Evolution dynamics modeling and simulation of logistics enterprise's core competence based on service innovation

NASA Astrophysics Data System (ADS)

Yang, Bo; Tong, Yuting

2017-04-01

With the rapid development of economy, the development of logistics enterprises in China is also facing a huge challenge, especially the logistics enterprises generally lack of core competitiveness, and service innovation awareness is not strong. Scholars in the process of studying the core competitiveness of logistics enterprises are mainly from the perspective of static stability, not from the perspective of dynamic evolution to explore. So the author analyzes the influencing factors and the evolution process of the core competence of logistics enterprises, using the method of system dynamics to study the cause and effect of the evolution of the core competence of logistics enterprises, construct a system dynamics model of evolution of core competence logistics enterprises, which can be simulated by vensim PLE. The analysis for the effectiveness and sensitivity of simulation model indicates the model can be used as the fitting of the evolution process of the core competence of logistics enterprises and reveal the process and mechanism of the evolution of the core competence of logistics enterprises, and provide management strategies for improving the core competence of logistics enterprises. The construction and operation of computer simulation model offers a kind of effective method for studying the evolution of logistics enterprise core competence.

Molecular dynamics: Deciphering the data

NASA Astrophysics Data System (ADS)

Dauber-Osguthorpe, Pnina; Maunder, Colette M.; Osguthorpe, David J.

1996-06-01

The dynamic behaviour of molecules is important in determining their activity. Molecular dynamics (MD) simulations give a detailed description of motion, from small fluctuations to conformational transitions, and can include solvent effects. However, extracting useful information about conformational motion from a trajectory is not trivial. We have used digital signal-processing techniques to characterise the motion in MD simulations, including: calculating the frequency distribution, applying filtering functions, and extraction of vectors defining the characteristic motion for each frequency in an MD simulation. We describe here some typical results obtained for peptides and proteins. The nature of the low-frequency modes of motion, as obtained from MD and normal mode (NM) analysis, of Ace-(Ala)31-Nma and of a proline mutant is discussed. Low-frequency modes extracted from the MD trajectories of Rop protein and phospholipase A2 reveal characteristic motions of secondary structure elements, as well as concerted motions that are of significance to the protein's biological activity. MD simulations are also used frequently as a tool for conformational searches and for investigating protein folding/unfolding. We have developed a novel method that uses time-domain filtering to channel energy into conformational motion and thus enhance conformational transitions. The selectively enhanced molecular dynamics method is tested on the small molecule hexane.

Simulation study of the initial crystallization processes of poly(3-hexylthiophene) in solution: ordering dynamics of main chains and side chains.

PubMed

Takizawa, Yuumi; Shimomura, Takeshi; Miura, Toshiaki

2013-05-23

We study the initial nucleation dynamics of poly(3-hexylthiophene) (P3HT) in solution, focusing on the relationship between the ordering process of main chains and that of side chains. We carried out Langevin dynamics simulation and found that the initial nucleation processes consist of three steps: the ordering of ring orientation, the ordering of main-chain vectors, and the ordering of side chains. At the start, the normal vectors of thiophene rings aligned in a very short time, followed by alignment of main-chain end-to-end vectors. The flexible side-chain ordering took almost 5 times longer than the rigid-main-chain ordering. The simulation results indicated that the ordering of side chains was induced after the formation of the regular stack structure of main chains. This slow ordering dynamics of flexible side chains is one of the factors that cause anisotropic nuclei growth, which would be closely related to the formation of nanofiber structures without external flow field. Our simulation results revealed how the combined structure of the planar and rigid-main-chain backbones and the sparse flexible side chains lead to specific ordering behaviors that are not observed in ordinary linear polymer crystallization processes.

Dynamical role of Ekman pumping in rapidly rotating convection

NASA Astrophysics Data System (ADS)

Stellmach, Stephan; Julien, Keith; Cheng, Jonathan; Aurnou, Jonathan

2015-04-01

The exact nature of the mechanical boundary conditions (i.e. no-slip versus stress-free) is usually considered to be of secondary importance in the rapidly rotating parameter regime characterizing planetary cores. While they have considerable influence for the Ekman numbers achievable in today's global simulations, for planetary values both the viscous Ekman layers and the associated secondary flows are generally expected to become negligibly small. In fact, usually the main purpose of using stress-free boundary conditions in numerical dynamo simulations is to suppress unrealistically large friction and pumping effects. In this study, we investigate the influence of the mechanical boundary conditions on core convection systematically. By restricting ourselves to the idealized case of rapidly rotating Rayleigh-Bénard convection, we are able to combine results from direct numerical simulations (DNS), laboratory experiments and asymptotic theory into a coherent picture. Contrary to the general expectation, we show that the dynamical effects of Ekman pumping increase with decreasing Ekman number over the investigated parameter range. While stress-free DNS results converge to the asymptotic predictions, both no-slip simulations and laboratory experiments consistently reveal increasingly large deviations from the existing asymptotic theory based on dynamically passive Ekman layers. The implications of these results for core dynamics are discussed briefly.

How the Dynamics of a Supramolecular Polymer Determines Its Dynamic Adaptivity and Stimuli-Responsiveness: Structure-Dynamics-Property Relationships From Coarse-Grained Simulations.

PubMed

Torchi, Andrea; Bochicchio, Davide; Pavan, Giovanni M

2018-04-12

The rational design of supramolecular polymers that can adapt or respond in time to specific stimuli in a controlled way is interesting for many applications, but this requires understanding the molecular factors that make the material faster or slower in responding to the stimulus. To this end, it is necessary to study the dynamic adaptive properties at submolecular resolution, which is difficult at an experimental level. Here we show coarse-grained molecular dynamics simulations (<5 Å resolution) demonstrating how the dynamic adaptivity and stimuli responsiveness of a supramolecular polymer is controlled by the intrinsic dynamics of the assembly, which is in turn determined by the structure of the monomers. As a representative case, we focus on a water-soluble 1,3,5-benzenetricarboxamide (BTA) supramolecular polymer incorporating (charged) receptor monomers, experimentally seen to undergo dynamic clustering following the superselective binding to a multivalent recruiter. Our simulations show that the dynamic reorganization of the supramolecular structure proceeds via monomer diffusion on the dynamic fiber surface (exchange within the fiber). Rationally changing the structure of the monomers to make the fiber surface more or less dynamic allows tuning the rate of response to the stimulus and of supramolecular reconfiguration. Simple in silico experiments draw a structure-dynamics-property relationship revealing the key factors underpinning the dynamic adaptivity and stimuli-responsiveness of these supramolecular polymers. We come out with clear evidence that to master the bioinspired properties of these fibers, it is necessary to control their intrinsic dynamics, while the high-resolution of our molecular models permits us to show how.

Ultrafast transformation of graphite to diamond: an ab initio study of graphite under shock compression.

PubMed

Mundy, Christopher J; Curioni, Alessandro; Goldman, Nir; Will Kuo, I-F; Reed, Evan J; Fried, Laurence E; Ianuzzi, Marcella

2008-05-14

We report herein ab initio molecular dynamics simulations of graphite under shock compression in conjunction with the multiscale shock technique. Our simulations reveal that a novel short-lived layered diamond intermediate is formed within a few hundred of femtoseconds upon shock loading at a shock velocity of 12 kms (longitudinal stress>130 GPa), followed by formation of cubic diamond. The layered diamond state differs from the experimentally observed hexagonal diamond intermediate found at lower pressures and previous hydrostatic calculations in that a rapid buckling of the graphitic planes produces a mixture of hexagonal and cubic diamond (layered diamond). Direct calculation of the x-ray absorption spectra in our simulations reveals that the electronic structure of the final state closely resembles that of compressed cubic diamond.

Structural dynamics of supercooled water from quasielastic neutron scattering and molecular simulations.

PubMed

Qvist, Johan; Schober, Helmut; Halle, Bertil

2011-04-14

One of the outstanding challenges presented by liquid water is to understand how molecules can move on a picosecond time scale despite being incorporated in a three-dimensional network of relatively strong H-bonds. This challenge is exacerbated in the supercooled state, where the dramatic slowing down of structural dynamics is reminiscent of the, equally poorly understood, generic behavior of liquids near the glass transition temperature. By probing single-molecule dynamics on a wide range of time and length scales, quasielastic neutron scattering (QENS) can potentially reveal the mechanistic details of water's structural dynamics, but because of interpretational ambiguities this potential has not been fully realized. To resolve these issues, we present here an extensive set of high-quality QENS data from water in the range 253-293 K and a corresponding set of molecular dynamics (MD) simulations to facilitate and validate the interpretation. Using a model-free approach, we analyze the QENS data in terms of two motional components. Based on the dynamical clustering observed in MD trajectories, we identify these components with two distinct types of structural dynamics: picosecond local (L) structural fluctuations within dynamical basins and slower interbasin jumps (J). The Q-dependence of the dominant QENS component, associated with J dynamics, can be quantitatively rationalized with a continuous-time random walk (CTRW) model with an apparent jump length that depends on low-order moments of the jump length and waiting time distributions. Using a simple coarse-graining algorithm to quantitatively identify dynamical basins, we map the newtonian MD trajectory on a CTRW trajectory, from which the jump length and waiting time distributions are computed. The jump length distribution is gaussian and the rms jump length increases from 1.5 to 1.9 Å as the temperature increases from 253 to 293 K. The rms basin radius increases from 0.71 to 0.75 Å over the same range. The waiting time distribution is exponential at all investigated temperatures, ruling out significant dynamical heterogeneity. However, a simulation at 238 K reveals a small but significant dynamical heterogeneity. The macroscopic diffusion coefficient deduced from the QENS data agrees quantitatively with NMR and tracer results. We compare our QENS analysis with existing approaches, arguing that the apparent dynamical heterogeneity implied by stretched exponential fitting functions results from the failure to distinguish intrabasin (L) from interbasin (J) structural dynamics. We propose that the apparent dynamical singularity at ∼220 K corresponds to freezing out of J dynamics, while the calorimetric glass transition corresponds to freezing out of L dynamics.

Structural dynamics of supercooled water from quasielastic neutron scattering and molecular simulations

NASA Astrophysics Data System (ADS)

Qvist, Johan; Schober, Helmut; Halle, Bertil

2011-04-01

One of the outstanding challenges presented by liquid water is to understand how molecules can move on a picosecond time scale despite being incorporated in a three-dimensional network of relatively strong H-bonds. This challenge is exacerbated in the supercooled state, where the dramatic slowing down of structural dynamics is reminiscent of the, equally poorly understood, generic behavior of liquids near the glass transition temperature. By probing single-molecule dynamics on a wide range of time and length scales, quasielastic neutron scattering (QENS) can potentially reveal the mechanistic details of water's structural dynamics, but because of interpretational ambiguities this potential has not been fully realized. To resolve these issues, we present here an extensive set of high-quality QENS data from water in the range 253-293 K and a corresponding set of molecular dynamics (MD) simulations to facilitate and validate the interpretation. Using a model-free approach, we analyze the QENS data in terms of two motional components. Based on the dynamical clustering observed in MD trajectories, we identify these components with two distinct types of structural dynamics: picosecond local (L) structural fluctuations within dynamical basins and slower interbasin jumps (J). The Q-dependence of the dominant QENS component, associated with J dynamics, can be quantitatively rationalized with a continuous-time random walk (CTRW) model with an apparent jump length that depends on low-order moments of the jump length and waiting time distributions. Using a simple coarse-graining algorithm to quantitatively identify dynamical basins, we map the Newtonian MD trajectory on a CTRW trajectory, from which the jump length and waiting time distributions are computed. The jump length distribution is Gaussian and the rms jump length increases from 1.5 to 1.9 Å as the temperature increases from 253 to 293 K. The rms basin radius increases from 0.71 to 0.75 Å over the same range. The waiting time distribution is exponential at all investigated temperatures, ruling out significant dynamical heterogeneity. However, a simulation at 238 K reveals a small but significant dynamical heterogeneity. The macroscopic diffusion coefficient deduced from the QENS data agrees quantitatively with NMR and tracer results. We compare our QENS analysis with existing approaches, arguing that the apparent dynamical heterogeneity implied by stretched exponential fitting functions results from the failure to distinguish intrabasin (L) from interbasin (J) structural dynamics. We propose that the apparent dynamical singularity at ˜220 K corresponds to freezing out of J dynamics, while the calorimetric glass transition corresponds to freezing out of L dynamics.

Role of Dynamics in the Autoinhibition and Activation of the Exchange Protein Directly Activated by Cyclic AMP (EPAC)*

PubMed Central

VanSchouwen, Bryan; Selvaratnam, Rajeevan; Fogolari, Federico; Melacini, Giuseppe

2011-01-01

The exchange protein directly activated by cAMP (EPAC) is a key receptor of cAMP in eukaryotes and controls critical signaling pathways. Currently, no residue resolution information is available on the full-length EPAC dynamics, which are known to be pivotal determinants of allostery. In addition, no information is presently available on the intermediates for the classical induced fit and conformational selection activation pathways. Here these questions are addressed through molecular dynamics simulations on five key states along the thermodynamic cycle for the cAMP-dependent activation of a fully functional construct of EPAC2, which includes the cAMP-binding domain and the integral catalytic region. The simulations are not only validated by the agreement with the experimental trends in cAMP-binding domain dynamics determined by NMR, but they also reveal unanticipated dynamic attributes, rationalizing previously unexplained aspects of EPAC activation and autoinhibition. Specifically, the simulations show that cAMP binding causes an extensive perturbation of dynamics in the distal catalytic region, assisting the recognition of the Rap1b substrate. In addition, analysis of the activation intermediates points to a possible hybrid mechanism of EPAC allostery incorporating elements of both the induced fit and conformational selection models. In this mechanism an entropy compensation strategy results in a low free-energy pathway of activation. Furthermore, the simulations indicate that the autoinhibitory interactions of EPAC are more dynamic than previously anticipated, leading to a revised model of autoinhibition in which dynamics fine tune the stability of the autoinhibited state, optimally sensitizing it to cAMP while avoiding constitutive activation. PMID:21873431

Event Detection and Sub-state Discovery from Bio-molecular Simulations Using Higher-Order Statistics: Application To Enzyme Adenylate Kinase

PubMed Central

Ramanathan, Arvind; Savol, Andrej J.; Agarwal, Pratul K.; Chennubhotla, Chakra S.

2012-01-01

Biomolecular simulations at milli-second and longer timescales can provide vital insights into functional mechanisms. Since post-simulation analyses of such large trajectory data-sets can be a limiting factor in obtaining biological insights, there is an emerging need to identify key dynamical events and relating these events to the biological function online, that is, as simulations are progressing. Recently, we have introduced a novel computational technique, quasi-anharmonic analysis (QAA) (PLoS One 6(1): e15827), for partitioning the conformational landscape into a hierarchy of functionally relevant sub-states. The unique capabilities of QAA are enabled by exploiting anharmonicity in the form of fourth-order statistics for characterizing atomic fluctuations. In this paper, we extend QAA for analyzing long time-scale simulations online. In particular, we present HOST4MD - a higher-order statistical toolbox for molecular dynamics simulations, which (1) identifies key dynamical events as simulations are in progress, (2) explores potential sub-states and (3) identifies conformational transitions that enable the protein to access those sub-states. We demonstrate HOST4MD on micro-second time-scale simulations of the enzyme adenylate kinase in its apo state. HOST4MD identifies several conformational events in these simulations, revealing how the intrinsic coupling between the three sub-domains (LID, CORE and NMP) changes during the simulations. Further, it also identifies an inherent asymmetry in the opening/closing of the two binding sites. We anticipate HOST4MD will provide a powerful and extensible framework for detecting biophysically relevant conformational coordinates from long time-scale simulations. PMID:22733562

Ab initio study of the structure and dynamics of bulk liquid Fe

NASA Astrophysics Data System (ADS)

Marqués, M.; González, L. E.; González, D. J.

2015-10-01

Several static and dynamic properties of bulk liquid Fe at a thermodynamic state near its triple point have been evaluated by ab initio molecular dynamics simulations. The calculated static structure shows very good agreement with the available experimental data, including an asymmetric second peak in the structure factor which underlines a substantial local icosahedral short-range order in the liquid. The dynamical structure reveals propagating density fluctuations, with an associated dispersion relation which closely follows the experimental data. The dynamic structure factors S (q ,ω ) show a good agreement with their experimental counterparts which have been recently measured by an inelastic x-ray scattering experiment. The dynamical processes behind the S (q ,ω ) have been analyzed by using a model with two decay channels (a fast and a slow) associated with the relaxations of the collective excitations. The recent finding of transverselike excitation modes in the IXS data is analyzed by using the present ab initio simulation results. Several transport coefficients have been evaluated and the results are compared with the available experimental data.

Hyporheic Zone Residence Time Distributions in Regulated River Corridors

NASA Astrophysics Data System (ADS)

Song, X.; Chen, X.; Shuai, P.; Gomez-Velez, J. D.; Ren, H.; Hammond, G. E.

2017-12-01

Regulated rivers exhibit stage fluctuations at multiple frequencies due to both natural processes (e.g., seasonal cycle) and anthropogenic activities (e.g., dam operation). The interaction between the dynamic river flow conditions and the heterogeneous aquifer properties results in complex hydrologic exchange pathways that are ubiquitous in free-flowing and regulated river corridors. The dynamic nature of the exchange flow is reflected in the residence time distribution (RTD) of river water within the groundwater system, which is a key metric that links river corridor biogeochemical processes with the hydrologic exchange. Understanding the dynamics of RTDs is critical to gain the mechanistic understanding of hydrologic exchange fluxes and propose new parsimonious models for river corridors, yet it is understudied primarily due to the high computational demands. In this study, we developed parallel particle tracking algorithms to reveal how river flow variations affect the RTD of river water in the alluvial aquifer. Particle tracking was conducted using the velocity outputs generated by three-dimensional groundwater flow simulations of PFLOTRAN in a 1600 x 800 x 20m model domain within the DOE Hanford Site. Long-term monitoring data of inland well water levels and river stage were used for eight years of flow simulation. Nearly a half million particles were continually released along the river boundary to calculate the RTDs. Spectral analysis of the river stage data revealed high-frequency (sub-daily to weekly) river stage fluctuations caused by dam operations. The higher frequencies of stage variation were progressively filtered to generate multiple sets of flow boundary conditions. A series of flow simulations were performed by using the filtered flow boundary conditions and various degrees of subsurface heterogeneity to study the relative contribution of flow dynamics and physical heterogeneity on river water RTD. Our results revealed multimodal RTDs of river water as a result of the highly variable exchange pathways driven by interactions between dynamic flow and aquifer heterogeneity. A relationship between the RTD and frequency of flow variation was built for each heterogeneity structure, which can be used to assess the potential ecological consequences of dam operations in regulated rivers.

Matching the reaction-diffusion simulation to dynamic [18F]FMISO PET measurements in tumors: extension to a flow-limited oxygen-dependent model.

PubMed

Shi, Kuangyu; Bayer, Christine; Gaertner, Florian C; Astner, Sabrina T; Wilkens, Jan J; Nüsslin, Fridtjof; Vaupel, Peter; Ziegler, Sibylle I

2017-02-01

Positron-emission tomography (PET) with hypoxia specific tracers provides a noninvasive method to assess the tumor oxygenation status. Reaction-diffusion models have advantages in revealing the quantitative relation between in vivo imaging and the tumor microenvironment. However, there is no quantitative comparison of the simulation results with the real PET measurements yet. The lack of experimental support hampers further applications of computational simulation models. This study aims to compare the simulation results with a preclinical [ 18 F]FMISO PET study and to optimize the reaction-diffusion model accordingly. Nude mice with xenografted human squamous cell carcinomas (CAL33) were investigated with a 2 h dynamic [ 18 F]FMISO PET followed by immunofluorescence staining using the hypoxia marker pimonidazole and the endothelium marker CD 31. A large data pool of tumor time-activity curves (TAC) was simulated for each mouse by feeding the arterial input function (AIF) extracted from experiments into the model with different configurations of the tumor microenvironment. A measured TAC was considered to match a simulated TAC when the difference metric was below a certain, noise-dependent threshold. As an extension to the well-established Kelly model, a flow-limited oxygen-dependent (FLOD) model was developed to improve the matching between measurements and simulations. The matching rate between the simulated TACs of the Kelly model and the mouse PET data ranged from 0 to 28.1% (on average 9.8%). By modifying the Kelly model to an FLOD model, the matching rate between the simulation and the PET measurements could be improved to 41.2-84.8% (on average 64.4%). Using a simulation data pool and a matching strategy, we were able to compare the simulated temporal course of dynamic PET with in vivo measurements. By modifying the Kelly model to a FLOD model, the computational simulation was able to approach the dynamic [ 18 F]FMISO measurements in the investigated tumors.

Modeling soil thermal and carbon dynamics of a fire chronosequence in interior Alaska

USGS Publications Warehouse

Zhuang, Q.; McGuire, A.D.; O'Neill, K. P.; Harden, J.W.; Romanovsky, V.E.; Yarie, J.

2003-01-01

In this study, the dynamics of soil thermal, hydrologic, and ecosystem processes were coupled to project how the carbon budgets of boreal forests will respond to changes in atmospheric CO2, climate, and fire disturbance. The ability of the model to simulate gross primary production and ecosystem respiration was verified for a mature black spruce ecosystem in Canada, the age-dependent pattern of the simulated vegetation carbon was verified with inventory data on aboveground growth of Alaskan black spruce forests, and the model was applied to a postfire chronosequence in interior Alaska. The comparison between the simulated soil temperature and field-based estimates during the growing season (May to September) of 1997 revealed that the model was able to accurately simulate monthly temperatures at 10 cm (R > 0.93) for control and burned stands of the fire chronosequence. Similarly, the simulated and field-based estimates of soil respiration for control and burned stands were correlated (R = 0.84 and 0.74 for control and burned stands, respectively). The simulated and observed decadal to century-scale dynamics of soil temperature and carbon dynamics, which are represented by mean monthly values of these variables during the growing season, were correlated among stands (R = 0.93 and 0.71 for soil temperature at 20- and 10-cm depths, R = 0.95 and 0.91 for soil respiration and soil carbon, respectively). Sensitivity analyses indicate that along with differences in fire and climate history a number of other factors influence the response of carbon dynamics to fire disturbance. These factors include nitrogen fixation, the growth of moss, changes in the depth of the organic layer, soil drainage, and fire severity.

Tailoring characteristic thermal stability of Ni-Au binary nanocrystals via structure and composition engineering: theoretical insights into structural evolution and atomic inter-diffusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Bangquan; Wang, Hailong; Xing, Guozhong

We report on the structural evolution and atomic inter-diffusion characteristics of the bimetallic Ni-Au nanocrystals (NCs) by molecular dynamics simulations studies. Our results reveal that the thermal stability dynamics of Ni-Au NCs strongly depends on the atomic configurations. By engineering the structural construction with Ni:Au = 1:1 atomic composition, compared with core-shell Au@Ni and alloy NCs, the melting point of core-shell Ni@Au NCs is significantly enhanced up to 1215 K. Unexpectedly, with atomic ratio of Au:Ni= 1:9, the melting process initiates from the atoms in the shell of Ni@Au and alloy NCs, while starts from the core of Au@Ni NCs.more » The corresponding features and evolution process of structural motifs, mixing and segregation are illustrated via a series of dynamic simulations videos. Moreover, our results revealed that the face centered cubic phase Au{sub 0.75}Ni{sub 0.25} favorably stabilizes in NCs form but does not exist in the bulk counterpart, which elucidates the anomalies of previously reported experimental results on such bimetallic NCs.« less

Molecular Dynamic Simulation of Space and Earth-Grown Crystal Structures of Thermostable T1 Lipase Geobacillus zalihae Revealed a Better Structure.

PubMed

Ishak, Siti Nor Hasmah; Aris, Sayangku Nor Ariati Mohamad; Halim, Khairul Bariyyah Abd; Ali, Mohd Shukuri Mohamad; Leow, Thean Chor; Kamarudin, Nor Hafizah Ahmad; Masomian, Malihe; Rahman, Raja Noor Zaliha Raja Abd

2017-09-25

Less sedimentation and convection in a microgravity environment has become a well-suited condition for growing high quality protein crystals. Thermostable T1 lipase derived from bacterium Geobacillus zalihae has been crystallized using the counter diffusion method under space and earth conditions. Preliminary study using YASARA molecular modeling structure program for both structures showed differences in number of hydrogen bond, ionic interaction, and conformation. The space-grown crystal structure contains more hydrogen bonds as compared with the earth-grown crystal structure. A molecular dynamics simulation study was used to provide insight on the fluctuations and conformational changes of both T1 lipase structures. The analysis of root mean square deviation (RMSD), radius of gyration, and root mean square fluctuation (RMSF) showed that space-grown structure is more stable than the earth-grown structure. Space-structure also showed more hydrogen bonds and ion interactions compared to the earth-grown structure. Further analysis also revealed that the space-grown structure has long-lived interactions, hence it is considered as the more stable structure. This study provides the conformational dynamics of T1 lipase crystal structure grown in space and earth condition.

A Program for Solving the Brain Ischemia Problem

PubMed Central

DeGracia, Donald J.

2013-01-01

Our recently described nonlinear dynamical model of cell injury is here applied to the problems of brain ischemia and neuroprotection. We discuss measurement of global brain ischemia injury dynamics by time course analysis. Solutions to proposed experiments are simulated using hypothetical values for the model parameters. The solutions solve the global brain ischemia problem in terms of “master bifurcation diagrams” that show all possible outcomes for arbitrary durations of all lethal cerebral blood flow (CBF) decrements. The global ischemia master bifurcation diagrams: (1) can map to a single focal ischemia insult, and (2) reveal all CBF decrements susceptible to neuroprotection. We simulate measuring a neuroprotectant by time course analysis, which revealed emergent nonlinear effects that set dynamical limits on neuroprotection. Using over-simplified stroke geometry, we calculate a theoretical maximum protection of approximately 50% recovery. We also calculate what is likely to be obtained in practice and obtain 38% recovery; a number close to that often reported in the literature. The hypothetical examples studied here illustrate the use of the nonlinear cell injury model as a fresh avenue of approach that has the potential, not only to solve the brain ischemia problem, but also to advance the technology of neuroprotection. PMID:24961411

Hetero-diffusion of Au epitaxy on stepped Ag(110) surface: Study of the jump rate and diffusion coefficient

NASA Astrophysics Data System (ADS)

Benlattar, M.; El koraychy, E.; Kotri, A.; Mazroui, M.

2017-12-01

We have used molecular dynamics simulations combined with an interatomic potential derived from the embedded atom method, to investigate the hetero-diffusion of Au adatom near a stepped Ag(110) surface with the height of one monoatomic layer. The activation energies for different diffusion processes, which occur on the terrace and near the step edge, are calculated both by molecular statics and molecular dynamics simulations. Static energies are found by the drag method, whereas the dynamic barriers are computed at high temperature from the Arrhenius plots. Our numerical results reveal that the jump process requires very high activation energy compared to the exchange process either on the terrace or near the step edge. In this work, other processes, such as upward and downward diffusion at step edges, have also been discussed.

Probing the Energy Landscape of Activation Gating of the Bacterial Potassium Channel KcsA

PubMed Central

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

2013-01-01

The bacterial potassium channel KcsA, which has been crystallized in several conformations, offers an ideal model to investigate activation gating of ion channels. In this study, essential dynamics simulations are applied to obtain insights into the transition pathways and the energy profile of KcsA pore gating. In agreement with previous hypotheses, our simulations reveal a two phasic activation gating process. In the first phase, local structural rearrangements in TM2 are observed leading to an intermediate channel conformation, followed by large structural rearrangements leading to full opening of KcsA. Conformational changes of a highly conserved phenylalanine, F114, at the bundle crossing region are crucial for the transition from a closed to an intermediate state. 3.9 µs umbrella sampling calculations reveal that there are two well-defined energy barriers dividing closed, intermediate, and open channel states. In agreement with mutational studies, the closed state was found to be energetically more favorable compared to the open state. Further, the simulations provide new insights into the dynamical coupling effects of F103 between the activation gate and the selectivity filter. Investigations on individual subunits support cooperativity of subunits during activation gating. PMID:23658510

Non-linear dynamical classification of short time series of the rössler system in high noise regimes.

PubMed

Lainscsek, Claudia; Weyhenmeyer, Jonathan; Hernandez, Manuel E; Poizner, Howard; Sejnowski, Terrence J

2013-01-01

Time series analysis with delay differential equations (DDEs) reveals non-linear properties of the underlying dynamical system and can serve as a non-linear time-domain classification tool. Here global DDE models were used to analyze short segments of simulated time series from a known dynamical system, the Rössler system, in high noise regimes. In a companion paper, we apply the DDE model developed here to classify short segments of encephalographic (EEG) data recorded from patients with Parkinson's disease and healthy subjects. Nine simulated subjects in each of two distinct classes were generated by varying the bifurcation parameter b and keeping the other two parameters (a and c) of the Rössler system fixed. All choices of b were in the chaotic parameter range. We diluted the simulated data using white noise ranging from 10 to -30 dB signal-to-noise ratios (SNR). Structure selection was supervised by selecting the number of terms, delays, and order of non-linearity of the model DDE model that best linearly separated the two classes of data. The distances d from the linear dividing hyperplane was then used to assess the classification performance by computing the area A' under the ROC curve. The selected model was tested on untrained data using repeated random sub-sampling validation. DDEs were able to accurately distinguish the two dynamical conditions, and moreover, to quantify the changes in the dynamics. There was a significant correlation between the dynamical bifurcation parameter b of the simulated data and the classification parameter d from our analysis. This correlation still held for new simulated subjects with new dynamical parameters selected from each of the two dynamical regimes. Furthermore, the correlation was robust to added noise, being significant even when the noise was greater than the signal. We conclude that DDE models may be used as a generalizable and reliable classification tool for even small segments of noisy data.

Non-Linear Dynamical Classification of Short Time Series of the Rössler System in High Noise Regimes

PubMed Central

Lainscsek, Claudia; Weyhenmeyer, Jonathan; Hernandez, Manuel E.; Poizner, Howard; Sejnowski, Terrence J.

2013-01-01

Time series analysis with delay differential equations (DDEs) reveals non-linear properties of the underlying dynamical system and can serve as a non-linear time-domain classification tool. Here global DDE models were used to analyze short segments of simulated time series from a known dynamical system, the Rössler system, in high noise regimes. In a companion paper, we apply the DDE model developed here to classify short segments of encephalographic (EEG) data recorded from patients with Parkinson’s disease and healthy subjects. Nine simulated subjects in each of two distinct classes were generated by varying the bifurcation parameter b and keeping the other two parameters (a and c) of the Rössler system fixed. All choices of b were in the chaotic parameter range. We diluted the simulated data using white noise ranging from 10 to −30 dB signal-to-noise ratios (SNR). Structure selection was supervised by selecting the number of terms, delays, and order of non-linearity of the model DDE model that best linearly separated the two classes of data. The distances d from the linear dividing hyperplane was then used to assess the classification performance by computing the area A′ under the ROC curve. The selected model was tested on untrained data using repeated random sub-sampling validation. DDEs were able to accurately distinguish the two dynamical conditions, and moreover, to quantify the changes in the dynamics. There was a significant correlation between the dynamical bifurcation parameter b of the simulated data and the classification parameter d from our analysis. This correlation still held for new simulated subjects with new dynamical parameters selected from each of the two dynamical regimes. Furthermore, the correlation was robust to added noise, being significant even when the noise was greater than the signal. We conclude that DDE models may be used as a generalizable and reliable classification tool for even small segments of noisy data. PMID:24379798

Molecular-dynamics Simulation-based Cohesive Zone Representation of Intergranular Fracture Processes in Aluminum

NASA Technical Reports Server (NTRS)

Yamakov, Vesselin I.; Saether, Erik; Phillips, Dawn R.; Glaessgen, Edward H.

2006-01-01

A traction-displacement relationship that may be embedded into a cohesive zone model for microscale problems of intergranular fracture is extracted from atomistic molecular-dynamics simulations. A molecular-dynamics model for crack propagation under steady-state conditions is developed to analyze intergranular fracture along a flat 99 [1 1 0] symmetric tilt grain boundary in aluminum. Under hydrostatic tensile load, the simulation reveals asymmetric crack propagation in the two opposite directions along the grain boundary. In one direction, the crack propagates in a brittle manner by cleavage with very little or no dislocation emission, and in the other direction, the propagation is ductile through the mechanism of deformation twinning. This behavior is consistent with the Rice criterion for cleavage vs. dislocation blunting transition at the crack tip. The preference for twinning to dislocation slip is in agreement with the predictions of the Tadmor and Hai criterion. A comparison with finite element calculations shows that while the stress field around the brittle crack tip follows the expected elastic solution for the given boundary conditions of the model, the stress field around the twinning crack tip has a strong plastic contribution. Through the definition of a Cohesive-Zone-Volume-Element an atomistic analog to a continuum cohesive zone model element - the results from the molecular-dynamics simulation are recast to obtain an average continuum traction-displacement relationship to represent cohesive zone interaction along a characteristic length of the grain boundary interface for the cases of ductile and brittle decohesion. Keywords: Crack-tip plasticity; Cohesive zone model; Grain boundary decohesion; Intergranular fracture; Molecular-dynamics simulation

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.

Molecular dynamics study of the adsorption of anionic surfactant in a nonionic polymer brush.

PubMed

Wang, Hua; Zhang, Heng; Yuan, Shiling; Liu, Chengbu; Xu, Zhen

2014-06-01

The adsorption of the anionic surfactant, sodium dodecylsulfate (SDS) in poly(ethylene oxide) (PEO) brush was studied by molecular dynamics simulations. Our simulations revealed that surfactant can adsorb in polymer brush as micellar aggregates and the polymer would reside at the hydrocarbon-water interface of SDS micelles. This association between surfactant and polymer was mainly driven by the hydrophobic interaction between the polymer and surfactant tails. In the simulation, with the increasing of surfactant concentration, a plateau value representing saturated adsorption was observed. The height of polymer brush was mainly affected by the adsorbed surfactant at low grafting density of polymer; however, it was primarily controlled by the grafting density at high grafting density. Our conclusions at the molecular level were in close agreement with experiment about the adsorption of surfactant in polymer brushes.

Temperature dependent micro-rheology of a glass-forming polymer melt studied by molecular dynamics simulation.

PubMed

Kuhnhold, A; Paul, W

2014-09-28

We present a Molecular Dynamics simulation study of a micro-rheological probing of the glass transition in a polymer melt. Our model system consists of short bead-spring chains and the temperature ranges from well above the glass transition temperature to about 10% above it. The nano-particle clearly couples to the slowing down of the polymer segments and the calculated storage and loss moduli reveal the approach to the glass transition. At temperatures close to the mode coupling Tc of the polymer melt, the micro-rheological moduli measure the local viscoelastic response of the cage of monomers surrounding the nano-particle and no longer reveal the true melt moduli. The incoherent scattering function of the nano-particle exhibits a stretched exponential decay, typical for the α-process in glass forming systems. We find no indication of a strong superdiffusive regime as has been deduced from a recent experiment in the same temperature range but for smaller momentum transfers.

Lattice dynamics and thermal transport in multiferroic CuCrO2

NASA Astrophysics Data System (ADS)

Bansal, Dipanshu; Niedziela, Jennifer L.; May, Andrew F.; Said, Ayman; Ehlers, Georg; Abernathy, Douglas L.; Huq, Ashfia; Kirkham, Melanie; Zhou, Haidong; Delaire, Olivier

2017-02-01

Inelastic neutron and x-ray scattering measurements of phonons and spin waves were performed in the delafossite compound CuCrO2 over a wide range of temperature, and complemented with first-principles lattice dynamics simulations. The phonon dispersions and density of states are well reproduced by our density functional calculations, and reveal a strong anisotropy of Cu vibrations, which exhibit low-frequency modes of large amplitude parallel to the basal plane of the layered delafossite structure. The low frequency in-plane modes also show a systematic temperature dependence of neutron and x-ray scattering intensities. In addition, we find that spin fluctuations persist above 300 K, far above the Néel temperature for long-range antiferromagnetic order, TN≃24 K . Our modeling of the thermal conductivity, based on our phonon measurements and simulations, reveals a significant anisotropy and indicates that spin fluctuations above TN constitute an important source of phonon scattering, considerably suppressing the thermal conductivity compared to that of the isostructural but nonmagnetic compound CuAlO2.

Atomistic modeling of La3+ doping segregation effect on nanocrystalline yttria-stabilized zirconia.

PubMed

Zhang, Shenli; Sha, Haoyan; Castro, Ricardo H R; Faller, Roland

2018-05-16

The effect of La3+ doping on the structure and ionic conductivity change in nanocrystalline yttria-stabilized zirconia (YSZ) was studied using a combination of Monte Carlo and molecular dynamics simulations. The simulation revealed the segregation of La3+ at eight tilt grain boundary (GB) structures and predicted an average grain boundary (GB) energy decrease of 0.25 J m-2, which is close to the experimental values reported in the literature. Cation stabilization was found to be the main reason for the GB energy decrease, and energy fluctuations near the grain boundary are smoothed out with La3+ segregation. Both dynamic and energetic analysis on the Σ13(510)/[001] GB structure revealed La3+ doping hinders O2- diffusion in the GB region, where the diffusion coefficient monotonically decreases with increasing La3+ doping concentration. The effect was attributed to the increase in the site-dependent migration barriers for O2- hopping caused by segregated La3+, which also leads to anisotropic diffusion at the GB.

Antigen-dependent fluorescence response of anti-c-Myc Quenchbody studied by molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Mori, Yoshiharu; Okumura, Hisashi; Watanabe, Takayoshi; Hohsaka, Takahiro

2018-04-01

We performed metadynamics molecular dynamics simulations to reveal mechanism of antigen-dependent fluorescence response observed for site-specifically fluorescent-labeled single-chain antibody against c-Myc peptide antigen. We found that VH and VL bind with each other only when the antigen exists and that the fluorophore labeled at the N-terminus of VH interacts with Trp103 most stably. These results support the mechanism proposed from previous experiments: In the absence of antigen, Trp residues are partially exposed at the interface of VH and quench the fluorophore. In the presence of antigen, the Trp residues are buried between VH and VL , and the quenching is eliminated.

Direct Observation of Dynamical Quantum Phase Transitions in an Interacting Many-Body System

NASA Astrophysics Data System (ADS)

Jurcevic, P.; Shen, H.; Hauke, P.; Maier, C.; Brydges, T.; Hempel, C.; Lanyon, B. P.; Heyl, M.; Blatt, R.; Roos, C. F.

2017-08-01

The theory of phase transitions represents a central concept for the characterization of equilibrium matter. In this work we study experimentally an extension of this theory to the nonequilibrium dynamical regime termed dynamical quantum phase transitions (DQPTs). We investigate and measure DQPTs in a string of ions simulating interacting transverse-field Ising models. During the nonequilibrium dynamics induced by a quantum quench we show for strings of up to 10 ions the direct detection of DQPTs by revealing nonanalytic behavior in time. Moreover, we provide a link between DQPTs and the dynamics of other quantities such as the magnetization, and we establish a connection between DQPTs and entanglement production.

Direct Observation of Dynamical Quantum Phase Transitions in an Interacting Many-Body System.

PubMed

Jurcevic, P; Shen, H; Hauke, P; Maier, C; Brydges, T; Hempel, C; Lanyon, B P; Heyl, M; Blatt, R; Roos, C F

2017-08-25

The theory of phase transitions represents a central concept for the characterization of equilibrium matter. In this work we study experimentally an extension of this theory to the nonequilibrium dynamical regime termed dynamical quantum phase transitions (DQPTs). We investigate and measure DQPTs in a string of ions simulating interacting transverse-field Ising models. During the nonequilibrium dynamics induced by a quantum quench we show for strings of up to 10 ions the direct detection of DQPTs by revealing nonanalytic behavior in time. Moreover, we provide a link between DQPTs and the dynamics of other quantities such as the magnetization, and we establish a connection between DQPTs and entanglement production.

A general stochastic model for studying time evolution of transition networks

NASA Astrophysics Data System (ADS)

Zhan, Choujun; Tse, Chi K.; Small, Michael

2016-12-01

We consider a class of complex networks whose nodes assume one of several possible states at any time and may change their states from time to time. Such networks represent practical networks of rumor spreading, disease spreading, language evolution, and so on. Here, we derive a model describing the dynamics of this kind of network and a simulation algorithm for studying the network evolutionary behavior. This model, derived at a microscopic level, can reveal the transition dynamics of every node. A numerical simulation is taken as an ;experiment; or ;realization; of the model. We use this model to study the disease propagation dynamics in four different prototypical networks, namely, the regular nearest-neighbor (RN) network, the classical Erdös-Renyí (ER) random graph, the Watts-Strogátz small-world (SW) network, and the Barabási-Albert (BA) scalefree network. We find that the disease propagation dynamics in these four networks generally have different properties but they do share some common features. Furthermore, we utilize the transition network model to predict user growth in the Facebook network. Simulation shows that our model agrees with the historical data. The study can provide a useful tool for a more thorough understanding of the dynamics networks.

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.

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

Molecular dynamics simulations of human E3 ubiquitin ligase Parkin.

PubMed

Qiu, Shi; Zhu, Shun; Xu, Shan; Han, Yanyan; Liu, Wen; Zuo, Ji

2017-10-01

Human E3 ubiquitin protein ligase parkin (Parkin) mediates mitophagy to maintain mitochondrial homeostasis. Parkin mutations are common genetic causes of early onset familial Parkinson's disease. The molecular mechanism of Parkin activation has been widely studied with emerging evidence suggesting an essential role of the phosphorylated (phospho)‑ubiquitin interaction. However, the underlying mecha-nism of the phospho‑ubiquitin interaction remains elusive. In the present study, replica exchange molecular dynamics simulations were performed to examine the conformational dynamics of Parkin in monomer and phospho‑ubiquitin‑bound states. In the Parkin monomer state, high structural flexi-bilities were observed in the majority of regions of Parkin particularly in the loop domain between the ubiquitin‑like (UBL) and really interesting new gene (RING)0 domain. Binding of phospho‑ubiquitin stabilizes the RING1/RING in between RING interface but destabilizes the RING1‑UBL interface. Furthermore, using steered molecular dynamics simulations of Parkin mutations, it was demonstrated that salt bridge interactions contribute significantly to the interdomain interactions between the RING1 and UBL domain. Taken together, the results of the present study revealed the conformational dynamics of human full‑length Parkin in monomer and phospho‑ubiquitin‑bound states, providing insights into designing potential therapeutics against Parkinson's disease.

Early Dynamics and Stabilization Mechanisms of Oil-in-Water Emulsions Containing Colloidal Particles Modified with Short Amphiphiles: A Numerical Study.

PubMed

Cerbelaud, Manuella; Videcoq, Arnaud; Alison, Lauriane; Tervoort, Elena; Studart, André R

2017-12-19

Emulsions stabilized by mixtures of particles and amphiphilic molecules are relevant for a wide range of applications, but their dynamics and stabilization mechanisms on the colloidal level are poorly understood. Given the challenges to experimentally probe the early dynamics and mechanisms of droplet stabilization, Brownian dynamics simulations are developed here to study the behavior of oil-in-water emulsions stabilized by colloidal particles modified with short amphiphiles. Simulation parameters are based on an experimental system that consists of emulsions obtained with octane as the oil phase and a suspension of alumina colloidal particles modified with short carboxylic acids as the continuous aqueous medium. The numerical results show that attractive forces between the colloidal particles favor the formation of closely packed clusters on the droplet surface or of a percolating network of particles throughout the continuous phase, depending on the amphiphile concentration. Simulations also reveal the importance of a strong adsorption of particles at the liquid interface to prevent their depletion from the droplet surface when another droplet approaches. Strongly adsorbed particles remain immobile on the droplet surface, generating an effective steric barrier against droplet coalescence. These findings provide new insights into the early dynamics and mechanisms of stabilization of emulsions using particles and amphiphilic molecules.

Structural and dynamic characteristics in monolayer square ice.

PubMed

Zhu, YinBo; Wang, FengChao; Wu, HengAn

2017-07-28

When water is constrained between two sheets of graphene, it becomes an intriguing monolayer solid with a square pattern due to the ultrahigh van der Waals pressure. However, the square ice phase has become a matter of debate due to the insufficient experimental interpretation and the slightly rhomboidal feature in simulated monolayer square-like structures. Here, we performed classical molecular dynamics simulations to reveal monolayer square ice in graphene nanocapillaries from the perspective of structure and dynamic characteristics. Monolayer square-like ice (instantaneous snapshot), assembled square-rhombic units with stacking faults, is a long-range ordered structure, in which the square and rhombic units are assembled in an order of alternative distribution, and the other rhombic unit forms stacking faults (polarized water chains). Spontaneous flipping of water molecules in monolayer square-like ice is intrinsic and induces transformations among different elementary units, resulting in the structural evolution of monolayer square ice in dynamics. The existence of stacking faults should be attributed to the spontaneous flipping behavior of water molecules under ambient temperature. Statistical averaging results (thermal average positions) demonstrate the inherent square characteristic of monolayer square ice. The simulated data and insight obtained here might be significant for understanding the topological structure and dynamic behavior of monolayer square ice.

Large scale atomistic simulation of single-layer graphene growth on Ni(111) surface: molecular dynamics simulation based on a new generation of carbon-metal potential

NASA Astrophysics Data System (ADS)

Xu, Ziwei; Yan, Tianying; Liu, Guiwu; Qiao, Guanjun; Ding, Feng

2015-12-01

To explore the mechanism of graphene chemical vapor deposition (CVD) growth on a catalyst surface, a molecular dynamics (MD) simulation of carbon atom self-assembly on a Ni(111) surface based on a well-designed empirical reactive bond order potential was performed. We simulated single layer graphene with recorded size (up to 300 atoms per super-cell) and reasonably good quality by MD trajectories up to 15 ns. Detailed processes of graphene CVD growth, such as carbon atom dissolution and precipitation, formation of carbon chains of various lengths, polygons and small graphene domains were observed during the initial process of the MD simulation. The atomistic processes of typical defect healing, such as the transformation from a pentagon into a hexagon and from a pentagon-heptagon pair (5|7) to two adjacent hexagons (6|6), were revealed as well. The study also showed that higher temperature and longer annealing time are essential to form high quality graphene layers, which is in agreement with experimental reports and previous theoretical results.To explore the mechanism of graphene chemical vapor deposition (CVD) growth on a catalyst surface, a molecular dynamics (MD) simulation of carbon atom self-assembly on a Ni(111) surface based on a well-designed empirical reactive bond order potential was performed. We simulated single layer graphene with recorded size (up to 300 atoms per super-cell) and reasonably good quality by MD trajectories up to 15 ns. Detailed processes of graphene CVD growth, such as carbon atom dissolution and precipitation, formation of carbon chains of various lengths, polygons and small graphene domains were observed during the initial process of the MD simulation. The atomistic processes of typical defect healing, such as the transformation from a pentagon into a hexagon and from a pentagon-heptagon pair (5|7) to two adjacent hexagons (6|6), were revealed as well. The study also showed that higher temperature and longer annealing time are essential to form high quality graphene layers, which is in agreement with experimental reports and previous theoretical results. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06016h

Study of diffusion and local structure of sodium-silicate liquid: the molecular dynamic simulation

NASA Astrophysics Data System (ADS)

Hung, Pham Khac; Noritake, Fumiya; San, Luyen Thi; Van, To Ba; Vinh, Le The

2017-10-01

A systematic analysis on sodium-silicate melt with various silica contents was carried out. The simulation revealed two diffusion mechanisms occurred in the melt: the bond-breaking and hopping between sites. The local structure was analyzed through T-simplexes. It was revealed that T-clusters have a non-spherical shape and represent the diffusion channel, in which Na atoms are dominant, but no any O atoms are located. The SiO2-poor melt acquires a long channel. In contrast, the SiO2-rich melt consists of unconnected short channels. The simulation also revealed the immobile and mobile regions which differ in local structure and constituent composition. We propose a new CL-function to characterizing the spatial distribution of different atom component. The spatial distribution of mobile and immobile atoms is found quite different. In particular, the immobile atoms are concentrated in high-density regions possessing very large density of immobile atoms. The spatial distribution of mobile atoms in contrast is more homogeneous.

The dynamic behavior of a liquid ethanol-water mixture: a perspective from quantum chemical topology.

PubMed

Mejía, Sol M; Mills, Matthew J L; Shaik, Majeed S; Mondragon, Fanor; Popelier, Paul L A

2011-05-07

Quantum Chemical Topology (QCT) is used to reveal the dynamics of atom-atom interactions in a liquid. A molecular dynamics simulation was carried out on an ethanol-water liquid mixture at its azeotropic concentration (X(ethanol)=0.899), using high-rank multipolar electrostatics. A thousand (ethanol)(9)-water heterodecamers, respecting the water-ethanol ratio of the azeotropic mixture, were extracted from the simulation. Ab initio electron densities were computed at the B3LYP/6-31+G(d) level for these molecular clusters. A video shows the dynamical behavior of a pattern of bond critical points and atomic interaction lines, fluctuating over 1 ns. A bond critical point distribution revealed the fluctuating behavior of water and ethanol molecules in terms of O-H···O, C-H···O and H···H interactions. Interestingly, the water molecule formed one to six C-H···O and one to four O-H···O interactions as a proton acceptor. We found that the more localized a dynamical bond critical point distribution, the higher the average electron density at its bond critical points. The formation of multiple C-H···O interactions affected the shape of the oxygen basin of the water molecule, which is shown in three dimensions. The hydrogen atoms of water strongly preferred to form H···H interactions with ethanol's alkyl hydrogen atoms over its hydroxyl hydrogen. This journal is © the Owner Societies 2011

Buckling Causes Nonlinear Dynamics of Filamentous Viruses Driven through Nanopores.

PubMed

McMullen, Angus; de Haan, Hendrick W; Tang, Jay X; Stein, Derek

2018-02-16

Measurements and Langevin dynamics simulations of filamentous viruses driven through solid-state nanopores reveal a superlinear rise in the translocation velocity with driving force. The mobility also scales with the length of the virus in a nontrivial way that depends on the force. These dynamics are consequences of the buckling of the leading portion of a virus as it emerges from the nanopore and is put under compressive stress by the viscous forces it encounters. The leading tip of a buckled virus stalls and this reduces the total viscous drag force. We present a scaling theory that connects the solid mechanics to the nonlinear dynamics of polyelectrolytes translocating nanopores.

Buckling Causes Nonlinear Dynamics of Filamentous Viruses Driven through Nanopores

NASA Astrophysics Data System (ADS)

McMullen, Angus; de Haan, Hendrick W.; Tang, Jay X.; Stein, Derek

2018-02-01

Measurements and Langevin dynamics simulations of filamentous viruses driven through solid-state nanopores reveal a superlinear rise in the translocation velocity with driving force. The mobility also scales with the length of the virus in a nontrivial way that depends on the force. These dynamics are consequences of the buckling of the leading portion of a virus as it emerges from the nanopore and is put under compressive stress by the viscous forces it encounters. The leading tip of a buckled virus stalls and this reduces the total viscous drag force. We present a scaling theory that connects the solid mechanics to the nonlinear dynamics of polyelectrolytes translocating nanopores.

Dynamic characteristic of electromechanical coupling effects in motor-gear system

NASA Astrophysics Data System (ADS)

Bai, Wenyu; Qin, Datong; Wang, Yawen; Lim, Teik C.

2018-06-01

Dynamic characteristics of an electromechanical model which combines a nonlinear permeance network model (PNM) of a squirrel-cage induction motor and a coupled lateral-torsional dynamic model of a planetary geared rotor system is analyzed in this study. The simulations reveal the effects of internal excitations or parameters like machine slotting, magnetic saturation, time-varying mesh stiffness and shaft stiffness on the system dynamics. The responses of the electromechanical system with PNM motor model are compared with those responses of the system with dynamic motor model. The electromechanical coupling due to the interactions between the motor and gear system are studied. Furthermore, the frequency analysis of the electromechanical system dynamic characteristics predicts an efficient way to detect work condition of unsymmetrical voltage sag.

Absorptive capacity, technological innovation, and product life cycle: a system dynamics model.

PubMed

Zou, Bo; Guo, Feng; Guo, Jinyu

2016-01-01

While past research has recognized the importance of the dynamic nature of absorptive capacity, there is limited knowledge on how to generate a fair and comprehensive analytical framework. Based on interviews with 24 Chinese firms, this study develops a system-dynamics model that incorporates an important feedback loop among absorptive capacity, technological innovation, and product life cycle (PLC). The simulation results reveal that (1) PLC affects the dynamic process of absorptive capacity; (2) the absorptive capacity of a firm peaks in the growth stage of PLC, and (3) the market demand at different PLC stages is the main driving force in firms' technological innovations. This study also explores a sensitivity simulation using the variables of (1) time spent in founding an external knowledge network, (2) research and development period, and (3) knowledge diversity. The sensitivity simulation results show that the changes of these three variables have a greater impact on absorptive capacity and technological innovation during growth and maturity stages than in the introduction and declining stages of PLC. We provide suggestions on how firms can adjust management policies to improve their absorptive capacity and technological innovation performance during different PLC stages.

Genetic drift and selection in many-allele range expansions.

PubMed

Weinstein, Bryan T; Lavrentovich, Maxim O; Möbius, Wolfram; Murray, Andrew W; Nelson, David R

2017-12-01

We experimentally and numerically investigate the evolutionary dynamics of four competing strains of E. coli with differing expansion velocities in radially expanding colonies. We compare experimental measurements of the average fraction, correlation functions between strains, and the relative rates of genetic domain wall annihilations and coalescences to simulations modeling the population as a one-dimensional ring of annihilating and coalescing random walkers with deterministic biases due to selection. The simulations reveal that the evolutionary dynamics can be collapsed onto master curves governed by three essential parameters: (1) an expansion length beyond which selection dominates over genetic drift; (2) a characteristic angular correlation describing the size of genetic domains; and (3) a dimensionless constant quantifying the interplay between a colony's curvature at the frontier and its selection length scale. We measure these parameters with a new technique that precisely measures small selective differences between spatially competing strains and show that our simulations accurately predict the dynamics without additional fitting. Our results suggest that the random walk model can act as a useful predictive tool for describing the evolutionary dynamics of range expansions composed of an arbitrary number of genotypes with different fitnesses.

Cooperative behavior and phase transitions in co-evolving stag hunt game

NASA Astrophysics Data System (ADS)

Zhang, W.; Li, Y. S.; Xu, C.; Hui, P. M.

2016-02-01

Cooperative behavior and different phases in a co-evolving network dynamics based on the stag hunt game is studied. The dynamical processes are parameterized by a payoff r that tends to promote non-cooperative behavior and a probability q for a rewiring attempt that could isolate the non-cooperators. The interplay between the parameters leads to different phases. Detailed simulations and a mean field theory are employed to reveal the properties of different phases. For small r, the cooperators are the majority and form a connected cluster while the non-cooperators increase with q but remain isolated over the whole range of q, and it is a static phase. For sufficiently large r, cooperators disappear in an intermediate range qL ≤ q ≤qU and a dynamical all-non-cooperators phase results. For q >qU, a static phase results again. A mean field theory based on how the link densities change in time by the co-evolving dynamics is constructed. The theory gives a phase diagram in the q- r parameter space that is qualitatively in agreement with simulation results. The sources of discrepancies between theory and simulations are discussed.

Modeling detour behavior of pedestrian dynamics under different conditions

NASA Astrophysics Data System (ADS)

Qu, Yunchao; Xiao, Yao; Wu, Jianjun; Tang, Tao; Gao, Ziyou

2018-02-01

Pedestrian simulation approach has been widely used to reveal the human behavior and evaluate the performance of crowd evacuation. In the existing pedestrian simulation models, the social force model is capable of predicting many collective phenomena. Detour behavior occurs in many cases, and the important behavior is a dominate factor of the crowd evacuation efficiency. However, limited attention has been attracted for analyzing and modeling the characteristics of detour behavior. In this paper, a modified social force model integrated by Voronoi diagram is proposed to calculate the detour direction and preferred velocity. Besides, with the consideration of locations and velocities of neighbor pedestrians, a Logit-based choice model is built to describe the detour direction choice. The proposed model is applied to analyze pedestrian dynamics in a corridor scenario with either unidirectional or bidirectional flow, and a building scenario in real-world. Simulation results show that the modified social force model including detour behavior could reduce the frequency of collision and deadlock, increase the average speed of the crowd, and predict more practical crowd dynamics with detour behavior. This model can also be potentially applied to understand the pedestrian dynamics and design emergent management strategies for crowd evacuations.

Non-Adiabatic Molecular Dynamics Methods for Materials Discovery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Furche, Filipp; Parker, Shane M.; Muuronen, Mikko J.

2017-04-04

The flow of radiative energy in light-driven materials such as photosensitizer dyes or photocatalysts is governed by non-adiabatic transitions between electronic states and cannot be described within the Born-Oppenheimer approximation commonly used in electronic structure theory. The non-adiabatic molecular dynamics (NAMD) methods based on Tully surface hopping and time-dependent density functional theory developed in this project have greatly extended the range of molecular materials that can be tackled by NAMD simulations. New algorithms to compute molecular excited state and response properties efficiently were developed. Fundamental limitations of common non-linear response methods were discovered and characterized. Methods for accurate computations ofmore » vibronic spectra of materials such as black absorbers were developed and applied. It was shown that open-shell TDDFT methods capture bond breaking in NAMD simulations, a longstanding challenge for single-reference molecular dynamics simulations. The methods developed in this project were applied to study the photodissociation of acetaldehyde and revealed that non-adiabatic effects are experimentally observable in fragment kinetic energy distributions. Finally, the project enabled the first detailed NAMD simulations of photocatalytic water oxidation by titania nanoclusters, uncovering the mechanism of this fundamentally important reaction for fuel generation and storage.« less

Pathways from disordered to ordered nanostructures from defect guided dewetting of ultrathin bilayers.

PubMed

Hens, Abhiram; Mondal, Kartick; Biswas, Gautam; Bandyopadhyay, Dipankar

2016-03-01

Transitions from spinodal to pattern-guided dewetting of a bilayer of ultrathin films (<10nm) confined between a pair of patterned surfaces have been explored employing molecular dynamic (MD) simulations. The physical or chemical defects of different sizes and shapes are decorated on the confining substrates by either removal or addition of multiple layers of similar or dissimilar atoms. The simulations are performed to identify the transition from spinodal pathway to the heterogeneous nucleation route, with the variation in the size of the substrate patterns. The MD simulations reveal the limits beyond which the defects can guide the dewetting to generate ordered patterns of nanoscopic size and periodicity. Comparing the results obtained from the MD simulations with the more widely employed continuum dynamics approach highlights the importance of the MD approach in quantitatively analyzing the dynamics of the dewetting of ultrathin films. The study demonstrates that the pattern-guided dewetting of confined bilayers can lead to ordered holes, droplets, and stripes with size and periodicity less than 10nm, which are yet to be realized experimentally and can be of significance for a number of future applications. Copyright © 2015 Elsevier Inc. All rights reserved.

Conformational Sampling and Nucleotide-Dependent Transitions of the GroEL Subunit Probed by Unbiased Molecular Dynamics Simulations

PubMed Central

Skjaerven, Lars; Grant, Barry; Muga, Arturo; Teigen, Knut; McCammon, J. Andrew; Reuter, Nathalie; Martinez, Aurora

2011-01-01

GroEL is an ATP dependent molecular chaperone that promotes the folding of a large number of substrate proteins in E. coli. Large-scale conformational transitions occurring during the reaction cycle have been characterized from extensive crystallographic studies. However, the link between the observed conformations and the mechanisms involved in the allosteric response to ATP and the nucleotide-driven reaction cycle are not completely established. Here we describe extensive (in total long) unbiased molecular dynamics (MD) simulations that probe the response of GroEL subunits to ATP binding. We observe nucleotide dependent conformational transitions, and show with multiple 100 ns long simulations that the ligand-induced shift in the conformational populations are intrinsically coded in the structure-dynamics relationship of the protein subunit. Thus, these simulations reveal a stabilization of the equatorial domain upon nucleotide binding and a concomitant “opening” of the subunit, which reaches a conformation close to that observed in the crystal structure of the subunits within the ADP-bound oligomer. Moreover, we identify changes in a set of unique intrasubunit interactions potentially important for the conformational transition. PMID:21423709

Adaptive Calibration of Dynamic Accommodation—Implications for Accommodating Intraocular Lenses

PubMed Central

Schor, Clifton M.; Bharadwaj, Shrikant R.

2009-01-01

PURPOSE When the aging lens is replaced with prosthetic accommodating intraocular lenses (IOLs), with effective viscoelasticities different from those of the natural lens, mismatches could arise between the neural control of accommodation and the biomechanical properties of the new lens. These mismatches could lead to either unstable oscillations or sluggishness of dynamic accommodation. Using computer simulations, we investigated whether optimal accommodative responses could be restored through recalibration of the neural control of accommodation. Using human experiments, we also investigated whether the accommodative system has the capacity for adaptive recalibration in response to changes in lens biomechanics. METHODS Dynamic performance of two accommodating IOL prototypes was simulated for a 45-year-old accommodative system, before and after neural recalibration, using a dynamic model of accommodation. Accommodating IOL I, a prototype for an injectable accommodating IOL, was less stiff and less viscous than the natural 45-year-old lens. Accommodating IOL II, a prototype for a translating accommodating IOL, was less stiff and more viscous than the natural 45-year-old lens. Short-term adaptive recalibration of dynamic accommodation was stimulated using a double-step adaptation paradigm that optically induced changes in neuromuscular effort mimicking responses to changes in lens biomechanics. RESULTS Model simulations indicate that the unstable oscillations or sluggishness of dynamic accommodation resulting from mismatches between neural control and lens biomechanics might be restored through neural recalibration. CONCLUSIONS Empirical measures reveal that the accommodative system is capable of adaptive recalibration in response to optical loads that simulate effects of changing lens biomechanics. PMID:19044245

Conformational Ensemble of the Poliovirus 3CD Precursor Observed by MD Simulations and Confirmed by SAXS: A Strategy to Expand the Viral Proteome?

PubMed

Moustafa, Ibrahim M; Gohara, David W; Uchida, Akira; Yennawar, Neela; Cameron, Craig E

2015-11-23

The genomes of RNA viruses are relatively small. To overcome the small-size limitation, RNA viruses assign distinct functions to the processed viral proteins and their precursors. This is exemplified by poliovirus 3CD protein. 3C protein is a protease and RNA-binding protein. 3D protein is an RNA-dependent RNA polymerase (RdRp). 3CD exhibits unique protease and RNA-binding activities relative to 3C and is devoid of RdRp activity. The origin of these differences is unclear, since crystal structure of 3CD revealed "beads-on-a-string" structure with no significant structural differences compared to the fully processed proteins. We performed molecular dynamics (MD) simulations on 3CD to investigate its conformational dynamics. A compact conformation of 3CD was observed that was substantially different from that shown crystallographically. This new conformation explained the unique properties of 3CD relative to the individual proteins. Interestingly, simulations of mutant 3CD showed altered interface. Additionally, accelerated MD simulations uncovered a conformational ensemble of 3CD. When we elucidated the 3CD conformations in solution using small-angle X-ray scattering (SAXS) experiments a range of conformations from extended to compact was revealed, validating the MD simulations. The existence of conformational ensemble of 3CD could be viewed as a way to expand the poliovirus proteome, an observation that may extend to other viruses.

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

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.

Density Functional Computations and Molecular Dynamics Simulations of the Triethylammonium Triflate Protic Ionic Liquid.

PubMed

Mora Cardozo, Juan F; Burankova, T; Embs, J P; Benedetto, A; Ballone, P

2017-12-21

Systematic molecular dynamics simulations based on an empirical force field have been carried out for samples of triethylammonium trifluoromethanesulfonate (triethylammonium triflate, [TEA][Tf]), covering a wide temperature range 200 K ≤ T ≤ 400 K and analyzing a broad set of properties, from self-diffusion and electrical conductivity to rotational relaxation and hydrogen-bond dynamics. The study is motivated by recent quasi-elastic neutron scattering and differential scanning calorimetry measurements on the same system, revealing two successive first order transitions at T ≈ 230 and 310 K (on heating), as well as an intriguing and partly unexplained variety of subdiffusive motions of the acidic proton. Simulations show a weakly discontinuous transition at T = 310 K and highlight an anomaly at T = 260 K in the rotational relaxation of ions that we identify with the simulation analogue of the experimental transition at T = 230 K. Thus, simulations help identifying the nature of the experimental transitions, confirming that the highest temperature one corresponds to melting, while the one taking place at lower T is a transition from the crystal, stable at T ≤ 260 K, to a plastic phase (260 ≤ T ≤ 310 K), in which molecules are able to rotate without diffusing. Rotations, in particular, account for the subdiffusive motion seen at intermediate T both in the experiments and in the simulation. The structure, distribution, and strength of hydrogen bonds are investigated by molecular dynamics and by density functional computations. Clustering of ions of the same sign and the effect of contamination by water at 1% wgt concentration are discussed as well.

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

PubMed Central

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.

2016-01-01

The molecular basis of enzyme catalytic power and specificity derives from dynamic interactions between enzyme and substrate during catalysis. Although 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, we examine the importance of substrate dynamics in the cleavage of Kunitz-bovine pancreatic trypsin inhibitor 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. By using long all-atom molecular dynamics simulations of acyl-enzyme intermediates with proteolysis rates spanning 3 orders of magnitude, we identify global and local dynamic features of substrates on the nanosecond-microsecond time scale 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 substrate-like and product-like states, linking substrate dynamics on the nanosecond-microsecond time scale with large collective substrate motions on the much slower time scale of catalysis. Our findings implicate substrate flexibility as a critical determinant of catalysis. PMID:27810896

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

Development of a computer-simulation model for a plant-nematode system.

PubMed

Ferris, H

1976-07-01

A computer-simulation model (MELSIM) of a Meloidogyne-grapevine system is developed. The objective is to attempt a holistic approach to the study of nematode population dynamics by using experimental data from controlled environmental conditions. A simulator with predictive ability would be useful in considering pest management alternatives and in teaching. Rates of flow and interaction between the components of the system are governed by environmental conditions. Equations for these rates are determined by fitting curves to data from controlled environment studies. Development of the model and trial simulations have revealed deficiencies in understanding of the system and identified areas where further research is necessary.

Ab initio multiple spawning dynamics study of dimethylnitramine and dimethylnitramine-Fe complex to model their ultrafast nonadiabatic chemistry

NASA Astrophysics Data System (ADS)

Bera, Anupam; Ghosh, Jayanta; Bhattacharya, Atanu

2017-07-01

Conical intersections are now firmly established to be the key features in the excited electronic state processes of polyatomic energetic molecules. In the present work, we have explored conical intersection-mediated nonadiabatic chemical dynamics of a simple analogue nitramine molecule, dimethylnitramine (DMNA, containing one N-NO2 energetic group), and its complex with an iron atom (DMNA-Fe). For this task, we have used the ab initio multiple spawning (AIMS) dynamics simulation at the state averaged-complete active space self-consistent field(8,5)/6-31G(d) level of theory. We have found that DMNA relaxes back to the ground (S0) state following electronic excitation to the S1 excited state [which is an (n,π*) excited state] with a time constant of approximately 40 fs. This AIMS result is in very good agreement with the previous surface hopping-result and femtosecond laser spectroscopy result. DMNA does not dissociate during this fast internal conversion from the S1 to the S0 state. DMNA-Fe also undergoes extremely fast relaxation from the upper S1 state to the S0 state; however, this relaxation pathway is dissociative in nature. DMNA-Fe undergoes initial Fe-O, N-O, and N-N bond dissociations during relaxation from the upper S1 state to the ground S0 state through the respective conical intersection. The AIMS simulation reveals the branching ratio of these three channels as N-N:Fe-O:N-O = 6:3:1 (based on 100 independent simulations). Furthermore, the AIMS simulation reveals that the Fe-O bond dissociation channel exhibits the fastest (time constant 24 fs) relaxation, while the N-N bond dissociation pathway features the slowest (time constant 128 fs) relaxation. An intermediate time constant (30 fs) is found for the N-O bond dissociation channel. This is the first nonadiabatic chemical dynamics study of metal-contained energetic molecules through conical intersections.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fischer, Sean A.; Aprà, Edoardo; Govind, Niranjan

2017-02-03

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 withmore » 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.« less

Time-resolved observation of protein allosteric communication

PubMed Central

Buchenberg, Sebastian; Sittel, Florian; Stock, Gerhard

2017-01-01

Allostery represents a fundamental mechanism of biological regulation that is mediated via long-range communication between distant protein sites. Although little is known about the underlying dynamical process, recent time-resolved infrared spectroscopy experiments on a photoswitchable PDZ domain (PDZ2S) have indicated that the allosteric transition occurs on multiple timescales. Here, using extensive nonequilibrium molecular dynamics simulations, a time-dependent picture of the allosteric communication in PDZ2S is developed. The simulations reveal that allostery amounts to the propagation of structural and dynamical changes that are genuinely nonlinear and can occur in a nonlocal fashion. A dynamic network model is constructed that illustrates the hierarchy and exceeding structural heterogeneity of the process. In compelling agreement with experiment, three physically distinct phases of the time evolution are identified, describing elastic response (≲0.1 ns), inelastic reorganization (∼100 ns), and structural relaxation (≳1μs). Issues such as the similarity to downhill folding as well as the interpretation of allosteric pathways are discussed. PMID:28760989

Identification of promising DNA GyrB inhibitors for Tuberculosis using pharmacophore-based virtual screening, molecular docking and molecular dynamics studies.

PubMed

Islam, Md Ataul; Pillay, Tahir S

2017-08-01

In this study, we searched for potential DNA GyrB inhibitors using pharmacophore-based virtual screening followed by molecular docking and molecular dynamics simulation approaches. For this purpose, a set of 248 DNA GyrB inhibitors was collected from the literature and a well-validated pharmacophore model was generated. The best pharmacophore model explained that two each of hydrogen bond acceptors and hydrophobicity regions were critical for inhibition of DNA GyrB. Good statistical results of the pharmacophore model indicated that the model was robust in nature. Virtual screening of molecular databases revealed three molecules as potential antimycobacterial agents. The final screened promising compounds were evaluated in molecular docking and molecular dynamics simulation studies. In the molecular dynamics studies, RMSD and RMSF values undoubtedly explained that the screened compounds formed stable complexes with DNA GyrB. Therefore, it can be concluded that the compounds identified may have potential for the treatment of TB. © 2017 John Wiley & Sons A/S.

Analysis of Species-Selectivity of Human, Mouse and Rat Cytochrome P450 1A and 2B Subfamily Enzymes using Molecular Modeling, Docking and Dynamics Simulations.

PubMed

Karthikeyan, Bagavathy Shanmugam; Suvaithenamudhan, Suvaiyarasan; Akbarsha, Mohammad Abdulkader; Parthasarathy, Subbiah

2018-06-01

Cytochrome P450 (CYP) 1A and 2B subfamily enzymes are important drug metabolizing enzymes, and are highly conserved across species in terms of sequence homology. However, there are major to minor structural and macromolecular differences which provide for species-selectivity and substrate-selectivity. Therefore, species-selectivity of CYP1A and CYP2B subfamily proteins across human, mouse and rat was analyzed using molecular modeling, docking and dynamics simulations when the chiral molecules quinine and quinidine were used as ligands. The three-dimensional structures of 17 proteins belonging to CYP1A and CYP2B subfamilies of mouse and rat were predicted by adopting homology modeling using the available structures of human CYP1A and CYP2B proteins as templates. Molecular docking and dynamics simulations of quinine and quinidine with CYP1A subfamily proteins revealed the existence of species-selectivity across the three species. On the other hand, in the case of CYP2B subfamily proteins, no role for chirality of quinine and quinidine in forming complexes with CYP2B subfamily proteins of the three species was indicated. Our findings reveal the roles of active site amino acid residues of CYP1A and CYP2B subfamily proteins and provide insights into species-selectivity of these enzymes across human, mouse, and rat.

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

Characterization of the Interaction between Gallic Acid and Lysozyme by Molecular Dynamics Simulation and Optical Spectroscopy

PubMed Central

Zhan, Minzhong; Guo, Ming; Jiang, Yanke; Wang, Xiaomeng

2015-01-01

The binding interaction between gallic acid (GA) and lysozyme (LYS) was investigated and compared by molecular dynamics (MD) simulation and spectral techniques. The results from spectroscopy indicate that GA binds to LYS to generate a static complex. The binding constants and thermodynamic parameters were calculated. MD simulation revealed that the main driving forces for GA binding to LYS are hydrogen bonding and hydrophobic interactions. The root-mean-square deviation verified that GA and LYS bind to form a stable complex, while the root-mean-square fluctuation results showed that the stability of the GA-LYS complex at 298 K was higher than that at 310 K. The calculated free binding energies from the molecular mechanics/Poisson-Boltzmann surface area method showed that van der Waals forces and electrostatic interactions are the predominant intermolecular forces. The MD simulation was consistent with the spectral experiments. This study provides a reference for future study of the pharmacological mechanism of GA. PMID:26140374

Characterization of the Interaction between Gallic Acid and Lysozyme by Molecular Dynamics Simulation and Optical Spectroscopy.

PubMed

Zhan, Minzhong; Guo, Ming; Jiang, Yanke; Wang, Xiaomeng

2015-07-01

The binding interaction between gallic acid (GA) and lysozyme (LYS) was investigated and compared by molecular dynamics (MD) simulation and spectral techniques. The results from spectroscopy indicate that GA binds to LYS to generate a static complex. The binding constants and thermodynamic parameters were calculated. MD simulation revealed that the main driving forces for GA binding to LYS are hydrogen bonding and hydrophobic interactions. The root-mean-square deviation verified that GA and LYS bind to form a stable complex, while the root-mean-square fluctuation results showed that the stability of the GA-LYS complex at 298 K was higher than that at 310 K. The calculated free binding energies from the molecular mechanics/Poisson-Boltzmann surface area method showed that van der Waals forces and electrostatic interactions are the predominant intermolecular forces. The MD simulation was consistent with the spectral experiments. This study provides a reference for future study of the pharmacological mechanism of GA.

Functional rotation induced by alternating protonation states in the multidrug transporter AcrB: all-atom molecular dynamics simulations.

PubMed

Yamane, Tsutomu; Murakami, Satoshi; Ikeguchi, Mitsunori

2013-10-29

The multidrug transporter AcrB actively exports a wide variety of noxious compounds using proton-motive force as an energy source in Gram-negative bacteria. AcrB adopts an asymmetric structure comprising three protomers with different conformations that are sequentially converted during drug export; these cyclic conformational changes during drug export are referred to as functional rotation. To investigate functional rotation driven by proton-motive force, all-atom molecular dynamics simulations were performed. Using different protonation states for the titratable residues in the middle of the transmembrane domain, our simulations revealed the correlation between the specific protonation states and the side-chain configurations. Changing the protonation state for Asp408 induced a spontaneous structural transition, which suggests that the proton translocation stoichiometry may be one proton per functional rotation cycle. Furthermore, our simulations demonstrate that alternating the protonation states in the transmembrane domain induces functional rotation in the porter domain, which is primarily responsible for drug transport.

Event detection and sub-state discovery from biomolecular simulations using higher-order statistics: application to enzyme adenylate kinase.

PubMed

Ramanathan, Arvind; Savol, Andrej J; Agarwal, Pratul K; Chennubhotla, Chakra S

2012-11-01

Biomolecular simulations at millisecond and longer time-scales can provide vital insights into functional mechanisms. Because post-simulation analyses of such large trajectory datasets can be a limiting factor in obtaining biological insights, there is an emerging need to identify key dynamical events and relating these events to the biological function online, that is, as simulations are progressing. Recently, we have introduced a novel computational technique, quasi-anharmonic analysis (QAA) (Ramanathan et al., PLoS One 2011;6:e15827), for partitioning the conformational landscape into a hierarchy of functionally relevant sub-states. The unique capabilities of QAA are enabled by exploiting anharmonicity in the form of fourth-order statistics for characterizing atomic fluctuations. In this article, we extend QAA for analyzing long time-scale simulations online. In particular, we present HOST4MD--a higher-order statistical toolbox for molecular dynamics simulations, which (1) identifies key dynamical events as simulations are in progress, (2) explores potential sub-states, and (3) identifies conformational transitions that enable the protein to access those sub-states. We demonstrate HOST4MD on microsecond timescale simulations of the enzyme adenylate kinase in its apo state. HOST4MD identifies several conformational events in these simulations, revealing how the intrinsic coupling between the three subdomains (LID, CORE, and NMP) changes during the simulations. Further, it also identifies an inherent asymmetry in the opening/closing of the two binding sites. We anticipate that HOST4MD will provide a powerful and extensible framework for detecting biophysically relevant conformational coordinates from long time-scale simulations. Copyright © 2012 Wiley Periodicals, Inc.

Molecular dynamics simulation study reveals potential substrate entry path into γ-secretase/presenilin-1.

PubMed

Kong, Ren; Chang, Shan; Xia, Weiming; Wong, Stephen T C

2015-08-01

Presenilin 1 (PS1) is the catalytic unit of γ-secretase which cleaves more than one hundred substrates. Among them, amyloid precursor protein (APP) and Notch are notable for their pivotal role in the pathogenesis of Alzheimer's disease (AD) and certain types of cancer. The hydrolysis process occurring inside the hydrophobic lipid bilayer remains unclear. With the aim to understand the mechanism of intramembrane proteolysis by γ-secretase, we constructed a homology model of human PS1 and performed molecular dynamics simulation in explicit membrane phospholipids with different components. During the simulation, TM9 was found to exhibit a high level of flexibility that involved in "gate-open" movement of TM2 and TM6, and thus partially exposed the catalytic residues. The highly conserved PALP motif acts as an anchor to mediate the conformation changes of TM6 induced by TM9. Moreover, direct interactions were observed between 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) and the active site of γ-secretase, indicating that the lipid molecules have the potential to modulate γ-secretase by contacting with the catalytic residues, i.e., ASP 257 and ASP 385 of PS1. The intermediate states indicate a potential substrate penetration pathway through the interface of TM2 and TM6, which may be induced by changes of TM9. To our knowledge, this is the first molecular simulation study that reveals dynamic behavior of the human PS1 structure in the lipid bilayer and provides insight into the substrate entry path for subsequent intramembrane hydrolysis, which is critical information required for new strategy development of γ-secretase modulators to alleviate devastating AD. Copyright © 2015 Elsevier Inc. All rights reserved.

Computational Study on Full-length Human Ku70 with Double Stranded DNA: Dynamics, Interactions and Functional Implications

NASA Technical Reports Server (NTRS)

Hu, Shaowen; Cucinotta, Francis A.

2009-01-01

The Ku70/80 heterodimer is the first repair protein in the initial binding of double-strand break (DSB) ends following DNA damage, and is a component of nonhomologous end joining repair, the primary pathway for DSB repair in mammalian cells. In this study we constructed a full-length human Ku70 structure based on its crystal structure, and performed 20 ns conventional molecular dynamic (CMD) simulations on this protein and several other complexes with short DNA duplexes of different sequences. The trajectories of these simulations indicated that, without the topological support of Ku80, the residues in the bridge and C-terminal arm of Ku70 are more flexible than other experimentally identified domains. We studied the two missing loops in the crystal structure and predicted that they are also very flexible. Simulations revealed that they make an important contribution to the Ku70 interaction with DNA. Dislocation of the previously studied SAP domain was observed in several systems, implying its role in DNA binding. Targeted molecular dynamic (TMD) simulation was also performed for one system with a far-away 14bp DNA duplex. The TMD trajectory and energetic analysis disclosed detailed interactions of the DNA-binding residues during the DNA dislocation, and revealed a possible conformational transition for a DSB end when encountering Ku70 in solution. Compared to experimentally based analysis, this study identified more detailed interactions between DNA and Ku70. Free energy analysis indicated Ku70 alone is able to bind DNA with relatively high affinity, with consistent contributions from various domains of Ku70 in different systems. The functional implications of these domains in the processes of Ku heterodimerization and DNA damage recognition and repair can be characterized in detail based upon this analysis.

Detection of one-dimensional migration of single self-interstitial atoms in tungsten using high-voltage electron microscopy

PubMed Central

Amino, T.; Arakawa, K.; Mori, H.

2016-01-01

The dynamic behaviour of atomic-size disarrangements of atoms—point defects (self-interstitial atoms (SIAs) and vacancies)—often governs the macroscopic properties of crystalline materials. However, the dynamics of SIAs have not been fully uncovered because of their rapid migration. Using a combination of high-voltage transmission electron microscopy and exhaustive kinetic Monte Carlo simulations, we determine the dynamics of the rapidly migrating SIAs from the formation process of the nanoscale SIA clusters in tungsten as a typical body-centred cubic (BCC) structure metal under the constant-rate production of both types of point defects with high-energy electron irradiation, which must reflect the dynamics of individual SIAs. We reveal that the migration dimension of SIAs is not three-dimensional (3D) but one-dimensional (1D). This result overturns the long-standing and well-accepted view of SIAs in BCC metals and supports recent results obtained by ab-initio simulations. The SIA dynamics clarified here will be one of the key factors to accurately predict the lifetimes of nuclear fission and fusion materials. PMID:27185352

Infrared signatures of the peptide dynamical transition: A molecular dynamics simulation study

NASA Astrophysics Data System (ADS)

Kobus, Maja; Nguyen, Phuong H.; Stock, Gerhard

2010-07-01

Recent two-dimensional infrared (2D-IR) experiments on a short peptide 310-helix in chloroform solvent [E. H. G. Backus et al., J. Phys. Chem. B 113, 13405 (2009)] revealed an intriguing temperature dependence of the homogeneous line width, which was interpreted in terms of a dynamical transition of the peptide. To explain these findings, extensive molecular dynamics simulations at various temperatures were performed in order to construct the free energy landscape of the system. The study recovers the familiar picture of a glass-forming system, which below the glass transition temperature Tg is trapped in various energy basins, while it diffuses freely between these basins above Tg. In fact, one finds at Tg≈270 K a sharp rise of the fluctuations of the backbone dihedral angles, which reflects conformational transitions of the peptide. The corresponding CO frequency fluctuations are found to be a sensitive probe of the peptide conformational dynamics from femtosecond to nanosecond time scales and lead to 2D-IR spectra that qualitatively match the experiment. The calculated homogeneous line width, however, does not show the biphasic temperature dependence observed in experiment.

Dynamic behaviors of cavitation bubble for the steady cavitating flow

NASA Astrophysics Data System (ADS)

Cai, Jun; Huai, Xiulan; Li, Xunfeng

2009-12-01

In this paper, by introducing the flow velocity item into the classical Rayleigh-Plesset dynamic equation, a new equation, which does not involve the time term and can describe the motion of cavitation bubble in the steady cavitating flow, has been obtained. By solving the new motion equation using Runge-Kutta fourth order method with adaptive step size control, the dynamic behaviors of cavitation bubble driven by the varying pressure field downstream of a venturi cavitation reactor are numerically simulated. The effects of liquid temperature (corresponding to the saturated vapor pressure of liquid), cavitation number and inlet pressure of venturi on radial motion of bubble and pressure pulse due to the radial motion are analyzed and discussed in detail. Some dynamic behaviors of bubble different from those in previous papers are displayed. In addition, the internal relationship between bubble dynamics and process intensification is also discussed. The simulation results reported in this work reveal the variation laws of cavitation intensity with the flow conditions of liquid, and will lay a foundation for the practical application of hydrodynamic cavitation technology.

Structure and dynamics of human vimentin intermediate filament dimer and tetramer in explicit and implicit solvent models.

PubMed

Qin, Zhao; Buehler, Markus J

2011-01-01

Intermediate filaments, in addition to microtubules and microfilaments, are one of the three major components of the cytoskeleton in eukaryotic cells, and play an important role in mechanotransduction as well as in providing mechanical stability to cells at large stretch. The molecular structures, mechanical and dynamical properties of the intermediate filament basic building blocks, the dimer and the tetramer, however, have remained elusive due to persistent experimental challenges owing to the large size and fibrillar geometry of this protein. We have recently reported an atomistic-level model of the human vimentin dimer and tetramer, obtained through a bottom-up approach based on structural optimization via molecular simulation based on an implicit solvent model (Qin et al. in PLoS ONE 2009 4(10):e7294, 9). Here we present extensive simulations and structural analyses of the model based on ultra large-scale atomistic-level simulations in an explicit solvent model, with system sizes exceeding 500,000 atoms and simulations carried out at 20 ns time-scales. We report a detailed comparison of the structural and dynamical behavior of this large biomolecular model with implicit and explicit solvent models. Our simulations confirm the stability of the molecular model and provide insight into the dynamical properties of the dimer and tetramer. Specifically, our simulations reveal a heterogeneous distribution of the bending stiffness along the molecular axis with the formation of rather soft and highly flexible hinge-like regions defined by non-alpha-helical linker domains. We report a comparison of Ramachandran maps and the solvent accessible surface area between implicit and explicit solvent models, and compute the persistence length of the dimer and tetramer structure of vimentin intermediate filaments for various subdomains of the protein. Our simulations provide detailed insight into the dynamical properties of the vimentin dimer and tetramer intermediate filament building blocks, which may guide the development of novel coarse-grained models of intermediate filaments, and could also help in understanding assembly mechanisms.

Toward elucidating the heat activation mechanism of the TRPV1 channel gating by molecular dynamics simulation

PubMed Central

Wen, Han; Qin, Feng; Zheng, Wenjun

2016-01-01

As a key cellular sensor, the TRPV1 cation channel undergoes a gating transition from a closed state to an open state in response to various physical and chemical stimuli including noxious heat. Despite years of study, the heat activation mechanism of TRPV1 gating remains enigmatic at the molecular level. Toward elucidating the structural and energetic basis of TRPV1 gating, we have performed molecular dynamics (MD) simulations (with cumulative simulation time of 3 μs), starting from the high-resolution closed and open structures of TRPV1 solved by cryo-electron microscopy. In the closed-state simulations at 30°C, we observed a stably closed channel constricted at the lower gate (near residue I679), while the upper gate (near residues G643 and M644) is dynamic and undergoes flickery opening/closing. In the open-state simulations at 60°C, we found higher conformational variation consistent with a large entropy increase required for the heat activation, and both the lower and upper gates are dynamic with transient opening/closing. Through ensemble-based structural analyses of the closed state vs. the open state, we revealed pronounced closed-to-open conformational changes involving the membrane proximal domain (MPD) linker, the outer pore, and the TRP helix, which are accompanied by breaking/forming of a network of closed/open-state specific hydrogen bonds. By comparing the closed-state simulations at 30°C and 60°C, we observed heat-activated conformational changes in the MPD linker, the outer pore, and the TRP helix that resemble the closed-to-open conformational changes, along with partial formation of the open-state specific hydrogen bonds. Some of the residues involved in the above key hydrogen bonds were validated by previous mutational studies. Taken together, our MD simulations have offered rich structural and dynamic details beyond the static structures of TRPV1, and promising targets for future mutagenesis and functional studies of the TRPV1 channel. PMID:27699868

QAARM: quasi-anharmonic autoregressive model reveals molecular recognition pathways in ubiquitin

PubMed Central

Savol, Andrej J.; Burger, Virginia M.; Agarwal, Pratul K.; Ramanathan, Arvind; Chennubhotla, Chakra S.

2011-01-01

Motivation: Molecular dynamics (MD) simulations have dramatically improved the atomistic understanding of protein motions, energetics and function. These growing datasets have necessitated a corresponding emphasis on trajectory analysis methods for characterizing simulation data, particularly since functional protein motions and transitions are often rare and/or intricate events. Observing that such events give rise to long-tailed spatial distributions, we recently developed a higher-order statistics based dimensionality reduction method, called quasi-anharmonic analysis (QAA), for identifying biophysically-relevant reaction coordinates and substates within MD simulations. Further characterization of conformation space should consider the temporal dynamics specific to each identified substate. Results: Our model uses hierarchical clustering to learn energetically coherent substates and dynamic modes of motion from a 0.5 μs ubiqutin simulation. Autoregressive (AR) modeling within and between states enables a compact and generative description of the conformational landscape as it relates to functional transitions between binding poses. Lacking a predictive component, QAA is extended here within a general AR model appreciative of the trajectory's temporal dependencies and the specific, local dynamics accessible to a protein within identified energy wells. These metastable states and their transition rates are extracted within a QAA-derived subspace using hierarchical Markov clustering to provide parameter sets for the second-order AR model. We show the learned model can be extrapolated to synthesize trajectories of arbitrary length. Contact: ramanathana@ornl.gov; chakracs@pitt.edu PMID:21685101

Biological evaluation, docking and molecular dynamic simulation of some novel diaryl urea derivatives bearing quinoxalindione moiety

PubMed Central

Sadeghian-Rizi, Sedighe; Khodarahmi, Ghadamali Ali; Sakhteman, Amirhossein; Jahanian-Najafabadi, Ali; Rostami, Mahboubeh; Mirzaei, Mahmoud; Hassanzadeh, Farshid

2017-01-01

In this study a series of diarylurea derivatives containing quinoxalindione group were biologically evaluated for their cytotoxic activities using MTT assay against MCF-7 and HepG2 cell lines. Antibacterial activities of these compounds were also evaluated by Microplate Alamar Blue Assay (MABA) against three Gram-negative (Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi), three Gram-positive (Staphylococcus aureus, Bacillus subtilis and Listeria monocitogenes) and one yeast-like fungus (Candida albicans) strain. Furthermore, molecular docking was carried out to study the binding pattern of the compounds to the active site of B-RAF kinase (PDB code: 1UWH). Molecular dynamics simulation was performed on the best ligand (16e) to investigate the ligand binding dynamics in the physiological environment. Cytotoxic evaluation revealed the most prominent cytotoxicity for 6 compounds with IC50 values of 10-18 μM against two mentioned cell lines. None of the synthesized compounds showed significant antimicrobial activity. The obtained results of the molecular docking study showed that all compounds fitted in the binding site of enzyme with binding energy range of -11.22 to -12.69 kcal/mol vs sorafenib binding energy -11.74 kcal/mol as the lead compound. Molecular dynamic simulation indicated that the binding of ligand (16e) was stable in the active site of B-RAF during the simulation. PMID:29204178

Sequence selection by dynamical symmetry breaking in an autocatalytic binary polymer model

NASA Astrophysics Data System (ADS)

Fellermann, Harold; Tanaka, Shinpei; Rasmussen, Steen

2017-12-01

Template-directed replication of nucleic acids is at the essence of all living beings and a major milestone for any origin of life scenario. We present an idealized model of prebiotic sequence replication, where binary polymers act as templates for their autocatalytic replication, thereby serving as each others reactants and products in an intertwined molecular ecology. Our model demonstrates how autocatalysis alters the qualitative and quantitative system dynamics in counterintuitive ways. Most notably, numerical simulations reveal a very strong intrinsic selection mechanism that favors the appearance of a few population structures with highly ordered and repetitive sequence patterns when starting from a pool of monomers. We demonstrate both analytically and through simulation how this "selection of the dullest" is caused by continued symmetry breaking through random fluctuations in the transient dynamics that are amplified by autocatalysis and eventually propagate to the population level. The impact of these observations on related prebiotic mathematical models is discussed.

Free-energy landscape of a hyperstable RNA tetraloop.

PubMed

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

2016-06-14

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

Role of flexural stiffness of leukocyte microvilli in adhesion dynamics

NASA Astrophysics Data System (ADS)

Wu, Tai-Hsien; Qi, Dewei

2018-03-01

Previous work reported that microvillus deformation has an important influence on dynamics of cell adhesion. However, the existing studies were limited to the extensional deformation of microvilli and did not consider the effects of their bending deformation on cell adhesion. This Rapid Communication investigates the effects of flexural stiffness of microvilli on the rolling process related to adhesion of leukocytes by using a lattice-Boltzmann lattice-spring method (LLM) combined with adhesive dynamics (AD) simulations. The simulation results reveal that the flexural stiffness of microvilli and their bending deformation have a profound effect on rolling velocity and adhesive forces. As the flexural stiffness of the microvilli decreases, their bending angles increase, resulting in an increase in the number of receptor-ligand bonds and adhesive bonding force and a decrease in the rolling velocity of leukocytes. The effects of flexural stiffness on deformation and adhesion represent crucial factors involved in cell adhesion.

How Augmented Reality Enables Conceptual Understanding of Challenging Science Content

ERIC Educational Resources Information Center

Yoon, Susan; Anderson, Emma; Lin, Joyce; Elinich, Karen

2017-01-01

Research on learning about science has revealed that students often hold robust misconceptions about a number of scientific ideas. Digital simulation and dynamic visualization tools have helped to ameliorate these learning challenges by providing scaffolding to understand various aspects of the phenomenon. In this study we hypothesize that…

Welfare Reform when Recipients Are Forward-Looking

ERIC Educational Resources Information Center

Swann, Christopher A.

2005-01-01

By studying recipients of aid under the Temporary Assistance for Needy Families (TANF) welfare scheme, the effect of time limits of welfare schemes on forward looking recipients is assessed using a discrete-choice dynamic programming framework model. The policy simulations for the preferred specification of utility reveal that two year time limits…

Quantum Chemical Molecular Dynamics Simulations of 1,3-Dichloropropene Combustion.

PubMed

Ahubelem, Nwakamma; Shah, Kalpit; Moghtaderi, Behdad; Page, Alister J

2015-09-03

Oxidative decomposition of 1,3-dichloropropene was investigated using quantum chemical molecular dynamics (QM/MD) at 1500 and 3000 K. Thermal oxidation of 1,3-dichloropropene was initiated by (1) abstraction of allylic H/Cl by O2 and (2) intra-annular C-Cl bond scission and elimination of allylic Cl. A kinetic analysis shows that (2) is the more dominant initiation pathway, in agreement with QM/MD results. These QM/MD simulations reveal new routes to the formation of major products (H2O, CO, HCl, CO2), which are propagated primarily by the chloroperoxy (ClO2), OH, and 1,3-dichloropropene derived radicals. In particular, intra-annular C-C/C-H bond dissociation reactions of intermediate aldehydes/ketones are shown to play a dominant role in the formation of CO and CO2. Our simulations demonstrate that both combustion temperature and radical concentration can influence the product yield, however not the combustion mechanism.

The free-energy barrier to hydride transfer across a dipalladium complex

DOE PAGES

Ramirez-Cuesta, Anibal J.

2015-01-01

We use density-functional theory molecular dynamics (DFT-MD) simulations to determine the hydride transfer coordinate between palladium centres of the crystallographically observed terminal hydride locations, Pd-Pd-H, originally postulated for the solution dynamics of the complex bis-NHC dipalladium hydride [{(MesIm)(2)CH2}(2)Pd2H][PF6], and then calculate the free-energy along this coordinate. We estimate the transfer barrier-height to be about 20 kcal mol(-1) with a hydride transfer rate in the order of seconds at room temperature. We validate our DFT-MD modelling using inelastic neutron scattering which reveals anharmonicity of the hydride environment that is so pronounced that there is complete failure of the harmonic model formore » the hydride ligand. The simulations are extended to high temperature to bring the H-transfer to a rate that is accessible to the simulation technique.« less

Synthesis, QSAR, and Molecular Dynamics Simulation of Amidino-substituted Benzimidazoles as Dipeptidyl Peptidase III Inhibitors.

PubMed

Rastija, Vesna; Agić, Dejan; Tomiš, Sanja; Nikolič, Sonja; Hranjec, Marijana; Grace, Karminski-Zamola; Abramić, Marija

2015-01-01

A molecular modeling study is performed on series of benzimidazol-based inhibitors of human dipeptidyl peptidase III (DPP III). An eight novel compounds were synthesized in excellent yields using green chemistry approach. This study is aimed to elucidate the structural features of benzimidazole derivatives required for antagonism of human DPP III activity using Quantitative Structure-Activity Relationship (QSAR) analysis, and to understand the mechanism of one of the most potent inhibitor binding into the active site of this enzyme, by molecular dynamics (MD) simulations. The best model obtained includes S3K and RDF045m descriptors which have explained 89.4 % of inhibitory activity. Depicted moiety for strong inhibition activity matches to the structure of most potent compound. MD simulation has revealed importance of imidazolinyl and phenyl groups in the mechanism of binding into the active site of human DPP III.

Deciphering Cryptic Binding Sites on Proteins by Mixed-Solvent Molecular Dynamics.

PubMed

Kimura, S Roy; Hu, Hai Peng; Ruvinsky, Anatoly M; Sherman, Woody; Favia, Angelo D

2017-06-26

In recent years, molecular dynamics simulations of proteins in explicit mixed solvents have been applied to various problems in protein biophysics and drug discovery, including protein folding, protein surface characterization, fragment screening, allostery, and druggability assessment. In this study, we perform a systematic study on how mixtures of organic solvent probes in water can reveal cryptic ligand binding pockets that are not evident in crystal structures of apo proteins. We examine a diverse set of eight PDB proteins that show pocket opening induced by ligand binding and investigate whether solvent MD simulations on the apo structures can induce the binding site observed in the holo structures. The cosolvent simulations were found to induce conformational changes on the protein surface, which were characterized and compared with the holo structures. Analyses of the biological systems, choice of probes and concentrations, druggability of the resulting induced pockets, and application to drug discovery are discussed here.

Investigation of different modeling approaches for computational fluid dynamics simulation of high-pressure rocket combustors

NASA Astrophysics Data System (ADS)

Ivancic, B.; Riedmann, H.; Frey, M.; Knab, O.; Karl, S.; Hannemann, K.

2016-07-01

The paper summarizes technical results and first highlights of the cooperation between DLR and Airbus Defence and Space (DS) within the work package "CFD Modeling of Combustion Chamber Processes" conducted in the frame of the Propulsion 2020 Project. Within the addressed work package, DLR Göttingen and Airbus DS Ottobrunn have identified several test cases where adequate test data are available and which can be used for proper validation of the computational fluid dynamics (CFD) tools. In this paper, the first test case, the Penn State chamber (RCM1), is discussed. Presenting the simulation results from three different tools, it is shown that the test case can be computed properly with steady-state Reynolds-averaged Navier-Stokes (RANS) approaches. The achieved simulation results reproduce the measured wall heat flux as an important validation parameter very well but also reveal some inconsistencies in the test data which are addressed in this paper.

Membrane Compartmentalization Reducing the Mobility of Lipids and Proteins within a Model Plasma Membrane.

PubMed

Koldsø, Heidi; Reddy, Tyler; Fowler, Philip W; Duncan, Anna L; Sansom, Mark S P

2016-09-01

The cytoskeleton underlying cell membranes may influence the dynamic organization of proteins and lipids within the bilayer by immobilizing certain transmembrane (TM) proteins and forming corrals within the membrane. Here, we present coarse-grained resolution simulations of a biologically realistic membrane model of asymmetrically organized lipids and TM proteins. We determine the effects of a model of cytoskeletal immobilization of selected membrane proteins using long time scale coarse-grained molecular dynamics simulations. By introducing compartments with varying degrees of restraints within the membrane models, we are able to reveal how compartmentalization caused by cytoskeletal immobilization leads to reduced and anomalous diffusional mobility of both proteins and lipids. This in turn results in a reduced rate of protein dimerization within the membrane and of hopping of membrane proteins between compartments. These simulations provide a molecular realization of hierarchical models often invoked to explain single-molecule imaging studies of membrane proteins.

Internal force corrections with machine learning for quantum mechanics/molecular mechanics simulations.

PubMed

Wu, Jingheng; Shen, Lin; Yang, Weitao

2017-10-28

Ab initio quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulation is a useful tool to calculate thermodynamic properties such as potential of mean force for chemical reactions but intensely time consuming. In this paper, we developed a new method using the internal force correction for low-level semiempirical QM/MM molecular dynamics samplings with a predefined reaction coordinate. As a correction term, the internal force was predicted with a machine learning scheme, which provides a sophisticated force field, and added to the atomic forces on the reaction coordinate related atoms at each integration step. We applied this method to two reactions in aqueous solution and reproduced potentials of mean force at the ab initio QM/MM level. The saving in computational cost is about 2 orders of magnitude. The present work reveals great potentials for machine learning in QM/MM simulations to study complex chemical processes.

Mutated form (G52E) of inactive diphtheria toxin CRM197: molecular simulations clearly display effect of the mutation to NAD binding.

PubMed

Salmas, Ramin Ekhteiari; Mestanoglu, Mert; Unlu, Ayhan; Yurtsever, Mine; Durdagi, Serdar

2016-11-01

Mutated form (G52E) of diphtheria toxin (DT) CRM197 is an inactive and nontoxic enzyme. Here, we provided a molecular insight using comparative molecular dynamics (MD) simulations to clarify the influence of a single point mutation on overall protein and active-site loop. Post-processing MD analysis (i.e. stability, principal component analysis, hydrogen-bond occupancy, etc.) is carried out on both wild and mutated targets to investigate and to better understand the mechanistic differences of structural and dynamical properties on an atomic scale especially at nicotinamide adenine dinucleotide (NAD) binding site when a single mutation (G52E) happens at the DT. In addition, a docking simulation is performed for wild and mutated forms. The docking scoring analysis and docking poses results revealed that mutant form is not able to properly accommodate the NAD molecule.

Molecular dynamics simulation of premelting and melting phase transitions in stoichiometric uranium dioxide

NASA Astrophysics Data System (ADS)

Yakub, Eugene; Ronchi, Claudio; Staicu, Dragos

2007-09-01

Results of molecular dynamics (MD) simulation of UO2 in a wide temperature range are presented and discussed. A new approach to the calibration of a partly ionic Busing-Ida-type model is proposed. A potential parameter set is obtained reproducing the experimental density of solid UO2 in a wide range of temperatures. A conventional simulation of the high-temperature stoichiometric UO2 on large MD cells, based on a novel fast method of computation of Coulomb forces, reveals characteristic features of a premelting λ transition at a temperature near to that experimentally observed (Tλ=2670K ). A strong deviation from the Arrhenius behavior of the oxygen self-diffusion coefficient was found in the vicinity of the transition point. Predictions for liquid UO2, based on the same potential parameter set, are in good agreement with existing experimental data and theoretical calculations.

Unraveling the Geometry Dependence of In-Nozzle Cavitation in High-Pressure Injectors

PubMed Central

Im, Kyoung-Su; Cheong, Seong-Kyun; Powell, Christopher F.; Lai, Ming-chia D.; Wang, Jin

2013-01-01

Cavitation is an intricate multiphase phenomenon that interplays with turbulence in fluid flows. It exhibits clear duality in characteristics, being both destructive and beneficial in our daily lives and industrial processes. Despite the multitude of occurrences of this phenomenon, highly dynamic and multiphase cavitating flows have not been fundamentally well understood in guiding the effort to harness the transient and localized power generated by this process. In a microscale, multiphase flow liquid injection system, we synergistically combined experiments using time-resolved x-radiography and a novel simulation method to reveal the relationship between the injector geometry and the in-nozzle cavitation quantitatively. We demonstrate that a slight alteration of the geometry on the micrometer scale can induce distinct laminar-like or cavitating flows, validating the multiphase computational fluid dynamics simulation. Furthermore, the simulation identifies a critical geometric parameter with which the high-speed flow undergoes an intriguing transition from non-cavitating to cavitating. PMID:23797665

Loop-driven conformational transition between the alternative and collapsed form of prethrombin-2: targeted molecular dynamics study.

PubMed

Wu, Sangwook

2017-01-01

Two distinct crystal structures of prethrombin-2, the alternative and collapsed forms, are elucidated by X-ray crystallogrphy. We analyzed the conformational transition from the alternative to the collapsed form employing targeted molecular dynamics (TMD) simulation. Despite small RMSD difference in the two X-ray crystal structures, some hydrophobic residues (W60d, W148, W215, and F227) show a significant difference between the two conformations. TMD simulation shows that the four hydrophobic residues undergo concerted movement from dimer to trimer transition via tetramer state in the conformational change from the alternative to the collapsed form. We reveal that the concerted movement of the four hydrophobic residues is controlled by movement of specific loop regions behind. In this paper, we propose a sequential scenario for the conformational transition from the alternative form to the collapsed form, which is partially supported by the mutant W148A simulation.

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.

MD simulation of the Tat/Cyclin T1/CDK9 complex revealing the hidden catalytic cavity within the CDK9 molecule upon Tat binding.

PubMed

Asamitsu, Kaori; Hirokawa, Takatsugu; Okamoto, Takashi

2017-01-01

In this study, we applied molecular dynamics (MD) simulation to analyze the dynamic behavior of the Tat/CycT1/CDK9 tri-molecular complex and revealed the structural changes of P-TEFb upon Tat binding. We found that Tat could deliberately change the local flexibility of CycT1. Although the structural coordinates of the H1 and H2 helices did not substantially change, H1', H2', and H3' exhibited significant changes en masse. Consequently, the CycT1 residues involved in Tat binding, namely Tat-recognition residues (TRRs), lost their flexibility with the addition of Tat to P-TEFb. In addition, we clarified the structural variation of CDK9 in complex with CycT1 in the presence or absence of Tat. Interestingly, Tat addition significantly reduced the structural variability of the T-loop, thus consolidating the structural integrity of P-TEFb. Finally, we deciphered the formation of the hidden catalytic cavity of CDK9 upon Tat binding. MD simulation revealed that the PITALRE signature sequence of CDK9 flips the inactive kinase cavity of CDK9 into the active form by connecting with Thr186, which is crucial for its activity, thus presumably recruiting the substrate peptide such as the C-terminal domain of RNA pol II. These findings provide vital information for the development of effective novel anti-HIV drugs with CDK9 catalytic activity as the target.

Simulation of weak polyelectrolytes: a comparison between the constant pH and the reaction ensemble method

NASA Astrophysics Data System (ADS)

Landsgesell, Jonas; Holm, Christian; Smiatek, Jens

2017-03-01

The reaction ensemble and the constant pH method are well-known chemical equilibrium approaches to simulate protonation and deprotonation reactions in classical molecular dynamics and Monte Carlo simulations. In this article, we demonstrate the similarity between both methods under certain conditions. We perform molecular dynamics simulations of a weak polyelectrolyte in order to compare the titration curves obtained by both approaches. Our findings reveal a good agreement between the methods when the reaction ensemble is used to sweep the reaction constant. Pronounced differences between the reaction ensemble and the constant pH method can be observed for stronger acids and bases in terms of adaptive pH values. These deviations are due to the presence of explicit protons in the reaction ensemble method which induce a screening of electrostatic interactions between the charged titrable groups of the polyelectrolyte. The outcomes of our simulation hint to a better applicability of the reaction ensemble method for systems in confined geometries and titrable groups in polyelectrolytes with different pKa values.

Spontaneous quaternary and tertiary T-R transitions of human hemoglobin in molecular dynamics simulation.

PubMed

Hub, Jochen S; Kubitzki, Marcus B; de Groot, Bert L

2010-05-06

We present molecular dynamics simulations of unliganded human hemoglobin (Hb) A under physiological conditions, starting from the R, R2, and T state. The simulations were carried out with protonated and deprotonated HC3 histidines His(beta)146, and they sum up to a total length of 5.6 micros. We observe spontaneous and reproducible T-->R quaternary transitions of the Hb tetramer and tertiary transitions of the alpha and beta subunits, as detected from principal component projections, from an RMSD measure, and from rigid body rotation analysis. The simulations reveal a marked asymmetry between the alpha and beta subunits. Using the mutual information as correlation measure, we find that the beta subunits are substantially more strongly linked to the quaternary transition than the alpha subunits. In addition, the tertiary populations of the alpha and beta subunits differ substantially, with the beta subunits showing a tendency towards R, and the alpha subunits showing a tendency towards T. Based on the simulation results, we present a transition pathway for coupled quaternary and tertiary transitions between the R and T conformations of Hb.

Spontaneous Quaternary and Tertiary T-R Transitions of Human Hemoglobin in Molecular Dynamics Simulation

PubMed Central

de Groot, Bert L.

2010-01-01

We present molecular dynamics simulations of unliganded human hemoglobin (Hb) A under physiological conditions, starting from the R, R2, and T state. The simulations were carried out with protonated and deprotonated HC3 histidines His(β)146, and they sum up to a total length of 5.6µs. We observe spontaneous and reproducible T→R quaternary transitions of the Hb tetramer and tertiary transitions of the α and β subunits, as detected from principal component projections, from an RMSD measure, and from rigid body rotation analysis. The simulations reveal a marked asymmetry between the α and β subunits. Using the mutual information as correlation measure, we find that the β subunits are substantially more strongly linked to the quaternary transition than the α subunits. In addition, the tertiary populations of the α and β subunits differ substantially, with the β subunits showing a tendency towards R, and the α subunits showing a tendency towards T. Based on the simulation results, we present a transition pathway for coupled quaternary and tertiary transitions between the R and T conformations of Hb. PMID:20463873

Using Wavelet Analysis To Assist in Identification of Significant Events in Molecular Dynamics Simulations.

PubMed

Heidari, Zahra; Roe, Daniel R; Galindo-Murillo, Rodrigo; Ghasemi, Jahan B; Cheatham, Thomas E

2016-07-25

Long time scale molecular dynamics (MD) simulations of biological systems are becoming increasingly commonplace due to the availability of both large-scale computational resources and significant advances in the underlying simulation methodologies. Therefore, it is useful to investigate and develop data mining and analysis techniques to quickly and efficiently extract the biologically relevant information from the incredible amount of generated data. Wavelet analysis (WA) is a technique that can quickly reveal significant motions during an MD simulation. Here, the application of WA on well-converged long time scale (tens of μs) simulations of a DNA helix is described. We show how WA combined with a simple clustering method can be used to identify both the physical and temporal locations of events with significant motion in MD trajectories. We also show that WA can not only distinguish and quantify the locations and time scales of significant motions, but by changing the maximum time scale of WA a more complete characterization of these motions can be obtained. This allows motions of different time scales to be identified or ignored as desired.

Investigations of Takeout proteins' ligand binding and release mechanism using molecular dynamics simulation.

PubMed

Zhang, Huijing; Yu, Hui; Zhao, Xi; Liu, Xiaoguang; Feng, Xianli; Huang, Xuri

2017-05-01

Takeout (To) proteins exist in a diverse range of insect species. They are involved in many important processes of insect physiology and behaviors. As the ligand carriers, To proteins can transport the small molecule to the target tissues. However, ligand release mechanism of To proteins is unclear so far. In this contribution, the process and pathway of the ligand binding and release are revealed by conventional molecular dynamics simulation, steered molecular dynamics simulation and umbrella sampling methods. Our results show that the α4-side of the protein is the unique gate for the ligand binding and release. The structural analysis confirms that the internal cavity of the protein has high rigidity, which is in accordance with the recent experimental results. By using the potential of mean force calculations in combination with residue cross correlation calculation, we concluded that the binding between the ligand and To proteins is a process of conformational selection. Furthermore, the conformational changes of To proteins and the hydrophobic interactions both are the key factors for ligand binding and release.

Femtosecond excitation tuning and site energy memory of population transfer in poly(p-phenylenevinylene): Gated luminescence experiments and simulation

NASA Astrophysics Data System (ADS)

Sperling, J.; Milota, F.; Tortschanoff, A.; Warmuth, Ch.; Mollay, B.; Bässler, H.; Kauffmann, H. F.

2002-12-01

We present a comprehensive experimental and computational study on fs-relaxational dynamics of optical excitations in the conjugated polymer poly(p-phenylenevinylene) (PPV) under selective excitation tuning conditions into the long-wavelength, low-vibrational S1ν=0-density-of-states (DOS). The dependence of single-wavelength luminescence kinetics and time-windowed spectral transients on distinct, initial excitation boundaries at 1.4 K and at room temperature was measured applying the luminescence up-conversion technique. The typical energy-dispersive intra-DOS energy transfer was simulated by a combination of static Monte Carlo method with a dynamical algorithm for solving the energy-space transport Master-Equation in population-space. For various, selective excitations that give rise to specific S1-population distributions in distinct spatial and energetic subspaces inside the DOS, simulations confirm the experimental results and show that the subsequent, energy-dissipative, multilevel relaxation is hierarchically constrained, and reveals a pronounced site-energy memory effect with a migration-threshold, characteristic of the (dressed) excitation dynamics in the disordered PPV many-body system.

Dynamic calibration and analysis of crack tip propagation in energetic materials using real-time radiography

NASA Astrophysics Data System (ADS)

Butt, Ali

Crack propagation in a solid rocket motor environment is difficult to measure directly. This experimental and analytical study evaluated the viability of real-time radiography for detecting bore regression and propellant crack propagation speed. The scope included the quantitative interpretation of crack tip velocity from simulated radiographic images of a burning, center-perforated grain and actual real-time radiographs taken on a rapid-prototyped model that dynamically produced the surface movements modeled in the simulation. The simplified motor simulation portrayed a bore crack that propagated radially at a speed that was 10 times the burning rate of the bore. Comparing the experimental image interpretation with the calibrated surface inputs, measurement accuracies were quantified. The average measurements of the bore radius were within 3% of the calibrated values with a maximum error of 7%. The crack tip speed could be characterized with image processing algorithms, but not with the dynamic calibration data. The laboratory data revealed that noise in the transmitted X-Ray intensity makes sensing the crack tip propagation using changes in the centerline transmitted intensity level impractical using the algorithms employed.

The dynamics of aloof baby Skyrmions

DOE PAGES

Salmi, Petja; Sutcliffe, Paul

2016-01-25

The aloof baby Skyrme model is a (2+1)-dimensional theory with solitons that are lightly bound. It is a low-dimensional analogue of a similar Skyrme model in (3+1)- dimensions, where the lightly bound solitons have binding energies comparable to nuclei. A previous study of static solitons in the aloof baby Skyrme model revealed that multi-soliton bound states have a cluster structure, with constituents that preserve their individual identities due to the short-range repulsion and long-range attraction between solitons. Furthermore, there are many different local energy minima that are all well-described by a simple binary species particle model. In this paper wemore » present the first results on soliton dynamics in the aloof baby Skyrme model. Numerical field theory simulations reveal that the lightly bound cluster structure results in a variety of exotic soliton scattering events that are novel in comparison to standard Skyrmion scattering. A dynamical version of the binary species point particle model is shown to provide a good qualitative description of the dynamics.« less

The dynamics of aloof baby Skyrmions

NASA Astrophysics Data System (ADS)

Salmi, Petja; Sutcliffe, Paul

2016-01-01

The aloof baby Skyrme model is a (2+1)-dimensional theory with solitons that are lightly bound. It is a low-dimensional analogue of a similar Skyrme model in (3+1)-dimensions, where the lightly bound solitons have binding energies comparable to nuclei. A previous study of static solitons in the aloof baby Skyrme model revealed that multi-soliton bound states have a cluster structure, with constituents that preserve their individual identities due to the short-range repulsion and long-range attraction between solitons. Furthermore, there are many different local energy minima that are all well-described by a simple binary species particle model. In this paper we present the first results on soliton dynamics in the aloof baby Skyrme model. Numerical field theory simulations reveal that the lightly bound cluster structure results in a variety of exotic soliton scattering events that are novel in comparison to standard Skyrmion scattering. A dynamical version of the binary species point particle model is shown to provide a good qualitative description of the dynamics.

Snapshot of the equilibrium dynamics of a drug bound to HIV-1 reverse transcriptase

NASA Astrophysics Data System (ADS)

Kuroda, Daniel G.; Bauman, Joseph D.; Challa, J. Reddy; Patel, Disha; Troxler, Thomas; Das, Kalyan; Arnold, Eddy; Hochstrasser, Robin M.

2013-03-01

The anti-AIDS drug rilpivirine undergoes conformational changes to bind HIV-1 reverse transcriptase (RT), which is an essential enzyme for the replication of HIV. These changes allow it to retain potency against mutations that otherwise would render the enzyme resistant. Here we report that water molecules play an essential role in this binding process. Femtosecond experiments and theory expose the molecular level dynamics of rilpivirine bound to HIV-1 RT. Two nitrile substituents, one on each arm of the drug, are used as vibrational probes of the structural dynamics within the binding pocket. Two-dimensional vibrational echo spectroscopy reveals that one nitrile group is unexpectedly hydrogen-bonded to a mobile water molecule, not identified in previous X-ray structures. Ultrafast nitrile-water dynamics are confirmed by simulations. A higher (1.51 Å) resolution X-ray structure also reveals a water-drug interaction network. Maintenance of a crucial anchoring hydrogen bond may help retain the potency of rilpivirine against pocket mutations despite the structural variations they cause.

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

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.

Single polymer dynamics under large amplitude oscillatory extension

NASA Astrophysics Data System (ADS)

Zhou, Yuecheng; Schroeder, Charles M.

2016-09-01

Understanding the conformational dynamics of polymers in time-dependent flows is of key importance for controlling materials properties during processing. Despite this importance, however, it has been challenging to study polymer dynamics in controlled time-dependent or oscillatory extensional flows. In this work, we study the dynamics of single polymers in large-amplitude oscillatory extension (LAOE) using a combination of experiments and Brownian dynamics (BD) simulations. Two-dimensional LAOE flow is generated using a feedback-controlled stagnation point device known as the Stokes trap, thereby generating an oscillatory planar extensional flow with alternating principal axes of extension and compression. Our results show that polymers experience periodic cycles of compression, reorientation, and extension in LAOE, and dynamics are generally governed by a dimensionless flow strength (Weissenberg number Wi) and dimensionless frequency (Deborah number De). Single molecule experiments are compared to BD simulations with and without intramolecular hydrodynamic interactions (HI) and excluded volume (EV) interactions, and good agreement is obtained across a range of parameters. Moreover, transient bulk stress in LAOE is determined from simulations using the Kramers relation, which reveals interesting and unique rheological signatures for this time-dependent flow. We further construct a series of single polymer stretch-flow rate curves (defined as single molecule Lissajous curves) as a function of Wi and De, and we observe qualitatively different dynamic signatures (butterfly, bow tie, arch, and line shapes) across the two-dimensional Pipkin space defined by Wi and De. Finally, polymer dynamics spanning from the linear to nonlinear response regimes are interpreted in the context of accumulated fluid strain in LAOE.

Decrypting the structural, dynamic, and energetic basis of a monomeric kinesin interacting with a tubulin dimer in three ATPase states by all-atom molecular dynamics simulation.

PubMed

Chakraborty, Srirupa; Zheng, Wenjun

2015-01-27

We have employed molecular dynamics (MD) simulation to investigate, with atomic details, the structural dynamics and energetics of three major ATPase states (ADP, APO, and ATP state) of a human kinesin-1 monomer in complex with a tubulin dimer. Starting from a recently solved crystal structure of ATP-like kinesin-tubulin complex by the Knossow lab, we have used flexible fitting of cryo-electron-microscopy maps to construct new structural models of the kinesin-tubulin complex in APO and ATP state, and then conducted extensive MD simulations (total 400 ns for each state), followed by flexibility analysis, principal component analysis, hydrogen bond analysis, and binding free energy analysis. Our modeling and simulation have revealed key nucleotide-dependent changes in the structure and flexibility of the nucleotide-binding pocket (featuring a highly flexible and open switch I in APO state) and the tubulin-binding site, and allosterically coupled motions driving the APO to ATP transition. In addition, our binding free energy analysis has identified a set of key residues involved in kinesin-tubulin binding. On the basis of our simulation, we have attempted to address several outstanding issues in kinesin study, including the possible roles of β-sheet twist and neck linker docking in regulating nucleotide release and binding, the structural mechanism of ADP release, and possible extension and shortening of α4 helix during the ATPase cycle. This study has provided a comprehensive structural and dynamic picture of kinesin's major ATPase states, and offered promising targets for future mutational and functional studies to investigate the molecular mechanism of kinesin motors.

Principal component and normal mode analysis of proteins; a quantitative comparison using the GroEL subunit.

PubMed

Skjaerven, Lars; Martinez, Aurora; Reuter, Nathalie

2011-01-01

Principal component analysis (PCA) and normal mode analysis (NMA) have emerged as two invaluable tools for studying conformational changes in proteins. To compare these approaches for studying protein dynamics, we have used a subunit of the GroEL chaperone, whose dynamics is well characterized. We first show that both PCA on trajectories from molecular dynamics (MD) simulations and NMA reveal a general dynamical behavior in agreement with what has previously been described for GroEL. We thus compare the reproducibility of PCA on independent MD runs and subsequently investigate the influence of the length of the MD simulations. We show that there is a relatively poor one-to-one correspondence between eigenvectors obtained from two independent runs and conclude that caution should be taken when analyzing principal components individually. We also observe that increasing the simulation length does not improve the agreement with the experimental structural difference. In fact, relatively short MD simulations are sufficient for this purpose. We observe a rapid convergence of the eigenvectors (after ca. 6 ns). Although there is not always a clear one-to-one correspondence, there is a qualitatively good agreement between the movements described by the first five modes obtained with the three different approaches; PCA, all-atoms NMA, and coarse-grained NMA. It is particularly interesting to relate this to the computational cost of the three methods. The results we obtain on the GroEL subunit contribute to the generalization of robust and reproducible strategies for the study of protein dynamics, using either NMA or PCA of trajectories from MD simulations. © 2010 Wiley-Liss, Inc.

Hierarchy of forward-backward stochastic Schrödinger equation

NASA Astrophysics Data System (ADS)

Ke, Yaling; Zhao, Yi

2016-07-01

Driven by the impetus to simulate quantum dynamics in photosynthetic complexes or even larger molecular aggregates, we have established a hierarchy of forward-backward stochastic Schrödinger equation in the light of stochastic unravelling of the symmetric part of the influence functional in the path-integral formalism of reduced density operator. The method is numerically exact and is suited for Debye-Drude spectral density, Ohmic spectral density with an algebraic or exponential cutoff, as well as discrete vibrational modes. The power of this method is verified by performing the calculations of time-dependent population differences in the valuable spin-boson model from zero to high temperatures. By simulating excitation energy transfer dynamics of the realistic full FMO trimer, some important features are revealed.

Nonlinear Dust Acoustic Waves in a Magnetized Dusty Plasma with Trapped and Superthermal Electrons

NASA Astrophysics Data System (ADS)

Ahmadi, Abrishami S.; Nouri, Kadijani M.

2014-06-01

In this work, the effects of superthermal and trapped electrons on the oblique propagation of nonlinear dust-acoustic waves in a magnetized dusty (complex) plasma are investigated. The dynamic of electrons is simulated by the generalized Lorentzian (κ) distribution function (DF). The dust grains are cold and their dynamics are simulated by hydrodynamic equations. Using the standard reductive perturbation technique (RPT) a nonlinear modified Korteweg-de Vries (mKdV) equation is derived. Two types of solitary waves; fast and slow dust acoustic solitons, exist in this plasma. Calculations reveal that compressive solitary structures are likely to propagate in this plasma where dust grains are negatively (or positively) charged. The properties of dust acoustic solitons (DASs) are also investigated numerically.

Development of a Higher Fidelity Model for the Cascade Distillation Subsystem (CDS)

NASA Technical Reports Server (NTRS)

Perry, Bruce; Anderson, Molly

2014-01-01

Significant improvements have been made to the ACM model of the CDS, enabling accurate predictions of dynamic operations with fewer assumptions. The model has been utilized to predict how CDS performance would be impacted by changing operating parameters, revealing performance trade-offs and possibilities for improvement. CDS efficiency is driven by the THP coefficient of performance, which in turn is dependent on heat transfer within the system. Based on the remaining limitations of the simulation, priorities for further model development include: center dot Relaxing the assumption of total condensation center dot Incorporating dynamic simulation capability for the buildup of dissolved inert gasses in condensers center dot Examining CDS operation with more complex feeds center dot Extending heat transfer analysis to all surfaces

Dynamic transition in the structure of an energetic crystal during chemical reactions at shock front prior to detonation.

PubMed

Nomura, Ken-Ichi; Kalia, Rajiv K; Nakano, Aiichiro; Vashishta, Priya; van Duin, Adri C T; Goddard, William A

2007-10-05

Mechanical stimuli in energetic materials initiate chemical reactions at shock fronts prior to detonation. Shock sensitivity measurements provide widely varying results, and quantum-mechanical calculations are unable to handle systems large enough to describe shock structure. Recent developments in reactive force-field molecular dynamics (ReaxFF-MD) combined with advances in parallel computing have paved the way to accurately simulate reaction pathways along with the structure of shock fronts. Our multimillion-atom ReaxFF-MD simulations of l,3,5-trinitro-l,3,5-triazine (RDX) reveal that detonation is preceded by a transition from a diffuse shock front with well-ordered molecular dipoles behind it to a disordered dipole distribution behind a sharp front.

Lipoxygenase directed anti-inflammatory and anti-cancerous secondary metabolites: ADMET-based screening, molecular docking and dynamics simulation.

PubMed

Singh, Swati; Awasthi, Manika; Pandey, Veda P; Dwivedi, Upendra N

2017-02-01

Lipoxygenases (LOXs), key enzymes involved in the biosynthesis of leukotrienes, are well known to participate in the inflammatory and immune responses. With the recent reports of involvement of 5-LOX (one of the isozymes of LOX in human) in cancer, there is a need to find out selective inhibitors of 5-LOX for their therapeutic application. In the present study, plant-derived 300 anti-inflammatory and anti-cancerous secondary metabolites (100 each of alkaloids, flavonoids and terpenoids) have been screened for their pharmacokinetic properties and subsequently docked for identification of potent inhibitors of 5-LOX. Pharmacokinetic analyses revealed that only 18 alkaloids, 26 flavonoids, and 9 terpenoids were found to fulfill all the absorption, distribution, metabolism, excretion, and toxicity descriptors as well as those of Lipinski's Rule of Five. Docking analyses of pharmacokinetically screened metabolites and their comparison with a known inhibitor (drug), namely zileuton revealed that only three alkaloids, six flavonoids and three terpenoids were found to dock successfully with 5-LOX with the flavonoid, velutin being the most potent inhibitor among all. The results of the docking analyses were further validated by performing molecular dynamics simulation and binding energy calculations for the complexes of 5-LOX with velutin, galangin, chrysin (in order of LibDock scores), and zileuton. The data revealed stabilization of all the complexes within 15 ns of simulation with velutin complex exhibiting least root-mean-square deviation value (.285 ± .007 nm) as well as least binding energy (ΔG bind  = -203.169 kJ/mol) as compared to others during the stabilization phase of simulation.

Matters of simulation of the semicircular canal system

NASA Technical Reports Server (NTRS)

Gurfinkel, V. S.; Petukhov, S. V.

1977-01-01

A scale model of the human semicircular canal system was developed based on the theory of dynamic similitude. This enlarged model makes it convenient to conduct tests on the vestibular processes and dynamics in the semicircular canals. Tests revealed hydromechanical interaction between canals, with asymmetry of the conditions of movement of the endolymph in the canals in opposite directions. A type of vestibular reactions, occurring with angular oscillations of the head, was predicted and demonstrated using this model and human test subjects.

Dynamic microscale temperature gradient in a gold nanorod solution measured by diffraction-limited nanothermometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Chengmingyue; Gan, Xiaosong; Li, Xiangping

2015-09-21

We quantify the dynamic microscale temperature gradient in a gold nanorod solution using quantum-dot-based microscopic fluorescence nanothermometry. By incorporating CdSe quantum dots into the solution as a nanothermometer, precise temperature mapping with diffraction-limited spatial resolution and sub-degree temperature resolution is achieved. The acquired data on heat generation and dissipation show an excellent agreement with theoretical simulations. This work reveals an effective approach for noninvasive temperature regulation with localized nanoheaters in microfluidic environment.

Spatiotemporal Dynamics of a Network of Coupled Time-Delay Digital Tanlock Loops

NASA Astrophysics Data System (ADS)

Paul, Bishwajit; Banerjee, Tanmoy; Sarkar, B. C.

The time-delay digital tanlock loop (TDTLs) is an important class of phase-locked loop that is widely used in electronic communication systems. Although nonlinear dynamics of an isolated TDTL has been studied in the past but the collective behavior of TDTLs in a network is an important topic of research and deserves special attention as in practical communication systems separate entities are rarely isolated. In this paper, we carry out the detailed analysis and numerical simulations to explore the spatiotemporal dynamics of a network of a one-dimensional ring of coupled TDTLs with nearest neighbor coupling. The equation representing the network is derived and we carry out analytical calculations using the circulant matrix formalism to obtain the stability criteria. An extensive numerical simulation reveals that with the variation of gain parameter and coupling strength the network shows a variety of spatiotemporal dynamics such as frozen random pattern, pattern selection, spatiotemporal intermittency and fully developed spatiotemporal chaos. We map the distinct dynamical regions of the system in two-parameter space. Finally, we quantify the spatiotemporal dynamics by using quantitative measures like Lyapunov exponent and the average quadratic deviation of the full network.

2D-HB-Network at the air-water interface: A structural and dynamical characterization by means of ab initio and classical molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Pezzotti, Simone; Serva, Alessandra; Gaigeot, Marie-Pierre

2018-05-01

Following our previous work where the existence of a special 2-Dimensional H-Bond (2D-HB)-Network was revealed at the air-water interface [S. Pezzotti et al., J. Phys. Chem. Lett. 8, 3133 (2017)], we provide here a full structural and dynamical characterization of this specific arrangement by means of both Density Functional Theory based and Force Field based molecular dynamics simulations. We show in particular that water at the interface with air reconstructs to maximize H-Bonds formed between interfacial molecules, which leads to the formation of an extended and non-interrupted 2-Dimensional H-Bond structure involving on average ˜90% of water molecules at the interface. We also show that the existence of such an extended structure, composed of H-Bonds all oriented parallel to the surface, constrains the reorientional dynamics of water that is hence slower at the interface than in the bulk. The structure and dynamics of the 2D-HB-Network provide new elements to possibly rationalize several specific properties of the air-water interface, such as water surface tension, anisotropic reorientation of interfacial water under an external field, and proton hopping.

Synchronisation and Circuit Realisation of Chaotic Hartley System

NASA Astrophysics Data System (ADS)

Varan, Metin; Akgül, Akif; Güleryüz, Emre; Serbest, Kasım

2018-06-01

Hartley chaotic system is topologically the simplest, but its dynamical behaviours are very rich and its synchronisation has not been seen in literature. This paper aims to introduce a simple chaotic system which can be used as alternative to classical chaotic systems in synchronisation fields. Time series, phase portraits, and bifurcation diagrams reveal the dynamics of the mentioned system. Chaotic Hartley model is also supported with electronic circuit model simulations. Its exponential dynamics are hard to realise on circuit model; this paper is the first in literature that handles such a complex modelling problem. Modelling, synchronisation, and circuit realisation of the Hartley system are implemented respectively in MATLAB-Simulink and ORCAD environments. The effectiveness of the applied synchronisation method is revealed via numerical methods, and the results are discussed. Retrieved results show that this complex chaotic system can be used in secure communication fields.

Orientation influence on grain size-effects in ultrafine-grained magnesium

DOE PAGES

Fan, Haidong; Aubry, Sylvie; Arsenlis, A.; ...

2014-11-08

The mechanical behavior of ultrafine-grained magnesium was studied by discrete dislocation dynamics (DDD) simulations. Our results show basal slip yields a strong size effect, while prismatic and pyramidal slips produce a weak one. We developed a new size-strength model that considers dislocation transmission across grain boundaries. Good agreement between this model, current DDD simulations and previous experiments is observed. These results reveal that the grain size effect depends on 3 factors: Peierls stress, dislocation source strength and grain boundary strength.

CRISPR-Cas9 conformational activation as elucidated from enhanced molecular simulations

PubMed Central

Miao, Yinglong; Walker, Ross C.; Jinek, Martin; McCammon, J. Andrew

2017-01-01

CRISPR-Cas9 has become a facile genome editing technology, yet the structural and mechanistic features underlying its function are unclear. Here, we perform extensive molecular simulations in an enhanced sampling regime, using a Gaussian-accelerated molecular dynamics (GaMD) methodology, which probes displacements over hundreds of microseconds to milliseconds, to reveal the conformational dynamics of the endonuclease Cas9 during its activation toward catalysis. We disclose the conformational transition of Cas9 from its apo form to the RNA-bound form, suggesting a mechanism for RNA recruitment in which the domain relocations cause the formation of a positively charged cavity for nucleic acid binding. GaMD also reveals the conformation of a catalytically competent Cas9, which is prone for catalysis and whose experimental characterization is still limited. We show that, upon DNA binding, the conformational dynamics of the HNH domain triggers the formation of the active state, explaining how the HNH domain exerts a conformational control domain over DNA cleavage [Sternberg SH et al. (2015) Nature, 527, 110–113]. These results provide atomic-level information on the molecular mechanism of CRISPR-Cas9 that will inspire future experimental investigations aimed at fully clarifying the biophysics of this unique genome editing machinery and at developing new tools for nucleic acid manipulation based on CRISPR-Cas9. PMID:28652374

CRISPR-Cas9 conformational activation as elucidated from enhanced molecular simulations.

PubMed

Palermo, Giulia; Miao, Yinglong; Walker, Ross C; Jinek, Martin; McCammon, J Andrew

2017-07-11

CRISPR-Cas9 has become a facile genome editing technology, yet the structural and mechanistic features underlying its function are unclear. Here, we perform extensive molecular simulations in an enhanced sampling regime, using a Gaussian-accelerated molecular dynamics (GaMD) methodology, which probes displacements over hundreds of microseconds to milliseconds, to reveal the conformational dynamics of the endonuclease Cas9 during its activation toward catalysis. We disclose the conformational transition of Cas9 from its apo form to the RNA-bound form, suggesting a mechanism for RNA recruitment in which the domain relocations cause the formation of a positively charged cavity for nucleic acid binding. GaMD also reveals the conformation of a catalytically competent Cas9, which is prone for catalysis and whose experimental characterization is still limited. We show that, upon DNA binding, the conformational dynamics of the HNH domain triggers the formation of the active state, explaining how the HNH domain exerts a conformational control domain over DNA cleavage [Sternberg SH et al. (2015) Nature , 527 , 110-113]. These results provide atomic-level information on the molecular mechanism of CRISPR-Cas9 that will inspire future experimental investigations aimed at fully clarifying the biophysics of this unique genome editing machinery and at developing new tools for nucleic acid manipulation based on CRISPR-Cas9.

Sobol' sensitivity analysis for stressor impacts on honeybee ...

EPA Pesticide Factsheets

We employ Monte Carlo simulation and nonlinear sensitivity analysis techniques to describe the dynamics of a bee exposure model, VarroaPop. Daily simulations are performed of hive population trajectories, taking into account queen strength, foraging success, mite impacts, weather, colony resources, population structure, and other important variables. This allows us to test the effects of defined pesticide exposure scenarios versus controlled simulations that lack pesticide exposure. The daily resolution of the model also allows us to conditionally identify sensitivity metrics. We use the variancebased global decomposition sensitivity analysis method, Sobol’, to assess firstand secondorder parameter sensitivities within VarroaPop, allowing us to determine how variance in the output is attributed to each of the input variables across different exposure scenarios. Simulations with VarroaPop indicate queen strength, forager life span and pesticide toxicity parameters are consistent, critical inputs for colony dynamics. Further analysis also reveals that the relative importance of these parameters fluctuates throughout the simulation period according to the status of other inputs. Our preliminary results show that model variability is conditional and can be attributed to different parameters depending on different timescales. By using sensitivity analysis to assess model output and variability, calibrations of simulation models can be better informed to yield more

Sticking properties of ice grains

NASA Astrophysics Data System (ADS)

Jongmanns, M.; Kumm, M.; Wurm, G.; Wolf, D. E.; Teiser, J.

2017-06-01

We study the size dependence of pull-off forces of water ice in laboratory experiments and numerical simulations. To determine the pull-off force in our laboratory experiments, we use a liquid nitrogen cooled centrifuge. Depending on its rotation frequency, spherical ice grains detach due to the centrifugal force which is related to the adhesive properties. Numerical simulations are conducted by means of molecular dynamics simulations of hexagonal ice using a standard coarse-grained water potential. The pull-off force of a single contact between two spherical ice grains is measured due to strain controlled simulations. Both, the experimental study and the simulations reveal a dependence between the pull-off force and the (reduced) particle radii, which differ significantly from the linear dependence of common contact theories.

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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Experimental and numerical study of premixed hydrogen/air flame propagating in a combustion chamber.

PubMed

Xiao, Huahua; Sun, Jinhua; Chen, Peng

2014-03-15

An experimental and numerical study of dynamics of premixed hydrogen/air flame in a closed explosion vessel is described. High-speed shlieren cinematography and pressure recording are used to elucidate the dynamics of the combustion process in the experiment. A dynamically thickened flame model associated with a detailed reaction mechanism is employed in the numerical simulation to examine the flame-flow interaction and effect of wall friction on the flame dynamics. The shlieren photographs show that the flame develops into a distorted tulip shape after a well-pronounced classical tulip front has been formed. The experimental results reveal that the distorted tulip flame disappears with the primary tulip cusp and the distortions merging into each other, and then a classical tulip is repeated. The combustion dynamics is reasonably reproduced in the numerical simulations, including the variations in flame shape and position, pressure build-up and periodically oscillating behavior. It is found that both the tulip and distorted tulip flames can be created in the simulation with free-slip boundary condition at the walls of the vessel and behave in a manner quite close to that in the experiments. This means that the wall friction could be unimportant for the tulip and distorted tulip formation although the boundary layer formed along the sidewalls has an influence to a certain extent on the flame behavior near the sidewalls. The distorted tulip flame is also observed to be produced in the absence of vortex flow in the numerical simulations. The TF model with a detailed chemical scheme is reliable for investigating the dynamics of distorted tulip flame propagation and its underlying mechanism. Copyright © 2014 Elsevier B.V. All rights reserved.

BIM (BCL-2 interacting mediator of cell death) SAHB (stabilized α helix of BCL2) not always convinces BAX (BCL-2-associated X protein) for apoptosis.

PubMed

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

2016-06-01

The interaction of BAX (BCL-2-associated X protein) with BIM (BCL-2 interacting mediator of cell death) SAHB (stabilized α helix of BCL2) directly initiates BAX-mediated mitochondrial apoptosis. This molecular dynamics study reveals that BIM SAHB forms a stable complex with BAX but it remains in a non-functional conformation. N terminal of BAX folds towards the core which has been reported exposed in the functional monomer. The α1-α2 loop, which has been reported in open conformation in functional BAX, acquires a closed conformation during the simulation. BH3/α2 remains less exposed as compared to initial structure. The hydrophobic residues of BIM accommodates in the rear pocket of BAX during the simulation. A steep decrease in radius of gyration and solvent accessible surface area (SASA) indicates the complex folding to acquire a more stable but inactive conformation. Further the covariance matrix reveals that the backbone atoms' motions favour the inactive conformation of the complex. This is the first report on the non-functional BAX-BIM SAHB complex by molecular dynamics simulation in the best of our knowledge. Copyright © 2016 Elsevier Inc. All rights reserved.

Structural evolution dynamics in fusion of sumanenes and corannulenes: defects formation and self-healing mechanism

NASA Astrophysics Data System (ADS)

Sorkin, Anastassia; Su, Haibin

2018-06-01

The fusion processes of structures consisting of various combinations between sumanene and corannulene, leading to the formation of graphene nanoribbons (GNRs) under heating are simulated by density-functional-based tight-binding molecular dynamics. Distinct stages are unraveled in the course of GNR formation. Firstly, the carbon fragments coalescence into highly strained framework. Secondly, structural reconstruction invokes breaking most strained bonds to form a GNR structure containing numerous defects. Lastly, defects are remedied by the delicate ‘edge-facilitated self-healing’ process through two synergized edge-related effects: elevated mobility of defects and promoted structure reconstructions owing to the remarkable dynamics associated with edges. Importantly, detailed dynamics in the course of forming GNRs with defects and grain boundaries simulated in this work is valuable to provide better understanding at the atomistic scale of defect formation as well as self-healing in the context of the sp2 carbon network. In particular, edges play important roles in not only generating Stone–Wales (SW), 5-8-5 types of defects, 8-5-5-8 and pentagon–heptagon grain boundaries. In addition, our simulations predict the existence of one novel defect, coined as the Inverse SW defect, which is to be confirmed in future experimental studies. This study of dynamic structural evolution reveals that edges are prone to intrinsic and extrinsic modifications such as atomic-scale defects, structural distortions and inhomogeneity.

Effects of temperature and pressure on the nucleation and growth of silver clusters from supersaturated vapor: A molecular dynamics analysis

NASA Astrophysics Data System (ADS)

Wang, Qin; Xie, Hui; Chen, Yongshi; Liu, Chao

2017-04-01

The nucleation and growth of silver nanoparticles in the supersaturated system are investigated by molecular dynamics simulation at different temperatures and pressures. The variety of the atoms in the biggest cluster and the size of average clusters in the system versus the time are estimated to reveal the relationship between the nucleation as well as cluster growth. The nucleation rates in different situations are calculated with the threshold method. The effect of temperature and pressure on the nucleation rate is identified as obeying a linear function. Finally, the development of basal elements, such as monomers, dimers and trimmers, is revealed how the temperature and pressure affect the nucleation and growth of the silver cluster.

The dynamics of magma chamber refilling at the Campi Flegrei caldera.

NASA Astrophysics Data System (ADS)

Montagna, Chiara Paola; Vassalli, Melissa; Longo, Antonella; Papale, Paolo; Giudice, Salvatore; Saccorotti, Gilberto

2010-05-01

The volcanologic and petrologic reconstructions of several eruptions during the last tens of thousand years of volcanism at the Campi Flegrei caldera show that in most cases a small, chemically evolved, partially degassed magma chamber was refilled by magma of deeper origin shortly before the eruption. New magma input in a shallow chamber is revealed from a variety of indicators, well described in the literature, that include major-trace element and isotope heterogeneities, and crystal-liquid disequilibria (e.g., Arienzo et al., Bull. Volcanol., 2009). In the case of the 4100 BP Agnano Monte Spina eruption, representing the highest intensity and magnitude event of the last epoch of activity, it has been suggested that the refilling occurred within a few tens of hours from the start of the eruption. Notably, in such a case the two end-member magmas that mixed shortly before eruption onset are not recognized as individual members in the deposits, rather, their composition and characteristics are reconstructed from small scale disequilibria, revealing that a relatively short time was sufficient for efficient mixing of the liquid components. In order to investigate the dynamics of magma chamber refilling and mixing at Campi Flegrei we have applied the GALES code (Longo et al., Geophys. Res. Lett., 2006) in a series of numerical simulations. The initial and boundary conditions have been defined in the frame of two subsequent projects coordinated by INGV and funded by the Italian Civil Protection Department, that gather a large number of experts on Campi Flegrei, and are consistent with the bulk of knowledge on the deep magmatic system. In all cases an initial compositional interface is placed at a certain depth, with non-degassed, buoyant magma placed below. The simulations investigate both the dynamics in a very large, 8 km deep reservoir revealed by seismic tomography (Zollo et al., Geophys. Res. Lett., 2008), and those in shallower and smaller chamber systems connected by dykes and representative of pre-eruptive conditions. The numerical results reveal the complex dynamics of magma mixing, dominated by the interplay between buoyant magma rise and dense magma sinking. In all simulated cases efficient mixing takes place at dyke levels, the buoyant magma entering the chamber is already a mixture of the two initial end-members, and the initial deep magma is never found as an individual component in the chamber. Over the time scale of our longest simulation (about 8 hours of real time), and with reference to the spatial resolution of our simulations (max 1 m), the magma chamber is occupied by a nearly homogeneous mixture of the two initial end-members, with minor but still visible density stratification continuously perturbed by the rise of small buoyant plumes. Consistent with the observations, an eruption occurring a few tens of hours after new magma ingression would be characterized by a magmatic composition intermediate between the two initial end-members, that can therefore be revealed only from small-scale heterogeneities and possibly from crystal-liquid disequilibria.

Simulation of the atmospheric thermal circulation of a martian volcano using a mesoscale numerical model.

PubMed

Rafkin, Scot C R; Sta Maria, Magdalena R V; Michaels, Timothy I

2002-10-17

Mesoscale (<100 km) atmospheric phenomena are ubiquitous on Mars, as revealed by Mars Orbiter Camera images. Numerical models provide an important means of investigating martian atmospheric dynamics, for which data availability is limited. But the resolution of general circulation models, which are traditionally used for such research, is not sufficient to resolve mesoscale phenomena. To provide better understanding of these relatively small-scale phenomena, mesoscale models have recently been introduced. Here we simulate the mesoscale spiral dust cloud observed over the caldera of the volcano Arsia Mons by using the Mars Regional Atmospheric Modelling System. Our simulation uses a hierarchy of nested models with grid sizes ranging from 240 km to 3 km, and reveals that the dust cloud is an indicator of a greater but optically thin thermal circulation that reaches heights of up to 30 km, and transports dust horizontally over thousands of kilometres.

The dynamics of camphor in the cytochrome P450 CYP101D2

PubMed Central

Vohra, Shabana; Musgaard, Maria; Bell, Stephen G; Wong, Luet-Lok; Zhou, Weihong; Biggin, Philip C

2013-01-01

The recent crystal structures of CYP101D2, a cytochrome P450 protein from the oligotrophic bacterium Novosphingobium aromaticivorans DSM12444 revealed that both the native (substrate-free) and camphor-soaked forms have open conformations. Furthermore, two other potential camphor-binding sites were also identified from electron densities in the camphor-soaked structure, one being located in the access channel and the other in a cavity on the surface near the F-helix side of the F-G loop termed the substrate recognition site. These latter sites may be key intermediate positions on the pathway for substrate access to or product egress from the active site. Here, we show via the use of unbiased atomistic molecular dynamics simulations that despite the open conformation of the native and camphor-bound crystal structures, the underlying dynamics of CYP101D2 appear to be very similar to other CYP proteins. Simulations of the native structure demonstrated that the protein is capable of sampling many different conformational substates. At the same time, simulations with the camphor positioned at various locations within the access channel or recognition site show that movement towards the active site or towards bulk solvent can readily occur on a short timescale, thus confirming many previously reported in silico studies using steered molecular dynamics. The simulations also demonstrate how the fluctuations of an aromatic gate appear to control access to the active site. Finally, comparison of camphor-bound simulations with the native simulations suggests that the fluctuations can be of similar level and thus are more representative of the conformational selection model rather than induced fit. PMID:23832606

Unraveling the martian water cycle with high-resolution global climate simulations

NASA Astrophysics Data System (ADS)

Pottier, Alizée; Forget, François; Montmessin, Franck; Navarro, Thomas; Spiga, Aymeric; Millour, Ehouarn; Szantai, André; Madeleine, Jean-Baptiste

2017-07-01

Global climate modeling of the Mars water cycle is usually performed at relatively coarse resolution (200 - 300km), which may not be sufficient to properly represent the impact of waves, fronts, topography effects on the detailed structure of clouds and surface ice deposits. Here, we present new numerical simulations of the annual water cycle performed at a resolution of 1° × 1° (∼ 60 km in latitude). The model includes the radiative effects of clouds, whose influence on the thermal structure and atmospheric dynamics is significant, thus we also examine simulations with inactive clouds to distinguish the direct impact of resolution on circulation and winds from the indirect impact of resolution via water ice clouds. To first order, we find that the high resolution does not dramatically change the behavior of the system, and that simulations performed at ∼ 200 km resolution capture well the behavior of the simulated water cycle and Mars climate. Nevertheless, a detailed comparison between high and low resolution simulations, with reference to observations, reveal several significant changes that impact our understanding of the water cycle active today on Mars. The key northern cap edge dynamics are affected by an increase in baroclinic wave strength, with a complication of northern summer dynamics. South polar frost deposition is modified, with a westward longitudinal shift, since southern dynamics are also influenced. Baroclinic wave mode transitions are observed. New transient phenomena appear, like spiral and streak clouds, already documented in the observations. Atmospheric circulation cells in the polar region exhibit a large variability and are fine structured, with slope winds. Most modeled phenomena affected by high resolution give a picture of a more turbulent planet, inducing further variability. This is challenging for long-period climate studies.

Resting state networks in empirical and simulated dynamic functional connectivity.

PubMed

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

2017-10-01

It is well-established that patterns of functional connectivity (FC) - measures of correlated activity between pairs of voxels or regions observed in the human brain using neuroimaging - are robustly expressed in spontaneous activity during rest. These patterns are not static, but exhibit complex spatio-temporal dynamics. Over the last years, a multitude of methods have been proposed to reveal these dynamics on the level of the whole brain. One finding is that the brain transitions through different FC configurations over time, and substantial effort has been put into characterizing these configurations. However, the dynamics governing these transitions are more elusive, specifically, the contribution of stationary vs. non-stationary dynamics is an active field of inquiry. In this study, we use a whole-brain approach, considering FC dynamics between 66 ROIs covering the entire cortex. We combine an innovative dimensionality reduction technique, tensor decomposition, with a mean field model which possesses stationary dynamics. It has been shown to explain resting state FC averaged over time and multiple subjects, however, this average FC summarizes the spatial distribution of correlations while hiding their temporal dynamics. First, we apply tensor decomposition to resting state scans from 24 healthy controls in order to characterize spatio-temporal dynamics present in the data. We simultaneously utilize temporal and spatial information by creating tensors that are subsequently decomposed into sets of brain regions ("communities") that share similar temporal dynamics, and their associated time courses. The tensors contain pairwise FC computed inside of overlapping sliding windows. Communities are discovered by clustering features pooled from all subjects, thereby ensuring that they generalize. We find that, on the group level, the data give rise to four distinct communities that resemble known resting state networks (RSNs): default mode network, visual network, 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.

Novel mutant of Escherichia coli asparaginase II to reduction of the glutaminase activity in treatment of acute lymphocytic leukemia by molecular dynamics simulations and QM-MM studies.

PubMed

Ardalan, Noeman; Mirzaie, Sako; Sepahi, Abbas Akhavan; Khavari-Nejad, Ramazan Ali

2018-03-01

L-Asparaginases (ASNase) belong to a family of amidohydrolases, have both asparaginase and glutaminase activity. Acute lymphocytic leukemia (ALL) is an outrageous disease worldwide. Bacterial ASNase has been used for the treatment of ALL. Glutaminase activity of enzyme causes some side effect and it is not essential for anticancer activity. The aim of this study was engineering of Escherichia coli asparaginase II to find a mutant with reduced glutaminase activity by molecular docking, molecular dynamics (MD) and QM-MM (Quantum mechanics molecular dynamics) simulations. Residues with low free energy of binding to Asn and high free binding energy to Gln were chosen for mutagenesis. Then, a mutant with higher glutaminase free binding energy was selected for further studies. Additionally, the MD simulation and QM-MM computation of wild type (WT) were employed and the selected mutated ASNase were analyzed and discussed. Our data showed that V27T is a good candidate to reduction the glutaminase activity, while has no remarkable effect on asparaginase activity of the enzyme. The simulation analysis revealed that V27T mutant is more stable than WT and mutant simulation was successful completely. QM-MM results confirmed the successfulness of our mutagenesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Molecular dynamics simulations of void defects in the energetic material HMX.

PubMed

Duan, Xiao Hui; Li, Wen Peng; Pei, Chong Hua; Zhou, Xiao Qing

2013-09-01

A molecular dynamics (MD) simulation was carried out to characterize the dynamic evolution of void defects in crystalline octahydro-1, 3, 5, 7-tetranitro-1, 3, 5, 7-tetrazocine (HMX). Different models were constructed with the same concentration of vacancies (10 %) to discuss the size effects of void. Energetic ground state properties were determined by annealing simulations. The void formation energy per molecule removed was found to be 55-63 kcal/mol(-1), and the average binding energy per molecule was between 32 and 34 kcal/mol(-1) according to the change in void size. Voids with larger size had lower formation energy. Local binding energies for molecules directly on the void surface decreased greatly compared to those in defect-free lattice, and then gradually increased until the distance away from the void surface was around 10 Å. Analysis of 1 ns MD simulations revealed that the larger the void size, the easier is void collapse. Mean square displacements (MSDs) showed that HMX molecules that had collapsed into void present liquid structure characteristics. Four unique low-energy conformers were found for HMX molecules in void: two whose conformational geometries corresponded closely to those found in HMX polymorphs and two, additional, lower energy conformers that were not seen in the crystalline phases. The ratio of different conformers changed with the simulated temperature, in that the ratio of α conformer increased with the increase in temperature.

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

Magnetohydrodynamic Simulation of the X2.2 Solar Flare on 2011 February 15. I. Comparison with the Observations

NASA Astrophysics Data System (ADS)

Inoue, S.; Hayashi, K.; Magara, T.; Choe, G. S.; Park, Y. D.

2014-06-01

We performed a magnetohydrodynamic (MHD) simulation using a nonlinear force-free field (NLFFF) in solar active region 11158 to clarify the dynamics of an X2.2-class solar flare. We found that the NLFFF never shows the dramatic dynamics seen in observations, i.e., it is in a stable state against the perturbations. On the other hand, the MHD simulation shows that when the strongly twisted lines are formed at close to the neutral line, which are produced via tether-cutting reconnection in the twisted lines of the NLFFF, they consequently erupt away from the solar surface via the complicated reconnection. This result supports the argument that the strongly twisted lines formed in NLFFF via tether-cutting reconnection are responsible for breaking the force balance condition of the magnetic fields in the lower solar corona. In addition to this, the dynamical evolution of these field lines reveals that at the initial stage the spatial pattern of the footpoints caused by the reconnection of the twisted lines appropriately maps the distribution of the observed two-ribbon flares. Interestingly, after the flare, the reconnected field lines convert into a structure like the post-flare loops, which is analogous to the extreme ultraviolet image taken by the Solar Dynamics Observatory. Eventually, we found that the twisted lines exceed a critical height at which the flux tube becomes unstable to the torus instability. These results illustrate the reliability of our simulation and also provide an important relationship between flare and coronal mass ejection dynamics.

Conformational dynamics of dry lamellar crystals of sugar based lipids: an atomistic simulation study.

PubMed

ManickamAchari, Vijayan; Bryce, Richard A; Hashim, Rauzah

2014-01-01

The rational design of a glycolipid application (e.g. drug delivery) with a tailored property depends on the detailed understanding of its structure and dynamics. Because of the complexity of sugar stereochemistry, we have undertaken a simulation study on the conformational dynamics of a set of synthetic glycosides with different sugar groups and chain design, namely dodecyl β-maltoside, dodecyl β-cellobioside, dodecyl β-isomaltoside and a C12C10 branched β-maltoside under anhydrous conditions. We examined the chain structure in detail, including the chain packing, gauche/trans conformations and chain tilting. In addition, we also investigated the rotational dynamics of the headgroup and alkyl chains. Monoalkylated glycosides possess a small amount of gauche conformers (∼20%) in the hydrophobic region of the lamellar crystal (LC) phase. In contrast, the branched chain glycolipid in the fluid Lα phase has a high gauche population of up to ∼40%. Rotational diffusion analysis reveals that the carbons closest to the headgroup have the highest correlation times. Furthermore, its value depends on sugar type, where the rotational dynamics of an isomaltose was found to be 11-15% and more restrained near the sugar, possibly due to the chain disorder and partial inter-digitation compared to the other monoalkylated lipids. Intriguingly, the present simulation demonstrates the chain from the branched glycolipid bilayer has the ability to enter into the hydrophilic region. This interesting feature of the anhydrous glycolipid bilayer simulation appears to arise from a combination of lipid crowding and the amphoteric nature of the sugar headgroups.

Excited state non-adiabatic dynamics of the smallest polyene, trans 1,3-butadiene. II. Ab initio multiple spawning simulations

NASA Astrophysics Data System (ADS)

Glover, William J.; Mori, Toshifumi; Schuurman, Michael S.; Boguslavskiy, Andrey E.; Schalk, Oliver; Stolow, Albert; Martínez, Todd J.

2018-04-01

The excited state non-adiabatic dynamics of the smallest polyene, trans 1,3-butadiene (BD), has long been the subject of controversy due to its strong coupling, ultrafast time scales and the difficulties that theory faces in describing the relevant electronic states in a balanced fashion. Here we apply Ab Initio Multiple Spawning (AIMS) using state-averaged complete active space multistate second order perturbation theory [SA-3-CAS(4/4)-MSPT2] which describes both static and dynamic electron correlation effects, providing a balanced description of both the initially prepared bright 11Bu (ππ*) state and non-adiabatically coupled dark 21Ag state of BD. Importantly, AIMS allows for on-the-fly calculations of experimental observables. We validate our approach by directly simulating the time resolved photoelectron-photoion coincidence spectroscopy results presented in Paper I [A. E. Boguslavskiy et al., J. Chem. Phys. 148, 164302 (2018)], demonstrating excellent agreement with experiment. Our simulations reveal that the initial excitation to the 11Bu state rapidly evolves via wavepacket dynamics that follow both bright- and dark-state pathways as well as mixtures of these. In order to test the sensitivity of the AIMS results to the relative ordering of states, we considered two hypothetical scenarios biased toward either the bright 1Bu or the dark 21Ag state. In contrast with AIMS/SA-3-CAS(4/4)-MSPT2 simulations, neither of these scenarios yields favorable agreement with experiment. Thus, we conclude that the excited state non-adiabatic dynamics in BD involves both of these ultrafast pathways.

Binding free energies for nicotine analogs inhibiting cytochrome P450 2A6 by a combined use of molecular dynamics simulations and QM/MM-PBSA calculations.

PubMed

Lu, Haiting; Huang, Xiaoqin; AbdulHameed, Mohamed Diwan M; Zhan, Chang-Guo

2014-04-01

Molecular dynamics (MD) simulations and hybrid quantum mechanical/molecular mechanical (QM/MM) calculations have been performed to explore the dynamic behaviors of cytochrome P450 2A6 (CYP2A6) binding with nicotine analogs (that are typical inhibitors) and to calculate their binding free energies in combination with Poisson-Boltzmann surface area (PBSA) calculations. The combined MD simulations and QM/MM-PBSA calculations reveal that the most important structural parameters affecting the CYP2A6-inhibitor binding affinity are two crucial internuclear distances, that is, the distance between the heme iron atom of CYP2A6 and the coordinating atom of the inhibitor, and the hydrogen-bonding distance between the N297 side chain of CYP2A6 and the pyridine nitrogen of the inhibitor. The combined MD simulations and QM/MM-PBSA calculations have led to dynamic CYP2A6-inhibitor binding structures that are consistent with the observed dynamic behaviors and structural features of CYP2A6-inhibitor binding, and led to the binding free energies that are in good agreement with the experimentally-derived binding free energies. The agreement between the calculated binding free energies and the experimentally-derived binding free energies suggests that the combined MD and QM/MM-PBSA approach may be used as a valuable tool to accurately predict the CYP2A6-inhibitor binding affinities in future computational design of new, potent and selective CYP2A6 inhibitors. Copyright © 2014 Elsevier Ltd. All rights reserved.

Conformational Transition Pathways in Signaling and Enzyme Catalysis Explored by Computational Methods

NASA Astrophysics Data System (ADS)

Pachov, Dimitar V.

Biomolecules are dynamic in nature and visit a number of states while performing their biological function. However, understanding how they interconvert between functional substates is a challenging task. In this thesis, we employ enhanced computational strategies to reveal in atomistic resolution transition states and molecular mechanism along conformational pathways of the signaling protein Nitrogen Regulatory Protein C (NtrC) and the enzyme Adenylate Kinase (Adk). Targeted Molecular Dynamics (TMD) simulations and NMR experiments have previously found the active/inactive interconversion of NtrC is stabilized by non-native transient contacts. To find where along the conformational pathway they lie and probe the existence of multiple intermediates, a beyond 8mus-extensive mapping of the conformational landscape was performed by a multitude of straightforward MD simulations relaxed from the biased TMD pathway. A number of metastable states stabilized by local interactions was found to underline the conformational pathway of NtrC. Two spontaneous transitions of the last stage of the active-to-inactive conversion were identified and used in path sampling procedures to generate an ensemble of truly dynamic reactive pathways. The transition state ensemble (TSE) and mechanistic descriptors of this transition were revealed in atomic detail and verified by committor analysis. By analyzing how pressure affects the dynamics and function of two homologous Adk proteins - the P.Profundum Adk surviving at 700atm pressure in the deep sea, and the E. coli Adk that lives at ambient pressures - we indirectly obtained atomic information about the TSE of the large-amplitude rate-limiting conformational opening of the Adk lids. Guided by NMR experiments showing significantly decreased activation volumes of the piezophile compared to its mesophilic counterpart, TMD simulations revealed the formation of an extended hydrogen-bonded water network in the transition state of the piezophile that can explain the experimentally measured activation volume differences. The transition state of the conformational change was proposed to lie close to the closed state. Additionally, a number of descriptors were used to characterize the free energy landscape of the mesophile. It was found that the features of landscape are highly sensitive to the binding of different ligands, their protonation states and the presence of magnesium.

Manipulating Protein-Protein Interactions in Nonribosomal Peptide Synthetase Type II Peptidyl Carrier Proteins.

PubMed

Jaremko, Matt J; Lee, D John; Patel, Ashay; Winslow, Victoria; Opella, Stanley J; McCammon, J Andrew; Burkart, Michael D

2017-10-10

In an effort to elucidate and engineer interactions in type II nonribosomal peptide synthetases, we analyzed biomolecular recognition between the essential peptidyl carrier proteins and adenylation domains using nuclear magnetic resonance (NMR) spectroscopy, molecular dynamics, and mutational studies. Three peptidyl carrier proteins, PigG, PltL, and RedO, in addition to their cognate adenylation domains, PigI, PltF, and RedM, were investigated for their cross-species activity. Of the three peptidyl carrier proteins, only PigG showed substantial cross-pathway activity. Characterization of the novel NMR solution structure of holo-PigG and molecular dynamics simulations of holo-PltL and holo-PigG revealed differences in structures and dynamics of these carrier proteins. NMR titration experiments revealed perturbations of the chemical shifts of the loop 1 residues of these peptidyl carrier proteins upon their interaction with the adenylation domain. These experiments revealed a key region for the protein-protein interaction. Mutational studies supported the role of loop 1 in molecular recognition, as mutations to this region of the peptidyl carrier proteins significantly modulated their activities.

Machine Learning and Network Analysis of Molecular Dynamics Trajectories Reveal Two Chains of Red/Ox-specific Residue Interactions in Human Protein Disulfide Isomerase.

PubMed

Karamzadeh, Razieh; Karimi-Jafari, Mohammad Hossein; Sharifi-Zarchi, Ali; Chitsaz, Hamidreza; Salekdeh, Ghasem Hosseini; Moosavi-Movahedi, Ali Akbar

2017-06-16

The human protein disulfide isomerase (hPDI), is an essential four-domain multifunctional enzyme. As a result of disulfide shuffling in its terminal domains, hPDI exists in two oxidation states with different conformational preferences which are important for substrate binding and functional activities. Here, we address the redox-dependent conformational dynamics of hPDI through molecular dynamics (MD) simulations. Collective domain motions are identified by the principal component analysis of MD trajectories and redox-dependent opening-closing structure variations are highlighted on projected free energy landscapes. Then, important structural features that exhibit considerable differences in dynamics of redox states are extracted by statistical machine learning methods. Mapping the structural variations to time series of residue interaction networks also provides a holistic representation of the dynamical redox differences. With emphasizing on persistent long-lasting interactions, an approach is proposed that compiled these time series networks to a single dynamic residue interaction network (DRIN). Differential comparison of DRIN in oxidized and reduced states reveals chains of residue interactions that represent potential allosteric paths between catalytic and ligand binding sites of hPDI.

A New Approach to Simulate Groundwater Table Dynamics and Its Validation in China

NASA Astrophysics Data System (ADS)

Lv, M.; Lu, H.; Dan, L.; Yang, K.

2017-12-01

The groundwater has very important role in hydrology-climate-human activity interaction. But the groundwater table dynamics currently is not well simulated in global-scale land surface models. Meanwhile, almost all groundwater schemes are adopting a specific yield method to estimate groundwater table, in which how to determine the proper specific yield value remains a big challenge. In this study, we developed a Soil Moisture Correlation (SMC) method to simulate groundwater table dynamics. We coupled SMC with a hydrological model (named as NEW) and compared it with the original model in which a specific yield method is used (named as CTL). Both NEW and CTL were tested in Tangnaihai Subbasin of Yellow River and Jialingjiang Subbasin along Yangtze River, where underground water is less impacted by human activities. The simulated discharges by NEW and CTL are compared against gauge observations. The comparison results reveal that after calibration both models are able to reproduce the discharge well. However, there is no parameter needed to be calibrated for SMC. It indicates that SMC method is more efficient and easy-to-use than the specific yield method. Since there is no direct groundwater table observation in these two basins, simulated groundwater table were compared with a global data set provided by Fan et al. (2013). Both NEW and CTL estimate lower depths than Fan does. Moreover, when comparing the variation of terrestrial water storage (TWS) derived from NEW with that observed by GRACE, good agreements were confirmed. It demonstrated that SMC method is able to reproduce groundwater level dynamics reliably.

Lattice dynamics and thermal transport in multiferroic CuCrO 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bansal, Dipanshu; Niedziela, Jennifer L.; May, Andrew F.

Inelastic neutron and x-ray scattering measurements of phonons and spin waves in CuCrO 2 were performed over a wide range of temperature, and complemented with first-principles simulations. The phonon dispersions and density of states are well reproduced by our density functional cal- culations, and reveal a strong anisotropy of Cu vibrations, with large amplitudes of low-frequency in-plane motions. In addition, we find that spin fluctuations persist above 300 K, far above the N eel temperature for long-range antiferromagnetic order, TN. Modeling of the thermal conductivity, based on our phonon measurements and simulations, reveals a significant anisotropy and indicates that themore » spin fluctuations above TN constitute a strong source of phonon scattering.« less

Lattice dynamics and thermal transport in multiferroic CuCrO 2

DOE PAGES

Bansal, Dipanshu; Niedziela, Jennifer L.; May, Andrew F.; ...

2017-02-09

Inelastic neutron and x-ray scattering measurements of phonons and spin waves in CuCrO 2 were performed over a wide range of temperature, and complemented with first-principles simulations. The phonon dispersions and density of states are well reproduced by our density functional cal- culations, and reveal a strong anisotropy of Cu vibrations, with large amplitudes of low-frequency in-plane motions. In addition, we find that spin fluctuations persist above 300 K, far above the N eel temperature for long-range antiferromagnetic order, TN. Modeling of the thermal conductivity, based on our phonon measurements and simulations, reveals a significant anisotropy and indicates that themore » spin fluctuations above TN constitute a strong source of phonon scattering.« less

Electronic polarization stabilizes tertiary structure prediction of HP-36.

PubMed

Duan, Li L; Zhu, Tong; Zhang, Qing G; Tang, Bo; Zhang, John Z H

2014-04-01

Molecular dynamic (MD) simulations with both implicit and explicit solvent models have been carried out to study the folding dynamics of HP-36 protein. Starting from the extended conformation, the secondary structure of all three helices in HP-36 was formed in about 50 ns and remained stable in the remaining simulation. However, the formation of the tertiary structure was difficult. Although some intermediates were close to the native structure, the overall conformation was not stable. Further analysis revealed that the large structure fluctuation of loop and hydrophobic core regions was devoted mostly to the instability of the structure during MD simulation. The backbone root-mean-square deviation (RMSD) of the loop and hydrophobic core regions showed strong correlation with the backbone RMSD of the whole protein. The free energy landscape indicated that the distribution of main chain torsions in loop and turn regions was far away from the native state. Starting from an intermediate structure extracted from the initial AMBER simulation, HP-36 was found to generally fold to the native state under the dynamically adjusted polarized protein-specific charge (DPPC) simulation, while the peptide did not fold into the native structure when AMBER force filed was used. The two best folded structures were extracted and taken into further simulations in water employing AMBER03 charge and DPPC for 25 ns. Result showed that introducing polarization effect into interacting potential could stabilize the near-native protein structure.

Molecular dynamics simulations of propane in slit shaped silica nano-pores: direct comparison with quasielastic neutron scattering experiments.

PubMed

Gautam, Siddharth; Le, Thu; Striolo, Alberto; Cole, David

2017-12-13

Molecular motion under confinement has important implications for a variety of applications including gas recovery and catalysis. Propane confined in mesoporous silica aerogel as studied using quasielastic neutron scattering (QENS) showed anomalous pressure dependence in its diffusion coefficient (J. Phys. Chem. C, 2015, 119, 18188). Molecular dynamics (MD) simulations are often employed to complement the information obtained from QENS experiments. Here, we report an MD simulation study to probe the anomalous pressure dependence of propane diffusion in silica aerogel. Comparison is attempted based on the self-diffusion coefficients and on the time scales of the decay of the simulated intermediate scattering functions. While the self-diffusion coefficients obtained from the simulated mean squared displacement profiles do not exhibit the anomalous pressure dependence observed in the experiments, the time scales of the decay of the intermediate scattering functions calculated from the simulation data match the corresponding quantities obtained in the QENS experiment and thus confirm the anomalous pressure dependence of the diffusion coefficient. The origin of the anomaly in pressure dependence lies in the presence of an adsorbed layer of propane molecules that seems to dominate the confined propane dynamics at low pressure, thereby lowering the diffusion coefficient. Further, time scales for rotational motion obtained from the simulations explain the absence of rotational contribution to the QENS spectra in the experiments. In particular, the rotational motion of the simulated propane molecules is found to exhibit large angular jumps at lower pressure. The present MD simulation work thus reveals important new insights into the origin of anomalous pressure dependence of propane diffusivity in silica mesopores and supplements the information obtained experimentally by QENS data.

Collision-Induced Dissociation of Electrosprayed NaCl Clusters: Using Molecular Dynamics Simulations to Visualize Reaction Cascades in the Gas Phase

NASA Astrophysics Data System (ADS)

Schachel, Tilo D.; Metwally, Haidy; Popa, Vlad; Konermann, Lars

2016-11-01

Infusion of NaCl solutions into an electrospray ionization (ESI) source produces [Na( n+1)Cl n ]+ and other gaseous clusters. The n = 4, 13, 22 magic number species have cuboid ground state structures and exhibit elevated abundance in ESI mass spectra. Relatively few details are known regarding the mechanisms whereby these clusters undergo collision-induced dissociation (CID). The current study examines to what extent molecular dynamics (MD) simulations can be used to garner insights into the sequence of events taking place during CID. Experiments on singly charged clusters reveal that the loss of small neutrals is the dominant fragmentation pathway. MD simulations indicate that the clusters undergo extensive structural fluctuations prior to decomposition. Consistent with the experimentally observed behavior, most of the simulated dissociation events culminate in ejection of small neutrals ([NaCl] i , with i = 1, 2, 3). The MD data reveal that the prevalence of these dissociation channels is linked to the presence of short-lived intermediates where a relatively compact core structure carries a small [NaCl] i protrusion. The latter can separate from the parent cluster via cleavage of a single Na-Cl contact. Fragmentation events of this type are kinetically favored over other dissociation channels that would require the quasi-simultaneous rupture of multiple electrostatic contacts. The CID behavior of NaCl cluster ions bears interesting analogies to that of collisionally activated protein complexes. Overall, it appears that MD simulations represent a valuable tool for deciphering the dissociation of noncovalently bound systems in the gas phase.

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…

Molecular dynamic simulations reveal the structural determinants of fatty acid binding to oxy-myoglobin

USDA-ARS?s Scientific Manuscript database

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 metabolite...

Understanding the impact of Fc glycosylation on its conformational changes by molecular dynamics simulations and bioinformatics.

PubMed

Zhang, Yubo

2015-12-01

N-linked glycosylation of Fc at N297 plays an important role in its effector function, aberrance of which would cause disease pathogenesis. Here, we performed all-atom molecular dynamics simulations to explore the effects of Fc glycosylation on its dynamics behaviors. Firstly, equilibrium simulations suggested that Fc deglycosylation was able to induce residual flexibility in its CH2 domain. Besides, the free energy landscape revealed three minimum energy wells in deglycosylated Fc, representing its "open", "semi-closed" and "closed" states. However, we could only observe the "open" state of glycosylated Fc. Supportively, principal component analysis emphasized the prominent motion of delyclosylated Fc and dynamically depicted how it changed from the "open" state to its "closed" state. Secondly, we studied the recognition mechanism of the Fc binding to its partners. Energy decomposition analysis identified key residues of Fc to recognize its two partners P13 and P34. Evidently, electrostatic potential surfaces showed that electrostatic attraction helped to stabilize the interaction between Fc and its partners. Also, relative binding free energies explained different binding affinities in Fc-P13 and Fc-P34. Collectively, these results together provided the structural basis for understanding conformational changes of deglycosylated Fc and the recognition mechanism of the Fc binding to its partners.

Functional Loop Dynamics of the Streptavidin-Biotin Complex

PubMed Central

Song, Jianing; Li, Yongle; Ji, Changge; Zhang, John Z. H.

2015-01-01

Accelerated molecular dynamics (aMD) simulation is employed to study the functional dynamics of the flexible loop3-4 in the strong-binding streptavidin-biotin complex system. Conventional molecular (cMD) simulation is also performed for comparison. The present study reveals the following important properties of the loop dynamics: (1) The transition of loop3-4 from open to closed state is observed in 200 ns aMD simulation. (2) In the absence of biotin binding, the open-state streptavidin is more stable, which is consistent with experimental evidences. The free energy (ΔG) difference is about 5 kcal/mol between two states. But with biotin binding, the closed state is more stable due to electrostatic and hydrophobic interactions between the loop3-4 and biotin. (3) The closure of loop3-4 is concerted to the stable binding of biotin to streptavidin. When the loop3-4 is in its open-state, biotin moves out of the binding pocket, indicating that the interactions between the loop3-4 and biotin are essential in trapping biotin in the binding pocket. (4) In the tetrameric streptavidin system, the conformational change of the loop3-4 in each monomer is independent of each other. That is, there is no cooperative binding for biotin bound to the four subunits of the tetramer. PMID:25601277

On the onset of surface condensation: formation and transition mechanisms of condensation mode

PubMed Central

Sheng, Qiang; Sun, Jie; Wang, Qian; Wang, Wen; Wang, Hua Sheng

2016-01-01

Molecular dynamics simulations have been carried out to investigate the onset of surface condensation. On surfaces with different wettability, we snapshot different condensation modes (no-condensation, dropwise condensation and filmwise condensation) and quantitatively analyze their characteristics by temporal profiles of surface clusters. Two different types of formation of nanoscale droplets are identified, i.e. the formations with and without film-like condensate. We exhibit the effect of surface tensions on the formations of nanoscale droplets and film. We reveal the formation mechanisms of different condensation modes at nanoscale based on our simulation results and classical nucleation theory, which supplements the ‘classical hypotheses’ of the onset of dropwise condensation. We also reveal the transition mechanism between different condensation modes based on the competition between surface tensions and reveal that dropwise condensation represents the transition states from no-condensation to filmwise condensation. PMID:27481071

On the onset of surface condensation: formation and transition mechanisms of condensation mode.

PubMed

Sheng, Qiang; Sun, Jie; Wang, Qian; Wang, Wen; Wang, Hua Sheng

2016-08-02

Molecular dynamics simulations have been carried out to investigate the onset of surface condensation. On surfaces with different wettability, we snapshot different condensation modes (no-condensation, dropwise condensation and filmwise condensation) and quantitatively analyze their characteristics by temporal profiles of surface clusters. Two different types of formation of nanoscale droplets are identified, i.e. the formations with and without film-like condensate. We exhibit the effect of surface tensions on the formations of nanoscale droplets and film. We reveal the formation mechanisms of different condensation modes at nanoscale based on our simulation results and classical nucleation theory, which supplements the 'classical hypotheses' of the onset of dropwise condensation. We also reveal the transition mechanism between different condensation modes based on the competition between surface tensions and reveal that dropwise condensation represents the transition states from no-condensation to filmwise condensation.

The RNA-Binding Site of Poliovirus 3C Protein Doubles as a Phosphoinositide-Binding Domain.

PubMed

Shengjuler, Djoshkun; Chan, Yan Mei; Sun, Simou; Moustafa, Ibrahim M; Li, Zhen-Lu; Gohara, David W; Buck, Matthias; Cremer, Paul S; Boehr, David D; Cameron, Craig E

2017-12-05

Some viruses use phosphatidylinositol phosphate (PIP) to mark membranes used for genome replication or virion assembly. PIP-binding motifs of cellular proteins do not exist in viral proteins. Molecular-docking simulations revealed a putative site of PIP binding to poliovirus (PV) 3C protein that was validated using nuclear magnetic resonance spectroscopy. The PIP-binding site was located on a highly dynamic α helix, which also functions in RNA binding. Broad PIP-binding activity was observed in solution using a fluorescence polarization assay or in the context of a lipid bilayer using an on-chip, fluorescence assay. All-atom molecular dynamics simulations of the 3C protein-membrane interface revealed PIP clustering and perhaps PIP-dependent conformations. PIP clustering was mediated by interaction with residues that interact with the RNA phosphodiester backbone. We conclude that 3C binding to membranes will be determined by PIP abundance. We suggest that the duality of function observed for 3C may extend to RNA-binding proteins of other viruses. Copyright © 2017 Elsevier Ltd. All rights reserved.

Structural Basis of Pullulanase Membrane Binding and Secretion Revealed by X-Ray Crystallography, Molecular Dynamics and Biochemical Analysis.

PubMed

East, Alexandra; Mechaly, Ariel E; Huysmans, Gerard H M; Bernarde, Cédric; Tello-Manigne, Diana; Nadeau, Nathalie; Pugsley, Anthony P; Buschiazzo, Alejandro; Alzari, Pedro M; Bond, Peter J; Francetic, Olivera

2016-01-05

The Klebsiella lipoprotein pullulanase (PulA) is exported to the periplasm, triacylated, and anchored via lipids in the inner membrane (IM) prior to its transport to the bacterial surface through a type II secretion system (T2SS). X-Ray crystallography and atomistic molecular dynamics (MD) simulations of PulA in a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) model membrane provided an unprecedented molecular view of an N-terminal unstructured tether and the IM lipoprotein retention signal, and revealed novel interactions with the IM via N-terminal immunoglobulin-like domains in PulA. An efficiently secreted nonacylated variant (PulANA) showed similar peripheral membrane association during MD simulations, consistent with the binding of purified PulANA to liposomes. Remarkably, combined X-ray, MD, and functional studies identified a novel subdomain, Ins, inserted in the α-amylase domain, which is required for PulA secretion. Available data support a model in which PulA binding to the IM promotes interactions with the T2SS, possibly via the Ins subdomain. Copyright © 2016 Elsevier Ltd. All rights reserved.

Energy transport in the three coupled α-polypeptide chains of collagen molecule with long-range interactions effect

NASA Astrophysics Data System (ADS)

Mvogo, Alain; Ben-Bolie, G. H.; Kofané, T. C.

2015-06-01

The dynamics of three coupled α-polypeptide chains of a collagen molecule is investigated with the influence of power-law long-range exciton-exciton interactions. The continuum limit of the discrete equations reveal that the collagen dynamics is governed by a set of three coupled nonlinear Schrödinger equations, whose dispersive coefficient depends on the LRI parameter r. We construct the analytic symmetric and asymmetric (antisymmetric) soliton solutions, which match with the structural features of collagen related with the acupuncture channels. These solutions are used as initial conditions for the numerical simulations of the discrete equations, which reveal a coherent transport of energy in the molecule for r > 3. The results also indicate that the width of the solitons is a decreasing function of r, which help to stabilize the solitons propagating in the molecule. To confirm further the efficiency of energy transport in the molecule, the modulational instability of the system is performed and the numerical simulations show that the energy can flow from one polypeptide chain to another in the form of nonlinear waves.

Membrane association of the PTEN tumor suppressor: Neutron scattering and MD simulations reveal the structure of protein-membranes complexes

PubMed Central

Nanda, Hirsh; Heinrich, Frank; Lösche, Mathias

2014-01-01

Neutron reflection (NR) from planar interfaces is an emerging technology that provides unique and otherwise inaccessible structural information on disordered molecular systems such as membrane proteins associated with fluid bilayers, thus addressing one of the remaining challenges of structural biology. Although intrinsically a low-resolution technique, using structural information from crystallography or NMR allows the construction of NR models that describe the architecture of protein-membrane complexes at high resolution. In addition, a combination of these methods with molecular dynamics (MD) simulations has the potential to reveal the dynamics of protein interactions with the bilayer in atomistic detail. We review recent advances in this area by discussing the application of these techniques to the complex formed by the PTEN phosphatase with the plasma membrane. These studies provide insights in the cellular regulation of PTEN, its interaction with PI(4,5)P2 in the inner plasma membrane and the pathway by which its substrate, PI(3,4,5)P3, accesses the PTEN catalytic site. PMID:25461777

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

PubMed

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

2016-12-16

The molecular basis of enzyme catalytic power and specificity derives from dynamic interactions between enzyme and substrate during catalysis. Although 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, we examine the importance of substrate dynamics in the cleavage of Kunitz-bovine pancreatic trypsin inhibitor 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. By using long all-atom molecular dynamics simulations of acyl-enzyme intermediates with proteolysis rates spanning 3 orders of magnitude, we identify global and local dynamic features of substrates on the nanosecond-microsecond time scale 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 substrate-like and product-like states, linking substrate dynamics on the nanosecond-microsecond time scale with large collective substrate motions on the much slower time scale of catalysis. Our findings implicate substrate flexibility as a critical determinant of catalysis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Molecular dynamics simulation of shock wave and spallation phenomena in metal foils irradiated by femtosecond laser pulse

NASA Astrophysics Data System (ADS)

Zhakhovsky, Vasily; Demaske, Brian; Inogamov, Nail; Oleynik, Ivan

2010-03-01

Femtosecond laser irradiation of metals is an effective technique to create a high-pressure frontal layer of 100-200 nm thickness. The associated ablation and spallation phenomena can be studied in the laser pump-probe experiments. We present results of a large-scale MD simulation of ablation and spallation dynamics developing in 1,2,3μm thick Al and Au foils irradiated by a femtosecond laser pulse. Atomic-scale mechanisms of laser energy deposition, transition from pressure wave to shock, reflection of the shock from the rear-side of the foil, and the nucleation of cracks in the reflected tensile wave, having a very high strain rate, were all studied. To achieve a realistic description of the complex phenomena induced by strong compression and rarefaction waves, we developed new embedded atom potentials for Al and Au based on cold pressure curves. MD simulations revealed the complex interplay between spallation and ablation processes: dynamics of spallation depends on the pressure profile formed in the ablated zone at the early stage of laser energy absorption. It is shown that the essential information such as material properties at high strain rate and spall strength can be extracted from the simulated rear-side surface velocity as a function of time.

Characterization of the glass transition of water predicted by molecular dynamics simulations using nonpolarizable intermolecular potentials.

PubMed

Kreck, Cara A; Mancera, Ricardo L

2014-02-20

Molecular dynamics simulations allow detailed study of the experimentally inaccessible liquid state of supercooled water below its homogeneous nucleation temperature and the characterization of the glass transition. Simple, nonpolarizable intermolecular potentials are commonly used in classical molecular dynamics simulations of water and aqueous systems due to their lower computational cost and their ability to reproduce a wide range of properties. Because the quality of these predictions varies between the potentials, the predicted glass transition of water is likely to be influenced by the choice of potential. We have thus conducted an extensive comparative investigation of various three-, four-, five-, and six-point water potentials in both the NPT and NVT ensembles. The T(g) predicted from NPT simulations is strongly correlated with the temperature of minimum density, whereas the maximum in the heat capacity plot corresponds to the minimum in the thermal expansion coefficient. In the NVT ensemble, these points are instead related to the maximum in the internal pressure and the minimum of its derivative, respectively. A detailed analysis of the hydrogen-bonding properties at the glass transition reveals that the extent of hydrogen-bonds lost upon the melting of the glassy state is related to the height of the heat capacity peak and varies between water potentials.

On the kinetics of the capillary imbibition of a simple fluid through a designed nanochannel using the molecular dynamics simulation approach.

PubMed

Ahadian, Samad; Mizuseki, Hiroshi; Kawazoe, Yoshiyuki

2010-12-15

A molecular dynamics (MD) approach was employed to simulate the imbibition of a designed nanopore by a simple fluid (i.e., a Lennard-Jones (LJ) fluid). The length of imbibition as a function of time for various interactions between the LJ fluid and the pore wall was recorded for this system (i.e., the LJ fluid and the nanopore). By and large, the kinetics of imbibition was successfully described by the Lucas-Washburn (LW) equation, although deviation from it was observed in some cases. This lack of agreement is due to the neglect of the dynamic contact angle (DCA) in the LW equation. Two commonly used models (i.e., hydrodynamic and molecular-kinetic (MK) models) were thus employed to calculate the DCA. It is demonstrated that the MK model is able to justify the simulation results in which are not in good agreement with the simple LW equation. However, the hydrodynamic model is not capable of doing that. Further investigation of the MD simulation data revealed an interesting fact that there is a direct relationship between the wall-fluid interaction and the speed of the capillary imbibition. More evidence to support this claim is presented. Copyright © 2010 Elsevier Inc. All rights reserved.

Stress Distribution During Deformation of Polycrystalline Aluminum by Molecular-Dynamics and Finite-Element Modeling

NASA Technical Reports Server (NTRS)

Yamakov, V.; Saether, E.; Phillips, D.; Glaessgen, E. H.

2004-01-01

In this paper, a multiscale modelling strategy is used to study the effect of grain-boundary sliding on stress localization in a polycrystalline microstructure with an uneven distribution of grain size. The development of the molecular dynamics (MD) analysis used to interrogate idealized grain microstructures with various types of grain boundaries and the multiscale modelling strategies for modelling large systems of grains is discussed. Both molecular-dynamics and finite-element (FE) simulations for idealized polycrystalline models of identical geometry are presented with the purpose of demonstrating the effectiveness of the adapted finite-element method using cohesive zone models to reproduce grain-boundary sliding and its effect on the stress distribution in a polycrystalline metal. The yield properties of the grain-boundary interface, used in the FE simulations, are extracted from a MD simulation on a bicrystal. The models allow for the study of the load transfer between adjacent grains of very different size through grain-boundary sliding during deformation. A large-scale FE simulation of 100 grains of a typical microstructure is then presented to reveal that the stress distribution due to grain-boundary sliding during uniform tensile strain can lead to stress localization of two to three times the background stress, thus suggesting a significant effect on the failure properties of the metal.

Molecular Dynamics based on a Generalized Born solvation model: application to protein folding

NASA Astrophysics Data System (ADS)

Onufriev, Alexey

2004-03-01

An accurate description of the aqueous environment is essential for realistic biomolecular simulations, but may become very expensive computationally. We have developed a version of the Generalized Born model suitable for describing large conformational changes in macromolecules. The model represents the solvent implicitly as continuum with the dielectric properties of water, and include charge screening effects of salt. The computational cost associated with the use of this model in Molecular Dynamics simulations is generally considerably smaller than the cost of representing water explicitly. Also, compared to traditional Molecular Dynamics simulations based on explicit water representation, conformational changes occur much faster in implicit solvation environment due to the absence of viscosity. The combined speed-up allow one to probe conformational changes that occur on much longer effective time-scales. We apply the model to folding of a 46-residue three helix bundle protein (residues 10-55 of protein A, PDB ID 1BDD). Starting from an unfolded structure at 450 K, the protein folds to the lowest energy state in 6 ns of simulation time, which takes about a day on a 16 processor SGI machine. The predicted structure differs from the native one by 2.4 A (backbone RMSD). Analysis of the structures seen on the folding pathway reveals details of the folding process unavailable form experiment.

Extended molecular dynamics of a c-kit promoter quadruplex

PubMed Central

Islam, Barira; Stadlbauer, Petr; Krepl, Miroslav; Koca, Jaroslav; Neidle, Stephen; Haider, Shozeb; Sponer, Jiri

2015-01-01

The 22-mer c-kit promoter sequence folds into a parallel-stranded quadruplex with a unique structure, which has been elucidated by crystallographic and NMR methods and shows a high degree of structural conservation. We have carried out a series of extended (up to 10 μs long, ∼50 μs in total) molecular dynamics simulations to explore conformational stability and loop dynamics of this quadruplex. Unfolding no-salt simulations are consistent with a multi-pathway model of quadruplex folding and identify the single-nucleotide propeller loops as the most fragile part of the quadruplex. Thus, formation of propeller loops represents a peculiar atomistic aspect of quadruplex folding. Unbiased simulations reveal μs-scale transitions in the loops, which emphasizes the need for extended simulations in studies of quadruplex loops. We identify ion binding in the loops which may contribute to quadruplex stability. The long lateral-propeller loop is internally very stable but extensively fluctuates as a rigid entity. It creates a size-adaptable cleft between the loop and the stem, which can facilitate ligand binding. The stability gain by forming the internal network of GA base pairs and stacks of this loop may be dictating which of the many possible quadruplex topologies is observed in the ground state by this promoter quadruplex. PMID:26245347

Multimillion atom simulations of dynamics of oxidation of an aluminum nanoparticle and nanoindentation on ceramics.

PubMed

Vashishta, Priya; Kalia, Rajiv K; Nakano, Aiichiro

2006-03-02

We have developed a first-principles-based hierarchical simulation framework, which seamlessly integrates (1) a quantum mechanical description based on the density functional theory (DFT), (2) multilevel molecular dynamics (MD) simulations based on a reactive force field (ReaxFF) that describes chemical reactions and polarization, a nonreactive force field that employs dynamic atomic charges, and an effective force field (EFF), and (3) an atomistically informed continuum model to reach macroscopic length scales. For scalable hierarchical simulations, we have developed parallel linear-scaling algorithms for (1) DFT calculation based on a divide-and-conquer algorithm on adaptive multigrids, (2) chemically reactive MD based on a fast ReaxFF (F-ReaxFF) algorithm, and (3) EFF-MD based on a space-time multiresolution MD (MRMD) algorithm. On 1920 Intel Itanium2 processors, we have demonstrated 1.4 million atom (0.12 trillion grid points) DFT, 0.56 billion atom F-ReaxFF, and 18.9 billion atom MRMD calculations, with parallel efficiency as high as 0.953. Through the use of these algorithms, multimillion atom MD simulations have been performed to study the oxidation of an aluminum nanoparticle. Structural and dynamic correlations in the oxide region are calculated as well as the evolution of charges, surface oxide thickness, diffusivities of atoms, and local stresses. In the microcanonical ensemble, the oxidizing reaction becomes explosive in both molecular and atomic oxygen environments, due to the enormous energy release associated with Al-O bonding. In the canonical ensemble, an amorphous oxide layer of a thickness of approximately 40 angstroms is formed after 466 ps, in good agreement with experiments. Simulations have been performed to study nanoindentation on crystalline, amorphous, and nanocrystalline silicon nitride and silicon carbide. Simulation on nanocrystalline silicon carbide reveals unusual deformation mechanisms in brittle nanophase materials, due to coexistence of brittle grains and soft amorphous-like grain boundary phases. Simulations predict a crossover from intergranular continuous deformation to intragrain discrete deformation at a critical indentation depth.

A Modern Picture of Barred Galaxy Dynamics

NASA Astrophysics Data System (ADS)

Petersen, Michael; Weinberg, Martin; Katz, Neal

2018-01-01

Observations of disk galaxies suggest that bars are responsible for altering global galaxy parameters (e.g. structures, gas fraction, star formation rate). The canonical understanding of the mechanisms underpinning bar-driven secular dynamics in disk galaxies has been largely built upon the analysis of linear theory, despite galactic bars being clearly demonstrated to be nonlinear phenomena in n-body simulations. We present simulations of barred Milky Way-like galaxy models designed to elucidate nonlinear barred galaxy dynamics. We have developed two new methodologies for analyzing n-body simulations that give the best of both powerful analytic linear theory and brute force simulation analysis: orbit family identification and multicomponent torque analysis. The software will be offered publicly to the community for their own simulation analysis.The orbit classifier reveals that the details of kinematic components in galactic disks (e.g. the bar, bulge, thin disk, and thick disk components) are powerful discriminators of evolutionary paradigms (i.e. violent instabilities and secular evolution) as well as the basic parameters of the dark matter halo (mass distribution, angular momentum distribution). Multicomponent torque analysis provides a thorough accounting of the transfer of angular momentum between orbits, global patterns, and distinct components in order to better explain the underlying physics which govern the secular evolution of barred disk galaxies.Using these methodologies, we are able to identify the successes and failures of linear theory and traditional n-body simulations en route to a detailed understanding of the control bars exhibit over secular evolution in galaxies. We present explanations for observed physical and velocity structures in observations of barred galaxies alongside predictions for how structures will vary with dynamical properties from galaxy to galaxy as well as over the lifetime of a galaxy, finding that the transfer of angular momentum through previously unidentified channels can more fully explain the observed dynamics.

Investigation of structural dynamics of Thrombocytopenia Cargeeg mutants of human apoptotic cytochrome c: A molecular dynamics simulation approach.

PubMed

Muneeswaran, Gurusamy; Kartheeswaran, Subramanian; Pandiaraj, Manickam; Muthukumar, Kaliappan; Sankaralingam, Muniyandi; Arunachalam, Saravanavadivu

2017-11-01

Naturally occurring mutations to cytochrome c (cyt-c) have been identified recently in patients with mild autosomal dominant thrombocytopenia (low platelet levels), which yield cyt-c mutants with enhanced apoptotic activity. However, the molecular mechanism underlying this low platelet production and enhanced apoptosis remain unclear. Therefore, an attempt is made herein for the first time to investigate the effects of mutations of glycine 41 by serine (G41S) and tyrosine 48 by histidine (Y48H) on the conformational and dynamic changes of apoptotic (Fe 3+ ) cyt-c using all atom molecular dynamics (MD) simulations in explicit water solvent. Our 30ns MD simulations demonstrate considerable structural differences in G41S and Y48H compared to wild type (WT) cyt-c, such as increasing distances between the critical electron transfer residues results in open conformation at the heme active site, large fluctuations in β-turns and α-helices. Additionally, although the β-sheets remain mostly unaffected in all the three cyt-c simulations, the α-helices undergo conformational switch to β-turns in both the mutant simulations. Importantly, this conformational switch of α-helix to β-turn around heme active site should attributes to the loss of intraprotein H-bonds in the mutant simulations especially between NE2 (His26) and O (Pro44) in agreement with the experimental report. Further, essential dynamics analysis reveals that overall motions of WT cyt-c is mainly involved only in the first eigenvector, but in G41S and Y48H the overall motions are mainly in three and two eigenvectors respectively. Overall, the detailed atomistic level information provide a unifying description for the molecular mechanism of structural destabilization, disregulation of platelet formation and enhanced peroxidase activity of the mutant cyt-c's in the pathology of intrinsic apoptosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Retrodicting the Cenozoic evolution of the mantle: Implications for dynamic surface topography

NASA Astrophysics Data System (ADS)

Glišović, Petar; Forte, Alessandro; Rowley, David; Simmons, Nathan; Grand, Stephen

2014-05-01

Seismic tomography is the essential starting ingredient for constructing realistic models of the mantle convective flow and for successfully predicting a wide range of convection-related surface observables. However, the lack of knowledge of the initial thermal state of the mantle in the geological past is still an outstanding problem in mantle convection. The resolution of this problem requires models of 3-D mantle evolution that yield maximum consistency with a wide suite of geophysical constraints. Quantifying the robustness of the reconstructed thermal evolution is another major concern. We have carried out mantle dynamic simulations (Glišović & Forte, EPSL 2014) using a pseudo-spectral solution for compressible-flow thermal convection in 3-D spectral geometry that directly incorporate: 1) joint seismic-geodynamic inversions of mantle density structure with constraints provided by mineral physics data (Simmons et al., GJI 2009); and 2) constraints on mantle viscosity inferred by inversion of a suite of convection-related and glacial isostatic adjustment data sets (Mitrovica & Forte, EPSL 2004) characterised by Earth-like Rayleigh numbers. These time-reversed convection simulations reveal how the buoyancy associated with hot, active upwellings is a major driver of the mantle-wide convective circulation and the changes in dynamic topography at the Earth's surface. These simulations reveal, for example, a stable and long-lived superplume under the East Pacific Rise (centred under the Easter and Pitcairn hotspots) that was previously identified by Rowley et al. (AGU 2011, Nature in review) on the basis of plate kinematic data. We also present 65 Myr reconstructions of the Reunion plume that gave rise to the Deccan Traps.

Fluorescence and NMR spectroscopy together with molecular simulations reveal amphiphilic characteristics of a Burkholderia biofilm exopolysaccharide.

PubMed

Kuttel, Michelle M; Cescutti, Paola; Distefano, Marco; Rizzo, Roberto

2017-06-30

Biofilms are a collective mode of bacterial life in which a self-produced matrix confines cells in close proximity to each other. Biofilms confer many advantages, including protection from chemicals (including antibiotics), entrapment of useful extracellular enzymes and nutrients, as well as opportunities for efficient recycling of molecules from dead cells. Biofilm matrices are aqueous gel-like structures composed of polysaccharides, proteins, and DNA stabilized by intermolecular interactions that may include non-polar connections. Recently, polysaccharides extracted from biofilms produced by species of the Burkholderia cepacia complex were shown to possess clusters of rhamnose, a 6-deoxy sugar with non-polar characteristics. Molecular dynamics simulations are well suited to characterizing the structure and dynamics of polysaccharides, but only relatively few such studies exist of their interaction with non-polar molecules. Here we report an investigation into the hydrophobic properties of the exopolysaccharide produced by Burkholderia multivorans strain C1576. Fluorescence experiments with two hydrophobic fluorescent probes established that this polysaccharide complexes hydrophobic species, and NMR experiments confirmed these interactions. Molecular simulations to model the hydrodynamics of the polysaccharide and the interaction with guest species revealed a very flexible, amphiphilic carbohydrate chain that has frequent dynamic interactions with apolar molecules; both hexane and a long-chain fatty acid belonging to the quorum-sensing system of B. multivorans were tested. A possible role of the non-polar domains of the exopolysaccharide in facilitating the diffusion of aliphatic species toward specific targets within the biofilm aqueous matrix is proposed. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Shock-induced poration, cholesterol flip-flop and small interfering RNA transfection in a phospholipid membrane: Multimillion atom, microsecond molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Choubey, Amit

Biological cell membranes provide mechanical stability to cells and understanding their structure, dynamics and mechanics are important biophysics problems. Experiments coupled with computational methods such as molecular dynamics (MD) have provided insight into the physics of membranes. We use long-time and large-scale MD simulations to study the structure, dynamics and mechanical behavior of membranes. We investigate shock-induced collapse of nanobubbles in water using MD simulations based on a reactive force field. We observe a focused jet at the onset of bubble shrinkage and a secondary shock wave upon bubble collapse. The jet length scales linearly with the nanobubble radius, as observed in experiments on micron-to-millimeter size bubbles. Shock induces dramatic structural changes, including an ice-VII-like structural motif at a particle velocity of 1 km/s. The incipient ice VII formation and the calculated Hugoniot curve are in good agreement with experimental results. We also investigate molecular mechanisms of poration in lipid bilayers due to shock-induced collapse of nanobubbles. Our multimillion-atom MD simulations reveal that the jet impact generates shear flow of water on bilayer leaflets and pressure gradients across them. This transiently enhances the bilayer permeability by creating nanopores through which water molecules translocate rapidly across the bilayer. Effects of nanobubble size and temperature on the porosity of lipid bilayers are examined. The second research project focuses on cholesterol (CHOL) dynamics in phospholipid bilayers. Several experimental and computational studies have been performed on lipid bilayers consisting of dipalmitoylphosphatidylcholine (DPPC) and CHOL molecules. CHOL interleaflet transport (flip-flop) plays an important role in interleaflet coupling and determining CHOL flip-flop rate has been elusive. Various studies report that the rate ranges between milliseconds to seconds. We calculate CHOL flip-flop rates by performing a 15 mus all-atom MD simulation of a DPPC-CHOL bilayer. We find that the CHOL flip-flop rates are on the sub microsecond timescale. These results are verified by performing various independent parallel replica (PR) simulations. Our PR simulations provide significant boost in sampling of the flip-flop events. We observe that the CHOL flip-flop can induce membrane order, regulate membrane-bending energy, and facilitate membrane relaxation. The rapid flip-flop rates reported here have important implications for the role of CHOL in mechanical properties of cell membranes, formation of domains, and maintaining CHOL concentration asymmetry in plasma membrane. Our PR approach can reach submillisecond time scales and bridge the gap between MD simulations and Nuclear Magnetic Resonance (NMR) experiments on CHOL flip-flop dynamics in membranes. The last project deals with transfection barriers encountered by a bare small interfering RNA (siRNA) in a phospholipid bilayer. SiRNA molecules play a pivotal role in therapeutic applications. A key limitation to the widespread implementation of siRNA-based therapeutics is the difficulty of delivering siRNA-based drugs to cells. We have examined structural and mechanical barriers to siRNA passage across a phospholipid bilayer using all-atom MD simulations. We find that the electrostatic interaction between the anionic siRNA and head groups of phospholipid molecules induces a phase transformation from the liquid crystalline to ripple phase. Steered MD simulations reveal that the siRNA transfection through the ripple phase requires a force of ˜ 1.5 nN.

Meteorologically Driven Simulations of Dengue Epidemics in San Juan, PR

PubMed Central

Morin, Cory W.; Monaghan, Andrew J.; Hayden, Mary H.; Barrera, Roberto; Ernst, Kacey

2015-01-01

Meteorological factors influence dengue virus ecology by modulating vector mosquito population dynamics, viral replication, and transmission. Dynamic modeling techniques can be used to examine how interactions among meteorological variables, vectors and the dengue virus influence transmission. We developed a dengue fever simulation model by coupling a dynamic simulation model for Aedes aegypti, the primary mosquito vector for dengue, with a basic epidemiological Susceptible-Exposed-Infectious-Recovered (SEIR) model. Employing a Monte Carlo approach, we simulated dengue transmission during the period of 2010–2013 in San Juan, PR, where dengue fever is endemic. The results of 9600 simulations using varied model parameters were evaluated by statistical comparison (r2) with surveillance data of dengue cases reported to the Centers for Disease Control and Prevention. To identify the most influential parameters associated with dengue virus transmission for each period the top 1% of best-fit model simulations were retained and compared. Using the top simulations, dengue cases were simulated well for 2010 (r2 = 0.90, p = 0.03), 2011 (r2 = 0.83, p = 0.05), and 2012 (r2 = 0.94, p = 0.01); however, simulations were weaker for 2013 (r2 = 0.25, p = 0.25) and the entire four-year period (r2 = 0.44, p = 0.002). Analysis of parameter values from retained simulations revealed that rain dependent container habitats were more prevalent in best-fitting simulations during the wetter 2010 and 2011 years, while human managed (i.e. manually filled) container habitats were more prevalent in best-fitting simulations during the drier 2012 and 2013 years. The simulations further indicate that rainfall strongly modulates the timing of dengue (e.g., epidemics occurred earlier during rainy years) while temperature modulates the annual number of dengue fever cases. Our results suggest that meteorological factors have a time-variable influence on dengue transmission relative to other important environmental and human factors. PMID:26275146

Classical black holes: the nonlinear dynamics of curved spacetime.

PubMed

Thorne, Kip S

2012-08-03

Numerical simulations have revealed two types of physical structures, made from curved spacetime, that are attached to black holes: tendexes, which stretch or squeeze anything they encounter, and vortexes, which twist adjacent inertial frames relative to each other. When black holes collide, their tendexes and vortexes interact and oscillate (a form of nonlinear dynamics of curved spacetime). These oscillations generate gravitational waves, which can give kicks up to 4000 kilometers per second to the merged black hole. The gravitational waves encode details of the spacetime dynamics and will soon be observed and studied by the Laser Interferometer Gravitational Wave Observatory and its international partners.

Classical Black Holes: The Nonlinear Dynamics of Curved Spacetime

NASA Astrophysics Data System (ADS)

Thorne, Kip S.

2012-08-01

Numerical simulations have revealed two types of physical structures, made from curved spacetime, that are attached to black holes: tendexes, which stretch or squeeze anything they encounter, and vortexes, which twist adjacent inertial frames relative to each other. When black holes collide, their tendexes and vortexes interact and oscillate (a form of nonlinear dynamics of curved spacetime). These oscillations generate gravitational waves, which can give kicks up to 4000 kilometers per second to the merged black hole. The gravitational waves encode details of the spacetime dynamics and will soon be observed and studied by the Laser Interferometer Gravitational Wave Observatory and its international partners.

Warm Dense Matter Demonstrating Non-Drude Conductivity from Observations of Nonlinear Plasmon Damping

NASA Astrophysics Data System (ADS)

Witte, B. B. L.; Fletcher, L. B.; Galtier, E.; Gamboa, E.; Lee, H. J.; Zastrau, U.; Redmer, R.; Glenzer, S. H.; Sperling, P.

2017-06-01

We present simulations using finite-temperature density-functional-theory molecular dynamics to calculate the dynamic electrical conductivity in warm dense aluminum. The comparison between exchange-correlation functionals in the Perdew-Burke-Enzerhof and Heyd-Scuseria-Enzerhof (HSE) approximation indicates evident differences in the density of states and the dc conductivity. The HSE calculations show excellent agreement with experimental Linac Coherent Light Source x-ray plasmon scattering spectra revealing plasmon damping below the widely used random phase approximation. These findings demonstrate non-Drude-like behavior of the dynamic conductivity that needs to be taken into account to determine the optical properties of warm dense matter.

On unravelling mechanism of interplay between cloud and large scale circulation: a grey area in climate science

NASA Astrophysics Data System (ADS)

De, S.; Agarwal, N. K.; Hazra, Anupam; Chaudhari, Hemantkumar S.; Sahai, A. K.

2018-04-01

The interaction between cloud and large scale circulation is much less explored area in climate science. Unfolding the mechanism of coupling between these two parameters is imperative for improved simulation of Indian summer monsoon (ISM) and to reduce imprecision in climate sensitivity of global climate model. This work has made an effort to explore this mechanism with CFSv2 climate model experiments whose cloud has been modified by changing the critical relative humidity (CRH) profile of model during ISM. Study reveals that the variable CRH in CFSv2 has improved the nonlinear interactions between high and low frequency oscillations in wind field (revealed as internal dynamics of monsoon) and modulates realistically the spatial distribution of interactions over Indian landmass during the contrasting monsoon season compared to the existing CRH profile of CFSv2. The lower tropospheric wind error energy in the variable CRH simulation of CFSv2 appears to be minimum due to the reduced nonlinear convergence of error to the planetary scale range from long and synoptic scales (another facet of internal dynamics) compared to as observed from other CRH experiments in normal and deficient monsoons. Hence, the interplay between cloud and large scale circulation through CRH may be manifested as a change in internal dynamics of ISM revealed from scale interactive quasi-linear and nonlinear kinetic energy exchanges in frequency as well as in wavenumber domain during the monsoon period that eventually modify the internal variance of CFSv2 model. Conversely, the reduced wind bias and proper modulation of spatial distribution of scale interaction between the synoptic and low frequency oscillations improve the eastward and northward extent of water vapour flux over Indian landmass that in turn give feedback to the realistic simulation of cloud condensates attributing improved ISM rainfall in CFSv2.

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.

Functional mechanism of C-terminal tail in the enzymatic role of porcine testicular carbonyl reductase: a combined experiment and molecular dynamics simulation study of the C-terminal tail in the enzymatic role of PTCR.

PubMed

Son, Minky; Bang, Woo Young; Park, Chanin; Lee, Yuno; Kwon, Seul Gi; Kim, Sam Woong; Kim, Chul Wook; Lee, Keun Woo

2014-01-01

Porcine testicular carbonyl reductase, PTCR which is one of the short chain dehydrogenases/reductases (SDR) superfamily catalyzes the NADPH-dependent reduction of carbonyl compounds including steroids and prostaglandins. Previously we reported C-terminal tail of PTCR was deleted due to a nonsynonymous single nucleotide variation (nsSNV). Here we identified from kinetic studies that the enzymatic properties for 5α-dihydrotestosterone (5α-DHT) were different between wild-type and C-terminal-deleted PTCRs. Compared to wild-type PTCR, C-terminal-deleted PTCR has much higher reduction rate. To investigate structural difference between wild-type and C-terminal-deleted PTCRs upon 5α-DHT binding, we performed molecular dynamics simulations for two complexes. Using trajectories, molecular interactions including hydrogen bonding patterns, distance between 5α-DHT and catalytic Tyr193, and interaction energies are analyzed and compared. During the MD simulation time, the dynamic behavior of C-terminal tail in wild-type PTCR is also examined using essential dynamics analysis. The results of our simulations reveal that the binding conformation of 5α-DHT in C-terminal-deleted PTCR is more favorable for reduction reaction in PTCR, which shows strong agreement with kinetic data. These structural findings provide valuable information to understand substrate specificity of PTCR and further kinetic properties of enzymes belonging to the SDR superfamily.

Visualization of early events in acetic acid denaturation of HIV-1 protease: a molecular dynamics study.

PubMed

Borkar, Aditi Narendra; Rout, Manoj Kumar; Hosur, Ramakrishna V

2011-01-01

Protein denaturation plays a crucial role in cellular processes. In this study, denaturation of HIV-1 Protease (PR) was investigated by all-atom MD simulations in explicit solvent. The PR dimer and monomer were simulated separately in 9 M acetic acid (9 M AcOH) solution and water to study the denaturation process of PR in acetic acid environment. Direct visualization of the denaturation dynamics that is readily available from such simulations has been presented. Our simulations in 9 M AcOH reveal that the PR denaturation begins by separation of dimer into intact monomers and it is only after this separation that the monomer units start denaturing. The denaturation of the monomers is flagged off by the loss of crucial interactions between the α-helix at C-terminal and surrounding β-strands. This causes the structure to transit from the equilibrium dynamics to random non-equilibrating dynamics. Residence time calculations indicate that denaturation occurs via direct interaction of the acetic acid molecules with certain regions of the protein in 9 M AcOH. All these observations have helped to decipher a picture of the early events in acetic acid denaturation of PR and have illustrated that the α-helix and the β-sheet at the C-terminus of a native and functional PR dimer should maintain both the stability and the function of the enzyme and thus present newer targets for blocking PR function.

Functional Mechanism of C-Terminal Tail in the Enzymatic Role of Porcine Testicular Carbonyl Reductase: A Combined Experiment and Molecular Dynamics Simulation Study of the C-Terminal Tail in the Enzymatic Role of PTCR

PubMed Central

Park, Chanin; Lee, Yuno; Kwon, Seul Gi; Kim, Sam Woong; Kim, Chul Wook; Lee, Keun Woo

2014-01-01

Porcine testicular carbonyl reductase, PTCR which is one of the short chain dehydrogenases/reductases (SDR) superfamily catalyzes the NADPH-dependent reduction of carbonyl compounds including steroids and prostaglandins. Previously we reported C- terminal tail of PTCR was deleted due to a nonsynonymous single nucleotide variation (nsSNV). Here we identified from kinetic studies that the enzymatic properties for 5α-dihydrotestosterone (5α-DHT) were different between wild-type and C-terminal-deleted PTCRs. Compared to wild-type PTCR, C-terminal-deleted PTCR has much higher reduction rate. To investigate structural difference between wild-type and C-terminal-deleted PTCRs upon 5α-DHT binding, we performed molecular dynamics simulations for two complexes. Using trajectories, molecular interactions including hydrogen bonding patterns, distance between 5α-DHT and catalytic Tyr193, and interaction energies are analyzed and compared. During the MD simulation time, the dynamic behavior of C-terminal tail in wild-type PTCR is also examined using essential dynamics analysis. The results of our simulations reveal that the binding conformation of 5α-DHT in C-terminal-deleted PTCR is more favorable for reduction reaction in PTCR, which shows strong agreement with kinetic data. These structural findings provide valuable information to understand substrate specificity of PTCR and further kinetic properties of enzymes belonging to the SDR superfamily. PMID:24646606

Cations Modulate Actin Bundle Mechanics, Assembly Dynamics, and Structure.

PubMed

Castaneda, Nicholas; Zheng, Tianyu; Rivera-Jacquez, Hector J; Lee, Hyun-Ju; Hyun, Jaekyung; Balaeff, Alexander; Huo, Qun; Kang, Hyeran

2018-04-12

Actin bundles are key factors in the mechanical support and dynamic reorganization of the cytoskeleton. High concentrations of multivalent counterions promote bundle formation through electrostatic attraction between actin filaments that are negatively charged polyelectrolytes. In this study, we evaluate how physiologically relevant divalent cations affect the mechanical, dynamic, and structural properties of actin bundles. Using a combination of total internal reflection fluorescence microscopy, transmission electron microscopy, and dynamic light scattering, we demonstrate that divalent cations modulate bundle stiffness, length distribution, and lateral growth. Molecular dynamics simulations of an all-atom model of the actin bundle reveal specific actin residues coordinate cation-binding sites that promote the bundle formation. Our work suggests that specific cation interactions may play a fundamental role in the assembly, structure, and mechanical properties of actin bundles.

Dynamics of movie competition and popularity spreading in recommender systems.

PubMed

Yeung, C H; Cimini, G; Jin, C-H

2011-01-01

We introduce a simple model to study movie competition in recommender systems. Movies of heterogeneous quality compete against each other through viewers' reviews and generate interesting dynamics at the box office. By assuming mean-field interactions between the competing movies, we show that the runaway effect of popularity spreading is triggered by defeating the average review score, leading to box-office hits: Popularity rises and peaks before fade-out. The average review score thus characterizes the critical movie quality necessary for transition from box-office bombs to blockbusters. The major factors affecting the critical review score are examined. By iterating the mean-field dynamical equations, we obtain qualitative agreements with simulations and real systems in the dynamical box-office forms, revealing the significant role of competition in understanding box-office dynamics.

Identifying and correcting non-Markov states in peptide conformational dynamics

NASA Astrophysics Data System (ADS)

Nerukh, Dmitry; Jensen, Christian H.; Glen, Robert C.

2010-02-01

Conformational transitions in proteins define their biological activity and can be investigated in detail using the Markov state model. The fundamental assumption on the transitions between the states, their Markov property, is critical in this framework. We test this assumption by analyzing the transitions obtained directly from the dynamics of a molecular dynamics simulated peptide valine-proline-alanine-leucine and states defined phenomenologically using clustering in dihedral space. We find that the transitions are Markovian at the time scale of ≈50 ps and longer. However, at the time scale of 30-40 ps the dynamics loses its Markov property. Our methodology reveals the mechanism that leads to non-Markov behavior. It also provides a way of regrouping the conformations into new states that now possess the required Markov property of their dynamics.

Dynamics of movie competition and popularity spreading in recommender systems

NASA Astrophysics Data System (ADS)

Yeung, C. H.; Cimini, G.; Jin, C.-H.

2011-01-01

We introduce a simple model to study movie competition in recommender systems. Movies of heterogeneous quality compete against each other through viewers’ reviews and generate interesting dynamics at the box office. By assuming mean-field interactions between the competing movies, we show that the runaway effect of popularity spreading is triggered by defeating the average review score, leading to box-office hits: Popularity rises and peaks before fade-out. The average review score thus characterizes the critical movie quality necessary for transition from box-office bombs to blockbusters. The major factors affecting the critical review score are examined. By iterating the mean-field dynamical equations, we obtain qualitative agreements with simulations and real systems in the dynamical box-office forms, revealing the significant role of competition in understanding box-office dynamics.

Peptide aggregation and solvent electrostriction in a simple zwitterionic dipeptide via molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Tulip, P. R.; Bates, S. P.

2009-07-01

We investigate the structure of the glycyl-l-alanine dipeptide in aqueous solution at a 1:20 peptide:water concentration via classical, atomistic molecular dynamics simulations using the CHARMM22 force field, and compare to recent neutron diffraction data [S. E. McLain, A. K. Soper, and A. Watts, Eur. Biophys. J. 37, 647 (2008); S. E. McLain, A. K. Soper, I. Diadone, J. C. Smith, and A. Watts, Angew. Chem. Int. Ed. 47, 9059 (2008)]. Comparison between simulations and experiments is made using the static structure factor S (Q ) . The effect of water model (TIP3P, TIP4P, and SPC/E) upon the solution structure is investigated. Agreement between experiment and simulation is generally good across the entire Q range, although some model-dependent variation is observed, particularly in the predicted intensities of features in S (Q ) . Peptide aggregation is found to be driven by "hydrophilic" (often bifurcated) hydrogen bonds formed between carboxy and amine functional groups, although simulations suggest that the degree of aggregation is less than that observed experimentally. It is found that hydrophobic association is not significant, with hydrophobic hydration being preferred to association. Detailed examination of the solute structural motifs reveals the existence of bifurcated motifs that are suggested to be an artifact of the CHARMM force field, and may imply that classical force fields provide a flawed structural and dynamical description of such molecular fluids. Investigation of the water structure reveals the presence of an electrostrictive effect which manifests itself as an increase in the number of interstitial molecules in the water second coordination shell, in contradiction to suggestions that this phenomenon arises owing to hydrogen bond bending. Detailed analysis based upon two-dimensional distribution functions suggests an intimate link between the phenomenon of electrostriction and the behavior of water under high-pressure compression. We find the magnitude of the electrostrictive effect inferred from the neutron diffraction data to be greater than that found in the simulations. Investigation of the solvation structure suggests that the CHARMM force field overhydrates the terminal carboxy group, and that this overhydration is accompanied by the presence of bifurcated hydrogen bonds.

Slow dynamics in translation-invariant quantum lattice models

NASA Astrophysics Data System (ADS)

Michailidis, Alexios A.; Žnidarič, Marko; Medvedyeva, Mariya; Abanin, Dmitry A.; Prosen, Tomaž; Papić, Z.

2018-03-01

Many-body quantum systems typically display fast dynamics and ballistic spreading of information. Here we address the open problem of how slow the dynamics can be after a generic breaking of integrability by local interactions. We develop a method based on degenerate perturbation theory that reveals slow dynamical regimes and delocalization processes in general translation invariant models, along with accurate estimates of their delocalization time scales. Our results shed light on the fundamental questions of the robustness of quantum integrable systems and the possibility of many-body localization without disorder. As an example, we construct a large class of one-dimensional lattice models where, despite the absence of asymptotic localization, the transient dynamics is exceptionally slow, i.e., the dynamics is indistinguishable from that of many-body localized systems for the system sizes and time scales accessible in experiments and numerical simulations.

Recent progress in simulating galaxy formation from the largest to the smallest scales

NASA Astrophysics Data System (ADS)

Faucher-Giguère, Claude-André

2018-05-01

Galaxy formation simulations are an essential part of the modern toolkit of astrophysicists and cosmologists alike. Astrophysicists use the simulations to study the emergence of galaxy populations from the Big Bang, as well as the formation of stars and supermassive black holes. For cosmologists, galaxy formation simulations are needed to understand how baryonic processes affect measurements of dark matter and dark energy. Owing to the extreme dynamic range of galaxy formation, advances are driven by novel approaches using simulations with different tradeoffs between volume and resolution. Large-volume but low-resolution simulations provide the best statistics, while higher-resolution simulations of smaller cosmic volumes can be evolved with self-consistent physics and reveal important emergent phenomena. I summarize recent progress in galaxy formation simulations, including major developments in the past five years, and highlight some key areas likely to drive further advances over the next decade.

The molecular dynamics simulation on the mechanical properties of Ni glass with external pressure

NASA Astrophysics Data System (ADS)

Zhang, Chuan-Hui; Wang, Ying; Sun, Dong-Bai

2017-08-01

In this paper, rapid quenching of Ni from crystal to metallic glass (MG) at different external pressures is simulated by molecular dynamics. The pair distribution functions (PDFs), mean-square displacement, glass transition temperature (Tg) and elastic property are calculated and compared with each other. The split of the second PDF peak means the liquid’s transition to glass state starts as previously reported for other MGs. And the Ri/R1 ratio rule is found to hold very well in Ni MG and reveals the SPO structural feature in the configurations. Moreover, with high external pressure, Tg values are more approximated by density-temperature and enthalpy-temperature curves. At last, the elastic modulus and mechanics modulus of quenching models produced a monotonous effect with increasing external pressure and temperature.

Nitriles at Silica Interfaces Resemble Supported Lipid Bilayers.

PubMed

Berne, Bruce J; Fourkas, John T; Walker, Robert A; Weeks, John D

2016-09-20

Nitriles are important solvents not just for bulk reactions but also for interfacial processes such as separations, heterogeneous catalysis, and electrochemistry. Although nitriles have a polar end and a lipophilic end, the cyano group is not hydrophilic enough for these substances to be thought of as prototypical amphiphiles. This picture is now changing, as research is revealing that at a silica surface nitriles can organize into structures that, in many ways, resemble lipid bilayers. This unexpected organization may be a key component of unique interfacial behavior of nitriles that make them the solvents of choice for so many applications. The first hints of this lipid-bilayer-like (LBL) organization of nitriles at silica interfaces came from optical Kerr effect (OKE) experiments on liquid acetonitrile confined in the pores of sol-gel glasses. The orientational dynamics revealed by OKE spectroscopy suggested that the confined liquid is composed of a relatively immobile sublayer of molecules that accept hydrogen bonds from the surface silanol groups and an interdigitated, antiparallel layer that is capable of exchanging into the centers of the pores. This picture of acetonitrile has been borne out by molecular dynamics simulations and vibrational sum-frequency generation (VSFG) experiments. Remarkably, these simulations further indicate that the LBL organization is repeated with increasing disorder at least 20 Å into the liquid from a flat silica surface. Simulations and VSFG and OKE experiments indicate that extending the alkyl chain to an ethyl group leads to the formation of even more tightly packed LBL organization featuring entangled alkyl tails. When the alkyl portion of the molecule is a bulky t-butyl group, packing constraints prevent well-ordered LBL organization of the liquid. In each case, the surface-induced organization of the liquid is reflected in its interfacial dynamics. Acetonitrile/water mixtures are favored solvent systems for separations technologies such as hydrophilic interaction chromatography. Simulations had suggested that although a monolayer of water partitions to the silica surface in such mixtures, acetonitrile tends to associate with this monolayer. VSFG experiments reveal that, even at high water mole fractions, patches of well-ordered acetonitrile bilayers remain at the silica surface. Due to its ability to donate and accept hydrogen bonds, methanol also partitions to a silica surface in acetonitrile/methanol mixtures and can serve to take the place of acetonitrile in the sublayer closest to the surface. These studies reveal that liquid nitriles can exhibit an unexpected wealth of new organizational and dynamic behaviors at silica surfaces, and presumably at the surfaces of other chemically important materials as well. This behavior cannot be predicted from the bulk organization of these liquids. Our new understanding of the interfacial behavior of these liquids will have important implications for optimizing a wide range of chemical processes in nitrile solvents.

Research on dynamic creep strain and settlement prediction under the subway vibration loading.

PubMed

Luo, Junhui; Miao, Linchang

2016-01-01

This research aims to explore the dynamic characteristics and settlement prediction of soft soil. Accordingly, the dynamic shear modulus formula considering the vibration frequency was utilized and the dynamic triaxial test conducted to verify the validity of the formula. Subsequently, the formula was applied to the dynamic creep strain function, with the factors influencing the improved dynamic creep strain curve of soft soil being analyzed. Meanwhile, the variation law of dynamic stress with sampling depth was obtained through the finite element simulation of subway foundation. Furthermore, the improved dynamic creep strain curve of soil layer was determined based on the dynamic stress. Thereafter, it could to estimate the long-term settlement under subway vibration loading by norms. The results revealed that the dynamic shear modulus formula is straightforward and practical in terms of its application to the vibration frequency. The values predicted using the improved dynamic creep strain formula closed to the experimental values, whilst the estimating settlement closed to the measured values obtained in the field test.

Structure and dynamics of a constitutively active neurotensin receptor

DOE PAGES

Krumm, Brian E.; Lee, Sangbae; Bhattacharya, Supriyo; ...

2016-12-07

Many G protein-coupled receptors show constitutive activity, resulting in the production of a second messenger in the absence of an agonist; and naturally occurring constitutively active mutations in receptors have been implicated in diseases. To gain insight into mechanistic aspects of constitutive activity, we report here the 3.3 Å crystal structure of a constitutively active, agonist-bound neurotensin receptor (NTSR1) and molecular dynamics simulations of agonist-occupied and ligand-free receptor. Comparison with the structure of a NTSR1 variant that has little constitutive activity reveals uncoupling of the ligand-binding domain from conserved connector residues, that effect conformational changes during GPCR activation. Furthermore, molecularmore » dynamics simulations show strong contacts between connector residue side chains and increased flexibility at the intracellular receptor face as features that coincide with robust signalling in cells. In conclusion, the loss of correlation between the binding pocket and conserved connector residues, combined with altered receptor dynamics, possibly explains the reduced neurotensin efficacy in the constitutively active NTSR1 and a facilitated initial engagement with G protein in the absence of agonist.« less

Dynamics of Water Associated with Lithium Ions Distributed in Polyethylene Oxide

DOE PAGES

Zhang, Zhe; Ohl, Michael; Diallo, Souleymane O.; ...

2015-11-03

We studied the dynamics of water in polyethylene oxide (PEO)/LiCl solution with quasielastic neutron scattering experiments and molecular dynamics (MD) simulations. Two different time scales of water diffusion representing interfacial water and bulk water dynamics have been identified. Furthermore, the measured diffusion coefficient of interfacial water remained 5–10 times smaller than that of bulk water, but both were slowed by approximately 50% in the presence of Li +. Detailed analysis of MD trajectories suggests that Li + is favorably found at the surface of the hydration layer, and the probability to find the caged Li + configuration formed by themore » PEO is lower than for the noncaged Li +-PEO configuration. In both configurations, however, the slowing down of water molecules is driven by reorienting water molecules and creating water-Li + hydration complexes. Moreover, performing the MD simulation with different ions (Na + and K +) revealed that smaller ionic radius of the ions is a key factor in disrupting the formation of PEO cages by allowing spaces for water molecules to come in between the ion and PEO.« less

Will water act as a photocatalyst for cluster phase chemical reactions? Vibrational overtone-induced dehydration reaction of methanediol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kramer, Zeb C.; Takahashi, Kaito; Skodje, Rex T.

2012-04-28

The possibility of water catalysis in the vibrational overtone-induced dehydration reaction of methanediol is investigated using ab initio dynamical simulations of small methanediol-water clusters. Quantum chemistry calculations employing clusters with one or two water molecules reveal that the barrier to dehydration is lowered by over 20 kcal/mol because of hydrogen-bonding at the transition state. Nevertheless, the simulations of the reaction dynamics following OH-stretch excitation show little catalytic effect of water and, in some cases, even show an anticatalytic effect. The quantum yield for the dehydration reaction exhibits a delayed threshold effect where reaction does not occur until the photon energymore » is far above the barrier energy. Unlike thermally induced reactions, it is argued that competition between reaction and the irreversible dissipation of photon energy may be expected to raise the dynamical threshold for the reaction above the transition state energy. It is concluded that quantum chemistry calculations showing barrier lowering are not sufficient to infer water catalysis in photochemical reactions, which instead require dynamical modeling.« less

Structure and dynamics of a constitutively active neurotensin receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krumm, Brian E.; Lee, Sangbae; Bhattacharya, Supriyo

Many G protein-coupled receptors show constitutive activity, resulting in the production of a second messenger in the absence of an agonist; and naturally occurring constitutively active mutations in receptors have been implicated in diseases. To gain insight into mechanistic aspects of constitutive activity, we report here the 3.3 Å crystal structure of a constitutively active, agonist-bound neurotensin receptor (NTSR1) and molecular dynamics simulations of agonist-occupied and ligand-free receptor. Comparison with the structure of a NTSR1 variant that has little constitutive activity reveals uncoupling of the ligand-binding domain from conserved connector residues, that effect conformational changes during GPCR activation. Furthermore, molecularmore » dynamics simulations show strong contacts between connector residue side chains and increased flexibility at the intracellular receptor face as features that coincide with robust signalling in cells. In conclusion, the loss of correlation between the binding pocket and conserved connector residues, combined with altered receptor dynamics, possibly explains the reduced neurotensin efficacy in the constitutively active NTSR1 and a facilitated initial engagement with G protein in the absence of agonist.« less

Dynamics of Water Associated with Lithium Ions Distributed in Polyethylene Oxide

NASA Astrophysics Data System (ADS)

Zhang, Zhe; Ohl, Michael; Diallo, Souleymane O.; Jalarvo, Niina H.; Hong, Kunlun; Han, Youngkyu; Smith, Gregory S.; Do, Changwoo

2015-11-01

The dynamics of water in polyethylene oxide (PEO)/LiCl solution has been studied with quasielastic neutron scattering experiments and molecular dynamics (MD) simulations. Two different time scales of water diffusion representing interfacial water and bulk water dynamics have been identified. The measured diffusion coefficient of interfacial water remained 5-10 times smaller than that of bulk water, but both were slowed by approximately 50% in the presence of Li+ . Detailed analysis of MD trajectories suggests that Li+ is favorably found at the surface of the hydration layer, and the probability to find the caged Li+ configuration formed by the PEO is lower than for the noncaged Li+-PEO configuration. In both configurations, however, the slowing down of water molecules is driven by reorienting water molecules and creating water-Li+ hydration complexes. Performing the MD simulation with different ions (Na+ and K+ ) revealed that smaller ionic radius of the ions is a key factor in disrupting the formation of PEO cages by allowing spaces for water molecules to come in between the ion and PEO.

Dynamics of Water Associated with Lithium Ions Distributed in Polyethylene Oxide.

PubMed

Zhang, Zhe; Ohl, Michael; Diallo, Souleymane O; Jalarvo, Niina H; Hong, Kunlun; Han, Youngkyu; Smith, Gregory S; Do, Changwoo

2015-11-06

The dynamics of water in polyethylene oxide (PEO)/LiCl solution has been studied with quasielastic neutron scattering experiments and molecular dynamics (MD) simulations. Two different time scales of water diffusion representing interfacial water and bulk water dynamics have been identified. The measured diffusion coefficient of interfacial water remained 5-10 times smaller than that of bulk water, but both were slowed by approximately 50% in the presence of Li(+). Detailed analysis of MD trajectories suggests that Li(+) is favorably found at the surface of the hydration layer, and the probability to find the caged Li(+) configuration formed by the PEO is lower than for the noncaged Li(+)-PEO configuration. In both configurations, however, the slowing down of water molecules is driven by reorienting water molecules and creating water-Li(+) hydration complexes. Performing the MD simulation with different ions (Na(+) and K(+)) revealed that smaller ionic radius of the ions is a key factor in disrupting the formation of PEO cages by allowing spaces for water molecules to come in between the ion and PEO.

Structure and dynamics of a constitutively active neurotensin receptor

PubMed Central

Krumm, Brian E.; Lee, Sangbae; Bhattacharya, Supriyo; Botos, Istvan; White, Courtney F.; Du, Haijuan; Vaidehi, Nagarajan; Grisshammer, Reinhard

2016-01-01

Many G protein-coupled receptors show constitutive activity, resulting in the production of a second messenger in the absence of an agonist; and naturally occurring constitutively active mutations in receptors have been implicated in diseases. To gain insight into mechanistic aspects of constitutive activity, we report here the 3.3 Å crystal structure of a constitutively active, agonist-bound neurotensin receptor (NTSR1) and molecular dynamics simulations of agonist-occupied and ligand-free receptor. Comparison with the structure of a NTSR1 variant that has little constitutive activity reveals uncoupling of the ligand-binding domain from conserved connector residues, that effect conformational changes during GPCR activation. Furthermore, molecular dynamics simulations show strong contacts between connector residue side chains and increased flexibility at the intracellular receptor face as features that coincide with robust signalling in cells. The loss of correlation between the binding pocket and conserved connector residues, combined with altered receptor dynamics, possibly explains the reduced neurotensin efficacy in the constitutively active NTSR1 and a facilitated initial engagement with G protein in the absence of agonist. PMID:27924846

Role of Dynamically Frustrated Bond Disorder in a Li + Superionic Solid Electrolyte

DOE PAGES

Adelstein, Nicole; Wood, Brandon C.

2016-09-16

Inorganic lithium solid electrolytes are critical components in next-generation solid-state batteries, yet the fundamental nature of the cation-anion interactions and their relevance for ionic conductivity in these materials remains enigmatic. Here, we employ first-principles molecular dynamics simulations to explore the interplay between chemistry, structure, and functionality of a highly conductive Li + solid electrolyte, Li3InBr6. Using local-orbital projections to dynamically track the evolution of the electronic charge density, the simulations reveal rapid, correlated fluctuations between cation-anion interactions with different degrees of directional covalent character. These chemical bond dynamics are shown to correlate with Li + mobility, and are enabled thermallymore » by intrinsic frustration between the preferred geometries of chemical bonding and lattice symmetry. We suggest that the fluctuating chemical environment from the polarizable anions functions similar to a solvent, contributing to the superionic behavior of Li 3InBr 6 by temporarily stabilizing configurations favorable for migrating Li +. The generality of these conclusions for understanding solid electrolytes and key factors governing the superionic phase transition is discussed.« less

Atomistic modeling of crystal-to-amorphous transition and associated kinetics in the Ni-Nb system by molecular dynamics simulations.

PubMed

Dai, X D; Li, J H; Liu, B X

2005-03-17

With the aid of ab initio calculations, an n-body potential of the Ni-Nb system is constructed under the Finnis-Sinclair formalism and the constructed potential is capable of not only reproducing some static physical properties but also revealing the atomistic mechanism of crystal-to-amorphous transition and associated kinetics. With application of the constructed potential, molecular dynamics simulations using the solid solution models reveal that the physical origin of crystal-to-amorphous transition is the crystalline lattice collapsing while the solute atoms are exceeding the critical solid solubilities, which are determined to be 19 atom % Ni and 13 atom % Nb for the Nb- and Ni-based solid solutions, respectively. It follows that an intrinsic glass-forming ability of the Ni-Nb system is within 19-87 atom % Ni, which matches well with that observed in ion beam mixing/solid-state reaction experiments. Simulations using the Nb/Ni/Nb (Ni/Nb/Ni) sandwich models indicate that the amorphous layer at the interfaces grows in a layer-by-layer mode and that, upon dissolving solute atoms, the Ni lattice approaches and exceeds its critical solid solubility faster than the Nb lattice, revealing an asymmetric behavior in growth kinetics. Moreover, an energy diagram is obtained by computing the energetic sequence of the Ni(x)Nb(100)(-)(x) alloy in fcc, bcc, and amorphous structures, respectively, over the entire composition range, and the diagram could serve as a guide for predicting the metastable alloy formation in the Ni-Nb system.

Finite Element Simulation of the Shear Effect of Ultrasonic on Heat Exchanger Descaling

NASA Astrophysics Data System (ADS)

Lu, Shaolv; Wang, Zhihua; Wang, Hehui

2018-03-01

The shear effect on the interface of metal plate and its attached scale is an important mechanism of ultrasonic descaling, which is caused by the different propagation speed of ultrasonic wave in two different mediums. The propagating of ultrasonic wave on the shell is simulated based on the ANSYS/LS-DYNA explicit dynamic analysis. The distribution of shear stress in different paths under ultrasonic vibration is obtained through the finite element analysis and it reveals the main descaling mechanism of shear effect. The simulation result is helpful and enlightening to the reasonable design and the application of the ultrasonic scaling technology on heat exchanger.

Slow dynamics in protein fluctuations revealed by time-structure based independent component analysis: The case of domain motions

NASA Astrophysics Data System (ADS)

Naritomi, Yusuke; Fuchigami, Sotaro

2011-02-01

Protein dynamics on a long time scale was investigated using all-atom molecular dynamics (MD) simulation and time-structure based independent component analysis (tICA). We selected the lysine-, arginine-, ornithine-binding protein (LAO) as a target protein and focused on its domain motions in the open state. A MD simulation of the LAO in explicit water was performed for 600 ns, in which slow and large-amplitude domain motions of the LAO were observed. After extracting domain motions by rigid-body domain analysis, the tICA was applied to the obtained rigid-body trajectory, yielding slow modes of the LAO's domain motions in order of decreasing time scale. The slowest mode detected by the tICA represented not a closure motion described by a largest-amplitude mode determined by the principal component analysis but a twist motion with a time scale of tens of nanoseconds. The slow dynamics of the LAO were well described by only the slowest mode and were characterized by transitions between two basins. The results show that tICA is promising for describing and analyzing slow dynamics of proteins.

Slow dynamics in protein fluctuations revealed by time-structure based independent component analysis: the case of domain motions.

PubMed

Naritomi, Yusuke; Fuchigami, Sotaro

2011-02-14

Protein dynamics on a long time scale was investigated using all-atom molecular dynamics (MD) simulation and time-structure based independent component analysis (tICA). We selected the lysine-, arginine-, ornithine-binding protein (LAO) as a target protein and focused on its domain motions in the open state. A MD simulation of the LAO in explicit water was performed for 600 ns, in which slow and large-amplitude domain motions of the LAO were observed. After extracting domain motions by rigid-body domain analysis, the tICA was applied to the obtained rigid-body trajectory, yielding slow modes of the LAO's domain motions in order of decreasing time scale. The slowest mode detected by the tICA represented not a closure motion described by a largest-amplitude mode determined by the principal component analysis but a twist motion with a time scale of tens of nanoseconds. The slow dynamics of the LAO were well described by only the slowest mode and were characterized by transitions between two basins. The results show that tICA is promising for describing and analyzing slow dynamics of proteins.

The role of sulfates on antifreeze protein activity.

PubMed

Meister, Konrad; Duman, John G; Xu, Yao; DeVries, Arthur L; Leitner, David M; Havenith, Martina

2014-07-17

In the present study, we have investigated the effect of sodium sulfate (Na2SO4) buffer on the antifreeze activity of DAFP-1, the primary AFP in the hemolymph of the beetle Dendroides canadensis. In contrast to previous studies, we found evidence that sodium sulfate does not suppress antifreeze activity of DAFP-1. Terahertz absorption spectroscopy (THz) studies were combined with molecular dynamics (MD) simulations to investigate the change in collective hydrogen bond dynamics in the vicinity of the AFP upon addition of sodium sulfate. The MD simulations revealed that the gradient of H-bond dynamics toward the ice-binding site is even more pronounced when adding sodium sulfate: The cosolute dramatically slows the hydrogen bond dynamics on the ice-binding plane of DAFP-1, whereas it has a more modest effect in the vicinity of other parts of the protein. These theoretical predictions are in agreement with the experimentally observed increase in THz absorption for solvated DAFP-1 upon addition of sodium sulfate. These studies support our previously postulated mechanism for AF activity, with a preferred ice binding by threonine on nanoice crystals which is supported by a long-range effect on hydrogen bond dynamics.

Molecular dynamics simulations and structure-based network analysis reveal structural and functional aspects of G-protein coupled receptor dimer interactions.

PubMed

Baltoumas, Fotis A; Theodoropoulou, Margarita C; Hamodrakas, Stavros J

2016-06-01

A significant amount of experimental evidence suggests that G-protein coupled receptors (GPCRs) do not act exclusively as monomers but also form biologically relevant dimers and oligomers. However, the structural determinants, stoichiometry and functional importance of GPCR oligomerization remain topics of intense speculation. In this study we attempted to evaluate the nature and dynamics of GPCR oligomeric interactions. A representative set of GPCR homodimers were studied through Coarse-Grained Molecular Dynamics simulations, combined with interface analysis and concepts from network theory for the construction and analysis of dynamic structural networks. Our results highlight important structural determinants that seem to govern receptor dimer interactions. A conserved dynamic behavior was observed among different GPCRs, including receptors belonging in different GPCR classes. Specific GPCR regions were highlighted as the core of the interfaces. Finally, correlations of motion were observed between parts of the dimer interface and GPCR segments participating in ligand binding and receptor activation, suggesting the existence of mechanisms through which dimer formation may affect GPCR function. The results of this study can be used to drive experiments aimed at exploring GPCR oligomerization, as well as in the study of transmembrane protein-protein interactions in general.

Molecular dynamics simulations and structure-based network analysis reveal structural and functional aspects of G-protein coupled receptor dimer interactions

NASA Astrophysics Data System (ADS)

Baltoumas, Fotis A.; Theodoropoulou, Margarita C.; Hamodrakas, Stavros J.

2016-06-01

A significant amount of experimental evidence suggests that G-protein coupled receptors (GPCRs) do not act exclusively as monomers but also form biologically relevant dimers and oligomers. However, the structural determinants, stoichiometry and functional importance of GPCR oligomerization remain topics of intense speculation. In this study we attempted to evaluate the nature and dynamics of GPCR oligomeric interactions. A representative set of GPCR homodimers were studied through Coarse-Grained Molecular Dynamics simulations, combined with interface analysis and concepts from network theory for the construction and analysis of dynamic structural networks. Our results highlight important structural determinants that seem to govern receptor dimer interactions. A conserved dynamic behavior was observed among different GPCRs, including receptors belonging in different GPCR classes. Specific GPCR regions were highlighted as the core of the interfaces. Finally, correlations of motion were observed between parts of the dimer interface and GPCR segments participating in ligand binding and receptor activation, suggesting the existence of mechanisms through which dimer formation may affect GPCR function. The results of this study can be used to drive experiments aimed at exploring GPCR oligomerization, as well as in the study of transmembrane protein-protein interactions in general.

Emergent dynamic structures and statistical law in spherical lattice gas automata.

PubMed

Yao, Zhenwei

2017-12-01

Various lattice gas automata have been proposed in the past decades to simulate physics and address a host of problems on collective dynamics arising in diverse fields. In this work, we employ the lattice gas model defined on the sphere to investigate the curvature-driven dynamic structures and analyze the statistical behaviors in equilibrium. Under the simple propagation and collision rules, we show that the uniform collective movement of the particles on the sphere is geometrically frustrated, leading to several nonequilibrium dynamic structures not found in the planar lattice, such as the emergent bubble and vortex structures. With the accumulation of the collision effect, the system ultimately reaches equilibrium in the sense that the distribution of the coarse-grained speed approaches the two-dimensional Maxwell-Boltzmann distribution despite the population fluctuations in the coarse-grained cells. The emergent regularity in the statistical behavior of the system is rationalized by mapping our system to a generalized random walk model. This work demonstrates the capability of the spherical lattice gas automaton in revealing the lattice-guided dynamic structures and simulating the equilibrium physics. It suggests the promising possibility of using lattice gas automata defined on various curved surfaces to explore geometrically driven nonequilibrium physics.

Emergent dynamic structures and statistical law in spherical lattice gas automata

NASA Astrophysics Data System (ADS)

Yao, Zhenwei

2017-12-01

Various lattice gas automata have been proposed in the past decades to simulate physics and address a host of problems on collective dynamics arising in diverse fields. In this work, we employ the lattice gas model defined on the sphere to investigate the curvature-driven dynamic structures and analyze the statistical behaviors in equilibrium. Under the simple propagation and collision rules, we show that the uniform collective movement of the particles on the sphere is geometrically frustrated, leading to several nonequilibrium dynamic structures not found in the planar lattice, such as the emergent bubble and vortex structures. With the accumulation of the collision effect, the system ultimately reaches equilibrium in the sense that the distribution of the coarse-grained speed approaches the two-dimensional Maxwell-Boltzmann distribution despite the population fluctuations in the coarse-grained cells. The emergent regularity in the statistical behavior of the system is rationalized by mapping our system to a generalized random walk model. This work demonstrates the capability of the spherical lattice gas automaton in revealing the lattice-guided dynamic structures and simulating the equilibrium physics. It suggests the promising possibility of using lattice gas automata defined on various curved surfaces to explore geometrically driven nonequilibrium physics.

Equilibration of energy in slow–fast systems

PubMed Central

Shah, Kushal; Gelfreich, Vassili; Rom-Kedar, Vered

2017-01-01

Ergodicity is a fundamental requirement for a dynamical system to reach a state of statistical equilibrium. However, in systems with several characteristic timescales, the ergodicity of the fast subsystem impedes the equilibration of the whole system because of the presence of an adiabatic invariant. In this paper, we show that violation of ergodicity in the fast dynamics can drive the whole system to equilibrium. To show this principle, we investigate the dynamics of springy billiards, which are mechanical systems composed of a small particle bouncing elastically in a bounded domain, where one of the boundary walls has finite mass and is attached to a linear spring. Numerical simulations show that the springy billiard systems approach equilibrium at an exponential rate. However, in the limit of vanishing particle-to-wall mass ratio, the equilibration rates remain strictly positive only when the fast particle dynamics reveal two or more ergodic components for a range of wall positions. For this case, we show that the slow dynamics of the moving wall can be modeled by a random process. Numerical simulations of the corresponding springy billiards and their random models show equilibration with similar positive rates. PMID:29183966

Microsecond protein dynamics observed at the single-molecule level

NASA Astrophysics Data System (ADS)

Otosu, Takuhiro; Ishii, Kunihiko; Tahara, Tahei

2015-07-01

How polypeptide chains acquire specific conformations to realize unique biological functions is a central problem of protein science. Single-molecule spectroscopy, combined with fluorescence resonance energy transfer, is utilized to study the conformational heterogeneity and the state-to-state transition dynamics of proteins on the submillisecond to second timescales. However, observation of the dynamics on the microsecond timescale is still very challenging. This timescale is important because the elementary processes of protein dynamics take place and direct comparison between experiment and simulation is possible. Here we report a new single-molecule technique to reveal the microsecond structural dynamics of proteins through correlation of the fluorescence lifetime. This method, two-dimensional fluorescence lifetime correlation spectroscopy, is applied to clarify the conformational dynamics of cytochrome c. Three conformational ensembles and the microsecond transitions in each ensemble are indicated from the correlation signal, demonstrating the importance of quantifying microsecond dynamics of proteins on the folding free energy landscape.

Microsecond protein dynamics observed at the single-molecule level

PubMed Central

Otosu, Takuhiro; Ishii, Kunihiko; Tahara, Tahei

2015-01-01

How polypeptide chains acquire specific conformations to realize unique biological functions is a central problem of protein science. Single-molecule spectroscopy, combined with fluorescence resonance energy transfer, is utilized to study the conformational heterogeneity and the state-to-state transition dynamics of proteins on the submillisecond to second timescales. However, observation of the dynamics on the microsecond timescale is still very challenging. This timescale is important because the elementary processes of protein dynamics take place and direct comparison between experiment and simulation is possible. Here we report a new single-molecule technique to reveal the microsecond structural dynamics of proteins through correlation of the fluorescence lifetime. This method, two-dimensional fluorescence lifetime correlation spectroscopy, is applied to clarify the conformational dynamics of cytochrome c. Three conformational ensembles and the microsecond transitions in each ensemble are indicated from the correlation signal, demonstrating the importance of quantifying microsecond dynamics of proteins on the folding free energy landscape. PMID:26151767

Impact of hydration and temperature history on the structure and dynamics of lignin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vural, Derya; Gainaru, C.; O'Neill, Hugh Michael

The full utilization of plant biomass for the production of energy and novel materials often involves high temperature treatment. Examples include melt spinning of lignin for manufacturing low-cost carbon fiber and the relocalization of lignin to increase the accessibility of cellulose for production of biofuels. These temperature-induced effects arise from poorly understood changes in lignin flexibility. Here, we combine molecular dynamics simulations with neutron scattering and dielectric spectroscopy experiments to probe the dependence of lignin dynamics on hydration and thermal history. We find a dynamical and structural hysteresis: at a given temperature, the lignin molecules are more expanded and theirmore » dynamics faster when the lignin is cooled than when heated. The structural hysteresis is more pronounced for dry lignin. The difference in dynamics, however, follows a different trend, it is found to be more significant at high temperatures and high hydration levels. The simulations also reveal syringyl units to be more dynamic than guiacyl. The results provide an atomic-detailed description of lignin dynamics, important for understanding lignin role in plant cell wall mechanics and for rationally improving lignin processing. The lignin glass transition, at which the polymer softens, is lower when lignin is cooled than when heated, therefore extending the cooling phase of processing and shortening the heating phase may offer ways to lower processing costs.« less

Impact of hydration and temperature history on the structure and dynamics of lignin

DOE PAGES

Vural, Derya; Gainaru, C.; O'Neill, Hugh Michael; ...

2018-03-16

The full utilization of plant biomass for the production of energy and novel materials often involves high temperature treatment. Examples include melt spinning of lignin for manufacturing low-cost carbon fiber and the relocalization of lignin to increase the accessibility of cellulose for production of biofuels. These temperature-induced effects arise from poorly understood changes in lignin flexibility. Here, we combine molecular dynamics simulations with neutron scattering and dielectric spectroscopy experiments to probe the dependence of lignin dynamics on hydration and thermal history. We find a dynamical and structural hysteresis: at a given temperature, the lignin molecules are more expanded and theirmore » dynamics faster when the lignin is cooled than when heated. The structural hysteresis is more pronounced for dry lignin. The difference in dynamics, however, follows a different trend, it is found to be more significant at high temperatures and high hydration levels. The simulations also reveal syringyl units to be more dynamic than guiacyl. The results provide an atomic-detailed description of lignin dynamics, important for understanding lignin role in plant cell wall mechanics and for rationally improving lignin processing. The lignin glass transition, at which the polymer softens, is lower when lignin is cooled than when heated, therefore extending the cooling phase of processing and shortening the heating phase may offer ways to lower processing costs.« less

Understanding homogeneous nucleation in solidification of aluminum by molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Mahata, Avik; Asle Zaeem, Mohsen; Baskes, Michael I.

2018-02-01

Homogeneous nucleation from aluminum (Al) melt was investigated by million-atom molecular dynamics simulations utilizing the second nearest neighbor modified embedded atom method potentials. The natural spontaneous homogenous nucleation from the Al melt was produced without any influence of pressure, free surface effects and impurities. Initially isothermal crystal nucleation from undercooled melt was studied at different constant temperatures, and later superheated Al melt was quenched with different cooling rates. The crystal structure of nuclei, critical nucleus size, critical temperature for homogenous nucleation, induction time, and nucleation rate were determined. The quenching simulations clearly revealed three temperature regimes: sub-critical nucleation, super-critical nucleation, and solid-state grain growth regimes. The main crystalline phase was identified as face-centered cubic, but a hexagonal close-packed (hcp) and an amorphous solid phase were also detected. The hcp phase was created due to the formation of stacking faults during solidification of Al melt. By slowing down the cooling rate, the volume fraction of hcp and amorphous phases decreased. After the box was completely solid, grain growth was simulated and the grain growth exponent was determined for different annealing temperatures.

Modeling Water Redistribution in a Near-Surface Arid Soil

NASA Astrophysics Data System (ADS)

Luo, Y.; Ghezzehei, T. A.; Berli, M.; Dijkema, J.; Koonce, J.

2017-12-01

Desert soils cover about one third of the Earth's land surface and play an important role in the ecology and hydrology of arid environments. Despite their large extend, relatively little is known about their near-surface (top centimeters to meter) water dynamics. Recent studies by Koonce (2016) and Dijkema et al. (2017) shed light on the water dynamics of near-surface arid soil but also revealed some of the challenges to simulate the water redistribution in arid soils. The goal of this study was to improve water redistribution simulations in near-surface arid soils by employing more advanced hydraulic conductivity functions. Expanding on the work by Dijkema et al. (2017), we used a HYDRUS-1D model with different hydraulic conductivity functions to simulate water redistribution within the soil as a function of precipitation, evaporation and drainage. Model calculations were compared with measured data from the SEPHAS weighing lysimeters in Boulder City, NV. Preliminary results indicate that water redistribution simulations of near-surface arid soils can be improved by using hydraulic conductivity functions that can capture capillary, film and vapor flow, like for example the Peter-Durner-Iden (PDI) model.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohmura, Satoshi; Nagaya, Kiyonobu; Yao, Makoto

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-chargedmore » 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)« less

Combined quantum-mechanics/molecular-mechanics dynamics simulation of A-DNA double strands irradiated by ultra-low-energy carbon ions

NASA Astrophysics Data System (ADS)

Ngaojampa, C.; Nimmanpipug, P.; Yu, L. D.; Anuntalabhochai, S.; Lee, V. S.

2011-02-01

In order to promote understanding of the fundamentals of ultra-low-energy ion interaction with DNA, molecular dynamics simulations using combined quantum-mechanics/molecular-mechanics of poly-AT and poly-GC A-DNA double strands irradiated by <200 eV carbon ions were performed to investigate the molecular implications of mutation bias. The simulations were focused on the responses of the DNA backbones and nitrogenous bases to irradiation. Analyses of the root mean square displacements of the backbones and non-hydrogen atoms of base rings of the simulated DNA structure after irradiation revealed a potential preference of DNA double strand separation, dependent on the irradiating energy. The results show that for the backbones, the large difference in the displacement between poly-GC and poly-AT in the initial time period could be the reason for the backbone breakage; for the nitrogenous base pairs, A-T is 30% more sensitive or vulnerable to ion irradiation than G-C, demonstrating a preferential, instead of random, effect of irradiation-induced mutation.

The atomic-scale nucleation mechanism of NiTi metallic glasses upon isothermal annealing studied via molecular dynamics simulations.

PubMed

Li, Yang; Li, JiaHao; Liu, BaiXin

2015-10-28

Nucleation is one of the most essential transformation paths in phase transition and exerts a significant influence on the crystallization process. Molecular dynamics simulations were performed to investigate the atomic-scale nucleation mechanisms of NiTi metallic glasses upon devitrification at various temperatures (700 K, 750 K, 800 K, and 850 K). Our simulations reveal that at 700 K and 750 K, nucleation is polynuclear with high nucleation density, while at 800 K it is mononuclear. The underlying nucleation mechanisms have been clarified, manifesting that nucleation can be induced either by the initial ordered clusters (IOCs) or by the other precursors of nuclei evolved directly from the supercooled liquid. IOCs and other precursors stem from the thermal fluctuations of bond orientational order in supercooled liquids during the quenching process and during the annealing process, respectively. The simulation results not only elucidate the underlying nucleation mechanisms varied with temperature, but also unveil the origin of nucleation. These discoveries offer new insights into the devitrification mechanism of metallic glasses.

Backbone conformations and side chain flexibility of two somatostatin mimics investigated by molecular dynamics simulations.

PubMed

Interlandi, Gianluca

2009-05-15

Molecular dynamics simulations with two designed somatostatin mimics, SOM230 and SMS 201-995, were performed in explicit water for a total aggregated time of 208 ns. Analysis of the runs with SOM230 revealed the presence of two clusters of conformations. Strikingly, the two sampled conformers correspond to the two main X-ray structures in the asymmetric unit of SMS 201-995. Structural comparison between the residues of SOM230 and SMS 201-995 provides an explanation for the high binding affinity of SOM230 to four of five somatostatin receptors. Similarly, cluster analysis of the simulations with SMS 201-995 shows that the backbone of the peptide interconverts between its two main crystallographic conformers. The conformations of SMS 201-995 sampled in the two clusters violated two different sets of NOE distance constraints in agreement with a previous NMR study. Differences in side chain fluctuations between SOM230 and SMS 201-995 observed in the simulations may contribute to the relatively higher binding affinity of SOM230 to most somatostatin receptors.

An ab initio study of the structure and dynamics of bulk liquid Ag and its liquid-vapor interface

NASA Astrophysics Data System (ADS)

Gonzalez Del Rio, Beatriz; Gonzalez Tesedo, Luis Enrique; Gonzalez Fernandez, David Jose

Several static and dynamic properties of bulk liquid Ag at a thermodynamic state near its triple point have been calculated by means of ab initio molecular dynamics simulations. The calculated static structure shows a very good agreement with the available experimental data. The dynamical structure reveals collective density excitations with an associated dispersion relation which points to a small positive dispersion. Results are also reported at a slightly higher temperature in order to study the structure of the free liquid surface. The ionic density profile shows an oscillatory behaviour with two different wavelenghts, as the spacing between the outer and first inner layer is different from that between the other inner layers.

Molecular dynamics simulations to calculate glass transition temperature and elastic constants of novel polyethers.

PubMed

Sarangapani, Radhakrishnan; Reddy, Sreekantha T; Sikder, Arun K

2015-04-01

Molecular dynamics simulations studies are carried out on hydroxyl terminated polyethers that are useful in energetic polymeric binder applications. Energetic polymers derived from oxetanes with heterocyclic side chains with different energetic substituents are designed and simulated under the ensembles of constant particle number, pressure, temperature (NPT) and constant particle number, volume, temperature (NVT). Specific volume of different amorphous polymeric models is predicted using NPT-MD simulations as a function of temperature. Plots of specific volume versus temperature exhibited a characteristic change in slope when amorphous systems change from glassy to rubbery state. Several material properties such as Young's, shear, and bulk modulus, Poisson's ratio, etc. are predicted from equilibrated structures and established the structure-property relations among designed polymers. Energetic performance parameters of these polymers are calculated and results reveal that the performance of the designed polymers is comparable to the benchmark energetic polymers like polyNIMMO, polyAMMO and polyBAMO. Overall, it is worthy remark that this molecular simulations study on novel energetic polyethers provides a good guidance on mastering the design principles and allows us to design novel polymers of tailored properties. Copyright © 2015 Elsevier Inc. All rights reserved.

Mechanical response of two polyimides through coarse-grained molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Sudarkodi, V.; Sooraj, K.; Nair, Nisanth N.; Basu, Sumit; Parandekar, Priya V.; Sinha, Nishant K.; Prakash, Om; Tsotsis, Tom

2018-03-01

Coarse-grained molecular dynamics (MD) simulations allow us to predict the mechanical responses of polymers, starting merely with a description of their molecular architectures. It is interesting to ask whether, given two competing molecular architectures, coarse-grained MD simulations can predict the differences that can be expected in their mechanical responses. We have studied two crosslinked polyimides PMR15 and HFPE52—both used in high- temperature applications—to assess whether the subtle differences in their uniaxial stress-strain responses, revealed by experiments, can be reproduced by carefully coarse-grained MD models. The coarse graining procedure for PMR15 is outlined in this work, while the coarse grain forcefields for HFPE52 are borrowed from an earlier one (Pandiyan et al 2015 Macromol. Theory Simul. 24 513-20). We show that the stress-strain responses of both these polyimides are qualitatively reproduced, and important insights into their deformation and failure mechanisms are obtained. More importantly, the differences in the molecular architecture between the polyimides carry over to the differences in the stress-strain responses in a manner that parallels the experimental results. A critical assessment of the successes and shortcomings of predicting mechanical responses through coarse-grained MD simulations has been made.

Atomistic Simulations of the pH Induced Functional Rearrangement of Influenza Hemagglutinin

NASA Astrophysics Data System (ADS)

Lin, Xingcheng; Noel, Jeffrey; Wang, Qinghua; Ma, Jianpeng; Onuchic, Jose

Influenza hemagglutinin (HA), a surface glycoprotein responsible for the entry and replication of flu viruses in their host cells, functions by starting a dramatic conformational rearrangement, which leads to a fusion of the viral and endosomal membranes. It has been claimed that a loop-to-coiled-coil transition of the B-loop domain of HA drives the HA-induced membrane fusion. On the lack of dynamical details, however, the microscopic picture for this proposed ``spring-loaded'' movement is missing. To elaborate on the transition of the B-loop, we performed a set of unbiased all-atom molecular dynamics simulations of the full B-loop structure with the CHARMM36 force field. The complete free-energy profile constructed from our simulations reveals a slow transition rate for the B-loop that is incompatible with a downhill process. Additionally, our simulations indicate two potential sources of kinetic traps in the structural switch of the B-loop: Desolvation barriers and non-native secondary structure formation. The slow timescale of the B-loop transition also confirms our previous discovery from simulations using a coarse-grained structure-based model, which identified two competitive pathways both with a slow B-loop transition for HA to guide the membrane fusion.

Multiscale Molecular Dynamics Simulations of Beta-Amyloid Interactions with Neurons

NASA Astrophysics Data System (ADS)

Qiu, Liming; Vaughn, Mark; Cheng, Kelvin

2012-10-01

Early events of human beta-amyloid protein interactions with cholesterol-containing membranes are critical to understanding the pathogenesis of Alzheimer's disease (AD) and to exploring new therapeutic interventions of AD. Atomistic molecular dynamics (AMD) simulations have been extensively used to study the protein-lipid interaction at high atomic resolutions. However, traditional MD simulations are not efficient in sampling the phase space of complex lipid/protein systems with rugged free energy landscapes. Meanwhile, coarse-grained MD (CGD) simulations are efficient in the phase space sampling but suffered from low spatial resolutions and from the fact that the energy landscapes are not identical to those of the AMD. Here, a multiscale approach was employed to simulate the protein-lipid interactions of beta-amyloid upon its release from proteolysis residing in the neuronal membranes. We utilized a forward (AMD to CGD) and reverse (CGD-AMD) strategy to explore new transmembrane and surface protein configuration and evaluate the stabilization mechanisms by measuring the residue-specific protein-lipid or protein conformations. The detailed molecular interactions revealed in this multiscale MD approach will provide new insights into understanding the early molecular events leading to the pathogenesis of AD.

Using Dynamic Simulation to Evaluate Attemperator Operation in a Natural Gas Combined Cycle With Duct Burners in the Heat Recovery Steam Generator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liese, Eric; Zitney, Stephen E.

A generic training simulator of a natural gas combined cycle was modified to match operations at a real plant. The objective was to use the simulator to analyze cycling operations of the plant. Initial operation of the simulator revealed the potential for saturation conditions in the final high pressure superheater as the attemperator tried to control temperature at the superheater outlet during gas turbine loading and unloading. Subsequent plant operational data confirmed simulation results. Multiple simulations were performed during loading and unloading of the gas turbine to determine operational strategies that prevented saturation and increased the approach to saturation temperature.more » The solutions included changes to the attemperator temperature control setpoints and strategic control of the steam turbine inlet pressure control valve.« less

Photodissociation Dynamics of Phenol: Multistate Trajectory Simulations including Tunneling

DOE PAGES

Xu, Xuefei; Zheng, Jingjing; Yang, Ke R.; ...

2014-10-27

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 S 1more » state, namely, tunneling in a coherent mixture of states starting in a smaller R OH (~0.9–1.0 Å) region than has previously been invoked. The simulations also show that most trajectories do not pass close to the S 1–S 2 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.« less

Conformational analysis of GT1B ganglioside and its interaction with botulinum neurotoxin type B: a study by molecular modeling and molecular dynamics.

PubMed

Venkateshwari, Sureshkumar; Veluraja, Kasinadar

2012-01-01

The conformational property of oligosaccharide GT1B in aqueous environment was studied by molecular dynamics (MD) simulation using all-atom model. Based on the trajectory analysis, three prominent conformational models were proposed for GT1B. Direct and water-mediated hydrogen bonding interactions stabilize these structures. The molecular modeling and 15 ns MD simulation of the Botulinum Neuro Toxin/B (BoNT/B) - GT1B complex revealed that BoNT/B can accommodate the GT1B in the single binding mode. Least mobility was seen for oligo-GT1B in the binding pocket. The bound conformation of GT1B obtained from the MD simulation of the BoNT/B-GT1B complex bear a close conformational similarity with the crystal structure of BoNT/A-GT1B complex. The mobility noticed for Arg 1268 in the dynamics was accounted for its favorable interaction with terminal NeuNAc. The internal NeuNAc1 tends to form 10 hydrogen bonds with BoNT/B, hence specifying this particular site as a crucial space for the therapeutic design that can restrict the pathogenic activity of BoNT/B.

Pattern does not equal process: what does patch occupancy really tell us about metapopulation dynamics?

PubMed

Clinchy, Michael; Haydon, Daniel T; Smith, Andrew T

2002-04-01

Patch occupancy surveys are commonly used to parameterize metapopulation models. If isolation predicts patch occupancy, this is generally attributed to a balance between distance-dependent recolonization and spatially independent extinctions. We investigated whether similar patterns could also be generated by a process of spatially correlated extinctions following a unique colonization event (analogous to nonequilibrium processes in island biogeography). We simulated effects of spatially correlated extinctions on patterns of patch occupancy among pikas (Ochotona princeps) at Bodie, California, using randomly located extinction disks to represent the likely effects of predation. Our simulations produced similar patterns to those cited as evidence of balanced metapopulation dynamics. Simulations using a variety of disk sizes and patch configurations confirmed that our results are potentially applicable to a broad range of species and sites. Analyses of the observed patterns of patch occupancy at Bodie revealed little evidence of rescue effects and strong evidence that most recolonizations are ephemeral in nature. Persistence will be overestimated if static or declining patterns of patch occupancy are mistakenly attributed to dynamically stable metapopulation processes. Consequently, simple patch occupancy surveys should not be considered as substitutes for detailed experimental tests of hypothesized population processes, particularly when conservation concerns are involved.

Complex Dynamics of Delay-Coupled Neural Networks

NASA Astrophysics Data System (ADS)

Mao, Xiaochen

2016-09-01

This paper reveals the complicated dynamics of a delay-coupled system that consists of a pair of sub-networks and multiple bidirectional couplings. Time delays are introduced into the internal connections and network-couplings, respectively. The stability and instability of the coupled network are discussed. The sufficient conditions for the existence of oscillations are given. Case studies of numerical simulations are given to validate the analytical results. Interesting and complicated neuronal activities are observed numerically, such as rest states, periodic oscillations, multiple switches of rest states and oscillations, and the coexistence of different types of oscillations.

Time-dependent first-principles study of angle-resolved secondary electron emission from atomic sheets

NASA Astrophysics Data System (ADS)

Ueda, Yoshihiro; Suzuki, Yasumitsu; Watanabe, Kazuyuki

2018-02-01

Angle-resolved secondary electron emission (ARSEE) spectra were analyzed for two-dimensional atomic sheets using a time-dependent first-principles simulation of electron scattering. We demonstrate that the calculated ARSEE spectra capture the unoccupied band structure of the atomic sheets. The excitation dynamics that lead to SEE have also been revealed by the time-dependent Kohn-Sham decomposition scheme. In the present study, the mechanism for the experimentally observed ARSEE from atomic sheets is elucidated with respect to both energetics and the dynamical aspects of SEE.

Making molecular balloons in laser-induced explosive boiling of polymer solutions.

PubMed

Leveugle, Elodie; Sellinger, Aaron; Fitz-Gerald, James M; Zhigilei, Leonid V

2007-05-25

The effect of the dynamic molecular rearrangements leading to compositional segregation is revealed in coarse-grained molecular dynamics simulations of short pulse laser interaction with a polymer solution in a volatile matrix. An internal release of matrix vapor at the onset of the explosive boiling of the overheated liquid is capable of pushing polymer molecules to the outskirts of a transient bubble, forming a polymer-rich surface layer enclosing the volatile matrix material. The results explain unexpected "deflated balloon" structures observed in films deposited by the matrix-assisted pulsed laser evaporation technique.

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.

Toward elucidating the heat activation mechanism of the TRPV1 channel gating by molecular dynamics simulation.

PubMed

Wen, Han; Qin, Feng; Zheng, Wenjun

2016-12-01

As a key cellular sensor, the TRPV1 cation channel undergoes a gating transition from a closed state to an open state in response to various physical and chemical stimuli including noxious heat. Despite years of study, the heat activation mechanism of TRPV1 gating remains enigmatic at the molecular level. Toward elucidating the structural and energetic basis of TRPV1 gating, we have performed molecular dynamics (MD) simulations (with cumulative simulation time of 3 μs), starting from the high-resolution closed and open structures of TRPV1 solved by cryo-electron microscopy. In the closed-state simulations at 30°C, we observed a stably closed channel constricted at the lower gate (near residue I679), while the upper gate (near residues G643 and M644) is dynamic and undergoes flickery opening/closing. In the open-state simulations at 60°C, we found higher conformational variation consistent with a large entropy increase required for the heat activation, and both the lower and upper gates are dynamic with transient opening/closing. Through ensemble-based structural analyses of the closed state versus the open state, we revealed pronounced closed-to-open conformational changes involving the membrane proximal domain (MPD) linker, the outer pore, and the TRP helix, which are accompanied by breaking/forming of a network of closed/open-state specific hydrogen bonds. By comparing the closed-state simulations at 30°C and 60°C, we observed heat-activated conformational changes in the MPD linker, the outer pore, and the TRP helix that resemble the closed-to-open conformational changes, along with partial formation of the open-state specific hydrogen bonds. Some of the residues involved in the above key hydrogen bonds were validated by previous mutational studies. Taken together, our MD simulations have offered rich structural and dynamic details beyond the static structures of TRPV1, and promising targets for future mutagenesis and functional studies of the TRPV1 channel. Proteins 2016; 84:1938-1949. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Compact Conformations of Human Protein Disulfide Isomerase

PubMed Central

Cui, Lei; Ding, Xiang; Niu, Lili; Yang, Fuquan; Wang, Chao; Wang, Chih-chen; Lou, Jizhong

2014-01-01

Protein disulfide isomerase (PDI) composed of four thioredoxin-like domains a, b, b', and a', is a key enzyme catalyzing oxidative protein folding in the endoplasmic reticulum. Large scale molecular dynamics simulations starting from the crystal structures of human PDI (hPDI) in the oxidized and reduced states were performed. The results indicate that hPDI adopts more compact conformations in solution than in the crystal structures, which are stabilized primarily by inter-domain interactions, including the salt bridges between domains a and b' observed for the first time. A prominent feature of the compact conformations is that the two catalytic domains a and a' can locate close enough for intra-molecular electron transfer, which was confirmed by the characterization of an intermediate with a disulfide between the two domains. Mutations, which disrupt the inter-domain interactions, lead to decreased reductase activity of hPDI. Our molecular dynamics simulations and biochemical experiments reveal the intrinsic conformational dynamics of hPDI and its biological impact. PMID:25084354

Coupled Leidenfrost states as a monodisperse granular clock

NASA Astrophysics Data System (ADS)

Liu, Rui; Yang, Mingcheng; Chen, Ke; Hou, Meiying; To, Kiwing

2016-08-01

Using an event-driven molecular dynamics simulation, we show that simple monodisperse granular beads confined in coupled columns may oscillate as a different type of granular clock. To trigger this oscillation, the system needs to be driven against gravity into a density-inverted state, with a high-density clustering phase supported from below by a gaslike low-density phase (Leidenfrost effect) in each column. Our analysis reveals that the density-inverted structure and the relaxation dynamics between the phases can amplify any small asymmetry between the columns, and lead to a giant oscillation. The oscillation occurs only for an intermediate range of the coupling strength, and the corresponding phase diagram can be universally described with a characteristic height of the density-inverted structure. A minimal two-phase model is proposed and a linear stability analysis shows that the triggering mechanism of the oscillation can be explained as a switchable two-parameter Andronov-Hopf bifurcation. Numerical solutions of the model also reproduce similar oscillatory dynamics to the simulation results.

Structural and Dynamic Insights into the Mechanism of Allosteric Signal Transmission in ERK2-Mediated MKP3 Activation.

PubMed

Lu, Chang; Liu, Xin; Zhang, Chen-Song; Gong, Haipeng; Wu, Jia-Wei; Wang, Zhi-Xin

2017-11-21

The mitogen-activated protein kinases (MAPKs) are key components of cellular signal transduction pathways, which are down-regulated by the MAPK phosphatases (MKPs). Catalytic activity of the MKPs is controlled both by their ability to recognize selective MAPKs and by allosteric activation upon binding to MAPK substrates. Here, we use a combination of experimental and computational techniques to elucidate the molecular mechanism for the ERK2-induced MKP3 activation. Mutational and kinetic study shows that the 334 FNFM 337 motif in the MKP3 catalytic domain is essential for MKP3-mediated ERK2 inactivation and is responsible for ERK2-mediated MKP3 activation. The long-term molecular dynamics (MD) simulations further reveal a complete dynamic process in which the catalytic domain of MKP3 gradually changes to a conformation that resembles an active MKP catalytic domain over the time scale of the simulation, providing a direct time-dependent observation of allosteric signal transmission in ERK2-induced MKP3 activation.

Dynamic Monte Carlo simulations of radiatively accelerated GRB fireballs

NASA Astrophysics Data System (ADS)

Chhotray, Atul; Lazzati, Davide

2018-05-01

We present a novel Dynamic Monte Carlo code (DynaMo code) that self-consistently simulates the Compton-scattering-driven dynamic evolution of a plasma. We use the DynaMo code to investigate the time-dependent expansion and acceleration of dissipationless gamma-ray burst fireballs by varying their initial opacities and baryonic content. We study the opacity and energy density evolution of an initially optically thick, radiation-dominated fireball across its entire phase space - in particular during the Rph < Rsat regime. Our results reveal new phases of fireball evolution: a transition phase with a radial extent of several orders of magnitude - the fireball transitions from Γ ∝ R to Γ ∝ R0, a post-photospheric acceleration phase - where fireballs accelerate beyond the photosphere and a Thomson-dominated acceleration phase - characterized by slow acceleration of optically thick, matter-dominated fireballs due to Thomson scattering. We quantify the new phases by providing analytical expressions of Lorentz factor evolution, which will be useful for deriving jet parameters.

Free-energy landscape of a hyperstable RNA tetraloop

PubMed Central

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

2016-01-01

We report the characterization of the energy landscape and the folding/unfolding thermodynamics of a hyperstable RNA tetraloop obtained through high-performance molecular dynamics simulations at microsecond timescales. Sampling of the configurational landscape is conducted using temperature replica exchange molecular dynamics over three isochores at high, ambient, and negative pressures to determine the thermodynamic stability and the free-energy landscape of the tetraloop. The simulations reveal reversible folding/unfolding transitions of the tetraloop into the canonical A-RNA conformation and the presence of two alternative configurations, including a left-handed Z-RNA conformation and a compact purine Triplet. Increasing hydrostatic pressure shows a stabilizing effect on the A-RNA conformation and a destabilization of the left-handed Z-RNA. Our results provide a comprehensive description of the folded free-energy landscape of a hyperstable RNA tetraloop and highlight the significant advances of all-atom molecular dynamics in describing the unbiased folding of a simple RNA secondary structure motif. PMID:27233937

Multiple molecular dynamics simulations of human LOX-1 and Trp150Ala mutant reveal the structural determinants causing the full deactivation of the receptor.

PubMed

Iacovelli, Federico; Tucci, Fabio Giovanni; Macari, Gabriele; Falconi, Mattia

2017-10-01

Multiple classical molecular dynamics simulations have been applied to the human LOX-1 receptor to clarify the role of the Trp150Ala mutation in the loss of binding activity. Results indicate that the substitution of this crucial residue, located at the dimer interface, markedly disrupts the wild-type receptor dynamics. The mutation causes an irreversible rearrangement of the subunits interaction pattern that in the wild-type protein allows the maintaining of a specific symmetrical motion of the monomers. The subunits dislocation determines a loss of linearity of the arginines residues composing the basic spine and a consequent alteration of the long-range electrostatic attraction of the substrate. Moreover, the anomalous subunits arrangement observed in the mutated receptor also affects the integrity of the hydrophobic tunnel, actively involved in the short-range hydrophobic recognition of the substrate. The combined effect of these structural rearrangements generates the impairing of the receptor function. © 2017 Wiley Periodicals, Inc.

Molecular dynamics simulations revealed structural differences among WRKY domain-DNA interaction in barley (Hordeum vulgare).

PubMed

Pandey, Bharati; Grover, Abhinav; Sharma, Pradeep

2018-02-12

The WRKY transcription factors are a class of DNA-binding proteins involved in diverse plant processes play critical roles in response to abiotic and biotic stresses. Genome-wide divergence analysis of WRKY gene family in Hordeum vulgare provided a framework for molecular evolution and functional roles. So far, the crystal structure of WRKY from barley has not been resolved; moreover, knowledge of the three-dimensional structure of WRKY domain is pre-requisites for exploring the protein-DNA recognition mechanisms. Homology modelling based approach was used to generate structures for WRKY DNA binding domain (DBD) and its variants using AtWRKY1 as a template. Finally, the stability and conformational changes of the generated model in unbound and bound form was examined through atomistic molecular dynamics (MD) simulations for 100 ns time period. In this study, we investigated the comparative binding pattern of WRKY domain and its variants with W-box cis-regulatory element using molecular docking and dynamics (MD) simulations assays. The atomic insight into WRKY domain exhibited significant variation in the intermolecular hydrogen bonding pattern, leading to the structural anomalies in the variant type and differences in the DNA-binding specificities. Based on the MD analysis, residual contribution and interaction contour, wild-type WRKY (HvWRKY46) were found to interact with DNA through highly conserved heptapeptide in the pre- and post-MD simulated complexes, whereas heptapeptide interaction with DNA was missing in variants (I and II) in post-MD complexes. Consequently, through principal component analysis, wild-type WRKY was also found to be more stable by obscuring a reduced conformational space than the variant I (HvWRKY34). Lastly, high binding free energy for wild-type and variant II allowed us to conclude that wild-type WRKY-DNA complex was more stable relative to variants I. The results of our study revealed complete dynamic and structural information about WRKY domain-DNA interactions. However, no structure base information reported to date for WRKY variants and their mechanism of interaction with DNA. Our findings highlighted the importance of selecting a sequence to generate newer transgenic plants that would be increasingly tolerance to stress conditions.

Network-based simulation of aircraft at gates in airport terminals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Y.

1998-03-01

Simulation is becoming an essential tool for planning, design, and management of airport facilities. A simulation of aircraft at gates at an airport can be applied for various periodically performed applications, relating to the dynamic behavior of aircraft at gates in airport terminals for analyses, evaluations, and decision supports. Conventionally, such simulations are implemented using an event-driven method. For a more efficient simulation, this paper proposes a network-based method. The basic idea is to transform all the sequence constraint relations of aircraft at gates into a network. The simulation is done by calculating the longest path to all the nodesmore » in the network. The effect of the algorithm of the proposed method has been examined by experiments, and the superiority of the proposed method over the event-driven method is revealed through comprehensive comparisons of their overall simulation performance.« less

Dynamic Maternal Gradients Control Timing and Shift-Rates for Drosophila Gap Gene Expression

PubMed Central

Verd, Berta; Crombach, Anton

2017-01-01

Pattern formation during development is a highly dynamic process. In spite of this, few experimental and modelling approaches take into account the explicit time-dependence of the rules governing regulatory systems. We address this problem by studying dynamic morphogen interpretation by the gap gene network in Drosophila melanogaster. Gap genes are involved in segment determination during early embryogenesis. They are activated by maternal morphogen gradients encoded by bicoid (bcd) and caudal (cad). These gradients decay at the same time-scale as the establishment of the antero-posterior gap gene pattern. We use a reverse-engineering approach, based on data-driven regulatory models called gene circuits, to isolate and characterise the explicitly time-dependent effects of changing morphogen concentrations on gap gene regulation. To achieve this, we simulate the system in the presence and absence of dynamic gradient decay. Comparison between these simulations reveals that maternal morphogen decay controls the timing and limits the rate of gap gene expression. In the anterior of the embyro, it affects peak expression and leads to the establishment of smooth spatial boundaries between gap domains. In the posterior of the embryo, it causes a progressive slow-down in the rate of gap domain shifts, which is necessary to correctly position domain boundaries and to stabilise the spatial gap gene expression pattern. We use a newly developed method for the analysis of transient dynamics in non-autonomous (time-variable) systems to understand the regulatory causes of these effects. By providing a rigorous mechanistic explanation for the role of maternal gradient decay in gap gene regulation, our study demonstrates that such analyses are feasible and reveal important aspects of dynamic gene regulation which would have been missed by a traditional steady-state approach. More generally, it highlights the importance of transient dynamics for understanding complex regulatory processes in development. PMID:28158178

Dynamic Maternal Gradients Control Timing and Shift-Rates for Drosophila Gap Gene Expression.

PubMed

Verd, Berta; Crombach, Anton; Jaeger, Johannes

2017-02-01

Pattern formation during development is a highly dynamic process. In spite of this, few experimental and modelling approaches take into account the explicit time-dependence of the rules governing regulatory systems. We address this problem by studying dynamic morphogen interpretation by the gap gene network in Drosophila melanogaster. Gap genes are involved in segment determination during early embryogenesis. They are activated by maternal morphogen gradients encoded by bicoid (bcd) and caudal (cad). These gradients decay at the same time-scale as the establishment of the antero-posterior gap gene pattern. We use a reverse-engineering approach, based on data-driven regulatory models called gene circuits, to isolate and characterise the explicitly time-dependent effects of changing morphogen concentrations on gap gene regulation. To achieve this, we simulate the system in the presence and absence of dynamic gradient decay. Comparison between these simulations reveals that maternal morphogen decay controls the timing and limits the rate of gap gene expression. In the anterior of the embyro, it affects peak expression and leads to the establishment of smooth spatial boundaries between gap domains. In the posterior of the embryo, it causes a progressive slow-down in the rate of gap domain shifts, which is necessary to correctly position domain boundaries and to stabilise the spatial gap gene expression pattern. We use a newly developed method for the analysis of transient dynamics in non-autonomous (time-variable) systems to understand the regulatory causes of these effects. By providing a rigorous mechanistic explanation for the role of maternal gradient decay in gap gene regulation, our study demonstrates that such analyses are feasible and reveal important aspects of dynamic gene regulation which would have been missed by a traditional steady-state approach. More generally, it highlights the importance of transient dynamics for understanding complex regulatory processes in development.

Formation and Growth of Stacking Fault Tetrahedra in Ni via Vacancy Aggregation Mechanism

DOE PAGES

Aidhy, Dilpuneet S.; Lu, Chenyang; Jin, Ke; ...

2015-12-29

Using molecular dynamics simulations, the formation and growth of stacking fault tetrahedra (SFT) are captured by vacancy cluster diffusion and aggregation mechanisms in Ni. The vacancytetrahedron acts as a nucleation point for SFT formation. Simulations show that perfect SFT can grow to the next size perfect SFT via a vacancy aggregation mechanism. The stopping and range of ions in matter (SRIM) calculations and transmission electron microscopy (TEM) observations reveal that SFT can form farther away from the initial cascade-event locations, indicating the operation of diffusion-based vacancy-aggregation mechanism.

Formation and Growth of Stacking Fault Tetrahedra in Ni via Vacancy Aggregation Mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aidhy, Dilpuneet S.; Lu, Chenyang; Jin, Ke

Using molecular dynamics simulations, the formation and growth of stacking fault tetrahedra (SFT) are captured by vacancy cluster diffusion and aggregation mechanisms in Ni. The vacancytetrahedron acts as a nucleation point for SFT formation. Simulations show that perfect SFT can grow to the next size perfect SFT via a vacancy aggregation mechanism. The stopping and range of ions in matter (SRIM) calculations and transmission electron microscopy (TEM) observations reveal that SFT can form farther away from the initial cascade-event locations, indicating the operation of diffusion-based vacancy-aggregation mechanism.

Constant pH simulations of pH responsive polymers

NASA Astrophysics Data System (ADS)

Sharma, Arjun; Smith, J. D.; Walters, Keisha B.; Rick, Steven W.

2016-12-01

Polyacidic polymers can change structure over a narrow range of pH in a competition between the hydrophobic effect, which favors a compact state, and electrostatic repulsion, which favors an extended state. Constant pH molecular dynamics computer simulations of poly(methacrylic acid) reveal that there are two types of structural changes, one local and one global, which make up the overall response. The local structural response depends on the tacticity of the polymer and leads to different cooperative effects for polymers with different stereochemistries, demonstrating both positive and negative cooperativities.

Atomic-scale structural signature of dynamic heterogeneities in metallic liquids

NASA Astrophysics Data System (ADS)

Pasturel, Alain; Jakse, Noel

2017-08-01

With sufficiently high cooling rates, liquids will cross their equilibrium melting temperatures and can be maintained in a metastable undercooled state before solidifying. Studies of undercooled liquids reveal several intriguing dynamic phenomena and because explicit connections between liquid structure and liquids dynamics are difficult to identify, it remains a major challenge to capture the underlying structural link to these phenomena. Ab initio molecular dynamics (AIMD) simulations are yet especially powerful in providing atomic-scale details otherwise not accessible in experiments. Through the AIMD-based study of Cr additions in Al-based liquids, we evidence for the first time a close relationship between the decoupling of component diffusion and the emergence of dynamic heterogeneities in the undercooling regime. In addition, we demonstrate that the origin of both phenomena is related to a structural heterogeneity caused by a strong interplay between chemical short-range order (CSRO) and local fivefold topology (ISRO) at the short-range scale in the liquid phase that develops into an icosahedral-based medium-range order (IMRO) upon undercooling. Finally, our findings reveal that this structural signature is also captured in the temperature dependence of partial pair-distribution functions which opens up the route to more elaborated experimental studies.

Bifurcation analysis of an automatic dynamic balancing mechanism for eccentric rotors

NASA Astrophysics Data System (ADS)

Green, K.; Champneys, A. R.; Lieven, N. J.

2006-04-01

We present a nonlinear bifurcation analysis of the dynamics of an automatic dynamic balancing mechanism for rotating machines. The principle of operation is to deploy two or more masses that are free to travel around a race at a fixed distance from the hub and, subsequently, balance any eccentricity in the rotor. Mathematically, we start from a Lagrangian description of the system. It is then shown how under isotropic conditions a change of coordinates into a rotating frame turns the problem into a regular autonomous dynamical system, amenable to a full nonlinear bifurcation analysis. Using numerical continuation techniques, curves are traced of steady states, limit cycles and their bifurcations as parameters are varied. These results are augmented by simulations of the system trajectories in phase space. Taking the case of a balancer with two free masses, broad trends are revealed on the existence of a stable, dynamically balanced steady-state solution for specific rotation speeds and eccentricities. However, the analysis also reveals other potentially attracting states—non-trivial steady states, limit cycles, and chaotic motion—which are not in balance. The transient effects which lead to these competing states, which in some cases coexist, are investigated.

Dipteran insect flight dynamics. Part 1 Longitudinal motion about hover.

PubMed

Faruque, Imraan; Sean Humbert, J

2010-05-21

This paper presents a reduced-order model of longitudinal hovering flight dynamics for dipteran insects. The quasi-steady wing aerodynamics model is extended by including perturbation states from equilibrium and paired with rigid body equations of motion to create a nonlinear simulation of a Drosophila-like insect. Frequency-based system identification tools are used to identify the transfer functions from biologically inspired control inputs to rigid body states. Stability derivatives and a state space linear system describing the dynamics are also identified. The vehicle control requirements are quantified with respect to traditional human pilot handling qualities specification. The heave dynamics are found to be decoupled from the pitch/fore/aft dynamics. The haltere-on system revealed a stabilized system with a slow (heave) and fast subsidence mode, and a stable oscillatory mode. The haltere-off (bare airframe) system revealed a slow (heave) and fast subsidence mode and an unstable oscillatory mode, a modal structure in agreement with CFD studies. The analysis indicates that passive aerodynamic mechanisms contribute to stability, which may help explain how insects are able to achieve stable locomotion on a very small computational budget. Copyright (c) 2010. Published by Elsevier Ltd.

Excited state non-adiabatic dynamics of the smallest polyene, trans 1,3-butadiene. II. Ab initio multiple spawning simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glover, William J.; Mori, Toshifumi; Schuurman, Michael S.

The excited state non-adiabatic dynamics of the smallest polyene, trans 1,3-butadiene (BD), has long been the subject of controversy due to its strong coupling, ultrafast time scales and the difficulties that theory faces in describing the relevant electronic states in a balanced fashion. Here we apply Ab Initio Multiple Spawning (AIMS) using state-averaged complete active space multistate second order perturbation theory [SA-3-CAS(4/4)-MSPT2] which describes both static and dynamic electron correlation effects, providing a balanced description of both the initially prepared bright 1 1B u (ππ*) state and non-adiabatically coupled dark 2 1A g state of BD. Importantly, AIMS allows formore » on-the-fly calculations of experimental observables. We validate our approach by directly simulating the time resolved photoelectron-photoion coincidence spectroscopy results presented in Paper I [A. E. Boguslavskiy et al., J. Chem. Phys. 148, 164302 (2018)], demonstrating excellent agreement with experiment. Our simulations reveal that the initial excitation to the 1 1B u state rapidly evolves via wavepacket dynamics that follow both bright- and dark-state pathways as well as mixtures of these. In order to test the sensitivity of the AIMS results to the relative ordering of states, we considered two hypothetical scenarios biased toward either the bright 1B u or the dark 2 1A g state. In contrast with AIMS/SA-3-CAS(4/4)-MSPT2 simulations, neither of these scenarios yields favorable agreement with experiment. Thus, we conclude that the excited state non-adiabatic dynamics in BD involves both of these ultrafast pathways.« less

Excited state non-adiabatic dynamics of the smallest polyene, trans 1,3-butadiene. II. Ab initio multiple spawning simulations.

PubMed

Glover, William J; Mori, Toshifumi; Schuurman, Michael S; Boguslavskiy, Andrey E; Schalk, Oliver; Stolow, Albert; Martínez, Todd J

2018-04-28

The excited state non-adiabatic dynamics of the smallest polyene, trans 1,3-butadiene (BD), has long been the subject of controversy due to its strong coupling, ultrafast time scales and the difficulties that theory faces in describing the relevant electronic states in a balanced fashion. Here we apply Ab Initio Multiple Spawning (AIMS) using state-averaged complete active space multistate second order perturbation theory [SA-3-CAS(4/4)-MSPT2] which describes both static and dynamic electron correlation effects, providing a balanced description of both the initially prepared bright 1 1 B u (ππ*) state and non-adiabatically coupled dark 2 1 A g state of BD. Importantly, AIMS allows for on-the-fly calculations of experimental observables. We validate our approach by directly simulating the time resolved photoelectron-photoion coincidence spectroscopy results presented in Paper I [A. E. Boguslavskiy et al., J. Chem. Phys. 148, 164302 (2018)], demonstrating excellent agreement with experiment. Our simulations reveal that the initial excitation to the 1 1 B u state rapidly evolves via wavepacket dynamics that follow both bright- and dark-state pathways as well as mixtures of these. In order to test the sensitivity of the AIMS results to the relative ordering of states, we considered two hypothetical scenarios biased toward either the bright 1 B u or the dark 2 1 A g state. In contrast with AIMS/SA-3-CAS(4/4)-MSPT2 simulations, neither of these scenarios yields favorable agreement with experiment. Thus, we conclude that the excited state non-adiabatic dynamics in BD involves both of these ultrafast pathways.

Insights into Stability and Folding of GNRA and UNCG Tetraloops Revealed by Microsecond Molecular Dynamics and Well-Tempered Metadynamics.

PubMed

Haldar, Susanta; Kührová, Petra; Banáš, Pavel; Spiwok, Vojtěch; Šponer, Jiří; Hobza, Pavel; Otyepka, Michal

2015-08-11

RNA hairpins capped by 5'-GNRA-3' or 5'-UNCG-3' tetraloops (TLs) are prominent RNA structural motifs. Despite their small size, a wealth of experimental data, and recent progress in theoretical simulations of their structural dynamics and folding, our understanding of the folding and unfolding processes of these small RNA elements is still limited. Theoretical description of the folding and unfolding processes requires robust sampling, which can be achieved by either an exhaustive time scale in standard molecular dynamics simulations or sophisticated enhanced sampling methods, using temperature acceleration or biasing potentials. Here, we study structural dynamics of 5'-GNRA-3' and 5'-UNCG-3' TLs by 15-μs-long standard simulations and a series of well-tempered metadynamics, attempting to accelerate sampling by bias in a few chosen collective variables (CVs). Both methods provide useful insights. The unfolding and refolding mechanisms of the GNRA TL observed by well-tempered metadynamics agree with the (reverse) folding mechanism suggested by recent replica exchange molecular dynamics simulations. The orientation of the glycosidic bond of the GL4 nucleobase is critical for the UUCG TL folding pathway, and our data strongly support the hypothesis that GL4-anti forms a kinetic trap along the folding pathway. Along with giving useful insight, our study also demonstrates that using only a few CVs apparently does not capture the full folding landscape of the RNA TLs. Despite using several sophisticated selections of the CVs, formation of the loop appears to remain a hidden variable, preventing a full convergence of the metadynamics. Finally, our data suggest that the unfolded state might be overstabilized by the force fields used.

Unique Features of Metformin: A Combined Experimental, Theoretical, and Simulation Study of Its Structure, Dynamics, and Interaction Energetics with DNA Grooves.

PubMed

Mondal, Sayantan; Samajdar, Rudra N; Mukherjee, Saumyak; Bhattacharyya, Aninda J; Bagchi, Biman

2018-03-01

There are certain small molecules that exhibit extraordinarily diverse biological activities. Metformin is one of them. It is widely used as an antidiabetic drug for type-two diabetes. Recent lines of evidence of its role in antitumor activities and increasing the survival rates of cancer patients (namely, colorectal, breast, pancreas, and prostate cancer) are emerging. However, theoretical studies of the structure and dynamics of metformin have not yet been fully explored. In this work, we investigate the characteristic structural and dynamical features of three monoprotonated forms of metformin hydrochloride with the help of experiments, quantum chemical calculations, and atomistic molecular dynamics simulations. We validate our force field by comparing simulation results to those of the experimental findings. Energetics of proton transfer between two planar monoprotonated forms reveals a low energy barrier, which leads us to speculate a possible coexistence of them. Nevertheless, among the protonation states, we find that the nonplanar tautomeric form is the most stable. Our calculated values of the self-diffusion coefficient agree quantitatively with NMR results. Metformin forms strong hydrogen bonds with surrounding water molecules, and its solvation dynamics shows unique features. Because of an extended positive charge distribution, metformin possesses features of being a permanent cationic partner toward several targets. We study its interaction and binding ability with DNA using UV spectroscopy, circular dichroism, fluorimetry, and metadynamics simulation. We find a nonintercalative mode of interaction. Metformin feasibly forms a minor/major groove-bound state within a few tens of nanoseconds, preferably with AT-rich domains. A significant decrease in the free energy of binding is observed when it binds to a minor groove of DNA.

Excited state non-adiabatic dynamics of the smallest polyene, trans 1,3-butadiene. II. Ab initio multiple spawning simulations

DOE PAGES

Glover, William J.; Mori, Toshifumi; Schuurman, Michael S.; ...

2018-04-28

The excited state non-adiabatic dynamics of the smallest polyene, trans 1,3-butadiene (BD), has long been the subject of controversy due to its strong coupling, ultrafast time scales and the difficulties that theory faces in describing the relevant electronic states in a balanced fashion. Here we apply Ab Initio Multiple Spawning (AIMS) using state-averaged complete active space multistate second order perturbation theory [SA-3-CAS(4/4)-MSPT2] which describes both static and dynamic electron correlation effects, providing a balanced description of both the initially prepared bright 1 1B u (ππ*) state and non-adiabatically coupled dark 2 1A g state of BD. Importantly, AIMS allows formore » on-the-fly calculations of experimental observables. We validate our approach by directly simulating the time resolved photoelectron-photoion coincidence spectroscopy results presented in Paper I [A. E. Boguslavskiy et al., J. Chem. Phys. 148, 164302 (2018)], demonstrating excellent agreement with experiment. Our simulations reveal that the initial excitation to the 1 1B u state rapidly evolves via wavepacket dynamics that follow both bright- and dark-state pathways as well as mixtures of these. In order to test the sensitivity of the AIMS results to the relative ordering of states, we considered two hypothetical scenarios biased toward either the bright 1B u or the dark 2 1A g state. In contrast with AIMS/SA-3-CAS(4/4)-MSPT2 simulations, neither of these scenarios yields favorable agreement with experiment. Thus, we conclude that the excited state non-adiabatic dynamics in BD involves both of these ultrafast pathways.« less

Multiple Conformational States Contribute to the 3D Structure of a Glucan Decasaccharide: A Combined SAXS and MD Simulation Study.

PubMed

Jo, Sunhwan; Myatt, Daniel; Qi, Yifei; Doutch, James; Clifton, Luke A; Im, Wonpil; Widmalm, Göran

2018-01-25

The inherent flexibility of carbohydrates is dependent on stereochemical arrangements, and characterization of their influence and importance will give insight into the three-dimensional structure and dynamics. In this study, a β-(1→4)/β-(1→3)-linked glucosyl decasaccharide is experimentally investigated by synchrotron small-angle X-ray scattering from which its radius of gyration (R g ) is obtained. Molecular dynamics (MD) simulations of the decasaccharide show four populated states at each glycosidic linkage, namely, syn- and anti-conformations. The calculated R g values from the MD simulation reveal that in addition to syn-conformers the presence of anti-ψ conformational states is required to reproduce experimental scattering data, unveiling inherent glycosidic linkage flexibility. The CHARMM36 force field for carbohydrates thus describes the conformational flexibility of the decasaccharide very well and captures the conceptual importance that anti-conformers are to be anticipated at glycosidic linkages of carbohydrates.

Understanding the mechanisms of amorphous creep through molecular simulation

NASA Astrophysics Data System (ADS)

Cao, Penghui; Short, Michael P.; Yip, Sidney

2017-12-01

Molecular processes of creep in metallic glass thin films are simulated at experimental timescales using a metadynamics-based atomistic method. Space-time evolutions of the atomic strains and nonaffine atom displacements are analyzed to reveal details of the atomic-level deformation and flow processes of amorphous creep in response to stress and thermal activations. From the simulation results, resolved spatially on the nanoscale and temporally over time increments of fractions of a second, we derive a mechanistic explanation of the well-known variation of creep rate with stress. We also construct a deformation map delineating the predominant regimes of diffusional creep at low stress and high temperature and deformational creep at high stress. Our findings validate the relevance of two original models of the mechanisms of amorphous plasticity: one focusing on atomic diffusion via free volume and the other focusing on stress-induced shear deformation. These processes are found to be nonlinearly coupled through dynamically heterogeneous fluctuations that characterize the slow dynamics of systems out of equilibrium.

Homogeneous nucleation and microstructure evolution in million-atom molecular dynamics simulation

PubMed Central

Shibuta, Yasushi; Oguchi, Kanae; Takaki, Tomohiro; Ohno, Munekazu

2015-01-01

Homogeneous nucleation from an undercooled iron melt is investigated by the statistical sampling of million-atom molecular dynamics (MD) simulations performed on a graphics processing unit (GPU). Fifty independent instances of isothermal MD calculations with one million atoms in a quasi-two-dimensional cell over a nanosecond reveal that the nucleation rate and the incubation time of nucleation as functions of temperature have characteristic shapes with a nose at the critical temperature. This indicates that thermally activated homogeneous nucleation occurs spontaneously in MD simulations without any inducing factor, whereas most previous studies have employed factors such as pressure, surface effect, and continuous cooling to induce nucleation. Moreover, further calculations over ten nanoseconds capture the microstructure evolution on the order of tens of nanometers from the atomistic viewpoint and the grain growth exponent is directly estimated. Our novel approach based on the concept of “melting pots in a supercomputer” is opening a new phase in computational metallurgy with the aid of rapid advances in computational environments. PMID:26311304

Molecular dynamics simulations and CD spectroscopy reveal hydration-induced unfolding of the intrinsically disordered LEA proteins COR15A and COR15B from Arabidopsis thaliana.

PubMed

Navarro-Retamal, Carlos; Bremer, Anne; Alzate-Morales, Jans; Caballero, Julio; Hincha, Dirk K; González, Wendy; Thalhammer, Anja

2016-10-07

The LEA (late embryogenesis abundant) proteins COR15A and COR15B from Arabidopsis thaliana are intrinsically disordered under fully hydrated conditions, but obtain α-helical structure during dehydration, which is reversible upon rehydration. To understand this unusual structural transition, both proteins were investigated by circular dichroism (CD) and molecular dynamics (MD) approaches. MD simulations showed unfolding of the proteins in water, in agreement with CD data obtained with both HIS-tagged and untagged recombinant proteins. Mainly intramolecular hydrogen bonds (H-bonds) formed by the protein backbone were replaced by H-bonds with water molecules. As COR15 proteins function in vivo as protectants in leaves partially dehydrated by freezing, unfolding was further assessed under crowded conditions. Glycerol reduced (40%) or prevented (100%) unfolding during MD simulations, in agreement with CD spectroscopy results. H-bonding analysis indicated that preferential exclusion of glycerol from the protein backbone increased stability of the folded state.

The effect of cross linking density on the mechanical properties and structure of the epoxy polymers: molecular dynamics simulation.

PubMed

Shokuhfar, Ali; Arab, Behrouz

2013-09-01

Recently, great attention has been focused on using epoxy polymers in different fields such as aerospace, automotive, biotechnology, and electronics, owing to their superior properties. In this study, the classical molecular dynamics (MD) was used to simulate the cross linking of diglycidyl ether of bisphenol-A (DGEBA) with diethylenetriamine (DETA) curing agent, and to study the behavior of resulted epoxy polymer with different conversion rates. The constant-strain (static) approach was then applied to calculate the mechanical properties (Bulk, shear and Young's moduli, elastic stiffness constants, and Poisson's ratio) of the uncured and cross-linked systems. Estimated material properties were found to be in good agreement with experimental observations. Moreover, the dependency of mechanical properties on the cross linking density was investigated and revealed improvements in the mechanical properties with increasing the cross linking density. The radial distribution function (RDF) was also used to study the evolution of local structures of the simulated systems as a function of cross linking density.