Science.gov

Sample records for molecular dynamics reveals

  1. Personal Omics Profiling Reveals Dynamic Molecular and Medical Phenotypes

    PubMed Central

    Chen, Rui; Mias, George I.; Li-Pook-Than, Jennifer; Jiang, Lihua; Lam, Hugo Y. K.; Chen, Rong; Miriami, Elana; Karczewski, Konrad J.; Hariharan, Manoj; Dewey, Frederick E.; Cheng, Yong; Clark, Michael J.; Im, Hogune; Habegger, Lukas; Balasubramanian, Suganthi; O'Huallachain, Maeve; Dudley, Joel T.; Hillenmeyer, Sara; Haraksingh, Rajini; Sharon, Donald; Euskirchen, Ghia; Lacroute, Phil; Bettinger, Keith; Boyle, Alan P.; Kasowski, Maya; Grubert, Fabian; Seki, Scott; Garcia, Marco; Whirl-Carrillo, Michelle; Gallardo, Mercedes; Blasco, Maria A.; Greenberg, Peter L.; Snyder, Phyllis; Klein, Teri E.; Altman, Russ B.; Butte, Atul; Ashley, Euan A.; Nadeau, Kari C.; Gerstein, Mark; Tang, Hua; Snyder, Michael

    2012-01-01

    SUMMARY Personalized medicine is expected to benefit from combining genomic information with regular monitoring of physiological states by multiple high-throughput methods. Here we present an integrative Personal Omics Profile (iPOP), an analysis that combines genomic, transcriptomic, proteomic, metabolomic, and autoantibody profiles from a single individual over a 14-month period. Our iPOP analysis revealed various medical risks, including Type II diabetes. It also uncovered extensive, dynamic changes in diverse molecular components and biological pathways across healthy and diseased conditions. Extremely high coverage genomic and transcriptomic data, which provide the basis of our iPOP, discovered extensive heteroallelic changes during healthy and diseased states and an unexpected RNA editing mechanism. This study demonstrates that longitudinal iPOP can be used to interpret healthy and disease states by connecting genomic information with additional dynamic omics activity. PMID:22424236

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

    SciTech Connect

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

    2014-03-22

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

  3. Shapiro like steps reveals molecular nanomagnets’ spin dynamics

    SciTech Connect

    Abdollahipour, Babak; Abouie, Jahanfar Ebrahimi, Navid

    2015-09-15

    We present an accurate way to detect spin dynamics of a nutating molecular nanomagnet by inserting it in a tunnel Josephson junction and studying the current voltage (I-V) characteristic. The spin nutation of the molecular nanomagnet is generated by applying two circularly polarized magnetic fields. We demonstrate that modulation of the Josephson current by the nutation of the molecular nanomagnet’s spin appears as a stepwise structure like Shapiro steps in the I-V characteristic of the junction. Width and heights of these Shapiro-like steps are determined by two parameters of the spin nutation, frequency and amplitude of the nutation, which are simply tuned by the applied magnetic fields.

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

    NASA Astrophysics Data System (ADS)

    Wu, Bin

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

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

    SciTech Connect

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

    2011-01-01

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

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

    PubMed

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

    2013-05-01

    Virus-like particles (VLPs) are highly organized nanoparticles that have great potential in vaccinology, gene therapy, drug delivery, and materials science. However, the application of VLPs is hindered by obstacles in their design and production due to low efficiency of self-assembly. In the present study, all-atom (AA) molecular dynamics (MD) simulations coupled with the molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) method are utilized to examine the molecular interactions in the capsomere of a murine polyomavirus (MPV) VLP. It is found that both low ionic strength and the intracapsomere disulfide bonds are favorable for maintaining a stable capsomere. Simulation results examining the effects of solution conditions on the stabilization of a capsomere were verified by calorimetry experiments. Simulation results of free energy decomposition indicate that hydrophobic interaction is favorable for the formation of a capsomere, whereas electrostatic interaction is unfavorable. With increasing ionic strength, the dominant interaction for the stabilization of a capsomere changes from hydrophobic to electrostatic. By comprehensive analyses, the key amino acid residues (hot spots) in VP1 protein aiding formation of a capsomere in different solution conditions have been identified. These results provide molecular insights into the stabilization of building blocks for VLP and are expected to have implications in their partitioning between the correct and off-pathway reactions in VLP assembly. PMID:23586433

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

    NASA Astrophysics Data System (ADS)

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

    2010-06-01

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

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

    PubMed

    Tan, Cheng; Terakawa, Tsuyoshi; Takada, Shoji

    2016-07-13

    Protein binding to DNA changes the DNA's structure, and altered DNA structure can, in turn, modulate the dynamics of protein binding. This mutual dependency is poorly understood. Here we investigated dynamic couplings among protein binding to DNA, protein sliding on DNA, and DNA bending by applying a coarse-grained simulation method to the bacterial architectural protein HU and 14 other DNA-binding proteins. First, we verified our method by showing that the simulated HU exhibits a weak preference for A/T-rich regions of DNA and a much higher affinity for gapped and nicked DNA, consistent with biochemical experiments. The high affinity was attributed to a local DNA bend, but not the specific chemical moiety of the gap/nick. The long-time dynamic analysis revealed that HU sliding is associated with the movement of the local DNA bending site. Deciphering single sliding steps, we found the coupling between HU sliding and DNA bending is akin to neither induced-fit nor population-shift; instead they moved concomitantly. This is reminiscent of a cation transfer on DNA and can be viewed as a protein version of polaron-like sliding. Interestingly, on shorter time scales, HU paused when the DNA was highly bent at the bound position and escaped from pauses once the DNA spontaneously returned to a less bent structure. The HU sliding is largely regulated by DNA bending dynamics. With 14 other proteins, we explored the generality and versatility of the dynamic coupling and found that 6 of the 15 assayed proteins exhibit the polaron-like sliding. PMID:27309278

  9. Single-molecule chemical reaction reveals molecular reaction kinetics and dynamics.

    PubMed

    Zhang, Yuwei; Song, Ping; Fu, Qiang; Ruan, Mingbo; Xu, Weilin

    2014-06-25

    Understanding the microscopic elementary process of chemical reactions, especially in condensed phase, is highly desirable for improvement of efficiencies in industrial chemical processes. Here we show an approach to gaining new insights into elementary reactions in condensed phase by combining quantum chemical calculations with a single-molecule analysis. Elementary chemical reactions in liquid-phase, revealed from quantum chemical calculations, are studied by tracking the fluorescence of single dye molecules undergoing a reversible redox process. Statistical analyses of single-molecule trajectories reveal molecular reaction kinetics and dynamics of elementary reactions. The reactivity dynamic fluctuations of single molecules are evidenced and probably arise from either or both of the low-frequency approach of the molecule to the internal surface of the SiO2 nanosphere or the molecule diffusion-induced memory effect. This new approach could be applied to other chemical reactions in liquid phase to gain more insight into their molecular reaction kinetics and the dynamics of elementary steps.

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

    PubMed Central

    Hertig, Samuel

    2016-01-01

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

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

    PubMed

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

    2016-06-01

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

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

    SciTech Connect

    Nutt, David; Smith, Jeremy C

    2008-10-01

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

  13. The Molecular Architecture of Cell Adhesion: Dynamic Remodeling Revealed by Videonanoscopy

    PubMed Central

    Sergé, Arnauld

    2016-01-01

    The plasma membrane delimits the cell, which is the basic unit of living organisms, and is also a privileged site for cell communication with the environment. Cell adhesion can occur through cell-cell and cell-matrix contacts. Adhesion proteins such as integrins and cadherins also constitute receptors for inside-out and outside-in signaling within proteolipidic platforms. Adhesion molecule targeting and stabilization relies on specific features such as preferential segregation by the sub-membrane cytoskeleton meshwork and within membrane proteolipidic microdomains. This review presents an overview of the recent insights brought by the latest developments in microscopy, to unravel the molecular remodeling occurring at cell contacts. The dynamic aspect of cell adhesion was recently highlighted by super-resolution videomicroscopy, also named videonanoscopy. By circumventing the diffraction limit of light, nanoscopy has allowed the monitoring of molecular localization and behavior at the single-molecule level, on fixed and living cells. Accessing molecular-resolution details such as quantitatively monitoring components entering and leaving cell contacts by lateral diffusion and reversible association has revealed an unexpected plasticity. Adhesion structures can be highly specialized, such as focal adhesion in motile cells, as well as immune and neuronal synapses. Spatiotemporal reorganization of adhesion molecules, receptors, and adaptors directly relates to structure/function modulation. Assembly of these supramolecular complexes is continuously balanced by dynamic events, remodeling adhesions on various timescales, notably by molecular conformation switches, lateral diffusion within the membrane and endo/exocytosis. Pathological alterations in cell adhesion are involved in cancer evolution, through cancer stem cell interaction with stromal niches, growth, extravasation, and metastasis. PMID:27200348

  14. Molecular dynamics

    SciTech Connect

    Ladd, A.J.C.

    1988-08-01

    The basic methodology of equilibrium molecular dynamics is described. Examples from the literature are used to illustrate how molecular dynamics has been used to resolve theoretical controversies, provide data to test theories, and occasionally to discover new phenomena. The emphasis is on the application of molecular dynamics to an understanding of the microscopic physics underlying the transport properties of simple fluids. 98 refs., 4 figs.

  15. Molecular evolutionary signatures reveal the role of host ecological dynamics in viral disease emergence and spread

    PubMed Central

    Duke-Sylvester, Scott M.; Biek, Roman; Real, Leslie A.

    2013-01-01

    RNA viruses account for numerous emerging and perennial infectious diseases, and are characterized by rapid rates of molecular evolution. The ecological dynamics of most emerging RNA viruses are still poorly understood and difficult to ascertain. The availability of genome sequence data for many RNA viruses, in principle, could be used to infer ecological dynamics if changes in population numbers produced a lasting signature within the pattern of genome evolution. As a result, the rapidly emerging phylogeographic structure of a pathogen, shaped by the rise and fall in the number of infections and their spatial distribution, could be used as a surrogate for direct ecological assessments. Based on rabies virus as our example, we use a model combining ecological and evolutionary processes to test whether variation in the rate of host movement results in predictive diagnostic patterns of pathogen genetic structure. We identify several linearizable relationships between host dispersal rate and measures of phylogenetic structure suggesting genetic information can be used to directly infer ecological process. We also find phylogenetic structure may be more revealing than demography for certain ecological processes. Our approach extends the reach of current analytic frameworks for infectious disease dynamics by linking phylogeography back to underlying ecological processes. PMID:23382419

  16. Revealing molecular structure and dynamics through high harmonic generation driven by mid-IR fields

    NASA Astrophysics Data System (ADS)

    Marangos, Jonathan

    2010-03-01

    High harmonic generation (HHG) from molecules has recently been shown to be a promising tool for measuring instantaneous molecular structure, sub-femtosecond domain structural rearrangements in molecules and even hole dynamics initiated by laser field ionisation. To fully exploit this promise it is essential that we can; (1) systematically decouple structural and dynamic effects so that both may simultaneously be determined in the measurement, (2) can extend the method of molecular HHG imaging to a wide range of molecules. Here we demonstrate important steps towards both these objectives. Up until now HHG imaging measurements have been restricted to drive laser wavelengths close to 800nm, due to the availability of CPA titanium sapphire lasers, which dictates the use of relatively high intensities (> 2.5 x 10^14 Wcm-2) if a harmonic spectrum spanning to ˜70 eV is to be observed which is required for extracting structural data from most small molecules. By using a mid-IR laser (at 1300 nm) we show that with an intensity ˜ 1 x 10^14 W cm-2 we can observe a wide molecular harmonic spectrum spanning to ˜ 70 eV even in molecules where ionization saturation would clamp the cut-off to much lower energies if an 800nm field were used. Thus we have been able to observe evidence for two-centre interference in two new molecules, N2O and C2H2 for the first time. Moreover we can use the ability to observe a broad harmonic spectrum over a large range of intensities to reveal the subtle interplay between structural and dynamic effects in CO2 and so provide a new window into hole dynamics. [4pt] In collaboration with R. Torres, Blackett Laboratory, Imperial College London; O. Smirnova, Max-Born-Institute, Berlin; T. Siegel and L. Brugnera, Blackett Laboratory, Imperial College London; I. Procino and Jonathan G. Underwood, Department of Physics and Astronomy, University College London; C. Altucci and R. Velotta, CNSIM and Dipartimento di Scienze Fisiche, Universita di Napoli

  17. Molecular dynamics simulations reveal proton transfer pathways in cytochrome C-dependent nitric oxide reductase.

    PubMed

    Pisliakov, Andrei V; Hino, Tomoya; Shiro, Yoshitsugu; Sugita, Yuji

    2012-01-01

    Nitric oxide reductases (NORs) are membrane proteins that catalyze the reduction of nitric oxide (NO) to nitrous oxide (N(2)O), which is a critical step of the nitrate respiration process in denitrifying bacteria. Using the recently determined first crystal structure of the cytochrome c-dependent NOR (cNOR) [Hino T, Matsumoto Y, Nagano S, Sugimoto H, Fukumori Y, et al. (2010) Structural basis of biological N2O generation by bacterial nitric oxide reductase. Science 330: 1666-70.], we performed extensive all-atom molecular dynamics (MD) simulations of cNOR within an explicit membrane/solvent environment to fully characterize water distribution and dynamics as well as hydrogen-bonded networks inside the protein, yielding the atomic details of functionally important proton channels. Simulations reveal two possible proton transfer pathways leading from the periplasm to the active site, while no pathways from the cytoplasmic side were found, consistently with the experimental observations that cNOR is not a proton pump. One of the pathways, which was newly identified in the MD simulation, is blocked in the crystal structure and requires small structural rearrangements to allow for water channel formation. That pathway is equivalent to the functional periplasmic cavity postulated in cbb(3) oxidase, which illustrates that the two enzymes share some elements of the proton transfer mechanisms and confirms a close evolutionary relation between NORs and C-type oxidases. Several mechanisms of the critical proton transfer steps near the catalytic center are proposed. PMID:22956904

  18. Molecular dynamics.

    PubMed

    Cheng, Xiaolin; Ivanov, Ivaylo

    2012-01-01

    Molecular dynamics (MD) simulation holds the promise of revealing the mechanisms of biological processes in their ultimate detail. It is carried out by computing the interaction forces acting on each atom and then propagating the velocities and positions of the atoms by numerical integration of Newton's equations of motion. In this review, we present an overview of how the MD simulation can be conducted to address computational toxicity problems. The study cases will cover a standard MD simulation performed to investigate the overall flexibility of a cytochrome P450 (CYP) enzyme and a set of more advanced MD simulations to examine the barrier to ion conduction in a human α7 nicotinic acetylcholine receptor (nAChR).

  19. Molecular Mechanisms of Influenza Inhibition by Surfactant Protein D Revealed by Large-scale Molecular Dynamics Simulation†

    PubMed Central

    Goh, Boon Chong; Rynkiewicz, Michael J.; Cafarella, Tanya R.; White, Mitchell R.; Hartshorn, Kevan L.; Allen, Kimberly; Crouch, Erika C.; Calin, Oliviana; Seeberger, Peter H.; Schulten, Klaus; Seaton, Barbara A.

    2013-01-01

    Surfactant protein D (SP-D), a mammalian C-type lectin, is the primary innate inhibitor of influenza A virus (IAV) in the lung. SP-D interactions with highly branched viral N-linked glycans on hemagglutinin (HA), an abundant IAV envelope protein and critical virulence factor, promote viral aggregation and neutralization through as yet unknown molecular mechanisms. Two truncated human SP-D forms, wild-type (WT) and double mutant D325A+R343V, representing neck and carbohydrate recognition domains are compared in this study. Whereas both WT and D325A+R343V bind to isolated glycosylated HA, WT does not inhibit IAV in neutralization assays; in contrast, D325A+R343V neutralization compares well with full-length native SP-D. To elucidate the mechanism for these biochemical observations, we have solved crystal structures of D325A+R343V in the presence and absence of a viral nonamannoside (Man9). Based on the D325A+R343V/Man9 structure and other crystallographic data, models of complexes between HA and WT or D325A+R343V were produced and subjected to molecular dynamics. Simulations reveal that whereas WT and D325A+R343V both block the sialic acid receptor site of HA, the D325A+R343V complex is more stable, with stronger binding due to additional hydrogen bonds and hydrophobic interactions with HA residues. Furthermore, the blocking mechanism of HA differs for WT and D325A+R343V due to alternate glycan binding modes. The combined results suggest a mechanism through which the mode of SP-D/HA interaction could significantly influence viral aggregation and neutralization. These studies provide the first atomic-level molecular view of an innate host defense lectin inhibiting its viral glycoprotein target. PMID:24224757

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

  1. The Gating Mechanism of the Human Aquaporin 5 Revealed by Molecular Dynamics Simulations

    PubMed Central

    Janosi, Lorant; Ceccarelli, Matteo

    2013-01-01

    Aquaporins are protein channels located across the cell membrane with the role of conducting water or other small sugar alcohol molecules (aquaglyceroporins). The high-resolution X-ray structure of the human aquaporin 5 (HsAQP5) shows that HsAQP5, as all the other known aquaporins, exhibits tetrameric structure. By means of molecular dynamics simulations we analyzed the role of spontaneous fluctuations on the structural behavior of the human AQP5. We found that different conformations within the tetramer lead to a distribution of monomeric channel structures, which can be characterized as open or closed. The switch between the two states of a channel is a tap-like mechanism at the cytoplasmic end which regulates the water passage through the pore. The channel is closed by a translation of the His67 residue inside the pore. Moreover, water permeation rate calculations revealed that the selectivity filter, located at the other end of the channel, regulates the flow rate of water molecules when the channel is open, by locally modifying the orientation of His173. Furthermore, the calculated permeation rates of a fully open channel are in good agreement with the reported experimental value. PMID:23565173

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  4. 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.

  5. STED-FLCS: An Advanced Tool to Reveal Spatiotemporal Heterogeneity of Molecular Membrane Dynamics.

    PubMed

    Vicidomini, Giuseppe; Ta, Haisen; Honigmann, Alf; Mueller, Veronika; Clausen, Mathias P; Waithe, Dominic; Galiani, Silvia; Sezgin, Erdinc; Diaspro, Alberto; Hell, Stefan W; Eggeling, Christian

    2015-09-01

    Heterogeneous diffusion dynamics of molecules play an important role in many cellular signaling events, such as of lipids in plasma membrane bioactivity. However, these dynamics can often only be visualized by single-molecule and super-resolution optical microscopy techniques. Using fluorescence lifetime correlation spectroscopy (FLCS, an extension of fluorescence correlation spectroscopy, FCS) on a super-resolution stimulated emission depletion (STED) microscope, we here extend previous observations of nanoscale lipid dynamics in the plasma membrane of living mammalian cells. STED-FLCS allows an improved determination of spatiotemporal heterogeneity in molecular diffusion and interaction dynamics via a novel gated detection scheme, as demonstrated by a comparison between STED-FLCS and previous conventional STED-FCS recordings on fluorescent phosphoglycerolipid and sphingolipid analogues in the plasma membrane of live mammalian cells. The STED-FLCS data indicate that biophysical and biochemical parameters such as the affinity for molecular complexes strongly change over space and time within a few seconds. Drug treatment for cholesterol depletion or actin cytoskeleton depolymerization not only results in the already previously observed decreased affinity for molecular interactions but also in a slight reduction of the spatiotemporal heterogeneity. STED-FLCS specifically demonstrates a significant improvement over previous gated STED-FCS experiments and with its improved spatial and temporal resolution is a novel tool for investigating how heterogeneities of the cellular plasma membrane may regulate biofunctionality. PMID:26235350

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

    SciTech Connect

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

    2015-03-20

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

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

    DOE PAGES

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

    2015-03-20

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

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

    PubMed Central

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

    2015-01-01

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

  9. 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

    2015-08-01

    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.

  10. Venus trap in the mouse embryo reveals distinct molecular dynamics underlying specification of first embryonic lineages.

    PubMed

    Dietrich, Jens-Erik; Panavaite, Laura; Gunther, Stefan; Wennekamp, Sebastian; Groner, Anna C; Pigge, Anton; Salvenmoser, Stefanie; Trono, Didier; Hufnagel, Lars; Hiiragi, Takashi

    2015-08-01

    Mammalian development begins with the segregation of embryonic and extra-embryonic lineages in the blastocyst. Recent studies revealed cell-to-cell gene expression heterogeneity and dynamic cell rearrangements during mouse blastocyst formation. Thus, mechanistic understanding of lineage specification requires quantitative description of gene expression dynamics at a single-cell resolution in living embryos. However, only a few fluorescent gene expression reporter mice are available and quantitative live image analysis is limited so far. Here, we carried out a fluorescence gene-trap screen and established reporter mice expressing Venus specifically in the first lineages. Lineage tracking, quantitative gene expression and cell position analyses allowed us to build a comprehensive lineage map of mouse pre-implantation development. Our systematic analysis revealed that, contrary to the available models, the timing and mechanism of lineage specification may be distinct between the trophectoderm and the inner cell mass. While expression of our trophectoderm-specific lineage marker is upregulated in outside cells upon asymmetric divisions at 8- and 16-cell stages, the inside-specific upregulation of the inner-cell-mass marker only becomes evident at the 64-cell stage. This study thus provides a framework toward systems-level understanding of embryogenesis marked by high dynamicity and stochastic variability. PMID:26142281

  11. Venus trap in the mouse embryo reveals distinct molecular dynamics underlying specification of first embryonic lineages.

    PubMed

    Dietrich, Jens-Erik; Panavaite, Laura; Gunther, Stefan; Wennekamp, Sebastian; Groner, Anna C; Pigge, Anton; Salvenmoser, Stefanie; Trono, Didier; Hufnagel, Lars; Hiiragi, Takashi

    2015-08-01

    Mammalian development begins with the segregation of embryonic and extra-embryonic lineages in the blastocyst. Recent studies revealed cell-to-cell gene expression heterogeneity and dynamic cell rearrangements during mouse blastocyst formation. Thus, mechanistic understanding of lineage specification requires quantitative description of gene expression dynamics at a single-cell resolution in living embryos. However, only a few fluorescent gene expression reporter mice are available and quantitative live image analysis is limited so far. Here, we carried out a fluorescence gene-trap screen and established reporter mice expressing Venus specifically in the first lineages. Lineage tracking, quantitative gene expression and cell position analyses allowed us to build a comprehensive lineage map of mouse pre-implantation development. Our systematic analysis revealed that, contrary to the available models, the timing and mechanism of lineage specification may be distinct between the trophectoderm and the inner cell mass. While expression of our trophectoderm-specific lineage marker is upregulated in outside cells upon asymmetric divisions at 8- and 16-cell stages, the inside-specific upregulation of the inner-cell-mass marker only becomes evident at the 64-cell stage. This study thus provides a framework toward systems-level understanding of embryogenesis marked by high dynamicity and stochastic variability.

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

    NASA Astrophysics Data System (ADS)

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

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

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

    SciTech Connect

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

    2015-03-04

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

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

    DOE PAGES

    Zhang, Meng; Charles, River; Tong, Huimin; Zhang, Lei; Patel, Mili; Wang, Francis; Rames, Matthew J.; Ren, Amy; Rye, Kerry-Anne; Qiu, Xiayang; et al

    2015-03-04

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

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

    PubMed

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

    2016-07-08

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

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

    PubMed Central

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

    2016-01-01

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

  18. Benzene Probes in Molecular Dynamics Simulations Reveal Novel Binding Sites for Ligand Design.

    PubMed

    Tan, Yaw Sing; Reeks, Judith; Brown, Christopher J; Thean, Dawn; Ferrer Gago, Fernando Jose; Yuen, Tsz Ying; Goh, Eunice Tze Leng; Lee, Xue Er Cheryl; Jennings, Claire E; Joseph, Thomas L; Lakshminarayanan, Rajamani; Lane, David P; Noble, Martin E M; Verma, Chandra S

    2016-09-01

    Protein flexibility poses a major challenge in binding site identification. Several computational pocket detection methods that utilize small-molecule probes in molecular dynamics (MD) simulations have been developed to address this issue. Although they have proven hugely successful at reproducing experimental structural data, their ability to predict new binding sites that are yet to be identified and characterized has not been demonstrated. Here, we report the use of benzenes as probe molecules in ligand-mapping MD (LMMD) simulations to predict the existence of two novel binding sites on the surface of the oncoprotein MDM2. One of them was serendipitously confirmed by biophysical assays and X-ray crystallography to be important for the binding of a new family of hydrocarbon stapled peptides that were specifically designed to target the other putative site. These results highlight the predictive power of LMMD and suggest that predictions derived from LMMD simulations can serve as a reliable basis for the identification of novel ligand binding sites in structure-based drug design. PMID:27532490

  19. Molecular dynamics generation of nonarbitrary membrane models reveals lipid orientational correlations.

    PubMed Central

    Takaoka, Y; Pasenkiewicz-Gierula, M; Miyagawa, H; Kitamura, K; Tamura, Y; Kusumi, A

    2000-01-01

    This report addresses the following problems associated with the generation of computer models of phospholipid bilayer membranes using molecular dynamics simulations: arbitrary initial structures and short equilibration periods, an Ewald-induced strong coupling of phospholipids, uncertainty regarding which value should be used for surface tension to alleviate the problem of the small size of the membrane, and simultaneous realization of both order parameters and the surface area. We generated a computer model of the liquid-crystalline L-alpha-dimyristoylphosphatidylcholine (DMPC) bilayer, starting from a configuration based on a crystal structure (rather than from an arbitrary structure). To break the crystalline structure, a 20-ps high-temperature pulse of 510 K (but not 450 or 480 K) was effective. The system finally obtained is an all-atom model, with Ewald summation to evaluate Coulombic interactions and a constant surface tension of 35 dynes/cm/water-membrane interface, equilibrated for 12 ns (over 50 ns total calculation time), which reproduces all of the experimentally observed parameters examined in this work. Furthermore, this model shows the presence of significant orientational correlations between neighboring alkyl chains and between shoulder vectors (which show the orientations of the lipids about their long axes) of neighboring DMPCs. PMID:11106617

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

    NASA Astrophysics Data System (ADS)

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

    2016-07-01

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

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

    PubMed Central

    Rog, Tomasz; Koivuniemi, Artturi

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Oroguchi, Tomotaka; Ikeguchi, Mitsunori

    2011-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2006-03-01

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

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

    PubMed

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Naritomi, Yusuke; Fuchigami, Sotaro

    2013-12-01

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

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

    SciTech Connect

    Naritomi, Yusuke; Fuchigami, Sotaro

    2013-12-07

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

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

    PubMed

    Naritomi, Yusuke; Fuchigami, Sotaro

    2013-12-01

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

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

    PubMed Central

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

    2015-01-01

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

  9. Molecular markers reveal infestation dynamics of the bed bug (Hemiptera: Cimicidae) within apartment buildings.

    PubMed

    Booth, Warren; Saenz, Virna L; Santangelo, Richard G; Wang, Changlu; Schal, Coby; Vargo, Edward L

    2012-05-01

    The bed bug, Cimex lectularius L. (Hemiptera: Cimicidae), has experienced an extraordinary global resurgence in recent years, the reasons for which remain poorly understood. Once considered a pest of lower socioeconomic classes, bed bugs are now found extensively across all residential settings, with widespread infestations established in multiapartment buildings. Within such buildings, understanding the population genetic structure and patterns of dispersal may prove critical to the development of effective control strategies. Here, we describe the development of 24 high-resolution microsatellite markers through next generation 454 pyrosequencing and their application to elucidate infestation dynamics within three multistory apartment buildings in the United States. Results reveal contrasting characteristics potentially representative of geographic or locale differences. In Raleigh, NC, an infestation within an apartment building seemed to have started from a single introduction followed by extensive spread. In Jersey City, NJ, two or more introductions followed by spread are evident in two buildings. Populations within single apartments in all buildings were characterized by high levels of relatedness and low levels of diversity, indicative of foundation from small, genetically depauperate propagules. Regardless of the number of unique introductions, genetic data indicate that spread within buildings is extensive, supporting both active and human-mediated dispersal within and between adjacent rooms or apartments spanning multiple floors. PMID:22679860

  10. Unbinding pathways of GW4064 from human farnesoid X receptor as revealed by molecular dynamics simulations.

    PubMed

    Li, Weihua; Fu, Jing; Cheng, Feixiong; Zheng, Mingyue; Zhang, Jian; Liu, Guixia; Tang, Yun

    2012-11-26

    Farnesoid X receptor (FXR, NR1H4) is a member of a nuclear receptor superfamily, which plays important roles in bile acid homeostasis, lipoprotein and glucose metabolism, and hepatic regeneration. GW4064 is a potent and selective FXR agonist and has become a tool compound to probe the physiological functions of FXR. Until now, the mechanism of GW4064 entering and leaving the FXR pocket is still poorly understood. Here, we report a computational study of GW4064 unbinding pathways from FXR by using several molecular dynamics (MD) simulation techniques. Based on the crystal structure of FXR in complex with GW4064, conventional MD was first used to refine the binding and check the stability of GW4064 in the FXR pocket. Random acceleration MD simulations were then performed to explore the possible unbinding pathways of GW4064 from FXR. Four main pathway clusters were found, among which three subpathways, namely Paths 2A, 2B, and 1B, were observed most frequently. Multiple steered MD simulations were further employed to estimate the maximum rupture force and the sum of the forces and to characterize the intermediate states of the ligand unbinding process. By comparing the average force profiles and structural changes, Paths 2A and 2B were identified to be the most favorable unbinding pathways. The former is located between the H1-H2 loop and the H5-H6 loop, and the latter is located in the cleft formed by the H5-H6 loop, H6, and H7. Moreover, the residues lining the pathways were analyzed for their roles in ligand unbinding. Based on our results, the possible structural modification strategies on GW4064 were also proposed.

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

    PubMed Central

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

    2014-01-01

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

  12. Hydrated germanium (II): irregular structural and dynamical properties revealed by a quantum mechanical charge field molecular dynamics study.

    PubMed

    Azam, S Sikander; Lim, Len Herald V; Hofer, Thomas S; Randolf, Bernhard R; Rode, Bernd M

    2010-01-30

    Structural and dynamical properties of Ge (II) in aqueous solution have been investigated using the novel ab initio quantum mechanical charge field (QMCF) molecular dynamics (MD) formalism. The first and second hydration shells were treated by ab initio quantum mechanics at restricted Hartree-Fock (RHF) level using the cc-pVDZ-PP basis set for Ge (II) and Dunning double-zeta plus polarization basis sets for O and H. Besides ligand exchange processes and mean ligand residence times to observe dynamics, tilt- and theta-angle distributions along with an advanced structural parameter, namely radial and angular distribution functions (RAD) for different regions were also evaluated. The combined radial and angular distribution depicted through surface plot and contour map is presented to provide a detailed insight into the density distribution of water molecules around the Ge(2+) ion. A strongly distorted hydration structure with two trigonal pyramidal substructures within the first hydration shell is observed, which demonstrates the lone-pair influence and provides a new basis for the interpretation of the catalytic and pharmacological properties of germanium coordination compounds.

  13. The Dynamic Conformational Cycle of the Group I Chaperonin C-Termini Revealed via Molecular Dynamics Simulation

    PubMed Central

    Dalton, Kevin M.; Frydman, Judith; Pande, Vijay S.

    2015-01-01

    Chaperonins are large ring shaped oligomers that facilitate protein folding by encapsulation within a central cavity. All chaperonins possess flexible C-termini which protrude from the equatorial domain of each subunit into the central cavity. Biochemical evidence suggests that the termini play an important role in the allosteric regulation of the ATPase cycle, in substrate folding and in complex assembly and stability. Despite the tremendous wealth of structural data available for numerous orthologous chaperonins, little structural information is available regarding the residues within the C-terminus. Herein, molecular dynamics simulations are presented which localize the termini throughout the nucleotide cycle of the group I chaperonin, GroE, from Escherichia coli. The simulation results predict that the termini undergo a heretofore unappreciated conformational cycle which is coupled to the nucleotide state of the enzyme. As such, these results have profound implications for the mechanism by which GroE utilizes nucleotide and folds client proteins. PMID:25822285

  14. The dynamic conformational cycle of the group I chaperonin C-termini revealed via molecular dynamics simulation.

    PubMed

    Dalton, Kevin M; Frydman, Judith; Pande, Vijay S

    2015-01-01

    Chaperonins are large ring shaped oligomers that facilitate protein folding by encapsulation within a central cavity. All chaperonins possess flexible C-termini which protrude from the equatorial domain of each subunit into the central cavity. Biochemical evidence suggests that the termini play an important role in the allosteric regulation of the ATPase cycle, in substrate folding and in complex assembly and stability. Despite the tremendous wealth of structural data available for numerous orthologous chaperonins, little structural information is available regarding the residues within the C-terminus. Herein, molecular dynamics simulations are presented which localize the termini throughout the nucleotide cycle of the group I chaperonin, GroE, from Escherichia coli. The simulation results predict that the termini undergo a heretofore unappreciated conformational cycle which is coupled to the nucleotide state of the enzyme. As such, these results have profound implications for the mechanism by which GroE utilizes nucleotide and folds client proteins. PMID:25822285

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

    PubMed

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

    2015-07-24

    By employing united atom molecular dynamics simulation, we have investigated the effects of polymer-graphene interaction ε(np) volume fraction of grapheme φ thermodynamics of polymer matrix (rubbery versus glassy), interfacial interaction in the case of the same dispersion state, shape of nanoparticles (NPs) such as C60 CNT and graphene at the same loading on the toughening efficiency of polymer nanocomposites. By beginning with the pure polymer, we observe that a plateau stress occurs at long chain length because entangled polymer chains in fibrils cannot become broken. We find that the work needed to dissipate during the failure increases with the increase of ε(np) and φ and the yield point in the stress-strain behavior occurs at a smaller strain for an attractive NPs filled system compared to the pure case, attributed to the more mechanically heterogeneous environment. The thermodynamics of the polymer matrix (below and above Tg) seems to have a significant effect on the toughening efficiency of graphene sheets. In the case of the same dispersion state, stronger interfacial interaction always induces long and highly orientated polymer fibrils along the deformation direction, with graphene sheets being encapsulated in these fiber-like bundles. By characterizing the interaction energy between polymer-polymer and polymer-graphene as a function of the strain, we find that the separation of polymer chains from the graphene sheets cease immediately after the yield point, followed by the continuous propagation of the cavities by excluding surrounded polymer chains and graphene sheets together. We also find that at the same attractive interfacial interaction and same loading, the toughening efficiency exhibits the following order: graphene > CNT > C60 Generally, the toughening mechanism of graphene sheets results from the formation of long and highly orientated polymer fibrils to prevent the occurrence of the rupture, which can be greatly improved by the strong

  16. Reorientational dynamics in molecular liquids as revealed by dynamic light scattering: From boiling point to glass transition temperature

    NASA Astrophysics Data System (ADS)

    Schmidtke, B.; Petzold, N.; Kahlau, R.; Rössler, E. A.

    2013-08-01

    We determine the reorientational correlation time τ of a series of molecular liquids by performing depolarized light scattering experiments (double monochromator, Fabry-Perot interferometry, and photon correlation spectroscopy). Correlation times in the range 10-12 s-100 s are compiled, i.e., the full temperature interval between the boiling point and the glass transition temperature Tg is covered. We focus on low-Tg liquids for which the high-temperature limit τ ≅ 10-12 s is easily accessed by standard spectroscopic equipment (up to 440 K). Regarding the temperature dependence three interpolation formulae of τ(T) with three parameters each are tested: (i) Vogel-Fulcher-Tammann equation, (ii) the approach recently discussed by Mauro et al. [Proc. Natl. Acad. Sci. U.S.A. 106, 19780 (2009)], and (iii) our approach decomposing the activation energy E(T) in a constant high temperature value E∞ and a "cooperative part" Ecoop(T) depending exponentially on temperature [Schmidtke et al., Phys. Rev. E 86, 041507 (2012)], 10.1103/PhysRevE.86.041507. On the basis of the present data, approaches (i) and (ii) are insufficient as they do not provide the correct crossover to the high-temperature Arrhenius law clearly identified in the experimental data while approach (iii) reproduces the salient features of τ(T). It allows to discuss the temperature dependence of the liquid's dynamics in terms of a Ecoop(T)/E∞ vs. T/E∞ plot and suggests that E∞ controls the energy scale of the glass transition phenomenon.

  17. Reorientational dynamics in molecular liquids as revealed by dynamic light scattering: from boiling point to glass transition temperature.

    PubMed

    Schmidtke, B; Petzold, N; Kahlau, R; Rössler, E A

    2013-08-28

    We determine the reorientational correlation time τ of a series of molecular liquids by performing depolarized light scattering experiments (double monochromator, Fabry-Perot interferometry, and photon correlation spectroscopy). Correlation times in the range 10(-12) s-100 s are compiled, i.e., the full temperature interval between the boiling point and the glass transition temperature T(g) is covered. We focus on low-T(g) liquids for which the high-temperature limit τ ≅ 10(-12) s is easily accessed by standard spectroscopic equipment (up to 440 K). Regarding the temperature dependence three interpolation formulae of τ(T) with three parameters each are tested: (i) Vogel-Fulcher-Tammann equation, (ii) the approach recently discussed by Mauro et al. [Proc. Natl. Acad. Sci. U.S.A. 106, 19780 (2009)], and (iii) our approach decomposing the activation energy E(T) in a constant high temperature value E∞ and a "cooperative part" E(coop)(T) depending exponentially on temperature [Schmidtke et al., Phys. Rev. E 86, 041507 (2012)]. On the basis of the present data, approaches (i) and (ii) are insufficient as they do not provide the correct crossover to the high-temperature Arrhenius law clearly identified in the experimental data while approach (iii) reproduces the salient features of τ(T). It allows to discuss the temperature dependence of the liquid's dynamics in terms of a E(coop)(T)/E∞ vs. T/E∞ plot and suggests that E∞ controls the energy scale of the glass transition phenomenon. PMID:24007015

  18. Reorientational dynamics in molecular liquids as revealed by dynamic light scattering: from boiling point to glass transition temperature.

    PubMed

    Schmidtke, B; Petzold, N; Kahlau, R; Rössler, E A

    2013-08-28

    We determine the reorientational correlation time τ of a series of molecular liquids by performing depolarized light scattering experiments (double monochromator, Fabry-Perot interferometry, and photon correlation spectroscopy). Correlation times in the range 10(-12) s-100 s are compiled, i.e., the full temperature interval between the boiling point and the glass transition temperature T(g) is covered. We focus on low-T(g) liquids for which the high-temperature limit τ ≅ 10(-12) s is easily accessed by standard spectroscopic equipment (up to 440 K). Regarding the temperature dependence three interpolation formulae of τ(T) with three parameters each are tested: (i) Vogel-Fulcher-Tammann equation, (ii) the approach recently discussed by Mauro et al. [Proc. Natl. Acad. Sci. U.S.A. 106, 19780 (2009)], and (iii) our approach decomposing the activation energy E(T) in a constant high temperature value E∞ and a "cooperative part" E(coop)(T) depending exponentially on temperature [Schmidtke et al., Phys. Rev. E 86, 041507 (2012)]. On the basis of the present data, approaches (i) and (ii) are insufficient as they do not provide the correct crossover to the high-temperature Arrhenius law clearly identified in the experimental data while approach (iii) reproduces the salient features of τ(T). It allows to discuss the temperature dependence of the liquid's dynamics in terms of a E(coop)(T)/E∞ vs. T/E∞ plot and suggests that E∞ controls the energy scale of the glass transition phenomenon.

  19. Molecular force modulation spectroscopy revealing the dynamic response of single bacteriorhodopsins.

    PubMed

    Janovjak, Harald; Müller, Daniel J; Humphris, Andrew D L

    2005-02-01

    Recent advances in atomic force microscopy allowed globular and membrane proteins to be mechanically unfolded on a single-molecule level. Presented is an extension to the existing force spectroscopy experiments. While unfolding single bacteriorhodopsins from native purple membranes, small oscillation amplitudes (6-9 nm) were supplied to the vertical displacement of the cantilever at a frequency of 3 kHz. The phase and amplitude response of the cantilever-protein system was converted to reveal the elastic (conservative) and viscous (dissipative) contributions to the unfolding process. The elastic response (stiffness) of the extended parts of the protein were in the range of a few tens pN/nm and could be well described by the derivative of the wormlike chain model. Discrete events in the viscous response coincided with the unfolding of single secondary structure elements and were in the range of 1 microNs/m. In addition, these force modulation spectroscopy experiments revealed novel mechanical unfolding intermediates of bacteriorhodopsin. We found that kinks result in a loss of unfolding cooperativity in transmembrane helices. Reconstructing force-distance spectra by the integration of amplitude-distance spectra verified their position, offering a novel approach to detect intermediates during the forced unfolding of single proteins. PMID:15574708

  20. Molecular dynamics of neutral polymer bonding agent (NPBA) as revealed by solid-state NMR spectroscopy.

    PubMed

    Hu, Wei; Su, Yongchao; Zhou, Lei; Pang, Aimin; Cai, Rulin; Ma, Xingang; Li, Shenhui

    2014-01-22

    Neutral polymer bonding agent (NPBA) is one of the most promising polymeric materials, widely used in nitrate ester plasticized polyether (NEPE) propellant as bonding agent. The structure and dynamics of NPBA under different conditions of temperatures and sample processing are comprehensively investigated by solid state NMR (SSNMR). The results indicate that both the main chain and side chain of NPBA are quite rigid below its glass transition temperature (Tg). In contrast, above the Tg, the main chain remains relatively immobilized, while the side chains become highly flexible, which presumably weakens the interaction between bonding agent and the binder or oxidant fillers and in turn destabilizes the high modulus layer formed around the oxidant fillers. In addition, no obvious variation is found for the microstructure of NPBA upon aging treatment or soaking with acetone. These experimental results provide useful insights for understanding the structural properties of NPBA and its interaction with other constituents of solid composite propellants under different processing and working conditions.

  1. Revealing Surface Waters on an Antifreeze Protein by Fusion Protein Crystallography Combined with Molecular Dynamic Simulations.

    PubMed

    Sun, Tianjun; Gauthier, Sherry Y; Campbell, Robert L; Davies, Peter L

    2015-10-01

    Antifreeze proteins (AFPs) adsorb to ice through an extensive, flat, relatively hydrophobic surface. It has been suggested that this ice-binding site (IBS) organizes surface waters into an ice-like clathrate arrangement that matches and fuses to the quasi-liquid layer on the ice surface. On cooling, these waters join the ice lattice and freeze the AFP to its ligand. Evidence for the generality of this binding mechanism is limited because AFPs tend to crystallize with their IBS as a preferred protein-protein contact surface, which displaces some bound waters. Type III AFP is a 7 kDa globular protein with an IBS made up two adjacent surfaces. In the crystal structure of the most active isoform (QAE1), the part of the IBS that docks to the primary prism plane of ice is partially exposed to solvent and has clathrate waters present that match this plane of ice. The adjacent IBS, which matches the pyramidal plane of ice, is involved in protein-protein crystal contacts with few surface waters. Here we have changed the protein-protein contacts in the ice-binding region by crystallizing a fusion of QAE1 to maltose-binding protein. In this 1.9 Å structure, the IBS that fits the pyramidal plane of ice is exposed to solvent. By combining crystallography data with MD simulations, the surface waters on both sides of the IBS were revealed and match well with the target ice planes. The waters on the pyramidal plane IBS were loosely constrained, which might explain why other isoforms of type III AFP that lack the prism plane IBS are less active than QAE1. The AFP fusion crystallization method can potentially be used to force the exposure to solvent of the IBS on other AFPs to reveal the locations of key surface waters.

  2. Structural Diversity of Ligand-Binding Androgen Receptors Revealed by Microsecond Long Molecular Dynamics Simulations and Enhanced Sampling.

    PubMed

    Duan, Mojie; Liu, Na; Zhou, Wenfang; Li, Dan; Yang, Minghui; Hou, Tingjun

    2016-09-13

    Androgen receptor (AR) plays important roles in the development of prostate cancer (PCa). The antagonistic drugs, which suppress the activity of AR, are widely used in the treatment of PCa. However, the molecular mechanism of antagonism about how ligands affect the structures of AR remains elusive. To better understand the conformational variability of ARs bound with agonists or antagonists, we performed long time unbiased molecular dynamics (MD) simulations and enhanced sampling simulations for the ligand binding domain of AR (AR-LBD) in complex with various ligands. Based on the simulation results, we proposed an allosteric pathway linking ligands and helix 12 (H12) of AR-LBD, which involves the interactions among the ligands and the residues W741, H874, and I899. The interaction pathway provides an atomistic explanation of how ligands affect the structure of AR-LBD. A repositioning of H12 was observed, but it is facilitated by the C-terminal of H12, instead of by the loop between helix 11 (H11) and H12. The bias-exchange metadynamics simulations further demonstrated the above observations. More importantly, the free energy profiles constructed by the enhanced sampling simulations revealed the transition process between the antagonistic form and agonistic form of AR-LBD. Our results would be helpful for the design of more efficient antagonists of AR to combat PCa. PMID:27560203

  3. Molecular dynamics simulations reveal the assembly mechanism of polysaccharides in marine aerosols.

    PubMed

    Sun, Lu; Li, Xin; Hede, Thomas; Tu, Yaoquan; Leck, Caroline; Ågren, Hans

    2014-12-21

    The high Arctic marine environment has recently detected polymer gels in atmospheric aerosol particles and cloud water originating from the surface microlayer of the open leads within the pack ice area. These polysaccharide molecules are water insoluble but water solvated, highly surface-active and highly hydrated (99% water). In order to add to the understanding and to complement missing laboratory characterization of marine polymer gels we have in this work performed an atomistic study of the assembly process and interfacial properties of polysaccharides. Our study reveals a number of salient features of the microscopic process behind polysaccharide assembly into nanogels. With three- and four-repeating units the polysaccharides assemble into a cluster in 50 ns. The aggregates grow quicker by absorbing one or two polymers each time, depending on the unit length and the type of inter-bridging cation. Although both the hydrophobic and hydrophilic domains are contracted, the latter dominates distinctly upon the contraction of solvent accessible surface areas. The establishment of inter-chain hydrogen-bonds is the key to the assembly while ionic bridges can further promote aggregation. During the assembly of the more bent four-unit polymers, intra-chain hydrogen bonds are significantly diminished by Ca(2+). Meanwhile, the percentage of Ca(2+) acting as an ionic bridge is more eminent, highlighting the significance of Ca(2+) ions for longer-chain polysaccharides. The aggregates are able to enhance surface tension more in the presence of Ca(2+) than in the presence of Na(+) owing to their more compact structure. These conclusions all demonstrate that studies of the present kind provide insight into the self-assembly process and interfacial properties of marine gels. We hope this understanding will keep up the interest in the complex and the fascinating relationship between marine microbiology, atmospheric aerosols, clouds and climate.

  4. A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest.

    PubMed

    Arenz, Stefan; Bock, Lars V; Graf, Michael; Innis, C Axel; Beckmann, Roland; Grubmüller, Helmut; Vaiana, Andrea C; Wilson, Daniel N

    2016-01-01

    Nascent polypeptides can induce ribosome stalling, regulating downstream genes. Stalling of ErmBL peptide translation in the presence of the macrolide antibiotic erythromycin leads to resistance in Streptococcus sanguis. To reveal this stalling mechanism we obtained 3.6-Å-resolution cryo-EM structures of ErmBL-stalled ribosomes with erythromycin. The nascent peptide adopts an unusual conformation with the C-terminal Asp10 side chain in a previously unseen rotated position. Together with molecular dynamics simulations, the structures indicate that peptide-bond formation is inhibited by displacement of the peptidyl-tRNA A76 ribose from its canonical position, and by non-productive interactions of the A-tRNA Lys11 side chain with the A-site crevice. These two effects combine to perturb peptide-bond formation by increasing the distance between the attacking Lys11 amine and the Asp10 carbonyl carbon. The interplay between drug, peptide and ribosome uncovered here also provides insight into the fundamental mechanism of peptide-bond formation. PMID:27380950

  5. A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest

    NASA Astrophysics Data System (ADS)

    Arenz, Stefan; Bock, Lars V.; Graf, Michael; Innis, C. Axel; Beckmann, Roland; Grubmüller, Helmut; Vaiana, Andrea C.; Wilson, Daniel N.

    2016-07-01

    Nascent polypeptides can induce ribosome stalling, regulating downstream genes. Stalling of ErmBL peptide translation in the presence of the macrolide antibiotic erythromycin leads to resistance in Streptococcus sanguis. To reveal this stalling mechanism we obtained 3.6-Å-resolution cryo-EM structures of ErmBL-stalled ribosomes with erythromycin. The nascent peptide adopts an unusual conformation with the C-terminal Asp10 side chain in a previously unseen rotated position. Together with molecular dynamics simulations, the structures indicate that peptide-bond formation is inhibited by displacement of the peptidyl-tRNA A76 ribose from its canonical position, and by non-productive interactions of the A-tRNA Lys11 side chain with the A-site crevice. These two effects combine to perturb peptide-bond formation by increasing the distance between the attacking Lys11 amine and the Asp10 carbonyl carbon. The interplay between drug, peptide and ribosome uncovered here also provides insight into the fundamental mechanism of peptide-bond formation.

  6. A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest

    PubMed Central

    Arenz, Stefan; Bock, Lars V.; Graf, Michael; Innis, C. Axel; Beckmann, Roland; Grubmüller, Helmut; Vaiana, Andrea C.; Wilson, Daniel N.

    2016-01-01

    Nascent polypeptides can induce ribosome stalling, regulating downstream genes. Stalling of ErmBL peptide translation in the presence of the macrolide antibiotic erythromycin leads to resistance in Streptococcus sanguis. To reveal this stalling mechanism we obtained 3.6-Å-resolution cryo-EM structures of ErmBL-stalled ribosomes with erythromycin. The nascent peptide adopts an unusual conformation with the C-terminal Asp10 side chain in a previously unseen rotated position. Together with molecular dynamics simulations, the structures indicate that peptide-bond formation is inhibited by displacement of the peptidyl-tRNA A76 ribose from its canonical position, and by non-productive interactions of the A-tRNA Lys11 side chain with the A-site crevice. These two effects combine to perturb peptide-bond formation by increasing the distance between the attacking Lys11 amine and the Asp10 carbonyl carbon. The interplay between drug, peptide and ribosome uncovered here also provides insight into the fundamental mechanism of peptide-bond formation. PMID:27380950

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

    PubMed Central

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

    2013-01-01

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

  8. 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.

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

    SciTech Connect

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

    2015-12-28

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

  10. Molecular dynamics simulations reveal a dielectric-responsive coronal structure in protein-polymer surfactant hybrid nanoconstructs.

    PubMed

    Brogan, Alex P S; Sessions, Richard B; Perriman, Adam W; Mann, Stephen

    2014-12-01

    Solvent-free liquid proteins are a new class of thermally stable hybrid bionanomaterials that are produced by extensive lyophilization of aqueous solutions of protein-polymer surfactant nanoconjugates followed by thermal annealing. The hybrid constructs, which consist of a globular protein core surrounded by a monolayer of electrostatically coupled polymer surfactant molecules, exhibit nativelike structure, function, and backbone dynamics over a large temperature range. Despite the key importance of the polymer surfactant shell, very little is known about the atomistic structure of the corona and how it influences the phase behavior and properties of these novel nanoscale objects. Here we present molecular dynamics simulations of protein-polymer surfactant nanoconjugates consisting of globular cores of myoglobin or lysozyme and demonstrate that the derived structural parameters are highly consistent with experimental values. We show that the coronal layer structure is responsive to the dielectric constant of the medium and that the mobility of the polymer surfactant molecules is significantly hindered in the solvent-free state, providing a basis for the origins of retained protein dynamics in these novel biofluids. Taken together, our results suggest that the extension of molecular dynamics simulations to hybrid nanoscale objects could be of generic value in diverse areas of soft matter chemistry, bioinspired engineering, and biomolecular nanotechnology.

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

    NASA Astrophysics Data System (ADS)

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

    2004-07-01

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

  12. Ab initio molecular dynamics simulations reveal localization and time evolution dynamics of an excess electron in heterogeneous CO{sub 2}–H{sub 2}O systems

    SciTech Connect

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

    2014-01-28

    In view of the important implications of excess electrons (EEs) interacting with CO{sub 2}–H{sub 2}O clusters in many fields, using ab initio molecular dynamics simulation technique, we reveal the structures and dynamics of an EE associated with its localization and subsequent time evolution in heterogeneous CO{sub 2}–H{sub 2}O mixed media. Our results indicate that although hydration can increase the electron-binding ability of a CO{sub 2} molecule, it only plays an assisting role. Instead, it is the bending vibrations that play the major role in localizing the EE. Due to enhanced attraction of CO{sub 2}, an EE can stably reside in the empty, low-lying π{sup *} orbital of a CO{sub 2} molecule via a localization process arising from its initial binding state. The localization is completed within a few tens of femtoseconds. After EE trapping, the ∠OCO angle of the core CO{sub 2}{sup −} oscillates in the range of 127°∼142°, with an oscillation period of about 48 fs. The corresponding vertical detachment energy of the EE is about 4.0 eV, which indicates extreme stability of such a CO{sub 2}-bound solvated EE in [CO{sub 2}(H{sub 2}O){sub n}]{sup −} systems. Interestingly, hydration occurs not only on the O atoms of the core CO{sub 2}{sup −} through formation of O⋯H–O H–bond(s), but also on the C atom, through formation of a C⋯H–O H–bond. In the latter binding mode, the EE cloud exhibits considerable penetration to the solvent water molecules, and its IR characteristic peak is relatively red-shifted compared with the former. Hydration on the C site can increase the EE distribution at the C atom and thus reduce the C⋯H distance in the C⋯H–O H–bonds, and vice versa. The number of water molecules associated with the CO{sub 2}{sup −} anion in the first hydration shell is about 4∼7. No dimer-core (C{sub 2}O{sub 4}{sup −}) and core-switching were observed in the double CO{sub 2} aqueous media. This work provides molecular dynamics

  13. Accelerated molecular dynamics methods

    SciTech Connect

    Perez, Danny

    2011-01-04

    The molecular dynamics method, although extremely powerful for materials simulations, is limited to times scales of roughly one microsecond or less. On longer time scales, dynamical evolution typically consists of infrequent events, which are usually activated processes. This course is focused on understanding infrequent-event dynamics, on methods for characterizing infrequent-event mechanisms and rate constants, and on methods for simulating long time scales in infrequent-event systems, emphasizing the recently developed accelerated molecular dynamics methods (hyperdynamics, parallel replica dynamics, and temperature accelerated dynamics). Some familiarity with basic statistical mechanics and molecular dynamics methods will be assumed.

  14. Mosaic of Water Orientation Structures at a Neutral Zwitterionic Lipid/Water Interface Revealed by Molecular Dynamics Simulations.

    PubMed

    Re, Suyong; Nishima, Wataru; Tahara, Tahei; Sugita, Yuji

    2014-12-18

    Ordering of water structures near the surface of biological membranes has been recently extensively studied using interface-selective techniques like vibrational sum frequency generation (VSFG) spectroscopy. The detailed structures of interface water have emerged for charged lipids, but those for neutral zwitterionic lipids remain obscure. We analyze an all-atom molecular dynamics (MD) trajectory of a hydrated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayer to characterize the orientation of interface waters in different chemical environments. The structure and dynamics of interfacial waters strongly depend on both their vertical position along the bilayer normal as well as vicinal lipid charged groups. Water orientation in the vicinity of phosphate groups is opposite to that around choline groups. The results are consistent with observed VSFG spectra and demonstrate that a mosaic of water orientation structures exists on the surface of a neutral zwitterionic phospholipid bilayer, reflecting rapid water exchange and the influence of local chemical environments. PMID:26273985

  15. Revealing molecular structure and dynamics through high-order harmonic generation driven by mid-IR fields

    SciTech Connect

    Torres, R.; Siegel, T.; Brugnera, L.; Ivanov, M. Yu.; Marangos, J. P.; Procino, I.; Underwood, Jonathan G.; Altucci, C.; Velotta, R.; Springate, E.; Froud, C.; Turcu, I. C. E.; Patchkovskii, S.; Smirnova, O.

    2010-05-15

    High-order harmonic generation (HHG) from molecules produces spectra that are modulated by interferences that encode both the static structure and the electron dynamics initiated by interaction with the laser field. Using a midinfrared (mid-IR) laser at 1300 nm, we are able to study the region of the harmonic spectrum containing such interferences in CO{sub 2} over a wide range of intensities. This allows for isolation and characterization of interference minima arising due to subcycle electronic dynamics triggered by the laser field, which had previously been identified but not systematically separated. Our experimental and theoretical results demonstrate important steps toward combining attosecond temporal and angstrom-scale spatial resolution in molecular HHG imaging.

  16. Formation Pathways of a Guanine-Quadruplex DNA Revealed by Molecular Dynamics and Thermodynamic Analysis of the Substates

    PubMed Central

    Štefl, Richard; Cheatham, Thomas E.; Špačková, Nad'a; Fadrná, Eva; Berger, Imre; Koča, Jaroslav; Šponer, Jiří

    2003-01-01

    The formation of a cation-stabilized guanine quadruplex (G-DNA) stem is an exceptionally slow process involving complex kinetics that has not yet been characterized at atomic resolution. Here, we investigate the formation of a parallel stranded G-DNA stem consisting of four strands of d(GGGG) using molecular dynamics simulations with explicit inclusion of counterions and solvent. Due to the limitations imposed by the nanosecond timescale of the simulations, rather than watching for the spontaneous formation of G-DNA, our approach probes the stability of possible supramolecular intermediates (including two-, three-, and four-stranded assemblies with out-of-register basepairing between guanines) on the formation pathway. The simulations suggest that “cross-like” two-stranded assemblies may serve as nucleation centers in the initial formation of parallel stranded G-DNA quadruplexes, proceeding through a series of rearrangements involving trapping of cations, association of additional strands, and progressive slippage of strands toward the full stem. To supplement the analysis, approximate free energies of the models are obtained with explicit consideration of the integral cations. The approach applied here serves as a prototype for qualitatively investigating other G-DNA molecules using molecular dynamics simulation and free-energy analysis. PMID:12944293

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

    DOE PAGES

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

    2015-04-13

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

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

    PubMed Central

    Fattebert, Jean-Luc; Emigh, Aiyana

    2015-01-01

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

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

    SciTech Connect

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

    2015-04-13

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

  20. Interactions of benzotriazole UV stabilizers with human serum albumin: Atomic insights revealed by biosensors, spectroscopies and molecular dynamics simulations.

    PubMed

    Zhuang, Shulin; Wang, Haifei; Ding, Keke; Wang, Jiaying; Pan, Liumeng; Lu, Yanli; Liu, Qingjun; Zhang, Chunlong

    2016-02-01

    Benzotriazole UV stabilizers (BZTs) belong to one prominent group of ultraviolet (UV) stabilizers and are widely used in various plastics materials. Their large production volumes, frequent detections in the environment and potential toxicities have raised increasing public concern. BZTs can be transported in vivo by transport proteins in plasma and the binding association to transport proteins may serve as a significant parameter to evaluate the bioaccumulative potential. We utilized a novel HSA biosensor, circular dichroism spectroscopy, fluorescence spectroscopy to detect the dynamic interactions of six BZTs (UV-326, UV-327, UV-328, UV-329, UV-P, and BZT) with human serum albumin (HSA), and characterized the corresponding structure-activity relationships (SAR) by molecular dynamics simulations. All test BZTs potently bind at Sudlow site I of HSA with a binding constant of 10(4) L/mol at 298 K. Minor changes in the moieties of BZTs affect their interactions with HSA and differently induce conformations of HSA. Their binding reduced electrochemical impedance spectra and α-helix content of HSA, caused slight red-shifted emission, and changed fluorescence lifetime components of HSA in a concentration-dependent mode. UV-327 and UV-329 form hydrogen bonds with HSA, while UV-329, UV-P and BZT bind HSA with more favorable electrostatic interactions. Our in vitro and in silico study offered a significant framework toward the understanding of risk assessment of BZTs and provides guide for future design of environmental benign BZTs-related materials.

  1. Interactions of benzotriazole UV stabilizers with human serum albumin: Atomic insights revealed by biosensors, spectroscopies and molecular dynamics simulations.

    PubMed

    Zhuang, Shulin; Wang, Haifei; Ding, Keke; Wang, Jiaying; Pan, Liumeng; Lu, Yanli; Liu, Qingjun; Zhang, Chunlong

    2016-02-01

    Benzotriazole UV stabilizers (BZTs) belong to one prominent group of ultraviolet (UV) stabilizers and are widely used in various plastics materials. Their large production volumes, frequent detections in the environment and potential toxicities have raised increasing public concern. BZTs can be transported in vivo by transport proteins in plasma and the binding association to transport proteins may serve as a significant parameter to evaluate the bioaccumulative potential. We utilized a novel HSA biosensor, circular dichroism spectroscopy, fluorescence spectroscopy to detect the dynamic interactions of six BZTs (UV-326, UV-327, UV-328, UV-329, UV-P, and BZT) with human serum albumin (HSA), and characterized the corresponding structure-activity relationships (SAR) by molecular dynamics simulations. All test BZTs potently bind at Sudlow site I of HSA with a binding constant of 10(4) L/mol at 298 K. Minor changes in the moieties of BZTs affect their interactions with HSA and differently induce conformations of HSA. Their binding reduced electrochemical impedance spectra and α-helix content of HSA, caused slight red-shifted emission, and changed fluorescence lifetime components of HSA in a concentration-dependent mode. UV-327 and UV-329 form hydrogen bonds with HSA, while UV-329, UV-P and BZT bind HSA with more favorable electrostatic interactions. Our in vitro and in silico study offered a significant framework toward the understanding of risk assessment of BZTs and provides guide for future design of environmental benign BZTs-related materials. PMID:26454115

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

    PubMed

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

    2014-12-01

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

  3. Using force-matching to reveal essential differences between density functionals in ab initio molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Izvekov, Sergei; Swanson, Jessica M. J.

    2011-05-01

    The exchange-correlation (XC) functional and value of the electronic fictitious mass μ can be two major sources of systematic errors in ab initio Car-Parrinello Molecular Dynamics (CPMD) simulations, and have a significant impact on the structural and dynamic properties of condensed-phase systems. In this work, an attempt is made to identify the origin of differences in liquid water properties generated from CPMD simulations run with the BLYP and HCTH/120 XC functionals and two different values of μ (representative of "small" and "large" limits) by analyzing the effective pairwise atom-atom interactions. The force-matching (FM) algorithm is used to map CPMD interactions into non-polarizable, empirical potentials defined by bonded interactions, pairwise short-ranged interactions in numerical form, and Coulombic interactions via atomic partial charges. The effective interaction models are derived for the BLYP XC functional with μ = 340 a.u. and μ = 1100 a.u. (BLYP-340 and BLYP-1100 simulations) and the HCTH/120 XC functional with μ = 340 a.u. (HCTH-340 simulation). The BLYP-340 simulation results in overstructured water with slow dynamics. In contrast, the BLYP-1100 and HCTH-340 simulations both produce radial distribution functions (indicative of structure) that are in reasonably good agreement with experiment. It is shown that the main difference between the BLYP-340 and HCTH-340 effective potentials arises in the short-ranged nonbonded interactions (in hydrogen bonding regions), while the difference between the BLYP-340 and BLYP-1100 interactions is mainly in the long-ranged electrostatic components. Collectively, these results demonstrate how the FM method can be used to further characterize various simulation ensembles (e.g., density-functional theory via CPMD). An analytical representation of each effective interaction water model, which is easy to implement, is presented.

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

    PubMed

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

    2011-02-01

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

  5. Molecular dynamics of the P450cam-Pdx complex reveals complex stability and novel interface contacts.

    PubMed

    Hollingsworth, Scott A; Poulos, Thomas L

    2015-01-01

    Cytochrome P450cam catalyzes the stereo and regiospecific hydroxylation of camphor to 5-exo-hydroxylcamphor. The two electrons for the oxidation of camphor are provided by putidaredoxin (Pdx), a Fe2 S2 containing protein. Two recent crystal structures of the P450cam-Pdx complex, one solved with the aid of covalent cross-linking and one without, have provided a structural picture of the redox partner interaction. To study the stability of the complex structure and the minor differences between the recent crystal structures, a 100 nanosecond molecular dynamics (MD) simulation of the cross-linked structure, mutated in silico to wild type and the linker molecule removed, was performed. The complex was stable over the course of the simulation though conformational changes including the movement of the C helix of P450cam further toward Pdx allowed for the formation of a number of new contacts at the complex interface that remained stable throughout the simulation. While several minor crystal contacts were lost in the simulation, all major contacts that had been experimentally studied previously were maintained. The equilibrated MD structure contained a mixture of contacts resembling both the cross-linked and noncovalent structures and the newly identified interactions. Finally, the reformation of the P450cam Asp251-Arg186 ion pair in the MD simulation mirrors the ion pair observed in the more promiscuous CYP101D1 and suggests that the Asp251-Arg186 ion pair may be important.

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

    PubMed

    Yi, Changhong; Wambo, Thierry O

    2015-09-21

    Beta-lactoglobulin (BLG), a bovine dairy protein, is a promiscuously interacting protein that can bind multiple hydrophobic ligands. Fatty acids (FAs), common hydrophobic molecules bound to BLG, are important sources of fuel for life because they yield large quantities of ATP when metabolized. The binding affinity increases with the length of the ligands, indicating the importance of the van der Waals (vdW) interactions between the hydrocarbon tail and the hydrophobic calyx of BLG. An exception to this rule is caprylic acid (OCA) which is two-carbon shorter but has a stronger binding affinity than capric acid. Theoretical calculations in the current literature are not accurate enough to shed light on the underlying physics of this exception. The computed affinity values are greater for longer fatty acids without respect for the caprylic exception and those values are generally several orders of magnitude away from the experimental data. In this work, we used hybrid steered molecular dynamics to accurately compute the binding free energies between BLG and the five saturated FAs of 8 to 16 carbon atoms. The computed binding free energies agree well with experimental data not only in rank but also in absolute values. We gained insights into the exceptional behavior of caprylic acid in the computed values of entropy and electrostatic interactions. We found that the electrostatic interaction between the carboxyl group of caprylic acid and the two amino groups of K60/69 in BLG is much stronger than the vdW force between the OCA's hydrophobic tail and the BLG calyx. This pulls OCA to the top of the beta barrel where it is easier to fluctuate, giving rise to greater entropy of OCA at the binding site. PMID:26272099

  7. Molecular dynamics reveal the essential role of linker motions in the function of cullin-RING E3 ligases

    PubMed Central

    Liu, Jin; Nussinov, Ruth

    2010-01-01

    Tagging proteins by polyubiquitin is a key step in protein degradation. Cullin-RING E3 ubiquitin ligases (CRLs) facilitate ubiquitin transfer from the E2 conjugating enzyme to the substrate; yet, crystallography indicates a large distance between the E2 and the substrate, raising the question of how this distance is bridged in the ubiquitin transfer reaction. Here, we demonstrate that the linker motions in the substrate binding proteins can allosterically shorten this distance to facilitate this crucial ubiquitin transfer step, and increase this distance to allow polyubiquitination. We performed molecular dynamics simulations for five substrate binding proteins, Skp2, Fbw7, β-TrCP1, Cdc4, and pVHL, in two forms: bound to their substrates, and bound to both substrate and adaptor. The adaptor connects the substrate binding proteins to the cullin. In the bound-to-both forms of all cases, we observed rotations of the substrate binding domain, shortening the gap between the tip of the substrate peptide and the E2 active site by 7~12Å compared to the crystal structures. Overall, together with our earlier simulations of the unbound and the bound-to-adaptor forms, the emerging picture is that the maximum 51~73Å distance between the substrate binding domain and the E2 active site in the modeled unbound forms of these five proteins shrinks to a minimum of 39~49Å in the bound-to-both forms. This large distance range, the result of allosterically-controlled linker motions, facilitates the ubiquitin transfer and polyubiquitination, and as such argues that the cullin-RING E3 ubiquitin ligase is under conformational control. We further observed that substrate binding proteins with multiple substrate acceptor lysines have larger distance range between the substrate and the E2 as compared to β-TrCP1, with only one acceptor lysine. PMID:20083119

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

    PubMed Central

    Yi, Changhong; Wambo, Thierry O.

    2015-01-01

    Beta-lactoglobulin (BLG), a bovine dairy protein, is a promiscuously interacting protein that can bind multiple hydrophobic ligands. Fatty acids (FAs), common hydrophobic molecules bound to BLG, are important sources of fuel for life because they yield large quantities of ATP when metabolized. The binding affinity increases with the length of the ligands, indicating the importance of the van der Waals (vdW) interactions between the hydrocarbon tail and the hydrophobic calyx of BLG. An exception to this rule is caprylic acid (OCA) which is two-carbon shorter but has a stronger binding affinity than capric acid. Theoretical calculations in the current literature are not accurate enough to shed light on the underlying physics of this exception. The computed affinity values are greater for longer fatty acids without respect for the caprylic exception and those values are generally several orders of magnitude away from the experimental data. In this work, we used hybrid steered molecular dynamics to accurately compute the binding free energies between BLG and the five saturated FAs of 8 to 16 carbon atoms. The computed binding free energies agree well with experimental data not only in rank but also in absolute values. We gained insights into the exceptional behavior of caprylic acid in the computed values of entropy and electrostatic interactions. We found that the electrostatic interaction between the carboxyl group of caprylic acid and the two amino groups of K60/69 in BLG is much stronger than the vdW force between OCA’s hydrophobic tail and the BLG calyx. This pulls OCA to the top of the beta barrel where it is easier to fluctuate, giving rise to greater entropy of OCA at the binding site. PMID:26272099

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

    NASA Astrophysics Data System (ADS)

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

    2016-07-01

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

  10. Ab initio molecular dynamics.

    PubMed

    Laasonen, Kari

    2013-01-01

    In this chapter, an introduction to ab initio molecular dynamics (AIMD) has been given. Many of the basic concepts, like the Hellman-Feynman forces, the difference between the Car-Parrinello molecular dynamics and AIMD, have been explained. Also a very versatile AIMD code, the CP2K, has been introduced. On the application, the emphasis was on the aqueous systems and chemical reactions. The biochemical applications have not been discussed in depth.

  11. Molecular dynamics reveal BCR-ABL1 polymutants as a unique mechanism of resistance to PAN-BCR-ABL1 kinase inhibitor therapy

    PubMed Central

    Gibbons, Don L.; Pricl, Sabrina; Posocco, Paola; Laurini, Erik; Fermeglia, Maurizio; Sun, Hanshi; Talpaz, Moshe; Donato, Nicholas; Quintás-Cardama, Alfonso

    2014-01-01

    The acquisition of mutations within the BCR-ABL1 kinase domain is frequently associated with tyrosine kinase inhibitor (TKI) failure in chronic myeloid leukemia. Sensitive sequencing techniques have revealed a high prevalence of compound BCR-ABL1 mutations (polymutants) in patients failing TKI therapy. To investigate the molecular consequences of such complex mutant proteins with regards to TKI resistance, we determined by cloning techniques the presence of polymutants in a cohort of chronic-phase patients receiving imatinib followed by dasatinib therapy. The analysis revealed a high frequency of polymutant BCR-ABL1 alleles even after failure of frontline imatinib, and also the progressive exhaustion of the pool of unmutated BCR-ABL1 alleles over the course of sequential TKI therapy. Molecular dynamics analyses of the most frequent polymutants in complex with TKIs revealed the basis of TKI resistance. Modeling of BCR-ABL1 in complex with the potent pan-BCR-ABL1 TKI ponatinib highlighted potentially effective therapeutic strategies for patients carrying these recalcitrant and complex BCR-ABL1 mutant proteins while unveiling unique mechanisms of escape to ponatinib therapy. PMID:24550512

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

    NASA Astrophysics Data System (ADS)

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

    2016-01-01

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

  13. Substructured multibody molecular dynamics.

    SciTech Connect

    Grest, Gary Stephen; Stevens, Mark Jackson; Plimpton, Steven James; Woolf, Thomas B. (Johns Hopkins University, Baltimore, MD); Lehoucq, Richard B.; Crozier, Paul Stewart; Ismail, Ahmed E.; Mukherjee, Rudranarayan M. (Rensselaer Polytechnic Institute, Troy, NY); Draganescu, Andrei I.

    2006-11-01

    We have enhanced our parallel molecular dynamics (MD) simulation software LAMMPS (Large-scale Atomic/Molecular Massively Parallel Simulator, lammps.sandia.gov) to include many new features for accelerated simulation including articulated rigid body dynamics via coupling to the Rensselaer Polytechnic Institute code POEMS (Parallelizable Open-source Efficient Multibody Software). We use new features of the LAMMPS software package to investigate rhodopsin photoisomerization, and water model surface tension and capillary waves at the vapor-liquid interface. Finally, we motivate the recipes of MD for practitioners and researchers in numerical analysis and computational mechanics.

  14. Large-Scale Structure of the Molecular Gas in Taurus Revealed by High Spatial Dynamic Range Spectral Line Mapping

    NASA Technical Reports Server (NTRS)

    Goldsmith, Paul F.

    2008-01-01

    Viewgraph topics include: optical image of Taurus; dust extinction in IR has provided a new tool for probing cloud morphology; observations of the gas can contribute critical information on gas temperature, gas column density and distribution, mass, and kinematics; the Taurus molecular cloud complex; average spectra in each mask region; mas 2 data; dealing with mask 1 data; behavior of mask 1 pixels; distribution of CO column densities; conversion to H2 column density; variable CO/H2 ratio with values much less than 10(exp -4) at low N indicated by UV results; histogram of N(H2) distribution; H2 column density distribution in Taurus; cumulative distribution of mass and area; lower CO fractional abundance in mask 0 and 1 regions greatly increases mass determined in the analysis; masses determined with variable X(CO) and including diffuse regions agrees well with the found from L(CO); distribution of young stars as a function of molecular column density; star formation efficiency; star formation rate and gas depletion; and enlarged images of some of the regions with numerous young stars. Additional slides examine the origin of the Taurus molecular cloud, evolution from HI gas, kinematics as a clue to its origin, and its relationship to star formation.

  15. Solution NMR and molecular dynamics reveal a persistent alpha helix within the dynamic region of PsbQ from photosystem II of higher plants

    PubMed Central

    Rathner, Petr; Rathner, Adriana; Horničáková, Michaela; Wohlschlager, Christian; Chandra, Kousik; Kohoutová, Jaroslava; Ettrich, Rüdiger; Wimmer, Reinhard

    2015-01-01

    ABSTRACT The extrinsic proteins of photosystem II of higher plants and green algae PsbO, PsbP, PsbQ, and PsbR are essential for stable oxygen production in the oxygen evolving center. In the available X‐ray crystallographic structure of higher plant PsbQ residues S14‐Y33 are missing. Building on the backbone NMR assignment of PsbQ, which includes this “missing link”, we report the extended resonance assignment including side chain atoms. Based on nuclear Overhauser effect spectra a high resolution solution structure of PsbQ with a backbone RMSD of 0.81 Å was obtained from torsion angle dynamics. Within the N‐terminal residues 1–45 the solution structure deviates significantly from the X‐ray crystallographic one, while the four‐helix bundle core found previously is confirmed. A short α‐helix is observed in the solution structure at the location where a β‐strand had been proposed in the earlier crystallographic study. NMR relaxation data and unrestrained molecular dynamics simulations corroborate that the N‐terminal region behaves as a flexible tail with a persistent short local helical secondary structure, while no indications of forming a β‐strand are found. Proteins 2015; 83:1677–1686. © 2015 The Authors. Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc. PMID:26138376

  16. Molecular data and ecological niche modelling reveal a highly dynamic evolutionary history of the East Asian Tertiary relict Cercidiphyllum (Cercidiphyllaceae).

    PubMed

    Qi, Xin-Shuai; Chen, Chen; Comes, Hans Peter; Sakaguchi, Shota; Liu, Yi-Hui; Tanaka, Nobuyuki; Sakio, Hitoshi; Qiu, Ying-Xiong

    2012-10-01

    East Asia's temperate deciduous forests served as sanctuary for Tertiary relict trees, but their ages and response to past climate change remain largely unknown. To address this issue, we elucidated the evolutionary and population demographic history of Cercdiphyllum, comprising species in China/Japan (Cercdiphyllum japonicum) and central Japan (Cercdiphyllum magnificum). Fifty-three populations were genotyped using chloroplast and ribosomal DNA sequences and microsatellite loci to assess molecular structure and diversity in relation to past (Last Glacial Maximum) and present distributions based on ecological niche modelling. Late Tertiary climate cooling was reflected in a relatively recent speciation event, dated at the Mio-/Pliocene boundary. During glacials, the warm-temperate C. japonicum experienced massive habitat losses in some areas (north-central China/north Japan) but increases in others (southwest/-east China, East China Sea landbridge, south Japan). In China, the Sichuan Basin and/or the middle-Yangtze were source areas of postglacial northward recolonization; in Japan, this may have been facilitated through introgressive hybridization with the cool-temperate C. magnificum. Our findings challenge the notion of relative evolutionary and demographic stability of Tertiary relict trees, and may serve as a guideline for assessing the impact of Neogene climate change on the evolution and distribution of East Asian temperate plants. PMID:22845876

  17. Molecular data and ecological niche modelling reveal a highly dynamic evolutionary history of the East Asian Tertiary relict Cercidiphyllum (Cercidiphyllaceae).

    PubMed

    Qi, Xin-Shuai; Chen, Chen; Comes, Hans Peter; Sakaguchi, Shota; Liu, Yi-Hui; Tanaka, Nobuyuki; Sakio, Hitoshi; Qiu, Ying-Xiong

    2012-10-01

    East Asia's temperate deciduous forests served as sanctuary for Tertiary relict trees, but their ages and response to past climate change remain largely unknown. To address this issue, we elucidated the evolutionary and population demographic history of Cercdiphyllum, comprising species in China/Japan (Cercdiphyllum japonicum) and central Japan (Cercdiphyllum magnificum). Fifty-three populations were genotyped using chloroplast and ribosomal DNA sequences and microsatellite loci to assess molecular structure and diversity in relation to past (Last Glacial Maximum) and present distributions based on ecological niche modelling. Late Tertiary climate cooling was reflected in a relatively recent speciation event, dated at the Mio-/Pliocene boundary. During glacials, the warm-temperate C. japonicum experienced massive habitat losses in some areas (north-central China/north Japan) but increases in others (southwest/-east China, East China Sea landbridge, south Japan). In China, the Sichuan Basin and/or the middle-Yangtze were source areas of postglacial northward recolonization; in Japan, this may have been facilitated through introgressive hybridization with the cool-temperate C. magnificum. Our findings challenge the notion of relative evolutionary and demographic stability of Tertiary relict trees, and may serve as a guideline for assessing the impact of Neogene climate change on the evolution and distribution of East Asian temperate plants.

  18. Excess electron reactivity in amino acid aqueous solution revealed by ab initio molecular dynamics simulation: anion-centered localization and anion-relayed electron transfer dissociation.

    PubMed

    Wu, Xiuxiu; Gao, Liang; Liu, Jinxiang; Yang, Hongfang; Wang, Shoushan; Bu, Yuxiang

    2015-10-28

    Studies on the structure, states, and reactivity of excess electrons (EEs) in biological media are of great significance. Although there is information about EE interaction with desolvated biological molecules, solution effects are hardly explored. In this work, we present an ab initio molecular dynamics simulation study on the interaction and reactivity of an EE with glycine in solution. Our simulations reveal two striking results. Firstly, a pre-solvated EE partially localizes on the negatively charged -COO(-) group of the zwitterionic glycine and the remaining part delocalizes over solvent water molecules, forming an anion-centered quasi-localized structure, due to relative alignment of the lowest unoccupied molecular orbital energy levels of potential sites for EE residence in the aqueous solution. Secondly, after a period of anion-centered localization of an EE, the zwitterionic glycine is induced to spontaneously fragment through the cleavage of the N-Cα bond, losing ammonia (deamination), and leaving a ˙CH2-COO(-) anion radical, in good agreement with experimental observations. Introduction of the same groups (-COO(-) or -NH3(+)) in the side chain (taking lysine and aspartic acid as examples) can affect EE localization, with the fragmentation of the backbone part of these amino acids dependent on the properties of the side chain groups. These findings provide insights into EE interaction mechanisms with the backbone parts of amino acids and low energy EE induced fragmentation of amino acids and even peptides and proteins.

  19. Open boundary molecular dynamics

    NASA Astrophysics Data System (ADS)

    Delgado-Buscalioni, R.; Sablić, J.; Praprotnik, M.

    2015-09-01

    This contribution analyzes several strategies and combination of methodologies to perform molecular dynamic simulations in open systems. Here, the term open indicates that the total system has boundaries where transfer of mass, momentum and energy can take place. This formalism, which we call Open Boundary Molecular Dynamics (OBMD), can act as interface of different schemes, such as Adaptive Resolution Scheme (AdResS) and Hybrid continuum-particle dynamics to link atomistic, coarse-grained (CG) and continuum (Eulerian) fluid dynamics in the general framework of fluctuating Navier-Stokes equations. The core domain of the simulation box is solved using all-atom descriptions. The CG layer introduced using AdResS is located at the outer part of the open box to make feasible the insertion of large molecules into the system. Communications between the molecular system and the outer world are carried out in the outer layers, called buffers. These coupling preserve momentum and mass conservation laws and can thus be linked with Eulerian hydro- dynamic solvers. In its simpler form, OBMD allows, however, to impose a local pressure tensor and a heat flux across the system's boundaries. For a one component molecular system, the external normal pressure and temperature determine the external chemical potential and thus the independent parameters of a grand-canonical ensemble simulation. Extended ensembles under non-equilibrium stationary states can also be simulated as well as time dependent forcings (e.g. oscillatory rheology). To illustrate the robustness of the combined OBMD-AdResS method, we present simulations of star-polymer melts at equilibrium and in sheared flow.

  20. A concurrent multiscale micromorphic molecular dynamics

    SciTech Connect

    Li, Shaofan Tong, Qi

    2015-04-21

    In this work, we have derived a multiscale micromorphic molecular dynamics (MMMD) from first principle to extend the (Andersen)-Parrinello-Rahman molecular dynamics to mesoscale and continuum scale. The multiscale micromorphic molecular dynamics is a con-current three-scale dynamics that couples a fine scale molecular dynamics, a mesoscale micromorphic dynamics, and a macroscale nonlocal particle dynamics together. By choosing proper statistical closure conditions, we have shown that the original Andersen-Parrinello-Rahman molecular dynamics is the homogeneous and equilibrium case of the proposed multiscale micromorphic molecular dynamics. In specific, we have shown that the Andersen-Parrinello-Rahman molecular dynamics can be rigorously formulated and justified from first principle, and its general inhomogeneous case, i.e., the three scale con-current multiscale micromorphic molecular dynamics can take into account of macroscale continuum mechanics boundary condition without the limitation of atomistic boundary condition or periodic boundary conditions. The discovered multiscale scale structure and the corresponding multiscale dynamics reveal a seamless transition from atomistic scale to continuum scale and the intrinsic coupling mechanism among them based on first principle formulation.

  1. Molecular dynamics simulations.

    PubMed

    Lindahl, Erik

    2015-01-01

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

  2. Molecular dynamics simulations.

    PubMed

    Lindahl, Erik R

    2008-01-01

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

  3. Multiscale reactive molecular dynamics

    PubMed Central

    Knight, Chris; Lindberg, Gerrick E.; Voth, Gregory A.

    2012-01-01

    Many processes important to chemistry, materials science, and biology cannot be described without considering electronic and nuclear-level dynamics and their coupling to slower, cooperative motions of the system. These inherently multiscale problems require computationally efficient and accurate methods to converge statistical properties. In this paper, a method is presented that uses data directly from condensed phase ab initio simulations to develop reactive molecular dynamics models that do not require predefined empirical functions. Instead, the interactions used in the reactive model are expressed as linear combinations of interpolating functions that are optimized by using a linear least-squares algorithm. One notable benefit of the procedure outlined here is the capability to minimize the number of parameters requiring nonlinear optimization. The method presented can be generally applied to multiscale problems and is demonstrated by generating reactive models for the hydrated excess proton and hydroxide ion based directly on condensed phase ab initio molecular dynamics simulations. The resulting models faithfully reproduce the water-ion structural properties and diffusion constants from the ab initio simulations. Additionally, the free energy profiles for proton transfer, which is sensitive to the structural diffusion of both ions in water, are reproduced. The high fidelity of these models to ab initio simulations will permit accurate modeling of general chemical reactions in condensed phase systems with computational efficiency orders of magnitudes greater than currently possible with ab initio simulation methods, thus facilitating a proper statistical sampling of the coupling to slow, large-scale motions of the system. PMID:23249062

  4. Functional roles of a structural element involving Na+-pi interactions in the catalytic site of T1 lipase revealed by molecular dynamics simulations.

    PubMed

    Hagiwara, Yohsuke; Matsumura, Hiroyoshi; Tateno, Masaru

    2009-11-25

    Interactions between metal ions and pi systems (metal-pi interactions) are known to confer significant stabilization energy. However, in biological systems, few structures with metal-pi coordination have been determined; thus, its roles must still be elucidated. The cation-pi interactions are not correctly described by current molecular mechanics even when using a polarizable force field, and thus they require quantum mechanical calculations for accurate estimation. However, the huge computational costs of the latter methodologies prohibit long-time molecular dynamics (MD) simulations. Accordingly, we developed a novel scheme to obtain an effective potential for calculating the interaction energy with an accuracy comparable to that of advanced ab initio calculations at the CCSD(T) levels, and with computational costs comparable to those of conventional MM calculations. Then, to elucidate the functional roles of the Na(+)-phenylalanine (Phe) complex in the catalytic site of T1 lipase, we performed MD simulations in the presence/absence of the accurate Na(+)-pi interaction energy. A comparison of these MD simulations revealed that a significantly large enthalpy gain in Na(+)-Phe16 substantially stabilizes the catalytic site, whereas a water molecule could not be substituted for Na(+) for sufficient stabilization energy. Thus, the cation-pi interaction in the lipase establishes a remarkably stable core structure by combining a hydrophobic aromatic ring and hydrophilic residues, of which the latter form the catalytic triad, thereby contributing to large structural changes from the complex with ligands to the free form of the lipase. This is the first report to elucidate the detailed functional mechanisms of Na(+)-pi interactions.

  5. Interactive molecular dynamics

    NASA Astrophysics Data System (ADS)

    Schroeder, Daniel V.

    2015-03-01

    Physics students now have access to interactive molecular dynamics simulations that can model and animate the motions of hundreds of particles, such as noble gas atoms, that attract each other weakly at short distances but repel strongly when pressed together. Using these simulations, students can develop an understanding of forces and motions at the molecular scale, nonideal fluids, phases of matter, thermal equilibrium, nonequilibrium states, the Boltzmann distribution, the arrow of time, and much more. This article summarizes the basic features and capabilities of such a simulation, presents a variety of student exercises using it at the introductory and intermediate levels, and describes some enhancements that can further extend its uses. A working simulation code, in html5 and javascript for running within any modern Web browser, is provided as an online supplement.

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

    PubMed

    Kaushik, Sandeep; Mohanty, Debasisa; Surolia, Avadhesha

    2012-01-01

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

  7. Protein dynamics: Moore's law in molecular biology.

    PubMed

    Vendruscolo, Michele; Dobson, Christopher M

    2011-01-25

    The millisecond barrier has been broken in molecular dynamics simulations of proteins. Such simulations are increasingly revealing the inner workings of biological systems by generating atomic-level descriptions of their behaviour that make testable predictions about key molecular processes.

  8. Introduction to Accelerated Molecular Dynamics

    SciTech Connect

    Perez, Danny

    2012-07-10

    Molecular Dynamics is the numerical solution of the equations of motion of a set of atoms, given an interatomic potential V and some boundary and initial conditions. Molecular Dynamics is the largest scale model that gives unbiased dynamics [x(t),p(t)] in full atomistic detail. Molecular Dynamics: is simple; is 'exact' for classical dynamics (with respect to a given V); can be used to compute any (atomistic) thermodynamical or dynamical properties; naturally handles complexity -- the system does the right thing at the right time. The physics derives only from the interatomic potential.

  9. Emergent Phenomena via Molecular Dynamics

    NASA Astrophysics Data System (ADS)

    Rapaport, D. C.

    Emergent phenomena are unusual because they are not obvious consequences of the design of the systems in which they appear, a feature no less relevant when they are being simulated. Several systems that exhibit surprisingly rich emergent behavior, each studied by molecular dynamics (MD) simulation, are described: (i) Modeling self-assembly processes associated with virus growth reveals the ability to achieve error-free assembly, where paradoxically, near-maximum yields are due to reversible bond formation. (ii) In fluids studied at the atomistic level, complex hydrodynamic phenomena in rotating and convecting fluids - the Taylor- Couette and Rayleigh-Bénard instabilities - can be reproduced, despite the limited length and time scales accessible by MD. (iii) Segregation studies of granular mixtures in a rotating drum reproduce the expected, but counterintuitive, axial and radial segregation, while for the case of a vertically vibrated layer a novel form of horizontal segregation is revealed.

  10. Na/Ca Intermixing around Silicate and Phosphate Groups in Bioactive Phosphosilicate Glasses Revealed by Heteronuclear Solid-State NMR and Molecular Dynamics Simulations.

    PubMed

    Mathew, Renny; Stevensson, Baltzar; Edén, Mattias

    2015-04-30

    We characterize the intermixing of network-modifying Na(+)/Ca(2+) ions around the silicate (QSi(n)) and phosphate (QP(n)) tetrahedra in a series of 16 Na2O–CaO–SiO2–P2O5 glasses, whose P content and silicate network connectivity were varied independently. The set includes both bioactive and bioinactive compositions and also encompasses two soda-lime-silicate members devoid of P, as well as two CaO–SiO2 glasses and one Na2O–SiO2–P2O5 glass. The various Si/P↔Na/Ca contacts were probed by molecular dynamics (MD) simulations together with heteronuclear magic-angle-spinning (MAS) nuclear magnetic resonance (NMR) experimentation utilizing (23)Na{(31)P} and (23)Na{(29)Si} REDOR, as well as (31)P{ (23)Na} and (29)Si{(23)Na} REAPDOR. We introduce an approach for quantifying the extent of Na(+)/Ca(2+) ordering around a given QP(n) or QSi(n) group, encoded by the preference factor 0⩽ PM ⩽ 1 conveying the relative weights of a random cation intermixing (PM = 0) and complete preference/ordering (PM = 1) for one of the species M, which represents either Na(+) or Ca(2+). The MD-derived preference factors reveal phosphate and silicate species surrounded by Na(+)/Ca(2+) ions intermixed nearly randomly (PM ≲ 0.15), except for the QSi(4) and QSi(1) groups, which manifest more significant cation ordering with preference for Na+ and Ca2+, respectively. The overall weak preferences are essentially independent of the Si and P contents of the glass, whereas PM primarily correlates with the total amount of network modifiers: as the latter is increased, the Na/Ca distribution around the {QP(0), QSi(1), QSi(2)} groups with preference for Ca2(+ )tend to randomize (i.e., PCa decreases), while the PNa-values grow slightly for the {QP(1), QSi(3), QSi(4)} species already preferring coordination of Na. The set of experimental preference factors {PCa} for the orthophosphate (QP(0)) groups extracted from (31)P{(23)Na} REAPDOR NMR-derived M2(P–Na) dipolar second moments agrees

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

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

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

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

    PubMed Central

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

    2014-01-01

    Clinical inhibitors Darunavir (DRV) and Amprenavir (APV) are less effective on HIV-2 protease (PR2) than on HIV-1 protease (PR1). To identify molecular basis associated with the lower inhibition, molecular dynamics (MD) simulations and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations were performed to investigate the effectiveness of the PR1 inhibitors DRV and APV against PR1/PR2. The rank of predicted binding free energies agrees with the experimental determined one. Moreover, our results show that two inhibitors bind less strongly to PR2 than to PR1, again in agreement with the experimental findings. The decrease in binding free energies for PR2 relative to PR1 is found to arise from the reduction of the van der Waals interactions induced by the structural adjustment of the triple mutant V32I, I47V and V82I. This result is further supported by the difference between the van der Waals interactions of inhibitors with each residue in PR2 and in PR1. The results from the principle component analysis suggest that inhibitor binding tends to make the flaps of PR2 close and the one of PR1 open. We expect that this study can theoretically provide significant guidance and dynamics information for the design of potent dual inhibitors targeting PR1/PR2. PMID:25362963

  13. The structure of human apolipoprotein A-IV as revealed by stable isotope-assisted cross-linking, molecular dynamics, and small angle x-ray scattering.

    PubMed

    Walker, Ryan G; Deng, Xiaodi; Melchior, John T; Morris, Jamie; Tso, Patrick; Jones, Martin K; Segrest, Jere P; Thompson, Thomas B; Davidson, W Sean

    2014-02-28

    Apolipoprotein (apo)A-IV plays important roles in dietary lipid and glucose metabolism, and knowledge of its structure is required to fully understand the molecular basis of these functions. However, typical of the entire class of exchangeable apolipoproteins, its dynamic nature and affinity for lipid has posed challenges to traditional high resolution structural approaches. We previously reported an x-ray crystal structure of a dimeric truncation mutant of apoA-IV, which showed a unique helix-swapping molecular interface. Unfortunately, the structures of the N and C termini that are important for lipid binding were not visualized. To build a more complete model, we used chemical cross-linking to derive distance constraints across the full-length protein. The approach was enhanced with stable isotope labeling to overcome ambiguities in determining molecular span of the cross-links given the remarkable similarities in the monomeric and dimeric apoA-IV structures. Using 51 distance constraints, we created a starting model for full-length monomeric apoA-IV and then subjected it to two modeling approaches: (i) molecular dynamics simulations and (ii) fitting to small angle x-ray scattering data. This resulted in the most detailed models yet for lipid-free monomeric or dimeric apoA-IV. Importantly, these models were of sufficient detail to direct the experimental identification of new functional residues that participate in a "clasp" mechanism to modulate apoA-IV lipid affinity. The isotope-assisted cross-linking approach should prove useful for further study of this family of apolipoproteins in both the lipid-free and -bound states. PMID:24425874

  14. Cold Adaptation of Zinc Metalloproteases in the Thermolysin Family from Deep Sea and Arctic Sea Ice Bacteria Revealed by Catalytic and Structural Properties and Molecular Dynamics

    PubMed Central

    Xie, Bin-Bin; Bian, Fei; Chen, Xiu-Lan; He, Hai-Lun; Guo, Jun; Gao, Xiang; Zeng, Yin-Xin; Chen, Bo; Zhou, Bai-Cheng; Zhang, Yu-Zhong

    2009-01-01

    Increased conformational flexibility is the prevailing explanation for the high catalytic efficiency of cold-adapted enzymes at low temperatures. However, less is known about the structural determinants of flexibility. We reported two novel cold-adapted zinc metalloproteases in the thermolysin family, vibriolysin MCP-02 from a deep sea bacterium and vibriolysin E495 from an Arctic sea ice bacterium, and compared them with their mesophilic homolog, pseudolysin from a terrestrial bacterium. Their catalytic efficiencies, kcat/Km (10–40 °C), followed the order pseudolysin < MCP-02 < E495 with a ratio of ∼1:2:4. MCP-02 and E495 have the same optimal temperature (Topt, 57 °C, 5 °C lower than pseudolysin) and apparent melting temperature (Tm = 64 °C, ∼10 °C lower than pseudolysin). Structural analysis showed that the slightly lower stabilities resulted from a decrease in the number of salt bridges. Fluorescence quenching experiments and molecular dynamics simulations showed that the flexibilities of the proteins were pseudolysin < MCP-02 < E495, suggesting that optimization of flexibility is a strategy for cold adaptation. Molecular dynamics results showed that the ordinal increase in flexibility from pseudolysin to MCP-02 and E495, especially the increase from MCP-02 to E495, mainly resulted from the decrease of hydrogen-bond stability in the dynamic structure, which was due to the increase in asparagine, serine, and threonine residues. Finally, a model for the cold adaptation of MCP-02 and E495 was proposed. This is the first report of the optimization of hydrogen-bonding dynamics as a strategy for cold adaptation and provides new insights into the structural basis underlying conformational flexibility. PMID:19181663

  15. 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.

  16. “Invisible” Conformers of an Antifungal Disulfide Protein Revealed by Constrained Cold and Heat Unfolding, CEST-NMR Experiments, and Molecular Dynamics Calculations

    PubMed Central

    Fizil, Ádám; Gáspári, Zoltán; Barna, Terézia; Marx, Florentine; Batta, Gyula

    2015-01-01

    Transition between conformational states in proteins is being recognized as a possible key factor of function. In support of this, hidden dynamic NMR structures were detected in several cases up to populations of a few percent. Here, we show by two- and three-state analysis of thermal unfolding, that the population of hidden states may weight 20–40 % at 298 K in a disulfide-rich protein. In addition, sensitive 15N-CEST NMR experiments identified a low populated (0.15 %) state that was in slow exchange with the folded PAF protein. Remarkably, other techniques failed to identify the rest of the NMR “dark matter”. Comparison of the temperature dependence of chemical shifts from experiments and molecular dynamics calculations suggests that hidden conformers of PAF differ in the loop and terminal regions and are most similar in the evolutionary conserved core. Our observations point to the existence of a complex conformational landscape with multiple conformational states in dynamic equilibrium, with diverse exchange rates presumably responsible for the completely hidden nature of a considerable fraction. PMID:25676351

  17. Transcriptome dynamics of a susceptible wheat upon Fusarium head blight reveals that molecular responses to Fusarium graminearum infection fit over the grain development processes.

    PubMed

    Chetouhi, Cherif; Bonhomme, Ludovic; Lasserre-Zuber, Pauline; Cambon, Florence; Pelletier, Sandra; Renou, Jean-Pierre; Langin, Thierry

    2016-03-01

    In many plant/pathogen interactions, host susceptibility factors are key determinants of disease development promoting pathogen growth and spreading in plant tissues. In the Fusarium head blight (FHB) disease, the molecular basis of wheat susceptibility is still poorly understood while it could provide new insights into the understanding of the wheat/Fusarium graminearum (Fg) interaction and guide future breeding programs to produce cultivars with sustainable resistance. To identify the wheat grain candidate genes, a genome-wide gene expression profiling was performed in the French susceptible wheat cultivar, Recital. Gene-specific two-way ANOVA of about 40 K transcripts at five grain developmental stages identified 1309 differentially expressed genes. Out of these, 536 were impacted by the Fg effect alone. Most of these Fg-responsive genes belonged to biological and molecular functions related to biotic and abiotic stresses indicating the activation of common stress pathways during susceptibility response of wheat grain to FHB. This analysis revealed also 773 other genes displaying either specific Fg-responsive profiles along with grain development stages or synergistic adjustments with the grain development effect. These genes were involved in various molecular pathways including primary metabolism, cell death, and gene expression reprogramming. An increasingly complex host response was revealed, as was the impact of both Fg infection and grain ontogeny on the transcription of wheat genes. This analysis provides a wealth of candidate genes and pathways involved in susceptibility responses to FHB and depicts new clues to the understanding of the susceptibility determinism in plant/pathogen interactions.

  18. Molecular photoionization dynamics

    SciTech Connect

    Dehmer, Joseph L.

    1982-05-01

    This program seeks to develop both physical insight and quantitative characterization of molecular photoionization processes. Progress is briefly described, and some publications resulting from the research are listed. (WHK)

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

    PubMed

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

    2016-09-01

    Heat shock protein (Hsp) 90 an emerging and attracting target in the anti-HIV drug discovery process due to the key role it plays in the pathogenicity of HIV-1 virus. In this research study, long-range all-atom molecular dynamics simulations were engaged for the bound and the unbound proteins to enhance the understanding of the molecular mechanisms of the Hsp90 dimerization and inhibition. Results evidently showed that coumermycin A1 (C-A1), a recently discovered Hsp90 inhibitor, binds at the dimer's active site of the Hsp90 protein and leads to a substantial parting between dimeric opposed residues, which include Arg591.B, Lys594.A, Ser663.A, Thr653.B, Ala665.A, Thr649.B, Leu646.B and Asn669.A. Significant differences in magnitudes were observed in radius of gyration, root-mean-square deviation and root-mean-square fluctuation, which confirms a reasonably more flexible state in the apo conformation associated with it dimerization. In contrast, the bound conformer of Hsp90 showed less flexibility. This visibly highpoints the inhibition process resulting from the binding of the ligand. These findings were further validated by principal component analysis. We believe that the detailed dynamic analyses of Hsp90 presented in this study, would give an imperative insight and better understanding to the function and mechanisms of inhibition. Furthermore, information obtained from the binding mode of the inhibitor would be of great assistance in the design of more potent inhibitors against the HIV target Hsp90. PMID:27376828

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

    PubMed

    Robbins, Timothy J; Wang, Yongmei

    2013-01-01

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

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

    PubMed

    Kogut, Mateusz; Kleist, Cyprian; Czub, Jacek

    2016-04-20

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

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

    PubMed Central

    Kogut, Mateusz; Kleist, Cyprian; Czub, Jacek

    2016-01-01

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

  3. Molecular scale dynamics of large ring polymers.

    PubMed

    Gooßen, S; Brás, A R; Krutyeva, M; Sharp, M; Falus, P; Feoktystov, A; Gasser, U; Pyckhout-Hintzen, W; Wischnewski, A; Richter, D

    2014-10-17

    We present neutron scattering data on the structure and dynamics of melts from polyethylene oxide rings with molecular weights up to ten times the entanglement mass of the linear counterpart. The data reveal a very compact conformation displaying a structure approaching a mass fractal, as hypothesized by recent simulation work. The dynamics is characterized by a fast Rouse relaxation of subunits (loops) and a slower dynamics displaying a lattice animal-like loop displacement. The loop size is an intrinsic property of the ring architecture and is independent of molecular weight. This is the first experimental observation of the space-time evolution of segmental motion in ring polymers illustrating the dynamic consequences of their topology that is unique among all polymeric systems of any other known architecture. PMID:25361284

  4. Molecular scale dynamics of large ring polymers.

    PubMed

    Gooßen, S; Brás, A R; Krutyeva, M; Sharp, M; Falus, P; Feoktystov, A; Gasser, U; Pyckhout-Hintzen, W; Wischnewski, A; Richter, D

    2014-10-17

    We present neutron scattering data on the structure and dynamics of melts from polyethylene oxide rings with molecular weights up to ten times the entanglement mass of the linear counterpart. The data reveal a very compact conformation displaying a structure approaching a mass fractal, as hypothesized by recent simulation work. The dynamics is characterized by a fast Rouse relaxation of subunits (loops) and a slower dynamics displaying a lattice animal-like loop displacement. The loop size is an intrinsic property of the ring architecture and is independent of molecular weight. This is the first experimental observation of the space-time evolution of segmental motion in ring polymers illustrating the dynamic consequences of their topology that is unique among all polymeric systems of any other known architecture.

  5. The mechanism of inhibition of the cyclin-dependent kinase-2 as revealed by the molecular dynamics study on the complex CDK2 with the peptide substrate HHASPRK

    PubMed Central

    Bártová, Iveta; Otyepka, Michal; KřÍž, Zdeněk; Koča, Jaroslav

    2005-01-01

    Molecular dynamics (MD) simulations were used to explain structural details of cyclin-dependent kinase-2 (CDK2) inhibition by phosphorylation at T14 and/or Y15 located in the glycine-rich loop (G-loop). Ten-nanosecond-long simulations of fully active CDK2 in a complex with a short peptide (HHASPRK) substrate and of CDK2 inhibited by phosphorylation of T14 and/or Y15 were produced. The inhibitory phosphorylations at T14 and/or Y15 show namely an ATP misalignment and a G-loop shift (~5 Å) causing the opening of the substrate binding box. The biological functions of the G-loop and GxGxxG motif evolutionary conservation in protein kinases are discussed. The position of the ATP γ-phosphate relative to the phosphorylation site (S/T) of the peptide substrate in the active CDK2 is described and compared with inhibited forms of CDK2. The MD results clearly provide an explanation previously not known as to why a basic residue (R/K) is preferred at the P2 position in phosphorylated S/T peptide substrates. PMID:15632290

  6. State-dependent molecular dynamics.

    PubMed

    Yang, Ciann-Dong; Weng, Hung-Jen

    2014-01-01

    This paper proposes a new mixed quantum mechanics (QM)-molecular mechanics (MM) approach, where MM is replaced by quantum Hamilton mechanics (QHM), which inherits the modeling capability of MM, while preserving the state-dependent nature of QM. QHM, a single mechanics playing the roles of QM and MM simultaneously, will be employed here to derive the three-dimensional quantum dynamics of diatomic molecules. The resulting state-dependent molecular dynamics including vibration, rotation and spin are shown to completely agree with the QM description and well match the experimental vibration-rotation spectrum. QHM can be incorporated into the framework of a mixed quantum-classical Bohmian method to enable a trajectory interpretation of orbital-spin interaction and spin entanglement in molecular dynamics.

  7. A sampling of molecular dynamics

    NASA Astrophysics Data System (ADS)

    Sindhikara, Daniel Jon

    The sheer vastness of the number of computations required to simulate a biological molecule puts incredible pressure on algorithms to be efficient while maintaining sufficient accuracy. This dissertation summarizes various projects whose purposes address the large span of types of problems in molecular dynamics simulations of biological systems including: increasing efficiency, measuring convergence, avoiding pitfalls, and an application and analysis of a biological system. Chapters 3 and 4 deal with an enhanced sampling algorithm called "replica exchange molecular dynamics" which is designed to speed-up molecular dynamics simulations. The optimization of a key parameter of these simulations is analyzed. In these successive projects, it was found conclusively that maximizing "exchange attempt frequency" is the most efficient way to run a replica exchange molecular dynamics simulation. Chapter 5 describes an enhanced metric for convergence in parallel simulations called the normalized ergodic measure. The metric is applied to several properties for several replica exchange simulations. Advantages of this metric over other methods are described. Chapter 6 describes the implementation and optimization of an enhanced sampling algorithm similar to replica exchange molecular dynamics called multicanonical algorithm replica exchange molecular dynamics. The algorithm was implemented into a biomolecular simulation suite called AMBER. Additionally several parameters were analyzed and optimized. In Chapter 7, a pitfall in molecular dynamics is observed in biological systems that is caused by negligent use of a simulation's "thermostat". It was found that if the same pseudorandom number seed were used for multiple systems, they eventually synchronize. In this project, synchronization was observed in biological molecules. Various negative effects including corruption of data are pointed out. Chapter 8 describes molecular dynamics simulation of NikR, a homotetrameric nickel

  8. Eye Movements Reveal Dynamics of Task Control

    ERIC Educational Resources Information Center

    Mayr, Ulrich; Kuhns, David; Rieter, Miranda

    2013-01-01

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

  9. Turn-directed α-β conformational transition of α-syn12 peptide at different pH revealed by unbiased molecular dynamics simulations.

    PubMed

    Liu, Lei; Cao, Zanxia

    2013-05-24

    The transition from α-helical to β-hairpin conformations of α-syn12 peptide is characterized here using long timescale, unbiased molecular dynamics (MD) simulations in explicit solvent models at physiological and acidic pH values. Four independent normal MD trajectories, each 2500 ns, are performed at 300 K using the GROMOS 43A1 force field and SPC water model. The most clustered structures at both pH values are β-hairpin but with different turns and hydrogen bonds. Turn9-6 and four hydrogen bonds (HB9-6, HB6-9, HB11-4 and HB4-11) are formed at physiological pH; turn8-5 and five hydrogen bonds (HB8-5, HB5-8, HB10-3, HB3-10 and HB12-1) are formed at acidic pH. A common folding mechanism is observed: the formation of the turn is always before the formation of the hydrogen bonds, which means the turn is always found to be the major determinant in initiating the transition process. Furthermore, two transition paths are observed at physiological pH. One of the transition paths tends to form the most-clustered turn and improper hydrogen bonds at the beginning, and then form the most-clustered hydrogen bonds. Another transition path tends to form the most-clustered turn, and turn5-2 firstly, followed by the formation of part hydrogen bonds, then turn5-2 is extended and more hydrogen bonds are formed. The transition path at acidic pH is as the same as the first path described at physiological pH.

  10. Nanoindentation of Zr by molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Lu (芦子哲), Zizhe; Chernatynskiy, Aleksandr; Noordhoek, Mark J.; Sinnott, Susan B.; Phillpot, Simon R.

    2015-12-01

    Molecular dynamics simulations of nanoindentation are used to study the deformation behaviors of single crystal Zr for four different surface orientations. The comparison of results for two different potentials, an embedded atom method potential and a charged optimized many body potential, reveals the influence of stable and unstable stacking fault energy on dislocation behaviors under nanoindentation. The load-displacement curve, hardness and deformation behaviors of the various surface orientations Zr are compared and the elastic and plastic deformation behaviors are analyzed.

  11. Molecular dynamics simulations of certain mutant peptide models from staphylococcal nuclease reveal that initial hydrophobic collapse associated with turn propensity drives β-hairpin folding.

    PubMed

    Shukla, Rashmi Tambe; Kumar, Naveen; Sasidhar, Yellamraju U

    2013-08-01

    An important nucleation event during the folding of staphylococcal nuclease involves the formation of a β-hairpin by the sequence (21) DTVKLMYKGQPMTFR(35) . Earlier studies show that the turn sequence 'YKGQP' has an important role in the folding of this β-hairpin. To understand the active or passive nature of the turn sequence 'YKGQP' in the folding of the aforementioned β-hairpin sequence, we studied glycine mutant peptides Ac-(2) DTVKLMYGGQPMTFR(16) -NMe (K9G:15), Ac-(2) DTVKLMYKGGPMTFR(16) -NMe (Q11G:15), Ac-(2) DTVKLMYGGGPMTFR(16) -NMe (K9G/Q11G:15), and Ac-(2) DTVKLMGGGGGMTFR(16) -NMe (penta-G:15) by using molecular dynamics simulations, starting with two different unfolded states, polyproline II and extended conformational forms. Further, 5mer mutant turn peptides Ac-(2) YGGQP(6) -NMe (K3G:5), Ac-(2) YKGGP(6) -NMe (Q5G:5), Ac-(2) YGGGP(6) -NMe (K3G/Q5G:5), and Ac-(2) GGGGG(6) -NMe (penta-G:5) were also studied individually. Our results show that an initial hydrophobic collapse and loop closure occurs in all 15mer mutants, but only K9G:15 mutant forms a stable native-like β-hairpin. In the other 15mer mutants, the hydrophobic collapsed state would not proceed to β-hairpin formation. Of the different simulations performed for the penta-G:15 mutant, in only one simulation a nonnative β-hairpin conformation is sampled with highly flexible loop region ((8) GGGGG(12) ), which has no specific conformational preference as a 5mer. While the sequence 'YGGQP' in the K3G:5 simulation shows relatively higher β-turn propensity, the presence of this sequence in K9G:15 peptide seems to be driving the β-hairpin formation. Thus, these results seem to suggest that for the formation of a stable β-hairpin, the initial hydrophobic collapse is to be assisted by a turn propensity. Initial hydrophobic collapse alone is not sufficient to guide β-hairpin formation.

  12. Molecular Exchange Dynamics in Block Copolymer Micelles

    NASA Astrophysics Data System (ADS)

    Bates, Frank; Lu, Jie; Choi, Soohyung; Lodge, Timothy

    2012-02-01

    Poly(styrene-b-ethylene propylene) (PS-PEP) diblock copolymers were mixed with squalane (C30H62) at 1% by weight resulting in the formation of spherical micelles. The structure and dynamics of molecular exchange were characterized by synchrotron small-angle x-ray scattering (SAXS) and time resolved small-angle neutron scattering (TR-SANS), respectively, between 100 C and 160 C. TR-SANS measurements were performed with solutions initially containing deuterium labeled micelle cores and normal cores dispersed in a contrast matched squalane. Monitoring the reduction in scattering intensity as a function of time at various temperatures revealed molecular exchange dynamics highly sensitive to the core molecular weight and molecular weight distribution. Time-temperature superposition of data acquired at different temperatures produced a single master curve for all the mixtures. Experiments conducted with isotopically labeled micelle cores, each formed from two different but relatively mondisperse PS blocks, confirmed a simple dynamical model based on first order kinetics and core Rouse single chain relaxation. These findings demonstrate a dramatic transition to nonergodicity with increasing micelle core molecular weight and confirm the origins of the logarithmic exchange kinetics in such systems.

  13. Dynamic fracture toughness determined using molecular dynamics

    SciTech Connect

    Swadener, J. G.; Baskes, M. I.; Nastasi, Michael Anthony,

    2004-01-01

    Molecular dynamics (MD) simulations of fracture in crystalline silicon are conducted in order to determine the dynamic fracture toughness. The MD simulations show how the potential energy released during fracture is partitioned into surface energy, energy stored in defects and kinetic energy. First, the MD fracture simulations are shown to produce brittle fracture and be in reasonable agreement with experimental results. Then dynamic hcture toughness is calculated as the sum of the surface energy and the energy stored as defects directly from the MD models. Models oriented to produce fracture on either (111) or (101) planes are used. For the (101) fracture orientation, equilibrium crack speeds of greater than 80% of the Rayleigh wave speed are obtained. Crack speeds initially show a steep increase with increasing energy release rate followed by a much more gradual increase. No plateau in crack speed is observed for static energy release rates up to 20 J/m{sup 2}. At the point where the change in crack speed behavior occur, the dynamic fracture toughness (J{sub d}) is still within 10% of two times the surface energy (2{gamma}{sub 0}) and changing very slowly. From these MD simulations, it appears that the change in crack speed behavior is due to a change in the kinetic energy generation during dynamic fracture. In addition, MD simulations of facture in silicon with defects were conducted. The addition of defects increases the inelastic dissipation and the energy stored in defects.

  14. Thomas-Fermi molecular dynamics

    SciTech Connect

    Clerouin, J.; Pollock, E.L. ); Zerah, G. )

    1992-10-15

    A three-dimensional density-functional molecular-dynamics code is developed for the Thomas-Fermi density functional as a prototype for density functionals using only the density. Following Car and Parrinello (Phys. Rev. Lett. 55, 2471 (1985)), the electronic density is treated as a dynamical variable. The electronic densities are verified against a multi-ion Thomas-Fermi algorithm due to Parker (Phys. Rev. A 38, 2205 (1988)). As an initial application, the effect of electronic polarization in enhancing ionic diffusion in strongly coupled plasmas is demonstrated.

  15. Available Instruments for Analyzing Molecular Dynamics Trajectories.

    PubMed

    Likhachev, I V; Balabaev, N K; Galzitskaya, O V

    2016-01-01

    Molecular dynamics trajectories are the result of molecular dynamics simulations. Trajectories are sequential snapshots of simulated molecular system which represents atomic coordinates at specific time periods. Based on the definition, in a text format trajectory files are characterized by their simplicity and uselessness. To obtain information from such files, special programs and information processing techniques are applied: from molecular dynamics animation to finding characteristics along the trajectory (versus time). In this review, we describe different programs for processing molecular dynamics trajectories. The performance of these programs, usefulness for analyses of molecular dynamics trajectories, strong and weak aspects are discussed. PMID:27053964

  16. Available Instruments for Analyzing Molecular Dynamics Trajectories

    PubMed Central

    Likhachev, I. V.; Balabaev, N. K.; Galzitskaya, O. V.

    2016-01-01

    Molecular dynamics trajectories are the result of molecular dynamics simulations. Trajectories are sequential snapshots of simulated molecular system which represents atomic coordinates at specific time periods. Based on the definition, in a text format trajectory files are characterized by their simplicity and uselessness. To obtain information from such files, special programs and information processing techniques are applied: from molecular dynamics animation to finding characteristics along the trajectory (versus time). In this review, we describe different programs for processing molecular dynamics trajectories. The performance of these programs, usefulness for analyses of molecular dynamics trajectories, strong and weak aspects are discussed. PMID:27053964

  17. From molecular dynamics to Brownian dynamics

    PubMed Central

    Erban, Radek

    2014-01-01

    Three coarse-grained molecular dynamics (MD) models are investigated with the aim of developing and analysing multi-scale methods which use MD simulations in parts of the computational domain and (less detailed) Brownian dynamics (BD) simulations in the remainder of the domain. The first MD model is formulated in one spatial dimension. It is based on elastic collisions of heavy molecules (e.g. proteins) with light point particles (e.g. water molecules). Two three-dimensional MD models are then investigated. The obtained results are applied to a simplified model of protein binding to receptors on the cellular membrane. It is shown that modern BD simulators of intracellular processes can be used in the bulk and accurately coupled with a (more detailed) MD model of protein binding which is used close to the membrane. PMID:25002825

  18. NMR investigations of molecular dynamics

    NASA Astrophysics Data System (ADS)

    Palmer, Arthur

    2011-03-01

    NMR spectroscopy is a powerful experimental approach for characterizing protein conformational dynamics on multiple time scales. The insights obtained from NMR studies are complemented and by molecular dynamics (MD) simulations, which provide full atomistic details of protein dynamics. Homologous mesophilic (E. coli) and thermophilic (T. thermophilus) ribonuclease H (RNase H) enzymes serve to illustrate how changes in protein sequence and structure that affect conformational dynamic processes can be monitored and characterized by joint analysis of NMR spectroscopy and MD simulations. A Gly residue inserted within a putative hinge between helices B and C is conserved among thermophilic RNases H, but absent in mesophilic RNases H. Experimental spin relaxation measurements show that the dynamic properties of T. thermophilus RNase H are recapitulated in E. coli RNase H by insertion of a Gly residue between helices B and C. Additional specific intramolecular interactions that modulate backbone and sidechain dynamical properties of the Gly-rich loop and of the conserved Trp residue flanking the Gly insertion site have been identified using MD simulations and subsequently confirmed by NMR spin relaxation measurements. These results emphasize the importance of hydrogen bonds and local steric interactions in restricting conformational fluctuations, and the absence of such interactions in allowing conformational adaptation to substrate binding.

  19. Scalable Molecular Dynamics with NAMD

    PubMed Central

    Phillips, James C.; Braun, Rosemary; Wang, Wei; Gumbart, James; Tajkhorshid, Emad; Villa, Elizabeth; Chipot, Christophe; Skeel, Robert D.; Kalé, Laxmikant; Schulten, Klaus

    2008-01-01

    NAMD is a parallel molecular dynamics code designed for high-performance simulation of large biomolecular systems. NAMD scales to hundreds of processors on high-end parallel platforms, as well as tens of processors on low-cost commodity clusters, and also runs on individual desktop and laptop computers. NAMD works with AMBER and CHARMM potential functions, parameters, and file formats. This paper, directed to novices as well as experts, first introduces concepts and methods used in the NAMD program, describing the classical molecular dynamics force field, equations of motion, and integration methods along with the efficient electrostatics evaluation algorithms employed and temperature and pressure controls used. Features for steering the simulation across barriers and for calculating both alchemical and conformational free energy differences are presented. The motivations for and a roadmap to the internal design of NAMD, implemented in C++ and based on Charm++ parallel objects, are outlined. The factors affecting the serial and parallel performance of a simulation are discussed. Next, typical NAMD use is illustrated with representative applications to a small, a medium, and a large biomolecular system, highlighting particular features of NAMD, e.g., the Tcl scripting language. Finally, the paper provides a list of the key features of NAMD and discusses the benefits of combining NAMD with the molecular graphics/sequence analysis software VMD and the grid computing/collaboratory software BioCoRE. NAMD is distributed free of charge with source code at www.ks.uiuc.edu. PMID:16222654

  20. Better, Cheaper, Faster Molecular Dynamics

    NASA Technical Reports Server (NTRS)

    Pohorille, Andrew; DeVincenzi, Donald L. (Technical Monitor)

    2001-01-01

    Recent, revolutionary progress in genomics and structural, molecular and cellular biology has created new opportunities for molecular-level computer simulations of biological systems by providing vast amounts of data that require interpretation. These opportunities are further enhanced by the increasing availability of massively parallel computers. For many problems, the method of choice is classical molecular dynamics (iterative solving of Newton's equations of motion). It focuses on two main objectives. One is to calculate the relative stability of different states of the system. A typical problem that has' such an objective is computer-aided drug design. Another common objective is to describe evolution of the system towards a low energy (possibly the global minimum energy), "native" state. Perhaps the best example of such a problem is protein folding. Both types of problems share the same difficulty. Often, different states of the system are separated by high energy barriers, which implies that transitions between these states are rare events. This, in turn, can greatly impede exploration of phase space. In some instances this can lead to "quasi non-ergodicity", whereby a part of phase space is inaccessible on time scales of the simulation. To overcome this difficulty and to extend molecular dynamics to "biological" time scales (millisecond or longer) new physical formulations and new algorithmic developments are required. To be efficient they should account for natural limitations of multi-processor computer architecture. I will present work along these lines done in my group. In particular, I will focus on a new approach to calculating the free energies (stability) of different states and to overcoming "the curse of rare events". I will also discuss algorithmic improvements to multiple time step methods and to the treatment of slowly decaying, log-ranged, electrostatic effects.

  1. Molecular dynamics of polymer growth

    NASA Astrophysics Data System (ADS)

    Akkermans, Reinier L. C.; Toxvaerd, Søren; Briels, W. J.

    1998-08-01

    The irreversible polymerization of a monomer liquid has been studied by molecular-dynamics simulation in two and three dimensions. The growth process is studied under good solvent conditions in the dilute regime and up to semidilute and concentrated regimes. In the dilute regime we observe a reaction limitation due to trapping of the growing centers, which is more pronounced in the lower dimension. At higher concentrations the presence of other chains decreases the monomer mobility and reaction rate. Conformational properties are studied by scaling analysis of end-to-end and gyration radii. A crossover from swollen conformations towards screened conformations is observed as growth proceeds.

  2. STRUCTURED MOLECULAR GAS REVEALS GALACTIC SPIRAL ARMS

    SciTech Connect

    Sawada, Tsuyoshi; Hasegawa, Tetsuo; Koda, Jin

    2012-11-01

    We explore the development of structures in molecular gas in the Milky Way by applying the analysis of the brightness distribution function and the brightness distribution index (BDI) in the archival data from the Boston University-Five College Radio Astronomy Observatory {sup 13}CO J = 1-0 Galactic Ring Survey. The BDI measures the fractional contribution of spatially confined bright molecular emission over faint emission extended over large areas. This relative quantity is largely independent of the amount of molecular gas and of any conventional, pre-conceived structures, such as cores, clumps, or giant molecular clouds. The structured molecular gas traced by higher BDI is located continuously along the spiral arms in the Milky Way in the longitude-velocity diagram. This clearly indicates that molecular gas changes its structure as it flows through the spiral arms. Although the high-BDI gas generally coincides with H II regions, there is also some high-BDI gas with no/little signature of ongoing star formation. These results support a possible evolutionary sequence in which unstructured, diffuse gas transforms itself into a structured state on encountering the spiral arms, followed by star formation and an eventual return to the unstructured state after the spiral arm passage.

  3. Radiation in molecular dynamic simulations

    SciTech Connect

    Glosli, J; Graziani, F; More, R; Murillo, M; Streitz, F; Surh, M

    2008-10-13

    Hot dense radiative (HDR) plasmas common to Inertial Confinement Fusion (ICF) and stellar interiors have high temperature (a few hundred eV to tens of keV), high density (tens to hundreds of g/cc) and high pressure (hundreds of Megabars to thousands of Gigabars). Typically, such plasmas undergo collisional, radiative, atomic and possibly thermonuclear processes. In order to describe HDR plasmas, computational physicists in ICF and astrophysics use atomic-scale microphysical models implemented in various simulation codes. Experimental validation of the models used to describe HDR plasmas are difficult to perform. Direct Numerical Simulation (DNS) of the many-body interactions of plasmas is a promising approach to model validation but, previous work either relies on the collisionless approximation or ignores radiation. We present a new numerical simulation technique to address a currently unsolved problem: the extension of molecular dynamics to collisional plasmas including emission and absorption of radiation. The new technique passes a key test: it relaxes to a blackbody spectrum for a plasma in local thermodynamic equilibrium. This new tool also provides a method for assessing the accuracy of energy and momentum exchange models in hot dense plasmas. As an example, we simulate the evolution of non-equilibrium electron, ion, and radiation temperatures for a hydrogen plasma using the new molecular dynamics simulation capability.

  4. Molecular dynamics of interface rupture

    NASA Technical Reports Server (NTRS)

    Koplik, Joel; Banavar, Jayanth R.

    1993-01-01

    Several situations have been studied in which a fluid-vapor or fluid-fluid interface ruptures, using molecular dynamics simulations of 3000 to 20,000 Lennard-Jones molecules in three dimensions. The cases studied are the Rayleigh instability of a liquid thread, the burst of a liquid drop immersed in a second liquid undergoing shear, and the rupture of a liquid sheet in an extensional flow. The late stages of the rupture process involve the gradual withdrawal of molecules from a thinning neck, or the appearance and growth of holes in a sheet. In all cases, it is found that despite the small size of the systems studied, tens of angstroms, the dynamics is in at least qualitative accord with the behavior expected from continuum calculations, and in some cases the agreement is to within tens of percent. Remarkably, this agreement occurs even though the Eulerian velocity and stress fields are essentially unmeasurable - dominated by thermal noise. The limitations and prospects for such molecular simulation techniques are assessed.

  5. Molecular docking and molecular dynamics studies reveal structural basis of inhibition and selectivity of inhibitors EGCG and OSU-03012 toward glucose regulated protein-78 (GRP78) overexpressed in glioblastoma.

    PubMed

    Bhattacharjee, Rituparna; Devi, Arpita; Mishra, Seema

    2015-10-01

    Glioblastoma (GBM), a malignant form of brain tumor, has a high mortality rate. GRP78, one of the HSP70 protein family members, is overexpressed in GBM. GRP78 is the key chaperone protein involved in the unfolded protein response. Upregulated GRP78 expression in cancer cells inhibits apoptosis and promotes chemoresistance. GRP78 has an ATPase domain, a substrate-binding domain, and a linker region. ATP-competitive inhibitors such as EGCG and OSU-03012 inhibit GRP78 activity and reduce its expression in GBM. However, there is a lack of structural data on the binding modes of these inhibitors to GRP78 ATPase domain. Further, the mode of selectivity of these inhibitors toward GRP78 also is unknown. Toward this end, molecular docking was performed with AutoDock Vina and confirmation obtained by docking using ROSIE. The stability and MM-PBSA binding energy of GRP78-inhibitor complexes as well as energetic contribution of individual residues was analyzed by 50 ns molecular dynamics run with GROMACS. MSA by ClustalW2 identified unique amino acid residues in the ATPase domain of GRP78 which were different from the residues present in other HSP70 proteins. Important and unique amino acid residues of GRP78 such as Ile61, Glu293, Arg297, and Arg367 played a major role in the intermolecular interactions with these inhibitors. The interactions with unique residues of GRP78 as compared with those of HSP70-1A provided the basis for selectivity. It was found that the binding affinity and specificity/selectivity of EGCG toward GRP78 was higher than that toward HSP70-1A, and selectivity was even better than OSU-03012. OSU-03012 was predicted to bind to GRP78. Analyses from MD runs showed tight binding and stability of complexes, and the highest number of hydrogen bonds during the trajectory runs were comparable to those found in the docking studies. Energetic contribution of individual inhibitor-interacting residues showed that energy values of Ile61 and Glu293 were among the most

  6. Dynamic Environmental Photosynthetic Imaging Reveals Emergent Phenotypes.

    PubMed

    Cruz, Jeffrey A; Savage, Linda J; Zegarac, Robert; Hall, Christopher C; Satoh-Cruz, Mio; Davis, Geoffry A; Kovac, William Kent; Chen, Jin; Kramer, David M

    2016-06-22

    Understanding and improving the productivity and robustness of plant photosynthesis requires high-throughput phenotyping under environmental conditions that are relevant to the field. Here we demonstrate the dynamic environmental photosynthesis imager (DEPI), an experimental platform for integrated, continuous, and high-throughput measurements of photosynthetic parameters during plant growth under reproducible yet dynamic environmental conditions. Using parallel imagers obviates the need to move plants or sensors, reducing artifacts and allowing simultaneous measurement on large numbers of plants. As a result, DEPI can reveal phenotypes that are not evident under standard laboratory conditions but emerge under progressively more dynamic illumination. We show examples in mutants of Arabidopsis of such "emergent phenotypes" that are highly transient and heterogeneous, appearing in different leaves under different conditions and depending in complex ways on both environmental conditions and plant developmental age. These emergent phenotypes appear to be caused by a range of phenomena, suggesting that such previously unseen processes are critical for plant responses to dynamic environments. PMID:27336966

  7. Molecular Dynamics: New Frontier in Personalized Medicine.

    PubMed

    Sneha, P; Doss, C George Priya

    2016-01-01

    The field of drug discovery has witnessed infinite development over the last decade with the demand for discovery of novel efficient lead compounds. Although the development of novel compounds in this field has seen large failure, a breakthrough in this area might be the establishment of personalized medicine. The trend of personalized medicine has shown stupendous growth being a hot topic after the successful completion of Human Genome Project and 1000 genomes pilot project. Genomic variant such as SNPs play a vital role with respect to inter individual's disease susceptibility and drug response. Hence, identification of such genetic variants has to be performed before administration of a drug. This process requires high-end techniques to understand the complexity of the molecules which might bring an insight to understand the compounds at their molecular level. To sustenance this, field of bioinformatics plays a crucial role in revealing the molecular mechanism of the mutation and thereby designing a drug for an individual in fast and affordable manner. High-end computational methods, such as molecular dynamics (MD) simulation has proved to be a constitutive approach to detecting the minor changes associated with an SNP for better understanding of the structural and functional relationship. The parameters used in molecular dynamic simulation elucidate different properties of a macromolecule, such as protein stability and flexibility. MD along with docking analysis can reveal the synergetic effect of an SNP in protein-ligand interaction and provides a foundation for designing a particular drug molecule for an individual. This compelling application of computational power and the advent of other technologies have paved a promising way toward personalized medicine. In this in-depth review, we tried to highlight the different wings of MD toward personalized medicine. PMID:26827606

  8. Molecular Dynamics: New Frontier in Personalized Medicine.

    PubMed

    Sneha, P; Doss, C George Priya

    2016-01-01

    The field of drug discovery has witnessed infinite development over the last decade with the demand for discovery of novel efficient lead compounds. Although the development of novel compounds in this field has seen large failure, a breakthrough in this area might be the establishment of personalized medicine. The trend of personalized medicine has shown stupendous growth being a hot topic after the successful completion of Human Genome Project and 1000 genomes pilot project. Genomic variant such as SNPs play a vital role with respect to inter individual's disease susceptibility and drug response. Hence, identification of such genetic variants has to be performed before administration of a drug. This process requires high-end techniques to understand the complexity of the molecules which might bring an insight to understand the compounds at their molecular level. To sustenance this, field of bioinformatics plays a crucial role in revealing the molecular mechanism of the mutation and thereby designing a drug for an individual in fast and affordable manner. High-end computational methods, such as molecular dynamics (MD) simulation has proved to be a constitutive approach to detecting the minor changes associated with an SNP for better understanding of the structural and functional relationship. The parameters used in molecular dynamic simulation elucidate different properties of a macromolecule, such as protein stability and flexibility. MD along with docking analysis can reveal the synergetic effect of an SNP in protein-ligand interaction and provides a foundation for designing a particular drug molecule for an individual. This compelling application of computational power and the advent of other technologies have paved a promising way toward personalized medicine. In this in-depth review, we tried to highlight the different wings of MD toward personalized medicine.

  9. Shear flow by molecular dynamics

    NASA Astrophysics Data System (ADS)

    Heyes, D. M.

    1985-08-01

    A detailed comparison is made between a number of methods for generating shear flow in Molecular Dynamics computer simulation. Algorithms which closely mimic most experimental methods for producing shear flow are those by Trozzi and Ciccotti, and Ashurst and Hoover. They employ hard wall boundaries and fluid walls respectively (with sheared cell periodicity being only in two dimensions). The sheared fluid properties are therefore inextricably linked with interfacial effects. These problems are largely eliminated by the Lees and Edwards scheme which creates a pseudo-infinite sheared material. There are a number of derivatives of this model including one favoured by the author for investigating non-linear viscoelastic phenomena. A number of results from this scheme pertaining to the Lennard-Jones liquid are presented.

  10. Buckybomb: Reactive Molecular Dynamics Simulation.

    PubMed

    Chaban, Vitaly V; Fileti, Eudes Eterno; Prezhdo, Oleg V

    2015-03-01

    Energetic materials, such as explosives, propellants, and pyrotechnics, are widely used in civilian and military applications. Nanoscale explosives represent a special group because of the high density of energetic covalent bonds. The reactive molecular dynamics (ReaxFF) study of nitrofullerene decomposition reported here provides a detailed chemical mechanism of explosion of a nanoscale carbon material. Upon initial heating, C60(NO2)12 disintegrates, increasing temperature and pressure by thousands of Kelvins and bars within tens of picoseconds. The explosion starts with NO2 group isomerization into C-O-N-O, followed by emission of NO molecules and formation of CO groups on the buckyball surface. NO oxidizes into NO2, and C60 falls apart, liberating CO2. At the highest temperatures, CO2 gives rise to diatomic carbon. The study shows that the initiation temperature and released energy depend strongly on the chemical composition and density of the material. PMID:26262672

  11. Buckybomb: Reactive Molecular Dynamics Simulation.

    PubMed

    Chaban, Vitaly V; Fileti, Eudes Eterno; Prezhdo, Oleg V

    2015-03-01

    Energetic materials, such as explosives, propellants, and pyrotechnics, are widely used in civilian and military applications. Nanoscale explosives represent a special group because of the high density of energetic covalent bonds. The reactive molecular dynamics (ReaxFF) study of nitrofullerene decomposition reported here provides a detailed chemical mechanism of explosion of a nanoscale carbon material. Upon initial heating, C60(NO2)12 disintegrates, increasing temperature and pressure by thousands of Kelvins and bars within tens of picoseconds. The explosion starts with NO2 group isomerization into C-O-N-O, followed by emission of NO molecules and formation of CO groups on the buckyball surface. NO oxidizes into NO2, and C60 falls apart, liberating CO2. At the highest temperatures, CO2 gives rise to diatomic carbon. The study shows that the initiation temperature and released energy depend strongly on the chemical composition and density of the material.

  12. Molecular dynamics of membrane proteins.

    SciTech Connect

    Woolf, Thomas B.; Crozier, Paul Stewart; Stevens, Mark Jackson

    2004-10-01

    Understanding the dynamics of the membrane protein rhodopsin will have broad implications for other membrane proteins and cellular signaling processes. Rhodopsin (Rho) is a light activated G-protein coupled receptor (GPCR). When activated by ligands, GPCRs bind and activate G-proteins residing within the cell and begin a signaling cascade that results in the cell's response to external stimuli. More than 50% of all current drugs are targeted toward G-proteins. Rho is the prototypical member of the class A GPCR superfamily. Understanding the activation of Rho and its interaction with its Gprotein can therefore lead to a wider understanding of the mechanisms of GPCR activation and G-protein activation. Understanding the dark to light transition of Rho is fully analogous to the general ligand binding and activation problem for GPCRs. This transition is dependent on the lipid environment. The effect of lipids on membrane protein activity in general has had little attention, but evidence is beginning to show a significant role for lipids in membrane protein activity. Using the LAMMPS program and simulation methods benchmarked under the IBIG program, we perform a variety of allatom molecular dynamics simulations of membrane proteins.

  13. Detecting Allosteric Networks Using Molecular Dynamics Simulation.

    PubMed

    Bowerman, S; Wereszczynski, J

    2016-01-01

    Allosteric networks allow enzymes to transmit information and regulate their catalytic activities over vast distances. In principle, molecular dynamics (MD) simulations can be used to reveal the mechanisms that underlie this phenomenon; in practice, it can be difficult to discern allosteric signals from MD trajectories. Here, we describe how MD simulations can be analyzed to reveal correlated motions and allosteric networks, and provide an example of their use on the coagulation enzyme thrombin. Methods are discussed for calculating residue-pair correlations from atomic fluctuations and mutual information, which can be combined with contact information to identify allosteric networks and to dynamically cluster a system into highly correlated communities. In the case of thrombin, these methods show that binding of the antagonist hirugen significantly alters the enzyme's correlation landscape through a series of pathways between Exosite I and the catalytic core. Results suggest that hirugen binding curtails dynamic diversity and enforces stricter venues of influence, thus reducing the accessibility of thrombin to other molecules. PMID:27497176

  14. Quasar feedback revealed by giant molecular outflows

    NASA Astrophysics Data System (ADS)

    Feruglio, C.; Maiolino, R.; Piconcelli, E.; Menci, N.; Aussel, H.; Lamastra, A.; Fiore, F.

    2010-07-01

    In the standard scenario for galaxy evolution young star-forming galaxies transform into red bulge-dominated spheroids, where star formation has been quenched. To explain this transformation, a strong negative feedback generated by accretion onto a central super-massive black hole is often invoked. The depletion of gas resulting from quasar-driven outflows should eventually stop star-formation across the host galaxy and lead the black hole to “suicide” by starvation. Direct observational evidence for a major quasar feedback onto the host galaxy is still missing, because outflows previously observed in quasars are generally associated with the ionized component of the gas, which only accounts for a minor fraction of the total gas content, and typically occurrs in the central regions. We used the IRAM PdB Interferometer to observe the CO(1-0) transition in Mrk 231, the closest quasar known. Thanks to the wide band we detected broad wings of the CO line, with velocities of up to 750 km s-1 and spatially resolved on the kpc scale. These broad CO wings trace a giant molecular outflow of about 700 M_⊙/year, far larger than the ongoing star-formation rate (~200 M_⊙/year) observed in the host galaxy. This wind will totally expel the cold gas reservoir in Mrk 231 in about 107 yrs, therefore halting the star-formation activity on the same timescale. The inferred kinetic energy in the molecular outflow is ~1.2 × 1044 erg/s, corresponding to a few percent of the AGN bolometric luminosity, which is very close to the fraction expected by models ascribing quasar feedback to highly supersonic shocks generated by radiatively accelerated nuclear winds. Instead, the contribution by the SNe associated with the starburst fall short by several orders of magnitude to account for the kinetic energy observed in the outflow. The direct observational evidence for quasar feedback reported here provides solid support to the scenarios ascribing the observed properties of local massive

  15. Neutron Imaging Reveals Internal Plant Hydraulic Dynamics

    SciTech Connect

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

    2013-01-01

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

  16. Apo- and Antagonist-Binding Structures of Vitamin D Receptor Ligand-Binding Domain Revealed by Hybrid Approach Combining Small-Angle X-ray Scattering and Molecular Dynamics.

    PubMed

    Anami, Yasuaki; Shimizu, Nobutaka; Ekimoto, Toru; Egawa, Daichi; Itoh, Toshimasa; Ikeguchi, Mitsunori; Yamamoto, Keiko

    2016-09-01

    Vitamin D receptor (VDR) controls the expression of numerous genes through the conformational change caused by binding 1α,25-dihydroxyvitamin D3. Helix 12 in the ligand-binding domain (LBD) is key to regulating VDR activation. The structures of apo VDR-LBD and the VDR-LBD/antagonist complex are unclear. Here, we reveal their unprecedented structures in solution using a hybrid method combining small-angle X-ray scattering and molecular dynamics simulations. In apo rat VDR-LBD, helix 12 is partially unraveled, and it is positioned around the canonical active position and fluctuates. Helix 11 greatly bends toward the outside at Q396, creating a kink. In the rat VDR-LBD/antagonist complex, helix 12 does not generate the activation function 2 surface, and loop 11-12 is remarkably flexible compared to that in the apo rat VDR-LBD. On the basis of these structural insights, we propose a "folding-door model" to describe the mechanism of agonism/antagonism of VDR-LBD. PMID:27535484

  17. Apo- and Antagonist-Binding Structures of Vitamin D Receptor Ligand-Binding Domain Revealed by Hybrid Approach Combining Small-Angle X-ray Scattering and Molecular Dynamics.

    PubMed

    Anami, Yasuaki; Shimizu, Nobutaka; Ekimoto, Toru; Egawa, Daichi; Itoh, Toshimasa; Ikeguchi, Mitsunori; Yamamoto, Keiko

    2016-09-01

    Vitamin D receptor (VDR) controls the expression of numerous genes through the conformational change caused by binding 1α,25-dihydroxyvitamin D3. Helix 12 in the ligand-binding domain (LBD) is key to regulating VDR activation. The structures of apo VDR-LBD and the VDR-LBD/antagonist complex are unclear. Here, we reveal their unprecedented structures in solution using a hybrid method combining small-angle X-ray scattering and molecular dynamics simulations. In apo rat VDR-LBD, helix 12 is partially unraveled, and it is positioned around the canonical active position and fluctuates. Helix 11 greatly bends toward the outside at Q396, creating a kink. In the rat VDR-LBD/antagonist complex, helix 12 does not generate the activation function 2 surface, and loop 11-12 is remarkably flexible compared to that in the apo rat VDR-LBD. On the basis of these structural insights, we propose a "folding-door model" to describe the mechanism of agonism/antagonism of VDR-LBD.

  18. Dynamical Localization in Molecular Systems.

    NASA Astrophysics Data System (ADS)

    Wang, Xidi

    In the first four chapters of this thesis we concentrate on the Davydov model which describes the vibrational energy quanta of Amide I bonds (C=O bonds on the alpha -helix) coupled to the acoustic phonon modes of the alpha-helix backbone in the form of a Frohlich Hamiltonian. Following a brief introduction in chapter one, in chapter two we formulate the dynamics of vibrational quanta at finite temperature by using coherent state products. The fluctuation-dissipation relation is derived. At zero temperature, in the continuum limit, we recover the original results of Davydov. We also achieve good agreement with numerical simulations. In chapter three, the net contraction of the lattice is calculated exactly at any temperature, and its relation to the so -call "topological stability" of the Davydov soliton is discussed. In the second section of the chapter three we calculate the overtone spectra of crystalline acetanilide (according to some opinions ACN provides experimental evidence for the existence of Davydov solitons). Good agreement with experimental data has been obtained. In chapter four we study the self-trapped vibrational excitations by the Quantum Monte Carlo technique. For a single excitation, the temperature dependence of different physical observables is calculated. The quasi-particle which resembles the Davydov soliton has been found to be fairly narrow using the most commonly used data for the alpha -helix; at temperatures above a few Kelvin, the quasi-particle reaches its smallest limit (extends over three sites), which implies diffusive motion of the small polaron-like quasi-particle at high temperatures. For the multi-excitation case, bound pairs and clusters of excitations are found at low temperatures; they gradually dissociate when the temperature of the system is increased as calculated from the density-density correlation function. In the last chapter of this thesis, we study a more general model of dynamical local modes in molecular systems

  19. Molecular dynamics on APE100

    NASA Astrophysics Data System (ADS)

    Barone, Luciano Maria; Simonazzi, Riccardo; Tenenbaum, Alexander

    1995-09-01

    We have studied portability, efficiency and accuracy of a standard Molecular Dynamics simulation on the SIMD parallel computer APE100. Computing speed performance and physical system size range have been analyzed and compared with those of a conventional computer. Short range and long range potentials have been considered, and the comparative advantage of different simulation approaches has been assessed. For long range potentials, APE turns out to be faster than a conventional computer; large systems can be conveniently simulated using either the cloning approach (up to ˜ 10 5 particles) or a domain decomposition with the systolic method. In the case of short range potentials and systems with diffusion (like a liquid), APE is convenient only when using a large number of processors. In a special case (a crystal without diffusion), a specific domain decomposition technique with frames makes APE advantageous for intermediate and large systems. Using the latter technique we have studied in detail the effect of different numerical error sources, and compared the accuracy of APE with that of a conventional computer.

  20. Molecular dynamics of the excitatory synapse.

    PubMed

    Okabe, Shigeo

    2012-01-01

    Molecular dynamics of synapses are one of the most important factors that control the remodeling of synaptic connection and efficacy of transmission. This chapter focuses on the dynamics of postsynaptic molecular machinery and describes the imaging technologies important for quantitative analyses of synapses, their application to the postsynaptic molecules, and the insights obtained from these analyses. New visualization techniques, such as super-resolution microscopy, will become an indispensable approach to reveal submicron changes of synaptic molecules. New methods of monitoring protein interactions will also be integrated with experimental paradigms of synaptic plasticity. Cell biological analyses, together with cutting-edge imaging technologies, have been applied to the studies of nascent synapse formation, synapse maintenance, and activity-dependent synapse remodeling. From these studies, a variety of new concepts emerged, such as local assembly of postsynaptic scaffolds, presence of "transport packets" of postsynaptic receptors, heterogeneity of actin movement within spines, and activity-free fluctuation of PSD/spine sizes. These new concepts are useful in understanding specific properties of postsynaptic functions and should be integrated in future to build a realistic model of the postsynaptic organization that can explain its remarkable stability and tunability. PMID:22351054

  1. Structure and Dynamics of Cellulose Molecular Solutions

    NASA Astrophysics Data System (ADS)

    Wang, Howard; Zhang, Xin; Tyagi, Madhusudan; Mao, Yimin; Briber, Robert

    Molecular dissolution of microcrystalline cellulose has been achieved through mixing with ionic liquid 1-Ethyl-3-methylimidazolium acetate (EMIMAc), and organic solvent dimethylformamide (DMF). The mechanism of cellulose dissolution in tertiary mixtures has been investigated by combining quasielastic and small angle neutron scattering (QENS and SANS). As SANS data show that cellulose chains take Gaussian-like conformations in homogenous solutions, which exhibit characteristics of having an upper critical solution temperature, the dynamic signals predominantly from EMIMAc molecules indicate strong association with cellulose in the dissolution state. The mean square displacement quantities support the observation of the stoichiometric 3:1 EMIMAc to cellulose unit molar ratio, which is a necessary criterion for the molecular dissolution of cellulose. Analyses of dynamics structure factors reveal the temperature dependence of a slow and a fast process for EMIMAc's bound to cellulose and in DMF, respectively, as well as a very fast process due possibly to the rotational motion of methyl groups, which persisted to near the absolute zero.

  2. Communication: Relation of centroid molecular dynamics and ring-polymer molecular dynamics to exact quantum dynamics.

    PubMed

    Hele, Timothy J H; Willatt, Michael J; Muolo, Andrea; Althorpe, Stuart C

    2015-05-21

    We recently obtained a quantum-Boltzmann-conserving classical dynamics by making a single change to the derivation of the "Classical Wigner" approximation. Here, we show that the further approximation of this "Matsubara dynamics" gives rise to two popular heuristic methods for treating quantum Boltzmann time-correlation functions: centroid molecular dynamics (CMD) and ring-polymer molecular dynamics (RPMD). We show that CMD is a mean-field approximation to Matsubara dynamics, obtained by discarding (classical) fluctuations around the centroid, and that RPMD is the result of discarding a term in the Matsubara Liouvillian which shifts the frequencies of these fluctuations. These findings are consistent with previous numerical results and give explicit formulae for the terms that CMD and RPMD leave out.

  3. Molecular dynamics simulations of wear processes

    NASA Astrophysics Data System (ADS)

    Yu, Hualiang

    Wear has been recognized as a vital problem in many industries. It results in a loss of durability, reliability, and efficiency and costs tens of billions of dollars annually. Significant effort has been devoted in both experimental and theoretical studies. However, the mechanisms of wear are still poorly understood and therefore wear control is far behind its demand. One way to study wear process is via computer simulation, which has become more powerful with the rapid development in computer facilities and efficient algorithms. It allows observation of atomic scale deformation and therefore it is a very good tool to study wear mechanisms at the nano-scale. This study presents a series of molecular dynamic simulation of some nano-scale wear processes, such as indentation and plowing, with the goal of exploring the factors that affect wear and predicting wear for different conditions. Molecular Dynamics simulations were carried out on a system that includes an aluminum substrate and a hard tip. Embedded atom method (EAM) and Lennard-Jones potentials were used to describe interactions between atoms. For nano-indentation simulations, both constant indent force and constant loading speed were applied to study the wear mechanisms as well as material properties. Some phenomenon, such as jump-to-contact, local melting, and dislocation nucleation were observed. More importantly, the effects of system temperature, indent force, substrate orientation, tip-substrate bond, indenter shape, boundary condition, and defect concentrations of the substrate were systematically investigated during indentation. The results are in qualitative agreement with limited experimental data. Similar simulations were carried out for plowing. The effects of plowing force, substrate orientation, the tip-substrate bond, and alloy elements are discussed based on the simulation results. In addition, a simple analytic model of plowing behavior is provided. The model reveals two parameters, static

  4. Time-Dependent Molecular Reaction Dynamics

    NASA Astrophysics Data System (ADS)

    Öhrn, Yngve

    2007-11-01

    This paper is a brief review of a time-dependent, direct, nonadiabatic theory of molecular processes called Electron Nuclear Dynamics (END). This approach to the study of molecular reaction dynamics is a hierarchical theory that can be applied at various levels of approximation. The simplest level of END uses classical nuclei and represents all electrons by a single, complex, determinantal wave function. The wave function parameters such as average nuclear positions and momenta, and molecular orbital coefcients carry the time dependence and serve as dynamical variables. Examples of application are given of the simplest level of END to ion-atom and ion-molecule reactions.

  5. Communication: Relation of centroid molecular dynamics and ring-polymer molecular dynamics to exact quantum dynamics

    SciTech Connect

    Hele, Timothy J. H.; Willatt, Michael J.; Muolo, Andrea; Althorpe, Stuart C.

    2015-05-21

    We recently obtained a quantum-Boltzmann-conserving classical dynamics by making a single change to the derivation of the “Classical Wigner” approximation. Here, we show that the further approximation of this “Matsubara dynamics” gives rise to two popular heuristic methods for treating quantum Boltzmann time-correlation functions: centroid molecular dynamics (CMD) and ring-polymer molecular dynamics (RPMD). We show that CMD is a mean-field approximation to Matsubara dynamics, obtained by discarding (classical) fluctuations around the centroid, and that RPMD is the result of discarding a term in the Matsubara Liouvillian which shifts the frequencies of these fluctuations. These findings are consistent with previous numerical results and give explicit formulae for the terms that CMD and RPMD leave out.

  6. Neutron Imaging Reveals Internal Plant Hydraulic Dynamics

    NASA Astrophysics Data System (ADS)

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

    2011-12-01

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

  7. Imaging the molecular dynamics of dissociative electron attachment to water

    SciTech Connect

    Adaniya, Hidihito; Rudek, B.; Osipov, Timur; Haxton, Dan; Weber, Thorsten; Rescigno, Thomas N.; McCurdy, C.W.; Belkacem, Ali

    2009-10-19

    Momentum imaging experiments on dissociative electron attachment to the water molecule are combined with ab initio theoretical calculations of the angular dependence of the quantum mechanical amplitude for electron attachment to provide a detailed picture of the molecular dynamics of dissociation attachment via the two lowest energy Feshbach resonances. The combination of momentum imaging experiments and theory can reveal dissociation dynamics for which the axial recoil approximation breaks down and thus provides a powerful reaction microscope for DEA to polyatomics.

  8. Molecular ions, Rydberg spectroscopy and dynamics

    SciTech Connect

    Jungen, Ch.

    2015-01-22

    Ion spectroscopy, Rydberg spectroscopy and molecular dynamics are closely related subjects. Multichannel quantum defect theory is a theoretical approach which draws on this close relationship and thereby becomes a powerful tool for the study of systems consisting of a positively charged molecular ion core interacting with an electron which may be loosely bound or freely scattering.

  9. Modeling the Hydrogen Bond within Molecular Dynamics

    ERIC Educational Resources Information Center

    Lykos, Peter

    2004-01-01

    The structure of a hydrogen bond is elucidated within the framework of molecular dynamics based on the model of Rahman and Stillinger (R-S) liquid water treatment. Thus, undergraduates are exposed to the powerful but simple use of classical mechanics to solid objects from a molecular viewpoint.

  10. Molecular Dynamics Simulations of Simple Liquids

    ERIC Educational Resources Information Center

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

    2004-01-01

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

  11. Parallel Molecular Dynamics Program for Molecules

    SciTech Connect

    Plimpton, Steve

    1995-03-07

    ParBond is a parallel classical molecular dynamics code that models bonded molecular systems, typically of an organic nature. It uses classical force fields for both non-bonded Coulombic and Van der Waals interactions and for 2-, 3-, and 4-body bonded (bond, angle, dihedral, and improper) interactions. It integrates Newton''s equation of motion for the molecular system and evaluates various thermodynamical properties of the system as it progresses.

  12. Dynamic molecular crystals with switchable physical properties.

    PubMed

    Sato, Osamu

    2016-06-21

    The development of molecular materials whose physical properties can be controlled by external stimuli - such as light, electric field, temperature, and pressure - has recently attracted much attention owing to their potential applications in molecular devices. There are a number of ways to alter the physical properties of crystalline materials. These include the modulation of the spin and redox states of the crystal's components, or the incorporation within the crystalline lattice of tunable molecules that exhibit stimuli-induced changes in their molecular structure. A switching behaviour can also be induced by changing the molecular orientation of the crystal's components, even in cases where the overall molecular structure is not affected. Controlling intermolecular interactions within a molecular material is also an effective tool to modulate its physical properties. This Review discusses recent advances in the development of such stimuli-responsive, switchable crystalline compounds - referred to here as dynamic molecular crystals - and suggests how different approaches can serve to prepare functional materials. PMID:27325090

  13. Molecular dynamics simulations: advances and applications

    PubMed Central

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

    2015-01-01

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

  14. Molecular dynamics simulations: advances and applications

    PubMed Central

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

    2015-01-01

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

  15. Molecular dynamics simulations of large macromolecular complexes

    PubMed Central

    Perilla, Juan R.; Goh, Boon Chong; Cassidy, C. Keith; Liu, Bo; Bernardi, Rafael C.; Rudack, Till; Yu, Hang; Wu, Zhe; Schulten, Klaus

    2015-01-01

    Connecting dynamics to structural data from diverse experimental sources, molecular dynamics simulations permit the exploration of biological phenomena in unparalleled detail. Advances in simulations are moving the atomic resolution descriptions of biological systems into the million-to-billion atom regime, in which numerous cell functions reside. In this opinion, we review the progress, driven by large-scale molecular dynamics simulations, in the study of viruses, ribosomes, bioenergetic systems, and other diverse applications. These examples highlight the utility of molecular dynamics simulations in the critical task of relating atomic detail to the function of supramolecular complexes, a task that cannot be achieved by smaller-scale simulations or existing experimental approaches alone. PMID:25845770

  16. Using Dynamic Graphs to Reveal Student Reasoning

    ERIC Educational Resources Information Center

    Lassak, Marshall

    2009-01-01

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

  17. Dispersion of Response Times Reveals Cognitive Dynamics

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  18. Deuterium reveals the dynamics of notch activation.

    PubMed

    Raphael, Kopan

    2011-04-13

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

  19. Single-Cell RNA-Seq with Waterfall Reveals Molecular Cascades underlying Adult Neurogenesis.

    PubMed

    Shin, Jaehoon; Berg, Daniel A; Zhu, Yunhua; Shin, Joseph Y; Song, Juan; Bonaguidi, Michael A; Enikolopov, Grigori; Nauen, David W; Christian, Kimberly M; Ming, Guo-li; Song, Hongjun

    2015-09-01

    Somatic stem cells contribute to tissue ontogenesis, homeostasis, and regeneration through sequential processes. Systematic molecular analysis of stem cell behavior is challenging because classic approaches cannot resolve cellular heterogeneity or capture developmental dynamics. Here we provide a comprehensive resource of single-cell transcriptomes of adult hippocampal quiescent neural stem cells (qNSCs) and their immediate progeny. We further developed Waterfall, a bioinformatic pipeline, to statistically quantify singe-cell gene expression along a de novo reconstructed continuous developmental trajectory. Our study reveals molecular signatures of adult qNSCs, characterized by active niche signaling integration and low protein translation capacity. Our analyses further delineate molecular cascades underlying qNSC activation and neurogenesis initiation, exemplified by decreased extrinsic signaling capacity, primed translational machinery, and regulatory switches in transcription factors, metabolism, and energy sources. Our study reveals the molecular continuum underlying adult neurogenesis and illustrates how Waterfall can be used for single-cell omics analyses of various continuous biological processes.

  20. Molecular dynamics studies on nanoscale gas transport

    NASA Astrophysics Data System (ADS)

    Barisik, Murat

    Three-dimensional molecular dynamics (MD) simulations of nanoscale gas flows are studied to reveal surface effects. A smart wall model that drastically reduces the memory requirements of MD simulations for gas flows is introduced. The smart wall molecular dynamics (SWMD) represents three-dimensional FCC walls using only 74 wall Molecules. This structure is kept in the memory and utilized for each gas molecule surface collision. Using SWMD, fluid behavior within nano-scale confinements is studied for argon in dilute gas, dense gas, and liquid states. Equilibrium MD method is employed to resolve the density and stress variations within the static fluid. Normal stress calculations are based on the Irving-Kirkwood method, which divides the stress tensor into its kinetic and virial parts. The kinetic component recovers pressure based on the ideal gas law. The particle-particle virial increases with increased density, while the surface-particle virial develops due to the surface force field effects. Normal stresses within nano-scale confinements show anisotropy induced primarily by the surface force-field and local variations in the fluid density near the surfaces. For dilute and dense gas cases, surface-force field that extends typically 1nm from each wall induces anisotropic normal stress. For liquid case, this effect is further amplified by the density fluctuations that extend beyond the three field penetration region. Outside the wall force-field penetration and density fluctuation regions the normal stress becomes isotropic and recovers the thermodynamic pressure, provided that sufficiently large force cut-off distances are utilized in the computations. Next, non-equilibrium SWMD is utilized to investigate the surface-gas interaction effects on nanoscale shear-driven gas flows in the transition and free molecular flow regimes. For the specified surface properties and gas-surface pair interactions, density and stress profiles exhibit a universal behavior inside the

  1. Dynamic signature of molecular association in methanol.

    PubMed

    Bertrand, C E; Self, J L; Copley, J R D; Faraone, A

    2016-07-01

    Quasielastic neutron scattering measurements and molecular dynamics simulations were combined to investigate the collective dynamics of deuterated methanol, CD3OD. In the experimentally determined dynamic structure factor, a slow, non-Fickian mode was observed in addition to the standard density-fluctuation heat mode. The simulation results indicate that the slow dynamical process originates from the hydrogen bonding of methanol molecules. The qualitative behavior of this mode is similar to the previously observed α-relaxation in supercooled water [M. C. Bellissent-Funel et al., Phys. Rev. Lett. 85, 3644 (2000)] which also originates from the formation and dissolution of hydrogen-bonded associates (supramolecular clusters). In methanol, however, this mode is distinguishable well above the freezing transition. This finding indicates that an emergent slow mode is not unique to supercooled water, but may instead be a general feature of hydrogen-bonding liquids and associating molecular liquids. PMID:27394112

  2. Dynamic signature of molecular association in methanol

    NASA Astrophysics Data System (ADS)

    Bertrand, C. E.; Self, J. L.; Copley, J. R. D.; Faraone, A.

    2016-07-01

    Quasielastic neutron scattering measurements and molecular dynamics simulations were combined to investigate the collective dynamics of deuterated methanol, CD3OD. In the experimentally determined dynamic structure factor, a slow, non-Fickian mode was observed in addition to the standard density-fluctuation heat mode. The simulation results indicate that the slow dynamical process originates from the hydrogen bonding of methanol molecules. The qualitative behavior of this mode is similar to the previously observed α-relaxation in supercooled water [M. C. Bellissent-Funel et al., Phys. Rev. Lett. 85, 3644 (2000)] which also originates from the formation and dissolution of hydrogen-bonded associates (supramolecular clusters). In methanol, however, this mode is distinguishable well above the freezing transition. This finding indicates that an emergent slow mode is not unique to supercooled water, but may instead be a general feature of hydrogen-bonding liquids and associating molecular liquids.

  3. Numerical methods for molecular dynamics

    SciTech Connect

    Skeel, R.D.

    1991-01-01

    This report summarizes our research progress to date on the use of multigrid methods for three-dimensional elliptic partial differential equations, with particular emphasis on application to the Poisson-Boltzmann equation of molecular biophysics. This research is motivated by the need for fast and accurate numerical solution techniques for three-dimensional problems arising in physics and engineering. In many applications these problems must be solved repeatedly, and the extremely large number of discrete unknowns required to accurately approximate solutions to partial differential equations in three-dimensional regions necessitates the use of efficient solution methods. This situation makes clear the importance of developing methods which are of optimal order (or nearly so), meaning that the number of operations required to solve the discrete problem is on the order of the number of discrete unknowns. Multigrid methods are generally regarded as being in this class of methods, and are in fact provably optimal order for an increasingly large class of problems. The fundamental goal of this research is to develop a fast and accurate numerical technique, based on multi-level principles, for the solutions of the Poisson-Boltzmann equation of molecular biophysics and similar equations occurring in other applications. An outline of the report is as follows. We first present some background material, followed by a survey of the literature on the use of multigrid methods for solving problems similar to the Poisson-Boltzmann equation. A short description of the software we have developed so far is then given, and numerical results are discussed. Finally, our research plans for the coming year are presented.

  4. Semiclassical guided optimal control of molecular dynamics

    SciTech Connect

    Kondorskiy, A.; Mil'nikov, G.; Nakamura, H.

    2005-10-15

    An efficient semiclassical optimal control theory applicable to multidimensional systems is formulated for controlling wave packet dynamics on a single adiabatic potential energy surface. The approach combines advantages of different formulations of optimal control theory: quantum and classical on one hand and global and local on the other. Numerical applications to the control of HCN-CNH isomerization demonstrate that this theory can provide an efficient tool to manipulate molecular dynamics of many degrees of freedom by laser pulses.

  5. Human dynamics revealed through Web analytics

    NASA Astrophysics Data System (ADS)

    Gonçalves, Bruno; Ramasco, José J.

    2008-08-01

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

  6. AVHRR imagery reveals Antarctic ice dynamics

    SciTech Connect

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

    1990-06-01

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

  7. Reaction dynamics in polyatomic molecular systems

    SciTech Connect

    Miller, W.H.

    1993-12-01

    The goal of this program is the development of theoretical methods and models for describing the dynamics of chemical reactions, with specific interest for application to polyatomic molecular systems of special interest and relevance. There is interest in developing the most rigorous possible theoretical approaches and also in more approximate treatments that are more readily applicable to complex systems.

  8. Shock induced phase transition of water: Molecular dynamics investigation

    NASA Astrophysics Data System (ADS)

    Neogi, Anupam; Mitra, Nilanjan

    2016-02-01

    Molecular dynamics simulations were carried out using numerous force potentials to investigate the shock induced phenomenon of pure bulk liquid water. Partial phase transition was observed at single shock velocity of 4.0 km/s without requirement of any external nucleators. Change in thermodynamic variables along with radial distribution function plots and spectral analysis revealed for the first time in the literature, within the context of molecular dynamic simulations, the thermodynamic pathway leading to formation of ice VII from liquid water on shock loading. The study also revealed information for the first time in the literature about the statistical time-frame after passage of shock in which ice VII formation can be observed and variations in degree of crystallinity of the sample over the entire simulation time of 100 ns.

  9. Multiscale coupling of molecular dynamics and peridynamics

    NASA Astrophysics Data System (ADS)

    Tong, Qi; Li, Shaofan

    2016-10-01

    We propose a multiscale computational model to couple molecular dynamics and peridynamics. The multiscale coupling model is based on a previously developed multiscale micromorphic molecular dynamics (MMMD) theory, which has three dynamics equations at three different scales, namely, microscale, mesoscale, and macroscale. In the proposed multiscale coupling approach, we divide the simulation domain into atomistic region and macroscale region. Molecular dynamics is used to simulate atom motions in atomistic region, and peridynamics is used to simulate macroscale material point motions in macroscale region, and both methods are nonlocal particle methods. A transition zone is introduced as a messenger to pass the information between the two regions or scales. We employ the "supercell" developed in the MMMD theory as the transition element, which is named as the adaptive multiscale element due to its ability of passing information from different scales, because the adaptive multiscale element can realize both top-down and bottom-up communications. We introduce the Cauchy-Born rule based stress evaluation into state-based peridynamics formulation to formulate atomistic-enriched constitutive relations. To mitigate the issue of wave reflection on the interface, a filter is constructed by switching on and off the MMMD dynamic equations at different scales. Benchmark tests of one-dimensional (1-D) and two-dimensional (2-D) wave propagations from atomistic region to macro region are presented. The mechanical wave can transit through the interface smoothly without spurious wave deflections, and the filtering process is proven to be efficient.

  10. Molecular dynamics modeling of a nanomaterials-water surface interaction

    NASA Astrophysics Data System (ADS)

    Nejat Pishkenari, Hossein; Keramati, Ramtin; Abdi, Ahmad; Minary-Jolandan, Majid

    2016-04-01

    In this article, we study the formation of nanomeniscus around a nanoneedle using molecular dynamics simulation approach. The results reveal three distinct phases in the time-evolution of meniscus before equilibrium according to the contact angle, meniscus height, and potential energy. In addition, we investigated the correlation between the nanoneedle diameter and nanomeniscus characteristics. The results have applications in various fields such as scanning probe microscopy and rheological measurements.

  11. MDMovie: a molecular dynamics viewing tool.

    PubMed

    Greenberg, J P

    1996-10-01

    The graphics program MDMovie (Molecular Dynamics Movie), written in C using IRIS GL graphics library calls, is designed to facilitate the visualization and interpretation of empirical force field data. MDMovie was created and initially adapted in accord with the needs of physical chemists and thereafter became an expandable analysis tool. Capabilities include the display of chemical structure, animation of molecular dynamics and Monte Carlo trajectories, and the visual representation of various vector and scalar dynamical properties. In addition to being a research tool, MDMovie has features for creating presentation videos and hardcopy output. A library is also available for linking to Fortran simulation codes running on a remote machine and connecting to MDMovie via a socket connection. MDMovie continues to be an ongoing research project and new features are actively being added in collaboration with various research groups. Future plans include porting to OpenGL and the design of an XII-based user interface.

  12. Polar solvation dynamics of lysozyme from molecular dynamics studies

    NASA Astrophysics Data System (ADS)

    Sinha, Sudipta Kumar; Bandyopadhyay, Sanjoy

    2012-05-01

    The solvation dynamics of a protein are believed to be sensitive to its secondary structures. We have explored such sensitivity in this article by performing room temperature molecular dynamics simulation of an aqueous solution of lysozyme. Nonuniform long-time relaxation patterns of the solvation time correlation function for different segments of the protein have been observed. It is found that relatively slower long-time solvation components of the α-helices and β-sheets of the protein are correlated with lower exposure of their polar probe residues to bulk solvent and hence stronger interactions with the dynamically restricted surface water molecules. These findings can be verified by appropriate experimental studies.

  13. Integrative network analysis reveals molecular mechanisms of blood pressure regulation.

    PubMed

    Huan, Tianxiao; Meng, Qingying; Saleh, Mohamed A; Norlander, Allison E; Joehanes, Roby; Zhu, Jun; Chen, Brian H; Zhang, Bin; Johnson, Andrew D; Ying, Saixia; Courchesne, Paul; Raghavachari, Nalini; Wang, Richard; Liu, Poching; O'Donnell, Christopher J; Vasan, Ramachandran; Munson, Peter J; Madhur, Meena S; Harrison, David G; Yang, Xia; Levy, Daniel

    2015-01-01

    Genome-wide association studies (GWAS) have identified numerous loci associated with blood pressure (BP). The molecular mechanisms underlying BP regulation, however, remain unclear. We investigated BP-associated molecular mechanisms by integrating BP GWAS with whole blood mRNA expression profiles in 3,679 individuals, using network approaches. BP transcriptomic signatures at the single-gene and the coexpression network module levels were identified. Four coexpression modules were identified as potentially causal based on genetic inference because expression-related SNPs for their corresponding genes demonstrated enrichment for BP GWAS signals. Genes from the four modules were further projected onto predefined molecular interaction networks, revealing key drivers. Gene subnetworks entailing molecular interactions between key drivers and BP-related genes were uncovered. As proof-of-concept, we validated SH2B3, one of the top key drivers, using Sh2b3(-/-) mice. We found that a significant number of genes predicted to be regulated by SH2B3 in gene networks are perturbed in Sh2b3(-/-) mice, which demonstrate an exaggerated pressor response to angiotensin II infusion. Our findings may help to identify novel targets for the prevention or treatment of hypertension.

  14. Integrative network analysis reveals molecular mechanisms of blood pressure regulation.

    PubMed

    Huan, Tianxiao; Meng, Qingying; Saleh, Mohamed A; Norlander, Allison E; Joehanes, Roby; Zhu, Jun; Chen, Brian H; Zhang, Bin; Johnson, Andrew D; Ying, Saixia; Courchesne, Paul; Raghavachari, Nalini; Wang, Richard; Liu, Poching; O'Donnell, Christopher J; Vasan, Ramachandran; Munson, Peter J; Madhur, Meena S; Harrison, David G; Yang, Xia; Levy, Daniel

    2015-04-01

    Genome-wide association studies (GWAS) have identified numerous loci associated with blood pressure (BP). The molecular mechanisms underlying BP regulation, however, remain unclear. We investigated BP-associated molecular mechanisms by integrating BP GWAS with whole blood mRNA expression profiles in 3,679 individuals, using network approaches. BP transcriptomic signatures at the single-gene and the coexpression network module levels were identified. Four coexpression modules were identified as potentially causal based on genetic inference because expression-related SNPs for their corresponding genes demonstrated enrichment for BP GWAS signals. Genes from the four modules were further projected onto predefined molecular interaction networks, revealing key drivers. Gene subnetworks entailing molecular interactions between key drivers and BP-related genes were uncovered. As proof-of-concept, we validated SH2B3, one of the top key drivers, using Sh2b3−/− mice. We found that a significant number of genes predicted to be regulated by SH2B3 in gene networks are perturbed in Sh2b3−/− mice, which demonstrate an exaggerated pressor response to angiotensin II infusion. Our findings may help to identify novel targets for the prevention or treatment of hypertension.

  15. Finite Temperature Quasicontinuum: Molecular Dynamics without all the Atoms

    SciTech Connect

    Dupuy, L; Tadmor, E B; Miller, R E; Phillips, R

    2005-02-02

    Using a combination of statistical mechanics and finite-element interpolation, the authors develop a coarse-grained (CG) alternative to molecular dynamics (MD) for crystalline solids at constant temperature. The new approach is significantly more efficient than MD and generalizes earlier work on the quasi-continuum method. The method is validated by recovering equilibrium properties of single crystal Ni as a function of temperature. CG dynamical simulations of nanoindentation reveal a strong dependence on temperature of the critical stress to nucleate dislocations under the indenter.

  16. Dynamic strength of molecular adhesion bonds.

    PubMed Central

    Evans, E; Ritchie, K

    1997-01-01

    In biology, molecular linkages at, within, and beneath cell interfaces arise mainly from weak noncovalent interactions. These bonds will fail under any level of pulling force if held for sufficient time. Thus, when tested with ultrasensitive force probes, we expect cohesive material strength and strength of adhesion at interfaces to be time- and loading rate-dependent properties. To examine what can be learned from measurements of bond strength, we have extended Kramers' theory for reaction kinetics in liquids to bond dissociation under force and tested the predictions by smart Monte Carlo (Brownian dynamics) simulations of bond rupture. By definition, bond strength is the force that produces the most frequent failure in repeated tests of breakage, i.e., the peak in the distribution of rupture forces. As verified by the simulations, theory shows that bond strength progresses through three dynamic regimes of loading rate. First, bond strength emerges at a critical rate of loading (> or = 0) at which spontaneous dissociation is just frequent enough to keep the distribution peak at zero force. In the slow-loading regime immediately above the critical rate, strength grows as a weak power of loading rate and reflects initial coupling of force to the bonding potential. At higher rates, there is crossover to a fast regime in which strength continues to increase as the logarithm of the loading rate over many decades independent of the type of attraction. Finally, at ultrafast loading rates approaching the domain of molecular dynamics simulations, the bonding potential is quickly overwhelmed by the rapidly increasing force, so that only naked frictional drag on the structure remains to retard separation. Hence, to expose the energy landscape that governs bond strength, molecular adhesion forces must be examined over an enormous span of time scales. However, a significant gap exists between the time domain of force measurements in the laboratory and the extremely fast scale

  17. Dynamical quenching of tunneling in molecular magnets

    NASA Astrophysics Data System (ADS)

    José Santander, María; Nunez, Alvaro S.; Roldán-Molina, A.; Troncoso, Roberto E.

    2015-12-01

    It is shown that a single molecular magnet placed in a rapidly oscillating magnetic field displays the phenomenon of quenching of tunneling processes. The results open a way to manipulate the quantum states of molecular magnets by means of radiation in the terahertz range. Our analysis separates the time evolution into slow and fast components thereby obtaining an effective theory for the slow dynamics. This effective theory presents quenching of the tunnel effect, in particular, stands out its difference with the so-called coherent destruction of tunneling. We support our prediction with numerical evidence based on an exact solution of Schrödinger's equation.

  18. Exciton dynamics in perturbed vibronic molecular aggregates

    PubMed Central

    Brüning, C.; Wehner, J.; Hausner, J.; Wenzel, M.; Engel, V.

    2015-01-01

    A site specific perturbation of a photo-excited molecular aggregate can lead to a localization of excitonic energy. We investigate this localization dynamics for laser-prepared excited states. Changing the parameters of the electric field significantly influences the exciton localization which offers the possibility for a selective control of this process. This is demonstrated for aggregates possessing a single vibrational degree of freedom per monomer unit. It is shown that the effects identified for the molecular dimer can be generalized to larger aggregates with a high density of vibronic states. PMID:26798840

  19. Efficient Molecular Dynamics Simulations of Multiple Radical Center Systems Based on the Fragment Molecular Orbital Method

    SciTech Connect

    Nakata, Hiroya; Schmidt, Michael W; Fedorov, Dmitri G; Kitaura, Kazuo; Nakamura, Shinichiro; Gordon, Mark S

    2014-10-16

    The fully analytic energy gradient has been developed and implemented for the restricted open-shell Hartree–Fock (ROHF) method based on the fragment molecular orbital (FMO) theory for systems that have multiple open-shell molecules. The accuracy of the analytic ROHF energy gradient is compared with the corresponding numerical gradient, illustrating the accuracy of the analytic gradient. The ROHF analytic gradient is used to perform molecular dynamics simulations of an unusual open-shell system, liquid oxygen, and mixtures of oxygen and nitrogen. These molecular dynamics simulations provide some insight about how triplet oxygen molecules interact with each other. Timings reveal that the method can calculate the energy gradient for a system containing 4000 atoms in only 6 h. Therefore, it is concluded that the FMO-ROHF method will be useful for investigating systems with multiple open shells.

  20. Efficient molecular dynamics simulations of multiple radical center systems based on the fragment molecular orbital method.

    PubMed

    Nakata, Hiroya; Schmidt, Michael W; Fedorov, Dmitri G; Kitaura, Kazuo; Nakamura, Shinichiro; Gordon, Mark S

    2014-10-16

    The fully analytic energy gradient has been developed and implemented for the restricted open-shell Hartree-Fock (ROHF) method based on the fragment molecular orbital (FMO) theory for systems that have multiple open-shell molecules. The accuracy of the analytic ROHF energy gradient is compared with the corresponding numerical gradient, illustrating the accuracy of the analytic gradient. The ROHF analytic gradient is used to perform molecular dynamics simulations of an unusual open-shell system, liquid oxygen, and mixtures of oxygen and nitrogen. These molecular dynamics simulations provide some insight about how triplet oxygen molecules interact with each other. Timings reveal that the method can calculate the energy gradient for a system containing 4000 atoms in only 6 h. Therefore, it is concluded that the FMO-ROHF method will be useful for investigating systems with multiple open shells.

  1. Molecular dynamic simulation methods for anisotropic liquids.

    PubMed

    Aoki, Keiko M; Yoneya, Makoto; Yokoyama, Hiroshi

    2004-03-22

    Methods of molecular dynamics simulations for anisotropic molecules are presented. The new methods, with an anisotropic factor in the cell dynamics, dramatically reduce the artifacts related to cell shapes and overcome the difficulties of simulating anisotropic molecules under constant hydrostatic pressure or constant volume. The methods are especially effective for anisotropic liquids, such as smectic liquid crystals and membranes, of which the stacks of layers are compressible (elastic in direction perpendicular to the layers) while the layer itself is liquid and only elastic under uniform compressive force. The methods can also be used for crystals and isotropic liquids as well.

  2. Molecular Dynamics Simulations of Alpha-synuclein

    NASA Astrophysics Data System (ADS)

    Sammalkorpi, Maria; Schreck, Carl; Nath, Abhinav; Dewitt, David; Rhoades, Elizabeth; O'Hern, Corey

    2011-03-01

    We investigate the conformational dynamics of single alpha-synuclein proteins, which have been implicated in amyloid diseases such as Parkinson's and Alzheimer's disease, in solution using unconstrained and constrained all-atom, explicit solvent molecular dynamics simulations. The constraints on inter-residue separations are obtained from our single-molecule FRET measurements of eleven FRET pairs that span the protein. By comparing the simulation data satisfying different combinations of FRET constraints, we are able to identify those constraints that are most important in determining the radius of gyration and key features of the contact map of the protein.

  3. Molecular dynamics at constant Cauchy stress

    NASA Astrophysics Data System (ADS)

    Miller, Ronald E.; Tadmor, Ellad B.; Gibson, Joshua S.; Bernstein, Noam; Pavia, Fabio

    2016-05-01

    The Parrinello-Rahman algorithm for imposing a general state of stress in periodic molecular dynamics simulations is widely used in the literature and has been implemented in many readily available molecular dynamics codes. However, what is often overlooked is that this algorithm controls the second Piola-Kirchhoff stress as opposed to the true (Cauchy) stress. This can lead to misinterpretation of simulation results because (1) the true stress that is imposed during the simulation depends on the deformation of the periodic cell, (2) the true stress is potentially very different from the imposed second Piola-Kirchhoff stress, and (3) the true stress can vary significantly during the simulation even if the imposed second Piola-Kirchhoff is constant. We propose a simple modification to the algorithm that allows the true Cauchy stress to be controlled directly. We then demonstrate the efficacy of the new algorithm with the example of martensitic phase transformations under applied stress.

  4. Improving structure-based function prediction using molecular dynamics

    PubMed Central

    Glazer, Dariya S.; Radmer, Randall J.; Altman, Russ B.

    2009-01-01

    Summary The number of molecules with solved three-dimensional structure but unknown function is increasing rapidly. Particularly problematic are novel folds with little detectable similarity to molecules of known function. Experimental assays can determine the functions of such molecules, but are time-consuming and expensive. Computational approaches can identify potential functional sites; however, these approaches generally rely on single static structures and do not use information about dynamics. In fact, structural dynamics can enhance function prediction: we coupled molecular dynamics simulations with structure-based function prediction algorithms that identify Ca2+ binding sites. When applied to 11 challenging proteins, both methods showed substantial improvement in performance, revealing 22 more sites in one case and 12 more in the other, with a modest increase in apparent false positives. Thus, we show that treating molecules as dynamic entities improves the performance of structure-based function prediction methods. PMID:19604472

  5. New faster CHARMM molecular dynamics engine

    PubMed Central

    Hynninen, Antti-Pekka; Crowley, Michael F

    2014-01-01

    We introduce a new faster molecular dynamics (MD) engine into the CHARMM software package. The new MD engine is faster both in serial (i.e., single CPU core) and parallel execution. Serial performance is approximately two times higher than in the previous version of CHARMM. The newly programmed parallelization method allows the MD engine to parallelize up to hundreds of CPU cores. PMID:24302199

  6. Molecular dynamics modelling of solidification in metals

    SciTech Connect

    Boercker, D.B.; Belak, J.; Glosli, J.

    1997-12-31

    Molecular dynamics modeling is used to study the solidification of metals at high pressure and temperature. Constant pressure MD is applied to a simulation cell initially filled with both solid and molten metal. The solid/liquid interface is tracked as a function of time, and the data are used to estimate growth rates of crystallites at high pressure and temperature in Ta and Mg.

  7. Structure and dynamics of complex liquid water: Molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    S, Indrajith V.; Natesan, Baskaran

    2015-06-01

    We have carried out detailed structure and dynamical studies of complex liquid water using molecular dynamics simulations. Three different model potentials, namely, TIP3P, TIP4P and SPC-E have been used in the simulations, in order to arrive at the best possible potential function that could reproduce the structure of experimental bulk water. All the simulations were performed in the NVE micro canonical ensemble using LAMMPS. The radial distribution functions, gOO, gOH and gHH and the self diffusion coefficient, Ds, were calculated for all three models. We conclude from our results that the structure and dynamical parameters obtained for SPC-E model matched well with the experimental values, suggesting that among the models studied here, the SPC-E model gives the best structure and dynamics of bulk water.

  8. Molecular crowding and protein enzymatic dynamics.

    PubMed

    Echeverria, Carlos; Kapral, Raymond

    2012-05-21

    The effects of molecular crowding on the enzymatic conformational dynamics and transport properties of adenylate kinase are investigated. This tridomain protein undergoes large scale hinge motions in the course of its enzymatic cycle and serves as prototype for the study of crowding effects on the cyclic conformational dynamics of proteins. The study is carried out at a mesoscopic level where both the protein and the solvent in which it is dissolved are treated in a coarse grained fashion. The amino acid residues in the protein are represented by a network of beads and the solvent dynamics is described by multiparticle collision dynamics that includes effects due to hydrodynamic interactions. The system is crowded by a stationary random array of hard spherical objects. Protein enzymatic dynamics is investigated as a function of the obstacle volume fraction and size. In addition, for comparison, results are presented for a modification of the dynamics that suppresses hydrodynamic interactions. Consistent with expectations, simulations of the dynamics show that the protein prefers a closed conformation for high volume fractions. This effect becomes more pronounced as the obstacle radius decreases for a given volume fraction since the average void size in the obstacle array is smaller for smaller radii. At high volume fractions for small obstacle radii, the average enzymatic cycle time and characteristic times of internal conformational motions of the protein deviate substantially from their values in solution or in systems with small density of obstacles. The transport properties of the protein are strongly affected by molecular crowding. Diffusive motion adopts a subdiffusive character and the effective diffusion coefficients can change by more than an order of magnitude. The orientational relaxation time of the protein is also significantly altered by crowding. PMID:22476233

  9. Control-volume representation of molecular dynamics.

    PubMed

    Smith, E R; Heyes, D M; Dini, D; Zaki, T A

    2012-05-01

    A molecular dynamics (MD) parallel to the control volume (CV) formulation of fluid mechanics is developed by integrating the formulas of Irving and Kirkwood [J. Chem. Phys. 18, 817 (1950)] over a finite cubic volume of molecular dimensions. The Lagrangian molecular system is expressed in terms of an Eulerian CV, which yields an equivalent to Reynolds' transport theorem for the discrete system. This approach casts the dynamics of the molecular system into a form that can be readily compared to the continuum equations. The MD equations of motion are reinterpreted in terms of a Lagrangian-to-control-volume (LCV) conversion function ϑ(i) for each molecule i. The LCV function and its spatial derivatives are used to express fluxes and relevant forces across the control surfaces. The relationship between the local pressures computed using the volume average [Lutsko, J. Appl. Phys. 64, 1152 (1988)] techniques and the method of planes [Todd et al., Phys. Rev. E 52, 1627 (1995)] emerges naturally from the treatment. Numerical experiments using the MD CV method are reported for equilibrium and nonequilibrium (start-up Couette flow) model liquids, which demonstrate the advantages of the formulation. The CV formulation of the MD is shown to be exactly conservative and is, therefore, ideally suited to obtain macroscopic properties from a discrete system.

  10. Control-volume representation of molecular dynamics

    NASA Astrophysics Data System (ADS)

    Smith, E. R.; Heyes, D. M.; Dini, D.; Zaki, T. A.

    2012-05-01

    A molecular dynamics (MD) parallel to the control volume (CV) formulation of fluid mechanics is developed by integrating the formulas of Irving and Kirkwood [J. Chem. Phys.JCPSA60021-960610.1063/1.1747782 18, 817 (1950)] over a finite cubic volume of molecular dimensions. The Lagrangian molecular system is expressed in terms of an Eulerian CV, which yields an equivalent to Reynolds’ transport theorem for the discrete system. This approach casts the dynamics of the molecular system into a form that can be readily compared to the continuum equations. The MD equations of motion are reinterpreted in terms of a Lagrangian-to-control-volume (LCV) conversion function ϑi for each molecule i. The LCV function and its spatial derivatives are used to express fluxes and relevant forces across the control surfaces. The relationship between the local pressures computed using the volume average [Lutsko, J. Appl. Phys.JAPIAU0021-897910.1063/1.341877 64, 1152 (1988)] techniques and the method of planes [Todd , Phys. Rev. EPLEEE81539-375510.1103/PhysRevE.52.1627 52, 1627 (1995)] emerges naturally from the treatment. Numerical experiments using the MD CV method are reported for equilibrium and nonequilibrium (start-up Couette flow) model liquids, which demonstrate the advantages of the formulation. The CV formulation of the MD is shown to be exactly conservative and is, therefore, ideally suited to obtain macroscopic properties from a discrete system.

  11. Molecular dynamics simulation study of methanesulfonic acid.

    PubMed

    Canales, Manel; Alemán, Carlos

    2014-03-27

    A molecular dynamics simulation study of methanesulfonic acid has been carried out using a reliable force field in a large range of temperatures. Several thermodynamic, structural, and dynamical properties have been calculated and compared with the available experimental data. The density, the shear viscosity, the heat of vaporization, and the melting temperature results, calculated from this force field, are in a good agreement with the experimental data. Analysis of the influence of the hydrogen bonds in structural and dynamical properties has also been performed. The continuous and interrupted methodologies to compute hydrogen bonding lifetimes have been applied. The interrupted hydrogen bond lifetimes values are consistent with the diffusion and viscosity coefficients. The activation energies of the self-diffusion, the reorientational motions, and the hydrogen bonding lifetimes are coincident.

  12. Molecular dynamics of CYP2D6 polymorphisms in the absence and presence of a mechanism-based inactivator reveals changes in local flexibility and dominant substrate access channels.

    PubMed

    de Waal, Parker W; Sunden, Kyle F; Furge, Laura Lowe

    2014-01-01

    Cytochrome P450 enzymes (CYPs) represent an important enzyme superfamily involved in metabolism of many endogenous and exogenous small molecules. CYP2D6 is responsible for ∼ 15% of CYP-mediated drug metabolism and exhibits large phenotypic diversity within CYPs with over 100 different allelic variants. Many of these variants lead to functional changes in enzyme activity and substrate selectivity. Herein, a molecular dynamics comparative analysis of four different variants of CYP2D6 was performed. The comparative analysis included simulations with and without SCH 66712, a ligand that is also a mechanism-based inactivator, in order to investigate the possible structural basis of CYP2D6 inactivation. Analysis of protein stability highlighted significantly altered flexibility in both proximal and distal residues from the variant residues. In the absence of SCH 66712, *34, *17-2, and *17-3 displayed more flexibility than *1, and *53 displayed more rigidity. SCH 66712 binding reversed flexibility in *17-2 and *17-3, through *53 remained largely rigid. Throughout simulations with docked SCH 66712, ligand orientation within the heme-binding pocket was consistent with previously identified sites of metabolism and measured binding energies. Subsequent tunnel analysis of substrate access, egress, and solvent channels displayed varied bottle-neck radii. Taken together, our results indicate that SCH 66712 should inactivate these allelic variants, although varied flexibility and substrate binding-pocket accessibility may alter its interaction abilities. PMID:25286176

  13. Annihilation of craters: Molecular dynamic simulations on a silver surface

    SciTech Connect

    Henriksson, K. O. E.; Nordlund, K.; Keinonen, J.

    2007-12-15

    The ability of silver cluster ions containing 13 atoms to fill in a preexisting crater with a radius of about 28 A ring on a silver (001) target has been investigated using molecular dynamics simulations and the molecular-dynamics-Monte Carlo corrected effective medium potential. The largest lateral distance r between crater and ion was about three times the radius of the preexisting crater, namely, 75 A ring . The results reveal that when r<20 A ring and r>60 A ring the preexisting crater is partially filled in, and for other distances there is a net growth of the crater. The lattice damage created by the cluster ions, the total sputtering yield, the cluster sputtering yield, and simulated transmission electron microscopy images of the irradiated targets are also presented.

  14. Polymer Fluid Dynamics: Continuum and Molecular Approaches.

    PubMed

    Bird, R B; Giacomin, A J

    2016-06-01

    To solve problems in polymer fluid dynamics, one needs the equations of continuity, motion, and energy. The last two equations contain the stress tensor and the heat-flux vector for the material. There are two ways to formulate the stress tensor: (a) One can write a continuum expression for the stress tensor in terms of kinematic tensors, or (b) one can select a molecular model that represents the polymer molecule and then develop an expression for the stress tensor from kinetic theory. The advantage of the kinetic theory approach is that one gets information about the relation between the molecular structure of the polymers and the rheological properties. We restrict the discussion primarily to the simplest stress tensor expressions or constitutive equations containing from two to four adjustable parameters, although we do indicate how these formulations may be extended to give more complicated expressions. We also explore how these simplest expressions are recovered as special cases of a more general framework, the Oldroyd 8-constant model. Studying the simplest models allows us to discover which types of empiricisms or molecular models seem to be worth investigating further. We also explore equivalences between continuum and molecular approaches. We restrict the discussion to several types of simple flows, such as shearing flows and extensional flows, which are of greatest importance in industrial operations. Furthermore, if these simple flows cannot be well described by continuum or molecular models, then it is not necessary to lavish time and energy to apply them to more complex flow problems. PMID:27276553

  15. Application of optimal prediction to molecular dynamics

    SciTech Connect

    Barber, IV, John Letherman

    2004-12-01

    Optimal prediction is a general system reduction technique for large sets of differential equations. In this method, which was devised by Chorin, Hald, Kast, Kupferman, and Levy, a projection operator formalism is used to construct a smaller system of equations governing the dynamics of a subset of the original degrees of freedom. This reduced system consists of an effective Hamiltonian dynamics, augmented by an integral memory term and a random noise term. Molecular dynamics is a method for simulating large systems of interacting fluid particles. In this thesis, I construct a formalism for applying optimal prediction to molecular dynamics, producing reduced systems from which the properties of the original system can be recovered. These reduced systems require significantly less computational time than the original system. I initially consider first-order optimal prediction, in which the memory and noise terms are neglected. I construct a pair approximation to the renormalized potential, and ignore three-particle and higher interactions. This produces a reduced system that correctly reproduces static properties of the original system, such as energy and pressure, at low-to-moderate densities. However, it fails to capture dynamical quantities, such as autocorrelation functions. I next derive a short-memory approximation, in which the memory term is represented as a linear frictional force with configuration-dependent coefficients. This allows the use of a Fokker-Planck equation to show that, in this regime, the noise is δ-correlated in time. This linear friction model reproduces not only the static properties of the original system, but also the autocorrelation functions of dynamical variables.

  16. Molecular Dynamics Simulation of Dynamic Response of Beryllium

    NASA Astrophysics Data System (ADS)

    Thompson, Aidan P.; Lane, J. Matthew D.; Baskes, Michael I.; Desjarlais, Michael P.

    2009-06-01

    The response of beryllium to dynamic loading has been extensively studied, both experimentally and theoretically, due to its importance in several technological areas. Compared to other metals, it is quite challenging to accurately represent the various anomalous behaviors of beryllium using classical interatomic potentials. The spherically-symmetric EAM potential can not reproduce the observed c/a ratio for α-Be under ambient conditions, which is significantly smaller than the ideal HCP value. The directional-dependence of the MEAM potential overcomes this problem, but introduces additional complexity. We will compare predictions of these classical potentials to experimental measurements of beryllium at ambient conditions, and also to theoretical calculations at high temperatures and pressures. Finally, we will present initial results from non-equilibrium molecular dynamics simulations of beryllium under dynamic loading. This work is supported by the Laboratory Directed Research and Development program at Sandia National Laboratories.

  17. Local Refinements in Classical Molecular Dynamics Simulations

    NASA Astrophysics Data System (ADS)

    Fackeldey, Konstantin; Weber, Marcus

    2014-03-01

    Quantum mechanics provide a detailed description of the physical and chemical behavior of molecules. However, with increasing size of the system the complexity rises exponentially, which is prohibitive for efficient dynamical simulation. In contrast, classical molecular dynamics procure a coarser description by using less degrees of freedom. Thus, it seems natural to seek for an adequate trade-off between accurateness and computational feasibility in the simulation of molecules. Here, we propose a novel method, which combines classical molecular simulations with quantum mechanics for molecular systems. For this we decompose the state space of the respective molecule into subsets, by employing a meshfree partition of unity. We show, that this partition allows us to localize an empirical force field and to run locally constrained classical trajectories. Within each subset, we compute the energy on the quantum level for a fixed number of spatial states (ab initio points). With these energy values from the ab initio points we have a local scattered data problem, which can be solved by the moving least squares method.

  18. Stochastic Event-Driven Molecular Dynamics

    SciTech Connect

    Donev, Aleksandar Garcia, Alejandro L.; Alder, Berni J.

    2008-02-01

    A novel Stochastic Event-Driven Molecular Dynamics (SEDMD) algorithm is developed for the simulation of polymer chains suspended in a solvent. SEDMD combines event-driven molecular dynamics (EDMD) with the Direct Simulation Monte Carlo (DSMC) method. The polymers are represented as chains of hard-spheres tethered by square wells and interact with the solvent particles with hard-core potentials. The algorithm uses EDMD for the simulation of the polymer chain and the interactions between the chain beads and the surrounding solvent particles. The interactions between the solvent particles themselves are not treated deterministically as in EDMD, rather, the momentum and energy exchange in the solvent is determined stochastically using DSMC. The coupling between the solvent and the solute is consistently represented at the particle level retaining hydrodynamic interactions and thermodynamic fluctuations. However, unlike full MD simulations of both the solvent and the solute, in SEDMD the spatial structure of the solvent is ignored. The SEDMD algorithm is described in detail and applied to the study of the dynamics of a polymer chain tethered to a hard-wall subjected to uniform shear. SEDMD closely reproduces results obtained using traditional EDMD simulations with two orders of magnitude greater efficiency. Results question the existence of periodic (cycling) motion of the polymer chain.

  19. HERSCHEL OBSERVATIONS REVEAL ANOMALOUS MOLECULAR ABUNDANCES TOWARD THE GALACTIC CENTER

    SciTech Connect

    Sonnentrucker, P.; Neufeld, D. A.; Indriolo, N.; Gerin, M.; De Luca, M.; Lis, D. C.; Goicoechea, J. R.

    2013-01-20

    We report the Herschel detections of hydrogen fluoride (HF) and para-water (p-H{sub 2}O) in gas intercepting the sight lines to two well-studied molecular clouds in the vicinity of the Sgr A complex: G-0.02-0.07 (the {sup +}50 km s{sup -1} cloud{sup )} and G-0.13-0.08 (the {sup +}20 km s{sup -1} cloud{sup )}. Toward both sight lines, HF and water absorption components are detected over a wide range of velocities covering {approx}250 km s{sup -1}. For all velocity components with V{sub LSR} > -85 km s{sup -1}, we find that the HF and water abundances are consistent with those measured toward other sight lines probing the Galactic disk gas. The velocity components with V{sub LSR} {<=} -85 km s{sup -1}, which are known to trace gas residing within {approx}200 pc of the Galactic center, however, exhibit water vapor abundances with respect to HF at least a factor three higher than those found in the Galactic disk gas. Comparison with CH data indicates that our observations are consistent with a picture where HF and a fraction of the H{sub 2}O absorption arise in diffuse molecular clouds showing Galactic disk-like abundances while the bulk of the water absorption arises in warmer (T {>=} 400 K) diffuse molecular gas for V{sub LSR} {<=} -85 km s{sup -1}. This diffuse Interstellar Medium (ISM) phase has also been recently revealed through observations of CO, HF, H{sup +}{sub 3}, and H{sub 3}O{sup +} absorption toward other sight lines probing the Galactic center inner region.

  20. Molecular profiling reveals primary mesothelioma cell lines recapitulate human disease.

    PubMed

    Chernova, T; Sun, X M; Powley, I R; Galavotti, S; Grosso, S; Murphy, F A; Miles, G J; Cresswell, L; Antonov, A V; Bennett, J; Nakas, A; Dinsdale, D; Cain, K; Bushell, M; Willis, A E; MacFarlane, M

    2016-07-01

    Malignant mesothelioma (MM) is an aggressive, fatal tumor strongly associated with asbestos exposure. There is an urgent need to improve MM patient outcomes and this requires functionally validated pre-clinical models. Mesothelioma-derived cell lines provide an essential and relatively robust tool and remain among the most widely used systems for candidate drug evaluation. Although a number of cell lines are commercially available, a detailed comparison of these commercial lines with freshly derived primary tumor cells to validate their suitability as pre-clinical models is lacking. To address this, patient-derived primary mesothelioma cell lines were established and characterized using complementary multidisciplinary approaches and bioinformatic analysis. Clinical markers of mesothelioma, transcriptional and metabolic profiles, as well as the status of p53 and the tumor suppressor genes CDKN2A and NF2, were examined in primary cell lines and in two widely used commercial lines. Expression of MM-associated markers, as well as the status of CDKN2A, NF2, the 'gatekeeper' in MM development, and their products demonstrated that primary cell lines are more representative of the tumor close to its native state and show a degree of molecular diversity, thus capturing the disease heterogeneity in a patient cohort. Molecular profiling revealed a significantly different transcriptome and marked metabolic shift towards a greater glycolytic phenotype in commercial compared with primary cell lines. Our results highlight that multiple, appropriately characterised, patient-derived tumor cell lines are required to enable concurrent evaluation of molecular profiles versus drug response. Furthermore, application of this approach to other difficult-to-treat tumors would generate improved cellular models for pre-clinical evaluation of novel targeted therapies.

  1. Molecular profiling reveals primary mesothelioma cell lines recapitulate human disease

    PubMed Central

    Chernova, T; Sun, X M; Powley, I R; Galavotti, S; Grosso, S; Murphy, F A; Miles, G J; Cresswell, L; Antonov, A V; Bennett, J; Nakas, A; Dinsdale, D; Cain, K; Bushell, M; Willis, A E; MacFarlane, M

    2016-01-01

    Malignant mesothelioma (MM) is an aggressive, fatal tumor strongly associated with asbestos exposure. There is an urgent need to improve MM patient outcomes and this requires functionally validated pre-clinical models. Mesothelioma-derived cell lines provide an essential and relatively robust tool and remain among the most widely used systems for candidate drug evaluation. Although a number of cell lines are commercially available, a detailed comparison of these commercial lines with freshly derived primary tumor cells to validate their suitability as pre-clinical models is lacking. To address this, patient-derived primary mesothelioma cell lines were established and characterized using complementary multidisciplinary approaches and bioinformatic analysis. Clinical markers of mesothelioma, transcriptional and metabolic profiles, as well as the status of p53 and the tumor suppressor genes CDKN2A and NF2, were examined in primary cell lines and in two widely used commercial lines. Expression of MM-associated markers, as well as the status of CDKN2A, NF2, the ‘gatekeeper' in MM development, and their products demonstrated that primary cell lines are more representative of the tumor close to its native state and show a degree of molecular diversity, thus capturing the disease heterogeneity in a patient cohort. Molecular profiling revealed a significantly different transcriptome and marked metabolic shift towards a greater glycolytic phenotype in commercial compared with primary cell lines. Our results highlight that multiple, appropriately characterised, patient-derived tumor cell lines are required to enable concurrent evaluation of molecular profiles versus drug response. Furthermore, application of this approach to other difficult-to-treat tumors would generate improved cellular models for pre-clinical evaluation of novel targeted therapies. PMID:26891694

  2. Flexibility at a glycosidic linkage revealed by molecular dynamics, stochastic modeling, and (13)C NMR spin relaxation: conformational preferences of α-L-Rhap-α-(1 → 2)-α-L-Rhap-OMe in water and dimethyl sulfoxide solutions.

    PubMed

    Pendrill, Robert; Engström, Olof; Volpato, Andrea; Zerbetto, Mirco; Polimeno, Antonino; Widmalm, Göran

    2016-01-28

    The monosaccharide L-rhamnose is common in bacterial polysaccharides and the disaccharide α-L-Rhap-α-(1 → 2)-α-L-Rhap-OMe represents a structural model for a part of Shigella flexneri O-antigen polysaccharides. Utilization of [1'-(13)C]-site-specific labeling in the anomeric position at the glycosidic linkage between the two sugar residues facilitated the determination of transglycosidic NMR (3)JCH and (3)JCC coupling constants. Based on these spin-spin couplings the major state and the conformational distribution could be determined with respect to the ψ torsion angle, which changed between water and dimethyl sulfoxide (DMSO) as solvents, a finding mirrored by molecular dynamics (MD) simulations with explicit solvent molecules. The (13)C NMR spin relaxation parameters T1, T2, and heteronuclear NOE of the probe were measured for the disaccharide in DMSO-d6 at two magnetic field strengths, with standard deviations ≤1%. The combination of MD simulation and a stochastic description based on the diffusive chain model resulted in excellent agreement between calculated and experimentally observed (13)C relaxation parameters, with an average error of <2%. The coupling between the global reorientation of the molecule and the local motion of the spin probe is deemed essential if reproduction of NMR relaxation parameters should succeed, since decoupling of the two modes of motion results in significantly worse agreement. Calculation of (13)C relaxation parameters based on the correlation functions obtained directly from the MD simulation of the solute molecule in DMSO as solvent showed satisfactory agreement with errors on the order of 10% or less. PMID:26741055

  3. Molecular dynamics in high electric fields

    NASA Astrophysics Data System (ADS)

    Apostol, M.; Cune, L. C.

    2016-06-01

    Molecular rotation spectra, generated by the coupling of the molecular electric-dipole moments to an external time-dependent electric field, are discussed in a few particular conditions which can be of some experimental interest. First, the spherical-pendulum molecular model is reviewed, with the aim of introducing an approximate method which consists in the separation of the azimuthal and zenithal motions. Second, rotation spectra are considered in the presence of a static electric field. Two particular cases are analyzed, corresponding to strong and weak fields. In both cases the classical motion of the dipoles consists of rotations and vibrations about equilibrium positions; this motion may exhibit parametric resonances. For strong fields a large macroscopic electric polarization may appear. This situation may be relevant for polar matter (like pyroelectrics, ferroelectrics), or for heavy impurities embedded in a polar solid. The dipolar interaction is analyzed in polar condensed matter, where it is shown that new polarization modes appear for a spontaneous macroscopic electric polarization (these modes are tentatively called "dipolons"); one of the polarization modes is related to parametric resonances. The extension of these considerations to magnetic dipoles is briefly discussed. The treatment is extended to strong electric fields which oscillate with a high frequency, as those provided by high-power lasers. It is shown that the effect of such fields on molecular dynamics is governed by a much weaker, effective, renormalized, static electric field.

  4. Molecular View on Supramolecular Chain and Association Dynamics

    NASA Astrophysics Data System (ADS)

    Monkenbusch, M.; Krutyeva, M.; Pyckhout-Hintzen, W.; Antonius, W.; Hövelmann, C. H.; Allgaier, J.; Brás, A.; Farago, B.; Wischnewski, A.; Richter, D.

    2016-09-01

    The chain and association dynamics of supramolecular polymer ensembles decisively determines their properties. Using neutron spin echo (NSE) spectroscopy we present molecular insight into the space and time evolution of this dynamics. Studying a well characterized ensemble of linearly associating telechelic poly(ethylene glycol) melts carrying triple H-bonding end groups, we show that H-bond breaking significantly impacts the mode spectrum of the associates. The breaking affects the mode contributions and not the relaxation times as was assumed previously. NSE spectra directly reveal the so far intangible H-bond lifetimes in the supramolecular melt and demonstrate that for both the microscopic and the macroscopic dynamics of the supramolecular ensemble the instantaneous average of the Mw distribution governs the system response at least as long as the Rouse picture applies.

  5. Hyperdynamics: Accelerated Molecular Dynamics of Infrequent Events

    SciTech Connect

    Voter, A.F.

    1997-05-01

    I derive a general method for accelerating the molecular-dynamics (MD) simulation of infrequent events in solids. A bias potential ({Delta}V{sub b}) raises the energy in regions other than the transition states between potential basins. Transitions occur at an accelerated rate and the elapsed time becomes a statistical property of the system. {Delta}V{sub b} can be constructed without knowing the location of the transition states and implementation requires only first derivatives. I examine the diffusion mechanisms of a 10-atom Ag cluster on the Ag(111) surface using a 220 {mu}s hyper-MD simulation. {copyright} {ital 1997} {ital The American Physical Society}

  6. [Oligoglycine surface structures: molecular dynamics simulation].

    PubMed

    Gus'kova, O A; Khalatur, P G; Khokhlov, A R; Chinarev, A A; Tsygankova, S V; Bovin, N V

    2010-01-01

    The full-atomic molecular dynamics (MD) simulation of adsorption mode for diantennary oligoglycines [H-Gly4-NH(CH2)5]2 onto graphite and mica surface is described. The resulting structure of adsorption layers is analyzed. The peptide second structure motives have been studied by both STRIDE (structural identification) and DSSP (dictionary of secondary structure of proteins) methods. The obtained results confirm the possibility of polyglycine II (PGII) structure formation in diantennary oligoglycine (DAOG) monolayers deposited onto graphite surface, which was earlier estimated based on atomic-force microscopy measurements.

  7. Molecular dynamics simulation of ice XII

    NASA Astrophysics Data System (ADS)

    Borzsák, István; Cummings, Peter T.

    1999-02-01

    Molecular dynamics simulations have been performed on the newly discovered metastable ice XII. This new crystalline ice phase [C. Lobban, J.L. Finney, W.F. Kuhs, Nature (London) 391 (1998) 268] is proton-disordered. Thus 90 possible configurations of the unit cell can be constructed which differ only in the orientations of the water molecules. The simulation used the TIP4P potential model for water at constant temperature and density. About one-quarter of the initial configurations did not melt in the course of the simulation. This result is supportive of the experimental structure and also demonstrates the ability of this water model to study ice phases.

  8. Crystallization of nickel nanoclusters by molecular dynamics

    NASA Astrophysics Data System (ADS)

    Chamati, H.; Gaminchev, K.

    2012-12-01

    We investigated the melting properties of bulk nickel and the crystallization of nickel nanocrystals via molecular dynamics using a potential in the framework of the second moment approximation of tight-binding theory. The melting behavior was simulated with the hysteresis approach by subsequently heating and cooling gradually the system over a wide range of temperatures. The crystallization of nickel nanoclusters consisting of 55, 147 and 309 atoms was achieved after repeatedly annealing and quenching the corresponding quasicrystals several times to avoid being trapped in a local energy minimum. The time over which the global minimum was reached was found to increase with the cluster size.

  9. Ultrafast Molecular Dynamics probed by Vacuum Ultraviolet Pulses

    NASA Astrophysics Data System (ADS)

    Cryan, James; Champenois, Elio; Shivaram, Niranjan; Wright, Travis; Yang, Chan-Shan; Falcone, Roger; Belkacem, Ali

    2014-05-01

    We present time-resolved measurements of the relaxation dynamics in small molecular systems (CO2 and C2H4) following ultraviolet (UV) photo-excitation. We probe these excitations through photoionization and velocity map imaging (VMI) spectroscopy. Vacuum and extreme ultraviolet (VUV/XUV) pump and probe pulses are created by exploiting strong-field high harmonic generation (HHG) from our state-of-the-art 30 mJ, 1 kHz laser system. Three dimensional photoelectron and photoion momentum images recorded with our VMI spectrometer reveal non-Born Oppenheimer dynamics in the vicinity of a conical intersection, and allow us track the state of the system as a function of time. We also present initial experiments with the goal of controlling the dynamics near a conical intersection using a strong-field IR pulse. Finally, we will show progress towards measurements of time-resolved molecular frame photoelectron angular distributions (TRMFPADs) by applying our VUV/XUV pulse sequence to an aligned molecular ensemble. Supported by Chemical Sciences, Geosciences and Biosciences division of BES/DOE.

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

    ERIC Educational Resources Information Center

    Tzuriel, David

    2011-01-01

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

  11. Molecular dynamics simulations of calcium binding in gramicidin A

    NASA Astrophysics Data System (ADS)

    Baştuğ, Turgut; Kuyucak, Serdar

    2006-06-01

    An important issue in molecular dynamics (MD) simulations of biomolecules is whether membrane proteins can be described using nonpolarizable force fields. To shed further light into this question, we study calcium ion binding and blocking of the gramicidin A channel which has not been investigated in MD simulations before. Potential of mean force calculations for calcium and potassium ions using a nonpolarizable force field reveal that calcium binding to the channel is much weaker compared to potassium, and hence calcium block of potassium current cannot be described. Inclusion of polarization interaction in force fields may help to rectify this problem.

  12. Molecular dynamics simulation of bicrystalline metal surface treatment

    SciTech Connect

    Nikonov, A. Yu.

    2015-10-27

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

  13. Exact dynamic properties of molecular motors

    NASA Astrophysics Data System (ADS)

    Boon, N. J.; Hoyle, R. B.

    2012-08-01

    Molecular motors play important roles within a biological cell, performing functions such as intracellular transport and gene transcription. Recent experimental work suggests that there are many plausible biochemical mechanisms that molecules such as myosin-V could use to achieve motion. To account for the abundance of possible discrete-stochastic frameworks that can arise when modeling molecular motor walks, a generalized and straightforward graphical method for calculating their dynamic properties is presented. It allows the calculation of the velocity, dispersion, and randomness ratio for any proposed system through analysis of its structure. This article extends work of King and Altman ["A schematic method of deriving the rate laws of enzyme-catalyzed reactions," J. Phys. Chem. 60, 1375-1378 (1956)], 10.1021/j150544a010 on networks of enzymatic reactions by calculating additional dynamic properties for spatially hopping systems. Results for n-state systems are presented: single chain, parallel pathway, divided pathway, and divided pathway with a chain. A novel technique for combining multiple system architectures coupled at a reference state is also demonstrated. Four-state examples illustrate the effectiveness and simplicity of these methods.

  14. MDLab: a molecular dynamics simulation prototyping environment.

    PubMed

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

    2010-05-01

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

  15. Molecular modifiers reveal a mechanism of pathological crystal growth inhibition

    NASA Astrophysics Data System (ADS)

    Chung, Jihae; Granja, Ignacio; Taylor, Michael G.; Mpourmpakis, Giannis; Asplin, John R.; Rimer, Jeffrey D.

    2016-08-01

    Crystalline materials are crucial to the function of living organisms, in the shells of molluscs, the matrix of bone, the teeth of sea urchins, and the exoskeletons of coccoliths. However, pathological biomineralization can be an undesirable crystallization process associated with human diseases. The crystal growth of biogenic, natural and synthetic materials may be regulated by the action of modifiers, most commonly inhibitors, which range from small ions and molecules to large macromolecules. Inhibitors adsorb on crystal surfaces and impede the addition of solute, thereby reducing the rate of growth. Complex inhibitor-crystal interactions in biomineralization are often not well elucidated. Here we show that two molecular inhibitors of calcium oxalate monohydrate crystallization—citrate and hydroxycitrate—exhibit a mechanism that differs from classical theory in that inhibitor adsorption on crystal surfaces induces dissolution of the crystal under specific conditions rather than a reduced rate of crystal growth. This phenomenon occurs even in supersaturated solutions where inhibitor concentration is three orders of magnitude less than that of the solute. The results of bulk crystallization, in situ atomic force microscopy, and density functional theory studies are qualitatively consistent with a hypothesis that inhibitor-crystal interactions impart localized strain to the crystal lattice and that oxalate and calcium ions are released into solution to alleviate this strain. Calcium oxalate monohydrate is the principal component of human kidney stones and citrate is an often-used therapy, but hydroxycitrate is not. For hydroxycitrate to function as a kidney stone treatment, it must be excreted in urine. We report that hydroxycitrate ingested by non-stone-forming humans at an often-recommended dose leads to substantial urinary excretion. In vitro assays using human urine reveal that the molecular modifier hydroxycitrate is as effective an inhibitor of nucleation

  16. Molecular modifiers reveal a mechanism of pathological crystal growth inhibition

    NASA Astrophysics Data System (ADS)

    Chung, Jihae; Granja, Ignacio; Taylor, Michael G.; Mpourmpakis, Giannis; Asplin, John R.; Rimer, Jeffrey D.

    2016-08-01

    Crystalline materials are crucial to the function of living organisms, in the shells of molluscs, the matrix of bone, the teeth of sea urchins, and the exoskeletons of coccoliths. However, pathological biomineralization can be an undesirable crystallization process associated with human diseases. The crystal growth of biogenic, natural and synthetic materials may be regulated by the action of modifiers, most commonly inhibitors, which range from small ions and molecules to large macromolecules. Inhibitors adsorb on crystal surfaces and impede the addition of solute, thereby reducing the rate of growth. Complex inhibitor–crystal interactions in biomineralization are often not well elucidated. Here we show that two molecular inhibitors of calcium oxalate monohydrate crystallization—citrate and hydroxycitrate—exhibit a mechanism that differs from classical theory in that inhibitor adsorption on crystal surfaces induces dissolution of the crystal under specific conditions rather than a reduced rate of crystal growth. This phenomenon occurs even in supersaturated solutions where inhibitor concentration is three orders of magnitude less than that of the solute. The results of bulk crystallization, in situ atomic force microscopy, and density functional theory studies are qualitatively consistent with a hypothesis that inhibitor–crystal interactions impart localized strain to the crystal lattice and that oxalate and calcium ions are released into solution to alleviate this strain. Calcium oxalate monohydrate is the principal component of human kidney stones and citrate is an often-used therapy, but hydroxycitrate is not. For hydroxycitrate to function as a kidney stone treatment, it must be excreted in urine. We report that hydroxycitrate ingested by non-stone-forming humans at an often-recommended dose leads to substantial urinary excretion. In vitro assays using human urine reveal that the molecular modifier hydroxycitrate is as effective an inhibitor of

  17. Molecular modifiers reveal a mechanism of pathological crystal growth inhibition.

    PubMed

    Chung, Jihae; Granja, Ignacio; Taylor, Michael G; Mpourmpakis, Giannis; Asplin, John R; Rimer, Jeffrey D

    2016-08-25

    Crystalline materials are crucial to the function of living organisms, in the shells of molluscs, the matrix of bone, the teeth of sea urchins, and the exoskeletons of coccoliths. However, pathological biomineralization can be an undesirable crystallization process associated with human diseases. The crystal growth of biogenic, natural and synthetic materials may be regulated by the action of modifiers, most commonly inhibitors, which range from small ions and molecules to large macromolecules. Inhibitors adsorb on crystal surfaces and impede the addition of solute, thereby reducing the rate of growth. Complex inhibitor-crystal interactions in biomineralization are often not well elucidated. Here we show that two molecular inhibitors of calcium oxalate monohydrate crystallization--citrate and hydroxycitrate--exhibit a mechanism that differs from classical theory in that inhibitor adsorption on crystal surfaces induces dissolution of the crystal under specific conditions rather than a reduced rate of crystal growth. This phenomenon occurs even in supersaturated solutions where inhibitor concentration is three orders of magnitude less than that of the solute. The results of bulk crystallization, in situ atomic force microscopy, and density functional theory studies are qualitatively consistent with a hypothesis that inhibitor-crystal interactions impart localized strain to the crystal lattice and that oxalate and calcium ions are released into solution to alleviate this strain. Calcium oxalate monohydrate is the principal component of human kidney stones and citrate is an often-used therapy, but hydroxycitrate is not. For hydroxycitrate to function as a kidney stone treatment, it must be excreted in urine. We report that hydroxycitrate ingested by non-stone-forming humans at an often-recommended dose leads to substantial urinary excretion. In vitro assays using human urine reveal that the molecular modifier hydroxycitrate is as effective an inhibitor of nucleation of

  18. Dynamic transitions in molecular dynamics simulations of supercooled silicon

    NASA Astrophysics Data System (ADS)

    Mei, Xiaojun; Eapen, Jacob

    2013-04-01

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

  19. The 2011 Dynamics of Molecular Collisions Conference

    SciTech Connect

    Nesbitt, David J.

    2011-07-11

    The Dynamics of Molecular Collisions Conference focuses on all aspects of molecular collisions--experimental & theoretical studies of elastic, inelastic, & reactive encounters involving atoms, molecules, ions, clusters, & surfaces--as well as half collisions--photodissociation, photo-induced reaction, & photodesorption. The scientific program for the meeting in 2011 included exciting advances in both the core & multidisciplinary forefronts of the study of molecular collision processes. Following the format of the 2009 meeting, we also invited sessions in special topics that involve interfacial dynamics, novel emerging spectroscopies, chemical dynamics in atmospheric, combustion & interstellar environments, as well as a session devoted to theoretical & experimental advances in ultracold molecular samples. Researchers working inside & outside the traditional core topics of the meeting are encouraged to join the conference. We invite contributions of work that seeks understanding of how inter & intra-molecular forces determine the dynamics of the phenomena under study. In addition to invited oral sessions & contributed poster sessions, the scientific program included a formal session consisting of five contributed talks selected from the submitted poster abstracts. The DMC has distinguished itself by having the Herschbach Medal Symposium as part of the meeting format. This tradition of the Herschbach Medal was first started in the 2007 meeting chaired by David Chandler, based on a generous donation of funds & artwork design by Professor Dudley Herschbach himself. There are two such awards made, one for experimental & one for theoretical contributions to the field of Molecular Collision Dynamics, broadly defined. The symposium is always held on the last night of the meeting & has the awardees are asked to deliver an invited lecture on their work. The 2011 Herschbach Medal was dedicated to the contributions of two long standing leaders in Chemical Physics, Professor

  20. Single-Cell RNA-Seq with Waterfall Reveals Molecular Cascades underlying Adult Neurogenesis.

    PubMed

    Shin, Jaehoon; Berg, Daniel A; Zhu, Yunhua; Shin, Joseph Y; Song, Juan; Bonaguidi, Michael A; Enikolopov, Grigori; Nauen, David W; Christian, Kimberly M; Ming, Guo-li; Song, Hongjun

    2015-09-01

    Somatic stem cells contribute to tissue ontogenesis, homeostasis, and regeneration through sequential processes. Systematic molecular analysis of stem cell behavior is challenging because classic approaches cannot resolve cellular heterogeneity or capture developmental dynamics. Here we provide a comprehensive resource of single-cell transcriptomes of adult hippocampal quiescent neural stem cells (qNSCs) and their immediate progeny. We further developed Waterfall, a bioinformatic pipeline, to statistically quantify singe-cell gene expression along a de novo reconstructed continuous developmental trajectory. Our study reveals molecular signatures of adult qNSCs, characterized by active niche signaling integration and low protein translation capacity. Our analyses further delineate molecular cascades underlying qNSC activation and neurogenesis initiation, exemplified by decreased extrinsic signaling capacity, primed translational machinery, and regulatory switches in transcription factors, metabolism, and energy sources. Our study reveals the molecular continuum underlying adult neurogenesis and illustrates how Waterfall can be used for single-cell omics analyses of various continuous biological processes. PMID:26299571

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

    NASA Astrophysics Data System (ADS)

    Hong, Liang; Smith, Jeremy; CenterMolecular Biophysics Team

    2014-03-01

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

  2. Osmosis : a molecular dynamics computer simulation study

    NASA Astrophysics Data System (ADS)

    Lion, Thomas

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

  3. Molecular stopwatches, cogwheels and ``spinflakes'': studying the dynamics of molecular superrotors

    NASA Astrophysics Data System (ADS)

    Korobenko, Aleksey; Milner, Alexander; Hepburn, John; Milner, Valery

    2015-05-01

    Using the technique of an optical centrifuge, we excite diatomic molecules to ultrafast synchronous rotation. Femtosecond velocity-map imaging allows us to visualize and study the coherent dynamics of molecular superrotors under field free conditions and in external magnetic field. We demonstrate that when the created rotational wave packet is narrow, its free evolution is nondispersing and follows the motion of a classically rotating dumbbell or a hand of the smallest natural stopwatch. For wider rotational distributions, we observe the breakdown of classical rotation, when a dumbbell shape changes to that of a ``quantum cogwheel'' - a molecular state simultaneously aligned along multiple direction. Our measurements in external magnetic field reveal other peculiar aspects of the rich dynamics of molecular superrotors. The rotation of a non-magnetic molecule interacts with the applied field only weakly, giving rise to slow precession of the molecular angular momentum around the field direction. In contrast, the electronic spin of a paramagnetic superrotor mediates this interaction, causing the initial disk-like angular distribution to split into several spatial components, each precessing with its own frequency determined by the spin projection.

  4. Molecular dynamics simulation of radiation damage cascades in diamond

    SciTech Connect

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

    2015-06-28

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

  5. Fiber lubrication: A molecular dynamics simulation study

    NASA Astrophysics Data System (ADS)

    Liu, Hongyi

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

  6. Development of semiclassical molecular dynamics simulation method.

    PubMed

    Nakamura, Hiroki; Nanbu, Shinkoh; Teranishi, Yoshiaki; Ohta, Ayumi

    2016-04-28

    Various quantum mechanical effects such as nonadiabatic transitions, quantum mechanical tunneling and coherence play crucial roles in a variety of chemical and biological systems. In this paper, we propose a method to incorporate tunneling effects into the molecular dynamics (MD) method, which is purely based on classical mechanics. Caustics, which define the boundary between classically allowed and forbidden regions, are detected along classical trajectories and the optimal tunneling path with minimum action is determined by starting from each appropriate caustic. The real phase associated with tunneling can also be estimated. Numerical demonstration with use of a simple collinear chemical reaction O + HCl → OH + Cl is presented in order to help the reader to well comprehend the method proposed here. Generalization to the on-the-fly ab initio version is rather straightforward. By treating the nonadiabatic transitions at conical intersections by the Zhu-Nakamura theory, new semiclassical MD methods can be developed. PMID:27067383

  7. Nonequilibrium molecular dynamics: The first 25 years

    SciTech Connect

    Hoover, W.G. |

    1992-08-01

    Equilibrium Molecular Dynamics has been generalized to simulate Nonequilibrium systems by adding sources of thermodynamic heat and work. This generalization incorporates microscopic mechanical definitions of macroscopic thermodynamic and hydrodynamic variables, such as temperature and stress, and augments atomistic forces with special boundary, constraint, and driving forces capable of doing work on, and exchanging heat with, an otherwise Newtonian system. The underlying Lyapunov instability of these nonequilibrium equations of motion links microscopic time-reversible deterministic trajectories to macroscopic time-irreversible hydrodynamic behavior as described by the Second Law of Thermodynamics. Green-Kubo linear-response theory has been checked. Nonlinear plastic deformation, intense heat conduction, shockwave propagation, and nonequilibrium phase transformation have all been simulated. The nonequilibrium techniques, coupled with qualitative improvements in parallel computer hardware, are enabling simulations to approximate real-world microscale and nanoscale experiments.

  8. Classical Molecular Dynamics Simulation of Nuclear Fuel

    SciTech Connect

    Devanathan, Ram; Krack, Matthias; Bertolus, Marjorie

    2015-10-10

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

  9. Molecular Dynamics Studies of Gold Surfaces

    NASA Astrophysics Data System (ADS)

    Ercolessi, F.; Bartolini, A.; Garofalo, M.; Parrinello, M.; Tosatti, E.

    1987-01-01

    In the glue model the total cohesion of a metal is determined by a pairwise atom-atom effective interaction plus a many-body force (the "glue") which is introduced to ensure optimal coordination. Using parameters optimized for gold, we have studied the structural behaviour of the low index surfaces Au(100), Au(110) and Au(111). We have used a simulated annealing strategy based on molecular dynamics to search the lowest surface energy configuration. In all cases the optimal structures are found to be reconstructed, and remarkably similar to some experimentally suggested reconstruction models. The main driving mechanism is the formation of close-packed triangular surface layers favoured by the glue term.

  10. Extended Lagrangian free energy molecular dynamics.

    PubMed

    Niklasson, Anders M N; Steneteg, Peter; Bock, Nicolas

    2011-10-28

    Extended free energy Lagrangians are proposed for first principles molecular dynamics simulations at finite electronic temperatures for plane-wave pseudopotential and local orbital density matrix-based calculations. Thanks to the extended Lagrangian description, the electronic degrees of freedom can be integrated by stable geometric schemes that conserve the free energy. For the local orbital representations both the nuclear and electronic forces have simple and numerically efficient expressions that are well suited for reduced complexity calculations. A rapidly converging recursive Fermi operator expansion method that does not require the calculation of eigenvalues and eigenfunctions for the construction of the fractionally occupied density matrix is discussed. An efficient expression for the Pulay force that is valid also for density matrices with fractional occupation occurring at finite electronic temperatures is also demonstrated.

  11. Development of semiclassical molecular dynamics simulation method.

    PubMed

    Nakamura, Hiroki; Nanbu, Shinkoh; Teranishi, Yoshiaki; Ohta, Ayumi

    2016-04-28

    Various quantum mechanical effects such as nonadiabatic transitions, quantum mechanical tunneling and coherence play crucial roles in a variety of chemical and biological systems. In this paper, we propose a method to incorporate tunneling effects into the molecular dynamics (MD) method, which is purely based on classical mechanics. Caustics, which define the boundary between classically allowed and forbidden regions, are detected along classical trajectories and the optimal tunneling path with minimum action is determined by starting from each appropriate caustic. The real phase associated with tunneling can also be estimated. Numerical demonstration with use of a simple collinear chemical reaction O + HCl → OH + Cl is presented in order to help the reader to well comprehend the method proposed here. Generalization to the on-the-fly ab initio version is rather straightforward. By treating the nonadiabatic transitions at conical intersections by the Zhu-Nakamura theory, new semiclassical MD methods can be developed.

  12. Nonequilibrium molecular dynamics of liquid crystals

    NASA Astrophysics Data System (ADS)

    Sarman, S. S.; Cummings, P. T.; Evans, D. J.

    1994-11-01

    During the last 15 years, noneyuilibrium molecular dynamics (NEMD) has been successfully applied to study transport phenomena in fluids that are isotropic at equilibrium. A natural extension is therefore to study liquid crystals, which are anisotropic al equilibrium. The lower symmetry of these systems means that the linear transport coefficients are considerably more complicated than in an isotropic system. Part of the reason for this is that there are crosscouplings between tensors of different rank and parity. Such couplings arc symmetry-forbidden in isotropic phases. In this paper. we review some of fundamental theoretical results we have derived concerning the rheology of liquid crystals. report NEMD simulations of thermal conductivity and shear viscosity of liquid crystals, and present NEMD simulations of shear cessation phenomena. All of the NEMD results are presented for a model liquid crystal fluid which is a modification of the Gay-Borne fluid. The results obtained are in qualitative agreement with experimental measurements on liquid crystal systems.

  13. Assessing Molecular Dynamics Simulations with Solvatochromism Modeling.

    PubMed

    Schwabe, Tobias

    2015-08-20

    For the modeling of solvatochromism with an explicit representation of the solvent molecules, the quality of preceding molecular dynamics simulations is crucial. Therefore, the possibility to apply force fields which are derived with as little empiricism as possible seems desirable. Such an approach is tested here by exploiting the sensitive solvatochromism of p-nitroaniline, and the use of reliable excitation energies based on approximate second-order coupled cluster results within a polarizable embedding scheme. The quality of the various MD settings for four different solvents, water, methanol, ethanol, and dichloromethane, is assessed. In general, good agreement with the experiment is observed when polarizable force fields and special treatment of hydrogen bonding are applied. PMID:26220273

  14. Molecular dynamics studies of metallic glasses

    NASA Astrophysics Data System (ADS)

    Lee, Hyon-Jee

    The thermodynamic, structural, and mechanical properties of metallic glasses are studied using molecular dynamics simulations. Molecular dynamics provides a computational framework to simulate the movement of interacting atoms in response to external perturbations, such as changes in temperature or pressure. In this thesis, a Sutton-Chen potential was chosen to describe the many-body interactions in metals and alloys. Our first application for this approach is to develop a simple model to derive the thermodynamic properties of metallic alloys (Chapter 2). Based on this model, we demonstrate that the glass transition is thermodynamically sensitive to differences between atomic radii and that there is an optimal difference for glass formation. Next, we extend these simulations to elucidate the details of structural organization in the glass (Chapter 3). We find that the liquid phase is characterized by a local five-fold symmetry, which becomes more prominent as the glass phase forms. This five-fold symmetry is related to the formation of icosahedral structures. The mechanical properties of glasses are also investigated and it is found that shear localization, which accompanies a sharp drop in the stress-strain curve, occurs at 45 degree with respect to the loading axis (Chapter 4). The generation of free volume is found to be the dominant mechanism that leads to shear localization, rather than adiabatic heating. Finally, generic first principle potentials are constructed to guide the experimental development of AlTiNi based metallic glasses (Chapter 5). Together, the results from these simulations improve our understanding of the thermodynamic, structural, and mechanical properties of metallic glasses and will aid computer-driven materials design.

  15. Molecular dynamics simulations of microscale fluid transport

    SciTech Connect

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

    1998-02-01

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

  16. Molecular dynamics simulations of supramolecular polymer rheology

    NASA Astrophysics Data System (ADS)

    Li, Zhenlong; Djohari, Hadrian; Dormidontova, Elena E.

    2010-11-01

    Using equilibrium and nonequilibrium molecular dynamics simulations, we studied the equilibrium and rheological properties of dilute and semidilute solutions of head-to-tail associating polymers. In our simulation model, a spontaneous complementary reversible association between the donor and the acceptor groups at the ends of oligomers was achieved by introducing a combination of truncated pseudo-Coulombic attractive potential and Lennard Jones repulsive potential between donor, acceptor, and neighboring groups. We have calculated the equilibrium properties of supramolecular polymers, such as the ring/chain equilibrium, average molecular weight, and molecular weight distribution of self-assembled chains and rings, which all agree well with previous analytical and computer modeling results. We have investigated shear thinning of solutions of 8- and 20-bead associating oligomers with different association energies at different temperatures and oligomer volume fractions. All reduced viscosity data for a given oligomer length can be collapsed into one master curve, exhibiting two power-law regions of shear-thinning behavior with an exponent of -0.55 at intermediate ranges of the reduced shear rate β and -0.8 (or -0.9) at larger shear rates. The equilibrium viscosity of supramolecular solutions with different oligomer lengths and associating energies is found to obey a power-law scaling dependence on oligomer volume fraction with an exponent of 1.5, in agreement with the experimental observations for several dilute or semidilute solutions of supramolecular polymers. This implies that dilute and semidilute supramolecular polymer solutions exhibit high polydispersity but may not be sufficiently entangled to follow the reptation mechanism of relaxation.

  17. Molecular beam studies of reaction dynamics

    SciTech Connect

    Lee, Y.T.

    1993-12-01

    The major thrust of this research project is to elucidate detailed dynamics of simple elementary reactions that are theoretically important and to unravel the mechanism of complex chemical reactions or photochemical processes that play important roles in many macroscopic processes. Molecular beams of reactants are used to study individual reactive encounters between molecules or to monitor photodissociation events in a collision-free environment. Most of the information is derived from measurement of the product fragment energy, angular, and state distributions. Recent activities are centered on the mechanisms of elementary chemical reactions involving oxygen atoms with unsaturated hydrocarbons, the dynamics of endothermic substitution reactions, the dependence of the chemical reactivity of electronically excited atoms on the alignment of excited orbitals, the primary photochemical processes of polyatomic molecules, intramolecular energy transfer of chemically activated and locally excited molecules, the energetics of free radicals that are important to combustion processes, the infrared-absorption spectra of carbonium ions and hydrated hydronium ions, and bond-selective photodissociation through electric excitation.

  18. Molecular-dynamic study of liquid ethylenediamine

    NASA Astrophysics Data System (ADS)

    Balabaev, N. K.; Kraevskii, S. V.; Rodnikova, M. N.; Solonina, I. A.

    2016-10-01

    Models of liquid ethylenediamine (ED) are built using the molecular dynamics approach at temperatures of 293-363 K and a size of 1000 molecules in a basic cell as a cuboid. The structural and dynamic characteristics of liquid ED versus temperature are derived. The gauche conformation of the ED molecule that is characteristic of the gas phase is shown to transition easily into the trans conformation of the molecules in the liquid. NH···N hydrogen bonds are analyzed in liquid ED. The number of H-bonds per ED molecule is found to vary from 5.02 at 293 K to 3.86 at 363 K. The lifetimes in the range of the temperatures and dissociation activation energy for several H-bonds in liquid ED are found to range from 0.574 to 4.524 ps at 293 K; the activation energies are 8.8 kJ/mol for 50% of the H-bonds and 16.3 kJ/mol for 6.25% of them. A weaker and more mobile spatial grid of H-bonds in liquid ED is observed, compared to data calculated earlier for monoethanolamine.

  19. Topological structure dynamics revealing collective evolution in active nematics

    PubMed Central

    Shi, Xia-qing; Ma, Yu-qiang

    2013-01-01

    Topological defects frequently emerge in active matter like bacterial colonies, cytoskeleton extracts on substrates, self-propelled granular or colloidal layers and so on, but their dynamical properties and the relations to large-scale organization and fluctuations in these active systems are seldom touched. Here we reveal, through a simple model for active nematics using self-driven hard elliptic rods, that the excitation, annihilation and transportation of topological defects differ markedly from those in non-active media. These dynamical processes exhibit strong irreversibility in active nematics in the absence of detailed balance. Moreover, topological defects are the key factors in organizing large-scale dynamic structures and collective flows, resulting in multi-spatial temporal effects. These findings allow us to control the self-organization of active matter through topological structures. PMID:24346733

  20. Molecular Mechanotransduction: how forces trigger cytoskeletal dynamics

    NASA Astrophysics Data System (ADS)

    Ehrlicher, Allen

    2012-02-01

    Mechanical stresses elicit cellular reactions mediated by chemical signals. Defective responses to forces underlie human medical disorders, such as cardiac failure and pulmonary injury. Despite detailed knowledge of the cytoskeleton's structure, the specific molecular switches that convert mechanical stimuli into chemical signals have remained elusive. Here we identify the actin-binding protein, filamin A (FLNa) as a central mechanotransduction element of the cytoskeleton by using Fluorescence Loss After photoConversion (FLAC), a novel high-speed alternative to FRAP. We reconstituted a minimal system consisting of actin filaments, FLNa and two FLNa-binding partners: the cytoplasmic tail of ß-integrin, and FilGAP. Integrins form an essential mechanical linkage between extracellular and intracellular environments, with ß integrin tails connecting to the actin cytoskeleton by binding directly to filamin. FilGAP is a FLNa-binding GTPase-activating protein specific for Rac, which in vivo regulates cell spreading and bleb formation. We demonstrate that both externally-imposed bulk shear and myosin II driven forces differentially regulate the binding of integrin and FilGAP to FLNa. Consistent with structural predictions, strain increases ß-integrin binding to FLNa, whereas it causes FilGAP to dissociate from FLNa, providing a direct and specific molecular basis for cellular mechanotransduction. These results identify the first molecular mechanotransduction element within the actin cytoskeleton, revealing that mechanical strain of key proteins regulates the binding of signaling molecules. Moreover, GAP activity has been shown to switch cell movement from mesenchymal to amoeboid motility, suggesting that mechanical forces directly impact the invasiveness of cancer.

  1. Inhibition of acetylcholinesterase by two genistein derivatives: kinetic analysis, molecular docking and molecular dynamics simulation.

    PubMed

    Fang, Jiansong; Wu, Ping; Yang, Ranyao; Gao, Li; Li, Chao; Wang, Dongmei; Wu, Song; Liu, Ai-Lin; Du, Guan-Hua

    2014-12-01

    In this study two genistein derivatives (G1 and G2) are reported as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), and differences in the inhibition of AChE are described. Although they differ in structure by a single methyl group, the inhibitory effect of G1 (IC50=264 nmol/L) on AChE was 80 times stronger than that of G2 (IC50=21,210 nmol/L). Enzyme-kinetic analysis, molecular docking and molecular dynamics (MD) simulations were conducted to better understand the molecular basis for this difference. The results obtained by kinetic analysis demonstrated that G1 can interact with both the catalytic active site and peripheral anionic site of AChE. The predicted binding free energies of two complexes calculated by the molecular mechanics/generalized born surface area (MM/GBSA) method were consistent with the experimental data. The analysis of the individual energy terms suggested that a difference between the net electrostatic contributions (ΔE ele+ΔG GB) was responsible for the binding affinities of these two inhibitors. Additionally, analysis of the molecular mechanics and MM/GBSA free energy decomposition revealed that the difference between G1 and G2 originated from interactions with Tyr124, Glu292, Val294 and Phe338 of AChE. In conclusion, the results reveal significant differences at the molecular level in the mechanism of inhibition of AChE by these structurally related compounds. PMID:26579414

  2. Internal Coordinate Molecular Dynamics: A Foundation for Multiscale Dynamics

    PubMed Central

    2015-01-01

    Internal coordinates such as bond lengths, bond angles, and torsion angles (BAT) are natural coordinates for describing a bonded molecular system. However, the molecular dynamics (MD) simulation methods that are widely used for proteins, DNA, and polymers are based on Cartesian coordinates owing to the mathematical simplicity of the equations of motion. However, constraints are often needed with Cartesian MD simulations to enhance the conformational sampling. This makes the equations of motion in the Cartesian coordinates differential-algebraic, which adversely impacts the complexity and the robustness of the simulations. On the other hand, constraints can be easily placed in BAT coordinates by removing the degrees of freedom that need to be constrained. Thus, the internal coordinate MD (ICMD) offers an attractive alternative to Cartesian coordinate MD for developing multiscale MD method. The torsional MD method is a special adaptation of the ICMD method, where all the bond lengths and bond angles are kept rigid. The advantages of ICMD simulation methods are the longer time step size afforded by freezing high frequency degrees of freedom and performing a conformational search in the more important low frequency torsional degrees of freedom. However, the advancements in the ICMD simulations have been slow and stifled by long-standing mathematical bottlenecks. In this review, we summarize the recent mathematical advancements we have made based on spatial operator algebra, in developing a robust long time scale ICMD simulation toolkit useful for various applications. We also present the applications of ICMD simulations to study conformational changes in proteins and protein structure refinement. We review the advantages of the ICMD simulations over the Cartesian simulations when used with enhanced sampling methods and project the future use of ICMD simulations in protein dynamics. PMID:25517406

  3. Influence of annealing on chain entanglement and molecular dynamics in weak dynamic asymmetry polymer blends.

    PubMed

    Lin, Yu; Tan, Yeqiang; Qiu, Biwei; Shangguan, Yonggang; Harkin-Jones, Eileen; Zheng, Qiang

    2013-01-17

    The influence of annealing above the glass transition temperature (T(g)) on chain entanglement and molecular dynamics of solution-cast poly(methyl methacrylate)/poly(styrene-co-maleic anhydride) (PMMA/SMA) blends was investigated via a combination of dynamic rheological measurement and broadband dielectric spectroscopy. Chain entanglement density increases when the annealing temperature and/or time increases, resulting from the increased efficiency of chain packing and entanglement recovery. The results of the annealing treatment without cooling revealed that the increase of the entanglement density occurred during the annealing process instead of the subsequent cooling procedure. Annealing above T(g) exerts a profound effect on segmental motion, including the transition temperature and dynamics. Namely, T(g) shifts to higher temperatures and the relaxation time (τ(max)) increases due to the increased entanglement density and decreased molecular mobility. Either T(g) or τ(max) approaches an equilibrium value gradually, corresponding to the equilibrium entanglement density that might be obtained through the theoretical predictions. However, no obvious distribution broadening is observed due to the unchanged heterogeneous dynamics. Furthermore, side group rotational motion could be freely achieved without overcoming the chain entanglement resistance. Hence, neither the dynamics nor the distribution width of the subglass relaxation (β- and γ-relaxation) processes is affected by chain entanglement resulting from annealing, indicating that the local environment of the segments is unchanged.

  4. Parametrizing linear generalized Langevin dynamics from explicit molecular dynamics simulations

    SciTech Connect

    Gottwald, Fabian; Karsten, Sven; Ivanov, Sergei D. Kühn, Oliver

    2015-06-28

    Fundamental understanding of complex dynamics in many-particle systems on the atomistic level is of utmost importance. Often the systems of interest are of macroscopic size but can be partitioned into a few important degrees of freedom which are treated most accurately and others which constitute a thermal bath. Particular attention in this respect attracts the linear generalized Langevin equation, which can be rigorously derived by means of a linear projection technique. Within this framework, a complicated interaction with the bath can be reduced to a single memory kernel. This memory kernel in turn is parametrized for a particular system studied, usually by means of time-domain methods based on explicit molecular dynamics data. Here, we discuss that this task is more naturally achieved in frequency domain and develop a Fourier-based parametrization method that outperforms its time-domain analogues. Very surprisingly, the widely used rigid bond method turns out to be inappropriate in general. Importantly, we show that the rigid bond approach leads to a systematic overestimation of relaxation times, unless the system under study consists of a harmonic bath bi-linearly coupled to the relevant degrees of freedom.

  5. Molecular dynamics studies of protein folding and aggregation

    NASA Astrophysics Data System (ADS)

    Ding, Feng

    This thesis applies molecular dynamics simulations and statistical mechanics to study: (i) protein folding; and (ii) protein aggregation. Most small proteins fold into their native states via a first-order-like phase transition with a major free energy barrier between the folded and unfolded states. A set of protein conformations corresponding to the free energy barrier, Delta G >> kBT, are the folding transition state ensemble (TSE). Due to their evasive nature, TSE conformations are hard to capture (probability ∝ exp(-DeltaG/k BT)) and characterize. A coarse-grained discrete molecular dynamics model with realistic steric constraints is constructed to reproduce the experimentally observed two-state folding thermodynamics. A kinetic approach is proposed to identify the folding TSE. A specific set of contacts, common to the TSE conformations, is identified as the folding nuclei which are necessary to be formed in order for the protein to fold. Interestingly, the amino acids at the site of the identified folding nuclei are highly conserved for homologous proteins sharing the same structures. Such conservation suggests that amino acids that are important for folding kinetics are under selective pressure to be preserved during the course of molecular evolution. In addition, studies of the conformations close to the transition states uncover the importance of topology in the construction of order parameter for protein folding transition. Misfolded proteins often form insoluble aggregates, amyloid fibrils, that deposit in the extracellular space and lead to a type of disease known as amyloidosis. Due to its insoluble and non-crystalline nature, the aggregation structure and, thus the aggregation mechanism, has yet to be uncovered. Discrete molecular dynamics studies reveal an aggregate structure with the same structural signatures as in experimental observations and show a nucleation aggregation scenario. The simulations also suggest a generic aggregation mechanism

  6. Modeling and Bio molecular Self-assembly via Molecular Dynamics and Dissipative Particle Dynamics

    NASA Astrophysics Data System (ADS)

    Rakesh, L.

    2009-09-01

    Surfactants like materials can be used to increase the solubility of poorly soluble drugs in water and to increase drug bioavailability. A typical case study will be demonstrated using DPD simulation to model the distribution of anti-inflammatory drug molecules. Computer simulation is a convenient approach to understand drug distribution and solubility concepts without much wastage and costly experiments in the laboratory. Often in molecular dynamics (MD) the atoms are represented explicitly and the equation of motion as described by Newtonian dynamics is integrated explicitly. MD has been used to study spontaneous formation of micelles by hydrophobic molecules with amphiphilic head groups in bulk water, as well as stability of pre-configured micelles and membranes. DPD is a state-of the- art mesoscale simulation, it is a more recent molecular dynamics technique, originally developed for simulating complex fluids but lately also applied to membrane dynamics, hemodynamic in biomedical applications. Such fluids pervade industrial research from paints to pharmaceuticals and from cosmetics to the controlled release of drugs. Dissipative particle dynamics (DPD) can provide structural and dynamic properties of fluids in equilibrium, under shear or confined to narrow cavities, at length- and time-scales beyond the scope of traditional atomistic molecular dynamics simulation methods. Mesoscopic particles are used to represent clusters of molecules. The interaction conserves mass and momentum and as a consequence the dynamics is consistent with Navier-Stokes equations. In addition to the conservative forces, stochastic drive and dissipation is introduced to represent internal degrees of freedom in the mesoscopic particles. In this research, an initial study is being conducted using the aqueous solubilization of the nonsteroidal, anti-inflammatory drug is studied theoretically in micellar solution of nonionic (dodecyl hexa(ethylene oxide), C12E6) surfactants possessing the

  7. Thermal transpiration: A molecular dynamics study

    NASA Astrophysics Data System (ADS)

    T, Joe Francis; Sathian, Sarith P.

    2014-12-01

    Thermal transpiration is a phenomenon where fluid molecules move from the cold end towards the hot end of a channel under the influence of longitudinal temperature gradient alone. Although the phenomenon of thermal transpiration is observed at rarefied gas conditions in macro systems, the phenomenon can occur at atmospheric pressure if the characteristic dimensions of the channel is less than 100 nm. The flow through these nanosized channels is characterized by the free molecular flow regimes and continuum theory is inadequate to describe the flow. Thus a non-continuum method like molecular dynamics (MD) is necessary to study such phenomenon. In the present work, MD simulations were carried out to investigate the occurance of thermal transpiration in copper and platinum nanochannels at atmospheric pressure conditions. The mean pressure of argon gas confined inside the nano channels was maintained around 1 bar. The channel height is maintained at 2nm. The argon atoms interact with each other and with the wall atoms through the Lennard-Jones potential. The wall atoms are modelled using an EAM potential. Further, separate simulations were carried out where a Harmonic potential is used for the atom-atom interaction in the platinum channel. A thermally insulating wall was introduced between the low and high temperature regions and those wall atoms interact with fluid atoms through a repulsive potential. A reduced cut off radius were used to achieve this. Thermal creep is induced by applying a temperature gradient along the channel wall. It was found that flow developed in the direction of the increasing temperature gradient of the wall. An increase in the volumetric flux was observed as the length of the cold and the hot regions of the wall were increased. The effect of temperature gradient and the wall-fluid interaction strength on the flow parameters have been studied to understand the phenomenon better.

  8. Thermal transpiration: A molecular dynamics study

    SciTech Connect

    T, Joe Francis; Sathian, Sarith P.

    2014-12-09

    Thermal transpiration is a phenomenon where fluid molecules move from the cold end towards the hot end of a channel under the influence of longitudinal temperature gradient alone. Although the phenomenon of thermal transpiration is observed at rarefied gas conditions in macro systems, the phenomenon can occur at atmospheric pressure if the characteristic dimensions of the channel is less than 100 nm. The flow through these nanosized channels is characterized by the free molecular flow regimes and continuum theory is inadequate to describe the flow. Thus a non-continuum method like molecular dynamics (MD) is necessary to study such phenomenon. In the present work, MD simulations were carried out to investigate the occurance of thermal transpiration in copper and platinum nanochannels at atmospheric pressure conditions. The mean pressure of argon gas confined inside the nano channels was maintained around 1 bar. The channel height is maintained at 2nm. The argon atoms interact with each other and with the wall atoms through the Lennard-Jones potential. The wall atoms are modelled using an EAM potential. Further, separate simulations were carried out where a Harmonic potential is used for the atom-atom interaction in the platinum channel. A thermally insulating wall was introduced between the low and high temperature regions and those wall atoms interact with fluid atoms through a repulsive potential. A reduced cut off radius were used to achieve this. Thermal creep is induced by applying a temperature gradient along the channel wall. It was found that flow developed in the direction of the increasing temperature gradient of the wall. An increase in the volumetric flux was observed as the length of the cold and the hot regions of the wall were increased. The effect of temperature gradient and the wall-fluid interaction strength on the flow parameters have been studied to understand the phenomenon better.

  9. Nanoscale deicing by molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Xiao, Senbo; He, Jianying; Zhang, Zhiliang

    2016-07-01

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

  10. How Dynamic Visualization Technology Can Support Molecular Reasoning

    ERIC Educational Resources Information Center

    Levy, Dalit

    2013-01-01

    This paper reports the results of a study aimed at exploring the advantages of dynamic visualization for the development of better understanding of molecular processes. We designed a technology-enhanced curriculum module in which high school chemistry students conduct virtual experiments with dynamic molecular visualizations of solid, liquid, and…

  11. Dissecting the molecular origins of specific protein-nucleic acid recognition: hydrostatic pressure and molecular dynamics.

    PubMed Central

    Lynch, Thomas W; Kosztin, Dorina; McLean, Mark A; Schulten, Klaus; Sligar, Stephen G

    2002-01-01

    The fundamental processes by which proteins recognize and bind to nucleic acids are critical to understanding cellular function. To explore the factors involved in protein-DNA recognition, we used hydrostatic pressure to perturb the binding of the BamHI endonuclease to cognate DNA, both in experiment and in molecular dynamic simulations. A new technique of high-pressure gel mobility shift analysis was used to test the effects of elevated hydrostatic pressure on the binding of BamHI to its cognate recognition sequence. Upon application of a pressure of 500 bar, the equilibrium dissociation constant of BamHI binding to the cognate site was found to increase nearly 10-fold. A challenge has been to link this type of pure thermodynamic measurement to functional events occurring at the molecular level. Thus, we used molecular dynamic simulations at both ambient and elevated pressures to reveal details of the direct and water-mediated interactions between BamHI and cognate DNA, which allow explanation of the effects of pressure on site-specific protein-DNA binding and complex stability. PMID:11751298

  12. Protons in polar media: An ab initio molecular dynamics study

    NASA Astrophysics Data System (ADS)

    von Rosenvinge, Tycho

    1998-10-01

    The hydrates of hydrogen chloride are ionic crystals that contain hydronium (H3O+). The hydronium in the monohydrate has been reported to be statistically disordered between two possible sites related by inversion symmetry. Ab initio molecular dynamics calculations are presented for the monohydrate, as well as the di-, and tri-hydrates, of hydrogen chloride using the density functional based Car-Parrinello technique. The simulations were carried out with the goal of investigating proton disorder in these crystals. The possible role of nuclear quantum effects has been explored via path integral molecular dynamic simulations. The present results suggest that the proposed disordered sites in the monohydrate are dynamically unstable and therefore unlikely to be responsible for the reported disorder. No useful information was obtained for the dihydrate because the large unit cell leads to difficulties in carrying out the simulations. Nuclear quantum effects are shown to be important for characterizing the proton distributions in the trihydrate. The structure and dynamical behavior of liquid HF with dissolved KF have been investigated using the Car- Parrinello ab initio molecular dynamics scheme. Specifically, a system with stoichiometry KFċ2HF was studied at temperatures of 400K and 1000K. This system, which was started from a phase separated mixture, rapidly formed into solvated potassium ions and HnFn+1/sp- polyfluoride anions with n = 1, 2, 3, and 4. The resulting polyfluoride anions were classified, and their structures and dynamical behavior were compared with the known structures and spectra of crystalline compounds KF/cdot xHF and with theoretical predictions of isolated gas phase species. The present study reveals dramatic frequency shifts in the H atom vibrational modes with variation in the HF coordination number of the polyfluoride anion. In particular the FH wagging motion red shifts while the FH stretch blue shifts as n increases. The present calculations

  13. Rempi Studies of Molecular Reaction Dynamics.

    NASA Astrophysics Data System (ADS)

    Black, John Forbes

    Available from UMI in association with The British Library. Requires signed TDF. Resonance-Enhanced Multi-Photon Ionisation (REMPI qv.) is used to prepare and probe systems undergoing unimolecular decomposition. It is shown that the highly efficient state selective nature of the REMPI process is well suited to both highly dynamical situations such as the "A-Band" dissociation of MeI at around 280nm and to the slower "Quasi-statistical" dissociations of the mainifold of states of the MeI(+) cation. In the study of the neutral dissociation we attempt to extract the population distributions of the quantum states "by implication" as has been done previously. We demonstrate the failings of the time-of-flight technique in being unable to do this effectively. A comparison with previous studies is made. We report the first rotationally resolved spectrum of a polyatomic (N atoms > 2) photofragment (Me from the "A-Band" photodissociation of MeI) and propose a mechanism to account for the observed differences of the rotational populations in the different dissociation channels. Two-photon linestrength theory incorporating alignment effects is extended to symmetric tops to analyse the data. The pre-dissociation dynamics of a high lying Rydberg state of the methyl radical have been extracted as part of a spectroscopic study performed on CH _3 and CD_3. The dynamics are compared to existing studies on the near-neighbours NH_3 and ND_3 with some apparent correlation. In the dissociations of the A and B states of the MeI(+) cation we are able to provide some more evidence for existing ideas that the A state dissociates by rapid inter-conversion to highly excited levels of the ground state whereas the B state dissociates in a more direct manner. We identify two existing features in the REMPI spectrum of MeI in the "A-Band" region as molecular Rydberg resonances and show that an interesting competition exists between the direct photodissociation and the "virtual" state involved in

  14. Molecular model and ReaxFF molecular dynamics simulation of coal vitrinite pyrolysis.

    PubMed

    Li, Wu; Zhu, Yan-ming; Wang, Geoff; Wang, Yang; Liu, Yu

    2015-08-01

    Vitrinite in coal, the mainly generating methane maceral, plays an important role in hydrocarbon generation of coal. This study aims at obtaining products formation mechanism of vitrinite pyrolysis, and hence determining the chemical bond, molecular liquefaction activity, and reactions mechanism of methane and C2-4 during pyrolysis. The ReaxFF molecular dynamics (MD) simulation was carried out at temperature of 1500 K in order to investigate the mechanism of vitrinite pyrolysis. Initially, a minimum energy conformational structure model was constrained by a combination of elemental and carbon-13 nuclear magnetic resonance ((13)C NMR) literature data. The model analysis shows the chemical and physical parameters of vitrinite pyrolysis are broadly consistent with the experimental data. Based on the molecular model, ReaxFF MD simulations further provide information of unimolecule such as bond length, and chemical shift, and hence the total population and energy of main products. Molecules bond and pyrolysis fragments, based on active bond analyzed, revealed pyrolysis products of single vitrinite molecule with aliphatic C-C bond, especially ring and chain aliphatic as liquefaction activity. The molecular cell whose density is 0.9 g/cm(3) with lowest energy accords with the experimental density 1.33 g/cm(3). The content of main products after pyrolysis, classifying as CH4, H2O, and H2, was changed along with the increasing temperature. The gas molecule, fragments and generation pathways of CO2, H2, CH4, and C2H6 were also elucidated. These results show agreement with experimental observations, implying that MD simulation can provide reasonable explanation for the reaction processes involved in coal vitrinite pyrolysis. Thus the mechanism of coal hydrocarbon generation was revealed at the molecular level.

  15. Molecular dynamics simulations of unsaturated lipid bilayers

    NASA Astrophysics Data System (ADS)

    Rabinovich, Alexander L.; Balabaev, Nikolay K.

    2001-02-01

    Molecular dynamics simulations were carried out for bilayers of lipid molecules having stearic acid (C18:0) chain in position '3-D' (using the nomenclature of M. Sundaralingam, 1972) and fatty acid chain C18:0, C18:1(omega 9), C18:2(omega 6), C18:3(omega 3), C20:4(omega 6) or C22:6(omega 3) in position '2-D'. To investigate the properties of the bilayers two models were considered. In the first model, the simulation cells of the bilayers consisted of 96 phosphatidylcholine (PC) molecules and 2304 water molecules: 48 lipid molecules per layer and 24 H2O molecules per lipid. The water was modeled by explicit TIP3P water molecules. In the second model, the head group of the lipid molecules was treated as an effective sphere -- diacylglycerolipids (DGs) were considered, the interface of each monolayer was modeled by a flat surface; no water molecules were present explicitly. The bilayers consisted of 48 X 2 equals 96 glycerolipids arranged in a rectangular simulation cell. Various properties of the bilayers -- the C-H bond order parameter -SCH profiles of the hydrocarbon tails, the root-mean-square values of the positional fluctuations of the lipid chain carbons, mass density distributions of lipid molecules and water along the normals were investigated.

  16. Molecular dynamics simulations of unsaturated lipid bilayers

    NASA Astrophysics Data System (ADS)

    Rabinovich, Alexander L.; Balabaev, Nikolay K.

    2000-02-01

    Molecular dynamics simulations were carried out for bilayers of lipid molecules having stearic acid (C18:0) chain in position '3-D' (using the nomenclature of M. Sundaralingam, 1972) and fatty acid chain C18:0, C18:1(omega 9), C18:2(omega 6), C18:3(omega 3), C20:4(omega 6) or C22:6(omega 3) in position '2-D'. To investigate the properties of the bilayers two models were considered. In the first model, the simulation cells of the bilayers consisted of 96 phosphatidylcholine (PC) molecules and 2304 water molecules: 48 lipid molecules per layer and 24 H2O molecules per lipid. The water was modeled by explicit TIP3P water molecules. In the second model, the head group of the lipid molecules was treated as an effective sphere -- diacylglycerolipids (DGs) were considered, the interface of each monolayer was modeled by a flat surface; no water molecules were present explicitly. The bilayers consisted of 48 X 2 equals 96 glycerolipids arranged in a rectangular simulation cell. Various properties of the bilayers -- the C-H bond order parameter -SCH profiles of the hydrocarbon tails, the root-mean-square values of the positional fluctuations of the lipid chain carbons, mass density distributions of lipid molecules and water along the normals were investigated.

  17. Molecular chaperone-mediated nuclear protein dynamics.

    PubMed

    Echtenkamp, Frank J; Freeman, Brian C

    2014-05-01

    Homeostasis requires effective action of numerous biological pathways including those working along a genome. The variety of processes functioning in the nucleus is considerable, yet the number of employed factors eclipses this total. Ideally, individual components assemble into distinct complexes and serially operate along a pathway to perform work. Adding to the complexity is a multitude of fluctuating internal and external signals that must be monitored to initiate, continue or halt individual activities. While cooperative interactions between proteins of the same process provide a mechanism for rapid and precise assembly, the inherent stability of such organized structures interferes with the proper timing of biological events. Further prolonging the longevity of biological complexes are crowding effects resulting from the high concentration of intracellular macromolecules. Hence, accessory proteins are required to destabilize the various assemblies to efficiently transition between structures, avoid off-pathway competitive interactions, and to terminate pathway activity. We suggest that molecular chaperones have evolved, in part, to manage these challenges by fostering a general and continuous dynamic protein environment within the nucleus. PMID:24694369

  18. Molecular chaperone-mediated nuclear protein dynamics.

    PubMed

    Echtenkamp, Frank J; Freeman, Brian C

    2014-05-01

    Homeostasis requires effective action of numerous biological pathways including those working along a genome. The variety of processes functioning in the nucleus is considerable, yet the number of employed factors eclipses this total. Ideally, individual components assemble into distinct complexes and serially operate along a pathway to perform work. Adding to the complexity is a multitude of fluctuating internal and external signals that must be monitored to initiate, continue or halt individual activities. While cooperative interactions between proteins of the same process provide a mechanism for rapid and precise assembly, the inherent stability of such organized structures interferes with the proper timing of biological events. Further prolonging the longevity of biological complexes are crowding effects resulting from the high concentration of intracellular macromolecules. Hence, accessory proteins are required to destabilize the various assemblies to efficiently transition between structures, avoid off-pathway competitive interactions, and to terminate pathway activity. We suggest that molecular chaperones have evolved, in part, to manage these challenges by fostering a general and continuous dynamic protein environment within the nucleus.

  19. Nanoscale deicing by molecular dynamics simulation.

    PubMed

    Xiao, Senbo; He, Jianying; Zhang, Zhiliang

    2016-08-14

    Deicing is important to human activities in low-temperature circumstances, and is critical for combating the damage caused by excessive accumulation of ice. The aim of creating anti-icing materials, surfaces and applications relies on the understanding of fundamental nanoscale ice adhesion mechanics. Here in this study, we employ all-atom modeling and molecular dynamics simulation to investigate ice adhesion. We apply force to detach and shear nano-sized ice cubes for probing the determinants of atomistic adhesion mechanics, and at the same time investigate the mechanical effect of a sandwiched aqueous water layer between ice and substrates. We observe that high interfacial energy restricts ice mobility and increases both ice detaching and shearing stresses. We quantify up to a 60% decrease in ice adhesion strength by an aqueous water layer, and provide atomistic details that support previous experimental studies. Our results contribute quantitative comparison of nanoscale adhesion strength of ice on hydrophobic and hydrophilic surfaces, and supply for the first time theoretical references for understanding the mechanics at the atomistic origins of macroscale ice adhesion. PMID:27431975

  20. Integrating influenza antigenic dynamics with molecular evolution

    PubMed Central

    Bedford, Trevor; Suchard, Marc A; Lemey, Philippe; Dudas, Gytis; Gregory, Victoria; Hay, Alan J; McCauley, John W; Russell, Colin A; Smith, Derek J; Rambaut, Andrew

    2014-01-01

    Influenza viruses undergo continual antigenic evolution allowing mutant viruses to evade host immunity acquired to previous virus strains. Antigenic phenotype is often assessed through pairwise measurement of cross-reactivity between influenza strains using the hemagglutination inhibition (HI) assay. Here, we extend previous approaches to antigenic cartography, and simultaneously characterize antigenic and genetic evolution by modeling the diffusion of antigenic phenotype over a shared virus phylogeny. Using HI data from influenza lineages A/H3N2, A/H1N1, B/Victoria and B/Yamagata, we determine patterns of antigenic drift across viral lineages, showing that A/H3N2 evolves faster and in a more punctuated fashion than other influenza lineages. We also show that year-to-year antigenic drift appears to drive incidence patterns within each influenza lineage. This work makes possible substantial future advances in investigating the dynamics of influenza and other antigenically-variable pathogens by providing a model that intimately combines molecular and antigenic evolution. DOI: http://dx.doi.org/10.7554/eLife.01914.001 PMID:24497547

  1. Molecular Dynamics Simulations of Coulomb Explosion

    SciTech Connect

    Bringa, E M

    2002-05-17

    A swift ion creates a track of electronic excitations in the target material. A net repulsion inside the track can cause a ''Coulomb Explosion'', which can lead to damage and sputtering of the material. Here we report results from molecular-dynamics (MD) simulations of Coulomb explosion for a cylindrical track as a function of charge density and neutralization/quenching time, {tau}. Screening by the free electrons is accounted for using a screened Coulomb potential for the interaction among charges. The yield exhibits a prompt component from the track core and a component, which dominates at higher excitation density, from the heated region produced. For the cases studied, the number of atoms ejected per incident ion, i.e. the sputtering yield Y, is quadratic with charge density along the track as suggested by simple models. Y({tau} = 0.2 Debye periods) is nearly 20% of the yield when there is no neutralization ({tau} {yields} {infinity}). The connections between ''Coulomb explosions'', thermal spikes and measurements of electronic sputtering are discussed.

  2. Fracture simulations via massively parallel molecular dynamics

    SciTech Connect

    Holian, B.L.; Abraham, F.F.; Ravelo, R.

    1993-09-01

    Fracture simulations at the atomistic level have heretofore been carried out for relatively small systems of particles, typically 10,000 or less. In order to study anything approaching a macroscopic system, massively parallel molecular dynamics (MD) must be employed. In two spatial dimensions (2D), it is feasible to simulate a sample that is 0.1 {mu}m on a side. We report on recent MD simulations of mode I crack extension under tensile loading at high strain rates. The method of uniaxial, homogeneously expanding periodic boundary conditions was employed to represent tensile stress conditions near the crack tip. The effects of strain rate, temperature, material properties (equation of state and defect energies), and system size were examined. We found that, in order to mimic a bulk sample, several tricks (in addition to expansion boundary conditions) need to be employed: (1) the sample must be pre-strained to nearly the condition at which the crack will spontaneously open; (2) to relieve the stresses at free surfaces, such as the initial notch, annealing by kinetic-energy quenching must be carried out to prevent unwanted rarefactions; (3) sound waves emitted as the crack tip opens and dislocations emitted from the crack tip during blunting must be absorbed by special reservoir regions. The tricks described briefly in this paper will be especially important to carrying out feasible massively parallel 3D simulations via MD.

  3. Molecular dynamics simulations of gold nanomaterials

    NASA Astrophysics Data System (ADS)

    Wang, Yanting

    We have carried out Molecular Dynamics simulations to study the thermal stability and melting behavior of gold nanoclusters and gold nanorods. The surface is found to play a very important role in both gold nanomaterials. Upon cooling from the liquid, we find that gold nanoclusters with 600-3000 atoms crystallize into a Mackay icosahedron. Upon heating, the {111} facets on the surface of the Mackay icosahedral gold nanoclusters soften but do not premelt below the bulk melting temperature. We attribute this surface softening to the increasing mobility of vertex and edge atoms with temperature, which leads to inter-layer and intra-layer diffusion, and a shrinkage of the average facet size. Upon heating, our simulated gold nanorods undergo a shape transformation preceding the melting transition. The shape transformation is induced by a minimization of the surface free energy, and is accompanied by a complete reconstruction of the internal structure driven by the surface change. During the transformation, the atoms on the end caps of the rod move to the sides of the rods, leading the rods to be shorter and wider. After the transformation, the surface of the stable intermediate state rod is mostly covered by the more stable {111} facets, other than the less stable {110} and {100} facets covering the sides of the initial constructed rod.

  4. Molecular dynamics studies of lanthanum chloride solutions

    SciTech Connect

    Meier, W.; Bopp, Ph. ); Probst, M.M. ); Spohr, E. ); Lin, J.L. )

    1990-05-31

    Molecular dynamics studies are reported for LaCl{sub 3} solutions at two different concentrations and temperatures, and for isolated aqueous La{sup 3+} ions. Ion-water clusters La(H{sub 2}O){sub n}{sup 3+} with n = 61 and n = 100 and systems consisting of one ion and 100 or 200 water molecules in the usual periodic box, as well as solutions of 7 (4) cations and 21 (12) anions in 190 (200) water molecules, corresponding to 2 and 1.1 m solutions, respectively, were investigated. The 2 m solution was investigated at two different temperatures. The results for the static structure, with special emphasis on the hydration structure of the La{sup 3+} ion, are discussed in terms of radial distribution functions and resulting hydration numbers, and various other correlations. These results are compared with X-ray data and discussed in light of the hydration numbers observed for aqueous ions in general.

  5. Efficient compression of molecular dynamics trajectory files.

    PubMed

    Marais, Patrick; Kenwood, Julian; Smith, Keegan Carruthers; Kuttel, Michelle M; Gain, James

    2012-10-15

    We investigate whether specific properties of molecular dynamics trajectory files can be exploited to achieve effective file compression. We explore two classes of lossy, quantized compression scheme: "interframe" predictors, which exploit temporal coherence between successive frames in a simulation, and more complex "intraframe" schemes, which compress each frame independently. Our interframe predictors are fast, memory-efficient and well suited to on-the-fly compression of massive simulation data sets, and significantly outperform the benchmark BZip2 application. Our schemes are configurable: atomic positional accuracy can be sacrificed to achieve greater compression. For high fidelity compression, our linear interframe predictor gives the best results at very little computational cost: at moderate levels of approximation (12-bit quantization, maximum error ≈ 10(-2) Å), we can compress a 1-2 fs trajectory file to 5-8% of its original size. For 200 fs time steps-typically used in fine grained water diffusion experiments-we can compress files to ~25% of their input size, still substantially better than BZip2. While compression performance degrades with high levels of quantization, the simulation error is typically much greater than the associated approximation error in such cases.

  6. Quantum molecular dynamics simulations of dense matter

    SciTech Connect

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

    1997-12-31

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

  7. Extended Lagrangian Born-Oppenheimer molecular dynamics simulations of the shock-induced chemistry of phenylacetylene

    SciTech Connect

    Cawkwell, M. J. Niklasson, Anders M. N.; Dattelbaum, Dana M.

    2015-02-14

    The initial chemical events that occur during the shock compression of liquid phenylacetylene have been investigated using self-consistent tight binding molecular dynamics simulations. The extended Lagrangian Born-Oppenheimer molecular dynamics formalism enabled us to compute microcanonical trajectories with precise conservation of the total energy. Our simulations revealed that the first density-increasing step under shock compression arises from the polymerization of phenylacetylene molecules at the acetylene moiety. The application of electronic structure-based molecular dynamics with long-term conservation of the total energy enabled us to identify electronic signatures of reactivity via monitoring changes in the HOMO-LUMO gap, and to capture directly adiabatic shock heating, transient non-equilibrium states, and changes in temperature arising from exothermic chemistry in classical molecular dynamics trajectories.

  8. Molecular Dynamics Study of Polyethylene under Extreme Confinement

    NASA Astrophysics Data System (ADS)

    Kritikos, G.; Sgouros, A.; Vogiatzis, G. G.; Theodorou, D. N.

    2016-08-01

    We present results concerning the dynamics and the structure of adsorbed layers of molten polyethylene (PE) between two graphite surfaces. The molecular weight of the monodisperse PE chains reaches the entanglement regime. We study three cases of interwall distances, equal to two, three and four times the unperturbed radius of gyration (Rg ) of PE chains. The confined system is equilibrated by use of efficient Monte Carlo (MC) algorithms. Conducting molecular dynamics (MD) simulations, we reveal the distribution of relaxation times as a function of distance from the graphite walls at the temperature of 450 K. From the atomic-level stresses we calculate a realistic estimate of the adhesion tension, which is not affected significantly by the width of the pore. Although the distance between the two walls is comparable to the width of the adsorbed layer, we do not record the formation of ‘glassy bridges’ under the studied conditions. The diffusion of polymer chains in the middle layer is not inhibited by the existence of the two adsorbed layers. Extreme confinement conditions imposed by the long range wall potentials bring about an increase in both the adsorption and desorption rates of chains. The presented results seem to cohere with a reduction in the calorimetric (heat capacity step) glass transition temperature (Tg ).

  9. Molecular dynamics in cytochrome c oxidase Moessbauer spectra deconvolution

    SciTech Connect

    Bossis, Fabrizio; Palese, Luigi L.

    2011-01-07

    Research highlights: {yields} Cytochrome c oxidase molecular dynamics serve to predict Moessbauer lineshape widths. {yields} Half height widths are used in modeling of Lorentzian doublets. {yields} Such spectral deconvolutions are useful in detecting the enzyme intermediates. -- Abstract: In this work low temperature molecular dynamics simulations of cytochrome c oxidase are used to predict an experimentally observable, namely Moessbauer spectra width. Predicted lineshapes are used to model Lorentzian doublets, with which published cytochrome c oxidase Moessbauer spectra were simulated. Molecular dynamics imposed constraints to spectral lineshapes permit to obtain useful information, like the presence of multiple chemical species in the binuclear center of cytochrome c oxidase. Moreover, a benchmark of quality for molecular dynamic simulations can be obtained. Despite the overwhelming importance of dynamics in electron-proton transfer systems, limited work has been devoted to unravel how much realistic are molecular dynamics simulations results. In this work, molecular dynamics based predictions are found to be in good agreement with published experimental spectra, showing that we can confidently rely on actual simulations. Molecular dynamics based deconvolution of Moessbauer spectra will lead to a renewed interest for application of this approach in bioenergetics.

  10. Endogenous molecular network reveals two mechanisms of heterogeneity within gastric cancer

    PubMed Central

    Li, Site; Zhu, Xiaomei; Liu, Bingya; Wang, Gaowei; Ao, Ping

    2015-01-01

    Intratumor heterogeneity is a common phenomenon and impedes cancer therapy and research. Gastric cancer (GC) cells have generally been classified into two heterogeneous cellular phenotypes, the gastric and intestinal types, yet the mechanisms of maintaining two phenotypes and controlling phenotypic transition are largely unknown. A qualitative systematic framework, the endogenous molecular network hypothesis, has recently been proposed to understand cancer genesis and progression. Here, a minimal network corresponding to such framework was found for GC and was quantified via a stochastic nonlinear dynamical system. We then further extended the framework to address the important question of intratumor heterogeneity quantitatively. The working network characterized main known features of normal gastric epithelial and GC cell phenotypes. Our results demonstrated that four positive feedback loops in the network are critical for GC cell phenotypes. Moreover, two mechanisms that contribute to GC cell heterogeneity were identified: particular positive feedback loops are responsible for the maintenance of intestinal and gastric phenotypes; GC cell progression routes that were revealed by the dynamical behaviors of individual key components are heterogeneous. In this work, we constructed an endogenous molecular network of GC that can be expanded in the future and would broaden the known mechanisms of intratumor heterogeneity. PMID:25962957

  11. Photodissociation of laboratory oriented molecules: Revealing molecular frame properties of nonaxial recoil

    SciTech Connect

    Brom, Alrik J. van den; Rakitzis, T. Peter; Janssen, Maurice H.M.

    2004-12-15

    We report the photodissociation of laboratory oriented OCS molecules. A molecular beam of OCS molecules is hexapole state-selected and spatially oriented in the electric field of a velocity map imaging lens. The oriented OCS molecules are dissociated at 230 nm with the linear polarization set at 45 deg. to the orientation direction of the OCS molecules. The CO({nu}=0,J) photofragments are quantum state-selectively ionized by the same 230 nm pulse and the angular distribution is measured using the velocity map imaging technique. The observed CO({nu}=0,J) images are strongly asymmetric and the degree of asymmetry varies with the CO rotational state J. From the observed asymmetry in the laboratory frame we can directly extract the molecular frame angles between the final photofragment recoil velocity and the permanent dipole moment and the transition dipole moment. The data for CO fragments with high rotational excitation reveal that the dissociation dynamics is highly nonaxial, even though conventional wisdom suggests that the nearly limiting {beta} parameter results from fast axial recoil dynamics. From our data we can extract the relative contribution of parallel and perpendicular transitions at 230 nm excitation.

  12. Combined molecular dynamics-spin dynamics simulations of bcc iron

    SciTech Connect

    Perera, Meewanage Dilina N; Yin, Junqi; Landau, David P; Nicholson, Don M; Stocks, George Malcolm; Eisenbach, Markus; Brown, Greg

    2014-01-01

    Using a classical model that treats translational and spin degrees of freedom on an equal footing, we study phonon-magnon interactions in BCC iron with combined molecular and spin dynamics methods. The atomic interactions are modeled via an empirical many-body potential while spin dependent interactions are established through a Hamiltonian of the Heisenberg form with a distance dependent magnetic exchange interaction obtained from first principles electronic structure calculations. The temporal evolution of translational and spin degrees of freedom was determined by numerically solving the coupled equations of motion, using an algorithm based on the second order Suzuki-Trotter decomposition of the exponential operators. By calculating Fourier transforms of space- and time-displaced correlation functions, we demonstrate that the the presence of lattice vibrations leads to noticeable softening and damping of spin wave modes. As a result of the interplay between lattice and spin subsystems, we also observe additional longitudinal spin wave excitations, with frequencies which coincide with that of the longitudinal lattice vibrations.

  13. Direct molecular dynamics observation of protein folding transition state ensemble.

    PubMed Central

    Ding, Feng; Dokholyan, Nikolay V; Buldyrev, Sergey V; Stanley, H Eugene; Shakhnovich, Eugene I

    2002-01-01

    The concept of the protein transition state ensemble (TSE), a collection of the conformations that have 50% probability to convert rapidly to the folded state and 50% chance to rapidly unfold, constitutes the basis of the modern interpretation of protein engineering experiments. It has been conjectured that conformations constituting the TSE in many proteins are the expanded and distorted forms of the native state built around a specific folding nucleus. This view has been supported by a number of on-lattice and off-lattice simulations. Here we report a direct observation and characterization of the TSE by molecular dynamic folding simulations of the C-Src SH3 domain, a small protein that has been extensively studied experimentally. Our analysis reveals a set of key interactions between residues, conserved by evolution, that must be formed to enter the kinetic basin of attraction of the native state. PMID:12496119

  14. Molecular Dynamics Simulation of Iron — A Review

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  15. Vibrational and ab initio molecular dynamics studies of bradykinin

    NASA Astrophysics Data System (ADS)

    Święch, Dominika; Kubisiak, Piotr; Andrzejak, Marcin; Borowski, Piotr; Proniewicz, Edyta

    2016-07-01

    In this study, the comprehensive theoretical and experimental investigations of Raman (RS) and infrared absorption (IR) spectra of bradykinin (BK) are presented. The ab initio Born-Oppenheimer molecular dynamics (BOMD) calculations, in the presence of water molecules that form the first coordination sphere, were used for conformational analysis of the BK structure. Based on the Density Functional Theory (DFT) calculations at the B3LYP/6-311G(d) level the vibrational spectra were interpreted. The calculated frequencies were scaled by means of the effective scaling frequency factor (ESFF) method. The theoretical data, which confirm the compact structure of BK in the presence of the water molecules revealed the remarkable effect of the intermolecular hydrogen bonding on the BK structural properties.

  16. Molecular dynamics of biaxial nematic liquid crystals

    NASA Astrophysics Data System (ADS)

    Sarman, Sten

    1996-01-01

    We devise a constraint algorithm that makes the angular velocity of the director of a liquid crystal a constant of motion. When the angular velocity is set equal to zero, a director based coordinate system becomes an inertial frame. This is a great advantage because most thermodynamic properties and time correlation functions of a liquid crystal are best expressed relative to a director based coordinate system. One also prevents the director reorientation from interfering with the tails of the time correlation functions. When the angular velocity is forced to be zero the constraints do not do any work on the system. This makes it possible to prove that ensemble averages of phase functions and time correlation functions are unaffected by the director constraint torques. The constraint algorithm also facilitates generalization of nonequilibrium molecular dynamics algorithms to liquid crystal phases. In order to test the algorithm numerically we have simulated a biaxial nematic phase of a variant of the Gay-Berne fluid [J. G. Gay and B. J. Berne, J. Chem. Phys. 74, 3316 (1981)]. The director constraint algorithm works very well. We have calculated the velocity autocorrelation functions and the self diffusion coefficients. In a biaxial nematic liquid crystal there are three independent components of the self-diffusion tensor. They have been found to be finite and different thus proving that we really simulate a liquid rather than a solid and that the symmetry is biaxial. Simulation of biaxial liquid crystals requires fairly large systems. We have therefore developed an algorithm that we run on a parallel computer instead of an ordinary work station.

  17. Ribosomal Dynamics: Intrinsic Instability of a Molecular Machine

    NASA Astrophysics Data System (ADS)

    Gao, Haixiao; Le Barron, Jamie; Frank, Joachim

    Ribosomes are molecular machines that translate genetic message into nascent peptides, through a complex dynamics interplay with mRNAs, tRNAs, and various protein factors. A prominent example of ribosomal dynamics is the rotation of small ribosomal subunit with respect to a large subunit, characterized as the "ratchet motion," which is triggered by the binding of several translation factors. Here, we analyze two kinds of ribosomal ratchet motions, induced by the binding of EF-G and RF3, respectively, as previously observed by cryo-electron microscopy. Using the flexible fitting technique (real-space refinement) and an RNA secondary structure display tool (coloRNA), we obtained quasi-atomic models of the ribosome in these ratchet-motion-related functional states and mapped the observed differences onto the highly conserved RNA secondary structure. Comparisons between two sets of ratchet motions revealed that, while the overall patterns of the RNA displacement are very similar, several local regions stand out in their differential behavior, including the highly conserved GAC (GTPase-associated-center) region. We postulate that these regions are important in modulating general ratchet motion and bestowing it with the dynamic characteristics required for the specific function.

  18. Probing ultrafast electronic and molecular dynamics with free-electron lasers

    NASA Astrophysics Data System (ADS)

    Fang, L.; Osipov, T.; Murphy, B. F.; Rudenko, A.; Rolles, D.; Petrovic, V. S.; Bostedt, C.; Bozek, J. D.; Bucksbaum, P. H.; Berrah, N.

    2014-06-01

    Molecular dynamics is an active area of research, focusing on revealing fundamental information on molecular structures and photon-molecule interaction and with broad impacts in chemical and biological sciences. Experimental investigation of molecular dynamics has been advanced by the development of new light sources and techniques, deepening our understanding of natural processes and enabling possible control and modification of chemical and biomolecular processes. Free-electron lasers (FELs) deliver unprecedented intense and short photon pulses in the vacuum ultraviolet and x-ray spectral ranges, opening a new era for the study of electronic and nuclear dynamics in molecules. This review focuses on recent molecular dynamics investigations using FELs. We present recent work concerning dynamics of molecular interaction with FELs using an intrinsic clock within a single x-ray pulse as well as using an external clock in a pump-probe scheme. We review the latest developments on correlated and coincident spectroscopy in FEL-based research and recent results revealing photo-induced interaction dynamics using these techniques. We also describe new instrumentations to conduct x-ray pump-x-ray probe experiments with spectroscopy and imaging detectors.

  19. Molecular analysis of Baylisascaris columnaris revealed mitochondrial and nuclear polymorphisms

    PubMed Central

    2013-01-01

    Background Baylisascaris species are intestinal nematodes of skunks, raccoons, badgers, and bears belonging to the genus Ascarididae. Oral uptake of embryonated Baylisascaris sp. eggs by a wide variety of mammals and birds can lead to visceral, ocular and neurological larva migrans. B. procyonis, the raccoon roundworm, is known to cause severe illness in intermediate hosts and in humans, whereas the skunk roundworm B. columnaris is probably less pathogenic. Skunks and raccoons are kept as pets in Europe, sometimes together with cats and dogs, living in close contact with humans. B. procyonis and B. columnaris are difficult to differentiate based on morphological criteria and molecular and phylogenetic information concerning B. columnaris is missing. This is the first study on the genetic characterisation of B. columnaris, based on mitochondrial and nuclear molecular markers. Methods B. columnaris worms were isolated from pet skunks, and used for molecular analysis. PCR primers targeted at mitochondrial cytochrome c oxidase 1 and 2 (CO1 and CO2), ribosomal ITS1-5.8S-ITS2 and ribosomal 28S genes were used. DNA sequences from B. columnaris, B. procyonis and B. transfuga from bears were analysed by cluster analysis. Results Four different multi-locus genotypes were found in B. columnaris, based on 14 single nucleotide polymorphisms (SNPs) and two insertions / deletions in CO1, CO2, ITS1-5.8S-ITS2 and 28S. Conclusions The genetic characteristics of B. columnaris show close resemblance to those of B. procyonis, but in contrast to B. procyonis, show several polymorphisms in both mitochondrial and nuclear markers. These polymorphisms could be used as a tool to differentiate B. columnaris from B. procyonis in molecular diagnostic assays, and to identify B. columnaris by PCR, in addition to or replacing morphometric analysis. This might lead to more insight into the zoonotic relevance of B. columnaris in humans. PMID:23627901

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

    PubMed Central

    Chang, Le; Takada, Shoji

    2016-01-01

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

  1. The study of dynamics heterogeneity and slow down of silica by molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    San, L. T.; Hung, P. K.; Hue, H. V.

    2016-06-01

    We have numerically studied the diffusion in silica liquids via the SiOx → SiOx±1, OSiy → OSiy±1 reactions and coordination cells (CC). Five models with temperatures from 1000 to 3500 K have been constructed by molecular dynamics simulation. We reveal that the reactions happen not randomly in the space. In addition, the reactions correlated strongly with the mobility of CC atom. Further we examine the clustering of atoms having unbroken bonds and restored bonds. The time evolution of these clusters under temperature is also considered. The simulation shows that both slow down and dynamic heterogeneity (DH) is related not only to the percolation of restored-rigid clusters near glass transition but also to their long lifetime.

  2. Dynamics of rhenium photocatalysts revealed through ultrafast multidimensional spectroscopy.

    PubMed

    Kiefer, Laura M; King, John T; Kubarych, Kevin J

    2015-04-21

    Rhenium catalysts have shown promise to promote carbon neutrality by reducing a prominent greenhouse gas, CO2, to CO and other starting materials. Much research has focused on identifying intermediates in the photocatalysis mechanism as well as time scales of relevant ultrafast processes. Recent studies have implemented multidimensional spectroscopies to characterize the catalyst's ultrafast dynamics as it undergoes the many steps of its photocycle. Two-dimensional infrared (2D-IR) spectroscopy is a powerful method to obtain molecular structure information while extracting time scales of dynamical processes with ultrafast resolution. Many observables result from 2D-IR experiments including vibrational lifetimes, intramolecular redistribution time scales, and, unique to 2D-IR, spectral diffusion, which is highly sensitive to solute-solvent interactions and motional dynamics. Spectral diffusion, a measure of how long a vibrational mode takes to sample its frequency space due to multiple solvent configurations, has various contributing factors. Properties of the solvent, the solute's structural flexibility, and electronic properties, as well as interactions between the solvent and solute, complicate identifying the origin of the spectral diffusion. With carefully chosen experiments, however, the source of the spectral diffusion can be unveiled. Within the context of a considerable body of previous work, here we discuss the spectral diffusion of several rhenium catalysts at multiple stages in the catalysis. These studies were performed in multiple polar liquids to aid in discovering the contributions of the solvent. We also performed electronic ground state 2D-IR and electronic excited state transient-2D-IR experiments to observe how spectral diffusion changes upon electronic excitation. Our results indicate that with the original Lehn catalyst in THF, relative to the ground state, the spectral diffusion slows by a factor of 3 in the equilibrated triplet metal

  3. Nullspace Sampling with Holonomic Constraints Reveals Molecular Mechanisms of Protein Gαs

    PubMed Central

    Pachov, Dimitar V.; van den Bedem, Henry

    2015-01-01

    Proteins perform their function or interact with partners by exchanging between conformational substates on a wide range of spatiotemporal scales. Structurally characterizing these exchanges is challenging, both experimentally and computationally. Large, diffusional motions are often on timescales that are difficult to access with molecular dynamics simulations, especially for large proteins and their complexes. The low frequency modes of normal mode analysis (NMA) report on molecular fluctuations associated with biological activity. However, NMA is limited to a second order expansion about a minimum of the potential energy function, which limits opportunities to observe diffusional motions. By contrast, kino-geometric conformational sampling (KGS) permits large perturbations while maintaining the exact geometry of explicit conformational constraints, such as hydrogen bonds. Here, we extend KGS and show that a conformational ensemble of the α subunit Gαs of heterotrimeric stimulatory protein Gs exhibits structural features implicated in its activation pathway. Activation of protein Gs by G protein-coupled receptors (GPCRs) is associated with GDP release and large conformational changes of its α-helical domain. Our method reveals a coupled α-helical domain opening motion while, simultaneously, Gαs helix α5 samples an activated conformation. These motions are moderated in the activated state. The motion centers on a dynamic hub near the nucleotide-binding site of Gαs, and radiates to helix α4. We find that comparative NMA-based ensembles underestimate the amplitudes of the motion. Additionally, the ensembles fall short in predicting the accepted direction of the full activation pathway. Taken together, our findings suggest that nullspace sampling with explicit, holonomic constraints yields ensembles that illuminate molecular mechanisms involved in GDP release and protein Gs activation, and further establish conformational coupling between key structural

  4. Intravital imaging technology reveals immune system dynamics in vivo.

    PubMed

    Ishii, Masaru

    2016-07-01

    Fluorescent 'intravital' imaging is a new research technique by which the interior of living tissues and organs (in living bodies, if possible) can be observed, revealing the kinetics of cell and molecular processes in real time. Recent technological innovations in optical equipment and fluorescence imaging techniques have enabled a variety of cellular phenomena in different tissues and organs to be characterized under completely native conditions. This shift from static to dynamic biology constitutes the beginning of a new era in biomedical sciences. PMID:27238377

  5. Temperature dependent dynamics of DegP-trimer: A molecular dynamics study

    PubMed Central

    Rai, Nivedita; Ramaswamy, Amutha

    2015-01-01

    DegP is a heat shock protein from high temperature requirement protease A family, which reacts to the environmental stress conditions in an ATP independent way. The objective of the present analysis emerged from the temperature dependent functional diversity of DegP between chaperonic and protease activities at temperatures below and above 28 °C, respectively. DegP is a multimeric protein and the minimal functional unit, DegP-trimer, is of great importance in understanding the DegP pathway. The structural aspects of DegP-trimer with respect to temperature variation have been studied using molecular dynamics simulations (for 100 ns) and principal component analysis to highlight the temperature dependent dynamics facilitating its functional diversity. The DegP-trimer revealed a pronounced dynamics at both 280 and 320 K, when compared to the dynamics observed at 300 K. The LA loop is identified as the highly flexible region during dynamics and at extreme temperatures, the residues 46–80 of LA loop express a flip towards right (at 280) and left ( at 320 K) with respect to the fixed β-sheet connecting the LA loop of protease for which Phe46 acts as one of the key residues. Such dynamics of LA loop facilitates inter-monomeric interaction with the PDZ1 domain of the neighbouring monomer and explains its active participation when DegP exists as trimer. Hence, the LA loop mediated dynamics of DegP-trimer is expected to provide further insight into the temperature dependent dynamics of DegP towards the understanding of its assembly and functional diversity in the presence of substrate. PMID:25987966

  6. Proton Transfer Dynamics in Crystalline Maleic Acid from Molecular Dynamics Calculations.

    PubMed

    Dopieralski, Przemyslaw D; Latajka, Zdzislaw; Olovsson, Ivar

    2010-05-11

    The crystal structure of maleic acid, the cis conformer of HOOC-CH═CH-COOH has been investigated by Car-Parrinello molecular dynamics (CPMD) and path integral molecular dynamics (PIMD) simulations. The interesting feature of this compound, compared to the trans conformer, fumaric acid, is that both intra- and intermolecular hydrogen bonds are present. CPMD simulations at 100 K indicate that the energy barrier height for proton transfer is too high for thermal jumps over the barrier in both the intra- and intermolecular hydrogen bonds. Dynamics at 295 K reveal that the occupancy ratio of the proton distribution in both the intra- and intermolecular hydrogen bonds is 0.96/0.04. The time lag between the proton transfers in the intra- and intermolecular hydrogen bonds is in the range of 2-9 fs. This is slightly shorter than the time lag obtained previously for fumaric acid, where only intermolecular hydrogen bonds are present. It is also interesting to notice that in most cases the proton transfer process starts in the intramolecular hydrogen bond and subsequently follows in the intermolecular hydrogen bond. Vibrational spectra of the investigated system and its deuterated analogs HOOC-CH═CH-COOD and DOOC-CH═CH-COOD have been calculated and compared with experimental data. PMID:26615682

  7. Molecular dynamics simulation of liquid water confined inside graphite channels: dielectric and dynamical properties.

    PubMed

    Martí, J; Nagy, G; Guàrdia, E; Gordillo, M C

    2006-11-30

    Electric and dielectric properties and microscopic dynamics of liquid water confined between graphite slabs are analyzed by means of molecular dynamics simulations for several graphite-graphite separations at ambient conditions. The electric potential across the interface shows oscillations due to water layering, and the overall potential drop is about -0.28 V. The total dielectric constant is larger than the corresponding value for the bulklike internal region of the system. This is mainly due to the preferential orientations of water nearest the graphite walls. Estimation of the capacitance of the system is reported, indicating large variations for the different adsorption layers. The main trend observed concerning water diffusion is 2-fold: on one hand, the overall diffusion of water is markedly smaller for the closest graphite-graphite separations, and on the other hand, water molecules diffuse in interfaces slightly slower than those in the bulklike internal areas. Molecular reorientational times are generally larger than those corresponding to those of unconstrained bulk water. The analysis of spectral densities revealed significant spectral shifts, compared to the bands in unconstrained water, in different frequency regions, and associated to confinement effects. These findings are important because of the scarce information available from experimental, theoretical, and computer simulation research into the dielectric and dynamical properties of confined water.

  8. 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

  9. Las Palmeras Molecular Dynamics: A flexible and modular molecular dynamics code

    NASA Astrophysics Data System (ADS)

    Davis, Sergio; Loyola, Claudia; González, Felipe; Peralta, Joaquín

    2010-12-01

    Las Palmeras Molecular Dynamics (LPMD) is a highly modular and extensible molecular dynamics (MD) code using interatomic potential functions. LPMD is able to perform equilibrium MD simulations of bulk crystalline solids, amorphous solids and liquids, as well as non-equilibrium MD (NEMD) simulations such as shock wave propagation, projectile impacts, cluster collisions, shearing, deformation under load, heat conduction, heterogeneous melting, among others, which involve unusual MD features like non-moving atoms and walls, unstoppable atoms with constant-velocity, and external forces like electric fields. LPMD is written in C++ as a compromise between efficiency and clarity of design, and its architecture is based on separate components or plug-ins, implemented as modules which are loaded on demand at runtime. The advantage of this architecture is the ability to completely link together the desired components involved in the simulation in different ways at runtime, using a user-friendly control file language which describes the simulation work-flow. As an added bonus, the plug-in API (Application Programming Interface) makes it possible to use the LPMD components to analyze data coming from other simulation packages, convert between input file formats, apply different transformations to saved MD atomic trajectories, and visualize dynamical processes either in real-time or as a post-processing step. Individual components, such as a new potential function, a new integrator, a new file format, new properties to calculate, new real-time visualizers, and even a new algorithm for handling neighbor lists can be easily coded, compiled and tested within LPMD by virtue of its object-oriented API, without the need to modify the rest of the code. LPMD includes already several pair potential functions such as Lennard-Jones, Morse, Buckingham, MCY and the harmonic potential, as well as embedded-atom model (EAM) functions such as the Sutton-Chen and Gupta potentials. Integrators to

  10. The Molecular Structure of a Phosphatidylserine Bilayer Determined by Scattering and Molecular Dynamics Simulations

    SciTech Connect

    Pan, Jianjun; Cheng, Xiaolin; Monticelli, Luca; Heberle, Frederick A; Kucerka, Norbert; Tieleman, D. Peter; Katsaras, John

    2014-01-01

    Phosphatidylserine (PS) lipids play essential roles in biological processes, including enzyme activation and apoptosis. We report on the molecular structure and atomic scale interactions of a fluid bilayer composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylserine (POPS). A scattering density profile model, aided by molecular dynamics (MD) simulations, was developed to jointly refine different contrast small-angle neutron and X-ray scattering data, which yielded a lipid area of 62.7 A2 at 25 C. MD simulations with POPS lipid area constrained at different values were also performed using all-atom and aliphatic united-atom models. The optimal simulated bilayer was obtained using a model-free comparison approach. Examination of the simulated bilayer, which agrees best with the experimental scattering data, reveals a preferential interaction between Na+ ions and the terminal serine and phosphate moieties. Long-range inter-lipid interactions were identified, primarily between the positively charged ammonium, and the negatively charged carboxylic and phosphate oxygens. The area compressibility modulus KA of the POPS bilayer was derived by quantifying lipid area as a function of surface tension from area-constrained MD simulations. It was found that POPS bilayers possess a much larger KA than that of neutral phosphatidylcholine lipid bilayers. We propose that the unique molecular features of POPS bilayers may play an important role in certain physiological functions.

  11. Molecular modeling and molecular dynamics studies of hydralazine with human DNA methyltransferase 1.

    PubMed

    Singh, Narender; Dueñas-González, Alfonso; Lyko, Frank; Medina-Franco, Jose L

    2009-05-01

    DNA methyltransferases (DNMTs) are a family of enzymes that methylate DNA at the C5 position of cytosine residues, and their inhibition is a promising strategy for the treatment of various developmental and proliferative diseases, particularly cancers. In the present study, a binding model for hydralazine, with a validated homology model of human DNMT, was developed by the use of automated molecular docking and molecular dynamics simulations. The docking protocol was validated by predicting the binding mode of 2'-deoxycytidine, 5-azacytidine, and 5-aza-2'-deoxycytidine. The inhibitory activity of hydralazine toward DNMT may be rationalized at the molecular level by similar interactions within the binding pocket (e.g., by a similar pharmacophore) as established by substrate-like deoxycytidine analogues. These interactions involve a complex network of hydrogen bonds with arginine and glutamic acid residues that also play a major role in the mechanism of DNA methylation. Despite the different scaffolds of other non-nucleoside DNMT inhibitors such as procaine and procainamide, the current modeling work reveals that these drugs exhibit similar interactions within the DNMT1 binding site. These findings are valuable in guiding the rational design and virtual screening of novel DNMT inhibitors.

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

    NASA Astrophysics Data System (ADS)

    Kuusela, Tom

    2004-03-01

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

  13. Coupled nucleotide covariations reveal dynamic RNA interaction patterns.

    PubMed Central

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

    2000-01-01

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

  14. Transcriptomic Analysis of Autistic Brain Reveals Convergent Molecular Pathology

    PubMed Central

    Voineagu, Irina; Wang, Xinchen; Johnston, Patrick; Lowe, Jennifer K.; Tian, Yuan; Horvath, Steve; Mill, Jonathan; Cantor, Rita; Blencowe, Benjamin J.; Geschwind, Daniel H.

    2011-01-01

    Autism spectrum disorder (ASD) is a common, highly heritable neuro-developmental condition characterized by marked genetic heterogeneity1–3. Thus, a fundamental question is whether autism represents an etiologically heterogeneous disorder in which the myriad genetic or environmental risk factors perturb common underlying molecular pathways in the brain4. Here, we demonstrate consistent differences in transcriptome organization between autistic and normal brain by gene co-expression network analysis. Remarkably, regional patterns of gene expression that typically distinguish frontal and temporal cortex are significantly attenuated in the ASD brain, suggesting abnormalities in cortical patterning. We further identify discrete modules of co-expressed genes associated with autism: a neuronal module enriched for known autism susceptibility genes, including the neuronal specific splicing factor A2BP1/FOX1, and a module enriched for immune genes and glial markers. Using high-throughput RNA-sequencing we demonstrate dysregulated splicing of A2BP1-dependent alternative exons in ASD brain. Moreover, using a published autism GWAS dataset, we show that the neuronal module is enriched for genetically associated variants, providing independent support for the causal involvement of these genes in autism. In contrast, the immune-glial module showed no enrichment for autism GWAS signals, indicating a non-genetic etiology for this process. Collectively, our results provide strong evidence for convergent molecular abnormalities in ASD, and implicate transcriptional and splicing dysregulation as underlying mechanisms of neuronal dysfunction in this disorder. PMID:21614001

  15. Frontiers in molecular dynamics simulations of DNA.

    PubMed

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

    2012-02-21

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

  16. CHARACTERIZING COUPLED CHARGE TRANSPORT WITH MULTISCALE MOLECULAR DYNAMICS

    SciTech Connect

    Swanson, Jessica

    2011-08-31

    This is the final progress report for Award DE-SC0004920, entitled 'Characterizing coupled charge transport with multi scale molecular dynamics'. The technical abstract will be provided in the uploaded report.

  17. Local RNA Conformational Dynamics Revealed by 2-Aminopurine Solvent Accessibility†

    PubMed Central

    Ballin, Jeff D.; Prevas, James P.; Bharill, Shashank; Gryczynski, Ignacy; Gryczynski, Zygmunt; Wilson, Gerald M.

    2008-01-01

    Acrylamide quenching is widely used to monitor the solvent exposure of fluorescent probes in vitro. Here, we tested the utility of this technique to discriminate local RNA secondary structures using the fluorescent adenine analogue 2-aminopurine (2-AP). Under native conditions, the solvent accessibilities of most 2-AP-labeled RNA substrates were poorly resolved by classical single population models; rather, a two-state quencher accessibility algorithm was required to model acrylamide-dependent changes in 2-AP fluorescence in structured RNA contexts. Comparing 2-AP quenching parameters between structured and unstructured RNA substrates permitted the effects of local RNA structure on 2-AP solvent exposure to be distinguished from nearest neighbor effects or environmental influences on intrinsic 2-AP photophysics. Using this strategy, the fractional accessibility of 2-AP for acrylamide (fa) was found to be highly sensitive to local RNA structure. Base-paired 2-AP exhibited relatively poor accessibility, consistent with extensive shielding by adjacent bases. 2-AP in a single base bulge was uniformly accessible to solvent, whereas the fractional accessibility of 2-AP in a hexanucleotide loop was indistinguishable from that of an unstructured RNA. However, these studies also provided evidence that the fa parameter reflects local conformational dynamics in base-paired RNA. Enhanced base pair dynamics at elevated temperatures were accompanied by increased fa values, while restricting local RNA breathing by adding a C-G base pair clamp or positioning 2-AP within extended RNA duplexes significantly decreased this parameter. Together, these studies show that 2-AP quenching studies can reveal local RNA structural and dynamic features beyond those measurable by conventional spectroscopic approaches. PMID:18543944

  18. EDITORIAL: 18th European Conference on Dynamics of Molecular Systems 18th European Conference on Dynamics of Molecular Systems

    NASA Astrophysics Data System (ADS)

    Varandas, A. J. C.

    2011-08-01

    This special section of Comments on Atomic, Molecular and Optical Physics (CAMOP) in Physica Scripta collects some of the papers that have been presented at the 18th European Conference on Dynamics of Molecular Systems MOLEC 2010 held in September 2010 in Curia, Portugal, as part of a series of biennial MOLEC conferences. This started in 1976 in Trento, Italy, and has continued, visiting 17 cities in 11 countries, namely Denmark, The Netherlands, Israel, France, Italy, Germany, Czech Republic, Spain, United Kingdom, Turkey and Russia. Following the MOLEC tradition, the scientific programme of the Curia meeting focused on experimental and theoretical studies of molecular interactions, collision dynamics, spectroscopy, and related fields. It included invited speakers from 22 countries, who were asked to summarize the problems reported in their presentations with the objective of revealing the current thinking of leading researchers in atomic, molecular and optical physics. It is hoped that their authoritative contributions presented in this CAMOP special section will also appeal to non-specialists through their clear and broad introductions to the field as well as references to the accessible literature. This CAMOP special section comprises ten contributions, which cover theoretical studies on the electronic structure of molecules and clusters as well as dynamics of elastic, inelastic and reactive encounters between atoms, molecules, ions, clusters and surfaces. Specifically, it includes electronic structure calculations using the traditional coupled-cluster method (Barreto et al 028111), the electron-attached equation-of-motion coupled cluster method (Hansen et al 028110), the diffusion Monte Carlo method (López-Durán et al 028107) and the path-integral Monte Carlo method (Barragán et al 028109). The contributions on molecular dynamics include on-the-fly quasi-classical trajectories on a five-atom molecule (Yu 028104), quantum reaction dynamics on triatomics

  19. Masses, luminosities and dynamics of galactic molecular clouds

    NASA Technical Reports Server (NTRS)

    Solomon, P. M.; Rivolo, A. R.; Mooney, T. J.; Barrett, J. W.; Sage, L. J.

    1987-01-01

    Star formation in galaxies takes place in molecular clouds and the Milky Way is the only galaxy in which it is possible to resolve and study the physical properties and star formation activity of individual clouds. The masses, luminosities, dynamics, and distribution of molecular clouds, primarily giant molecular clouds in the Milky Way are described and analyzed. The observational data sets are the Massachusetts-Stony Brook CO Galactic Plane Survey and the IRAS far IR images. The molecular mass and infrared luminosities of glactic clouds are then compared with the molecular mass and infrared luminosities of external galaxies.

  20. Circulating protein synthesis rates reveal skeletal muscle proteome dynamics

    PubMed Central

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

    2015-01-01

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

  1. Non-adiabatic molecular dynamic simulations of opening reaction of molecular junctions

    NASA Astrophysics Data System (ADS)

    Zobač, Vladmír; Lewis, James P.; Jelínek, Pavel

    2016-07-01

    We report non-adiabatic molecular dynamic simulations of the ring opening reaction of diarylethene (DAE) derivative molecules, both free standing and embedded between gold electrodes. Simulations are performed by the surface hopping method employing density functional theory. Typically, the free-standing molecules exhibit large quantum yields to open and close; however the process is quenched for the molecules embedded between electrodes. Our simulations reveal the importance of the DAE side chemical groups, which explain the efficiency of the quenching process. Namely, delocalization of the LUMO state contributes to electronic coupling between the molecule and electrodes, suppressing or enhancing the reaction process. The simulations indicate that a proper choice of the chemical side group, which provides the strong localization of the LUMO state, can substantially diminish the quenching mechanism. Additionally, we analyze a strong dependency of the quantum yield of the opening reaction coming from the mechanical strength of the molecules.

  2. Non-adiabatic molecular dynamic simulations of opening reaction of molecular junctions.

    PubMed

    Zobač, Vladmír; Lewis, James P; Jelínek, Pavel

    2016-07-15

    We report non-adiabatic molecular dynamic simulations of the ring opening reaction of diarylethene (DAE) derivative molecules, both free standing and embedded between gold electrodes. Simulations are performed by the surface hopping method employing density functional theory. Typically, the free-standing molecules exhibit large quantum yields to open and close; however the process is quenched for the molecules embedded between electrodes. Our simulations reveal the importance of the DAE side chemical groups, which explain the efficiency of the quenching process. Namely, delocalization of the LUMO state contributes to electronic coupling between the molecule and electrodes, suppressing or enhancing the reaction process. The simulations indicate that a proper choice of the chemical side group, which provides the strong localization of the LUMO state, can substantially diminish the quenching mechanism. Additionally, we analyze a strong dependency of the quantum yield of the opening reaction coming from the mechanical strength of the molecules. PMID:27255903

  3. Prospecting Environmental Mycobacteria: Combined Molecular Approaches Reveal Unprecedented Diversity

    PubMed Central

    Pontiroli, Alessandra; Khera, Tanya T.; Oakley, Brian B.; Mason, Sam; Dowd, Scot E.; Travis, Emma R.; Erenso, Girum; Aseffa, Abraham; Courtenay, Orin; Wellington, Elizabeth M. H.

    2013-01-01

    Background Environmental mycobacteria (EM) include species commonly found in various terrestrial and aquatic environments, encompassing animal and human pathogens in addition to saprophytes. Approximately 150 EM species can be separated into fast and slow growers based on sequence and copy number differences of their 16S rRNA genes. Cultivation methods are not appropriate for diversity studies; few studies have investigated EM diversity in soil despite their importance as potential reservoirs of pathogens and their hypothesized role in masking or blocking M. bovis BCG vaccine. Methods We report here the development, optimization and validation of molecular assays targeting the 16S rRNA gene to assess diversity and prevalence of fast and slow growing EM in representative soils from semi tropical and temperate areas. New primer sets were designed also to target uniquely slow growing mycobacteria and used with PCR-DGGE, tag-encoded Titanium amplicon pyrosequencing and quantitative PCR. Results PCR-DGGE and pyrosequencing provided a consensus of EM diversity; for example, a high abundance of pyrosequencing reads and DGGE bands corresponded to M. moriokaense, M. colombiense and M. riyadhense. As expected pyrosequencing provided more comprehensive information; additional prevalent species included M. chlorophenolicum, M. neglectum, M. gordonae, M. aemonae. Prevalence of the total Mycobacterium genus in the soil samples ranged from 2.3×107 to 2.7×108 gene targets g−1; slow growers prevalence from 2.9×105 to 1.2×107 cells g−1. Conclusions This combined molecular approach enabled an unprecedented qualitative and quantitative assessment of EM across soil samples. Good concordance was found between methods and the bioinformatics analysis was validated by random resampling. Sequences from most pathogenic groups associated with slow growth were identified in extenso in all soils tested with a specific assay, allowing to unmask them from the Mycobacterium whole genus, in

  4. Dynamical analysis of highly excited molecular spectra

    SciTech Connect

    Kellman, M.E.

    1993-12-01

    The goal of this program is new methods for analysis of spectra and dynamics of highly excited vibrational states of molecules. In these systems, strong mode coupling and anharmonicity give rise to complicated classical dynamics, and make the simple normal modes analysis unsatisfactory. New methods of spectral analysis, pattern recognition, and assignment are sought using techniques of nonlinear dynamics including bifurcation theory, phase space classification, and quantization of phase space structures. The emphasis is chaotic systems and systems with many degrees of freedom.

  5. The molecular architecture of axonemes revealed by cryoelectron tomography.

    PubMed

    Nicastro, Daniela; Schwartz, Cindi; Pierson, Jason; Gaudette, Richard; Porter, Mary E; McIntosh, J Richard

    2006-08-18

    Eukaryotic flagella and cilia are built on a 9 + 2 array of microtubules plus >250 accessory proteins, forming a biological machine called the axoneme. Here we describe the three-dimensional structure of rapidly frozen axonemes from Chlamydomonas and sea urchin sperm, using cryoelectron tomography and image processing to focus on the motor enzyme dynein. Our images suggest a model for the way dynein generates force to slide microtubules. They also reveal two dynein linkers that may provide "hard-wiring" to coordinate motor enzyme action, both circumferentially and along the axoneme. Periodic densities were also observed inside doublet microtubules; these may contribute to doublet stability. PMID:16917055

  6. Aggregation of model asphaltenes: a molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Costa, J. L. L. F. S.; Simionesie, D.; Zhang, Z. J.; Mulheran, P. A.

    2016-10-01

    Natural asphaltenes are defined as polyaromatic compounds whose chemical composition and structure are dependent on their geological origin and production history, hence are regarded as complex molecules with aromatic cores and aliphatic tails that occur in the heaviest fraction of crude oil. The aggregation of asphaltenes presents a range of technical challenges to the production and processing of oil. In this work we study the behaviour of the model asphaltene-like molecule hexa-tert-butylhexa-peri-hexabenzocoronene (HTBHBC) using molecular dynamics simulation. It was found that the regular arrangement of the tert-butyl side chains prevents the formation of strongly-bound dimers by severely restricting the configurational space of the aggregation pathway. In contrast, a modified molecule with only 3 side chains is readily able to form dimers. This work therefore confirms the influence of the molecular structure of polyaromatic compounds on their aggregation mechanism, and reveals the unexpected design rules required for model systems that can mimic the behavior of asphaltenes.

  7. NMR Studies of Molecular Orientation and Dynamics in Spider silk

    NASA Astrophysics Data System (ADS)

    Michal, Carl; Eles, Philip

    2004-05-01

    Spider dragline silk has a unique combination of strength and extensibility that has been difficult to achieve in synthetic polymer fibres and has inspired industrial efforts to produce genetically engineered analogues. In light of these efforts elsewhere, we describe solid-state NMR experiments that elucidate the molecular structure and dynamics of this remarkable material. These experiments include the use of a 2-D exchange NMR experiment known as DECODER in which the sample is reoriented through a discrete angle during the mixing time. This experiment allows a reconstruction of the orientation distribution of the protein backbone. Our data is well described by a two-component distribution where the protein backbones of both components are preferentially aligned along the silk fibre. This experiment is also sensitive to molecular motion on a wide range of time-scales, and is employed to study changes in the silk as a function of fibre extension and hydration. Hydrated silk undergoes a remarkable phenomena known as supercontraction where fibres shrink by up to 50% in length while swelling in diameter. DECODER NMR of fully and partially supercontracted silk reveals that supercontraction occurs through a process of local phase transitions where water disrupts inter- and intra-chain hydrogen bonds.

  8. Aggregation of model asphaltenes: a molecular dynamics study.

    PubMed

    Costa, J L L F S; Simionesie, D; Zhang, Z J; Mulheran, P A

    2016-10-01

    Natural asphaltenes are defined as polyaromatic compounds whose chemical composition and structure are dependent on their geological origin and production history, hence are regarded as complex molecules with aromatic cores and aliphatic tails that occur in the heaviest fraction of crude oil. The aggregation of asphaltenes presents a range of technical challenges to the production and processing of oil. In this work we study the behaviour of the model asphaltene-like molecule hexa-tert-butylhexa-peri-hexabenzocoronene (HTBHBC) using molecular dynamics simulation. It was found that the regular arrangement of the tert-butyl side chains prevents the formation of strongly-bound dimers by severely restricting the configurational space of the aggregation pathway. In contrast, a modified molecule with only 3 side chains is readily able to form dimers. This work therefore confirms the influence of the molecular structure of polyaromatic compounds on their aggregation mechanism, and reveals the unexpected design rules required for model systems that can mimic the behavior of asphaltenes. PMID:27465036

  9. HTMD: High-Throughput Molecular Dynamics for Molecular Discovery.

    PubMed

    Doerr, S; Harvey, M J; Noé, Frank; De Fabritiis, G

    2016-04-12

    Recent advances in molecular simulations have allowed scientists to investigate slower biological processes than ever before. Together with these advances came an explosion of data that has transformed a traditionally computing-bound into a data-bound problem. Here, we present HTMD, a programmable, extensible platform written in Python that aims to solve the data generation and analysis problem as well as increase reproducibility by providing a complete workspace for simulation-based discovery. So far, HTMD includes system building for CHARMM and AMBER force fields, projection methods, clustering, molecular simulation production, adaptive sampling, an Amazon cloud interface, Markov state models, and visualization. As a result, a single, short HTMD script can lead from a PDB structure to useful quantities such as relaxation time scales, equilibrium populations, metastable conformations, and kinetic rates. In this paper, we focus on the adaptive sampling and Markov state modeling features. PMID:26949976

  10. Femtosecond molecular dynamics studied with vacuum ultraviolet pulse pairs

    NASA Astrophysics Data System (ADS)

    Allison, Thomas K., III

    Atoms and molecules have most of their oscillator strength in the vacuum ultraviolet (VUV) and extreme ultraviolet (XUV), between the wavelengths of 200 nm and 30 nm. However, most femtosecond spectroscopy has been restricted to the visible and infrared due to a lack of sufficiently intense VUV and XUV femtosecond light sources. This thesis discusses extensions of pump/probe spectroscopy to the VUV and XUV, and its application to the dynamics of ethylene and oxygen molecules excited at 161 nm. I begin with a detailed discussion of the short wavelength light source used in this work. The source is based on the high order harmonics of a near infrared laser and can deliver > 1010 photons per shot in femtosecond pulses, corresponding to nearly 10 MW peak power in the XUV. Measurements of the harmonic yields as a function of the generation conditions reveal the roles of phase matching and ionization gating in the high order harmonic generation process. Pump/probe measurements are conducted using a unique VUV interferometer, capable of combining two different harmonics at a focus with variable delay. Measurements of VUV multiphoton ionization allows for characterization of the source and the interferometer. In molecules, time resolved measurements of fragment ion yields reveal the femtosecond dynamics of the system. The range of wavelengths available for pump and probe allows the dynamics to be followed from photo-excitation all the way to dissociation without detection window effects. The dynamics in ethylene upon pi → pi* excitation are protypical of larger molecules and have thus served as an important test case for advanced ab initio molecular dynamics theories. Femtosecond measurements to date, however, have been extremely lacking. In the present work, through a series of pump probe experiments using VUV and XUV pulses, time scales for the non-adiabatic relaxation of the electronic excitation, hydrogen migration across the double bond, and H2 molecule elimination

  11. Elucidation of molecular dynamics of invasive species of rice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cultivated rice fields are aggressively invaded by weedy rice in the U.S. and worldwide. Weedy rice results in loss of yield and seed contamination. The molecular dynamics of the evolutionary adaptive traits of weedy rice are not fully understood. To understand the molecular basis and identify the i...

  12. Attosecond molecular dynamics: fact or fiction?

    NASA Astrophysics Data System (ADS)

    Lépine, Franck; Ivanov, Misha Y.; Vrakking, Marc J. J.

    2014-03-01

    The emerging application of attosecond techniques to molecular systems allows the role of electronic coherence in the control of chemical reactions to be investigated. Prompt ionization of molecules by an attosecond pulse may induce charge migration across a molecular structure on attosecond to few-femtosecond timescales, thereby possibly determining the subsequent relaxation pathways that a molecule may take. We discuss how proposals for this 'charge-directed reactivity' fit within the current understanding of quantum control and review the current state of the art of attosecond molecular science. Specifically, we review the role of electronic coherence and coupling of the electronic and nuclear degrees of freedom in high-harmonic spectroscopy and in the first attosecond pump-probe experiments on molecular systems.

  13. Molecular dynamics simulation of interfacial adhesion

    SciTech Connect

    Yarovsky, I.; Chaffee, A.L.

    1996-12-31

    Chromium salts are often used in the pretreatment stages of steel painting processes in order to improve adhesion at the metal oxide/primer interface. Although well established empirically, the chemical basis for the improved adhesion conferred by chromia is not well understood. A molecular level understanding of this behaviour should provide a foundation for the design of materials offering improved adhesion control. Molecular modelling of adhesion involves simulation and analysis of molecular behaviour at the interface between two interacting phases. The present study concerns behaviour at the boundary between the metal coated steel surface (with or without chromium pretreatment) and an organic primer based on a solid epoxide resin produced from bisphenol A and epichlorohydrin. An epoxy resin oligomer of molecular weight 3750 was used as the model for the primer.

  14. Multitargeting by curcumin as revealed by molecular interaction studies

    PubMed Central

    Gupta, Subash C.; Prasad, Sahdeo; Kim, Ji Hye; Patchva, Sridevi; Webb, Lauren J.; Priyadarsini, Indira K.

    2012-01-01

    Curcumin (diferuloylmethane), the active ingredient in turmeric (Curcuma longa), is a highly pleiotropic molecule with anti-inflammatory, anti-oxidant, chemopreventive, chemosensitization, and radiosensitization activities. The pleiotropic activities attributed to curcumin come from its complex molecular structure and chemistry, as well as its ability to influence multiple signaling molecules. Curcumin has been shown to bind by multiple forces directly to numerous signaling molecules, such as inflammatory molecules, cell survival proteins, protein kinases, protein reductases, histone acetyltransferase, histone deacetylase, glyoxalase I, xanthine oxidase, proteasome, HIV1 integrase, HIV1 protease, sarco (endo) plasmic reticulum Ca2+ ATPase, DNA methyltransferases 1, FtsZ protofilaments, carrier proteins, and metal ions. Curcumin can also bind directly to DNA and RNA. Owing to its β-diketone moiety, curcumin undergoes keto–enol tautomerism that has been reported as a favorable state for direct binding. The functional groups on curcumin found suitable for interaction with other macromolecules include the α, β-unsaturated β-diketone moiety, carbonyl and enolic groups of the β-diketone moiety, methoxy and phenolic hydroxyl groups, and the phenyl rings. Various biophysical tools have been used to monitor direct interaction of curcumin with other proteins, including absorption, fluorescence, Fourier transform infrared (FTIR) and circular dichroism (CD) spectroscopy, surface plasmon resonance, competitive ligand binding, Forster type fluorescence resonance energy transfer (FRET), radiolabeling, site-directed mutagenesis, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), immunoprecipitation, phage display biopanning, electron microscopy, 1-anilino-8-naphthalene-sulfonate (ANS) displacement, and co-localization. Molecular docking, the most commonly employed computational tool for calculating binding affinities and predicting

  15. Visualizing Functional Motions of Membrane Transporters with Molecular Dynamics Simulations

    PubMed Central

    2013-01-01

    Computational modeling and molecular simulation techniques have become an integral part of modern molecular research. Various areas of molecular sciences continue to benefit from, indeed rely on, the unparalleled spatial and temporal resolutions offered by these technologies, to provide a more complete picture of the molecular problems at hand. Because of the continuous development of more efficient algorithms harvesting ever-expanding computational resources, and the emergence of more advanced and novel theories and methodologies, the scope of computational studies has expanded significantly over the past decade, now including much larger molecular systems and far more complex molecular phenomena. Among the various computer modeling techniques, the application of molecular dynamics (MD) simulation and related techniques has particularly drawn attention in biomolecular research, because of the ability of the method to describe the dynamical nature of the molecular systems and thereby to provide a more realistic representation, which is often needed for understanding fundamental molecular properties. The method has proven to be remarkably successful in capturing molecular events and structural transitions highly relevant to the function and/or physicochemical properties of biomolecular systems. Herein, after a brief introduction to the method of MD, we use a number of membrane transport proteins studied in our laboratory as examples to showcase the scope and applicability of the method and its power in characterizing molecular motions of various magnitudes and time scales that are involved in the function of this important class of membrane proteins. PMID:23298176

  16. Single-cell dynamics reveals sustained growth during diauxic shifts.

    PubMed

    Boulineau, Sarah; Tostevin, Filipe; Kiviet, Daniel J; ten Wolde, Pieter Rein; Nghe, Philippe; Tans, Sander J

    2013-01-01

    Stochasticity in gene regulation has been characterized extensively, but how it affects cellular growth and fitness is less clear. We study the growth of E. coli cells as they shift from glucose to lactose metabolism, which is characterized by an obligatory growth arrest in bulk experiments that is termed the lag phase. Here, we follow the growth dynamics of individual cells at minute-resolution using a single-cell assay in a microfluidic device during this shift, while also monitoring lac expression. Mirroring the bulk results, the majority of cells displays a growth arrest upon glucose exhaustion, and resume when triggered by stochastic lac expression events. However, a significant fraction of cells maintains a high rate of elongation and displays no detectable growth lag during the shift. This ability to suppress the growth lag should provide important selective advantages when nutrients are scarce. Trajectories of individual cells display a highly non-linear relation between lac expression and growth, with only a fraction of fully induced levels being sufficient for achieving near maximal growth. A stochastic molecular model together with measured dependencies between nutrient concentration, lac expression level, and growth accurately reproduces the observed switching distributions. The results show that a growth arrest is not obligatory in the classic diauxic shift, and underscore that regulatory stochasticity ought to be considered in terms of its impact on growth and survival. PMID:23637881

  17. How to identify dislocations in molecular dynamics simulations?

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

  18. 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

  19. Optical anisotropy reveals molecular order in a mouse enthesis.

    PubMed

    Vidal, Benedicto de Campos; Dos Anjos, Eli Heber M; Mello, Maria Luiza S

    2015-10-01

    Entheses are specialized biological structures that functionally anchor tendons to bones. The complexity, mechanical characteristics and properties of the entheses, particularly those related to exercise, mechanical load and pathologies, have been extensively analyzed; however, the macromolecular organization of the enthesis fibers, as assessed by polarization microscopy, has not yet been investigated. Morphological and optical anisotropy characteristics, such as birefringence, linear dichroism (LD) and differential interference contrast (DIC-PLM) properties, are thus analyzed in this study of a healthy adult mouse calcaneal tendon-bone enthesis. The molecular and supramolecular order of collagen and GAGs was determined for the collagen bundles of this enthesis. Based on a birefringence plot pattern as well as on metachromasy and linear dichroism after toluidine blue staining at pH 4.0, a similarity between the calcaneal tendon-bone enthesis and cartilage during ossification may be assumed. This similarity is assumed to favor the adequacy of this enthesis to support a compressive load. Considering that the collagen-proteoglycan complexes and the enthesis fibers themselves have a chiral nature, these structures could be acting via reciprocal signaling with the cellular environment of the enthesis. PMID:25866201

  20. Animated molecular dynamics simulations of hydrated caesium-smectite interlayers

    PubMed Central

    Sutton, Rebecca; Sposito, Garrison

    2002-01-01

    Computer animation of center of mass coordinates obtained from 800 ps molecular dynamics simulations of Cs-smectite hydrates (1/3 and 2/3 water monolayers) provided information concerning the structure and dynamics of the interlayer region that could not be obtained through traditional simulation analysis methods. Cs+ formed inner sphere complexes with the mineral surface, and could be seen to jump from one attracting location near a layer charge site to the next, while water molecules were observed to migrate from the hydration shell of one ion to that of another. Neighboring ions maintained a partial hydration shell by sharing water molecules, such that a single water molecule hydrated two ions simultaneously for hundreds of picoseconds. Cs-montmorillonite hydrates featured the largest extent of this sharing interaction, because interlayer ions were able to inhabit positions near surface cavities as well as at their edges, close to oxygen triads. The greater positional freedom of Cs+ within the montmorillonite interlayer, a result of structural hydroxyl orientation and low tetrahedral charge, promoted the optimization of distances between cations and water molecules required for water sharing. Preference of Cs+ for locations near oxygen triads was observed within interlayer beidellite and hectorite. Water molecules also could be seen to interact directly with the mineral surface, entering its surface cavities to approach attracting charge sites and structural hydroxyls. With increasing water content, water molecules exhibited increased frequency and duration of both cavity habitation and water sharing interactions. Competition between Cs+ and water molecules for surface sites was evident. These important cooperative and competitive features of interlayer molecular behavior were uniquely revealed by animation of an otherwise highly complex simulation output.

  1. Unsupervised Deconvolution of Dynamic Imaging Reveals Intratumor Vascular Heterogeneity and Repopulation Dynamics

    PubMed Central

    Chen, Li; Choyke, Peter L.; Wang, Niya; Clarke, Robert; Bhujwalla, Zaver M.; Hillman, Elizabeth M. C.; Wang, Ge; Wang, Yue

    2014-01-01

    With the existence of biologically distinctive malignant cells originated within the same tumor, intratumor functional heterogeneity is present in many cancers and is often manifested by the intermingled vascular compartments with distinct pharmacokinetics. However, intratumor vascular heterogeneity cannot be resolved directly by most in vivo dynamic imaging. We developed multi-tissue compartment modeling (MTCM), a completely unsupervised method of deconvoluting dynamic imaging series from heterogeneous tumors that can improve vascular characterization in many biological contexts. Applying MTCM to dynamic contrast-enhanced magnetic resonance imaging of breast cancers revealed characteristic intratumor vascular heterogeneity and therapeutic responses that were otherwise undetectable. MTCM is readily applicable to other dynamic imaging modalities for studying intratumor functional and phenotypic heterogeneity, together with a variety of foreseeable applications in the clinic. PMID:25379705

  2. Tunable Interfacial Thermal Conductance by Molecular Dynamics

    NASA Astrophysics Data System (ADS)

    Shen, Meng

    We study the mechanism of tunable heat transfer through interfaces between solids using a combination of non-equilibrium molecular dynamics simulation (NEMD), vibrational mode analysis and wave packet simulation. We investigate how heat transfer through interfaces is affected by factors including pressure, interfacial modulus, contact area and interfacial layer thickness, with an overreaching goal of developing fundamental knowledge that will allow one to tailor thermal properties of interfacial materials. The role of pressure and interfacial stiffness is unraveled by our studies on an epitaxial interface between two Lennard-Jones (LJ) crystals. The interfacial stiffness is varied by two different methods: (i) indirectly by applying pressure which due to anharmonic nature of bonding, increases interfacial stiffness, and (ii) directly by changing the interfacial bonding strength by varying the depth of the potential well of the LJ potential. When the interfacial bonding strength is low, quantitatively similar behavior to pressure tuning is observed when the interfacial thermal conductance is increased by directly varying the potential-well depth parameter of the LJ potential. By contrast, when the interfacial bonding strength is high, thermal conductance is almost pressure independent, and even slightly decreases with increasing pressure. This decrease can be explained by the change in overlap between the vibrational densities of states of the two crystalline materials. The role of contact area is studied by modeling structures comprised of Van der Waals junctions between single-walled nanotubes (SWCNT). Interfacial thermal conductance between SWCNTs is obtained from NEMD simulation as a function of crossing angle. In this case the junction conductance per unit area is essentially a constant. By contrast, interfacial thermal conductance between multiwalled carbon nanotubes (MWCNTs) is shown to increase with diameter of the nanotubes by recent experimental studies [1

  3. Tunable Interfacial Thermal Conductance by Molecular Dynamics

    NASA Astrophysics Data System (ADS)

    Shen, Meng

    We study the mechanism of tunable heat transfer through interfaces between solids using a combination of non-equilibrium molecular dynamics simulation (NEMD), vibrational mode analysis and wave packet simulation. We investigate how heat transfer through interfaces is affected by factors including pressure, interfacial modulus, contact area and interfacial layer thickness, with an overreaching goal of developing fundamental knowledge that will allow one to tailor thermal properties of interfacial materials. The role of pressure and interfacial stiffness is unraveled by our studies on an epitaxial interface between two Lennard-Jones (LJ) crystals. The interfacial stiffness is varied by two different methods: (i) indirectly by applying pressure which due to anharmonic nature of bonding, increases interfacial stiffness, and (ii) directly by changing the interfacial bonding strength by varying the depth of the potential well of the LJ potential. When the interfacial bonding strength is low, quantitatively similar behavior to pressure tuning is observed when the interfacial thermal conductance is increased by directly varying the potential-well depth parameter of the LJ potential. By contrast, when the interfacial bonding strength is high, thermal conductance is almost pressure independent, and even slightly decreases with increasing pressure. This decrease can be explained by the change in overlap between the vibrational densities of states of the two crystalline materials. The role of contact area is studied by modeling structures comprised of Van der Waals junctions between single-walled nanotubes (SWCNT). Interfacial thermal conductance between SWCNTs is obtained from NEMD simulation as a function of crossing angle. In this case the junction conductance per unit area is essentially a constant. By contrast, interfacial thermal conductance between multiwalled carbon nanotubes (MWCNTs) is shown to increase with diameter of the nanotubes by recent experimental studies [1

  4. Dynamics of nitrogen dissociation from direct molecular simulation

    NASA Astrophysics Data System (ADS)

    Valentini, Paolo; Schwartzentruber, Thomas E.; Bender, Jason D.; Candler, Graham V.

    2016-08-01

    dissociating nitrogen systems involving both atomic and molecular nitrogen. Such direct comparisons also illustrate how the DMS method is able to reveal all relevant nonequilibrium physics without the need to compute large numbers of state-transition probabilities. In this manner, DMS presents an accurate and tractable approach to construct models for direct-simulation Monte Carlo and computational fluid dynamics simulations from first principles.

  5. MOLECULAR DYNAMICS STUDY OF DIFFUSIONAL CREEP IN NANOCRYSTALLINE UO2

    SciTech Connect

    Tapan G. Desai; Paul C. Millett; Dieter Wolf

    2008-09-01

    We present the results of molecular dynamics (MD) simulations to study hightemperature deformation of nanocrystalline UO2. In qualitative agreement with experimental observations, the oxygen sub-lattice undergoes a structural transition at a temperature of about 2200 K (i.e., well below the melting point of 3450 K of our model system), whereas the uranium sub-lattice remains unchanged all the way up to melting. At temperatures well above this structural transition, columnar nanocrystalline model microstructures with a uniform grain size and grain shape were subjected to constantstress loading at levels low enough to avoid microcracking and dislocation nucleation from the GBs. Our simulations reveal that in the absence of grain growth, the material deforms via GB diffusion creep (also known as Coble creep). Analysis of the underlying self-diffusion behavior in undeformed nanocrystalline UO2 reveals that, on our MD time scale, the uranium ions diffuse only via the grain boundaries (GBs) whereas the much faster moving oxygen ions diffuse through both the lattice and the GBs. As expected for the Coble-creep mechanism, the creep activation energy agrees well with that for GB diffusion of the slowest moving species, i.e., of the uranium ions.

  6. Lytic Water Dynamics Reveal Evolutionarily Conserved Mechanisms of ATP Hydrolysis by TIP49 AAA+ ATPases

    PubMed Central

    Afanasyeva, Arina; Hirtreiter, Angela; Schreiber, Anne; Grohmann, Dina; Pobegalov, Georgii; McKay, Adam R.; Tsaneva, Irina; Petukhov, Michael; Käs, Emmanuel; Grigoriev, Mikhail; Werner, Finn

    2014-01-01

    Summary Eukaryotic TIP49a (Pontin) and TIP49b (Reptin) AAA+ ATPases play essential roles in key cellular processes. How their weak ATPase activity contributes to their important functions remains largely unknown and difficult to analyze because of the divergent properties of TIP49a and TIP49b proteins and of their homo- and hetero-oligomeric assemblies. To circumvent these complexities, we have analyzed the single ancient TIP49 ortholog found in the archaeon Methanopyrus kandleri (mkTIP49). All-atom homology modeling and molecular dynamics simulations validated by biochemical assays reveal highly conserved organizational principles and identify key residues for ATP hydrolysis. An unanticipated crosstalk between Walker B and Sensor I motifs impacts the dynamics of water molecules and highlights a critical role of trans-acting aspartates in the lytic water activation step that is essential for the associative mechanism of ATP hydrolysis. PMID:24613487

  7. Bidirectionality and compartmentation of metabolic fluxes are revealed in the dynamics of isotopomer networks.

    PubMed

    Schryer, David W; Peterson, Pearu; Paalme, Toomas; Vendelin, Marko

    2009-04-01

    Isotope labeling is one of the few methods of revealing the in vivo bidirectionality and compartmentalization of metabolic fluxes within metabolic networks. We argue that a shift from steady state to dynamic isotopomer analysis is required to deal with these cellular complexities and provide a review of dynamic studies of compartmentalized energy fluxes in eukaryotic cells including cardiac muscle, plants, and astrocytes. Knowledge of complex metabolic behaviour on a molecular level is prerequisite for the intelligent design of genetically modified organisms able to realize their potential of revolutionizing food, energy, and pharmaceutical production. We describe techniques to explore the bidirectionality and compartmentalization of metabolic fluxes using information contained in the isotopic transient, and discuss the integration of kinetic models with MFA. The flux parameters of an example metabolic network were optimized to examine the compartmentalization of metabolites and and the bidirectionality of fluxes in the TCA cycle of Saccharomyces uvarum for steady-state respiratory growth. PMID:19468334

  8. Molecular dynamics studies on the buffalo prion protein.

    PubMed

    Zhang, Jiapu; Wang, Feng; Chatterjee, Subhojyoti

    2016-01-01

    It was reported that buffalo is a low susceptibility species resisting to transmissible spongiform encephalopathies (TSEs) (same as rabbits, horses, and dogs). TSEs, also called prion diseases, are invariably fatal and highly infectious neurodegenerative diseases that affect a wide variety of species (except for rabbits, dogs, horses, and buffalo), manifesting as scrapie in sheep and goats; bovine spongiform encephalopathy (BSE or "mad-cow" disease) in cattle; chronic wasting disease in deer and elk; and Creutzfeldt-Jakob diseases, Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia, and Kulu in humans etc. In molecular structures, these neurodegenerative diseases are caused by the conversion from a soluble normal cellular prion protein (PrP(C)), predominantly with α-helices, into insoluble abnormally folded infectious prions (PrP(Sc)), rich in β-sheets. In this article, we studied the molecular structure and structural dynamics of buffalo PrP(C) (BufPrP(C)), in order to understand the reason why buffalo is resistant to prion diseases. We first did molecular modeling of a homology structure constructed by one mutation at residue 143 from the NMR structure of bovine and cattle PrP(124-227); immediately we found that for BufPrP(C)(124-227), there are five hydrogen bonds (HBs) at Asn143, but at this position, bovine/cattle do not have such HBs. Same as that of rabbits, dogs, or horses, our molecular dynamics studies also revealed there is a strong salt bridge (SB) ASP178-ARG164 (O-N) keeping the β2-α2 loop linked in buffalo. We also found there is a very strong HB SER170-TYR218 linking this loop with the C-terminal end of α-helix H3. Other information, such as (i) there is a very strong SB HIS187-ARG156 (N-O) linking α-helices H2 and H1 (if mutation H187R is made at position 187, then the hydrophobic core of PrP(C) will be exposed (L.H. Zhong (2010). Exposure of hydrophobic core in human prion protein pathogenic mutant H187R. Journal of

  9. Molecular dynamics studies on the buffalo prion protein.

    PubMed

    Zhang, Jiapu; Wang, Feng; Chatterjee, Subhojyoti

    2016-01-01

    It was reported that buffalo is a low susceptibility species resisting to transmissible spongiform encephalopathies (TSEs) (same as rabbits, horses, and dogs). TSEs, also called prion diseases, are invariably fatal and highly infectious neurodegenerative diseases that affect a wide variety of species (except for rabbits, dogs, horses, and buffalo), manifesting as scrapie in sheep and goats; bovine spongiform encephalopathy (BSE or "mad-cow" disease) in cattle; chronic wasting disease in deer and elk; and Creutzfeldt-Jakob diseases, Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia, and Kulu in humans etc. In molecular structures, these neurodegenerative diseases are caused by the conversion from a soluble normal cellular prion protein (PrP(C)), predominantly with α-helices, into insoluble abnormally folded infectious prions (PrP(Sc)), rich in β-sheets. In this article, we studied the molecular structure and structural dynamics of buffalo PrP(C) (BufPrP(C)), in order to understand the reason why buffalo is resistant to prion diseases. We first did molecular modeling of a homology structure constructed by one mutation at residue 143 from the NMR structure of bovine and cattle PrP(124-227); immediately we found that for BufPrP(C)(124-227), there are five hydrogen bonds (HBs) at Asn143, but at this position, bovine/cattle do not have such HBs. Same as that of rabbits, dogs, or horses, our molecular dynamics studies also revealed there is a strong salt bridge (SB) ASP178-ARG164 (O-N) keeping the β2-α2 loop linked in buffalo. We also found there is a very strong HB SER170-TYR218 linking this loop with the C-terminal end of α-helix H3. Other information, such as (i) there is a very strong SB HIS187-ARG156 (N-O) linking α-helices H2 and H1 (if mutation H187R is made at position 187, then the hydrophobic core of PrP(C) will be exposed (L.H. Zhong (2010). Exposure of hydrophobic core in human prion protein pathogenic mutant H187R. Journal of

  10. The Computer Simulation of Liquids by Molecular Dynamics.

    ERIC Educational Resources Information Center

    Smith, W.

    1987-01-01

    Proposes a mathematical computer model for the behavior of liquids using the classical dynamic principles of Sir Isaac Newton and the molecular dynamics method invented by other scientists. Concludes that other applications will be successful using supercomputers to go beyond simple Newtonian physics. (CW)

  11. Temperature dependence of protein hydration hydrodynamics by molecular dynamics simulations.

    SciTech Connect

    Lau, E Y; Krishnan, V V

    2007-07-18

    The dynamics of water molecules near the protein surface are different from those of bulk water and influence the structure and dynamics of the protein itself. To elucidate the temperature dependence hydration dynamics of water molecules, we present results from the molecular dynamic simulation of the water molecules surrounding two proteins (Carboxypeptidase inhibitor and Ovomucoid) at seven different temperatures (T=273 to 303 K, in increments of 5 K). Translational diffusion coefficients of the surface water and bulk water molecules were estimated from 2 ns molecular dynamics simulation trajectories. Temperature dependence of the estimated bulk water diffusion closely reflects the experimental values, while hydration water diffusion is retarded significantly due to the protein. Protein surface induced scaling of translational dynamics of the hydration waters is uniform over the temperature range studied, suggesting the importance protein-water interactions.

  12. Ab initio centroid molecular dynamics: a fully quantum method for condensed-phase dynamics simulations

    NASA Astrophysics Data System (ADS)

    Pavese, Marc; Berard, Daniel R.; Voth, Gregory A.

    1999-01-01

    A fully quantum molecular dynamics method is presented which combines ab initio Car-Parrinello molecular dynamics with centroid molecular dynamics. The first technique allows the forces on the atoms to be obtained from ab initio electronic structure. The second technique, given the forces on the atoms, allows one to calculate an approximate quantum time evolution for the nuclei. The combination of the two, therefore, represents the first feasible approach to simulating the fully quantum dynamics of a many-body system. An application to excess proton translocation along a model water wire will be presented.

  13. Molecular Dynamics in Self-Assembled Monolayers

    NASA Astrophysics Data System (ADS)

    Bochinski, Jason; Stevens, Derrick; Scott, Mary; Guy, Laura; Dedeugd, Casey; Clarke, Laura

    2007-03-01

    Silane self-assembled monolayers (SAMs) are an important tool for both scientific research and technological applications. Despite their widespread use, few experimental investigations have addressed molecular motion within these films, which offer a unique and useful physical system for fundamental scientific studies, such as observing dipolar and other glass transitions in two-dimensions. In addition, relaxations such as ``rotator'' phases where molecular groups rotate in a plane parallel to the surface have been correlated with film conductivity, adhesive, and wetting properties. We utilize surface-sensitive, dielectric relaxation spectroscopy to probe molecular motion as a function of temperature within silane chemistry-based monolayers formed upon interdigitated electrodes. Our latest results exploring a previously published motion as well as comparisons to linear polymer films will be discussed.

  14. On electronic representations in molecular reaction dynamics

    NASA Astrophysics Data System (ADS)

    Killian, Benjamin J.

    For many decades, the field of chemical reaction dynamics has utilized computational methods that rely on potential energy surfaces that are constructed using stationary-state calculations. These methods are typically devoid of dynamical couplings between the electronic and nuclear degrees of freedom, a fact that can result in incorrect descriptions of dynamical processes. Often, non-adiabatic coupling expressions are included in these methodologies. The Electron-Nuclear Dynamics (END) formalism, in contrast, circumvents these deficiencies by calculating all intermolecular forces directly at each time step in the dynamics and by explicitly maintaining all electronic-nuclear couplings. The purpose of this work is to offer two new frameworks for implementing electronic representations in dynamical calculations. Firstly, a new schema is proposed for developing atomic basis sets that are consistent with dynamical calculations. Traditionally, basis sets have been designed for use in stationary-state calculations of the structures and properties of molecules in their ground states. As a consequence of common construction techniques that utilize energy optimization methods, the unoccupied orbitals bear little resemblance to physical virtual atomic orbitals. We develop and implement a method for basis set construction that relies upon physical properties of atomic orbitals and that results in meaningful virtual orbitals. These basis sets are shown to provide a significant improvement in the accuracy of calculated dynamical properties such as charge transfer probabilities. Secondly, the theoretical framework of END is expanded to incorporate a multi-configurational representation for electrons. This formalism, named Vector Hartree-Fock, is based in the theory of vector coherent states and utilizes a complete active space electronic representation. The Vector Hartree-Fock method is fully disclosed, with derivation of the equations of motion. The expressions for the equation

  15. Multiple Differential Networks Strategy Reveals Carboplatin and Melphalan-Induced Dynamic Module Changes in Retinoblastoma.

    PubMed

    Chen, Cui; Ma, Feng-Wei; Du, Cui-Yun; Wang, Ping

    2016-01-01

    BACKGROUND Retinoblastoma (RB) is the most common malignant tumor of the eye in childhood. The objective of this paper was to investigate carboplatin (CAR)- and melphalan (MEL)-induced dynamic module changes in RB based on multiple (M) differential networks, and to generate systems-level insights into RB progression. MATERIAL AND METHODS To achieve this goal, we constructed M-differential co-expression networks (DCNs), assigned a weight to each edge, and identified seed genes in M DCNs by ranking genes based on their topological features. Starting with seed genes, a module search was performed to explore candidate modules in CAR and MEL condition. M-DMs were detected according to significance evaluations of M-modules, which originated from refinement of candidate modules. Further, we revealed dynamic changes in M-DM activity and connectivity on the basis of significance of Module Connectivity Dynamic Score (MCDS). RESULTS In the present study, M=2, a total of 21 seed genes were obtained. By assessing module search, refinement, and evaluation, we gained 18 2-DMs. Moreover, 3 significant 2-DMs (Module 1, Module 2, and Module 3) with dynamic changes across CAR and MEL condition were determined, and we denoted them as dynamic modules. Module 1 had 27 nodes of which 6 were seed genes and 56 edges. Module 2 was composed of 28 nodes and 54 edges. A total of 28 nodes interacted with 45 edges presented in Module 3. CONCLUSIONS We have identified 3 dynamic modules with changes induced by CAR and MEL in RB, which might give insights in revealing molecular mechanism for RB therapy. PMID:27144687

  16. Optimal control of molecular motion expressed through quantum fluid dynamics

    NASA Astrophysics Data System (ADS)

    Dey, Bijoy K.; Rabitz, Herschel; Askar, Attila

    2000-04-01

    A quantum fluid-dynamic (QFD) control formulation is presented for optimally manipulating atomic and molecular systems. In QFD the control quantum system is expressed in terms of the probability density ρ and the quantum current j. This choice of variables is motivated by the generally expected slowly varying spatial-temporal dependence of the fluid-dynamical variables. The QFD approach is illustrated for manipulation of the ground electronic state dynamics of HCl induced by an external electric field.

  17. Single Molecule Spectroscopy Illuminating the Molecular Dynamics of Life

    NASA Astrophysics Data System (ADS)

    Webb, Watt W.

    This chapter summarizes a series of new single-molecule spectroscopy investigations in the life sciences at Cornell University that began with our invention of Fluorescence Correlation Spectroscopy (FCS) about 1970. Our invention of FCS became my first focus on the "Molecular Dynamics of Life." It motivated my transition from research on quantum fluctuations and transport in condensed matter physics including superconductivity and in the molecular dynamics of coherent fluctuations and nano-transport in inanimate physical and chemical systems subject to the nonlinear dynamics of continuous phase transitions. These interdisciplinary transitions exemplify the productivity of such interdisciplinary interactions in science.

  18. Interfacial Molecular Searching Using Forager Dynamics

    NASA Astrophysics Data System (ADS)

    Monserud, Jon H.; Schwartz, Daniel K.

    2016-03-01

    Many biological and technological systems employ efficient non-Brownian intermittent search strategies where localized searches alternate with long flights. Coincidentally, molecular species exhibit intermittent behavior at the solid-liquid interface, where periods of slow motion are punctuated by fast flights through the liquid phase. Single-molecule tracking was used here to observe the interfacial search process of DNA for complementary DNA. Measured search times were qualitatively consistent with an intermittent-flight model, and ˜10 times faster than equivalent Brownian searches, suggesting that molecular searches for reactive sites benefit from similar efficiencies as biological organisms.

  19. Nuclear RNA-seq of single neurons reveals molecular signatures of activation

    PubMed Central

    Lacar, Benjamin; Linker, Sara B.; Jaeger, Baptiste N.; Krishnaswami, Suguna; Barron, Jerika; Kelder, Martijn; Parylak, Sarah; Paquola, Apuã; Venepally, Pratap; Novotny, Mark; O'Connor, Carolyn; Fitzpatrick, Conor; Erwin, Jennifer; Hsu, Jonathan Y.; Husband, David; McConnell, Michael J.; Lasken, Roger; Gage, Fred H.

    2016-01-01

    Single-cell sequencing methods have emerged as powerful tools for identification of heterogeneous cell types within defined brain regions. Application of single-cell techniques to study the transcriptome of activated neurons can offer insight into molecular dynamics associated with differential neuronal responses to a given experience. Through evaluation of common whole-cell and single-nuclei RNA-sequencing (snRNA-seq) methods, here we show that snRNA-seq faithfully recapitulates transcriptional patterns associated with experience-driven induction of activity, including immediate early genes (IEGs) such as Fos, Arc and Egr1. SnRNA-seq of mouse dentate granule cells reveals large-scale changes in the activated neuronal transcriptome after brief novel environment exposure, including induction of MAPK pathway genes. In addition, we observe a continuum of activation states, revealing a pseudotemporal pattern of activation from gene expression alone. In summary, snRNA-seq of activated neurons enables the examination of gene expression beyond IEGs, allowing for novel insights into neuronal activation patterns in vivo. PMID:27090946

  20. 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

  1. Nuclear RNA-seq of single neurons reveals molecular signatures of activation.

    PubMed

    Lacar, Benjamin; Linker, Sara B; Jaeger, Baptiste N; Krishnaswami, Suguna; Barron, Jerika; Kelder, Martijn; Parylak, Sarah; Paquola, Apuã; Venepally, Pratap; Novotny, Mark; O'Connor, Carolyn; Fitzpatrick, Conor; Erwin, Jennifer; Hsu, Jonathan Y; Husband, David; McConnell, Michael J; Lasken, Roger; Gage, Fred H

    2016-01-01

    Single-cell sequencing methods have emerged as powerful tools for identification of heterogeneous cell types within defined brain regions. Application of single-cell techniques to study the transcriptome of activated neurons can offer insight into molecular dynamics associated with differential neuronal responses to a given experience. Through evaluation of common whole-cell and single-nuclei RNA-sequencing (snRNA-seq) methods, here we show that snRNA-seq faithfully recapitulates transcriptional patterns associated with experience-driven induction of activity, including immediate early genes (IEGs) such as Fos, Arc and Egr1. SnRNA-seq of mouse dentate granule cells reveals large-scale changes in the activated neuronal transcriptome after brief novel environment exposure, including induction of MAPK pathway genes. In addition, we observe a continuum of activation states, revealing a pseudotemporal pattern of activation from gene expression alone. In summary, snRNA-seq of activated neurons enables the examination of gene expression beyond IEGs, allowing for novel insights into neuronal activation patterns in vivo. PMID:27090946

  2. Molecular and morphologic data reveal multiple species in Peromyscus pectoralis

    PubMed Central

    Bradley, Robert D.; Schmidly, David J.; Amman, Brian R.; Platt, Roy N.; Neumann, Kathy M.; Huynh, Howard M.; Muñiz-Martínez, Raúl; López-González, Celia; Ordóñez-Garza, Nicté

    2015-01-01

    DNA sequence and morphometric data were used to re-evaluate the taxonomy and systematics of Peromyscus pectoralis. Phylogenetic analyses (maximum likelihood and Bayesian inference) of DNA sequences from the mitochondrial cytochrome-b gene in 44 samples of P. pectoralis indicated 2 well-supported monophyletic clades. The 1st clade contained specimens from Texas historically assigned to P. p. laceianus; the 2nd was comprised of specimens previously referable to P. p. collinus, P. p. laceianus, and P. p. pectoralis obtained from northern and eastern Mexico. Levels of genetic variation (~7%) between these 2 clades indicated that the genetic divergence typically exceeded that reported for other species of Peromyscus. Samples of P. p. laceianus north and south of the Río Grande were not monophyletic. In addition, samples representing P. p. collinus and P. p. pectoralis formed 2 clades that differed genetically by 7.14%. Multivariate analyses of external and cranial measurements from 63 populations of P. pectoralis revealed 4 morpho-groups consistent with clades in the DNA sequence analysis: 1 from Texas and New Mexico assignable to P. p. laceianus; a 2nd from western and southern Mexico assignable to P. p. pectoralis; a 3rd from northern and central Mexico previously assigned to P. p. pectoralis but herein shown to represent an undescribed taxon; and a 4th from southeastern Mexico assignable to P. p. collinus. Based on the concordance of these results, populations from the United States are referred to as P. laceianus, whereas populations from Mexico are referred to as P. pectoralis (including some samples historically assigned to P. p. collinus, P. p. laceianus, and P. p. pectoralis). A new subspecies is described to represent populations south of the Río Grande in northern and central Mexico. Additional research is needed to discern if P. p. collinus warrants species recognition. PMID:26937045

  3. Molecular structure and dynamical properties of niosome bilayers with and without cholesterol incorporation: A molecular dynamics simulation study

    NASA Astrophysics Data System (ADS)

    Ritwiset, Aksornnarong; Krongsuk, Sriprajak; Johns, Jeffrey Roy

    2016-09-01

    Niosomes are non-ionic surfactant vesicles having a bilayer structure formed by self-assembly of hydrated surfactants, usually with cholesterol incorporation. Stability and mechanical properties of niosomes strongly depend on type of non-ionic surfactants and compositions used. In this study we present the structural and dynamical properties of niosome bilayers composed of sorbitan monostearate (Span60) with 0% and 50% cholesterol compositions which are investigated by using molecular dynamics simulations. The simulations reveal that niosome bilayer without cholesterol prefer to form in the gel phase with a higher order structure, while in the presence of cholesterol the bilayer exhibits more fluidity having a less ordered structure. The niosome bilayer with 50% cholesterol inclusion shows an increase of area per lipid (∼11%) and thickness (∼39%) compared with the niosome bilayer without cholesterol. The Span60 tailgroup orientation of the niosome bilayers without cholesterol exhibits more tilt (34.5o ± 0.5) than that of the bilayer with 50% cholesterol (15.4o ± 0.8). Additionally, our results show that the addition of cholesterol to the bilayer causes the higher in lateral and transverse diffusion, as well as an increase in the hydrogen bond number between Span60 and water. Such characteristics not only enhance the niosome stability but also increase the fluidity, which are necessary for the niosomal drug delivery.

  4. Dynamics of molecular superrotors in an external magnetic field

    NASA Astrophysics Data System (ADS)

    Korobenko, Aleksey; Milner, Valery

    2015-08-01

    We excite diatomic oxygen and nitrogen to high rotational states with an optical centrifuge and study their dynamics in an external magnetic field. Ion imaging is employed to directly visualize, and follow in time, the rotation plane of the molecular superrotors. The two different mechanisms of interaction between the magnetic field and the molecular angular momentum in paramagnetic oxygen and non-magnetic nitrogen lead to qualitatively different behaviour. In nitrogen, we observe the precession of the molecular angular momentum around the field vector. In oxygen, strong spin-rotation coupling results in faster and richer dynamics, encompassing the splitting of the rotation plane into three separate components. As the centrifuged molecules evolve with no significant dispersion of the molecular wave function, the observed magnetic interaction presents an efficient mechanism for controlling the plane of molecular rotation.

  5. First principles molecular dynamics without self-consistent field optimization

    SciTech Connect

    Souvatzis, Petros; Niklasson, Anders M. N.

    2014-01-28

    We present a first principles molecular dynamics approach that is based on time-reversible extended Lagrangian Born-Oppenheimer molecular dynamics [A. M. N. Niklasson, Phys. Rev. Lett. 100, 123004 (2008)] in the limit of vanishing self-consistent field optimization. The optimization-free dynamics keeps the computational cost to a minimum and typically provides molecular trajectories that closely follow the exact Born-Oppenheimer potential energy surface. Only one single diagonalization and Hamiltonian (or Fockian) construction are required in each integration time step. The proposed dynamics is derived for a general free-energy potential surface valid at finite electronic temperatures within hybrid density functional theory. Even in the event of irregular functional behavior that may cause a dynamical instability, the optimization-free limit represents a natural starting guess for force calculations that may require a more elaborate iterative electronic ground state optimization. Our optimization-free dynamics thus represents a flexible theoretical framework for a broad and general class of ab initio molecular dynamics simulations.

  6. VUV studies of molecular photofragmentation dynamics

    SciTech Connect

    White, M.G.

    1993-12-01

    State-resolved, photoion and photoelectron methods are used to study the neutral fragmentation and ionization dynamics of small molecules relevant to atmospheric and combustion chemistry. Photodissociation and ionization are initiated by coherent VUV radiation and the fragmentation dynamics are extracted from measurements of product rovibronic state distributions, kinetic energies and angular distributions. The general aim of these studies is to investigate the multichannel interactions between the electronic and nuclear motions which determine the evolution of the photoexcited {open_quotes}complex{close_quotes} into the observed asymptotic channels.

  7. Revealing the dynamics of Class 0 protostellar discs with ALMA

    NASA Astrophysics Data System (ADS)

    Seifried, D.; Sánchez-Monge, Á.; Walch, S.; Banerjee, R.

    2016-06-01

    We present synthetic ALMA observations of Keplerian, protostellar discs in the Class 0 stage studying the emission of molecular tracers like 13CO, C18O, HCO+, H13CO+, N2H+, and H2CO. We model the emission of discs around low- and intermediate-mass protostars. We show that under optimal observing conditions ALMA is able to detect the discs already in the earliest stage of protostellar evolution, although the emission is often concentrated to the innermost 50 au. Therefore, a resolution of a few 0.1 arcsec might be too low to detect Keplerian discs around Class 0 objects. We also demonstrate that under optimal conditions for edge-on discs Keplerian rotation signatures are recognisable, from which protostellar masses can be inferred. For this we here introduce a new approach, which allows us to determine protostellar masses with higher fidelity than before. Furthermore, we show that it is possible to reveal Keplerian rotation even for strongly inclined discs and that ALMA should be able to detect possible signs of fragmentation in face-on discs. In order to give some guidance for future ALMA observations, we investigate the influence of varying observing conditions and source distances. We show that it is possible to probe Keplerian rotation in inclined discs with an observing time of 2 h and a resolution of 0.1 arcsec, even in the case of moderate weather conditions. Furthermore, we demonstrate that under optimal conditions, Keplerian discs around intermediate-mass protostars should be detectable up to kpc distances.

  8. Three-Dimensional Molecular Theory of Solvation Coupled with Molecular Dynamics in Amber

    SciTech Connect

    Luchko, T.; Simmerling, C.; Gusarov, S.; Roe, D.R., Case, D.A.; Tuszynski, J.; Kovalenko, A.

    2010-02-01

    We present the three-dimensional molecular theory of solvation (also known as 3D-RISM) coupled with molecular dynamics (MD) simulation by contracting solvent degrees of freedom, accelerated by extrapolating solvent-induced forces and applying them in large multiple time steps (up to 20 fs) to enable simulation of large biomolecules. The method has been implemented in the Amber molecular modeling package and is illustrated here on alanine-dipeptide and protein-G.

  9. Three-dimensional molecular theory of solvation coupled with molecular dynamics in Amber

    PubMed Central

    Luchko, Tyler; Gusarov, Sergey; Roe, Daniel R.; Simmerling, Carlos; Case, David A.; Tuszynski, Jack; Kovalenko, Andriy

    2010-01-01

    We present the three-dimensional molecular theory of solvation (also known as 3D-RISM) coupled with molecular dynamics (MD) simulation by contracting solvent degrees of freedom, accelerated by extrapolating solvent-induced forces and applying them in large multi-time steps (up to 20 fs) to enable simulation of large biomolecules. The method has been implemented in the Amber molecular modeling package, and is illustrated here on alanine dipeptide and protein G. PMID:20440377

  10. Exploration of ice growth through molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Rozmanov, Dmitri

    Ice is the solid form of water, the most important chemical compound for life. A large number of atmospherically and biologically relevant processes occur at interfaces between these two phases. At the molecular level, crystallization in general, and ice growth in particular, is a less complex example of a natural process of self-assembling, where an ordered crystal is created from a disordered and mobile liquid. This thesis describes efforts to extend our understanding of the process of ice crystal growth by employing the technique of molecular simulations. Molecular simulations have become a de facto standard for these kinds of studies due to fundamental technical difficulties for experimental methods to probe growing interfaces. The study described in this thesis was done as a series of self-contained and relatively independent investigations linked together by one general goal of extending our understanding of the ice growth process. A new general simulation code was developed to answer technical demands of the project. This simulation code was used to perform all the simulations reported in here. The formal development necessary for this work lead to the publication of two new methods of integration of rotational equations of motion, as well as new simulation and data analysis techniques. An investigation of the diffusive behaviour of the TIP4P-2005 model of water was necessary for interpretation of our initial ice growth study and resulted in another research project component; which results provided information necessary for the analysis of ice growth kinetics and also revealed new details of the translational and rotational dynamics of the TIP4P-2005 model in liquid phase. The main body of work directly addressing the primary objective of the project, the process of ice growth, was done as four separate simulation studies which are described in this thesis in detail. The main results of this thesis can be summarized as follows. The molecular dynamics

  11. Effect of acetone accumulation on structure and dynamics of lipid membranes studied by molecular dynamics simulations.

    PubMed

    Posokhov, Yevgen O; Kyrychenko, Alexander

    2013-10-01

    The modulation of the properties and function of cell membranes by small volatile substances is important for many biomedical applications. Despite available experimental results, molecular mechanisms of action of inhalants and organic solvents, such as acetone, on lipid membranes remain not well understood. To gain a better understanding of how acetone interacts with membranes, we have performed a series of molecular dynamics (MD) simulations of a POPC bilayer in aqueous solution in the presence of acetone, whose concentration was varied from 2.8 to 11.2 mol%. The MD simulations of passive distribution of acetone between a bulk water phase and a lipid bilayer show that acetone favors partitioning into the water-free region of the bilayer, located near the carbonyl groups of the phospholipids and at the beginning of the hydrocarbon core of the lipid membrane. Using MD umbrella sampling, we found that the permeability barrier of ~0.5 kcal/mol exists for acetone partitioning into the membrane. In addition, a Gibbs free energy profile of the acetone penetration across a bilayer demonstrates a favorable potential energy well of -3.6 kcal/mol, located at 15-16Å from the bilayer center. The analysis of the structural and dynamics properties of the model membrane revealed that the POPC bilayer can tolerate the presence of acetone in the concentration range of 2.8-5.6 mol%. The accumulation of the higher acetone concentration of 11.2 mol% results, however, in drastic disordering of phospholipid packing and the increase in the membrane fluidity. The acetone molecules push the lipid heads apart and, hence, act as spacers in the headgroup region. This effect leads to the increase in the average headgroup area per molecule. In addition, the acyl tail region of the membrane also becomes less dense. We suggest, therefore, that the molecular mechanism of acetone action on the phospholipid bilayer has many common features with the effects of short chain alcohols, DMSO, and

  12. Dynamic Localization of Electronic Excitation in Photosynthetic Complexes Revealed with Chiral Two-Dimensional Spectroscopy

    PubMed Central

    Fidler, Andrew F.; Singh, Ved P.; Long, Phillip D.; Dahlberg, Peter D.; Engel, Gregory S.

    2014-01-01

    Time-resolved ultrafast optical probes of chiral dynamics provide a new window allowing us to explore how interactions with such structured environments drive electronic dynamics. Incorporating optical activity into time-resolved spectroscopies has proven challenging due to the small signal and large achiral background. Here, we demonstrate that two-dimensional electronic spectroscopy can be adapted to detect chiral signals and that these signals reveal how excitations delocalize and contract following excitation. We dynamically probe the evolution of chiral electronic structure in the light harvesting complex 2 of purple bacteria following photoexcitation by creating a chiral two-dimensional mapping. The dynamics of the chiral two-dimensional signal directly reports on changes in the degree of delocalization of the excitonic state following photoexcitation. The mechanism of energy transfer in this system may enhance transfer probability due to the coherent coupling among chromophores while suppressing fluorescence that arises from populating delocalized states. This generally applicable spectroscopy will provide an incisive tool to probe ultrafast transient molecular fluctuations that are obscured in non-chiral experiments. PMID:24504144

  13. Dynamic localization of electronic excitation in photosynthetic complexes revealed with chiral two-dimensional spectroscopy.

    PubMed

    Fidler, Andrew F; Singh, Ved P; Long, Phillip D; Dahlberg, Peter D; Engel, Gregory S

    2014-01-01

    Time-resolved ultrafast optical probes of chiral dynamics provide a new window allowing us to explore how interactions with such structured environments drive electronic dynamics. Incorporating optical activity into time-resolved spectroscopies has proven challenging because of the small signal and large achiral background. Here we demonstrate that two-dimensional electronic spectroscopy can be adapted to detect chiral signals and that these signals reveal how excitations delocalize and contract following excitation. We dynamically probe the evolution of chiral electronic structure in the light-harvesting complex 2 of purple bacteria following photoexcitation by creating a chiral two-dimensional mapping. The dynamics of the chiral two-dimensional signal directly reports on changes in the degree of delocalization of the excitonic states following photoexcitation. The mechanism of energy transfer in this system may enhance transfer probability because of the coherent coupling among chromophores while suppressing fluorescence that arises from populating delocalized states. This generally applicable spectroscopy will provide an incisive tool to probe ultrafast transient molecular fluctuations that are obscured in non-chiral experiments. PMID:24504144

  14. Comparison of mode-coupling theory with molecular dynamics simulations from a unified point of view.

    PubMed

    Narumi, Takayuki; Tokuyama, Michio

    2011-08-01

    We study the tagged-particle dynamics by solving equations of the mode-coupling theory (MCT). The numerical solutions are compared with results obtained by the molecular dynamics (MD) simulations from a unified point of view proposed by Tokuyama [Phys. Rev. E 80, 031503 (2009)]. We propose a way of comparison in which the reduced long-time self-diffusion coefficient is used to characterize states of the system. The comparison reveals that the tagged-particle dynamics calculated from MCT qualitatively deviates from that obtained by MD. Our results suggest that the deviation originates from the starting equation of MCT.

  15. The role of hydrogen bonds in an aqueous solution of acetylsalicylic acid: a molecular dynamics simulation study.

    PubMed

    Donnamaria, Maria Cristina; de Xammar Oro, Juan Roberto

    2011-10-01

    This work focuses on the role of the dynamic hydrogen bonds (HB) formed in an aqueous solution of aspirin using molecular dynamics simulation. The statistics reveal the existence of internal HB that inhibit the rotational movements of the acetyl and the carboxylic acid groups, forcing the molecule to adopt a closed conformer structure in water, and playing an important role in stabilizing this conformation.

  16. Combining Molecular Dynamics and Density Functional Theory

    NASA Astrophysics Data System (ADS)

    Kaxiras, Efthimios

    2015-03-01

    The time evolution of a system consisting of electrons and ions is often treated in the Born-Oppenheimer approximation, with electrons in their instantaneous ground state. This approach cannot capture many interesting processes that involved excitation of electrons and its effects on the coupled electron-ion dynamics. The time scale needed to accurately resolve the evolution of electron dynamics is atto-seconds. This poses a challenge to the simulation of important chemical processes that typically take place on time scales of pico-seconds and beyond, such as reactions at surfaces and charge transport in macromolecules. We will present a methodology based on time-dependent density functional theory for electrons, and classical (Ehrenfest) dynamics for the ions, that successfully captures such processes. We will give a review of key features of the method and several applications. These illustrate how the atomic and electronic structure evolution unravels the elementary steps that constitute a chemical reaction. In collaboration with: G. Kolesov, D. Vinichenko, G. Tritsaris, C.M. Friend, Departments of Physics and of Chemistry and Chemical Biology.

  17. Pseudorotational Dynamics of Small Molecular Systems

    NASA Astrophysics Data System (ADS)

    Hagelberg, Frank

    2001-03-01

    A variety of dynamic effects related to the pseudorotation of triatomic singly charged species is explored using the Electron Nuclear Dynamics(END)Theory. The concepts relevant to the motion studied are developed through the analysis of the simplest polyatomic molecule, namely H3+. It is shown that the limiting situation of circular pseudorotation is unattainable for this case. This observation is explained by the anisotropy of the ground state potential energy surface caused by the interaction between the D3h ground state of the molecule and its twofold degenerate first excited state. Further, pseudorotational motion is demonstrated to induce a rotational mode which in turn couples the two shape oscillation modes by action of the Coriolis force. Analogous phenomena are found for Li3+. The Jahn-Teller system C3+ exhibits a range of new motional effects. Particularly, a characteristic frequency shift between the two shape oscillation modes is obtained, resulting from the anisotropy in the curvature of the C2v minimum of C3+. The Jahn-Teller parameters of the system are determined from Electron Nuclear Dynamics simulations.

  18. Hydrolysis of Al3+ from constrained molecular dynamics

    NASA Astrophysics Data System (ADS)

    Ikeda, Takashi; Hirata, Masaru; Kimura, Takaumi

    2006-02-01

    We investigated the hydrolysis reactions of Al3+ in AlCl3 aqueous solution using the constrained molecular dynamics based on the Car-Parrinello molecular-dynamics method. By employing the proton-aluminum coordination number as a reaction coordinate in the constrained molecular dynamics the deprotonation as well as dehydration processes are successfully realized. From our free-energy difference of ΔG0≃8.0kcalmol-1 the hydrolysis constant pKa1 is roughly estimated as 5.8, comparable to the literature value of 5.07. We show that the free-energy difference for the hydrolysis of Al3+ in acidic conditions is at least 4kcalmol-1 higher than that in neutral condition, indicating that the hydrolysis reaction is inhibited by the presence of excess protons located around the hydrated ion, in agreement with the change of the predominant species by pH.

  19. Molecular dynamics insights into human aquaporin 2 water channel.

    PubMed

    Binesh, A R; Kamali, R

    2015-12-01

    In this study, the first molecular dynamics simulation of the human aquaporin 2 is performed and for a better understanding of the aquaporin 2 permeability performance, the characteristics of water transport in this protein channel and key biophysical parameters of AQP2 tetramer including osmotic and diffusive permeability constants and the pore radius are investigated. For this purpose, recently recovered high resolution X-ray crystal structure of` the human aquaporin 2 is used to perform twenty nanosecond molecular dynamics simulation of fully hydrated tetramer of this protein embedded in a lipid bilayer. The resulting water permeability characteristics of this protein channel showed that the water permeability of the human AQP2 is in a mean range in comparison with other human aquaporins family. Finally, the results reported in this research demonstrate that molecular dynamics simulation of human AQP2 provided useful insights into the mechanisms of water permeation and urine concentration in the human kidney. PMID:26489820

  20. Theoretical Analysis of Dynamic Processes for Interacting Molecular Motors

    PubMed Central

    Teimouri, Hamid; Kolomeisky, Anatoly B.; Mehrabiani, Kareem

    2015-01-01

    Biological transport is supported by collective dynamics of enzymatic molecules that are called motor proteins or molecular motors. Experiments suggest that motor proteins interact locally via short-range potentials. We investigate the fundamental role of these interactions by analyzing a new class of totally asymmetric exclusion processes where interactions are accounted for in a thermodynamically consistent fashion. It allows us to connect explicitly microscopic features of motor proteins with their collective dynamic properties. Theoretical analysis that combines various mean-field calculations and computer simulations suggests that dynamic properties of molecular motors strongly depend on interactions, and correlations are stronger for interacting motor proteins. Surprisingly, it is found that there is an optimal strength of interactions (weak repulsion) that leads to a maximal particle flux. It is also argued that molecular motors transport is more sensitive to attractive interactions. Applications of these results for kinesin motor proteins are discussed. PMID:25688287

  1. Molecular dynamics insights into human aquaporin 2 water channel.

    PubMed

    Binesh, A R; Kamali, R

    2015-12-01

    In this study, the first molecular dynamics simulation of the human aquaporin 2 is performed and for a better understanding of the aquaporin 2 permeability performance, the characteristics of water transport in this protein channel and key biophysical parameters of AQP2 tetramer including osmotic and diffusive permeability constants and the pore radius are investigated. For this purpose, recently recovered high resolution X-ray crystal structure of` the human aquaporin 2 is used to perform twenty nanosecond molecular dynamics simulation of fully hydrated tetramer of this protein embedded in a lipid bilayer. The resulting water permeability characteristics of this protein channel showed that the water permeability of the human AQP2 is in a mean range in comparison with other human aquaporins family. Finally, the results reported in this research demonstrate that molecular dynamics simulation of human AQP2 provided useful insights into the mechanisms of water permeation and urine concentration in the human kidney.

  2. Thermal Conductivity of Natural Rubber Using Molecular Dynamics Simulation.

    PubMed

    He, Yan; Ma, Lian-Xiang; Tang, Yuan-Zheng; Wang, Ze-Peng; Li, Wei; Kukulka, David

    2015-04-01

    Thermal conductivity of natural rubber has been studied by classic molecular dynamics simulations. These simulations are performed on natural rubber models using the adaptive intermolecular reactive empirical bond order (AIREBO) and the Green-Kubo molecular dynamics (MD) simulations. Thermal conductivity results are found to be very sensitive to the time step used in the simulations. For a time step of 0.1 fs, the converged thermal conductivity is 0.35 W/mK. Additionally the anisotropic thermal conductivity of a specially-modeled natural rubber model with straight molecular chains was studied and values of thermal conductivity parallel to the molecular chains was found to be 1.71 W/mK and the anisotropy, 2Kz/(Kx + Ky), was 2.67.

  3. Bridging fluctuating hydrodynamics and molecular dynamics simulations of fluids.

    PubMed

    Voulgarakis, Nikolaos K; Chu, Jhih-Wei

    2009-04-01

    A new multiscale coarse-graining (CG) methodology is developed to bridge molecular and hydrodynamic models of a fluid. The hydrodynamic representation considered in this work is based on the equations of fluctuating hydrodynamics (FH). The essence of this method is a mapping from the position and velocity vectors of a snapshot of a molecular dynamics (MD) simulation to the field variables on Eulerian cells of a hydrodynamic representation. By explicit consideration of the effective lengthscale d(mol) that characterizes the volume of a molecule, the computed density fluctuations from MD via our mapping procedure have volume dependence that corresponds to a grand canonical ensemble of a cold liquid even when a small cell length (5-10 A) is used in a hydrodynamic representation. For TIP3P water at 300 K and 1 atm, d(mol) is found to be 2.4 A, corresponding to the excluded radius of a water molecule as revealed by its center-of-mass radial distribution function. By matching the density fluctuations and autocorrelation functions of momentum fields computed from solving the FH equations with those computed from MD simulation, the sound velocity and shear and bulk viscosities of a CG hydrodynamic model can be determined directly from MD. Furthermore, a novel staggered discretization scheme is developed for solving the FH equations of an isothermal compressive fluid in a three dimensional space with a central difference method. This scheme demonstrates high accuracy in satisfying the fluctuation-dissipation theorem. Since the causative relationship between field variables and fluxes is captured, we demonstrate that the staggered discretization scheme also predicts correct physical behaviors in simulating transient fluid flows. The techniques presented in this work may also be employed to design multiscale strategies for modeling complex fluids and macromolecules in solution. PMID:19355721

  4. Studying Interactions by Molecular Dynamics Simulations at High Concentration

    PubMed Central

    Fogolari, Federico; Corazza, Alessandra; Toppo, Stefano; Tosatto, Silvio C. E.; Viglino, Paolo; Ursini, Fulvio; Esposito, Gennaro

    2012-01-01

    Molecular dynamics simulations have been used to study molecular encounters and recognition. In recent works, simulations using high concentration of interacting molecules have been performed. In this paper, we consider the practical problems for setting up the simulation and to analyse the results of the simulation. The simulation of beta 2-microglobulin association and the simulation of the binding of hydrogen peroxide by glutathione peroxidase are provided as examples. PMID:22500085

  5. Molecular dynamics analysis on buckling of defective carbon nanotubes.

    PubMed

    Kulathunga, D D T K; Ang, K K; Reddy, J N

    2010-09-01

    Owing to their remarkable mechanical properties, carbon nanotubes have been employed in many diverse areas of applications. However, similar to any of the many man-made materials used today, carbon nanotubes (CNTs) are also susceptible to various kinds of defects. Understanding the effect of defects on the mechanical properties and behavior of CNTs is essential in the design of nanotube-based devices and composites. It has been found in various past studies that these defects can considerably affect the tensile strength and fracture of CNTs. Comprehensive studies on the effect of defects on the buckling and vibration of nanotubes is however lacking in the literature. In this paper, the effects of various configurations of atomic vacancy defects, on axial buckling of single-walled carbon nanotubes (SWCNTs), in different thermal environments, is investigated using molecular dynamics simulations (MDS), based on a COMPASS force field. Our findings revealed that even a single missing atom can cause a significant reduction in the critical buckling strain and load of SWCNTs. In general, increasing the number of missing atoms, asymmetry of vacancy configurations and asymmetric distribution of vacancy clusters seemed to lead to higher deterioration in buckling properties. Further, SWCNTs with a single vacancy cluster, compared to SWCNTs with two or more vacancy clusters having the same number of missing atoms, appeared to cause higher deterioration of buckling properties. However, exceptions from the above mentioned trends could be expected due to chemical instabilities of defects. Temperature appeared to have less effect on defective CNTs compared to pristine CNTs.

  6. Molecular dynamics studies of the conformation of sorbitol

    PubMed Central

    Lerbret, A.; Mason, P.E.; Venable, R.M.; Cesàro, A.; Saboungi, M.-L.; Pastor, R.W.; Brady, J.W.

    2009-01-01

    Molecular dynamics simulations of a 3 m aqueous solution of D-sorbitol (also called D-glucitol) have been performed at 300 K, as well as at two elevated temperatures to promote conformational transitions. In principle, sorbitol is more flexible than glucose since it does not contain a constraining ring. However, a conformational analysis revealed that the sorbitol chain remains extended in solution, in contrast to the bent conformation found experimentally in the crystalline form. While there are 243 staggered conformations of the backbone possible for this open-chain polyol, only a very limited number were found to be stable in the simulations. Although many conformers were briefly sampled, only eight were significantly populated in the simulation. The carbon backbones of all but two of these eight conformers were completely extended, unlike the bent crystal conformation. These extended conformers were stabilized by a quite persistent intramolecular hydrogen bond between the hydroxyl groups of carbon C-2 and C-4. The conformational populations were found to be in good agreement with the limited available NMR data except for the C-2–C-3 torsion (spanned by the O-2–O-4 hydrogen bond), where the NMR data supports a more bent structure. PMID:19744646

  7. Cavity-coupled molecular vibrational spectra and dynamics

    NASA Astrophysics Data System (ADS)

    Owrutsky, Jeffrey; Dunkelberger, Adam; Long, James; Fears, Kenan; Dressick, Walter; Compton, Ryan; Spann, Bryan; Simpkins, Blake

    Coherent coupling between an optical transition and confined optical mode, when sufficiently strong, gives rise to new modes separated by the vacuum Rabi splitting. Such systems have been investigated for electronic-state transitions, for quantum wells and dots, however, only very recently have vibrational transitions been explored. Both static and dynamic results are described for vibrational bands strongly coupled to optical cavities. First, we experimentally and numerically describe coupling between a Fabry-Perot cavity and carbonyl stretch (~1730 cm1) in poly-methylmethacrylate as a function of several parameters of the system including absorber strength and concentration as well as cavity length. Similar studies are carried out for anions both in solution and exchanged into cationic polymers. Ultrafast pump-probe studies are performed on W(CO)6 in solution which reveals changes to the transient spectra and modified relaxation rates. We believe these modified relaxation rates are a consequence of the energy separation between the vibration-cavity polariton modes and excited state transitions. Cavity-modified vibrational states and energy transfer may provide a new avenue for systematic control of molecular processes and chemistry. The work supported by the Office of Naval Research through the Naval Research Laboratory.

  8. Steered molecular dynamics studies of titin I1 domain unfolding.

    PubMed Central

    Gao, Mu; Wilmanns, Matthias; Schulten, Klaus

    2002-01-01

    The cardiac muscle protein titin, responsible for developing passive elasticity and extensibility of muscle, possesses about 40 immunoglobulin-like (Ig) domains in its I-band region. Atomic force microscopy (AFM) and steered molecular dynamics (SMD) have been successfully combined to investigate the reversible unfolding of individual Ig domains. However, previous SMD studies of titin I-band modules have been restricted to I27, the only structurally known Ig domain from the distal region of the titin I-band. In this paper we report SMD simulations unfolding I1, the first structurally available Ig domain from the proximal region of the titin I-band. The simulations are carried out with a view toward upcoming atomic force microscopy experiments. Both constant velocity and constant force stretching have been employed to model mechanical unfolding of oxidized I1, which has a disulfide bond bridging beta-strands C and E, as well as reduced I1, in which the disulfide bridge is absent. The simulations reveal that I1 is protected against external stress mainly through six interstrand hydrogen bonds between its A and B beta-strands. The disulfide bond enhances the mechanical stability of oxidized I1 domains by restricting the rupture of backbone hydrogen bonds between the A'- and G-strands. The disulfide bond also limits the maximum extension of I1 to approximately 220 A. Comparison of the unfolding pathways of I1 and I27 are provided and implications to AFM experiments are discussed. PMID:12496110

  9. Mechanical properties of borophene films: a reactive molecular dynamics investigation

    NASA Astrophysics Data System (ADS)

    Quy Le, Minh; Mortazavi, Bohayra; Rabczuk, Timon

    2016-11-01

    The most recent experimental advances could provide ways for the fabrication of several atomic thick and planar forms of boron atoms. For the first time, we explore the mechanical properties of five types of boron films with various vacancy ratios ranging from 0.1–0.15, using molecular dynamics simulations with ReaxFF force field. It is found that the Young’s modulus and tensile strength decrease with increasing the temperature. We found that boron sheets exhibit an anisotropic mechanical response due to the different arrangement of atoms along the armchair and zigzag directions. At room temperature, 2D Young’s modulus and fracture stress of these five sheets appear in the range 63–136 N m‑1 and 12–19 N m‑1, respectively. In addition, the strains at tensile strength are in the ranges of 9%–14%, 11%–19%, and 10%–16% at 1, 300, and 600 K, respectively. This investigation not only reveals the remarkable stiffness of 2D boron, but establishes relations between the mechanical properties of the boron sheets to the loading direction, temperature and atomic structures.

  10. Homology model and molecular dynamics simulation of carp ovum cystatin.

    PubMed

    Su, Yuan-Chen; Lin, Jin-Chung; Liu, Hsuan-Liang

    2005-01-01

    In this study, a homology model of carp ovum cystatin was constructed based on the crystal structure of chicken egg white cystatin. The results of amino acid sequence alignment indicate that these two proteins exhibit 36.11% of sequence identity. The resultant homology model reveals that carp ovum cystatin shares similar folds as chicken egg white cystatin, particularly in the conserved regions of Q48-V49-G52 and P98-W99 and the locations of two disulfide bonds, C67-C76 and C90-C110. However, the results of 1 ns molecular dynamics simulations show that carp ovum cystatin exhibits less structural integrity than chicken egg white cystatin in explicit water at 300 K. The relatively hydrophilic Met62 of carp ovum cystatin, corresponding to the hydrophobic Leu68 of human cystatin C and Ile66 of chicken egg white cystatin, may destabilize the hydrophobic core and form a dimeric structure more easily through domain swapping. A total of 16 positively charged residues are equally distributed on the surface of carp ovum cystatin, resulting in agglutination with the negatively charged spermatozoa via electrostatic interaction. Thus, carp ovum cystatin is considered to be important in preventing carp eggs from polyspermy.

  11. Molecular dynamics simulations of water droplets on polymer surfaces.

    PubMed

    Hirvi, Janne T; Pakkanen, Tapani A

    2006-10-14

    Molecular dynamics simulations were used to study the wetting of polymer surfaces with water. Contact angles of water droplets on crystalline and two amorphous polyethylene (PE) and poly(vinyl chloride) (PVC) surfaces were extracted from atomistic simulations. Crystalline surfaces were produced by duplicating the unit cell of an experimental crystal structure, and amorphous surfaces by pressing the bulk polymer step by step at elevated temperature between two repulsive grid surfaces to a target density. Different-sized water droplets on the crystalline PE surface revealed a slightly positive line tension on the order of 10(-12)-10(-11) N, whereas droplets on crystalline PVC did not yield a definite line tension. Microscopic contact angles produced by the simple point charge (SPC) water model were mostly a few degrees smaller than those produced by the extended SPC model, which, as the model with lowest bulk energy, presents an upper boundary for contact angles. The macroscopic contact angle for the SPC model was 94 degrees on crystalline PVC and 113 degrees on crystalline PE. Amorphicity of the surface increased the water contact angle on PE but decreased it on PVC, for both water models. If the simulated contact angles on crystalline and amorphous surfaces are combined in proportion to the crystallinity of the polymer in question, simulated values in relatively good agreement with measured values are obtained.

  12. Mechanical properties of borophene films: a reactive molecular dynamics investigation.

    PubMed

    Le, Minh Quy; Mortazavi, Bohayra; Rabczuk, Timon

    2016-11-01

    The most recent experimental advances could provide ways for the fabrication of several atomic thick and planar forms of boron atoms. For the first time, we explore the mechanical properties of five types of boron films with various vacancy ratios ranging from 0.1-0.15, using molecular dynamics simulations with ReaxFF force field. It is found that the Young's modulus and tensile strength decrease with increasing the temperature. We found that boron sheets exhibit an anisotropic mechanical response due to the different arrangement of atoms along the armchair and zigzag directions. At room temperature, 2D Young's modulus and fracture stress of these five sheets appear in the range 63-136 N m(-1) and 12-19 N m(-1), respectively. In addition, the strains at tensile strength are in the ranges of 9%-14%, 11%-19%, and 10%-16% at 1, 300, and 600 K, respectively. This investigation not only reveals the remarkable stiffness of 2D boron, but establishes relations between the mechanical properties of the boron sheets to the loading direction, temperature and atomic structures. PMID:27678335

  13. Molecular-dynamics simulation of hydrogen diffusion in palladium

    NASA Astrophysics Data System (ADS)

    Li, Yinggang; Wahnström, Göran

    1992-12-01

    Molecular-dynamics simulations for hydrogen diffusion in Pd are performed for a system consisting of 256 Pd atoms and 8 H atoms at the temperature T=623 K. Under these conditions detailed quasielastic-neutron-scattering (QNS) data are available. For the interatomic interactions we use the embedded-atom method (EAM), which incorporates some essential many-body effects in metals. Based on the EAM approach, the wave-vector dependence of the width of the QNS peak is investigated in detail. It is found that a single electronically adiabatic potential-energy surface cannot reproduce the observed wave-vector dependence. After incorporating the coupling of hydrogen atoms to the low-lying electron-hole pair excitations among the conduction electrons, close agreement with the experimental data is obtained. This is a strong indication that one has to go beyond the Born-Oppenheimer approximation in order to characterize correctly the diffusive motion of hydrogen in metals. To reveal the diffusive behavior in more detail, the residence time distribution and the correlation character in diffusion direction are investigated. We found that including the nonadiabatic corrections reduces the probability for the H atoms to move over several lattice sites without getting trapped in between. As a result, the motion of the H atoms becomes more similar to that assumed in the Chudley-Elliott model, which describes well the QNS data for the wave-vector dependence of the width.

  14. Mechanical properties of borophene films: a reactive molecular dynamics investigation.

    PubMed

    Le, Minh Quy; Mortazavi, Bohayra; Rabczuk, Timon

    2016-11-01

    The most recent experimental advances could provide ways for the fabrication of several atomic thick and planar forms of boron atoms. For the first time, we explore the mechanical properties of five types of boron films with various vacancy ratios ranging from 0.1-0.15, using molecular dynamics simulations with ReaxFF force field. It is found that the Young's modulus and tensile strength decrease with increasing the temperature. We found that boron sheets exhibit an anisotropic mechanical response due to the different arrangement of atoms along the armchair and zigzag directions. At room temperature, 2D Young's modulus and fracture stress of these five sheets appear in the range 63-136 N m(-1) and 12-19 N m(-1), respectively. In addition, the strains at tensile strength are in the ranges of 9%-14%, 11%-19%, and 10%-16% at 1, 300, and 600 K, respectively. This investigation not only reveals the remarkable stiffness of 2D boron, but establishes relations between the mechanical properties of the boron sheets to the loading direction, temperature and atomic structures.

  15. State-to-state dynamics of molecular energy transfer

    SciTech Connect

    Gentry, W.R.; Giese, C.F.

    1993-12-01

    The goal of this research program is to elucidate the elementary dynamical mechanisms of vibrational and rotational energy transfer between molecules, at a quantum-state resolved level of detail. Molecular beam techniques are used to isolate individual molecular collisions, and to control the kinetic energy of collision. Lasers are used both to prepare specific quantum states prior to collision by stimulated-emission pumping (SEP), and to measure the distribution of quantum states in the collision products by laser-induced fluorescence (LIF). The results are interpreted in terms of dynamical models, which may be cast in a classical, semiclassical or quantum mechanical framework, as appropriate.

  16. AceCloud: Molecular Dynamics Simulations in the Cloud.

    PubMed

    Harvey, M J; De Fabritiis, G

    2015-05-26

    We present AceCloud, an on-demand service for molecular dynamics simulations. AceCloud is designed to facilitate the secure execution of large ensembles of simulations on an external cloud computing service (currently Amazon Web Services). The AceCloud client, integrated into the ACEMD molecular dynamics package, provides an easy-to-use interface that abstracts all aspects of interaction with the cloud services. This gives the user the experience that all simulations are running on their local machine, minimizing the learning curve typically associated with the transition to using high performance computing services.

  17. How Dynamic Visualization Technology can Support Molecular Reasoning

    NASA Astrophysics Data System (ADS)

    Levy, Dalit

    2012-11-01

    This paper reports the results of a study aimed at exploring the advantages of dynamic visualization for the development of better understanding of molecular processes. We designed a technology-enhanced curriculum module in which high school chemistry students conduct virtual experiments with dynamic molecular visualizations of solid, liquid, and gas. They interact with the visualizations and carry out inquiry activities to make and refine connections between observable phenomena and atomic level processes related to phase change. The explanations proposed by 300 pairs of students in response to pre/post-assessment items have been analyzed using a scale for measuring the level of molecular reasoning. Results indicate that from pretest to posttest, students make progress in their level of molecular reasoning and are better able to connect intermolecular forces and phase change in their explanations. The paper presents the results through the lens of improvement patterns and the metaphor of the "ladder of molecular reasoning," and discusses how this adds to our understanding of the benefits of interacting with dynamic molecular visualizations.

  18. Multiple time step integrators in ab initio molecular dynamics

    SciTech Connect

    Luehr, Nathan; Martínez, Todd J.; Markland, Thomas E.

    2014-02-28

    Multiple time-scale algorithms exploit the natural separation of time-scales in chemical systems to greatly accelerate the efficiency of molecular dynamics simulations. Although the utility of these methods in systems where the interactions are described by empirical potentials is now well established, their application to ab initio molecular dynamics calculations has been limited by difficulties associated with splitting the ab initio potential into fast and slowly varying components. Here we present two schemes that enable efficient time-scale separation in ab initio calculations: one based on fragment decomposition and the other on range separation of the Coulomb operator in the electronic Hamiltonian. We demonstrate for both water clusters and a solvated hydroxide ion that multiple time-scale molecular dynamics allows for outer time steps of 2.5 fs, which are as large as those obtained when such schemes are applied to empirical potentials, while still allowing for bonds to be broken and reformed throughout the dynamics. This permits computational speedups of up to 4.4x, compared to standard Born-Oppenheimer ab initio molecular dynamics with a 0.5 fs time step, while maintaining the same energy conservation and accuracy.

  19. Electron-phonon interaction within classical molecular dynamics

    DOE PAGES

    Tamm, A.; Samolyuk, G.; Correa, A. A.; Klintenberg, M.; Aabloo, A.; Caro, A.

    2016-07-14

    Here, we present a model for nonadiabatic classical molecular dynamics simulations that captures with high accuracy the wave-vector q dependence of the phonon lifetimes, in agreement with quantum mechanics calculations. It is based on a local view of the e-ph interaction where individual atom dynamics couples to electrons via a damping term that is obtained as the low-velocity limit of the stopping power of a moving ion in a host. The model is parameter free, as its components are derived from ab initio-type calculations, is readily extended to the case of alloys, and is adequate for large-scale molecular dynamics computermore » simulations. We also show how this model removes some oversimplifications of the traditional ionic damped dynamics commonly used to describe situations beyond the Born-Oppenheimer approximation.« less

  20. Electron-phonon interaction within classical molecular dynamics

    NASA Astrophysics Data System (ADS)

    Tamm, A.; Samolyuk, G.; Correa, A. A.; Klintenberg, M.; Aabloo, A.; Caro, A.

    2016-07-01

    We present a model for nonadiabatic classical molecular dynamics simulations that captures with high accuracy the wave-vector q dependence of the phonon lifetimes, in agreement with quantum mechanics calculations. It is based on a local view of the e -ph interaction where individual atom dynamics couples to electrons via a damping term that is obtained as the low-velocity limit of the stopping power of a moving ion in a host. The model is parameter free, as its components are derived from ab initio-type calculations, is readily extended to the case of alloys, and is adequate for large-scale molecular dynamics computer simulations. We also show how this model removes some oversimplifications of the traditional ionic damped dynamics commonly used to describe situations beyond the Born-Oppenheimer approximation.

  1. Numerical methods for molecular dynamics. Progress report

    SciTech Connect

    Skeel, R.D.

    1991-12-31

    This report summarizes our research progress to date on the use of multigrid methods for three-dimensional elliptic partial differential equations, with particular emphasis on application to the Poisson-Boltzmann equation of molecular biophysics. This research is motivated by the need for fast and accurate numerical solution techniques for three-dimensional problems arising in physics and engineering. In many applications these problems must be solved repeatedly, and the extremely large number of discrete unknowns required to accurately approximate solutions to partial differential equations in three-dimensional regions necessitates the use of efficient solution methods. This situation makes clear the importance of developing methods which are of optimal order (or nearly so), meaning that the number of operations required to solve the discrete problem is on the order of the number of discrete unknowns. Multigrid methods are generally regarded as being in this class of methods, and are in fact provably optimal order for an increasingly large class of problems. The fundamental goal of this research is to develop a fast and accurate numerical technique, based on multi-level principles, for the solutions of the Poisson-Boltzmann equation of molecular biophysics and similar equations occurring in other applications. An outline of the report is as follows. We first present some background material, followed by a survey of the literature on the use of multigrid methods for solving problems similar to the Poisson-Boltzmann equation. A short description of the software we have developed so far is then given, and numerical results are discussed. Finally, our research plans for the coming year are presented.

  2. Coarse-Grained Molecular Dynamics: Dissipation Due to Internal Modes

    SciTech Connect

    Rudd, R E

    2001-12-21

    We describe progress on the issue of pathological elastic wave reflection in atomistic and multiscale simulation. First we briefly review Coarse-Grained Molecular Dynamics (CGMD). Originally CGMD was formulated as a Hamiltonian system in which energy is conserved. This formulation is useful for many applications, but recently CGMD has been extended to include generalized Langevin forces. Here we describe how Langevin dynamics arise naturally in CGMD, and we examine the implication for elastic wave scattering.

  3. Plastic dislocation motion via nonequilibrium molecular and continuum dynamics

    SciTech Connect

    Hoover, W.G.; Ladd, A.J.C.; Hoover, N.E.

    1980-09-29

    The classical two-dimensional close-packed triangular lattice, with nearest-neighbor spring forces, is a convenient standard material for the investigation of dislocation motion and plastic flow. Two kinds of calculations, based on this standard material, are described here: (1) Molecular Dynamics simulations, incorporating adiabatic strains described with the help of Doll's Tensor, and (2) Continuum Dynamics simulations, incorporating periodic boundaries and dislocation interaction through stress-field superposition.

  4. Input File Creation for the Molecular Dynamics Program LAMMPS.

    2001-05-30

    The program creates an input data file for the molecular dynamics program LAMMPS. The input file created is a liquid mixture between two walls explicitly composed of particles. The liquid molecules are modeled as a bead-spring molecule. The input data file specifies the position and topology of the starting state. The data structure of input allows for dynamic bond creation (cross-linking) within the LAMMPS code.

  5. First principles calculation of oxygen K edge absorption spectrum of acetic acid: Relationship between the spectrum and molecular dynamics

    NASA Astrophysics Data System (ADS)

    Matsui, Yoshiki; Mizoguchi, Teruyasu

    2016-04-01

    First principles calculation of the oxygen K-edge absorption near-edge structure of liquid acetic acid was performed to investigate the relationship between the spectrum and the molecular dynamics in a liquid. The single and double bonded oxygens gave strong peaks at different energies. A liquid model constructed using a molecular dynamics simulation reproduced the experimental spectrum. We revealed that the effect of the dynamic behavior of molecules in a liquid clearly appears in the particular peak from a single-bond oxygen. The relationship between the bonding nature and the dynamic information of a molecule in a spectrum was determined and presented.

  6. Potential Role of the Last Half Repeat in TAL Effectors Revealed by a Molecular Simulation Study

    PubMed Central

    Wan, Hua; Chang, Shan; Hu, Jian-ping; Tian, Xu-hong

    2016-01-01

    TAL effectors (TALEs) contain a modular DNA-binding domain that is composed of tandem repeats. In all naturally occurring TALEs, the end of tandem repeats is invariantly a truncated half repeat. To investigate the potential role of the last half repeat in TALEs, we performed comparative molecular dynamics simulations for the crystal structure of DNA-bound TALE AvrBs3 lacking the last half repeat and its modeled structure having the last half repeat. The structural stability analysis indicates that the modeled system is more stable than the nonmodeled system. Based on the principle component analysis, it is found that the AvrBs3 increases its structural compactness in the presence of the last half repeat. The comparison of DNA groove parameters of the two systems implies that the last half repeat also causes the change of DNA major groove binding efficiency. The following calculation of hydrogen bond reveals that, by stabilizing the phosphate binding with DNA at the C-terminus, the last half repeat helps to adopt a compact conformation at the protein-DNA interface. It further mediates more contacts between TAL repeats and DNA nucleotide bases. Finally, we suggest that the last half repeat is required for the high-efficient recognition of DNA by TALE. PMID:27803930

  7. Parallel Molecular Dynamics Stencil : a new parallel computing environment for a large-scale molecular dynamics simulation of solids

    NASA Astrophysics Data System (ADS)

    Shimizu, Futoshi; Kimizuka, Hajime; Kaburaki, Hideo

    2002-08-01

    A new parallel computing environment, called as ``Parallel Molecular Dynamics Stencil'', has been developed to carry out a large-scale short-range molecular dynamics simulation of solids. The stencil is written in C language using MPI for parallelization and designed successfully to separate and conceal parts of the programs describing cutoff schemes and parallel algorithms for data communication. This has been made possible by introducing the concept of image atoms. Therefore, only a sequential programming of the force calculation routine is required for executing the stencil in parallel environment. Typical molecular dynamics routines, such as various ensembles, time integration methods, and empirical potentials, have been implemented in the stencil. In the presentation, the performance of the stencil on parallel computers of Hitachi, IBM, SGI, and PC-cluster using the models of Lennard-Jones and the EAM type potentials for fracture problem will be reported.

  8. Understanding antibody-antigen associations by molecular dynamics simulations: detection of important intra- and inter-molecular salt bridges.

    PubMed

    Sinha, Neeti; Li, Yili; Lipschultz, Claudia A; Smith-Gill, Sandra J

    2007-01-01

    1 NSec molecular dynamics (MD) simulation of anti-hen egg white antibody, HyHEL63 (HH63), complexed with HEL reveals important molecular interactions, not revealed in its X-ray crystal structure. These molecular interactions were predicted to be critical for the complex formation, based on structure-function studies of this complex and 3-other anti-HEL antibodies, HH8, HH10 and HH26, HEL complexes. All four antibodies belong to the same structural family, referred to here as HH10 family. Ala scanning results show that they recognize 'coincident epitopes'. 1 NSec explicit, with periodic boundary condition, MD simulation of HH63- HEL reveals the presence of functionally important saltbridges. Around 200 ps in vacuo and an additional 20 ps explicit simulation agree with the observations from 1 Nsec simulation. Intra-molecular salt-bridges predicted to play significant roles in the complex formation, were revealed during MD simulation. A very stabilizing saltbridge network, and another intra-molecular salt-bridge, at the binding site of HEL, revealed during the MD simulation, is proposed to predipose binding site geometry for specific binding. All the revealed saltbridges are present in one or more of the other three complexes and/or involve \\"hot-spot\\" epitope and paratope residues. Most of these charged epitope residues make large contribution to the binding free energy. The "hot spot" epitope residue Lys97Y, which significantly contributes to the free energy of binding in all the complexes, forms an intermolecular salt-bridge in several MD conformers. Our earlier computations have shown that this inter-molecular salt-bridge plays a significant role in determining specificity and flexibility of binding in the HH8-HEL and HH26-HEL complexes. Using a robust criterion of salt-bridge detection, this intermolecular salt-bridge was detected in the native structures of the HH8-HEL and HH26-HEL complexes, but was not revealed in the crystal structure of HH63-HEL complex

  9. Thermostatted molecular dynamics: How to avoid the Toda demon hidden in Nose-Hoover dynamics

    SciTech Connect

    Holian, B.L.; Voter, A.F.; Ravelo, R.

    1995-09-01

    The Nose-Hoover thermostat, which is often used in the hope of modifying molecular dynamics trajectories in order to achieve canonical-ensemble averages, has hidden in it a Toda ``demon,`` which can give rise to unwanted, noncanonical undulations in the instantaneous kinetic temperature. We show how these long-lived oscillations arise from insufficient coupling of the thermostat to the atoms, and give straightforward, practical procedures for avoiding this weak-coupling pathology in isothermal molecular dynamics simulations.

  10. Molecular circuits for dynamic noise filtering.

    PubMed

    Zechner, Christoph; Seelig, Georg; Rullan, Marc; Khammash, Mustafa

    2016-04-26

    The invention of the Kalman filter is a crowning achievement of filtering theory-one that has revolutionized technology in countless ways. By dealing effectively with noise, the Kalman filter has enabled various applications in positioning, navigation, control, and telecommunications. In the emerging field of synthetic biology, noise and context dependency are among the key challenges facing the successful implementation of reliable, complex, and scalable synthetic circuits. Although substantial further advancement in the field may very well rely on effectively addressing these issues, a principled protocol to deal with noise-as provided by the Kalman filter-remains completely missing. Here we develop an optimal filtering theory that is suitable for noisy biochemical networks. We show how the resulting filters can be implemented at the molecular level and provide various simulations related to estimation, system identification, and noise cancellation problems. We demonstrate our approach in vitro using DNA strand displacement cascades as well as in vivo using flow cytometry measurements of a light-inducible circuit in Escherichia coli. PMID:27078094

  11. Live Cell Imaging Reveals the Dynamics of Telomerase Recruitment to Telomeres.

    PubMed

    Schmidt, Jens C; Zaug, Arthur J; Cech, Thomas R

    2016-08-25

    Telomerase maintains genome integrity by adding repetitive DNA sequences to the chromosome ends in actively dividing cells, including 90% of all cancer cells. Recruitment of human telomerase to telomeres occurs during S-phase of the cell cycle, but the molecular mechanism of the process is only partially understood. Here, we use CRISPR genome editing and single-molecule imaging to track telomerase trafficking in nuclei of living human cells. We demonstrate that telomerase uses three-dimensional diffusion to search for telomeres, probing each telomere thousands of times each S-phase but only rarely forming a stable association. Both the transient and stable association events depend on the direct interaction of the telomerase protein TERT with the telomeric protein TPP1. Our results reveal that telomerase recruitment to telomeres is driven by dynamic interactions between the rapidly diffusing telomerase and the chromosome end. PMID:27523609

  12. Quantum dynamics of light-driven chiral molecular motors.

    PubMed

    Yamaki, Masahiro; Nakayama, Shin-ichiro; Hoki, Kunihito; Kono, Hirohiko; Fujimura, Yuichi

    2009-03-21

    The results of theoretical studies on quantum dynamics of light-driven molecular motors with internal rotation are presented. Characteristic features of chiral motors driven by a non-helical, linearly polarized electric field of light are explained on the basis of symmetry argument. The rotational potential of the chiral motor is characterized by a ratchet form. The asymmetric potential determines the directional motion: the rotational direction is toward the gentle slope of the asymmetric potential. This direction is called the intuitive direction. To confirm the unidirectional rotational motion, results of quantum dynamical calculations of randomly-oriented molecular motors are presented. A theoretical design of the smallest light-driven molecular machine is presented. The smallest chiral molecular machine has an optically driven engine and a running propeller on its body. The mechanisms of transmission of driving forces from the engine to the propeller are elucidated by using a quantum dynamical treatment. The results provide a principle for control of optically-driven molecular bevel gears. Temperature effects are discussed using the density operator formalism. An effective method for ultrafast control of rotational motions in any desired direction is presented with the help of a quantum control theory. In this method, visible or UV light pulses are applied to drive the motor via an electronic excited state. A method for driving a large molecular motor consisting of an aromatic hydrocarbon is presented. The molecular motor is operated by interactions between the induced dipole of the molecular motor and the electric field of light pulses. PMID:19290336

  13. Thermal stability and molecular microstructure of heat-induced cereal grains, revealed with Raman molecular microspectroscopy and differential scanning calorimetry.

    PubMed

    Khan, Md Majibur Rahman; Yu, Peiqiang

    2013-07-01

    The objectives of the present study were to use Raman molecular microspectroscopy and differential scanning calorimetry (DSC) to reveal molecular thermal stability and thermal degradation behavior of heat-induced cereal grains and reveal the molecular chemistry of the protein structures of cereal grain tissues affected by heat processing and to quantify the protein secondary structures using multicomponent peak modeling Gaussian and Lorentzian methods. Hierarchical cluster analysis (CLA) and principal components analysis (PCA) were also conducted to identify molecular differences in the Raman spectra. Three cereal grain seeds, wheat, triticale, and corn, were used as the model for feed protein in the experiment. The specimens were autoclaved (moist heating) and dry-heated (roasted) at 121 °C for 80 min, respectively. Raman spectroscopy results revealed that there are marked differences in the secondary structures of the proteins subjected to various heating treatments of different cereals. The sensitivity of cereals to moist heating was much higher than the sensitivity to dry heating. The multivariate analyses (CLA and PCA) showed that heat treatment was significantly isolated between the different Raman raw spectra. The DSC study revealed that the thermal degradation behavior of cereals was significantly changed after moist- and dry-heat treatments. The position of the major endothermic peak of dry-heated cereals shifted toward a higher temperature, from 131.7 to 134.0 °C, suggesting the high thermal stability of dry-heated cereals. In contrast, the endothermic peak position was slightly decreased to 132.1 °C in the case of moist autoclaved heating. The digestive behavior and nutritive value of rumen-undegradable protein in animals may be related to the changes of the protein secondary molecular structure and thermal stability of the cereal grain materials, which is attributed by Raman microspectroscopy and DSC endotherm profiles.

  14. Probing Molecular Dynamics by Laser-Induced Backscattering Holography.

    PubMed

    Haertelt, Marko; Bian, Xue-Bin; Spanner, Michael; Staudte, André; Corkum, Paul B

    2016-04-01

    We use differential holography to overcome the forward scattering problem in strong-field photoelectron holography. Our differential holograms of H_{2} and D_{2} molecules exhibit a fishbonelike structure, which arises from the backscattered part of the recolliding photoelectron wave packet. We demonstrate that the backscattering hologram can resolve the different nuclear dynamics between H_{2} and D_{2} with subangstrom spatial and subcycle temporal resolution. In addition, we show that attosecond electron dynamics can be resolved. These results open a new avenue for ultrafast studies of molecular dynamics in small molecules. PMID:27081975

  15. Probing Molecular Dynamics by Laser-Induced Backscattering Holography

    NASA Astrophysics Data System (ADS)

    Haertelt, Marko; Bian, Xue-Bin; Spanner, Michael; Staudte, André; Corkum, Paul B.

    2016-04-01

    We use differential holography to overcome the forward scattering problem in strong-field photoelectron holography. Our differential holograms of H2 and D2 molecules exhibit a fishbonelike structure, which arises from the backscattered part of the recolliding photoelectron wave packet. We demonstrate that the backscattering hologram can resolve the different nuclear dynamics between H2 and D2 with subangstrom spatial and subcycle temporal resolution. In addition, we show that attosecond electron dynamics can be resolved. These results open a new avenue for ultrafast studies of molecular dynamics in small molecules.

  16. Optimizing legacy molecular dynamics software with directive-based offload

    NASA Astrophysics Data System (ADS)

    Michael Brown, W.; Carrillo, Jan-Michael Y.; Gavhane, Nitin; Thakkar, Foram M.; Plimpton, Steven J.

    2015-10-01

    Directive-based programming models are one solution for exploiting many-core coprocessors to increase simulation rates in molecular dynamics. They offer the potential to reduce code complexity with offload models that can selectively target computations to run on the CPU, the coprocessor, or both. In this paper, we describe modifications to the LAMMPS molecular dynamics code to enable concurrent calculations on a CPU and coprocessor. We demonstrate that standard molecular dynamics algorithms can run efficiently on both the CPU and an x86-based coprocessor using the same subroutines. As a consequence, we demonstrate that code optimizations for the coprocessor also result in speedups on the CPU; in extreme cases up to 4.7X. We provide results for LAMMPS benchmarks and for production molecular dynamics simulations using the Stampede hybrid supercomputer with both Intel® Xeon Phi™ coprocessors and NVIDIA GPUs. The optimizations presented have increased simulation rates by over 2X for organic molecules and over 7X for liquid crystals on Stampede. The optimizations are available as part of the "Intel package" supplied with LAMMPS.

  17. Open boundary molecular dynamics of sheared star-polymer melts.

    PubMed

    Sablić, Jurij; Praprotnik, Matej; Delgado-Buscalioni, Rafael

    2016-02-28

    Open boundary molecular dynamics (OBMD) simulations of a sheared star polymer melt under isothermal conditions are performed to study the rheology and molecular structure of the melt under a fixed normal load. Comparison is made with the standard molecular dynamics (MD) in periodic (closed) boxes at a fixed shear rate (using the SLLOD dynamics). The OBMD system exchanges mass and momentum with adjacent reservoirs (buffers) where the external pressure tensor is imposed. Insertion of molecules in the buffers is made feasible by implementing there a low resolution model (blob-molecules with soft effective interactions) and then using the adaptive resolution scheme (AdResS) to connect with the bulk MD. Straining with increasing shear stress induces melt expansion and a significantly different redistribution of pressure compared with the closed case. In the open sample, the shear viscosity is also a bit lowered but more stable against the viscous heating. At a given Weissenberg number, molecular deformations and material properties (recoverable shear strain and normal stress ratio) are found to be similar in both setups. We also study the modelling effect of normal and tangential friction between monomers implemented in a dissipative particle dynamics (DPD) thermostat. Interestingly, the tangential friction substantially enhances the elastic response of the melt due to a reduction of the kinetic stress viscous contribution. PMID:26820315

  18. Clustering Molecular Dynamics Trajectories for Optimizing Docking Experiments

    PubMed Central

    De Paris, Renata; Quevedo, Christian V.; Ruiz, Duncan D.; Norberto de Souza, Osmar; Barros, Rodrigo C.

    2015-01-01

    Molecular dynamics simulations of protein receptors have become an attractive tool for rational drug discovery. However, the high computational cost of employing molecular dynamics trajectories in virtual screening of large repositories threats the feasibility of this task. Computational intelligence techniques have been applied in this context, with the ultimate goal of reducing the overall computational cost so the task can become feasible. Particularly, clustering algorithms have been widely used as a means to reduce the dimensionality of molecular dynamics trajectories. In this paper, we develop a novel methodology for clustering entire trajectories using structural features from the substrate-binding cavity of the receptor in order to optimize docking experiments on a cloud-based environment. The resulting partition was selected based on three clustering validity criteria, and it was further validated by analyzing the interactions between 20 ligands and a fully flexible receptor (FFR) model containing a 20 ns molecular dynamics simulation trajectory. Our proposed methodology shows that taking into account features of the substrate-binding cavity as input for the k-means algorithm is a promising technique for accurately selecting ensembles of representative structures tailored to a specific ligand. PMID:25873944

  19. Reasoning with Atomic-Scale Molecular Dynamic Models

    ERIC Educational Resources Information Center

    Pallant, Amy; Tinker, Robert F.

    2004-01-01

    The studies reported in this paper are an initial effort to explore the applicability of computational models in introductory science learning. Two instructional interventions are described that use a molecular dynamics model embedded in a set of online learning activities with middle and high school students in 10 classrooms. The studies indicate…

  20. Molecular dynamics simulation of size segregation in three dimensions

    NASA Astrophysics Data System (ADS)

    Gallas, Jason A. C.; Herrmann, Hans J.; Pöschel, Thorsten; Sokołowski, Stefan

    1996-01-01

    We report the first three-dimensional molecular dynamics simulation of particle segregation by shaking. Two different containers are considered: one cylindrical and another with periodic boundary conditions. The dependence of the time evolution of a test particle inside the material is studied as a function of the shaking frequency and amplitude, damping coefficients, and dispersivity.

  1. Quantum Molecular Dynamics Simulations of Nanotube Tip Assisted Reactions

    NASA Technical Reports Server (NTRS)

    Menon, Madhu

    1998-01-01

    In this report we detail the development and application of an efficient quantum molecular dynamics computational algorithm and its application to the nanotube-tip assisted reactions on silicon and diamond surfaces. The calculations shed interesting insights into the microscopic picture of tip surface interactions.

  2. Clustering molecular dynamics trajectories for optimizing docking experiments.

    PubMed

    De Paris, Renata; Quevedo, Christian V; Ruiz, Duncan D; Norberto de Souza, Osmar; Barros, Rodrigo C

    2015-01-01

    Molecular dynamics simulations of protein receptors have become an attractive tool for rational drug discovery. However, the high computational cost of employing molecular dynamics trajectories in virtual screening of large repositories threats the feasibility of this task. Computational intelligence techniques have been applied in this context, with the ultimate goal of reducing the overall computational cost so the task can become feasible. Particularly, clustering algorithms have been widely used as a means to reduce the dimensionality of molecular dynamics trajectories. In this paper, we develop a novel methodology for clustering entire trajectories using structural features from the substrate-binding cavity of the receptor in order to optimize docking experiments on a cloud-based environment. The resulting partition was selected based on three clustering validity criteria, and it was further validated by analyzing the interactions between 20 ligands and a fully flexible receptor (FFR) model containing a 20 ns molecular dynamics simulation trajectory. Our proposed methodology shows that taking into account features of the substrate-binding cavity as input for the k-means algorithm is a promising technique for accurately selecting ensembles of representative structures tailored to a specific ligand.

  3. Clustering molecular dynamics trajectories for optimizing docking experiments.

    PubMed

    De Paris, Renata; Quevedo, Christian V; Ruiz, Duncan D; Norberto de Souza, Osmar; Barros, Rodrigo C

    2015-01-01

    Molecular dynamics simulations of protein receptors have become an attractive tool for rational drug discovery. However, the high computational cost of employing molecular dynamics trajectories in virtual screening of large repositories threats the feasibility of this task. Computational intelligence techniques have been applied in this context, with the ultimate goal of reducing the overall computational cost so the task can become feasible. Particularly, clustering algorithms have been widely used as a means to reduce the dimensionality of molecular dynamics trajectories. In this paper, we develop a novel methodology for clustering entire trajectories using structural features from the substrate-binding cavity of the receptor in order to optimize docking experiments on a cloud-based environment. The resulting partition was selected based on three clustering validity criteria, and it was further validated by analyzing the interactions between 20 ligands and a fully flexible receptor (FFR) model containing a 20 ns molecular dynamics simulation trajectory. Our proposed methodology shows that taking into account features of the substrate-binding cavity as input for the k-means algorithm is a promising technique for accurately selecting ensembles of representative structures tailored to a specific ligand. PMID:25873944

  4. Optimizing legacy molecular dynamics software with directive-based offload

    SciTech Connect

    Michael Brown, W.; Carrillo, Jan-Michael Y.; Gavhane, Nitin; Thakkar, Foram M.; Plimpton, Steven J.

    2015-05-14

    The directive-based programming models are one solution for exploiting many-core coprocessors to increase simulation rates in molecular dynamics. They offer the potential to reduce code complexity with offload models that can selectively target computations to run on the CPU, the coprocessor, or both. In our paper, we describe modifications to the LAMMPS molecular dynamics code to enable concurrent calculations on a CPU and coprocessor. We also demonstrate that standard molecular dynamics algorithms can run efficiently on both the CPU and an x86-based coprocessor using the same subroutines. As a consequence, we demonstrate that code optimizations for the coprocessor also result in speedups on the CPU; in extreme cases up to 4.7X. We provide results for LAMMAS benchmarks and for production molecular dynamics simulations using the Stampede hybrid supercomputer with both Intel (R) Xeon Phi (TM) coprocessors and NVIDIA GPUs: The optimizations presented have increased simulation rates by over 2X for organic molecules and over 7X for liquid crystals on Stampede. The optimizations are available as part of the "Intel package" supplied with LAMMPS. (C) 2015 Elsevier B.V. All rights reserved.

  5. Optimizing legacy molecular dynamics software with directive-based offload

    DOE PAGES

    Michael Brown, W.; Carrillo, Jan-Michael Y.; Gavhane, Nitin; Thakkar, Foram M.; Plimpton, Steven J.

    2015-05-14

    The directive-based programming models are one solution for exploiting many-core coprocessors to increase simulation rates in molecular dynamics. They offer the potential to reduce code complexity with offload models that can selectively target computations to run on the CPU, the coprocessor, or both. In our paper, we describe modifications to the LAMMPS molecular dynamics code to enable concurrent calculations on a CPU and coprocessor. We also demonstrate that standard molecular dynamics algorithms can run efficiently on both the CPU and an x86-based coprocessor using the same subroutines. As a consequence, we demonstrate that code optimizations for the coprocessor also resultmore » in speedups on the CPU; in extreme cases up to 4.7X. We provide results for LAMMAS benchmarks and for production molecular dynamics simulations using the Stampede hybrid supercomputer with both Intel (R) Xeon Phi (TM) coprocessors and NVIDIA GPUs: The optimizations presented have increased simulation rates by over 2X for organic molecules and over 7X for liquid crystals on Stampede. The optimizations are available as part of the "Intel package" supplied with LAMMPS. (C) 2015 Elsevier B.V. All rights reserved.« less

  6. Particle Motion Analysis Reveals Nanoscale Bond Characteristics and Enhances Dynamic Range for Biosensing.

    PubMed

    Visser, Emiel W A; van IJzendoorn, Leo J; Prins, Menno W J

    2016-03-22

    Biofunctionalized colloidal particles are widely used as labels in bioanalytical assays, lab-on-chip devices, biophysical research, and in studies on live biological systems. With detection resolution going down to the level of single particles and single molecules, understanding the nature of the interaction of the particles with surfaces and substrates becomes of paramount importance. Here, we present a comprehensive study of motion patterns of colloidal particles maintained in close proximity to a substrate by short molecular tethers (40 nm). The motion of the particles (500-1000 nm) was optically tracked with a very high localization accuracy (below 3 nm). A surprisingly large variation in motion patterns was observed, which can be attributed to properties of the particle-molecule-substrate system, namely the bond number, the nature of the bond, particle protrusions, and substrate nonuniformities. Experimentally observed motion patterns were compared to numerical Monte Carlo simulations, revealing a close correspondence between the observed motion patterns and properties of the molecular system. Particles bound via single tethers show distinct disc-, ring-, and bell-shaped motion patterns, where the ring- and bell-shaped patterns are caused by protrusions on the particle in the direct vicinity of the molecular attachment point. Double and triple tethered particles exhibit stripe-shaped and triangular-shaped motion patterns, respectively. The developed motion pattern analysis allows for discrimination between particles bound by different bond types, which opens the possibility to improve the limit of detection and the dynamic range of bioanalytical assays, with a projected increase of dynamic range by nearly 2 orders of magnitude.

  7. A Molecular Dynamics Study of the Structure-Dynamics Relationships of Supercooled Liquids and Glasses

    NASA Astrophysics Data System (ADS)

    Soklaski, Ryan

    Central to the field of condensed matter physics is a decades old outstanding problem in the study of glasses -- namely explaining the extreme slowing of dynamics in a liquid as it is supercooled towards the so-called glass transition. Efforts to universally describe the stretched relaxation processes and heterogeneous dynamics that characteristically develop in supercooled liquids remain divided in both their approaches and successes. Towards this end, a consensus on the role that atomic and molecular structures play in the liquid is even more tenuous. However, mounting material science research efforts have culminated to reveal that the vast diversity of metallic glass species and their properties are rooted in an equally-broad set of structural archetypes. Herein lies the motivation of this dissertation: the detailed information available regarding the structure-property relationships of metallic glasses provides a new context in which one can study the evolution of a supercooled liquid by utilizing a structural motif that is known to dominate the glass. Cu64Zr36 is a binary alloy whose good glass-forming ability and simple composition makes it a canonical material to both empirical and numerical studies. Here, we perform classical molecular dynamics simulations and conduct a comprehensive analysis of the dynamical regimes of liquid Cu64Zr36, while focusing on the roles played by atomic icosahedral ordering -- a structural motif which ultimately percolates the glass' structure. Large data analysis techniques are leveraged to obtain uniquely detailed structural and dynamical information in this context. In doing so, we develop the first account of the origin of icosahedral order in this alloy, revealing deep connections between this incipient structural ordering, frustration-limited domain theory, and recent important empirical findings that are relevant to the nature of metallic liquids at large. Furthermore, important dynamical landmarks such as the breakdown

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

    SciTech Connect

    Ohmura, Satoshi; Nagaya, Kiyonobu; Yao, Makoto; Shimojo, Fuyuki

    2015-08-17

    The dynamic properties of liquid B{sub 2}O{sub 3} under pressure and highly-charged bromophenol molecule are studied by using molecular dynamics (MD) simulations based on density functional theory (DFT). Diffusion properties of covalent liquids under high pressure are very interesting in the sense that they show unexpected pressure dependence. It is found from our simulation that the magnitude relation of diffusion coefficients for boron and oxygen in liquid B{sub 2}O{sub 3} shows the anomalous pressure dependence. The simulation clarified the microscopic origin of the anomalous diffusion properties. Our simulation also reveals the dissociation mechanism in the coulomb explosion of the highly-charged bromophenol molecule. When the charge state n is 6, hydrogen atom in the hydroxyl group dissociates at times shorter than 20 fs while all hydrogen atoms dissociate when n is 8. After the hydrogen dissociation, the carbon ring breaks at about 100 fs. There is also a difference on the mechanism of the ring breaking depending on charge states, in which the ring breaks with expanding (n = 6) or shrink (n = 8)

  9. Energetics and dynamics in MbCN: CN--vibrational relaxation from molecular dynamics simulations.

    PubMed

    Danielsson, Jonas; Meuwly, Markus

    2007-01-11

    The dynamics of the cyanide anion bound to sperm-whale myoglobin is investigated using atomistic simulations. With density-functional theory, a 2D potential energy surface for the cyanide-heme complex is calculated. Two deep minima with a stabilization energy of approximately 50 kcal/mol corresponding to two different binding orientations (Fe-CN and Fe-NC) of the ligand are found. The Fe-CN conformation is favored over Fe-NC by several kcal/mol. Mixed quantum mechanics/molecular mechanics calculations show that the binding orientation affects the bond strength of the ligand, with a significantly different bond length and a 25 cm-1 shift in the fundamental CN-frequency. For the molecular dynamics (MD) simulations, a 3-center fluctuating charge model for the Fe-CN unit is developed that captures polarization and ligand-metal charge transfer. Stability arguments based on the energetics around the active site and the CN- frequency shifts suggest that the Fe-CN conformation with epsilon-protonation of His epsilon 64 are most likely, which is in agreement with experiment. Both equilibrium and nonequilibrium MD simulations are carried out to investigate the relaxation time scale and possible relaxation pathways in bound MbCN. The nonequilibrium MD simulations with a vibrationally excited ligand reveal that vibrational relaxation takes place on a time scale of hundreds of picoseconds within the active site. This finding supports the hypothesis that the experimentally observed relaxation rate (3.6 ps) reflects the repopulation of the electronic ground state.

  10. Rational Prediction with Molecular Dynamics for Hit Identification

    PubMed Central

    Nichols, Sara E; Swift, Robert V; Amaro, Rommie E

    2012-01-01

    Although the motions of proteins are fundamental for their function, for pragmatic reasons, the consideration of protein elasticity has traditionally been neglected in drug discovery and design. This review details protein motion, its relevance to biomolecular interactions and how it can be sampled using molecular dynamics simulations. Within this context, two major areas of research in structure-based prediction that can benefit from considering protein flexibility, binding site detection and molecular docking, are discussed. Basic classification metrics and statistical analysis techniques, which can facilitate performance analysis, are also reviewed. With hardware and software advances, molecular dynamics in combination with traditional structure-based prediction methods can potentially reduce the time and costs involved in the hit identification pipeline. PMID:23110535

  11. Diversity dynamics: molecular phylogenies need the fossil record.

    PubMed

    Quental, Tiago B; Marshall, Charles R

    2010-08-01

    Over the last two decades, new tools in the analysis of molecular phylogenies have enabled study of the diversification dynamics of living clades in the absence of information about extinct lineages. However, computer simulations and the fossil record show that the inability to access extinct lineages severely limits the inferences that can be drawn from molecular phylogenies. It appears that molecular phylogenies can tell us only when there have been changes in diversification rates, but are blind to the true diversity trajectories and rates of origination and extinction that have led to the species that are alive today. We need to embrace the fossil record if we want to fully understand the diversity dynamics of the living biota. PMID:20646780

  12. Collisional dynamics in a gas of molecular super-rotors.

    PubMed

    Khodorkovsky, Yuri; Steinitz, Uri; Hartmann, Jean-Michel; Averbukh, Ilya Sh

    2015-01-01

    Recently, femtosecond laser techniques have been developed that are capable of bringing gas molecules to extremely fast rotation in a very short time, while keeping their translational motion relatively slow. Here we study collisional equilibration dynamics of this new state of molecular gases. We show that the route to equilibrium starts with a metastable 'gyroscopic stage' in the course of which the molecules maintain their fast rotation and orientation of the angular momentum through many collisions. The inhibited rotational-translational relaxation is characterized by a persistent anisotropy in the molecular angular distribution, and is manifested in the optical birefringence and anisotropic diffusion in the gas. After a certain induction time, the 'gyroscopic stage' is abruptly terminated by an explosive rotational-translational energy exchange, leading the gas towards the final equilibrium. We illustrate our conclusions by direct molecular dynamics simulation of several gases of linear molecules. PMID:26160223

  13. Collisional dynamics in a gas of molecular super-rotors

    PubMed Central

    Khodorkovsky, Yuri; Steinitz, Uri; Hartmann, Jean-Michel; Averbukh, Ilya Sh.

    2015-01-01

    Recently, femtosecond laser techniques have been developed that are capable of bringing gas molecules to extremely fast rotation in a very short time, while keeping their translational motion relatively slow. Here we study collisional equilibration dynamics of this new state of molecular gases. We show that the route to equilibrium starts with a metastable ‘gyroscopic stage' in the course of which the molecules maintain their fast rotation and orientation of the angular momentum through many collisions. The inhibited rotational–translational relaxation is characterized by a persistent anisotropy in the molecular angular distribution, and is manifested in the optical birefringence and anisotropic diffusion in the gas. After a certain induction time, the ‘gyroscopic stage' is abruptly terminated by an explosive rotational–translational energy exchange, leading the gas towards the final equilibrium. We illustrate our conclusions by direct molecular dynamics simulation of several gases of linear molecules. PMID:26160223

  14. Isomorphic classical molecular dynamics model for an excess electronin a supercritical fluid

    SciTech Connect

    Miller III, Thomas F.

    2008-08-04

    Ring polymer molecular dynamics (RPMD) is used to directly simulate the dynamics of an excess electron in a supercritical fluid over a broad range of densities. The accuracy of the RPMD model is tested against numerically exact path integral statistics through the use of analytical continuation techniques. At low fluid densities, the RPMD model substantially underestimates the contribution of delocalized states to the dynamics of the excess electron. However, with increasing solvent density, the RPMD model improves, nearly satisfying analytical continuation constraints at densities approaching those of typical liquids. In the high density regime, quantum dispersion substantially decreases the self-diffusion of the solvated electron. In this regime where the dynamics of the electron is strongly coupled to the dynamics of the atoms in the fluid, trajectories that can reveal diffusive motion of the electron are long in comparison to {beta}{h_bar}.

  15. Nonadiabatic molecular dynamics simulations: synergies between theory and experiments.

    PubMed

    Tavernelli, Ivano

    2015-03-17

    Recent developments in nonadiabatic dynamics enabled ab inito simulations of complex ultrafast processes in the condensed phase. These advances have opened new avenues in the study of many photophysical and photochemical reactions triggered by the absorption of electromagnetic radiation. In particular, theoretical investigations can be combined with the most sophisticated femtosecond experimental techniques to guide the interpretation of measured time-resolved observables. At the same time, the availability of experimental data at high (spatial and time) resolution offers a unique opportunity for the benchmarking and the improvement of those theoretical models used to describe complex molecular systems in their natural environment. The established synergy between theory and experiments can produce a better understanding of new ultrafast physical and chemical processes at atomistic scale resolution. Furthermore, reliable ab inito molecular dynamics simulations can already be successfully employed as predictive tools to guide new experiments as well as the design of novel and better performing materials. In this paper, I will give a concise account on the state of the art of molecular dynamics simulations of complex molecular systems in their excited states. The principal aim of this approach is the description of a given system of interest under the most realistic ambient conditions including all environmental effects that influence experiments, for instance, the interaction with the solvent and with external time-dependent electric fields, temperature, and pressure. To this end, time-dependent density functional theory (TDDFT) is among the most efficient and accurate methods for the representation of the electronic dynamics, while trajectory surface hopping gives a valuable representation of the nuclear quantum dynamics in the excited states (including nonadiabatic effects). Concerning the environment and its effects on the dynamics, the quantum mechanics/molecular

  16. Nonadiabatic molecular dynamics simulations: synergies between theory and experiments.

    PubMed

    Tavernelli, Ivano

    2015-03-17

    Recent developments in nonadiabatic dynamics enabled ab inito simulations of complex ultrafast processes in the condensed phase. These advances have opened new avenues in the study of many photophysical and photochemical reactions triggered by the absorption of electromagnetic radiation. In particular, theoretical investigations can be combined with the most sophisticated femtosecond experimental techniques to guide the interpretation of measured time-resolved observables. At the same time, the availability of experimental data at high (spatial and time) resolution offers a unique opportunity for the benchmarking and the improvement of those theoretical models used to describe complex molecular systems in their natural environment. The established synergy between theory and experiments can produce a better understanding of new ultrafast physical and chemical processes at atomistic scale resolution. Furthermore, reliable ab inito molecular dynamics simulations can already be successfully employed as predictive tools to guide new experiments as well as the design of novel and better performing materials. In this paper, I will give a concise account on the state of the art of molecular dynamics simulations of complex molecular systems in their excited states. The principal aim of this approach is the description of a given system of interest under the most realistic ambient conditions including all environmental effects that influence experiments, for instance, the interaction with the solvent and with external time-dependent electric fields, temperature, and pressure. To this end, time-dependent density functional theory (TDDFT) is among the most efficient and accurate methods for the representation of the electronic dynamics, while trajectory surface hopping gives a valuable representation of the nuclear quantum dynamics in the excited states (including nonadiabatic effects). Concerning the environment and its effects on the dynamics, the quantum mechanics/molecular

  17. Dynamic and unique nucleolar microenvironment revealed by fluorescence correlation spectroscopy.

    PubMed

    Park, Hweon; Han, Sung-Sik; Sako, Yasushi; Pack, Chan-Gi

    2015-03-01

    Organization and functions of the nucleolus is maintained by mobilities and interactions of nucleolar factors. Because the nucleolus is a densely packed structure, molecular crowding effects determined by the molecular concentrations and mobilities in the nucleolus should also be important for regulating nucleolar organization and functions. However, such molecular property of nucleolar organization is not fully understood. To understand the biophysical property of nucleolar organization, the diffusional behaviors of inert green fluorescent protein (GFP) oligomers with or without nuclear localization signals (NLSs) were analyzed under various conditions by fluorescence correlation spectroscopy. Our result demonstrates that the mobility of GFPs inside the nucleolus and the nucleoplasm can be represented by single free diffusion under normal conditions, even though the mobility in the nucleolus is considerably slower than that in the chromatin region. Moreover, the free diffusion of GFPs is found to be significantly size- and NLS-dependent only in the nucleolus. Interestingly, the mobility in the nucleolus is highly sensitive to ATP depletion, as well as actinomycin D (ActD) treatment. In contrast, the ultra-structure of the nucleolus was not significantly changed by ATP depletion but was changed by ActD treatment. These results suggest that the nucleolus behaves similarly to an open aqueous-phase medium with an increased molecular crowding effect that depends on both energy and transcription.

  18. ALMA Reveals a Galaxy-Scale Fountain of Cold Molecular Gas Pumped by a Black Hole

    NASA Astrophysics Data System (ADS)

    Tremblay, Grant

    2016-01-01

    A new ALMA observation of the cool core brightest cluster galaxy in Abell 2597 reveals that a supermassive black hole can act much like a mechanical pump in a water fountain, driving a convective flow of molecular gas that drains into the black hole accretion reservoir, only to be pushed outward again in a jet-driven outflow that then rains back toward the galaxy center from which it came. The ALMA data reveal "shadows" cast by giant molecular clouds falling on ballistic trajectories towards the black hole in the innermost 500 parsecs of the galaxy, manifesting as deep redshifted continuum absorption features. The black hole accretion reservoir, fueled by these infalling cold clouds, powers an AGN that drives a jet-driven molecular outflow in the form of a 10 kpc-scale, billion solar mass expanding molecular bubble or plume. The molecular shell is permeated with young stars, perhaps triggered in situ by the jet. Buoyant X-ray cavities excavated by the propagating radio source may further uplift the molecular filaments, which are observed to fall inward toward the center of the galaxy from which they came, presumably keeping the fountain long-lived. The results show that cold molecular gas can couple to black hole growth via both feedback and feeding, in alignment with "cold chaotic accretion" models for the regulation of star formation in galaxies.

  19. An investigation of molecular dynamics simulation and molecular docking: interaction of citrus flavonoids and bovine β-lactoglobulin in focus.

    PubMed

    Sahihi, M; Ghayeb, Y

    2014-08-01

    Citrus flavonoids are natural compounds with important health benefits. The study of their interaction with a transport protein, such as bovine β-lactoglobulin (BLG), at the atomic level could be a valuable factor to control their transport to biological sites. In the present study, molecular docking and molecular dynamics simulation methods were used to investigate the interaction of hesperetin, naringenin, nobiletin and tangeretin as citrus flavonoids and BLG as transport protein. The molecular docking results revealed that these flavonoids bind in the internal cavity of BLG and the BLG affinity for binding the flavonoids follows naringenin>hesperetin>tangeretin>nobiletin. The docking results also indicated that the BLG-flavonoid complexes are stabilized through hydrophobic interactions, hydrogen bond interactions and π-π stacking interactions. The analysis of molecular dynamics (MD) simulation trajectories showed that the root mean square deviation (RMSD) of various systems reaches equilibrium and fluctuates around the mean value at various times. Time evolution of the radius of gyration, total solvent accessible surface of the protein and the second structure of protein showed as well that BLG and BLG-flavonoid complexes were stable around 2500ps, and there was not any conformational change as for BLG-flavonoid complexes. Further, the profiles of atomic fluctuations indicated the rigidity of the ligand binding site during the simulation.

  20. Ab initio molecular dynamics: Concepts, recent developments, and future trends

    PubMed Central

    Iftimie, Radu; Minary, Peter; Tuckerman, Mark E.

    2005-01-01

    The methodology of ab initio molecular dynamics, wherein finite-temperature dynamical trajectories are generated by using forces computed “on the fly” from electronic structure calculations, has had a profound influence in modern theoretical research. Ab initio molecular dynamics allows chemical processes in condensed phases to be studied in an accurate and unbiased manner, leading to new paradigms in the elucidation of microscopic mechanisms, rationalization of experimental data, and testable predictions of new phenomena. The purpose of this work is to give a brief introduction to the technique and to review several important recent developments in the field. Several illustrative examples showing the power of the technique have been chosen. Perspectives on future directions in the field also will be given. PMID:15870204

  1. Molecular Dynamics Simulations of Lignin Peroxidase in Solution

    PubMed Central

    Francesca Gerini, M.; Roccatano, Danilo; Baciocchi, Enrico; Nola, Alfredo Di

    2003-01-01

    The dynamical and structural properties of lignin peroxidase and its Trp171Ala mutant have been investigated in aqueous solution using molecular dynamics (MD) simulations. In both cases, the enzyme retained its overall backbone structure and all its noncovalent interactions in the course of the MD simulations. Very interestingly, the analysis of the MD trajectories showed the presence of large fluctuations in correspondence of the residues forming the heme access channel; these movements enlarge the opening and facilitate the access of substrates to the enzyme active site. Moreover, steered molecular dynamics docking simulations have shown that lignin peroxidase natural substrate (veratryl alcohol) can easily approach the heme edge through the access channel. PMID:12770894

  2. Dynamic combinatorial libraries: from exploring molecular recognition to systems chemistry.

    PubMed

    Li, Jianwei; Nowak, Piotr; Otto, Sijbren

    2013-06-26

    Dynamic combinatorial chemistry (DCC) is a subset of combinatorial chemistry where the library members interconvert continuously by exchanging building blocks with each other. Dynamic combinatorial libraries (DCLs) are powerful tools for discovering the unexpected and have given rise to many fascinating molecules, ranging from interlocked structures to self-replicators. Furthermore, dynamic combinatorial molecular networks can produce emergent properties at systems level, which provide exciting new opportunities in systems chemistry. In this perspective we will highlight some new methodologies in this field and analyze selected examples of DCLs that are under thermodynamic control, leading to synthetic receptors, catalytic systems, and complex self-assembled supramolecular architectures. Also reviewed are extensions of the principles of DCC to systems that are not at equilibrium and may therefore harbor richer functional behavior. Examples include self-replication and molecular machines.

  3. Insight into the molecular switch mechanism of human Rab5a from molecular dynamics simulations

    SciTech Connect

    Wang, Jing-Fang; Chou, Kuo-Chen

    2009-12-18

    Rab5a is currently a most interesting target because it is responsible for regulating the early endosome fusion in endocytosis and possibly the budding process. We utilized longtime-scale molecular dynamics simulations to investigate the internal motion of the wild-type Rab5a and its A30P mutant. It was observed that, after binding with GTP, the global flexibility of the two proteins is increasing, while the local flexibility in their sensitive sites (P-loop, switch I and II regions) is decreasing. Also, the mutation of Ala30 to Pro30 can cause notable flexibility variations in the sensitive sites. However, this kind of variations is dramatically reduced after binding with GTP. Such a remarkable feature is mainly caused by the water network rearrangements in the sensitive sites. These findings might be of use for revealing the profound mechanism of the displacements of Rab5a switch regions, as well as the mechanism of the GDP dissociation and GTP association.

  4. Nonadiabatic molecular dynamics simulations of the energy transfer between building blocks in a phenylene ethynylene dendrimer.

    PubMed

    Fernandez-Alberti, Sebastian; Kleiman, Valeria D; Tretiak, Sergei; Roitberg, Adrian E

    2009-07-01

    The ultrafast dynamics of electronic and vibrational energy transfer between two- and three-ring linear poly(phenylene ethynylene) units linked by meta-substitution is studied by nonadiabatic molecular dynamics simulations. The molecular dynamics with quantum transitions (1, 2) method is used including an "on the fly" calculation of the potential energy surfaces and electronic couplings. The results show that during the first 40 fs after a vertical photoexcitation to the S(2) state, the nonadiabatic coupling between S(2) and S(1) states causes a fast transfer of the electronic populations. A rapid decrease of the S(1)-S(2) energy gap is observed, reaching a first conical intersection at approximately 5 fs. Therefore, the first hopping events take place, and the S(2) state starts to depopulate. The analysis of the structural and energetic properties of the molecule during the jumps reveals the main role that the ethynylene triple bond plays in the unidirectional energy transfer process. PMID:19378966

  5. Fast Quantum Molecular Dynamics Simulations of Simple Organic Liquids under Shock Compression

    NASA Astrophysics Data System (ADS)

    Cawkwell, Marc; Niklasson, Anders; Manner, Virginia; McGrane, Shawn; Dattelbaum, Dana

    2013-06-01

    The responses of liquid formic acid, acrylonitrile, and nitromethane to shock compression have been studied using quantum-based molecular dynamics simulations with the self-consistent tight-binding code LATTE. Microcanonical Born-Oppenheimer trajectories with precise energy conservation were computed without relying on an iterative self-consistent field optimization of the electronic degrees of freedom at each time step via the Fast Quantum Mechanical Molecular Dynamics formalism. The input shock pressures required to initiate chemistry in our simulations agree very well with recent laser- and flyer-plate-driven shock compression experiments. On-the-fly analysis of the electronic structure of the liquids over hundreds of picoseconds after dynamic compression revealed that their reactivity is strongly correlated with the temperature and pressure dependence of their HOMO-LUMO gap.

  6. Molecular dynamics simulation study on the molecular structures of the amylin fibril models.

    PubMed

    Xu, Weixin; Su, Haibin; Zhang, John Z H; Mu, Yuguang

    2012-12-01

    The structural characterization of amyloid fibers is one of the most investigated areas in structural biology. Recently, protofibril models for amylin, i.e., the 37-residue human islet amyloid polypeptide or hIAPP were suggested by two groups based on NMR (Biochemistry 2007, 46, 13505-13522) and X-ray (Protein Sci. 2008, 17, 1467-1474) techniques. However, there are significant differences in the two models which maybe originate from the polymorphic nature of amylin fibrils. To obtain further insights into the packing and stability features of the different models, we performed a series of molecular dynamics simulations on them. Our analysis showed that even pairs of β-sheets composed of a limited number of β-strands are stable in the 100-ns simulations, which suggests that steric zipper interactions at a β-sheet-β-sheet interface strongly contribute to the stability of these amyloid aggregates. For both models, outer strands are more flexible, which might coincide with the dynamical requirement that outer strands act as growing sites facilitating conformational changes of new incoming chains. Moreover, simulation results showed that the X-ray models are structurally more compact than the NMR models and have more intimate patterns, which lead to more rigid amyloid models. As a result, the X-ray models are energetically more stable than the NMR models. Further modeling analyses verify the most likely amylin fibril model among both NMR and X-ray models. Upon further study of the force-induced dissociation of a single chain from the protofibrils, the binding energy and the mechanical stability of the fibril models are revealed. On these bases, it is possible to reconcile the crystallographic and the NMR data on the basic amylin fiber unit. PMID:23145779

  7. An Investigation of Molecular Docking and Molecular Dynamic Simulation on Imidazopyridines as B-Raf Kinase Inhibitors.

    PubMed

    Xie, Huiding; Li, Yupeng; Yu, Fang; Xie, Xiaoguang; Qiu, Kaixiong; Fu, Jijun

    2015-11-16

    In the recent cancer treatment, B-Raf kinase is one of key targets. Nowadays, a group of imidazopyridines as B-Raf kinase inhibitors have been reported. In order to investigate the interaction between this group of inhibitors and B-Raf kinase, molecular docking, molecular dynamic (MD) simulation and binding free energy (ΔGbind) calculation were performed in this work. Molecular docking was carried out to identify the key residues in the binding site, and MD simulations were performed to determine the detail binding mode. The results obtained from MD simulation reveal that the binding site is stable during the MD simulations, and some hydrogen bonds (H-bonds) in MD simulations are different from H-bonds in the docking mode. Based on the obtained MD trajectories, ΔGbind was computed by using Molecular Mechanics Generalized Born Surface Area (MM-GBSA), and the obtained energies are consistent with the activities. An energetic analysis reveals that both electrostatic and van der Waals contributions are important to ΔGbind, and the unfavorable polar solvation contribution results in the instability of the inhibitor with the lowest activity. These results are expected to understand the binding between B-Raf and imidazopyridines and provide some useful information to design potential B-Raf inhibitors.

  8. Understanding flocculation mechanism of graphene oxide for organic dyes from water: Experimental and molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Liu, Jun; Li, Peng; Xiao, Hang; Zhang, Yayun; Shi, Xiaoyang; Lü, Xiaomeng; Chen, Xi

    2015-11-01

    Flocculation treatment processes play an important role in water and wastewater pretreatment. Here we investigate experimentally and theoretically the possibility of using graphene oxide (GO) as a flocculant to remove methylene blue (MB) from water. Experimental results show that GO can remove almost all MB from aqueous solutions at its optimal dosages and molecular dynamics simulations indicate that MB cations quickly congregate around GO in water. Furthermore, PIXEL energy contribution analysis reveals that most of the strong interactions between GO and MB are of a van der Waals (London dispersion) character. These results offer new insights for shedding light on the molecular mechanism of interaction between GO and organic pollutants.

  9. Evaluation of forcefields for molecular mechanics/dynamics calculations involving halogenated anesthetics.

    PubMed

    Trudell, J R; Bertaccini, E

    1998-11-23

    (1) Successful application of molecular mechanics and molecular dynamics calculations to the binding of halogenated anesthetics requires forcefields with correct parameters for halocarbons. (2) Unfortunately, our survey of six popular forcefields revealed that some of them provide a very poor representation of electrostatic interactions for the halogens. (3) This problem is due to poor or missing assignments of partial atomic charges to the halogen atoms. (4) We describe the forcefields most appropriate for use with halogenated anesthetics and suggest a general method for editing the assignment of partial atomic charges by performing an initial quantum mechanics calculation. PMID:10049174

  10. Seeking new mutation clues from Bacillus licheniformis amylase by molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Lu, Tao

    2009-07-01

    Amylase is one of the most important industrial enzymes in the world. Researchers have been searching for a highly thermal stable mutant for many years, but most focus on point mutations of one or few nitrogenous bases. According to this molecular dynamic simulation of amylase from Bacillus licheniformis (BLA), the deletion of some nitrogenous bases would be more efficacious than point mutations. The simulation reveals strong fluctuation of the BLA structure at optimum temperature. The fluctuation of the outer domains of BLA is stronger than that of the core domain. Molecular simulation provides a clue to design thermal stable amylases through deletion mutations in the outer domain.

  11. GAS PHASE MOLECULAR DYNAMICS: HIGH-RESOLUTION SPECTROSCOPIC PROBES OF CHEMICAL DYNAMICS.

    SciTech Connect

    HALL, G.E.

    2006-05-30

    This research is carried out as part of the Gas Phase Molecular Dynamics group program in the Chemistry Department at Brookhaven National Laboratory. High-resolution spectroscopic tools are developed and applied to problems in chemical dynamics. Recent topics have included the state-resolved studies of collision-induced electronic energy transfer, dynamics of barrierless unimolecular reactions, and the kinetics and spectroscopy of transient species.

  12. A random rotor molecule: Vibrational analysis and molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Li, Yu; Zhang, Rui-Qin; Shi, Xing-Qiang; Lin, Zijing; Van Hove, Michel A.

    2012-12-01

    Molecular structures that permit intramolecular rotational motion have the potential to function as molecular rotors. We have employed density functional theory and vibrational frequency analysis to study the characteristic structure and vibrational behavior of the molecule (4',4″″-(bicyclo[2,2,2]octane-1,4-diyldi-4,1-phenylene)-bis-2,2':6',2″-terpyridine. IR active vibrational modes were found that favor intramolecular rotation. To demonstrate the rotor behavior of the isolated single molecule, ab initio molecular dynamics simulations at various temperatures were carried out. This molecular rotor is expected to be thermally triggered via excitation of specific vibrational modes, which implies randomness in its direction of rotation.

  13. Laser-enhanced dynamics in molecular rate processes

    NASA Technical Reports Server (NTRS)

    George, T. F.; Zimmerman, I. H.; Devries, P. L.; Yuan, J.-M.; Lam, K.-S.; Bellum, J. C.; Lee, H.-W.; Slutsky, M. S.

    1978-01-01

    The present discussion deals with some theoretical aspects associated with the description of molecular rate processes in the presence of intense laser radiation, where the radiation actually interacts with the molecular dynamics. Whereas for weak and even moderately intense radiation, the absorption and stimulated emission of photons by a molecular system can be described by perturbative methods, for intense radiation, perturbation theory is usually not adequate. Limiting the analysis to the gas phase, an attempt is made to describe nonperturbative approaches applicable to the description of such processes (in the presence of intense laser radiation) as electronic energy transfer in molecular (in particular atom-atom) collisions; collision-induced ionization and emission; and unimolecular dissociation.

  14. Molecular dynamics computer simulation of permeation in solids

    SciTech Connect

    Pohl, P.I.; Heffelfinger, G.S.; Fisler, D.K.; Ford, D.M.

    1997-12-31

    In this work the authors simulate permeation of gases and cations in solid models using molecular mechanics and a dual control volume grand canonical molecular dynamics technique. The molecular sieving nature of microporous zeolites are discussed and compared with that for amorphous silica made by sol-gel methods. One mesoporous and one microporous membrane model are tested with Lennard-Jones gases corresponding to He, H{sub 2}, Ar and CH{sub 4}. The mesoporous membrane model clearly follows a Knudsen diffusion mechanism, while the microporous model having a hard-sphere cutoff pore diameter of {approximately}3.4 {angstrom} demonstrates molecular sieving of the methane ({sigma} = 3.8 {angstrom}) but anomalous behavior for Ar ({sigma} = 3.4 {angstrom}). Preliminary results of Ca{sup +} diffusion in calcite and He/H{sub 2} diffusion in polyisobutylene are also presented.

  15. Rhodopsin Photoactivation Dynamics Revealed by Quasi-Elastic Neutron Scattering

    NASA Astrophysics Data System (ADS)

    Bhowmik, Debsindhu; Shrestha, Utsab; Perera, Suchhithranga M. C. D.; Chawla, Udeep; Mamontov, Eugene; Brown, Michael; Chu, Xiang-Qiang

    2015-03-01

    Rhodopsin is a G-protein-coupled receptor (GPCR) responsible for vision. During photoactivation, the chromophore retinal dissociates from protein yielding the opsin apoprotein. What are the changes in protein dynamics that occur during the photoactivation process? Here, we studied the microscopic dynamics of dark-state rhodopsin and the ligand-free opsin using quasielastic neutron scattering (QENS). The QENS technique tracks individual hydrogen atom motion because of the much higher neutron scattering cross-section of hydrogen than other atoms. We used protein with CHAPS detergent hydrated with heavy water. The activation of proteins is confirmed at low temperatures up to 300 K by mean-square displacement (MSD) analysis. The QENS experiments at temperatures ranging from 220 K to 300 K clearly indicate an increase in protein dynamic behavior with temperature. The relaxation time for the ligand-bound protein rhodopsin is faster compared to opsin, which can be correlated with the photoactivation. Moreover, the protein dynamics are orders of magnitude slower than the accompanying CHAPS detergent, which unlike protein, manifests localized motions.

  16. Study on the Characteristics of Gas Molecular Mean Free Path in Nanopores by Molecular Dynamics Simulations

    PubMed Central

    Liu, Qixin; Cai, Zhiyong

    2014-01-01

    This paper presents studies on the characteristics of gas molecular mean free path in nanopores by molecular dynamics simulation. Our study results indicate that the mean free path of all molecules in nanopores depend on both the radius of the nanopore and the gas-solid interaction strength. Besides mean free path of all molecules in the nanopore, this paper highlights the gas molecular mean free path at different positions of the nanopore and the anisotropy of the gas molecular mean free path at nanopores. The molecular mean free path varies with the molecule’s distance from the center of the nanopore. The least value of the mean free path occurs at the wall surface of the nanopore. The present paper found that the gas molecular mean free path is anisotropic when gas is confined in nanopores. The radial gas molecular mean free path is much smaller than the mean free path including all molecular collisions occuring in three directions. Our study results also indicate that when gas is confined in nanopores the gas molecule number density does not affect the gas molecular mean free path in the same way as it does for the gas in unbounded space. These study results may bring new insights into understanding the gas flow’s characteristic at nanoscale. PMID:25046745

  17. Molecular Docking and Molecular Dynamics to Identify a Novel Human Immunodeficiency Virus Inhibitor from Alkaloids of Toddalia asiatica

    PubMed Central

    Priya, R.; Sumitha, Rajendrarao; Doss, C. George Priya; Rajasekaran, C.; Babu, S.; Seenivasan, R.; Siva, R.

    2015-01-01

    Background: Acquired immunodeficiency syndrome caused by human immunodeficiency virus (HIV) is an immunosuppressive disease. Over the past decades, it has plagued human health due to the grave consequences in its harness. Objective: For this reason, anti-HIV agents are imperative, and the search for the same from natural resources would assure the safety. Materials and Methods: In this investigation we have performed molecular docking, molecular property prediction, drug-likeness score, and molecular dynamics (MD) simulation to develop a novel anti-HIV drug. We have screened 12 alkaloids from a medicinal plant Toddalia asiatica for its probabilistic binding with the active site of the HIV-1-reverse transcriptase (HIV-1-RT) domain (the major contributor to the onset of the disease). Results: The docking results were evaluated based on free energies of binding (ΔG), and the results suggested toddanol, toddanone, and toddalenone to be potent inhibitors of HIV-1-RT. In addition, the alkaloids were subjected to molecular property prediction analysis. Toddanol and toddanone with more rotatable bonds were found to have a drug-likeness score of 0.23 and 0.11, respectively. These scores were comparable with the standard anti-HIV drug zidovudine with a model score 0.28. Finally, two characteristic protein-ligand complexes were exposed to MD simulation to determine the stability of the predicted conformations. Conclusion: The toddanol-RT complex showed higher stability and stronger H-bonds than toddanone-RT complex. Based on these observations, we firmly believe that the alkaloid toddanol could aid in efficient HIV-1 drug discovery. SUMMARY In the present study, the molecular docking and MD simulations are performed to explore the possible binding mode of HIV 1 RT with 12 alkaloids of T. asiatica. Molecular docking by AutoDock4 revealed three alkaloids toddanol, toddanone, and toddalenone with highest binding affinity towards HIV 1 RT. The drug likeness model score revealed

  18. Rhodopsin photoactivation dynamics revealed by quasi-elastic neutron scattering

    DOE PAGES

    Bhowmik, Debsindhu; Shrestha, Utsab; Perera, Suchithranga M.d.c.; Chawla, Udeep; Mamontov, Eugene; Brown, Michael F.; Chu, Xiang -Qiang

    2015-01-27

    Rhodopsin is a G-protein-coupled receptor (GPCR) responsible for vision under dim light conditions. During rhodopsin photoactivation, the chromophore retinal undergoes cis-trans isomerization, and subsequently dissociates from the protein yielding the opsin apoprotein [1]. What are the changes in protein dynamics that occur during the rhodopsin photoactivation process? Here, we studied the microscopic dynamics of the dark-state rhodopsin and the ligand-free opsin using quasi-elastic neutron scattering (QENS). The QENS technique tracks the individual hydrogen atom motions in the protein molecules, because the neutron scattering cross-section of hydrogen is much higher than other atoms [2-4]. We used protein (rhodopsin/opsin) samples with CHAPSmore » detergent hydrated with heavy water. The solvent signal is suppressed due to the heavy water, so that only the signals from proteins and detergents are detected. The activation of proteins is confirmed at low temperatures up to 300 K by the mean-square displacement (MSD) analysis. Our QENS experiments conducted at temperatures ranging from 220 K to 300 K clearly indicate that the protein dynamic behavior increases with temperature. The relaxation time for the ligand-bound protein rhodopsin was longer compared to opsin, which can be correlated with the photoactivation. Moreover, the protein dynamics are orders of magnitude slower than the accompanying CHAPS detergent, which forms a band around the protein molecule in the micelle. Unlike the protein, the CHAPS detergent manifests localized motions that are the same as in the bulk empty micelles. Furthermore QENS provides unique understanding of the key dynamics involved in the activation of the GPCR involved in the visual process.« less

  19. Rhodopsin photoactivation dynamics revealed by quasi-elastic neutron scattering

    SciTech Connect

    Bhowmik, Debsindhu; Shrestha, Utsab; Perera, Suchithranga M.d.c.; Chawla, Udeep; Mamontov, Eugene; Brown, Michael F.; Chu, Xiang -Qiang

    2015-01-27

    Rhodopsin is a G-protein-coupled receptor (GPCR) responsible for vision under dim light conditions. During rhodopsin photoactivation, the chromophore retinal undergoes cis-trans isomerization, and subsequently dissociates from the protein yielding the opsin apoprotein [1]. What are the changes in protein dynamics that occur during the rhodopsin photoactivation process? Here, we studied the microscopic dynamics of the dark-state rhodopsin and the ligand-free opsin using quasi-elastic neutron scattering (QENS). The QENS technique tracks the individual hydrogen atom motions in the protein molecules, because the neutron scattering cross-section of hydrogen is much higher than other atoms [2-4]. We used protein (rhodopsin/opsin) samples with CHAPS detergent hydrated with heavy water. The solvent signal is suppressed due to the heavy water, so that only the signals from proteins and detergents are detected. The activation of proteins is confirmed at low temperatures up to 300 K by the mean-square displacement (MSD) analysis. Our QENS experiments conducted at temperatures ranging from 220 K to 300 K clearly indicate that the protein dynamic behavior increases with temperature. The relaxation time for the ligand-bound protein rhodopsin was longer compared to opsin, which can be correlated with the photoactivation. Moreover, the protein dynamics are orders of magnitude slower than the accompanying CHAPS detergent, which forms a band around the protein molecule in the micelle. Unlike the protein, the CHAPS detergent manifests localized motions that are the same as in the bulk empty micelles. Furthermore QENS provides unique understanding of the key dynamics involved in the activation of the GPCR involved in the visual process.

  20. Molecular dynamics simulation: A tool for exploration and discovery

    NASA Astrophysics Data System (ADS)

    Rapaport, Dennis C.

    2009-03-01

    The exploratory and didactic aspects of science both benefit from the ever-growing role played by computer simulation. One particularly important simulational approach is the molecular dynamics method, used for studying the nature of matter from the molecular to much larger scales. The effectiveness of molecular dynamics can be enhanced considerably by employing visualization and interactivity during the course of the computation and afterwards, allowing the modeler not only to observe the detailed behavior of the systems simulated in different ways, but also to steer the computations in alternative directions by manipulating parameters that govern the actual behavior. This facilitates the creation of potentially rich simulational environments for examining a multitude of complex phenomena, as well as offering an opportunity for enriching the learning process. A series of relatively advanced examples involving molecular dynamics will be used to demonstrate the value of this approach, in particular, atomistic simulations of spontaneously emergent structured fluid flows (the classic Rayleigh--B'enard and Taylor--Couette problems), supramolecular self-assembly of highly symmetric shell structures (involved in the formation of viral capsids), and that most counterintuitive of phenomena, granular segregation (e.g., axial and radial separation in a rotating cylinder).

  1. Molecular Dynamics of a Water-Lipid Bilayer Interface

    NASA Technical Reports Server (NTRS)

    Wilson, Michael A.; Pohorille, Andrew

    1994-01-01

    We present results of molecular dynamics simulations of a glycerol 1-monooleate bilayer in water. The total length of analyzed trajectories is 5ns. The calculated width of the bilayer agrees well with the experimentally measured value. The interior of the membrane is in a highly disordered fluid state. Atomic density profile, orientational and conformational distribution functions, and order parameters indicate that disorder increases toward the center of the bilayer. Analysis of out-of-plane thermal fluctuations of the bilayer surfaces occurring at the time scale of the present calculations reveals that the distribution of modes agrees with predictions of the capillary wave model. Fluctuations of both bilayer surfaces are uncorrelated, yielding Gaussian distribution of instantaneous widths of the membrane. Fluctuations of the width produce transient thinning defects in the bilayer which occasionally span almost half of the membrane. The leading mechanism of these fluctuations is the orientational and conformational motion of head groups rather than vertical motion of the whole molecules. Water considerably penetrates the head group region of the bilayer but not its hydrocarbon core. The total net excess dipole moment of the interfacial water points toward the aqueous phase, but the water polarization profile is non-monotonic. Both water and head groups significantly contribute to the surface potential across the interface. The calculated sign of the surface potential is in agreement with that from experimental measurements, but the value is markedly overestimated. The structural and electrical properties of the water-bilayer system are discussed in relation to membrane functions, in particular transport of ions and nonelectrolytes across membranes.

  2. Size dependence of cavity volume: a molecular dynamics study.

    PubMed

    Patel, Nisha; Dubins, David N; Pomès, Régis; Chalikian, Tigran V

    2012-02-01

    Partial molar volume, V°, has been used as a tool to sample solute hydration for decades. The efficacy of volumetric investigations of hydration depends on our ability to reliably discriminate between the cavity, V(C), and interaction, V(I), contributions to the partial molar volume. The cavity volume, V(C), consists of the intrinsic volume, V(M), of a solute molecule and the thermal volume, V(T), with the latter representing the volume of the effective void created around the solute. In this work, we use molecular dynamics simulations in conjunction with the Kirkwood-Buff theory to compute the partial molar volumes for organic solutes of varying sizes in water. We perform our computations using the Lennard-Jones and Coulombic pair potentials as well as truncated potentials which contain only the Lennard-Jones but not the Coulombic contribution. The partial molar volume computed with the Lennard-Jones potentials in the absence of the Coulombic term nearly coincides with the cavity volume, V(C). We determine the thermal volume, V(T), for each compound by subtracting its van der Waals volume, V(W), from V(C). Finally, we apply the spherical approximation of solute geometry to evaluate the thickness of the thermal volume, δ. Our results reveal an increase in the thickness of thermal volume, δ, with an increase in the size of the solute. This finding may be related to dewetting of large nonpolar solutes and the concomitant increase in the compressibility of water of hydration. PMID:22133917

  3. Tyrosine Aminotransferase: Biochemical and Structural Properties and Molecular Dynamics Simulations

    SciTech Connect

    P Mehere; Q Han; J Lemkul; C Vavricka; H Robinson; D Bevan; J Li

    2011-12-31

    Tyrosine aminotransferase (TAT) catalyzes the transamination of tyrosine and other aromatic amino acids. The enzyme is thought to play a role in tyrosinemia type II, hepatitis and hepatic carcinoma recovery. The objective of this study is to investigate its biochemical and structural characteristics and substrate specificity in order to provide insight regarding its involvement in these diseases. Mouse TAT (mTAT) was cloned from a mouse cDNA library, and its recombinant protein was produced using Escherichia coli cells and purified using various chromatographic techniques. The recombinant mTAT is able to catalyze the transamination of tyrosine using {alpha}-ketoglutaric acid as an amino group acceptor at neutral pH. The enzyme also can use glutamate and phenylalanine as amino group donors and p-hydroxy-phenylpyruvate, phenylpyruvate and alpha-ketocaproic acid as amino group acceptors. Through macromolecular crystallography we have determined the mTAT crystal structure at 2.9 {angstrom} resolution. The crystal structure revealed the interaction between the pyridoxal-5'-phosphate cofactor and the enzyme, as well as the formation of a disulphide bond. The detection of disulphide bond provides some rational explanation regarding previously observed TAT inactivation under oxidative conditions and reactivation of the inactive TAT in the presence of a reducing agent. Molecular dynamics simulations using the crystal structures of Trypanosoma cruzi TAT and human TAT provided further insight regarding the substrate-enzyme interactions and substrate specificity. The biochemical and structural properties of TAT and the binding of its cofactor and the substrate may help in elucidation of the mechanism of TAT inhibition and activation.

  4. Tyrosine aminotransferase: biochemical and structural properties and molecular dynamics simulations

    SciTech Connect

    Mehere, P.; Robinson, H.; Han, Q.; Lemkul, J. A.; Vavricka, C. J.; Bevan, D. R.; Li, J.

    2010-11-01

    Tyrosine aminotransferase (TAT) catalyzes the transamination of tyrosine and other aromatic amino acids. The enzyme is thought to play a role in tyrosinemia type II, hepatitis and hepatic carcinoma recovery. The objective of this study is to investigate its biochemical and structural characteristics and substrate specificity in order to provide insight regarding its involvement in these diseases. Mouse TAT (mTAT) was cloned from a mouse cDNA library, and its recombinant protein was produced using Escherichia coli cells and purified using various chromatographic techniques. The recombinant mTAT is able to catalyze the transamination of tyrosine using {alpha}-ketoglutaric acid as an amino group acceptor at neutral pH. The enzyme also can use glutamate and phenylalanine as amino group donors and p-hydroxy-phenylpyruvate, phenylpyruvate and alpha-ketocaproic acid as amino group acceptors. Through macromolecular crystallography we have determined the mTAT crystal structure at 2.9 {angstrom} resolution. The crystal structure revealed the interaction between the pyridoxal-5'-phosphate cofactor and the enzyme, as well as the formation of a disulphide bond. The detection of disulphide bond provides some rational explanation regarding previously observed TAT inactivation under oxidative conditions and reactivation of the inactive TAT in the presence of a reducing agent. Molecular dynamics simulations using the crystal structures of Trypanosoma cruzi TAT and human TAT provided further insight regarding the substrate-enzyme interactions and substrate specificity. The biochemical and structural properties of TAT and the binding of its cofactor and the substrate may help in elucidation of the mechanism of TAT inhibition and activation.

  5. Tyrosine aminotransferase: biochemical and structural properties and molecular dynamics simulations.

    PubMed

    Mehere, Prajwalini; Han, Qian; Lemkul, Justin A; Vavricka, Christopher J; Robinson, Howard; Bevan, David R; Li, Jianyong

    2010-11-01

    Tyrosine aminotransferase (TAT) catalyzes the transamination of tyrosine and other aromatic amino acids. The enzyme is thought to play a role in tyrosinemia type II, hepatitis and hepatic carcinoma recovery. The objective of this study is to investigate its biochemical and structural characteristics and substrate specificity in order to provide insight regarding its involvement in these diseases. Mouse TAT (mTAT) was cloned from a mouse cDNA library, and its recombinant protein was produced using Escherichia coli cells and purified using various chromatographic techniques. The recombinant mTAT is able to catalyze the transamination of tyrosine using α-ketoglutaric acid as an amino group acceptor at neutral pH. The enzyme also can use glutamate and phenylalanine as amino group donors and p-hydroxy-phenylpyruvate, phenylpyruvate and alpha-ketocaproic acid as amino group acceptors. Through macromolecular crystallography we have determined the mTAT crystal structure at 2.9 Å resolution. The crystal structure revealed the interaction between the pyridoxal-5'-phosphate cofactor and the enzyme, as well as the formation of a disulphide bond. The detection of disulphide bond provides some rational explanation regarding previously observed TAT inactivation under oxidative conditions and reactivation of the inactive TAT in the presence of a reducing agent. Molecular dynamics simulations using the crystal structures of Trypanosoma cruzi TAT and human TAT provided further insight regarding the substrate-enzyme interactions and substrate specificity. The biochemical and structural properties of TAT and the binding of its cofactor and the substrate may help in elucidation of the mechanism of TAT inhibition and activation.

  6. All-Atom Molecular Dynamics of Virus Capsids as Drug Targets

    PubMed Central

    2016-01-01

    Virus capsids are protein shells that package the viral genome. Although their morphology and biological functions can vary markedly, capsids often play critical roles in regulating viral infection pathways. A detailed knowledge of virus capsids, including their dynamic structure, interactions with cellular factors, and the specific roles that they play in the replication cycle, is imperative for the development of antiviral therapeutics. The following Perspective introduces an emerging area of computational biology that focuses on the dynamics of virus capsids and capsid–protein assemblies, with particular emphasis on the effects of small-molecule drug binding on capsid structure, stability, and allosteric pathways. When performed at chemical detail, molecular dynamics simulations can reveal subtle changes in virus capsids induced by drug molecules a fraction of their size. Here, the current challenges of performing all-atom capsid–drug simulations are discussed, along with an outlook on the applicability of virus capsid simulations to reveal novel drug targets. PMID:27128262

  7. Dynamic Compression of Chondrocyte-Agarose Constructs Reveals New Candidate Mechanosensitive Genes

    PubMed Central

    Bougault, Carole; Aubert-Foucher, Elisabeth; Paumier, Anne; Perrier-Groult, Emeline; Huot, Ludovic; Hot, David; Duterque-Coquillaud, Martine; Mallein-Gerin, Frédéric

    2012-01-01

    Articular cartilage is physiologically exposed to repeated loads. The mechanical properties of cartilage are due to its extracellular matrix, and homeostasis is maintained by the sole cell type found in cartilage, the chondrocyte. Although mechanical forces clearly control the functions of articular chondrocytes, the biochemical pathways that mediate cellular responses to mechanical stress have not been fully characterised. The aim of our study was to examine early molecular events triggered by dynamic compression in chondrocytes. We used an experimental system consisting of primary mouse chondrocytes embedded within an agarose hydrogel; embedded cells were pre-cultured for one week and subjected to short-term compression experiments. Using Western blots, we demonstrated that chondrocytes maintain a differentiated phenotype in this model system and reproduce typical chondrocyte-cartilage matrix interactions. We investigated the impact of dynamic compression on the phosphorylation state of signalling molecules and genome-wide gene expression. After 15 min of dynamic compression, we observed transient activation of ERK1/2 and p38 (members of the mitogen-activated protein kinase (MAPK) pathways) and Smad2/3 (members of the canonical transforming growth factor (TGF)-β pathways). A microarray analysis performed on chondrocytes compressed for 30 min revealed that only 20 transcripts were modulated more than 2-fold. A less conservative list of 325 modulated genes included genes related to the MAPK and TGF-β pathways and/or known to be mechanosensitive in other biological contexts. Of these candidate mechanosensitive genes, 85% were down-regulated. Down-regulation may therefore represent a general control mechanism for a rapid response to dynamic compression. Furthermore, modulation of transcripts corresponding to different aspects of cellular physiology was observed, such as non-coding RNAs or primary cilium. This study provides new insight into how chondrocytes respond

  8. Fluctuation power spectra reveal dynamical heterogeneity of peptides

    NASA Astrophysics Data System (ADS)

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

    2010-07-01

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

  9. A molecular dynamics study of polymer/graphene interfacial systems

    SciTech Connect

    Rissanou, Anastassia N.; Harmandaris, Vagelis

    2014-05-15

    Graphene based polymer nanocomposites are hybrid materials with a very broad range of technological applications. In this work, we study three hybrid polymer/graphene interfacial systems (polystyrene/graphene, poly(methyl methacrylate)/graphene and polyethylene/graphene) through detailed atomistic molecular dynamics (MD) simulations. Density profiles, structural characteristics and mobility aspects are being examined at the molecular level for all model systems. In addition, we compare the properties of the hybrid systems to the properties of the corresponding bulk ones, as well as to theoretical predictions.

  10. Adiponectin fine-tuning of liver regeneration dynamics revealed through cellular network modelling.

    PubMed

    Correnti, Jason M; Cook, Daniel; Aksamitiene, Edita; Swarup, Aditi; Ogunnaike, Babatunde; Vadigepalli, Rajanikanth; Hoek, Jan B

    2015-01-15

    Following partial hepatectomy, the liver initiates a regenerative programme involving hepatocyte priming and replication driven by the coordinated actions of cytokine and growth factors. We investigated the mechanisms underlying adiponectin's (Adn) regulation of liver regeneration through modulation of these mediators. Adn(-/-) mice showed delayed onset of hepatocyte replication, but accelerated cell cycle progression relative to wild-type mice, suggesting Adn has multiple effects fine-tuning the kinetics of liver regeneration. We developed a computational model describing the molecular and physiological kinetics of liver regeneration in Adn(-/-) mice. We employed this computational model to evaluate the underlying regulatory mechanisms. Our analysis predicted that Adn is required for an efficient early cytokine response to partial hepatectomy, but is inhibitory to later growth factor actions. Consistent with this prediction, Adn knockout reduced hepatocyte responses to interleukin-6 during the priming phase, but enhanced growth factor levels through peak hepatocyte replication. By contrast, supraphysiological concentrations of Adn resulting from rosiglitazone treatment suppressed regeneration by reducing growth factor levels during S phase, consistent with computational predictions. Together, these results revealed that Adn fine-tunes the progression of liver regeneration through dynamically modulating molecular mediator networks and cellular interactions within the liver.

  11. Adiponectin fine-tuning of liver regeneration dynamics revealed through cellular network modeling.

    PubMed

    Correnti, Jason M; Cook, Daniel; Aksamitiene, Edita; Swarup, Aditi; Ogunnaike, Babatunde; Vadigepalli, Rajanikanth; Hoek, Jan B

    2014-11-10

    Following partial hepatectomy, the liver initiates a regenerative program involving hepatocyte priming and replication driven by coordinated cytokine and growth factor actions. We investigated the mechanisms underlying Adiponectin's (Adn) regulation of liver regeneration through modulation of these mediators. Adn-/- mice showed delayed onset of hepatocyte replication, but accelerated cell cycle progression relative to wild-type mice, suggesting Adn has multiple effects fine-tuning the kinetics of liver regeneration. We developed a computational model describing the molecular and physiological kinetics of liver regeneration in Adn-/- mice. We employed this computational model to evaluate the underlying regulatory mechanisms. Our analysis predicted that Adn is required for an efficient early cytokine response to partial hepatectomy, but is inhibitory to later growth factor actions. Consistent with this prediction, Adn knockout reduced hepatocyte responses to IL-6 during the priming phase, but enhanced growth factor levels through peak hepatocyte replication. By contrast, supraphysiological concentrations of Adn resulting from rosiglitazone treatment suppressed regeneration by reducing growth factor levels during S phase, consistent with computational predictions. Together, these results revealed that Adn fine-tunes the progression of liver regeneration through dynamically modulating molecular mediator networks and cellular interactions within the liver. This article is protected by copyright. All rights reserved.

  12. Chemical Dynamics, Molecular Energetics, and Kinetics at the Synchrotron

    SciTech Connect

    Leone, Stephen R.; Ahmed, Musahid; Wilson, Kevin R.

    2010-03-14

    Scientists at the Chemical Dynamics Beamline of the Advanced Light Source in Berkeley are continuously reinventing synchrotron investigations of physical chemistry and chemical physics with vacuum ultraviolet light. One of the unique aspects of a synchrotron for chemical physics research is the widely tunable vacuum ultraviolet light that permits threshold ionization of large molecules with minimal fragmentation. This provides novel opportunities to assess molecular energetics and reaction mechanisms, even beyond simple gas phase molecules. In this perspective, significant new directions utilizing the capabilities at the Chemical Dynamics Beamline are presented, along with an outlook for future synchrotron and free electron laser science in chemical dynamics. Among the established and emerging fields of investigations are cluster and biological molecule spectroscopy and structure, combustion flame chemistry mechanisms, radical kinetics and product isomer dynamics, aerosol heterogeneous chemistry, planetary and interstellar chemistry, and secondary neutral ion-beam desorption imaging of biological matter and materials chemistry.

  13. Optogenetic perturbations reveal the dynamics of an oculomotor integrator

    PubMed Central

    Gonçalves, Pedro J.; Arrenberg, Aristides B.; Hablitzel, Bastian; Baier, Herwig; Machens, Christian K.

    2014-01-01

    Many neural systems can store short-term information in persistently firing neurons. Such persistent activity is believed to be maintained by recurrent feedback among neurons. This hypothesis has been fleshed out in detail for the oculomotor integrator (OI) for which the so-called “line attractor” network model can explain a large set of observations. Here we show that there is a plethora of such models, distinguished by the relative strength of recurrent excitation and inhibition. In each model, the firing rates of the neurons relax toward the persistent activity states. The dynamics of relaxation can be quite different, however, and depend on the levels of recurrent excitation and inhibition. To identify the correct model, we directly measure these relaxation dynamics by performing optogenetic perturbations in the OI of zebrafish expressing halorhodopsin or channelrhodopsin. We show that instantaneous, inhibitory stimulations of the OI lead to persistent, centripetal eye position changes ipsilateral to the stimulation. Excitatory stimulations similarly cause centripetal eye position changes, yet only contralateral to the stimulation. These results show that the dynamics of the OI are organized around a central attractor state—the null position of the eyes—which stabilizes the system against random perturbations. Our results pose new constraints on the circuit connectivity of the system and provide new insights into the mechanisms underlying persistent activity. PMID:24616666

  14. Accelerating ring-polymer molecular dynamics with parallel-replica dynamics

    NASA Astrophysics Data System (ADS)

    Lu, Chun-Yaung; Perez, Danny; Voter, Arthur F.

    2016-06-01

    Nuclear quantum effects are important for systems containing light elements, and the effects are more prominent in the low temperature regime where the dynamics also becomes sluggish. We show that parallel replica (ParRep) dynamics, an accelerated molecular dynamics approach for infrequent-event systems, can be effectively combined with ring-polymer molecular dynamics, a semiclassical trajectory approach that gives a good approximation to zero-point and tunneling effects in activated escape processes. The resulting RP-ParRep method is a powerful tool for reaching long time scales in complex infrequent-event systems where quantum dynamics are important. Two illustrative examples, symmetric Eckart barrier crossing and interstitial helium diffusion in Fe and Fe-Cr alloy, are presented to demonstrate the accuracy and long-time scale capability of this approach.

  15. Accelerating ring-polymer molecular dynamics with parallel-replica dynamics.

    PubMed

    Lu, Chun-Yaung; Perez, Danny; Voter, Arthur F

    2016-06-28

    Nuclear quantum effects are important for systems containing light elements, and the effects are more prominent in the low temperature regime where the dynamics also becomes sluggish. We show that parallel replica (ParRep) dynamics, an accelerated molecular dynamics approach for infrequent-event systems, can be effectively combined with ring-polymer molecular dynamics, a semiclassical trajectory approach that gives a good approximation to zero-point and tunneling effects in activated escape processes. The resulting RP-ParRep method is a powerful tool for reaching long time scales in complex infrequent-event systems where quantum dynamics are important. Two illustrative examples, symmetric Eckart barrier crossing and interstitial helium diffusion in Fe and Fe-Cr alloy, are presented to demonstrate the accuracy and long-time scale capability of this approach. PMID:27369499

  16. A Series of Molecular Dynamics and Homology Modeling Computer Labs for an Undergraduate Molecular Modeling Course

    ERIC Educational Resources Information Center

    Elmore, Donald E.; Guayasamin, Ryann C.; Kieffer, Madeleine E.

    2010-01-01

    As computational modeling plays an increasingly central role in biochemical research, it is important to provide students with exposure to common modeling methods in their undergraduate curriculum. This article describes a series of computer labs designed to introduce undergraduate students to energy minimization, molecular dynamics simulations,…

  17. Dynamic Monitoring Reveals Motor Task Characteristics in Prehistoric Technical Gestures

    PubMed Central

    Pfleging, Johannes; Stücheli, Marius; Iovita, Radu; Buchli, Jonas

    2015-01-01

    Reconstructing ancient technical gestures associated with simple tool actions is crucial for understanding the co-evolution of the human forelimb and its associated control-related cognitive functions on the one hand, and of the human technological arsenal on the other hand. Although the topic of gesture is an old one in Paleolithic archaeology and in anthropology in general, very few studies have taken advantage of the new technologies from the science of kinematics in order to improve replicative experimental protocols. Recent work in paleoanthropology has shown the potential of monitored replicative experiments to reconstruct tool-use-related motions through the study of fossil bones, but so far comparatively little has been done to examine the dynamics of the tool itself. In this paper, we demonstrate that we can statistically differentiate gestures used in a simple scraping task through dynamic monitoring. Dynamics combines kinematics (position, orientation, and speed) with contact mechanical parameters (force and torque). Taken together, these parameters are important because they play a role in the formation of a visible archaeological signature, use-wear. We present our new affordable, yet precise methodology for measuring the dynamics of a simple hide-scraping task, carried out using a pull-to (PT) and a push-away (PA) gesture. A strain gage force sensor combined with a visual tag tracking system records force, torque, as well as position and orientation of hafted flint stone tools. The set-up allows switching between two tool configurations, one with distal and the other one with perpendicular hafting of the scrapers, to allow for ethnographically plausible reconstructions. The data show statistically significant differences between the two gestures: scraping away from the body (PA) generates higher shearing forces, but requires greater hand torque. Moreover, most benchmarks associated with the PA gesture are more highly variable than in the PT gesture

  18. Dynamic Monitoring Reveals Motor Task Characteristics in Prehistoric Technical Gestures.

    PubMed

    Pfleging, Johannes; Stücheli, Marius; Iovita, Radu; Buchli, Jonas

    2015-01-01

    Reconstructing ancient technical gestures associated with simple tool actions is crucial for understanding the co-evolution of the human forelimb and its associated control-related cognitive functions on the one hand, and of the human technological arsenal on the other hand. Although the topic of gesture is an old one in Paleolithic archaeology and in anthropology in general, very few studies have taken advantage of the new technologies from the science of kinematics in order to improve replicative experimental protocols. Recent work in paleoanthropology has shown the potential of monitored replicative experiments to reconstruct tool-use-related motions through the study of fossil bones, but so far comparatively little has been done to examine the dynamics of the tool itself. In this paper, we demonstrate that we can statistically differentiate gestures used in a simple scraping task through dynamic monitoring. Dynamics combines kinematics (position, orientation, and speed) with contact mechanical parameters (force and torque). Taken together, these parameters are important because they play a role in the formation of a visible archaeological signature, use-wear. We present our new affordable, yet precise methodology for measuring the dynamics of a simple hide-scraping task, carried out using a pull-to (PT) and a push-away (PA) gesture. A strain gage force sensor combined with a visual tag tracking system records force, torque, as well as position and orientation of hafted flint stone tools. The set-up allows switching between two tool configurations, one with distal and the other one with perpendicular hafting of the scrapers, to allow for ethnographically plausible reconstructions. The data show statistically significant differences between the two gestures: scraping away from the body (PA) generates higher shearing forces, but requires greater hand torque. Moreover, most benchmarks associated with the PA gesture are more highly variable than in the PT gesture

  19. Dynamic Monitoring Reveals Motor Task Characteristics in Prehistoric Technical Gestures.

    PubMed

    Pfleging, Johannes; Stücheli, Marius; Iovita, Radu; Buchli, Jonas

    2015-01-01

    Reconstructing ancient technical gestures associated with simple tool actions is crucial for understanding the co-evolution of the human forelimb and its associated control-related cognitive functions on the one hand, and of the human technological arsenal on the other hand. Although the topic of gesture is an old one in Paleolithic archaeology and in anthropology in general, very few studies have taken advantage of the new technologies from the science of kinematics in order to improve replicative experimental protocols. Recent work in paleoanthropology has shown the potential of monitored replicative experiments to reconstruct tool-use-related motions through the study of fossil bones, but so far comparatively little has been done to examine the dynamics of the tool itself. In this paper, we demonstrate that we can statistically differentiate gestures used in a simple scraping task through dynamic monitoring. Dynamics combines kinematics (position, orientation, and speed) with contact mechanical parameters (force and torque). Taken together, these parameters are important because they play a role in the formation of a visible archaeological signature, use-wear. We present our new affordable, yet precise methodology for measuring the dynamics of a simple hide-scraping task, carried out using a pull-to (PT) and a push-away (PA) gesture. A strain gage force sensor combined with a visual tag tracking system records force, torque, as well as position and orientation of hafted flint stone tools. The set-up allows switching between two tool configurations, one with distal and the other one with perpendicular hafting of the scrapers, to allow for ethnographically plausible reconstructions. The data show statistically significant differences between the two gestures: scraping away from the body (PA) generates higher shearing forces, but requires greater hand torque. Moreover, most benchmarks associated with the PA gesture are more highly variable than in the PT gesture

  20. Kinetic analysis reveals the diversity of microscopic mechanisms through which molecular chaperones suppress amyloid formation

    NASA Astrophysics Data System (ADS)

    Arosio, Paolo; Michaels, Thomas C. T.; Linse, Sara; Månsson, Cecilia; Emanuelsson, Cecilia; Presto, Jenny; Johansson, Jan; Vendruscolo, Michele; Dobson, Christopher M.; Knowles, Tuomas P. J.

    2016-03-01

    It is increasingly recognized that molecular chaperones play a key role in modulating the formation of amyloid fibrils, a process associated with a wide range of human disorders. Understanding the detailed mechanisms by which they perform this function, however, has been challenging because of the great complexity of the protein aggregation process itself. In this work, we build on a previous kinetic approach and develop a model that considers pairwise interactions between molecular chaperones and different protein species to identify the protein components targeted by the chaperones and the corresponding microscopic reaction steps that are inhibited. We show that these interactions conserve the topology of the unperturbed reaction network but modify the connectivity weights between the different microscopic steps. Moreover, by analysing several protein-molecular chaperone systems, we reveal the striking diversity in the microscopic mechanisms by which molecular chaperones act to suppress amyloid formation.

  1. Kinetic analysis reveals the diversity of microscopic mechanisms through which molecular chaperones suppress amyloid formation

    PubMed Central

    Arosio, Paolo; Michaels, Thomas C. T.; Linse, Sara; Månsson, Cecilia; Emanuelsson, Cecilia; Presto, Jenny; Johansson, Jan; Vendruscolo, Michele; Dobson, Christopher M.; Knowles, Tuomas P. J.

    2016-01-01

    It is increasingly recognized that molecular chaperones play a key role in modulating the formation of amyloid fibrils, a process associated with a wide range of human disorders. Understanding the detailed mechanisms by which they perform this function, however, has been challenging because of the great complexity of the protein aggregation process itself. In this work, we build on a previous kinetic approach and develop a model that considers pairwise interactions between molecular chaperones and different protein species to identify the protein components targeted by the chaperones and the corresponding microscopic reaction steps that are inhibited. We show that these interactions conserve the topology of the unperturbed reaction network but modify the connectivity weights between the different microscopic steps. Moreover, by analysing several protein-molecular chaperone systems, we reveal the striking diversity in the microscopic mechanisms by which molecular chaperones act to suppress amyloid formation. PMID:27009901

  2. Concise NMR approach for molecular dynamics characterizations in organic solids.

    PubMed

    Aliev, Abil E; Courtier-Murias, Denis

    2013-08-22

    Molecular dynamics characterisations in solids can be carried out selectively using dipolar-dephasing experiments. Here we show that the introduction of a sum of Lorentzian and Gaussian functions greatly improve fittings of the "intensity versus time" data for protonated carbons in dipolar-dephasing experiments. The Lorentzian term accounts for remote intra- and intermolecular (1)H-(13)C dipole-dipole interactions, which vary from one molecule to another or for different carbons within the same molecule. Thus, by separating contributions from weak remote interactions, more accurate Gaussian decay constants, T(dd), can be extracted for directly bonded (1)H-(13)C dipole-dipole interactions. Reorientations of the (1)H-(13)C bonds lead to the increase of T(dd), and by measuring dipolar-dephasing constants, insight can be gained into dynamics in solids. We have demonstrated advantages of the method using comparative dynamics studies in the α and γ polymorphs of glycine, cyclic amino acids L-proline, DL-proline and trans-4-hydroxy-L-proline, the Ala residue in different dipeptides, as well as adamantane and hexamethylenetetramine. It was possible to distinguish subtle differences in dynamics of different carbon sites within a molecule in polymorphs and in L- and DL-forms. The presence of overall molecular motions is shown to lead to particularly large differences in dipolar-dephasing experiments. The differences in dynamics can be attributed to differences in noncovalent interactions. In the case of hexamethylenetetramine, for example, the presence of C-H···N interactions leads to nearly rigid molecules. Overall, the method allows one to gain insight into the role of noncovalent interactions in solids and their influence on the molecular dynamics.

  3. Molecular Dynamics Simulations of Laser Powered Carbon Nanotube Gears

    NASA Technical Reports Server (NTRS)

    Srivastava, Deepak; Globus, Al; Han, Jie; Chancellor, Marisa K. (Technical Monitor)

    1997-01-01

    Dynamics of laser powered carbon nanotube gears is investigated by molecular dynamics simulations with Brenner's hydrocarbon potential. We find that when the frequency of the laser electric field is much less than the intrinsic frequency of the carbon nanotube, the tube exhibits an oscillatory pendulam behavior. However, a unidirectional rotation of the gear with oscillating frequency is observed under conditions of resonance between the laser field and intrinsic gear frequencies. The operating conditions for stable rotations of the nanotube gears, powered by laser electric fields are explored, in these simulations.

  4. Molecular dynamical simulations of melting behaviors of metal clusters

    SciTech Connect

    Hamid, Ilyar; Fang, Meng; Duan, Haiming

    2015-04-15

    The melting behaviors of metal clusters are studied in a wide range by molecular dynamics simulations. The calculated results show that there are fluctuations in the heat capacity curves of some metal clusters due to the strong structural competition; For the 13-, 55- and 147-atom clusters, variations of the melting points with atomic number are almost the same; It is found that for different metal clusters the dynamical stabilities of the octahedral structures can be inferred in general by a criterion proposed earlier by F. Baletto et al. [J. Chem. Phys. 116 3856 (2002)] for the statically stable structures.

  5. Application of two dimensional periodic molecular dynamics to interfaces.

    NASA Astrophysics Data System (ADS)

    Gay, David H.; Slater, Ben; Catlow, C. Richard A.

    1997-08-01

    We have applied two-dimensional molecular dynamics to the surface of a crystalline aspartame and the interface between the crystal face and a solvent (water). This has allowed us to look at the dynamic processes at the surface. Understanding the surface structure and properties are important to controlling the crystal morphology. The thermodynamic ensemble was constant Number, surface Area and Temperature (NAT). The calculations have been carried out using a 2D Ewald summation and 2D periodic boundary conditions for the short range potentials. The equations of motion integration has been carried out using the standard velocity Verlet algorithm.

  6. Photochemical processes in laser ablation of organic solids: Molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Yingling, Yaroslava G.

    molecular clusters. These massive clusters later disintegrate in the plume into the smaller clusters and monomers due to ongoing chemical reactions. The ejection and disintegration of big clusters result in the higher material removal rates and higher plume density. The results from our molecular dynamics simulations are in good agreement with experiment and provide microscopic perspective of photochemical processes in laser ablation to experimental investigations. The ablation of material that is onset by pure photochemical processes has been investigated by molecular dynamics simulations. The simulations reveal that ablation by purely photochemical processes is accompanied by the ejection of relatively cold massive molecular clusters from the surface of the sample. The top of the plume exhibits high temperatures whereas the residual part of the sample is cold. The removal of the damaged material through big molecular cluster ejection is consistent with experimental observations of low heat damage of material. (Abstract shortened by UMI.)

  7. Visual verification and analysis of cluster detection for molecular dynamics.

    PubMed

    Grottel, Sebastian; Reina, Guido; Vrabec, Jadran; Ertl, Thomas

    2007-01-01

    A current research topic in molecular thermodynamics is the condensation of vapor to liquid and the investigation of this process at the molecular level. Condensation is found in many physical phenomena, e.g. the formation of atmospheric clouds or the processes inside steam turbines, where a detailed knowledge of the dynamics of condensation processes will help to optimize energy efficiency and avoid problems with droplets of macroscopic size. The key properties of these processes are the nucleation rate and the critical cluster size. For the calculation of these properties it is essential to make use of a meaningful definition of molecular clusters, which currently is a not completely resolved issue. In this paper a framework capable of interactively visualizing molecular datasets of such nucleation simulations is presented, with an emphasis on the detected molecular clusters. To check the quality of the results of the cluster detection, our framework introduces the concept of flow groups to highlight potential cluster evolution over time which is not detected by the employed algorithm. To confirm the findings of the visual analysis, we coupled the rendering view with a schematic view of the clusters' evolution. This allows to rapidly assess the quality of the molecular cluster detection algorithm and to identify locations in the simulation data in space as well as in time where the cluster detection fails. Thus, thermodynamics researchers can eliminate weaknesses in their cluster detection algorithms. Several examples for the effective and efficient usage of our tool are presented. PMID:17968118

  8. Visual verification and analysis of cluster detection for molecular dynamics.

    PubMed

    Grottel, Sebastian; Reina, Guido; Vrabec, Jadran; Ertl, Thomas

    2007-01-01

    A current research topic in molecular thermodynamics is the condensation of vapor to liquid and the investigation of this process at the molecular level. Condensation is found in many physical phenomena, e.g. the formation of atmospheric clouds or the processes inside steam turbines, where a detailed knowledge of the dynamics of condensation processes will help to optimize energy efficiency and avoid problems with droplets of macroscopic size. The key properties of these processes are the nucleation rate and the critical cluster size. For the calculation of these properties it is essential to make use of a meaningful definition of molecular clusters, which currently is a not completely resolved issue. In this paper a framework capable of interactively visualizing molecular datasets of such nucleation simulations is presented, with an emphasis on the detected molecular clusters. To check the quality of the results of the cluster detection, our framework introduces the concept of flow groups to highlight potential cluster evolution over time which is not detected by the employed algorithm. To confirm the findings of the visual analysis, we coupled the rendering view with a schematic view of the clusters' evolution. This allows to rapidly assess the quality of the molecular cluster detection algorithm and to identify locations in the simulation data in space as well as in time where the cluster detection fails. Thus, thermodynamics researchers can eliminate weaknesses in their cluster detection algorithms. Several examples for the effective and efficient usage of our tool are presented.

  9. Molecular Dynamics and Electron Density Studies of Siderophores and Peptides.

    NASA Astrophysics Data System (ADS)

    Fidelis, Krzysztof Andrzej

    1990-08-01

    The dissertation comprises three separate studies of siderophores and peptides. In the first of these studies the relative potential energies for a series of diastereomers of a siderophore neocoprogen I are evaluated with molecular mechanics force field methods. Charges on the hydroxamate moiety are determined with a synthetic model siderophore compound using valence population refinements, and alternatively, with the theoretical ab initio/ESP calculations. The single diastereomer found in the crystal structure is among four characterized by the low potential energy, while prevalence of Delta vs. Lambda configuration about the iron is found to be a property of the entire series. In the second study the crystal structure of a ferrichrome siderophore ferrirhodin is reported. The crystal structure conformation of the molecular backbone as well as the iron coordination geometry compare well with other ferrichrome structures. The differences between the acyl groups of ferrirubin and ferrirhodin are explored using the methods of molecular mechanics. The third study a 300 ps, 300 K, in vacuo molecular dynamics simulation of didemnin A and B yields distinct molecular conformers, which are different from the one found in the crystal structure or modeled in solution, using the Nuclear Overhauser Effect data. Evaluations of the relative potential energy are performed with short 10 ps simulations in solution. Didemnins are natural depsipeptides isolated from a Caribbean tunicate and characterized by particularly potent antiproliferative and immunomodulatory activity. Conformationally rigid and flexible regions of the molecule are described. A short review of the molecular mechanics methodology is given in the introduction.

  10. Near-membrane protein dynamics revealed by evanescent field microscopy

    NASA Astrophysics Data System (ADS)

    Bezzerides, Vassilios J.; Clapham, David E.

    2004-05-01

    Evanescent Field (EF) microscopy is used to investigate the spatial and temporal dynamics of proteins in living cells. A genetically engineered ion channel fused to a fluorescent tag is expressed in cells and imaged with an objective-based EF microscope. Images are obtained from a CCD and analyzed to determine fluorescence and velocity of individual protein containing vesicles. An inverse correlation between fluorescent intensity and average motility provides a method for determination of membrane localization. Stimulation and subsequent decrease in ion channel activity is correlated with loss of protein from membrane as shown by EF microscopy and patch-clamp electrophysiology.

  11. Extrapolated gradientlike algorithms for molecular dynamics and celestial mechanics simulations.

    PubMed

    Omelyan, I P

    2006-09-01

    A class of symplectic algorithms is introduced to integrate the equations of motion in many-body systems. The algorithms are derived on the basis of an advanced gradientlike decomposition approach. Its main advantage over the standard gradient scheme is the avoidance of time-consuming evaluations of force gradients by force extrapolation without any loss of precision. As a result, the efficiency of the integration improves significantly. The algorithms obtained are analyzed and optimized using an error-function theory. The best among them are tested in actual molecular dynamics and celestial mechanics simulations for comparison with well-known nongradient and gradient algorithms such as the Störmer-Verlet, Runge-Kutta, Cowell-Numerov, Forest-Ruth, Suzuki-Chin, and others. It is demonstrated that for moderate and high accuracy, the extrapolated algorithms should be considered as the most efficient for the integration of motion in molecular dynamics simulations. PMID:17025782

  12. Extrapolated gradientlike algorithms for molecular dynamics and celestial mechanics simulations.

    PubMed

    Omelyan, I P

    2006-09-01

    A class of symplectic algorithms is introduced to integrate the equations of motion in many-body systems. The algorithms are derived on the basis of an advanced gradientlike decomposition approach. Its main advantage over the standard gradient scheme is the avoidance of time-consuming evaluations of force gradients by force extrapolation without any loss of precision. As a result, the efficiency of the integration improves significantly. The algorithms obtained are analyzed and optimized using an error-function theory. The best among them are tested in actual molecular dynamics and celestial mechanics simulations for comparison with well-known nongradient and gradient algorithms such as the Störmer-Verlet, Runge-Kutta, Cowell-Numerov, Forest-Ruth, Suzuki-Chin, and others. It is demonstrated that for moderate and high accuracy, the extrapolated algorithms should be considered as the most efficient for the integration of motion in molecular dynamics simulations.

  13. Enhancing Protein Adsorption Simulations by Using Accelerated Molecular Dynamics

    PubMed Central

    Mücksch, Christian; Urbassek, Herbert M.

    2013-01-01

    The atomistic modeling of protein adsorption on surfaces is hampered by the different time scales of the simulation ( s) and experiment (up to hours), and the accordingly different ‘final’ adsorption conformations. We provide evidence that the method of accelerated molecular dynamics is an efficient tool to obtain equilibrated adsorption states. As a model system we study the adsorption of the protein BMP-2 on graphite in an explicit salt water environment. We demonstrate that due to the considerably improved sampling of conformational space, accelerated molecular dynamics allows to observe the complete unfolding and spreading of the protein on the hydrophobic graphite surface. This result is in agreement with the general finding of protein denaturation upon contact with hydrophobic surfaces. PMID:23755156

  14. Adiabatic molecular-dynamics-simulation-method studies of kinetic friction

    NASA Astrophysics Data System (ADS)

    Zhang, J.; Sokoloff, J. B.

    2005-06-01

    An adiabatic molecular-dynamics method is developed and used to study the Muser-Robbins model for dry friction (i.e., nonzero kinetic friction in the slow sliding speed limit). In this model, dry friction between two crystalline surfaces rotated with respect to each other is due to mobile molecules (i.e., dirt particles) adsorbed at the interface. Our adiabatic method allows us to quickly locate interface potential-well minima, which become unstable during sliding of the surfaces. Since dissipation due to friction in the slow sliding speed limit results from mobile molecules dropping out of such unstable wells, our method provides a way to calculate dry friction, which agrees extremely well with results found by conventional molecular dynamics for the same system, but our method is more than a factor of 10 faster.

  15. Coherent Amplification of Ultrafast Molecular Dynamics in an Optical Oscillator.

    PubMed

    Aharonovich, Igal; Pe'er, Avi

    2016-02-19

    Optical oscillators present a powerful optimization mechanism. The inherent competition for the gain resources between possible modes of oscillation entails the prevalence of the most efficient single mode. We harness this "ultrafast" coherent feedback to optimize an optical field in time, and show that, when an optical oscillator based on a molecular gain medium is synchronously pumped by ultrashort pulses, a temporally coherent multimode field can develop that optimally dumps a general, dynamically evolving vibrational wave packet, into a single vibrational target state. Measuring the emitted field opens a new window to visualization and control of fast molecular dynamics. The realization of such a coherent oscillator with hot alkali dimers appears within experimental reach.

  16. An implicit divalent counterion force field for RNA molecular dynamics

    NASA Astrophysics Data System (ADS)

    Henke, Paul S.; Mak, Chi H.

    2016-03-01

    How to properly account for polyvalent counterions in a molecular dynamics simulation of polyelectrolytes such as nucleic acids remains an open question. Not only do counterions such as Mg2+ screen electrostatic interactions, they also produce attractive intrachain interactions that stabilize secondary and tertiary structures. Here, we show how a simple force field derived from a recently reported implicit counterion model can be integrated into a molecular dynamics simulation for RNAs to realistically reproduce key structural details of both single-stranded and base-paired RNA constructs. This divalent counterion model is computationally efficient. It works with existing atomistic force fields, or coarse-grained models may be tuned to work with it. We provide optimized parameters for a coarse-grained RNA model that takes advantage of this new counterion force field. Using the new model, we illustrate how the structural flexibility of RNA two-way junctions is modified under different salt conditions.

  17. Molecular dynamics studies of U1A-RNA complexes.

    PubMed Central

    Reyes, C M; Kollman, P A

    1999-01-01

    The U1A protein binds to a hairpin RNA and an internal-loop RNA with picomolar affinities. To probe the molecular basis of U1A binding, we performed state-of-the-art nanosecond molecular dynamics simulations on both complexes. The good agreement with experimental structures supports the protocols used in the simulations. We compare the dynamics, hydrogen-bonding occupancies, and interfacial flexibility of both complexes and also describe a rigid-body motion in the U1A-internal loop complex that is not observed in the U1A-hairpin simulation. We relate these observations to experimental mutational studies and highlight their significance in U1A binding affinity and specificity. PMID:10024175

  18. Molecular dynamic simulation of non-melt laser annealing process

    NASA Astrophysics Data System (ADS)

    Liren, Yan; Dai, Li; Wei, Zhang; Zhihong, Liu; Wei, Zhou; Quan, Wang

    2016-03-01

    Molecular dynamic simulation is performed to study the process of material annealing caused by a 266 nm pulsed laser. A micro-mechanism describing behaviors of silicon and impurity atoms during the laser annealing at a non-melt regime is proposed. After ion implantation, the surface of the Si wafer is acted by a high energy laser pulse, which loosens the material and partially frees both Si and impurity atoms. While the residual laser energy is absorbed by valence electrons, these atoms are recoiled and relocated to finally form a crystal. Energy-related movement behavior is observed by using the molecular dynamic method. The non-melt laser anneal appears to be quite sensitive to the energy density of the laser, as a small excess energy may causes a significant impurity diffusion. Such a result is also supported by our laser anneal experiment.

  19. Long Timestep Molecular Dynamics on the Graphical Processing Unit

    PubMed Central

    Sweet, James C.; Nowling, Ronald J.; Cickovski, Trevor; Sweet, Christopher R.; Pande, Vijay S.; Izaguirre, Jesús A.

    2013-01-01

    Molecular dynamics (MD) simulations now play a key role in many areas of theoretical chemistry, biology, physics, and materials science. In many cases, such calculations are significantly limited by the massive amount of computer time needed to perform calculations of interest. Herein, we present Long Timestep Molecular Dynamics (LTMD), a method to significantly speed MD simulations. In particular, we discuss new methods to calculate the needed terms in LTMD as well as issues germane to a GPU implementation. The resulting code, implemented in the OpenMM MD library, can achieve a significant 6-fold speed increase, leading to MD simulations on the order of 5 μs/day using implicit solvent models. PMID:24436689

  20. Molecular dynamics analysis on impact behavior of carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Seifoori, Sajjad

    2015-01-01

    Dynamic analysis of impact of a nanoparticle on carbon nanotubes is investigated based on two degree of freedom model. The accuracy and stability of the present methods are verified by molecular dynamics (MD) simulations. The effect of different types of boundary condition on the maximum dynamic deflections is studied for zigzag and armchair SWCNTs with various aspect ratios (length/diameter). Besides, the influences of velocity of impactor on the dynamic deflections are studied. It is shown that the dynamic behavior on the armchair and zigzag single-walled carbon nanotubes are almost similar. Finally, by making use of the above MD simulation and theoretical results some insight has been obtained about the dynamic characteristics of the impact problems of nanobeam structures. Nonlocal Timoshenko beam models TBT2 should be employed for an accurate prediction of the dynamic deflection rather than nonlocal Euler-Bernoulli beam models EBT2 which ignores the effects of transverse shear deformation and rotary inertia that is especially significant for short beams. The results from nonlocal EBT2 and TBT2 models demonstrated good agreement with MD simulation. The EBT2 and TBT2 models also account for the relative motion between the nanoparticle and the nanobeam that is due to local indentation as can be seen in MD simulation.