives the folding at high salt. The balance between these two contributions determines the salt-dependent condensation. Importantly, the internucleosome and linker DNA–nucleosome attractions require histone tails; we find that the H3 tails, in particular, are crucial for stabilizing the moderately folded fiber at physiological monovalent salt. PMID:15919827

  1. Large-Scale Hybrid Dynamic Simulation Employing Field Measurements

    SciTech Connect

    Huang, Zhenyu; Guttromson, Ross T.; Hauer, John F.

    2004-06-30

    Simulation and measurements are two primary ways for power engineers to gain understanding of system behaviors and thus accomplish tasks in system planning and operation. Many well-developed simulation tools are available in today's market. On the other hand, large amount of measured data can be obtained from traditional SCADA systems and currently fast growing phasor networks. However, simulation and measurement are still two separate worlds. There is a need to combine the advantages of simulation and measurements. In view of this, this paper proposes the concept of hybrid dynamic simulation which opens up traditional simulation by providing entries for measurements. A method is presented to implement hybrid simulation with PSLF/PSDS. Test studies show the validity of the proposed hybrid simulation method. Applications of such hybrid simulation include system event playback, model validation, and software validation.

  2. Dynamics of adaptive structures: Design through simulations

    NASA Technical Reports Server (NTRS)

    Park, K. C.; Alexander, S.

    1993-01-01

    The use of a helical bi-morph actuator/sensor concept by mimicking the change of helical waveform in bacterial flagella is perhaps the first application of bacterial motions (living species) to longitudinal deployment of space structures. However, no dynamical considerations were analyzed to explain the waveform change mechanisms. The objective is to review various deployment concepts from the dynamics point of view and introduce the dynamical considerations from the outset as part of design considerations. Specifically, the impact of the incorporation of the combined static mechanisms and dynamic design considerations on the deployment performance during the reconfiguration stage is studied in terms of improved controllability, maneuvering duration, and joint singularity index. It is shown that intermediate configurations during articulations play an important role for improved joint mechanisms design and overall structural deployability.

  3. Energy dynamics in a simulation of LAPD turbulence

    SciTech Connect

    Friedman, B.; Carter, T. A.; Schaffner, D.; Umansky, M. V.; Dudson, B.

    2012-10-15

    Energy dynamics calculations in a 3D fluid simulation of drift wave turbulence in the linear Large Plasma Device [W. Gekelman et al., Rev. Sci. Instrum. 62, 2875 (1991)] illuminate processes that drive and dissipate the turbulence. These calculations reveal that a nonlinear instability dominates the injection of energy into the turbulence by overtaking the linear drift wave instability that dominates when fluctuations about the equilibrium are small. The nonlinear instability drives flute-like (k{sub Parallel-To }=0) density fluctuations using free energy from the background density gradient. Through nonlinear axial wavenumber transfer to k{sub Parallel-To }{ne}0 fluctuations, the nonlinear instability accesses the adiabatic response, which provides the requisite energy transfer channel from density to potential fluctuations as well as the phase shift that causes instability. The turbulence characteristics in the simulations agree remarkably well with experiment. When the nonlinear instability is artificially removed from the system through suppressing k{sub Parallel-To }=0 modes, the turbulence develops a coherent frequency spectrum which is inconsistent with experimental data. This indicates the importance of the nonlinear instability in producing experimentally consistent turbulence.

  4. Stabilizing simulations of complex stochastic representations for quantum dynamical systems

    NASA Astrophysics Data System (ADS)

    Perret, C.; Petersen, W. P.

    2011-03-01

    Path integral representations of quantum dynamics can often be formulated as stochastic differential equations (SDEs). In a series of papers, Corney and Drummond (2004 Phys. Rev. Lett. 93 260401), Deuar and Drummond (2001 Comput. Phys. Commun. 142 442-5), Drummond and Gardnier (1980 J. Phys. A: Math. Gen. 13 2353-68), Gardiner and Zoller (2004 Quantum Noise: A Handbook of Markovian and Non-Markovian Quantum Stochastic Methods with Applications to Quantum Optics (Springer Series in Synergetics) 3rd edn (Berlin: Springer)) and Gilchrist et al (1997 Phys. Rev. A 55 3014-32) and their collaborators have derived SDEs from coherent states representations for density matrices. Computationally, these SDEs are attractive because they seem simple to simulate. They can be quite unstable, however. In this paper, we consider some of the instabilities and propose a few remedies. Particularly, because the variances of the simulated paths typically grow exponentially, the processes become de-localized in relatively short times. Hence, the issues of boundary conditions and stable integration methods become important. We use the Bose-Einstein Hamiltonian as an example. Our results reveal that it is possible to significantly extend integration times and show the periodic structure of certain functionals.

  5. The collapsing bubble in a liquid by molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Xiao, C.; Heyes, D. M.; Powles, J. G.

    Molecular dynamics simulations have been made of a collapsing bubble or cavity in a simple liquid. Simulations of a Lennard-Jones liquid reveal that the collapsing process takes place in a series of stages. First, the 'hottest' molecules from the high kinetic energy tail in the Maxwell-Boltzmann distribution diffuse into the empty cavity. This is followed by a gradual filling in of the cavity until the density in the centre is a little lower than that of the bulk liquid. The system eventually reaches a final new equilibrium liquid state through a subsequent slower equilibration phase. The bubble fills in an oscillatory manner, by partly filling in, and then partially emptying, and so on, with ever decreasing amplitude towards the final uniform liquid state. These density oscillations are more obvious in systems with a larger bubble. Similar oscillations are observed in the kinetic energy of the molecules at selected radii from the centre of the initial bubble. The maximum temperature occurs typically at the end of the initial fillingin stage during which the density of the core undergoes a vapour-to-liquid phase transition, the released latent heat probably contributing to the temperatures achieved in this region. The average maximum temperature found in the smallest system examined is about nine times the critical temperature, which is about 6000K for water, thus suggesting a simple mechanism for producing molecules with the sorts of kinetic energies and lifetimes required for sonoluminescence.

  6. Perspective: Computer simulations of long time dynamics

    PubMed Central

    Elber, Ron

    2016-01-01

    Atomically detailed computer simulations of complex molecular events attracted the imagination of many researchers in the field as providing comprehensive information on chemical, biological, and physical processes. However, one of the greatest limitations of these simulations is of time scales. The physical time scales accessible to straightforward simulations are too short to address many interesting and important molecular events. In the last decade significant advances were made in different directions (theory, software, and hardware) that significantly expand the capabilities and accuracies of these techniques. This perspective describes and critically examines some of these advances. PMID:26874473

  7. Perspective: Computer simulations of long time dynamics

    SciTech Connect

    Elber, Ron

    2016-02-14

    Atomically detailed computer simulations of complex molecular events attracted the imagination of many researchers in the field as providing comprehensive information on chemical, biological, and physical processes. However, one of the greatest limitations of these simulations is of time scales. The physical time scales accessible to straightforward simulations are too short to address many interesting and important molecular events. In the last decade significant advances were made in different directions (theory, software, and hardware) that significantly expand the capabilities and accuracies of these techniques. This perspective describes and critically examines some of these advances.

  8. Rhodopsin Photoactivation Dynamics Revealed by Quasi-Elastic Neutron Scattering

    NASA Astrophysics Data System (ADS)

    Bhowmik, Debsindhu; Shrestha, Utsab; Perera, Suchhithranga M. C. D.; Chawla, Udeep; Mamontov, Eugene; Brown, Michael; Chu, Xiang-Qiang

    2015-03-01

    Rhodopsin is a G-protein-coupled receptor (GPCR) responsible for vision. During photoactivation, the chromophore retinal dissociates from protein yielding the opsin apoprotein. What are the changes in protein dynamics that occur during the photoactivation process? Here, we studied the microscopic dynamics of dark-state rhodopsin and the ligand-free opsin using quasielastic neutron scattering (QENS). The QENS technique tracks individual hydrogen atom motion because of the much higher neutron scattering cross-section of hydrogen than other atoms. We used protein with CHAPS detergent hydrated with heavy water. The activation of proteins is confirmed at low temperatures up to 300 K by mean-square displacement (MSD) analysis. The QENS experiments at temperatures ranging from 220 K to 300 K clearly indicate an increase in protein dynamic behavior with temperature. The relaxation time for the ligand-bound protein rhodopsin is faster compared to opsin, which can be correlated with the photoactivation. Moreover, the protein dynamics are orders of magnitude slower than the accompanying CHAPS detergent, which unlike protein, manifests localized motions.

  9. Communicability angles reveal critical edges for network consensus dynamics

    NASA Astrophysics Data System (ADS)

    Estrada, Ernesto; Vargas-Estrada, Eusebio; Ando, Hiroyasu

    2015-11-01

    We consider the question of determining how the topological structure influences a consensus dynamical processes taking place on a network. By considering a large data set of real-world networks we first determine that the removal of edges according to their communicability angle, an angle between position vectors of the nodes in an Euclidean communicability space, increases the average time of consensus by a factor of 5.68 in real-world networks. The edge betweenness centrality also identifies, in a smaller proportion, those critical edges for the consensus dynamics; i.e., its removal increases the time of consensus by a factor of 3.70 . We justify theoretically these findings on the basis of the role played by the algebraic connectivity and the isoperimetric number of networks on the dynamical process studied and their connections with the properties mentioned before. Finally, we study the role played by global topological parameters of networks on the consensus dynamics. We determine that the network density and the average distance-sum, which is analogous of the node degree for shortest-path distances, account for more than 80% of the variance of the average time of consensus in the real-world networks studied.

  10. Fire scars reveal variability and dynamics of eastern fire regimes

    Treesearch

    Richard P. Guyette; Daniel C. Dey; Michael C. Stambaugh; Rose-Marie Muzika

    2006-01-01

    Fire scar evidence in eastern North America is sparse and complex but shows promise in defining the dynamics of these fire regimes and their influence on ecosystems. We review fire scar data, methods, and limitations, and use this information to identify and examine the factors influencing fire regimes. Fire scar data from studies at more than 40 sites in Eastern North...

  11. Rhodopsin photoactivation dynamics revealed by quasi-elastic neutron scattering

    DOE PAGES

    Bhowmik, Debsindhu; Shrestha, Utsab; Perera, Suchithranga M.d.c.; ...

    2015-01-27

    Rhodopsin is a G-protein-coupled receptor (GPCR) responsible for vision under dim light conditions. During rhodopsin photoactivation, the chromophore retinal undergoes cis-trans isomerization, and subsequently dissociates from the protein yielding the opsin apoprotein [1]. What are the changes in protein dynamics that occur during the rhodopsin photoactivation process? Here, we studied the microscopic dynamics of the dark-state rhodopsin and the ligand-free opsin using quasi-elastic neutron scattering (QENS). The QENS technique tracks the individual hydrogen atom motions in the protein molecules, because the neutron scattering cross-section of hydrogen is much higher than other atoms [2-4]. We used protein (rhodopsin/opsin) samples with CHAPSmore » detergent hydrated with heavy water. The solvent signal is suppressed due to the heavy water, so that only the signals from proteins and detergents are detected. The activation of proteins is confirmed at low temperatures up to 300 K by the mean-square displacement (MSD) analysis. Our QENS experiments conducted at temperatures ranging from 220 K to 300 K clearly indicate that the protein dynamic behavior increases with temperature. The relaxation time for the ligand-bound protein rhodopsin was longer compared to opsin, which can be correlated with the photoactivation. Moreover, the protein dynamics are orders of magnitude slower than the accompanying CHAPS detergent, which forms a band around the protein molecule in the micelle. Unlike the protein, the CHAPS detergent manifests localized motions that are the same as in the bulk empty micelles. Furthermore QENS provides unique understanding of the key dynamics involved in the activation of the GPCR involved in the visual process.« less

  12. Rhodopsin photoactivation dynamics revealed by quasi-elastic neutron scattering

    SciTech Connect

    Bhowmik, Debsindhu; Shrestha, Utsab; Perera, Suchithranga M.d.c.; Chawla, Udeep; Mamontov, Eugene; Brown, Michael F.; Chu, Xiang -Qiang

    2015-01-27

    Rhodopsin is a G-protein-coupled receptor (GPCR) responsible for vision under dim light conditions. During rhodopsin photoactivation, the chromophore retinal undergoes cis-trans isomerization, and subsequently dissociates from the protein yielding the opsin apoprotein [1]. What are the changes in protein dynamics that occur during the rhodopsin photoactivation process? Here, we studied the microscopic dynamics of the dark-state rhodopsin and the ligand-free opsin using quasi-elastic neutron scattering (QENS). The QENS technique tracks the individual hydrogen atom motions in the protein molecules, because the neutron scattering cross-section of hydrogen is much higher than other atoms [2-4]. We used protein (rhodopsin/opsin) samples with CHAPS detergent hydrated with heavy water. The solvent signal is suppressed due to the heavy water, so that only the signals from proteins and detergents are detected. The activation of proteins is confirmed at low temperatures up to 300 K by the mean-square displacement (MSD) analysis. Our QENS experiments conducted at temperatures ranging from 220 K to 300 K clearly indicate that the protein dynamic behavior increases with temperature. The relaxation time for the ligand-bound protein rhodopsin was longer compared to opsin, which can be correlated with the photoactivation. Moreover, the protein dynamics are orders of magnitude slower than the accompanying CHAPS detergent, which forms a band around the protein molecule in the micelle. Unlike the protein, the CHAPS detergent manifests localized motions that are the same as in the bulk empty micelles. Furthermore QENS provides unique understanding of the key dynamics involved in the activation of the GPCR involved in the visual process.

  13. Climate dynamics experiments using a GCM simulations

    NASA Technical Reports Server (NTRS)

    Fitzjarrald, Dan; Robertson, Franklin R.; Christy, John R.; Lu, H.-I.; Sohn, B.; Srikishen, J.

    1991-01-01

    The study of surface-atmosphere interactions has begun with studies of the effect of altering the ocean and land boundaries. A ten year simulation of global climate using observed sea surface temperature anomalies has begun using the NCAR Community Climate Model (CCM1). The results for low resolution (R15) were computed for the first 8 years of the simulation and compared with the observed surface temperatures and the MSU (Microwave Sounding Unit) observations of tropospheric temperature. A simulation at higher resolution (T42) was done to ascertain the effect of interactive soil hydrology on the system response to an El Nino sea surface temperature perturbation. Initial analysis of this simulations was completed.

  14. Colloidal suspension simulates linear dynamic pressure profile

    NASA Technical Reports Server (NTRS)

    Mc Cann, R. J.

    1966-01-01

    Missile nose fairings immersed in colloidal suspension prepared with various specific gravities simulate pressure profiles very similar to those encountered during reentry. Stress and deflection conditions similar to those expected during atmospheric reentry are thus attained in the laboratory.

  15. Simulating Food Web Dynamics along a Gradient: Quantifying Human Influence

    PubMed Central

    Jordán, Ferenc; Gjata, Nerta; Mei, Shu; Yule, Catherine M.

    2012-01-01

    Realistically parameterized and dynamically simulated food-webs are useful tool to explore the importance of the functional diversity of ecosystems, and in particular relations between the dynamics of species and the whole community. We present a stochastic dynamical food web simulation for the Kelian River (Borneo). The food web was constructed for six different locations, arrayed along a gradient of increasing human perturbation (mostly resulting from gold mining activities) along the river. Along the river, the relative importance of grazers, filterers and shredders decreases with increasing disturbance downstream, while predators become more dominant in governing eco-dynamics. Human activity led to increased turbidity and sedimentation which adversely impacts primary productivity. Since the main difference between the study sites was not the composition of the food webs (structure is quite similar) but the strengths of interactions and the abundance of the trophic groups, a dynamical simulation approach seemed to be useful to better explain human influence. In the pristine river (study site 1), when comparing a structural version of our model with the dynamical model we found that structurally central groups such as omnivores and carnivores were not the most important ones dynamically. Instead, primary consumers such as invertebrate grazers and shredders generated a greater dynamical response. Based on the dynamically most important groups, bottom-up control is replaced by the predominant top-down control regime as distance downstream and human disturbance increased. An important finding, potentially explaining the poor structure to dynamics relationship, is that indirect effects are at least as important as direct ones during the simulations. We suggest that our approach and this simulation framework could serve systems-based conservation efforts. Quantitative indicators on the relative importance of trophic groups and the mechanistic modeling of eco-dynamics

  16. Simulating food web dynamics along a gradient: quantifying human influence.

    PubMed

    Jordán, Ferenc; Gjata, Nerta; Mei, Shu; Yule, Catherine M

    2012-01-01

    Realistically parameterized and dynamically simulated food-webs are useful tool to explore the importance of the functional diversity of ecosystems, and in particular relations between the dynamics of species and the whole community. We present a stochastic dynamical food web simulation for the Kelian River (Borneo). The food web was constructed for six different locations, arrayed along a gradient of increasing human perturbation (mostly resulting from gold mining activities) along the river. Along the river, the relative importance of grazers, filterers and shredders decreases with increasing disturbance downstream, while predators become more dominant in governing eco-dynamics. Human activity led to increased turbidity and sedimentation which adversely impacts primary productivity. Since the main difference between the study sites was not the composition of the food webs (structure is quite similar) but the strengths of interactions and the abundance of the trophic groups, a dynamical simulation approach seemed to be useful to better explain human influence. In the pristine river (study site 1), when comparing a structural version of our model with the dynamical model we found that structurally central groups such as omnivores and carnivores were not the most important ones dynamically. Instead, primary consumers such as invertebrate grazers and shredders generated a greater dynamical response. Based on the dynamically most important groups, bottom-up control is replaced by the predominant top-down control regime as distance downstream and human disturbance increased. An important finding, potentially explaining the poor structure to dynamics relationship, is that indirect effects are at least as important as direct ones during the simulations. We suggest that our approach and this simulation framework could serve systems-based conservation efforts. Quantitative indicators on the relative importance of trophic groups and the mechanistic modeling of eco-dynamics

  17. Sub-structure of laser generated harmonics reveals plasma dynamics of a relativistically oscillating mirror

    SciTech Connect

    Braenzel, J.; Schnürer, M.; Steinke, S.; Priebe, G.; Sandner, W.; Andreev, A.; Platonov, K.

    2013-08-15

    Theoretical and experimental investigations of the dynamics of a relativistically oscillating plasma slab reveal spectral line splitting in laser driven harmonic spectra, leading to double harmonic series. Both series are well characterized with harmonics arising by two fundamental frequencies. While a relativistic oscillation of the critical density drives the harmonic emission, the splitting is a result of an additional acceleration during the laser pulse duration. In comparison with the oscillatory movement, this acceleration is rather weak and can be described by a plasma shock wave driven by the pressure of light. We introduce particle in cell simulations and an analytical model explaining the harmonic line splitting. The derived analytical formula gives direct access between the splitting in the harmonic spectrum and the acceleration of the plasma surface.

  18. Temperature dependence of protein hydration hydrodynamics by molecular dynamics simulations.

    SciTech Connect

    Lau, E Y; Krishnan, V V

    2007-07-18

    The dynamics of water molecules near the protein surface are different from those of bulk water and influence the structure and dynamics of the protein itself. To elucidate the temperature dependence hydration dynamics of water molecules, we present results from the molecular dynamic simulation of the water molecules surrounding two proteins (Carboxypeptidase inhibitor and Ovomucoid) at seven different temperatures (T=273 to 303 K, in increments of 5 K). Translational diffusion coefficients of the surface water and bulk water molecules were estimated from 2 ns molecular dynamics simulation trajectories. Temperature dependence of the estimated bulk water diffusion closely reflects the experimental values, while hydration water diffusion is retarded significantly due to the protein. Protein surface induced scaling of translational dynamics of the hydration waters is uniform over the temperature range studied, suggesting the importance protein-water interactions.

  19. A Molecular Dynamics Simulation of C60-C60 Collision

    NASA Astrophysics Data System (ADS)

    Liu, Lei; Chen, Kaitai; Li, Yufen

    1993-12-01

    The formation process of C120-complex in C60-C60 collision has been clearly demonstrated by a molecular dynamics simulation. The complex, with a peanut-shell-like structure, is in a quite stable dynamical state. The results are consistent with recent observations.

  20. A Process for Comparing Dynamics of Distributed Space Systems Simulations

    NASA Technical Reports Server (NTRS)

    Cures, Edwin Z.; Jackson, Albert A.; Morris, Jeffery C.

    2009-01-01

    The paper describes a process that was developed for comparing the primary orbital dynamics behavior between space systems distributed simulations. This process is used to characterize and understand the fundamental fidelities and compatibilities of the modeling of orbital dynamics between spacecraft simulations. This is required for high-latency distributed simulations such as NASA s Integrated Mission Simulation and must be understood when reporting results from simulation executions. This paper presents 10 principal comparison tests along with their rationale and examples of the results. The Integrated Mission Simulation (IMSim) (formerly know as the Distributed Space Exploration Simulation (DSES)) is a NASA research and development project focusing on the technologies and processes that are related to the collaborative simulation of complex space systems involved in the exploration of our solar system. Currently, the NASA centers that are actively participating in the IMSim project are the Ames Research Center, the Jet Propulsion Laboratory (JPL), the Johnson Space Center (JSC), the Kennedy Space Center, the Langley Research Center and the Marshall Space Flight Center. In concept, each center participating in IMSim has its own set of simulation models and environment(s). These simulation tools are used to build the various simulation products that are used for scientific investigation, engineering analysis, system design, training, planning, operations and more. Working individually, these production simulations provide important data to various NASA projects.

  1. Student Diagnostic Strategies in a Dynamic Simulation Environment.

    ERIC Educational Resources Information Center

    Recker, Mimi M.; Govindaraj, T.; Vasandani, Vijay

    1998-01-01

    Demonstrates the use of simulation systems for studying diagnostic problem solving and presents results from two empirical studies in which undergraduates diagnosed faults that occurred in a computer-based, dynamic simulation. Discusses dual problem space search that includes generating and testing hypotheses; suggests implications for designing…

  2. Simulation, modeling and dynamical analysis of multibody flows

    NASA Astrophysics Data System (ADS)

    Blackmore, Denis; Rosato, Anthony; Sen, Surajit; Wu, Hao

    2017-04-01

    Recent particulate flow research using a discrete element simulation-dynamical systems approach is described. The simulation code used is very efficient and the mathematical model is an integro-partial differential equation. Examples are presented to show the effectiveness of the approach.

  3. Structure and Dynamics of Katabatic Flow Jumps: Idealised Simulations

    NASA Astrophysics Data System (ADS)

    Yu, Ye; Cai, Xiao-Ming

    2006-03-01

    For the first time, results from a high-resolution numerical simulation (with horizontal grid spacing of 35m) were used to reveal the detailed structure near an atmospheric katabatic jump over an idealized slope. The simulation represents flow over the slopes of Coats Land, Antarctica for austral winter conditions. The katabatic jump is characterised by an updraft with vertical velocities of order 1ms-1 and serves as a possible forcing mechanism for the gravity waves frequently observed over the ice shelves around the Antarctic. Results also indicate that strong turbulence is generally confined within a mixing zone near the top of the katabatic layer upstream of the jump and extends downstream through the top of the strong updraft associated with the jump. Detailed analyses of momentum and heat budgets across the katabatic jump indicate that, upstream of the jump, turbulent mixing is important in decelerating the upper part of the katabatic layer, while within the jump the upslope pressure gradient force associated with the pool of cold air plays a role in decelerating the flow near the surface. The heat budget near the jump reveals a simple two-term balance: the turbulent heat flux divergence is balanced by the advection. A comparison of model results with available theories indicates that mixing between layers of different potential temperature structure indeed plays some role in the development of katabatic flow jumps, especially for strong jumps. Theories used to study katabatic jumps should include this mixing process, of which the amount depends on the intensity of the jump. A conceptual model of a katabatic jump, including the main dynamical processes, is constructed from these detailed analyses.

  4. Studies of climate dynamics with innovative global-model simulations

    NASA Astrophysics Data System (ADS)

    Shi, Xiaoming

    Climate simulations with different degrees of idealization are essential for the development of our understanding of the climate system. Studies in this dissertation employ carefully designed global-model simulations for the goal of gaining theoretical and conceptual insights into some problems of climate dynamics. Firstly, global warming-induced changes in extreme precipitation are investigated using a global climate model with idealized geography. The precipitation changes over an idealized north-south mid-latitude mountain barrier at the western margin of an otherwise flat continent are studied. The intensity of the 40 most intense events on the western slopes increases by about ~4°C of surface warming. In contrast, the intensity of the top 40 events on the eastern mountain slopes increases at about ~6°C. This higher sensitivity is due to enhanced ascent during the eastern-slope events, which can be explained in terms of linear mountain-wave theory relating to global warming-induced changes in the upper-tropospheric static stability and the tropopause level. Dominated by different dynamical factors, changes in the intensity of extreme precipitation events over plains and oceans might differ from changes over mountains. So the response of extreme precipitation over mountains and flat areas are further compared using larger data sets of simulated extreme events over the two types of surfaces. It is found that the sensitivity of extreme precipitation to increases in global mean surface temperature is 3% per °C lower over mountains than over the oceans or the plains. The difference in sensitivity among these regions is not due to thermodynamic effects, but rather to differences between the gravity-wave dynamics governing vertical velocities over the mountains and the cyclone dynamics governing vertical motions over the oceans and plains. The strengthening of latent heating in the storms over oceans and plains leads to stronger ascent in the warming climate

  5. Dynamic neutron scattering from conformational dynamics. II. Application using molecular dynamics simulation and Markov modeling

    SciTech Connect

    Yi, Zheng; Lindner, Benjamin; Prinz, Jan -Hendrik; Noe, Frank; Smith, Jeremy C.

    2013-11-01

    Here, neutron scattering experiments directly probe the dynamics of complex molecules on the sub pico- to microsecond time scales. However, the assignment of the relaxations seen experimentally to specific structural rearrangements is difficult, since many of the underlying dynamical processes may exist on similar timescales. In an accompanying article, we present a theoretical approach to the analysis of molecular dynamics simulations with a Markov State Model (MSM) that permits the direct identification of structural transitions leading to each contributing relaxation process. Here, we demonstrate the use of the method by applying it to the configurational dynamics of the well-characterized alanine dipeptide. A practical procedure for deriving the MSM from an MD is introduced. The result is a 9-state MSM in the space of the backbone dihedral angles and the side-chain methyl group. The agreement between the quasielastic spectrum calculated directly from the atomic trajectories and that derived from the Markov state model is excellent. The dependence on the wavevector of the individual Markov processes is described. The procedure means that it is now practicable to interpret quasielastic scattering spectra in terms of well-defined intramolecular transitions with minimal a priori assumptions as to the nature of the dynamics taking place.

  6. Scanning angle interference microscopy reveals cell dynamics at the nanoscale.

    PubMed

    Paszek, Matthew J; DuFort, Christopher C; Rubashkin, Matthew G; Davidson, Michael W; Thorn, Kurt S; Liphardt, Jan T; Weaver, Valerie M

    2012-07-01

    Emerging questions in cell biology necessitate nanoscale imaging in live cells. Here we present scanning angle interference microscopy, which is capable of localizing fluorescent objects with nanoscale precision along the optical axis in motile cellular structures. We use this approach to resolve nanotopographical features of the cell membrane and cytoskeleton as well as the temporal evolution, three-dimensional architecture and nanoscale dynamics of focal adhesion complexes.

  7. A Dynamical Model Reveals Gene Co-Localizations in Nucleus

    PubMed Central

    Yao, Ye; Lin, Wei; Hennessy, Conor; Fraser, Peter; Feng, Jianfeng

    2011-01-01

    Co-localization of networks of genes in the nucleus is thought to play an important role in determining gene expression patterns. Based upon experimental data, we built a dynamical model to test whether pure diffusion could account for the observed co-localization of genes within a defined subnuclear region. A simple standard Brownian motion model in two and three dimensions shows that preferential co-localization is possible for co-regulated genes without any direct interaction, and suggests the occurrence may be due to a limitation in the number of available transcription factors. Experimental data of chromatin movements demonstrates that fractional rather than standard Brownian motion is more appropriate to model gene mobilizations, and we tested our dynamical model against recent static experimental data, using a sub-diffusion process by which the genes tend to colocalize more easily. Moreover, in order to compare our model with recently obtained experimental data, we studied the association level between genes and factors, and presented data supporting the validation of this dynamic model. As further applications of our model, we applied it to test against more biological observations. We found that increasing transcription factor number, rather than factory number and nucleus size, might be the reason for decreasing gene co-localization. In the scenario of frequency- or amplitude-modulation of transcription factors, our model predicted that frequency-modulation may increase the co-localization between its targeted genes. PMID:21760760

  8. Optogenetic perturbations reveal the dynamics of an oculomotor integrator

    PubMed Central

    Gonçalves, Pedro J.; Arrenberg, Aristides B.; Hablitzel, Bastian; Baier, Herwig; Machens, Christian K.

    2014-01-01

    Many neural systems can store short-term information in persistently firing neurons. Such persistent activity is believed to be maintained by recurrent feedback among neurons. This hypothesis has been fleshed out in detail for the oculomotor integrator (OI) for which the so-called “line attractor” network model can explain a large set of observations. Here we show that there is a plethora of such models, distinguished by the relative strength of recurrent excitation and inhibition. In each model, the firing rates of the neurons relax toward the persistent activity states. The dynamics of relaxation can be quite different, however, and depend on the levels of recurrent excitation and inhibition. To identify the correct model, we directly measure these relaxation dynamics by performing optogenetic perturbations in the OI of zebrafish expressing halorhodopsin or channelrhodopsin. We show that instantaneous, inhibitory stimulations of the OI lead to persistent, centripetal eye position changes ipsilateral to the stimulation. Excitatory stimulations similarly cause centripetal eye position changes, yet only contralateral to the stimulation. These results show that the dynamics of the OI are organized around a central attractor state—the null position of the eyes—which stabilizes the system against random perturbations. Our results pose new constraints on the circuit connectivity of the system and provide new insights into the mechanisms underlying persistent activity. PMID:24616666

  9. Dynamics of nitrogen dissociation from direct molecular simulation

    NASA Astrophysics Data System (ADS)

    Valentini, Paolo; Schwartzentruber, Thomas E.; Bender, Jason D.; Candler, Graham V.

    2016-08-01

    dissociating nitrogen systems involving both atomic and molecular nitrogen. Such direct comparisons also illustrate how the DMS method is able to reveal all relevant nonequilibrium physics without the need to compute large numbers of state-transition probabilities. In this manner, DMS presents an accurate and tractable approach to construct models for direct-simulation Monte Carlo and computational fluid dynamics simulations from first principles.

  10. ROCKET THRUST STAND SIMULATION OF SPACE VEHICLE FLIGHT DYNAMICS

    DTIC Science & Technology

    The concept of rocket thrust stand simulation of space vehicle flight dynamics is developed. An electro-mechanical system is described wherein the... space vehicle rocket motor attach point motion may be simulated. The physical dimensions of the system are small such that it may be used in conjunction...with current environmental test cells. The degree of space vehicle simulation is a consequence of the limitations on the excursions of the active

  11. Dynamic Monitoring Reveals Motor Task Characteristics in Prehistoric Technical Gestures

    PubMed Central

    Pfleging, Johannes; Stücheli, Marius; Iovita, Radu; Buchli, Jonas

    2015-01-01

    Reconstructing ancient technical gestures associated with simple tool actions is crucial for understanding the co-evolution of the human forelimb and its associated control-related cognitive functions on the one hand, and of the human technological arsenal on the other hand. Although the topic of gesture is an old one in Paleolithic archaeology and in anthropology in general, very few studies have taken advantage of the new technologies from the science of kinematics in order to improve replicative experimental protocols. Recent work in paleoanthropology has shown the potential of monitored replicative experiments to reconstruct tool-use-related motions through the study of fossil bones, but so far comparatively little has been done to examine the dynamics of the tool itself. In this paper, we demonstrate that we can statistically differentiate gestures used in a simple scraping task through dynamic monitoring. Dynamics combines kinematics (position, orientation, and speed) with contact mechanical parameters (force and torque). Taken together, these parameters are important because they play a role in the formation of a visible archaeological signature, use-wear. We present our new affordable, yet precise methodology for measuring the dynamics of a simple hide-scraping task, carried out using a pull-to (PT) and a push-away (PA) gesture. A strain gage force sensor combined with a visual tag tracking system records force, torque, as well as position and orientation of hafted flint stone tools. The set-up allows switching between two tool configurations, one with distal and the other one with perpendicular hafting of the scrapers, to allow for ethnographically plausible reconstructions. The data show statistically significant differences between the two gestures: scraping away from the body (PA) generates higher shearing forces, but requires greater hand torque. Moreover, most benchmarks associated with the PA gesture are more highly variable than in the PT gesture

  12. Dynamic Monitoring Reveals Motor Task Characteristics in Prehistoric Technical Gestures.

    PubMed

    Pfleging, Johannes; Stücheli, Marius; Iovita, Radu; Buchli, Jonas

    2015-01-01

    Reconstructing ancient technical gestures associated with simple tool actions is crucial for understanding the co-evolution of the human forelimb and its associated control-related cognitive functions on the one hand, and of the human technological arsenal on the other hand. Although the topic of gesture is an old one in Paleolithic archaeology and in anthropology in general, very few studies have taken advantage of the new technologies from the science of kinematics in order to improve replicative experimental protocols. Recent work in paleoanthropology has shown the potential of monitored replicative experiments to reconstruct tool-use-related motions through the study of fossil bones, but so far comparatively little has been done to examine the dynamics of the tool itself. In this paper, we demonstrate that we can statistically differentiate gestures used in a simple scraping task through dynamic monitoring. Dynamics combines kinematics (position, orientation, and speed) with contact mechanical parameters (force and torque). Taken together, these parameters are important because they play a role in the formation of a visible archaeological signature, use-wear. We present our new affordable, yet precise methodology for measuring the dynamics of a simple hide-scraping task, carried out using a pull-to (PT) and a push-away (PA) gesture. A strain gage force sensor combined with a visual tag tracking system records force, torque, as well as position and orientation of hafted flint stone tools. The set-up allows switching between two tool configurations, one with distal and the other one with perpendicular hafting of the scrapers, to allow for ethnographically plausible reconstructions. The data show statistically significant differences between the two gestures: scraping away from the body (PA) generates higher shearing forces, but requires greater hand torque. Moreover, most benchmarks associated with the PA gesture are more highly variable than in the PT gesture

  13. Dynamics Simulation Model for Space Tethers

    NASA Technical Reports Server (NTRS)

    Levin, E. M.; Pearson, J.; Oldson, J. C.

    2006-01-01

    This document describes the development of an accurate model for the dynamics of the Momentum Exchange Electrodynamic Reboost (MXER) system. The MXER is a rotating tether about 100-km long in elliptical Earth orbit designed to catch payloads in low Earth orbit and throw them to geosynchronous orbit or to Earth escape. To ensure successful rendezvous between the MXER tip catcher and a payload, a high-fidelity model of the system dynamics is required. The model developed here quantifies the major environmental perturbations, and can predict the MXER tip position to within meters over one orbit.

  14. Gamma ray observatory dynamics simulator in Ada (GRODY)

    NASA Technical Reports Server (NTRS)

    1990-01-01

    This experiment involved the parallel development of dynamics simulators for the Gamma Ray Observatory in both FORTRAN and Ada for the purpose of evaluating the applicability of Ada to the NASA/Goddard Space Flight Center's flight dynamics environment. The experiment successfully demonstrated that Ada is a viable, valuable technology for use in this environment. In addition to building a simulator, the Ada team evaluated training approaches, developed an Ada methodology appropriate to the flight dynamics environment, and established a baseline for evaluating future Ada projects.

  15. Gamma ray observatory dynamics simulator in Ada (GRODY)

    SciTech Connect

    Not Available

    1990-09-01

    This experiment involved the parallel development of dynamics simulators for the Gamma Ray Observatory in both FORTRAN and Ada for the purpose of evaluating the applicability of Ada to the NASA/Goddard Space Flight Center's flight dynamics environment. The experiment successfully demonstrated that Ada is a viable, valuable technology for use in this environment. In addition to building a simulator, the Ada team evaluated training approaches, developed an Ada methodology appropriate to the flight dynamics environment, and established a baseline for evaluating future Ada projects.

  16. Movement Characteristics Analysis and Dynamic Simulation of Collaborative Measuring Robot

    NASA Astrophysics Data System (ADS)

    guoqing, MA; li, LIU; zhenglin, YU; guohua, CAO; yanbin, ZHENG

    2017-03-01

    Human-machine collaboration is becoming increasingly more necessary, and so collaborative robot applications are also in high demand. We selected a UR10 robot as our research subject for this study. First, we applied D-H coordinate transformation of the robot to establish a link system, and we then used inverse transformation to solve the robot’s inverse kinematics and find all the joints. Use Lagrange method to analysis UR robot dynamics; use ADAMS multibody dynamics simulation software to dynamic simulation; verifying the correctness of the derived kinetic models.

  17. Semiconductor nanostructure properties. Molecular Dynamic Simulations

    NASA Astrophysics Data System (ADS)

    Podolska, N. I.; Zhmakin, A. I.

    2013-08-01

    The need for research is based on the fact that development of non-planar semiconductor nanosystems and nanomaterials with controlled properties is an important scientific and industrial problem. So, final scientific and technological problem is the creation of adequate modern methods and software for growth and properties simulation and optimization of various III-V (GaAs, InAs, InP, InGaAs etc.) nanostructures (e.g. nanowires) with controlled surface morphology, crystal structure, optical, transport properties etc. Accordingly, now we are developing a specialized computer code for atomistic simulation of structural (distribution of atoms and impurities, elastic and force constants, strain distribution etc.) and thermodynamic (mixing energy, interaction energy, surface energy etc.) properties of the nanostructures. Some simulation results are shown too.

  18. Computer simulation of multigrid body dynamics and control

    NASA Technical Reports Server (NTRS)

    Swaminadham, M.; Moon, Young I.; Venkayya, V. B.

    1990-01-01

    The objective is to set up and analyze benchmark problems on multibody dynamics and to verify the predictions of two multibody computer simulation codes. TREETOPS and DISCOS have been used to run three example problems - one degree-of-freedom spring mass dashpot system, an inverted pendulum system, and a triple pendulum. To study the dynamics and control interaction, an inverted planar pendulum with an external body force and a torsional control spring was modeled as a hinge connected two-rigid body system. TREETOPS and DISCOS affected the time history simulation of this problem. System state space variables and their time derivatives from two simulation codes were compared.

  19. Computer simulation of multigrid body dynamics and control

    NASA Technical Reports Server (NTRS)

    Swaminadham, M.; Moon, Young I.; Venkayya, V. B.

    1990-01-01

    The objective is to set up and analyze benchmark problems on multibody dynamics and to verify the predictions of two multibody computer simulation codes. TREETOPS and DISCOS have been used to run three example problems - one degree-of-freedom spring mass dashpot system, an inverted pendulum system, and a triple pendulum. To study the dynamics and control interaction, an inverted planar pendulum with an external body force and a torsional control spring was modeled as a hinge connected two-rigid body system. TREETOPS and DISCOS affected the time history simulation of this problem. System state space variables and their time derivatives from two simulation codes were compared.

  20. Molecular Dynamics Simulations of Crystal Copper: Bulk Modulus and Shocks

    NASA Astrophysics Data System (ADS)

    Warrier, M.; Rawat, S.; Chaturvedi, S.

    2011-07-01

    Molecular dynamics is used to study the response of single crystal copper target to impacts by single crystal copper at velocities in the range 1 km/s to 3 km/s. The Embedded Atom Method (EAM) potential by Foiles et al. for Cu [1] was used in the simulation. The potential and its implementation in the open source, Large-scale Atomic Molecular Massively Parallel Simulator (LAMMPS) [2] was verified by reproducing the experimental values of bulk modulus of Cu. The shock velocity (us) as a function of particle velocity (up) matches published experimental and molecular dynamic simulations results.