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Sample records for coarse grained simulations

  1. Coarse-grained models for biological simulations

    NASA Astrophysics Data System (ADS)

    Wu, Zhe; Cui, Qiang; Yethiraj, Arun

    2011-03-01

    The large timescales and length-scales of interest in biophysics preclude atomistic study of many systems and processes. One appealing approach is to use coarse-grained (CG) models where several atoms are grouped into a single CG site. In this work we describe a new CG force field for lipids, surfactants, and amino acids. The topology of CG sites is the same as in the MARTINI force field, but the new model is compatible with a recently developed CG electrostatic water (Big Multiple Water, BMW) model. The model not only gives correct structural, elastic properties and phase behavior for lipid and surfactants, but also reproduces electrostatic properties at water-membrane interface that agree with experiment and atomistic simulations, including the potential of mean force for charged amino acid residuals at membrane. Consequently, the model predicts stable attachment of cationic peptides (i.e., poly-Arg) on lipid bilayer surface, which is not shown in previous models with non-electrostatic water.

  2. Coarse-grained Simulations of Viral Assembly

    NASA Astrophysics Data System (ADS)

    Elrad, Oren M.

    2011-12-01

    The formation of viral capsids is a marvel of natural engineering and design. A large number (from 60 to thousands) of protein subunits assemble into complete, reproducible structures under a variety of conditions while avoiding kinetic and thermodynamic traps. Small single-stranded RNA viruses not only assemble their coat proteins in this fashion but also package their genome during the self-assembly process. Recent experiments have shown that the coat proteins are competent to assemble not merely around their own genomes but heterologous RNA, synthetic polyanions and even functionalized gold nanoparticles. Remarkably these viruses can even assemble around cargo not commensurate with their native state by adopting different morphologies. Understanding the properties that confer such exquisite precision and flexibility to the assembly process could aid biomedical research in the search for novel antiviral remedies, drug-delivery vehicles and contrast agents used in bioimaging. At the same time, viral assembly provides an excellent model system for the development of a statistical mechanical understanding of biological self-assembly, in the hopes of that we will identify some universal principles that underly such processes. This work consists of computational studies using coarse-grained representations of viral coat proteins and their cargoes. We find the relative strength of protein-cargo and protein-protein interactions has a profound effect on the assembly pathway, in some cases leading to assembly mechanisms that are markedly different from those found in previous work on the assembly of empty capsids. In the case of polymeric cargo, we find the first evidence for a previously theorized mechanism in which the polymer actively participates in recruiting free subunits to the assembly process through cooperative polymer-protein motions. We find that successful assembly is non-monotonic in protein-cargo affinity, such affinity can be detrimental to assembly if it

  3. Coarse-graining stochastic biochemical networks: adiabaticity and fast simulations

    SciTech Connect

    Nemenman, Ilya; Sinitsyn, Nikolai; Hengartner, Nick

    2008-01-01

    We propose a universal approach for analysis and fast simulations of stiff stochastic biochemical kinetics networks, which rests on elimination of fast chemical species without a loss of information about mesoscoplc, non-Poissonian fluctuations of the slow ones. Our approach, which is similar to the Born-Oppenhelmer approximation in quantum mechanics, follows from the stochastic path Integral representation of the cumulant generating function of reaction events. In applications with a small number of chemIcal reactions, It produces analytical expressions for cumulants of chemical fluxes between the slow variables. This allows for a low-dimensional, Interpretable representation and can be used for coarse-grained numerical simulation schemes with a small computational complexity and yet high accuracy. As an example, we derive the coarse-grained description for a chain of biochemical reactions, and show that the coarse-grained and the microscopic simulations are in an agreement, but the coarse-gralned simulations are three orders of magnitude faster.

  4. The power of coarse graining in biomolecular simulations

    PubMed Central

    Ingólfsson, Helgi I; Lopez, Cesar A; Uusitalo, Jaakko J; de Jong, Djurre H; Gopal, Srinivasa M; Periole, Xavier; Marrink, Siewert J

    2014-01-01

    Computational modeling of biological systems is challenging because of the multitude of spatial and temporal scales involved. Replacing atomistic detail with lower resolution, coarse grained (CG), beads has opened the way to simulate large-scale biomolecular processes on time scales inaccessible to all-atom models. We provide an overview of some of the more popular CG models used in biomolecular applications to date, focusing on models that retain chemical specificity. A few state-of-the-art examples of protein folding, membrane protein gating and self-assembly, DNA hybridization, and modeling of carbohydrate fibers are used to illustrate the power and diversity of current CG modeling. PMID:25309628

  5. Simulating the entropic collapse of coarse-grained chromosomes.

    PubMed

    Shendruk, Tyler N; Bertrand, Martin; de Haan, Hendrick W; Harden, James L; Slater, Gary W

    2015-02-17

    Depletion forces play a role in the compaction and decompaction of chromosomal material in simple cells, but it has remained debatable whether they are sufficient to account for chromosomal collapse. We present coarse-grained molecular dynamics simulations, which reveal that depletion-induced attraction is sufficient to cause the collapse of a flexible chain of large structural monomers immersed in a bath of smaller depletants. These simulations use an explicit coarse-grained computational model that treats both the supercoiled DNA structural monomers and the smaller protein crowding agents as combinatorial, truncated Lennard-Jones spheres. By presenting a simple theoretical model, we quantitatively cast the action of depletants on supercoiled bacterial DNA as an effective solvent quality. The rapid collapse of the simulated flexible chromosome at the predicted volume fraction of depletants is a continuous phase transition. Additional physical effects to such simple chromosome models, such as enthalpic interactions between structural monomers or chain rigidity, are required if the collapse is to be a first-order phase transition. PMID:25692586

  6. Simulating the Entropic Collapse of Coarse-Grained Chromosomes

    PubMed Central

    Shendruk, Tyler N.; Bertrand, Martin; de Haan, Hendrick W.; Harden, James L.; Slater, Gary W.

    2015-01-01

    Depletion forces play a role in the compaction and decompaction of chromosomal material in simple cells, but it has remained debatable whether they are sufficient to account for chromosomal collapse. We present coarse-grained molecular dynamics simulations, which reveal that depletion-induced attraction is sufficient to cause the collapse of a flexible chain of large structural monomers immersed in a bath of smaller depletants. These simulations use an explicit coarse-grained computational model that treats both the supercoiled DNA structural monomers and the smaller protein crowding agents as combinatorial, truncated Lennard-Jones spheres. By presenting a simple theoretical model, we quantitatively cast the action of depletants on supercoiled bacterial DNA as an effective solvent quality. The rapid collapse of the simulated flexible chromosome at the predicted volume fraction of depletants is a continuous phase transition. Additional physical effects to such simple chromosome models, such as enthalpic interactions between structural monomers or chain rigidity, are required if the collapse is to be a first-order phase transition. PMID:25692586

  7. Biomembranes in atomistic and coarse-grained simulations

    NASA Astrophysics Data System (ADS)

    Pluhackova, Kristyna; Böckmann, Rainer A.

    2015-08-01

    The architecture of biological membranes is tightly coupled to the localization, organization, and function of membrane proteins. The organelle-specific distribution of lipids allows for the formation of functional microdomains (also called rafts) that facilitate the segregation and aggregation of membrane proteins and thus shape their function. Molecular dynamics simulations enable to directly access the formation, structure, and dynamics of membrane microdomains at the molecular scale and the specific interactions among lipids and proteins on timescales from picoseconds to microseconds. This review focuses on the latest developments of biomembrane force fields for both atomistic and coarse-grained molecular dynamics (MD) simulations, and the different levels of coarsening of biomolecular structures. It also briefly introduces scale-bridging methods applicable to biomembrane studies, and highlights selected recent applications.

  8. Unconstrained Structure Formation in Coarse-Grained Protein Simulations

    NASA Astrophysics Data System (ADS)

    Bereau, Tristan

    The ability of proteins to fold into well-defined structures forms the basis of a wide variety of biochemical functions in and out of the cell membrane. Many of these processes, however, operate at time- and length-scales that are currently unattainable by all-atom computer simulations. To cope with this difficulty, increasingly more accurate and sophisticated coarse-grained models are currently being developed. In the present thesis, we introduce a solvent-free coarse-grained model for proteins. Proteins are modeled by four beads per amino acid, providing enough backbone resolution to allow for accurate sampling of local conformations. It relies on simple interactions that emphasize structure, such as hydrogen bonds and hydrophobicity. Realistic alpha/beta content is achieved by including an effective nearest-neighbor dipolar interaction. Parameters are tuned to reproduce both local conformations and tertiary structures. By studying both helical and extended conformations we make sure the force field is not biased towards any particular secondary structure. Without any further adjustments or bias a realistic oligopeptide aggregation scenario is observed. The model is subsequently applied to various biophysical problems: (i) kinetics of folding of two model peptides, (ii) large-scale amyloid-beta oligomerization, and (iii) protein folding cooperativity. The last topic---defined by the nature of the finite-size thermodynamic transition exhibited upon folding---was investigated from a microcanonical perspective: the accurate evaluation of the density of states can unambiguously characterize the nature of the transition, unlike its corresponding canonical analysis. Extending the results of lattice simulations and theoretical models, we find that it is the interplay between secondary structure and the loss of non-native tertiary contacts which determines the nature of the transition. Finally, we combine the peptide model with a high-resolution, solvent-free, lipid

  9. A Coarse-Grained Model for Simulating Chitosan Hydrogels

    NASA Astrophysics Data System (ADS)

    Xu, Hongcheng; Matysiak, Silvina

    Hydrogels are biologically-derived materials composed of water-filled cross-linking polymer chains. It has widely been used as biodegradable material and has many applications in medical devices. The chitosan hydrogel is stimuli-responsive for undergoing pH-sensitive self-assembly process, allowing programmable tuning of the chitosan deposition through electric pulse. To explore the self-assembly mechanism of chitosan hydroge, we have developed an explicit-solvent coarse-grained chitosan model that has roots in the MARTINI force field, and the pH change is modeled by protonating chitosan chains using the Henderson-Hasselbalch equation. The mechanism of hydrogel network formation will be presented. The self-assembled polymer network qualitatively reproduce many experimental observables such as the pH-dependent strain-stress curve, bulk moduli, and structure factor. Our model is also capable of simulating other similar polyelectrolyte polymer systems.

  10. Mesoscopic coarse-grained simulations of lysozyme adsorption.

    PubMed

    Yu, Gaobo; Liu, Jie; Zhou, Jian

    2014-05-01

    Coarse-grained simulations are adopted to study the adsorption behavior of lysozyme on different (hydrophobic, neutral hydrophilic, zwitterionic, negatively charged, and positively charged) surfaces at the mesoscopic microsecond time scale (1.2 μs). Simulation results indicate the following: (i) the conformation change of lysozyme on the hydrophobic surface is bigger than any other studied surfaces; (ii) the active sites of lysozyme are faced to the hydrophobic surface with a "top end-on" orientation, while they are exposed to the liquid phase on the hydrophilic surface with a "back-on" orientation; (iii) the neutral hydrophilic surface can induce the adsorption of lysozyme, while the nonspecific protein adsorption can be resisted by the zwitterionic surface; (iv) when the solution ionic strength is low, lysozyme can anchor on the negatively charged surface easily but cannot adsorb on the positively charged surface; (v) when the solution ionic strength is high, the positively charged lysozyme can also adsorb on the like-charged surface; (vi) the major positive potential center of lysozyme, especially the residue ARG128, plays a vital role in leading the adsorption of lysozyme on charged surfaces; (vii) when the ionic strength is high, a counterion layer is formed above the positively charged surface, which is the key factor why lysozyme can adsorb on a like-charged surface. The coarse-grained method based on the MARTINI force field for proteins and the BMW water model could provide an efficient way to understand protein interfacial adsorption behavior at a greater length scale and time scale. PMID:24785197

  11. Coarse-grained computer simulation of dynamics in thylakoid membranes: methods and opportunities

    PubMed Central

    Schneider, Anna R.; Geissler, Phillip L.

    2013-01-01

    Coarse-grained simulation is a powerful and well-established suite of computational methods for studying structure and dynamics in nanoscale biophysical systems. As our understanding of the plant photosynthetic apparatus has become increasingly nuanced, opportunities have arisen for coarse-grained simulation to complement experiment by testing hypotheses and making predictions. Here, we give an overview of best practices in coarse-grained simulation, with a focus on techniques and results that are applicable to the plant thylakoid membrane–protein system. We also discuss current research topics for which coarse-grained simulation has the potential to play a key role in advancing the field. PMID:24478781

  12. Coarse-grained molecular simulations of allosteric cooperativity

    NASA Astrophysics Data System (ADS)

    Nandigrami, Prithviraj; Portman, John J.

    2016-03-01

    Interactions between a protein and a ligand are often accompanied by a redistribution of the population of thermally accessible conformations. This dynamic response of the protein's functional energy landscape enables a protein to modulate binding affinities and control binding sensitivity to ligand concentration. In this paper, we investigate the structural origins of binding affinity and allosteric cooperativity of binding two Ca2+ ions to each domain of Calmodulin (CaM) through simulations of a simple coarse-grained model. In this model, the protein's conformational transitions between open and closed conformational ensembles are simulated explicitly and ligand binding and unbinding are treated implicitly within the grand canonical ensemble. Ligand binding is cooperative because the binding sites are coupled through a shift in the dominant conformational ensemble upon binding. The classic Monod-Wyman-Changeux model of allostery with appropriate binding free energies to the open and closed ensembles accurately describes the simulated binding thermodynamics. The simulations predict that the two domains of CaM have distinct binding affinity and cooperativity. In particular, the C-terminal domain binds Ca2+ with higher affinity and greater cooperativity than the N-terminal domain. From a structural point of view, the affinity of an individual binding loop depends sensitively on the loop's structural compatibility with the ligand in the bound ensemble, as well as the conformational flexibility of the binding site in the unbound ensemble.

  13. STOCK: Structure mapper and online coarse-graining kit for molecular simulations

    SciTech Connect

    Bevc, Staš; Junghans, Christoph; Praprotnik, Matej

    2015-03-15

    We present a web toolkit STructure mapper and Online Coarse-graining Kit for setting up coarse-grained molecular simulations. The kit consists of two tools: structure mapping and Boltzmann inversion tools. The aim of the first tool is to define a molecular mapping from high, e.g. all-atom, to low, i.e. coarse-grained, resolution. Using a graphical user interface it generates input files, which are compatible with standard coarse-graining packages, e.g. VOTCA and DL_CGMAP. Our second tool generates effective potentials for coarse-grained simulations preserving the structural properties, e.g. radial distribution functions, of the underlying higher resolution model. The required distribution functions can be provided by any simulation package. Simulations are performed on a local machine and only the distributions are uploaded to the server. The applicability of the toolkit is validated by mapping atomistic pentane and polyalanine molecules to a coarse-grained representation. Effective potentials are derived for systems of TIP3P (transferable intermolecular potential 3 point) water molecules and salt solution. The presented coarse-graining web toolkit is available at http://stock.cmm.ki.si.

  14. STOCK: Structure mapper and online coarse-graining kit for molecular simulations

    DOE PAGESBeta

    Bevc, Staš; Junghans, Christoph; Praprotnik, Matej

    2015-03-15

    We present a web toolkit STructure mapper and Online Coarse-graining Kit for setting up coarse-grained molecular simulations. The kit consists of two tools: structure mapping and Boltzmann inversion tools. The aim of the first tool is to define a molecular mapping from high, e.g. all-atom, to low, i.e. coarse-grained, resolution. Using a graphical user interface it generates input files, which are compatible with standard coarse-graining packages, e.g. VOTCA and DL_CGMAP. Our second tool generates effective potentials for coarse-grained simulations preserving the structural properties, e.g. radial distribution functions, of the underlying higher resolution model. The required distribution functions can be providedmore » by any simulation package. Simulations are performed on a local machine and only the distributions are uploaded to the server. The applicability of the toolkit is validated by mapping atomistic pentane and polyalanine molecules to a coarse-grained representation. Effective potentials are derived for systems of TIP3P (transferable intermolecular potential 3 point) water molecules and salt solution. The presented coarse-graining web toolkit is available at http://stock.cmm.ki.si.« less

  15. First-principle approach to rescale the dynamics of simulated coarse-grained macromolecular liquids

    NASA Astrophysics Data System (ADS)

    Lyubimov, I.; Guenza, M. G.

    2011-09-01

    We present a detailed derivation and testing of our approach to rescale the dynamics of mesoscale simulations of coarse-grained polymer melts (I. Y. Lyubimov, J. McCarty, A. Clark, and M. G. Guenza, J. Chem. Phys.JCPSA60021-960610.1063/1.3450301 132, 224903 (2010)). Starting from the first-principle Liouville equation and applying the Mori-Zwanzig projection operator technique, we derive the generalized Langevin equations (GLEs) for the coarse-grained representations of the liquid. The chosen slow variables in the projection operators define the length scale of coarse graining. Each polymer is represented at two levels of coarse graining: monomeric as a bead-and-spring model and molecular as a soft colloid. In the long-time regime where the center-of-mass follows Brownian motion and the internal dynamics is completely relaxed, the two descriptions must be equivalent. By enforcing this formal relation we derive from the GLEs the analytical rescaling factors to be applied to dynamical data in the coarse-grained representation to recover the monomeric description. Change in entropy and change in friction are the two corrections to be accounted for to compensate the effects of coarse graining on the polymer dynamics. The solution of the memory functions in the coarse-grained representations provides the dynamical rescaling of the friction coefficient. The calculation of the internal degrees of freedom provides the correction of the change in entropy due to coarse graining. The resulting rescaling formalism is a function of the coarse-grained model and thermodynamic parameters of the system simulated. The rescaled dynamics obtained from mesoscale simulations of polyethylene, represented as soft-colloidal particles, by applying our rescaling approach shows a good agreement with data of translational diffusion measured experimentally and from simulations. The proposed method is used to predict self-diffusion coefficients of new polyethylene samples.

  16. Coarse grained molecular simulations of melting kinetics of DPPC vesicles

    NASA Astrophysics Data System (ADS)

    Bolling-Patel, Lara A.; Kindt, James T.

    2015-03-01

    Phase transitions in unilamellar vesicles are of particular interest as the increase in permeability of lipid bilayers around the main phase transition temperature makes them candidates for drug encapsulation and temperature-responsive delivery. We study the transition between the gel and fluid phases of a unilamellar vesicle of MARTINI coarse grain DPPC lipids with a diameter of 40 nm following temperature jumps from 280 K to temperatures near the transition temperature of 295 K. At 290 K and 295 K vesicles show single exponential melting kinetics in qualitative agreement with the early stages of melting measured in IR temperature-jump experiments. These trajectories exhibit partial melting over 500 ns, accompanied by a decrease in the number of gel domains from 8 domains in the initial faceted structure to 5 and 3 respectively. Melting at 295 K results in a shape change to an asymmetric structure that appears to be transforming into an oblate solid. Complete melting is seen for temperature jumps to 300 K and 310 K, in which cases vesicles undergo shape transitions into prolate dumbbell shapes. The shape changes that accompany the phase transition indicate that the phase transition kinetics are correlated to changes in curvature. NSF CHE-1213904.

  17. Systematic coarse-graining of the wormlike chain model for dynamic simulations

    NASA Astrophysics Data System (ADS)

    Koslover, Elena; Spakowitz, Andrew

    2014-03-01

    One of the key goals of macromolecular modeling is to elucidate how macroscale physical properties arise from the microscale behavior of the polymer constituents. For many biological and industrial applications, a direct simulation approach is impractical due to to the wide range of length and time scales that must be spanned by the model, necessitating physically sound and practically relevant procedures for coarse-graining polymer systems. We present a highly general systematic coarse-graining procedure that maps any detailed polymer model onto effective elastic-chain models at intermediate and large length scales, and we specifically focus on the wormlike chain model of semiflexible polymers. Our approach defines a continuous flow of coarse-grained models starting from the wormlike chain model, proceeding through an intermediate-scale stretchable, shearable wormlike chain, and finally resolving to a Gaussian chain at the longest lengths. Using Brownian dynamic simulations of our coarse grained polymer, we show that this approach to coarse graining the wormlike chain model captures analytical predictions for stress relaxation in a semiflexible polymer. Since we can arbitrarily coarse grain the polymer in these dynamic simulations, our approach greatly accelerates simulations.

  18. Systematic and Simulation-Free Coarse-Graining of Polymer Melts using Soft Potentials

    NASA Astrophysics Data System (ADS)

    Yang, Delian; Wang, Qiang

    2014-03-01

    Full atomistic simulations of multi-chain systems are not feasible at present due to their formidable computational requirements. Molecular simulations with coarse-grained models have to be used instead, where each segment represents, for example, the center-of-mass of a group of atoms or real monomers. While atoms interact with hard excluded-volume interactions (e.g., the Lennard-Jones potential) and cannot overlap, the coarse-grained segments can certainly overlap and should therefore interact with soft potentials that allow complete particle overlapping. Coarse-grained models, however, reduce the chain conformational entropy, which plays an essential role in the behavior of polymeric systems. In this work, we use integral-equation theories, instead of molecular simulations, to perform both the structure-based and relative-entropy-based coarse-graining of homopolymer melts, and systematically examine how the coarse-grained soft potential varies with N (the number of segments on each chain) and how well the coarse-grained models reproduce both the structural and thermodynamic properties of the original system. This provides us with a quantitative basis for choosing small N-values that can still capture the chain conformational entropy, a characteristics of polymers.

  19. Coarse graining in micromagnetics.

    PubMed

    Grinstein, G; Koch, R H

    2003-05-23

    Numerical solutions of the micromagnetic Landau-Lifshitz-Gilbert equations provide valuable information at low temperatures (T), but produce egregious errors at higher T. For example, Curie temperatures are often overestimated by an order of magnitude. We show that these errors result from the use of block or coarse-grained variables, without a concomitant renormalization of the system parameters to account for the block size. Renormalization solves the problem of the Curie-point anomaly and improves the accuracy of more complicated micromagnetic simulations, even at low T. PMID:12785922

  20. YUP: A Molecular Simulation Program for Coarse-Grained and Multi-Scaled Models.

    PubMed

    Tan, Robert K Z; Petrov, Anton S; Harvey, Stephen C

    2006-05-01

    Coarse-grained models can be very different from all-atom models and are highly varied. Each class of model is assembled very differently and some models need customized versions of the standard molecular mechanics methods. The most flexible way to meet these diverse needs is to provide access to internal data structures and a programming language to manipulate these structures. We have created YUP, a general-purpose program for coarse-grained and multi-scaled models. YUP extends the Python programming language by adding new data types. We have then used the extended language to implement three classes of coarse-grained models. The coarse-grained RNA model type is an unusual non-linear polymer and the assembly was easily handled with a simple program. The molecular dynamics algorithm had to be extended for a coarse-grained DNA model so that it could detect a failure that is invisible to a standard implementation. A third model type took advantage of access to the force field to simulate the packing of DNA in viral capsid. We find that objects are easy to modify, extend and redeploy. Thus, new classes of coarse-grained models can be implemented easily. PMID:22844233

  1. Systematic and simulation-free coarse graining of homopolymer melts: A structure-based study

    NASA Astrophysics Data System (ADS)

    Yang, Delian; Wang, Qiang

    2015-02-01

    We propose a systematic and simulation-free strategy for coarse graining of homopolymer melts, where each chain of Nm monomers is uniformly divided into N segments, with the spatial position of each segment corresponding to the center-of-mass of its monomers. We use integral-equation theories suitable for the study of equilibrium properties of polymers, instead of many-chain molecular simulations, to obtain the structural and thermodynamic properties of both original and coarse-grained (CG) systems, and quantitatively examine how the effective pair potentials between CG segments and the thermodynamic properties of CG systems vary with N. Our systematic and simulation-free strategy is much faster than those using many-chain simulations, thus effectively solving the transferability problem in coarse graining, and provides the quantitative basis for choosing the appropriate N-values. It also avoids the problems caused by finite-size effects and statistical uncertainties in many-chain simulations. Taking the simple hard-core Gaussian thread model [K. S. Schweizer and J. G. Curro, Chem. Phys. 149, 105 (1990)] as the original system, we demonstrate our strategy applied to structure-based coarse graining, which is quite general and versatile, and compare in detail the various integral-equation theories and closures for coarse graining. Our numerical results show that the effective CG potentials for various N and closures can be collapsed approximately onto the same curve, and that structure-based coarse graining cannot give thermodynamic consistency between original and CG systems at any N < Nm.

  2. Systematic and simulation-free coarse graining of homopolymer melts: A structure-based study

    SciTech Connect

    Yang, Delian; Wang, Qiang

    2015-02-07

    We propose a systematic and simulation-free strategy for coarse graining of homopolymer melts, where each chain of N{sub m} monomers is uniformly divided into N segments, with the spatial position of each segment corresponding to the center-of-mass of its monomers. We use integral-equation theories suitable for the study of equilibrium properties of polymers, instead of many-chain molecular simulations, to obtain the structural and thermodynamic properties of both original and coarse-grained (CG) systems, and quantitatively examine how the effective pair potentials between CG segments and the thermodynamic properties of CG systems vary with N. Our systematic and simulation-free strategy is much faster than those using many-chain simulations, thus effectively solving the transferability problem in coarse graining, and provides the quantitative basis for choosing the appropriate N-values. It also avoids the problems caused by finite-size effects and statistical uncertainties in many-chain simulations. Taking the simple hard-core Gaussian thread model [K. S. Schweizer and J. G. Curro, Chem. Phys. 149, 105 (1990)] as the original system, we demonstrate our strategy applied to structure-based coarse graining, which is quite general and versatile, and compare in detail the various integral-equation theories and closures for coarse graining. Our numerical results show that the effective CG potentials for various N and closures can be collapsed approximately onto the same curve, and that structure-based coarse graining cannot give thermodynamic consistency between original and CG systems at any N < N{sub m}.

  3. A general method for spatially coarse-graining Metropolis Monte Carlo simulations onto a lattice

    NASA Astrophysics Data System (ADS)

    Liu, Xiao; Seider, Warren D.; Sinno, Talid

    2013-03-01

    A recently introduced method for coarse-graining standard continuous Metropolis Monte Carlo simulations of atomic or molecular fluids onto a rigid lattice of variable scale [X. Liu, W. D. Seider, and T. Sinno, Phys. Rev. E 86, 026708 (2012)], 10.1103/PhysRevE.86.026708 is further analyzed and extended. The coarse-grained Metropolis Monte Carlo technique is demonstrated to be highly consistent with the underlying full-resolution problem using a series of detailed comparisons, including vapor-liquid equilibrium phase envelopes and spatial density distributions for the Lennard-Jones argon and simple point charge water models. In addition, the principal computational bottleneck associated with computing a coarse-grained interaction function for evolving particle positions on the discretized domain is addressed by the introduction of new closure approximations. In particular, it is shown that the coarse-grained potential, which is generally a function of temperature and coarse-graining level, can be computed at multiple temperatures and scales using a single set of free energy calculations. The computational performance of the method relative to standard Monte Carlo simulation is also discussed.

  4. Systematic coarse graining flowing polymer melts: thermodynamically guided simulations and resulting constitutive model.

    PubMed

    Iig, Patrick

    2011-01-01

    Complex fluids, such as polymers, colloids, liquid-crystals etc., show intriguing viscoelastic properties, due to the complicated interplay between flow-induced structure formation and dynamical behavior. Starting from microscopic models of complex fluids, a systematic coarse-graining method is presented that allows us to derive closed-form and thermodynamically consistent constitutive equations for such fluids. Essential ingredients of the proposed approach are thermodynamically guided simulations within a consistent coarse-graining scheme. In addition to this new type of multiscale simulations, we reconstruct the building blocks that constitute the thermodynamically consistent coarse-grained model. We illustrate the method for low-molecular polymer melts, which are subject to different imposed flow fields like planar shear and different elongational flows. The constitutive equation for general flow conditions we obtain shows rheological behavior including shear thinning, normal stress differences, and elongational viscosities in good agreement with reference results. PMID:21678766

  5. Coarse-grained variables for particle-based models: diffusion maps and animal swarming simulations

    NASA Astrophysics Data System (ADS)

    Liu, Ping; Safford, Hannah R.; Couzin, Iain D.; Kevrekidis, Ioannis G.

    2014-12-01

    As microscopic (e.g. atomistic, stochastic, agent-based, particle-based) simulations become increasingly prevalent in the modeling of complex systems, so does the need to systematically coarse-grain the information they provide. Before even starting to formulate relevant coarse-grained equations, we need to determine the right macroscopic observables—the right variables in terms of which emergent behavior will be described. This paper illustrates the use of data mining (and, in particular, diffusion maps, a nonlinear manifold learning technique) in coarse-graining the dynamics of a particle-based model of animal swarming. Our computational data-driven coarse-graining approach extracts two coarse (collective) variables from the detailed particle-based simulations, and helps formulate a low-dimensional stochastic differential equation in terms of these two collective variables; this allows the efficient quantification of the interplay of "informed" and "naive" individuals in the collective swarm dynamics. We also present a brief exploration of swarm breakup and use data-mining in an attempt to identify useful predictors for it. In our discussion of the scope and limitations of the approach we focus on the key step of selecting an informative metric, allowing us to usefully compare different particle swarm configurations.

  6. Coarse-grained molecular dynamics simulations of nanopatterning with multivalent inks

    NASA Astrophysics Data System (ADS)

    Cieplak, Marek; Thompson, Damien

    2008-06-01

    A coarse-grained molecular dynamics (MD) model is developed to study the multivalent, or multisite, binding of small functionalized dendrimer molecules to β-cyclodextrin-terminated self-assembled monolayers, the so-called ``molecular printboards'' used to print ``ink'' molecules on surfaces with a high degree of positional control and specificity. Some current and future bionanotechnology applications are in the creation of nanoparticle assemblies, directed protein assembly, platforms for biosensing, and cell:surface attachment. The coarse-grained model allows us to probe up to microsecond timescales and model ink diffusion, crucial for the application of the printboard in, for example, medical diagnostics. Recent all-atom MD simulations identified and quantified the molecular strain limiting the stability of nanopatterns created with small dendrimer inks, and explained the different patterns obtained experimentally with different dendrimer inks. In the present work, the all-atom simulations are ``scaled up'' to longer timescales via coarse graining, without incurring significant additional computational expense, and, crucially, without significant loss in atom-scale detail, the coarse-grained MD simulations yielding properties similar to those obtained from the all-atom simulations. The anchoring of the ink molecules to the monolayer is of multivalent nature and the degree of multivalency shows a sharp dependence on temperature, control of temperature thus providing a further operational ``switch'' for directed molecular assembly. The computational protocol developed can, in principle, be extended to model any multivalent assembly, for example, virus-cell complexation.

  7. Coarse-grained simulation of amphiphilic self-assembly

    NASA Astrophysics Data System (ADS)

    Michel, David J.; Cleaver, Douglas J.

    2007-01-01

    The authors present a computer simulation study of amphiphilic self-assembly performed using a computationally efficient single-site model based on Gay-Berne [J. Chem. Phys. 74, 3316 (1981)] and Lennard-Jones particles. Molecular dynamics simulations of these systems show that free self-assembly of micellar, bilayer, and inverse micelle arrangements can be readily achieved for a single model parametrization. This self-assembly is predominantly driven by the anisotropy of the amphiphile-solvent interaction, amphiphile-amphiphile dispersive interactions being found to be of secondary importance. While amphiphile concentration is the main determinant of phase stability, molecular parameters such as head group size and interaction strength also have measurable affects on system properties.

  8. Coarse-grained simulation of amphiphilic self-assembly.

    PubMed

    Michel, David J; Cleaver, Douglas J

    2007-01-21

    The authors present a computer simulation study of amphiphilic self-assembly performed using a computationally efficient single-site model based on Gay-Berne [J. Chem. Phys. 74, 3316 (1981)] and Lennard-Jones particles. Molecular dynamics simulations of these systems show that free self-assembly of micellar, bilayer, and inverse micelle arrangements can be readily achieved for a single model parametrization. This self-assembly is predominantly driven by the anisotropy of the amphiphile-solvent interaction, amphiphile-amphiphile dispersive interactions being found to be of secondary importance. While amphiphile concentration is the main determinant of phase stability, molecular parameters such as head group size and interaction strength also have measurable affects on system properties. PMID:17249883

  9. Membrane pore formation in atomistic and coarse-grained simulations.

    PubMed

    Kirsch, Sonja A; Böckmann, Rainer A

    2016-10-01

    Biological cells and their organelles are protected by ultra thin membranes. These membranes accomplish a broad variety of important tasks like separating the cell content from the outer environment, they are the site for cell-cell interactions and many enzymatic reactions, and control the in- and efflux of metabolites. For certain physiological functions e.g. in the fusion of membranes and also in a number of biotechnological applications like gene transfection the membrane integrity needs to be compromised to allow for instance for the exchange of polar molecules across the membrane barrier. Mechanisms enabling the transport of molecules across the membrane involve membrane proteins that form specific pores or act as transporters, but also so-called lipid pores induced by external fields, stress, or peptides. Recent progress in the simulation field enabled to closely mimic pore formation as supposed to occur in vivo or in vitro. Here, we review different simulation-based approaches in the study of membrane pores with a focus on lipid pore properties such as their size and energetics, poration mechanisms based on the application of external fields, charge imbalances, or surface tension, and on pores that are induced by small molecules, peptides, and lipids. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg. PMID:26748016

  10. Coarse-grained simulation of dynamin-mediated fission

    NASA Astrophysics Data System (ADS)

    Muller, Marcus; Zhang, Guojie; Fuhrmans, Marc

    Fission is a process in which a region of a lipid bilayer is deformed and separated from its host membrane, so that an additional, topologically independent compartment surrounded by a continuous lipid bilayer is formed. It is a fundamental process in the compartmentalization of living organisms and carefully regulated by a number of membrane-shaping proteins. An important group within these is the dynamin family of proteins that are involved in the final severance of the hourglass-shaped neck, via which the growing compartment remains connected to the main volume until the completion of fission. We present computer simulations testing different hypotheses of how dynamin proteins facilitate fission by constriction and curvature. Our results on constraint-induced fission of cylindrical membrane tubes emphasize the importance of the local creation of positive curvature and reveal a complex picture of fission, in which the topological transformation can become arrested in an intermediate stage if the proteins constituting the fission machinery are not adaptive.

  11. Coarse-grained Monte Carlo simulations of non-equilibrium systems

    NASA Astrophysics Data System (ADS)

    Liu, Xiao; Crocker, John C.; Sinno, Talid

    2013-06-01

    We extend the scope of a recent method for generating coarse-grained lattice Metropolis Monte Carlo simulations [X. Liu, W. D. Seider, and T. Sinno, Phys. Rev. E 86, 026708 (2012), 10.1103/PhysRevE.86.026708; X. Liu, W. D. Seider, and T. Sinno, J. Chem. Phys. 138, 114104 (2013), 10.1063/1.4794686] from continuous interaction potentials to non-equilibrium situations. The original method has been shown to satisfy detailed balance at the coarse scale and to provide a good representation of various equilibrium properties in both atomic and molecular systems. However, we show here that the original method is inconsistent with non-equilibrium trajectories generated by full-resolution Monte Carlo simulations, which, under certain conditions, have been shown to correspond to Langevin dynamics. The modified coarse-grained method is generated by simultaneously biasing the forward and backward transition probability for every possible move, thereby preserving the detailed balance of the original method. The resulting coarse-grained Monte Carlo simulations are shown to provide trajectories that are consistent with overdamped Langevin (Smoluchowski) dynamics using a sequence of simple non-equilibrium examples. We first consider the purely diffusional spreading of a Gaussian pulse of ideal-gas particles and then include an external potential to study the influence of drift. Finally, we validate the method using a more general situation in which the particles interact via a Lennard-Jones interparticle potential.

  12. Coarse-grained Monte Carlo simulations of non-equilibrium systems.

    PubMed

    Liu, Xiao; Crocker, John C; Sinno, Talid

    2013-06-28

    We extend the scope of a recent method for generating coarse-grained lattice Metropolis Monte Carlo simulations [X. Liu, W. D. Seider, and T. Sinno, Phys. Rev. E 86, 026708 (2012); and J. Chem. Phys. 138, 114104 (2013)] from continuous interaction potentials to non-equilibrium situations. The original method has been shown to satisfy detailed balance at the coarse scale and to provide a good representation of various equilibrium properties in both atomic and molecular systems. However, we show here that the original method is inconsistent with non-equilibrium trajectories generated by full-resolution Monte Carlo simulations, which, under certain conditions, have been shown to correspond to Langevin dynamics. The modified coarse-grained method is generated by simultaneously biasing the forward and backward transition probability for every possible move, thereby preserving the detailed balance of the original method. The resulting coarse-grained Monte Carlo simulations are shown to provide trajectories that are consistent with overdamped Langevin (Smoluchowski) dynamics using a sequence of simple non-equilibrium examples. We first consider the purely diffusional spreading of a Gaussian pulse of ideal-gas particles and then include an external potential to study the influence of drift. Finally, we validate the method using a more general situation in which the particles interact via a Lennard-Jones interparticle potential. PMID:23822231

  13. Simulation of Coarse-Grained Protein-Protein Interactions with Graphics Processing Units.

    PubMed

    Tunbridge, Ian; Best, Robert B; Gain, James; Kuttel, Michelle M

    2010-11-01

    We report a hybrid parallel central and graphics processing units (CPU-GPU) implementation of a coarse-grained model for replica exchange Monte Carlo (REMC) simulations of protein assemblies. We describe the design, optimization, validation, and benchmarking of our algorithms, particularly the parallelization strategy, which is specific to the requirements of GPU hardware. Performance evaluation of our hybrid implementation shows scaled speedup as compared to a single-core CPU; reference simulations of small 100 residue proteins have a modest speedup of 4, while large simulations with thousands of residues are up to 1400 times faster. Importantly, the combination of coarse-grained models with highly parallel GPU hardware vastly increases the length- and time-scales accessible for protein simulation, making it possible to simulate much larger systems of interacting proteins than have previously been attempted. As a first step toward the simulation of the assembly of an entire viral capsid, we have demonstrated that the chosen coarse-grained model, together with REMC sampling, is capable of identifying the correctly bound structure, for a pair of fragments from the human hepatitis B virus capsid. Our parallel solution can easily be generalized to other interaction functions and other types of macromolecules and has implications for the parallelization of similar N-body problems that require random access lookups. PMID:26617104

  14. Coarse-Grain Model Simulations of Nonequilibrium Dynamics in Heterogeneous Materials.

    PubMed

    Brennan, John K; Lísal, Martin; Moore, Joshua D; Izvekov, Sergei; Schweigert, Igor V; Larentzos, James P

    2014-06-19

    A suite of computational tools is described for particle-based mesoscale simulations of the nonequilibrium dynamics of energetic solids, including mechanical deformation, phase transitions, and chemical reactivity triggered by shock or thermal loading. The method builds upon our recent advances both in generating coarse-grain models under high strains and in developing a variant of dissipative particle dynamics (DPD) that includes chemical reactions. To describe chemical reactivity, a coarse-grain particle equation-of-state was introduced into the constant-energy DPD variant that rigorously treats complex chemical reactions and the associated chemical energy release. As illustration of these developments, we present simulations of shock compression of an RDX crystal and its thermal decomposition under high temperatures. We also discuss our current efforts toward a highly scalable domain-decomposition implementation that extends applicability to micrometer-size simulations. With appropriate parametrization, the method is applicable to other materials whose dynamic response is driven by microstructural heterogeneities. PMID:26270506

  15. Strategies for articulated multibody-based adaptive coarse grain simulation of RNA

    PubMed Central

    Poursina, Mohammad; Bhalerao, Kishor D.; Flores, Samuel C.; Anderson, Kurt S.; Laederach, Alain

    2011-01-01

    Efficient modeling approaches are necessary to accurately predict large-scale structural behavior of biomolecular systems like RNA (Ribonucleic Acid). Coarse grained approximations of such complex systems can significantly reduce the computational costs of the simulation while maintaining sufficient fidelity to capture the biologically significant motions. However, given the coupling and nonlinearity of RNA systems (and effectively all biopolymers), it is expected that different parameters such as geometric and dynamic boundary conditions, states, and applied forces will affect the system’s dynamic behavior. Consequently, static coarse grained models (i.e., models for which the coarse graining is time invariant) are not always able to adequately sample the conformational space of the molecule. We introduce here the concept of adaptive coarse-grained molecular dynamics of RNA, which automatically adapts the coarseness of the model dynamically, in an effort to more optimally increase simulation speed, while maintaining accuracy. Adaptivity requires two basic algorithmic developments; first, a set of integrators that seamlessly allow transitions between higher and lower fidelity models while preserving the laws of motion. Secondly, we propose and validate metrics for determining when and where more or less fidelity needs to be integrated into the model to allow sufficiently accurate dynamics simulation. Given the central role that multibody dynamics plays in the proposed framework, and the nominally large number of dynamic degrees of freedom being considered in these applications, a computationally efficient multibody method which lends itself well to adaptivity is essential to the success of this effort. A suite of Divide-And-Conquer Algorithm (DCA)-based approaches are employed to this end, because these methods offer a good combination of computational efficiency and adaptive structure. PMID:21187222

  16. A Generic Force Field for Protein Coarse-Grained Molecular Dynamics Simulation

    PubMed Central

    Gu, Junfeng; Bai, Fang; Li, Honglin; Wang, Xicheng

    2012-01-01

    Coarse-grained (CG) force fields have become promising tools for studies of protein behavior, but the balance of speed and accuracy is still a challenge in the research of protein coarse graining methodology. In this work, 20 CG beads have been designed based on the structures of amino acid residues, with which an amino acid can be represented by one or two beads, and a CG solvent model with five water molecules was adopted to ensure the consistence with the protein CG beads. The internal interactions in protein were classified according to the types of the interacting CG beads, and adequate potential functions were chosen and systematically parameterized to fit the energy distributions. The proposed CG force field has been tested on eight proteins, and each protein was simulated for 1000 ns. Even without any extra structure knowledge of the simulated proteins, the Cα root mean square deviations (RMSDs) with respect to their experimental structures are close to those of relatively short time all atom molecular dynamics simulations. However, our coarse grained force field will require further refinement to improve agreement with and persistence of native-like structures. In addition, the root mean square fluctuations (RMSFs) relative to the average structures derived from the simulations show that the conformational fluctuations of the proteins can be sampled. PMID:23203075

  17. Coarse-Grained Simulations of Heme Proteins: Validation and Study of Large Conformational Transitions.

    PubMed

    Ramírez, Claudia L; Petruk, Ariel; Bringas, Mauro; Estrin, Dario A; Roitberg, Adrian E; Marti, Marcelo A; Capece, Luciana

    2016-07-12

    Heme proteins are ubiquitous in nature and perform many diverse functions in all kingdoms of life. Many of these functions are related to large-scale conformational transitions and allosteric processes. Sampling of these large conformational changes is computationally very challenging. In this context, coarse-grain simulations emerge as an efficient approach to explore the conformational landscape. In this work, we present a coarse-grained model of the heme group and thoroughly validate this model in different benchmark examples, which include the monomeric heme proteins myoglobin and neuroglobin and the tetrameric human hemoglobin where we evaluated the method's ability to explore conformational changes (as the formation of hexacoordinated species) and allosteric transitions (as the well-known R → T transition). The obtained results are compared with atomistic molecular dynamics simulations. Overall, the results indicate that this approach conserves the essential dynamical information on different allosteric processes. PMID:27267322

  18. Multiscale simulation of thin-film lubrication: Free-energy-corrected coarse graining

    NASA Astrophysics Data System (ADS)

    Wu, Z.-B.; Zeng, X. C.

    2014-09-01

    The quasicontinuum method was previously extended to the nonzero temperature conditions by implementing a free-energy correction on non-nodal atoms in coarse-grained solid systems to avoid the dynamical constraint, [Diestler, Wu, and Zeng, J. Chem. Phys. 121, 9279 (2004), 10.1063/1.1806811]. In this paper, we combine the extended quasicontinuum method and an atomistic simulation to treat the monolayer film lubrication with elastic (nonrigid) substrates. It is shown that the multiscale method with the coarse-graining local elements in the merging regions between the atomistic and continuous descriptions of the substrates can reasonably predict the shear stress profile, the mean separation curve, and the transverse stress profile in the fully atomistic simulation for the tribological system. Moreover, when the nonlocal elements are placed in the merging regions, the inhomogeneous solid atoms in the near regions covered by the cut-off circles of the nonlocal elements replace the homogeneous ones at the equilibrium configuration for the free-energy correction on the non-nodal atoms. The treatment can cause an unphysical sliding between the near and far regions of the upper substrate. It is shown that if the free-energy correction on the non-nodal atoms in the coarse-grained merging regions is removed, the multiscale method can still well reproduce the shear stress profile, the mean separation curve, and the transverse stress profile obtained from the fully atomistic simulation for the system.

  19. Adaptive resolution simulation of polarizable supramolecular coarse-grained water models

    SciTech Connect

    Zavadlav, Julija; Praprotnik, Matej; Melo, Manuel N.; Marrink, Siewert J.

    2015-06-28

    Multiscale simulations methods, such as adaptive resolution scheme, are becoming increasingly popular due to their significant computational advantages with respect to conventional atomistic simulations. For these kind of simulations, it is essential to develop accurate multiscale water models that can be used to solvate biophysical systems of interest. Recently, a 4-to-1 mapping was used to couple the bundled-simple point charge water with the MARTINI model. Here, we extend the supramolecular mapping to coarse-grained models with explicit charges. In particular, the two tested models are the polarizable water and big multiple water models associated with the MARTINI force field. As corresponding coarse-grained representations consist of several interaction sites, we couple orientational degrees of freedom of the atomistic and coarse-grained representations via a harmonic energy penalty term. This additional energy term aligns the dipole moments of both representations. We test this coupling by studying the system under applied static external electric field. We show that our approach leads to the correct reproduction of the relevant structural and dynamical properties.

  20. Coarse-grained Simulation of Complexation between Small Interfering RNA and Polycations

    NASA Astrophysics Data System (ADS)

    Wei, Zonghui; Ren, Yong; Williford, John-Michael; Mao, Hai-Quan; Luijten, Erik; Northwestern University Collaboration; Johns Hopkins University Collaboration

    Nanoparticles formed through self-assembly of polycations and nucleic acids are promising systems for gene delivery. A full understanding of the behavior of these particles in physiological context requires detailed knowledge of their physical properties. All-atom molecular dynamics simulations can provide insight into the interaction of polymeric carriers with genomic material, but only at limited time and length scales. To overcome these limitations and explore the full complexation process, a reliable coarse-grained model is needed. Here, we systematically develop such a model for a system comprised of small interfering RNA (siRNA) and polyethyleneimine-based carriers, and evaluate the quality of the coarse-grained model through comparison with all-atom simulations. We show that our coarse-grained model provides a reliable description of detailed binding pictures, charge characteristics, and water dynamics, while accelerating the simulations by two orders of magnitude. This makes it possible to quantitatively investigate nanoparticle formation involving multiple siRNA molecules and cationic copolymers.

  1. Classical density functional theory & simulations on a coarse-grained model of aromatic ionic liquids.

    PubMed

    Turesson, Martin; Szparaga, Ryan; Ma, Ke; Woodward, Clifford E; Forsman, Jan

    2014-05-14

    A new classical density functional approach is developed to accurately treat a coarse-grained model of room temperature aromatic ionic liquids. Our major innovation is the introduction of charge-charge correlations, which are treated in a simple phenomenological way. We test this theory on a generic coarse-grained model for aromatic RTILs with oligomeric forms for both cations and anions, approximating 1-alkyl-3-methyl imidazoliums and BF₄⁻, respectively. We find that predictions by the new density functional theory for fluid structures at charged surfaces are very accurate, as compared with molecular dynamics simulations, across a range of surface charge densities and lengths of the alkyl chain. Predictions of interactions between charged surfaces are also presented. PMID:24718295

  2. Coarse-Grained Molecular Dynamics Simulation of a Red Blood Cell

    NASA Astrophysics Data System (ADS)

    Jiang, Li-Guo; Wu, Heng-An; Zhou, Xiao-Zhou; Wang, Xiu-Xi

    2010-02-01

    A worm-like chain model based on a spectrin network is employed to study the biomechanics of red blood cells. Coarse-grained molecular dynamics simulations are performed to obtain a stable configuration free of external loadings. We also discuss the influence of two parameters: the average bending modulus and the persistence length. The change in shape of a malaria-infected red blood cell can contribute to the change in its molecular-based structure. As the persistence length of the membrane network in the infected red blood cell decreases, the deformability decreases and the biconcave shape is destroyed. The numerical results are comparable with previously reported experimental results. The coarse-grained model can be used to study the relationship between macro-mechanical properties and molecular-scale structures of cells.

  3. Coarse-grain molecular dynamics simulations of diblock copolymer surfactants interacting with a lipid bilayer

    NASA Astrophysics Data System (ADS)

    Srinivas, Goundla; Klein, Michael L.

    2004-01-01

    The interaction of surfactant diblock poly(ethylene oxide)-poly(ethylethylene) copolymers (PEO-PEE) with a lipid bilayer of dimyristoylphosphatidylcholine has been studied by means of coarse-grain molecular dynamics simulations. The effect of the surfactants on the lipid bilayer was studied over a wide range of diblock copolymer concentrations. The simulations show that the hydrophilic PEO chains adopt different structures at low and high concentrations. In particular, the computed density profiles reveal that the PEO chains extend over a longer range from the bilayer surface, with increasing copolymer concentration. The simulated density profiles are in agreement with the scaling law predictions.

  4. Simulation of λ-phage DNA in microchannels using a coarse-grained MD method

    NASA Astrophysics Data System (ADS)

    Symeonidis, Vasileios

    2005-11-01

    In this work we present Dissipative Particle Dynamics (dpd) simulations of polymers subject to the Marko-Siggia wormlike chain (wlc) spring law. We demonstrate the advantages of Lowe's dpd method, which simulates high Schmidt numbers for the solvent, and contrast it with the velocity-Verlet scheme. Shear flow results for the wormlike chain (wlc) simulating single dna molecules compare well with average extensions from experiments, irrespective of the number of beads. However, coarse-graining with more than a few beads degrades the agreement of the autocorrelation of the extension.

  5. A test of systematic coarse-graining of molecular dynamics simulations: Transport properties

    NASA Astrophysics Data System (ADS)

    Fu, Chia-Chun; Kulkarni, Pandurang M.; Shell, M. Scott; Leal, L. Gary

    2013-09-01

    To what extent can a "bottom-up" mesoscale fluid model developed through systematic coarse-graining techniques recover the physical properties of a molecular scale system? In a previous paper [C.-C. Fu, P. M. Kulkarni, M. S. Shell, and L. G. Leal, J. Chem. Phys. 137, 164106 (2012)], 10.1063/1.4759463, we addressed this question for thermodynamic properties through the development of coarse-grained (CG) fluid models using modified iterative Boltzmann inversion methods that reproduce correct pair structure and pressure. In the present work we focus on the dynamic behavior. Unlike the radial distribution function and the pressure, dynamical properties such as the self-diffusion coefficient and viscosity in a CG model cannot be matched during coarse-graining by modifying the pair interaction. Instead, removed degrees of freedom require a modification of the equations of motion to simulate their implicit effects on dynamics. A simple but approximate approach is to introduce a friction coefficient, γ, and random forces for the remaining degrees of freedom, in which case γ becomes an additional parameter in the coarse-grained model that can be tuned. We consider the non-Galilean-invariant Langevin and the Galilean-invariant dissipative particle dynamics (DPD) thermostats with CG systems in which we can systematically tune the fraction ϕ of removed degrees of freedom. Between these two choices, only DPD allows both the viscosity and diffusivity to match a reference Lennard-Jones liquid with a single value of γ for each degree of coarse-graining ϕ. This friction constant is robust to the pressure correction imposed on the effective CG potential, increases approximately linearly with ϕ, and also depends on the interaction cutoff length, rcut, of the pair interaction potential. Importantly, we show that the diffusion constant and viscosity are constrained by a simple scaling law that leads to a specific choice of DPD friction coefficient for a given degree of coarse-graining

  6. Model reduction for agent-based social simulation: coarse-graining a civil violence model.

    PubMed

    Zou, Yu; Fonoberov, Vladimir A; Fonoberova, Maria; Mezic, Igor; Kevrekidis, Ioannis G

    2012-06-01

    Agent-based modeling (ABM) constitutes a powerful computational tool for the exploration of phenomena involving emergent dynamic behavior in the social sciences. This paper demonstrates a computer-assisted approach that bridges the significant gap between the single-agent microscopic level and the macroscopic (coarse-grained population) level, where fundamental questions must be rationally answered and policies guiding the emergent dynamics devised. Our approach will be illustrated through an agent-based model of civil violence. This spatiotemporally varying ABM incorporates interactions between a heterogeneous population of citizens [active (insurgent), inactive, or jailed] and a population of police officers. Detailed simulations exhibit an equilibrium punctuated by periods of social upheavals. We show how to effectively reduce the agent-based dynamics to a stochastic model with only two coarse-grained degrees of freedom: the number of jailed citizens and the number of active ones. The coarse-grained model captures the ABM dynamics while drastically reducing the computation time (by a factor of approximately 20). PMID:23005161

  7. Model reduction for agent-based social simulation: Coarse-graining a civil violence model

    NASA Astrophysics Data System (ADS)

    Zou, Yu; Fonoberov, Vladimir A.; Fonoberova, Maria; Mezic, Igor; Kevrekidis, Ioannis G.

    2012-06-01

    Agent-based modeling (ABM) constitutes a powerful computational tool for the exploration of phenomena involving emergent dynamic behavior in the social sciences. This paper demonstrates a computer-assisted approach that bridges the significant gap between the single-agent microscopic level and the macroscopic (coarse-grained population) level, where fundamental questions must be rationally answered and policies guiding the emergent dynamics devised. Our approach will be illustrated through an agent-based model of civil violence. This spatiotemporally varying ABM incorporates interactions between a heterogeneous population of citizens [active (insurgent), inactive, or jailed] and a population of police officers. Detailed simulations exhibit an equilibrium punctuated by periods of social upheavals. We show how to effectively reduce the agent-based dynamics to a stochastic model with only two coarse-grained degrees of freedom: the number of jailed citizens and the number of active ones. The coarse-grained model captures the ABM dynamics while drastically reducing the computation time (by a factor of approximately 20).

  8. Coarse grained simulation reveals antifreeze properties of hyperactive antifreeze protein from Antarctic bacterium Colwellia sp.

    NASA Astrophysics Data System (ADS)

    Nguyen, Hung; Van, Thanh Dac; Le, Ly

    2015-10-01

    The novel hyperactive antifreeze protein (AFP) of Antarctic sea ice bacterium Colwellia sp. provides a target for studying the protection of psychrophilic microgoranisms against freezing environment. Interestingly, the Colwellia sp. hyperactive antifreeze protein (ColAFP) was crystallized without the structural dynamic characteristics. Here, the result indicated, through coarse grained simulation of ColAFP under various subfreezing temperature, that ColAFP remains active at temperature of equal and greater than 275 K (∼2 °C). Extensive simulation analyses also revealed the adaptive mechanism of ColAFP in subfreezing environment. Our result provides a structural dynamic understanding of the ColAFP.

  9. REACH coarse-grained biomolecular simulation: transferability between different protein structural classes.

    PubMed

    Moritsugu, Kei; Smith, Jeremy C

    2008-08-01

    Coarse graining of protein interactions provides a means of simulating large biological systems. The REACH (Realistic Extension Algorithm via Covariance Hessian) coarse-graining method, in which the force constants of a residue-scale elastic network model are calculated from the variance-covariance matrix obtained from atomistic molecular dynamics (MD) simulation, involves direct mapping between scales without the need for iterative optimization. Here, the transferability of the REACH force field is examined between protein molecules of different structural classes. As test cases, myoglobin (all alpha), plastocyanin (all beta), and dihydrofolate reductase (alpha/beta) are taken. The force constants derived are found to be closely similar in all three proteins. An MD version of REACH is presented, and low-temperature coarse-grained (CG) REACH MD simulations of the three proteins are compared with atomistic MD results. The mean-square fluctuations of the atomistic MD are well reproduced by the CGMD. Model functions for the CG interactions, derived by averaging over the three proteins, are also shown to produce fluctuations in good agreement with the atomistic MD. The results indicate that, similarly to the use of atomistic force fields, it is now possible to use a single, generic REACH force field for all protein studies, without having first to derive parameters from atomistic MD simulation for each individual system studied. The REACH method is thus likely to be a reliable way of determining spatiotemporal motion of a variety of proteins without the need for expensive computation of long atomistic MD simulations. PMID:18469078

  10. A simple, efficient polarizable coarse-grained water model for molecular dynamics simulations.

    PubMed

    Riniker, Sereina; van Gunsteren, Wilfred F

    2011-02-28

    The development of coarse-grained (CG) models that correctly represent the important features of compounds is essential to overcome the limitations in time scale and system size currently encountered in atomistic molecular dynamics simulations. Most approaches reported in the literature model one or several molecules into a single uncharged CG bead. For water, this implicit treatment of the electrostatic interactions, however, fails to mimic important properties, e.g., the dielectric screening. Therefore, a coarse-grained model for water is proposed which treats the electrostatic interactions between clusters of water molecules explicitly. Five water molecules are embedded in a spherical CG bead consisting of two oppositely charged particles which represent a dipole. The bond connecting the two particles in a bead is unconstrained, which makes the model polarizable. Experimental and all-atom simulated data of liquid water at room temperature are used for parametrization of the model. The experimental density and the relative static dielectric permittivity were chosen as primary target properties. The model properties are compared with those obtained from experiment, from clusters of simple-point-charge water molecules of appropriate size in the liquid phase, and for other CG water models if available. The comparison shows that not all atomistic properties can be reproduced by a CG model, so properties of key importance have to be selected when coarse graining is applied. Yet, the CG model reproduces the key characteristics of liquid water while being computationally 1-2 orders of magnitude more efficient than standard fine-grained atomistic water models. PMID:21361530

  11. Coarse-Grained Molecular Monte Carlo Simulations of Liquid Crystal-Nanoparticle Mixtures

    NASA Astrophysics Data System (ADS)

    Neufeld, Ryan; Kimaev, Grigoriy; Fu, Fred; Abukhdeir, Nasser M.

    Coarse-grained intermolecular potentials have proven capable of capturing essential details of interactions between complex molecules, while substantially reducing the number of degrees of freedom of the system under study. In the domain of liquid crystals, the Gay-Berne (GB) potential has been successfully used to model the behavior of rod-like and disk-like mesogens. However, only ellipsoid-like interaction potentials can be described with GB, making it a poor fit for many real-world mesogens. In this work, the results of Monte Carlo simulations of liquid crystal domains using the Zewdie-Corner (ZC) potential are presented. The ZC potential is constructed from an orthogonal series of basis functions, allowing for potentials of essentially arbitrary shapes to be modeled. We also present simulations of mixtures of liquid crystalline mesogens with nanoparticles. Experimentally these mixtures have been observed to exhibit microphase separation and formation of long-range networks under some conditions. This highlights the need for a coarse-grained approach which can capture salient details on the molecular scale while simulating sufficiently large domains to observe these phenomena. We compare the phase behavior of our simulations with that of a recently presented continuum theory. This work was made possible by the Natural Sciences and Engineering Research Council of Canada and Compute Ontario.

  12. Towards a unified framework for coarse-graining particle-based simulations.

    SciTech Connect

    Junghans, Christoph

    2012-06-28

    Different coarse-graining techniques for soft matter systems have been developed in recent years, however it is often very demanding to find the method most suitable for the problem studied. For this reason we began to develop the VOTCA toolkit to allow for easy comparison of different methods. We have incorporated 6 different techniques into the package and implemented a powerful and parallel analysis framework plus multiple simulation back-ends. We will discuss the specifics of the package by means of various studies, which have been performed with the toolkit and highlight problems we encountered along the way.

  13. Shock wave interaction with a phospholipid membrane: Coarse-grained computer simulations

    NASA Astrophysics Data System (ADS)

    Santo, Kolattukudy P.; Berkowitz, Max L.

    2014-02-01

    We used MARTINI coarse-grained force field to study poration of a lipid bilayer by a shock wave induced nanobubble collapse. Different systems containing different sized nanobubbles that were exposed to shock waves propagating with different velocities were simulated. We observed creation of pores and damage to bilayers and also subsequent pore closing and the bilayer recovery after shock wave passed the bilayer. In all our systems where bilayers were damaged, they recovered; nevertheless we observed that a large amount of water crossed the pore that was temporarily created. We also observed that not every lipid molecule remained in the bilayer after recovery, some lipids moved out into water and created micelles.

  14. Coarse-grained simulations of polyelectrolyte complexes: MARTINI models for poly(styrene sulfonate) and poly(diallyldimethylammonium)

    NASA Astrophysics Data System (ADS)

    Vögele, Martin; Holm, Christian; Smiatek, Jens

    2015-12-01

    We present simulations of aqueous polyelectrolyte complexes with new MARTINI models for the charged polymers poly(styrene sulfonate) and poly(diallyldimethylammonium). Our coarse-grained polyelectrolyte models allow us to study large length and long time scales with regard to chemical details and thermodynamic properties. The results are compared to the outcomes of previous atomistic molecular dynamics simulations and verify that electrostatic properties are reproduced by our MARTINI coarse-grained approach with reasonable accuracy. Structural similarity between the atomistic and the coarse-grained results is indicated by a comparison between the pair radial distribution functions and the cumulative number of surrounding particles. Our coarse-grained models are able to quantitatively reproduce previous findings like the correct charge compensation mechanism and a reduced dielectric constant of water. These results can be interpreted as the underlying reason for the stability of polyelectrolyte multilayers and complexes and validate the robustness of the proposed models.

  15. Coarse-grained simulations of polyelectrolyte complexes: MARTINI models for poly(styrene sulfonate) and poly(diallyldimethylammonium)

    SciTech Connect

    Vögele, Martin; Holm, Christian; Smiatek, Jens

    2015-12-28

    We present simulations of aqueous polyelectrolyte complexes with new MARTINI models for the charged polymers poly(styrene sulfonate) and poly(diallyldimethylammonium). Our coarse-grained polyelectrolyte models allow us to study large length and long time scales with regard to chemical details and thermodynamic properties. The results are compared to the outcomes of previous atomistic molecular dynamics simulations and verify that electrostatic properties are reproduced by our MARTINI coarse-grained approach with reasonable accuracy. Structural similarity between the atomistic and the coarse-grained results is indicated by a comparison between the pair radial distribution functions and the cumulative number of surrounding particles. Our coarse-grained models are able to quantitatively reproduce previous findings like the correct charge compensation mechanism and a reduced dielectric constant of water. These results can be interpreted as the underlying reason for the stability of polyelectrolyte multilayers and complexes and validate the robustness of the proposed models.

  16. Holliday Junction Thermodynamics and Structure: Coarse-Grained Simulations and Experiments

    PubMed Central

    Wang, Wujie; Nocka, Laura M.; Wiemann, Brianne Z.; Hinckley, Daniel M.; Mukerji, Ishita; Starr, Francis W.

    2016-01-01

    Holliday junctions play a central role in genetic recombination, DNA repair and other cellular processes. We combine simulations and experiments to evaluate the ability of the 3SPN.2 model, a coarse-grained representation designed to mimic B-DNA, to predict the properties of DNA Holliday junctions. The model reproduces many experimentally determined aspects of junction structure and stability, including the temperature dependence of melting on salt concentration, the bias between open and stacked conformations, the relative populations of conformers at high salt concentration, and the inter-duplex angle (IDA) between arms. We also obtain a close correspondence between the junction structure evaluated by all-atom and coarse-grained simulations. We predict that, for salt concentrations at physiological and higher levels, the populations of the stacked conformers are independent of salt concentration, and directly observe proposed tetrahedral intermediate sub-states implicated in conformational transitions. Our findings demonstrate that the 3SPN.2 model captures junction properties that are inaccessible to all-atom studies, opening the possibility to simulate complex aspects of junction behavior. PMID:26971574

  17. Coarse-grained molecular dynamics simulations of protein-ligand binding.

    PubMed

    Negami, Tatsuki; Shimizu, Kentaro; Terada, Tohru

    2014-09-30

    Coarse-grained molecular dynamics (CGMD) simulations with the MARTINI force field were performed to reproduce the protein-ligand binding processes. We chose two protein-ligand systems, the levansucrase-sugar (glucose or sucrose), and LinB-1,2-dichloroethane systems, as target systems that differ in terms of the size and shape of the ligand-binding pocket and the physicochemical properties of the pocket and the ligand. Spatial distributions of the Coarse-grained (CG) ligand molecules revealed potential ligand-binding sites on the protein surfaces other than the real ligand-binding sites. The ligands bound most strongly to the real ligand-binding sites. The binding and unbinding rate constants obtained from the CGMD simulation of the levansucrase-sucrose system were approximately 10 times greater than the experimental values; this is mainly due to faster diffusion of the CG ligand in the CG water model. We could obtain dissociation constants close to the experimental values for both systems. Analysis of the ligand fluxes demonstrated that the CG ligand molecules entered the ligand-binding pockets through specific pathways. The ligands tended to move through grooves on the protein surface. Thus, the CGMD simulations produced reasonable results for the two different systems overall and are useful for studying the protein-ligand binding processes. PMID:25043724

  18. Holliday Junction Thermodynamics and Structure: Coarse-Grained Simulations and Experiments

    NASA Astrophysics Data System (ADS)

    Wang, Wujie; Nocka, Laura M.; Wiemann, Brianne Z.; Hinckley, Daniel M.; Mukerji, Ishita; Starr, Francis W.

    2016-03-01

    Holliday junctions play a central role in genetic recombination, DNA repair and other cellular processes. We combine simulations and experiments to evaluate the ability of the 3SPN.2 model, a coarse-grained representation designed to mimic B-DNA, to predict the properties of DNA Holliday junctions. The model reproduces many experimentally determined aspects of junction structure and stability, including the temperature dependence of melting on salt concentration, the bias between open and stacked conformations, the relative populations of conformers at high salt concentration, and the inter-duplex angle (IDA) between arms. We also obtain a close correspondence between the junction structure evaluated by all-atom and coarse-grained simulations. We predict that, for salt concentrations at physiological and higher levels, the populations of the stacked conformers are independent of salt concentration, and directly observe proposed tetrahedral intermediate sub-states implicated in conformational transitions. Our findings demonstrate that the 3SPN.2 model captures junction properties that are inaccessible to all-atom studies, opening the possibility to simulate complex aspects of junction behavior.

  19. Conservative and dissipative force field for simulation of coarse-grained alkane molecules: A bottom-up approach

    NASA Astrophysics Data System (ADS)

    Trément, Sébastien; Schnell, Benoît.; Petitjean, Laurent; Couty, Marc; Rousseau, Bernard

    2014-04-01

    We apply operational procedures available in the literature to the construction of coarse-grained conservative and friction forces for use in dissipative particle dynamics (DPD) simulations. The full procedure rely on a bottom-up approach: large molecular dynamics trajectories of n-pentane and n-decane modeled with an anisotropic united atom model serve as input for the force field generation. As a consequence, the coarse-grained model is expected to reproduce at least semi-quantitatively structural and dynamical properties of the underlying atomistic model. Two different coarse-graining levels are studied, corresponding to five and ten carbon atoms per DPD bead. The influence of the coarse-graining level on the generated force fields contributions, namely, the conservative and the friction part, is discussed. It is shown that the coarse-grained model of n-pentane correctly reproduces self-diffusion and viscosity coefficients of real n-pentane, while the fully coarse-grained model for n-decane at ambient temperature over-predicts diffusion by a factor of 2. However, when the n-pentane coarse-grained model is used as a building block for larger molecule (e.g., n-decane as a two blobs model), a much better agreement with experimental data is obtained, suggesting that the force field constructed is transferable to large macro-molecular systems.

  20. Conservative and dissipative force field for simulation of coarse-grained alkane molecules: a bottom-up approach.

    PubMed

    Trément, Sébastien; Schnell, Benoît; Petitjean, Laurent; Couty, Marc; Rousseau, Bernard

    2014-04-01

    We apply operational procedures available in the literature to the construction of coarse-grained conservative and friction forces for use in dissipative particle dynamics (DPD) simulations. The full procedure rely on a bottom-up approach: large molecular dynamics trajectories of n-pentane and n-decane modeled with an anisotropic united atom model serve as input for the force field generation. As a consequence, the coarse-grained model is expected to reproduce at least semi-quantitatively structural and dynamical properties of the underlying atomistic model. Two different coarse-graining levels are studied, corresponding to five and ten carbon atoms per DPD bead. The influence of the coarse-graining level on the generated force fields contributions, namely, the conservative and the friction part, is discussed. It is shown that the coarse-grained model of n-pentane correctly reproduces self-diffusion and viscosity coefficients of real n-pentane, while the fully coarse-grained model for n-decane at ambient temperature over-predicts diffusion by a factor of 2. However, when the n-pentane coarse-grained model is used as a building block for larger molecule (e.g., n-decane as a two blobs model), a much better agreement with experimental data is obtained, suggesting that the force field constructed is transferable to large macro-molecular systems. PMID:24712786

  1. Simulation of ballistic performance of coarse-grained metals strengthened by nanotwinned regions

    NASA Astrophysics Data System (ADS)

    Yang, G.; Guo, X.; Weng, G. J.; Zhu, L. L.; Ji, R.

    2015-12-01

    Coarse-grained (CG) metals strengthened by nanotwinned (NT) regions have both ultrahigh strength and good ductility. The presence of the NT regions contributes to their ultrahigh strength, while their good ductility is attributed to the recrystallized coarse grains. These characteristics make them a potential candidate for bullet-proof material. In this paper, numerical simulations based on the mechanism-based strain gradient plasticity and the Johnson-Cook failure criterion are carried out to investigate the effects of twin spacing and microstructural attributes on the ballistic performance of CG copper strengthened by NT regions. We investigate the performance of fourteen idealized microstructures, and find that smaller twin spacing and regular distribution of NT regions are more conducive to the promotion of the ballistic performance. We also uncover that the role of the shape of NT regions is significantly affected by twin spacing. Furthermore, we make a comparison with its CG counterpart without NTs, and find that microstructures with array arrangement of NT regions have higher limit velocities and smaller relative displacements than the single phase CG structure. This makes them a strong candidate for helmets and other personal protective equipments. It is believed that the simulated results could provide useful insights into the development of this advanced class of metals for ballistic protection.

  2. Topological defects around a spherical nanoparticle in nematic liquid crystal: coarse-grained molecular dynamics simulations.

    PubMed

    Ilnytskyi, Jaroslav M; Trokhymchuk, Andrij; Schoen, Martin

    2014-09-21

    We consider the applicability of coarse-grained molecular dynamics for the simulation of defects in a nematic liquid crystal around a colloidal particle. Two types of colloids are considered, a soft colloid resembling a liquid crystal dendrimer or a similar macromolecule. In addition, a decorated colloid is used which could represent a gold nanoparticle with mesogen-modified surface. For both models we consider homeotropic and tangential anchoring. Precise control of the easy axis on the colloid's surface enables us to focus on specific planar arrangements in the case of a decorated colloid. The nematic phase is modelled explicitly via soft spherocylinders interacting through a potential, suggested by Lintuvuori and Wilson [J. Chem. Phys. 128, 044906 (2008)]. Properties of the nematic phase are studied by computing the Frank elastic constants. In addition, estimates for the nematic-isotropic transition and the coherence length allow us to establish a relation between energy and length scales with respect to experimental systems. Both models exhibit similar defect topologies, namely, that of a Saturn ring and a boojum-type of defect for homeotropic and tangential surface anchoring, respectively. In the decorated colloid model we tune the anchoring strength through the density of the mesogenic shell on the surface. We also found the biaxial boojum defect for the special case of longitudinal planar anchoring. The study demonstrates the potential of coarse-grained simulation methods for studying defects in liquid crystals. PMID:25240368

  3. Mixing MARTINI: electrostatic coupling in hybrid atomistic-coarse-grained biomolecular simulations.

    PubMed

    Wassenaar, Tsjerk A; Ingólfsson, Helgi I; Priess, Marten; Marrink, Siewert J; Schäfer, Lars V

    2013-04-01

    Hybrid molecular dynamics simulations of atomistic (AA) solutes embedded in coarse-grained (CG) environment can substantially reduce the computational cost with respect to fully atomistic simulations. However, interfacing both levels of resolution is a major challenge that includes a balanced description of the relevant interactions. This is especially the case for polar solvents such as water, which screen the electrostatic interactions and thus require explicit electrostatic coupling between AA and CG subsystems. Here, we present and critically test computationally efficient hybrid AA/CG models. We combined the Gromos atomistic force field with the MARTINI coarse-grained force field. To enact electrostatic coupling, two recently developed CG water models with explicit electrostatic interactions were used: the polarizable MARTINI water model and the BMW model. The hybrid model was found to be sensitive to the strength of the AA-CG electrostatic coupling, which was adjusted through the relative dielectric permittivity εr(AA-CG). Potentials of mean force (PMFs) between pairs of amino acid side chain analogues in water and partitioning free enthalpies of uncharged amino acid side chain analogues between apolar solvent and water show significant differences between the hybrid simulations and the fully AA or CG simulations, in particular for charged and polar molecules. For apolar molecules, the results obtained with the hybrid AA/CG models are in better agreement with the fully atomistic results. The structures of atomistic ubiquitin solvated in CG water and of a single atomistic transmembrane α-helix and the transmembrane portion of an atomistic mechanosensitive channel in CG lipid bilayers were largely maintained during 50-100 ns of AA/CG simulations, partly due to an overstabilization of intramolecular interactions. This work highlights some key challenges on the way toward hybrid AA/CG models that are both computationally efficient and sufficiently accurate for

  4. On Using Atomistic Solvent Layers in Hybrid All-Atom/Coarse-Grained Molecular Dynamics Simulations.

    PubMed

    Kuhn, Alexander B; Gopal, Srinivasa M; Schäfer, Lars V

    2015-09-01

    Hybrid all-atom/coarse-grained (AA-CG) simulations in which AA solutes are embedded in a CG environment can provide a significant computational speed-up over conventional fully atomistic simulations and thus alleviate the current length and time scale limitations of molecular dynamics (MD) simulations of large biomolecular systems. On one hand, coarse graining the solvent is particularly appealing, since it typically constitutes the largest part of the simulation system and thus dominates computational cost. On the other hand, retaining atomic-level solvent layers around the solute is desirable for a realistic description of hydrogen bonds and other local solvation effects. Here, we devise and systematically validate fixed resolution AA-CG schemes, both with and without atomistic water layers. To quantify the accuracy and diagnose possible pitfalls, Gibbs free energies of solvation of amino acid side chain analogues were calculated, and the influence of the nature of the CG solvent surrounding (polarizable vs nonpolarizable CG water) and the size of the AA solvent region was investigated. We show that distance restraints to keep the AA solvent around the solute lead to too high of a density in the inner shell. Together with a long-ranged effect due to orientational ordering of water molecules at the AA-CG boundary, this affects solvation free energies. Shifting the onset of the distance restraints slightly away from the central solute significantly improves solvation free energies, down to mean unsigned errors with respect to experiment of 2.3 and 2.6 kJ/mol for the polarizable and nonpolarizable CG water surrounding, respectively. The speed-up of the nonpolarizable model renders it computationally more attractive. The present work thus highlights challenges, and outlines possible solutions, involved with modeling the boundary between different levels of resolution in hybrid AA-CG simulations. PMID:26575936

  5. Thermal and mechanical properties of thermosetting polymers using coarse-grained simulation

    NASA Astrophysics Data System (ADS)

    Jang, C.; Abrams, C. F.

    2016-07-01

    We developed coarse-grained (CG) molecular representations of mixtures of diglycidyl ether of bisphenol-A (DGEBA) and poly(oxypropylene) diamine (POP-DA) for use in CG molecular dynamics (MD) simulations. In the CG representation, DGEBA is comprised of three beads of two types and POP-DA also by three beads of two types. Atomistic MD of liquid systems was performed to derive intra- and inter-bead potentials via Boltzmann inversion. While the bonded potentials, composed of bond stretching and angle bending, were parameterized directly from the distribution functions of all atomistic molecular dynamics trajectories, the non-bonded potentials were derived from the iterative Boltzmann Inversion with a given set of coarse-grained interactions. CG systems correctly reproduced liquid and crosslinked densities. Under uniaxial tension, the Young's modulus of the CG systems was much lower than the experimental value, and we show this arises from the assumed form of the extrapolated regions of the CG potentials. By stiffening these regions, we increased the CG Young's modulus of the crosslinked systems without sacrificing the correct prediction of density. This suggests that transferrable CG potentials can be optimized for use in non-equilibrium MD for property estimation.

  6. Molecular dynamics simulation of water in and around carbon nanotubes: A coarse-grained description

    NASA Astrophysics Data System (ADS)

    Pantawane, Sanwardhini; Choudhury, Niharendu

    2016-05-01

    In the present study, we intend to investigate behaviour of water in and around hydrophobic open ended carbon nanotubes (CNTs) using a coarse-grained, core-softened model potential for water. The model potential considered here for water has recently been shown to successfully reproduce dynamic, thermodynamic and structural anomalies of water. The epitome of the study is to understand the incarceration of this coarse-grained water in a single-file carbon nanotube. In order to examine the effect of fluid-water van der Waals interaction on the structure of fluid in and around the nanotube, we have simulated three different CNT-water systems with varying degree of solute-water dispersion interaction. The analyses of the radial one-particle density profiles reveal varying degree of permeation and wetting of the CNT interior depending on the degree of fluid-solute attractive van der Waals interaction. A peak in the radial density profile slightly off the nanotube axis signifies a zigzag chain of water molecule around the CNT axis. The average numbers of water molecules inside the CNT have been shown to increase with the increase in fluid-water attractive dispersion interaction.

  7. Aggregation of alpha-synuclein by a coarse-grained Monte Carlo simulation

    NASA Astrophysics Data System (ADS)

    Farmer, Barry; Pandey, Ras

    Alpha-synuclein, an intrinsic protein abundant in neurons, is believed to be a major cause of neurodegenerative diseases (e.g. Alzheimer, Parkinson's disease). Abnormal aggregation of ASN leads to Lewy bodies with specific morphologies. We investigate the self-organizing structures in a crowded environment of ASN proteins by a coarse-grained Monte Carlo simulation. ASN is a chain of 140 residues. Structure detail of residues is neglected but its specificity is captured via unique knowledge-based residue-residue interactions. Large-scale simulations are performed to analyze a number local and global physical quantities (e.g. mobility profile, contact map, radius of gyration, structure factor) as a function of temperature and protein concentration. Trend in multi-scale structural variations of the protein in a crowded environment is compared with that of a free protein chain.

  8. Emergence of attraction in simulations of coarse-grained double stranded DNA

    NASA Astrophysics Data System (ADS)

    Ghanbarian, Shahzad; Rottler, Joerg

    2015-03-01

    DNA condensation induced by multivalent counterions is believed to play an important role in DNA bundling and packing into the cell nucleus. We present a coarse-grained, implicit solvent representation of rigid ds-DNA molecules in the presence of divalent counterions. In order to include solvation effects arising from the discrete nature of the water molecules, short-ranged corrections are added to the pairwise interaction potentials such that the structure of counterions is consistent with results from corresponding explicit solvent simulations. The effective force between two DNA strands generated by these potentials provides an excellent match to that observed in the explicit solvent model. Importantly, this interaction features multiple minima and reproduces the like-charge attraction effect between DNA molecules observed in full atomistic simulations at significantly reduced computational expense. This result proves that it is possible to capture complex multibody interactions between polyelectrolyte strands with two-body potentials.

  9. Coarse-grained molecular dynamics simulations of depletion-induced interactions for soft matter systems

    SciTech Connect

    Shendruk, Tyler N.; Bertrand, Martin; Harden, James L.; Slater, Gary W.; Haan, Hendrick W. de

    2014-12-28

    Given the ubiquity of depletion effects in biological and other soft matter systems, it is desirable to have coarse-grained Molecular Dynamics (MD) simulation approaches appropriate for the study of complex systems. This paper examines the use of two common truncated Lennard-Jones (Weeks-Chandler-Andersen (WCA)) potentials to describe a pair of colloidal particles in a thermal bath of depletants. The shifted-WCA model is the steeper of the two repulsive potentials considered, while the combinatorial-WCA model is the softer. It is found that the depletion-induced well depth for the combinatorial-WCA model is significantly deeper than the shifted-WCA model because the resulting overlap of the colloids yields extra accessible volume for depletants. For both shifted- and combinatorial-WCA simulations, the second virial coefficients and pair potentials between colloids are demonstrated to be well approximated by the Morphometric Thermodynamics (MT) model. This agreement suggests that the presence of depletants can be accurately modelled in MD simulations by implicitly including them through simple, analytical MT forms for depletion-induced interactions. Although both WCA potentials are found to be effective generic coarse-grained simulation approaches for studying depletion effects in complicated soft matter systems, combinatorial-WCA is the more efficient approach as depletion effects are enhanced at lower depletant densities. The findings indicate that for soft matter systems that are better modelled by potentials with some compressibility, predictions from hard-sphere systems could greatly underestimate the magnitude of depletion effects at a given depletant density.

  10. Coarse-grained molecular dynamics simulations of depletion-induced interactions for soft matter systems

    NASA Astrophysics Data System (ADS)

    Shendruk, Tyler N.; Bertrand, Martin; Harden, James L.; Slater, Gary W.; de Haan, Hendrick W.

    2014-12-01

    Given the ubiquity of depletion effects in biological and other soft matter systems, it is desirable to have coarse-grained Molecular Dynamics (MD) simulation approaches appropriate for the study of complex systems. This paper examines the use of two common truncated Lennard-Jones (Weeks-Chandler-Andersen (WCA)) potentials to describe a pair of colloidal particles in a thermal bath of depletants. The shifted-WCA model is the steeper of the two repulsive potentials considered, while the combinatorial-WCA model is the softer. It is found that the depletion-induced well depth for the combinatorial-WCA model is significantly deeper than the shifted-WCA model because the resulting overlap of the colloids yields extra accessible volume for depletants. For both shifted- and combinatorial-WCA simulations, the second virial coefficients and pair potentials between colloids are demonstrated to be well approximated by the Morphometric Thermodynamics (MT) model. This agreement suggests that the presence of depletants can be accurately modelled in MD simulations by implicitly including them through simple, analytical MT forms for depletion-induced interactions. Although both WCA potentials are found to be effective generic coarse-grained simulation approaches for studying depletion effects in complicated soft matter systems, combinatorial-WCA is the more efficient approach as depletion effects are enhanced at lower depletant densities. The findings indicate that for soft matter systems that are better modelled by potentials with some compressibility, predictions from hard-sphere systems could greatly underestimate the magnitude of depletion effects at a given depletant density.

  11. Self-assembling dipeptides: conformational sampling in solvent-free coarse-grained simulation.

    PubMed

    Villa, Alessandra; Peter, Christine; van der Vegt, Nico F A

    2009-03-28

    We discuss the development of a coarse-grained (CG) model for molecular dynamics (MD) simulation of a hydrophobic dipeptide, diphenylalanine, in aqueous solution. The peptide backbone is described with two CG beads per amino acid, the side groups and charged end groups are each described with one CG bead. In the derivation of interaction functions between CG beads we follow a bottom-up strategy where we devise potentials such that the resulting CG simulation reproduces the conformational sampling and the intermolecular interactions observed in an atomistic simulation of the same peptide. In the CG model, conformational flexibility of the peptide is accounted for through a set of intra-molecular (bonded) potentials. The approach followed to obtain the bonded potentials is discussed in detail. The CG potentials for nonbonded interactions are based on potentials of mean force obtained by atomistic simulations in aqueous solution. Following this approach, solvent mediation effects are included in the effective bead-bead nonbonded interactions and computationally very efficient (solvent-free) simulations of self-assembly processes can be performed. We show that the conformational properties of the all-atom dipeptide in explicit solvent can be accurately reproduced with the CG model. Moreover, preliminary simulations of peptide self-assembly performed with the CG model illustrate good agreement with results obtained from all-atom, explicit solvent simulations. PMID:19280018

  12. Ion Correlation and Transport in Polymer Electrolytes at Finite Salt Concentrations; Coarse-Grained Simulation Study

    NASA Astrophysics Data System (ADS)

    Yamamoto, Umi; Wang, Zhen-Gang

    We present results from coarse-grained simulation for ion dynamics and structures in dry polymer electrolytes. To capture the thermodynamic, kinetic, and system-specific aspects of ion solvation and clustering, cation-monomer complexation is modeled via functionalized physical bonds whose functionality and lifetime vary due to local availability of binding monomers and competition with Coulombic interaction. By varying salt concentration, cation-monomer binding energy, dielectric constant, and maximal functionality of the physical bonds, we systematically study the growth of ion clustering activity as characterized by packing structures, and associated changes in electric conductivity via single-ion and collective charge mobility. Deviations from Nernst-Einstein predictions, and comparisons with existing experiments for concentration dependence of conductivity will be discussed.

  13. Coarse-grained simulations of flow-induced morphology dynamics in dispersed graphene

    NASA Astrophysics Data System (ADS)

    Xu, Yueyi; Green, Micah

    2013-11-01

    We investigated how flow fields affect graphene morphology dynamics in liquid phase using a coarse-grained model. Past simulations of the dynamics of dispersed graphene sheets are limited to static fluids on small timescales, with little attention devoted to flow dynamics, which is critical given the importance of graphene solution-processing of multifunctional devices and materials. We developed a Brownian Dynamics (BD) algorithm to study the morphology of sheetlike macromolecules in dilute solutions with an applied external flow field. We used a bead-rod lattice to represent the mesoscopic conformation of individual two dimensional sheets. We then analyzed the morphology dynamic modes (stretching, tumbling, crumpling) of these molecules as a function of sheet size, Weissenberg number, and bending stiffness. The physical properties (e. g. viscosity) affected by the morphology are also studied. Our results demonstrate how bending stiffness relates to relaxation modes during startup of shear.

  14. Coarse-grained simulation reveals key features of HIV-1 capsid self-assembly

    NASA Astrophysics Data System (ADS)

    Grime, John M. A.; Dama, James F.; Ganser-Pornillos, Barbie K.; Woodward, Cora L.; Jensen, Grant J.; Yeager, Mark; Voth, Gregory A.

    2016-05-01

    The maturation of HIV-1 viral particles is essential for viral infectivity. During maturation, many copies of the capsid protein (CA) self-assemble into a capsid shell to enclose the viral RNA. The mechanistic details of the initiation and early stages of capsid assembly remain to be delineated. We present coarse-grained simulations of capsid assembly under various conditions, considering not only capsid lattice self-assembly but also the potential disassembly of capsid upon delivery to the cytoplasm of a target cell. The effects of CA concentration, molecular crowding, and the conformational variability of CA are described, with results indicating that capsid nucleation and growth is a multi-stage process requiring well-defined metastable intermediates. Generation of the mature capsid lattice is sensitive to local conditions, with relatively subtle changes in CA concentration and molecular crowding influencing self-assembly and the ensemble of structural morphologies.

  15. Shock wave interaction with a phospholipid membrane: coarse-grained computer simulations.

    PubMed

    Santo, Kolattukudy P; Berkowitz, Max L

    2014-02-01

    We used MARTINI coarse-grained force field to study poration of a lipid bilayer by a shock wave induced nanobubble collapse. Different systems containing different sized nanobubbles that were exposed to shock waves propagating with different velocities were simulated. We observed creation of pores and damage to bilayers and also subsequent pore closing and the bilayer recovery after shock wave passed the bilayer. In all our systems where bilayers were damaged, they recovered; nevertheless we observed that a large amount of water crossed the pore that was temporarily created. We also observed that not every lipid molecule remained in the bilayer after recovery, some lipids moved out into water and created micelles. PMID:24511978

  16. Monte-Carlo simulations of a coarse-grained model for α-oligothiophenes

    NASA Astrophysics Data System (ADS)

    Almutairi, Amani; Luettmer-Strathmann, Jutta

    The interfacial layer of an organic semiconductor in contact with a metal electrode has important effects on the performance of thin-film devices. However, the structure of this layer is not easy to model. Oligothiophenes are small, π-conjugated molecules with applications in organic electronics that also serve as small-molecule models for polythiophenes. α-hexithiophene (6T) is a six-ring molecule, whose adsorption on noble metal surfaces has been studied extensively (see, e.g., Ref.). In this work, we develop a coarse-grained model for α-oligothiophenes. We describe the molecules as linear chains of bonded, discotic particles with Gay-Berne potential interactions between non-bonded ellipsoids. We perform Monte Carlo simulations to study the structure of isolated and adsorbed molecules

  17. Coarse-grained simulation reveals key features of HIV-1 capsid self-assembly.

    PubMed

    Grime, John M A; Dama, James F; Ganser-Pornillos, Barbie K; Woodward, Cora L; Jensen, Grant J; Yeager, Mark; Voth, Gregory A

    2016-01-01

    The maturation of HIV-1 viral particles is essential for viral infectivity. During maturation, many copies of the capsid protein (CA) self-assemble into a capsid shell to enclose the viral RNA. The mechanistic details of the initiation and early stages of capsid assembly remain to be delineated. We present coarse-grained simulations of capsid assembly under various conditions, considering not only capsid lattice self-assembly but also the potential disassembly of capsid upon delivery to the cytoplasm of a target cell. The effects of CA concentration, molecular crowding, and the conformational variability of CA are described, with results indicating that capsid nucleation and growth is a multi-stage process requiring well-defined metastable intermediates. Generation of the mature capsid lattice is sensitive to local conditions, with relatively subtle changes in CA concentration and molecular crowding influencing self-assembly and the ensemble of structural morphologies. PMID:27174390

  18. Kinetics of formation of bile salt micelles from coarse-grained Langevin dynamics simulations.

    PubMed

    Vila Verde, Ana; Frenkel, Daan

    2016-06-21

    We examine the mechanism of formation of micelles of dihydroxy bile salts using a coarse-grained, implicit solvent model and Langevin dynamics simulations. We find that bile salt micelles primarily form via addition and removal of monomers, similarly to surfactants with typical head-tail molecular structures, and not via a two-stage mechanism - involving formation of oligomers and their subsequent aggregation to form larger micelles - originally proposed for bile salts. The free energy barrier to removal of single bile monomers from micelles is ≈2kBT, much less than what has been observed for head-tail surfactants. Such a low barrier may be biologically relevant: it allows for rapid release of bile monomers into the intestine, possibly enabling the coverage of fat droplets by bile salt monomers and subsequent release of micelles containing fats and bile salts - a mechanism that is not possible for ionic head-tail surfactants of similar critical micellar concentrations. PMID:27199094

  19. Protein Simulations in Fluids: Coupling the OPEP Coarse-Grained Force Field with Hydrodynamics.

    PubMed

    Sterpone, Fabio; Derreumaux, Philippe; Melchionna, Simone

    2015-04-14

    A novel simulation framework that integrates the OPEP coarse-grained (CG) model for proteins with the Lattice Boltzmann (LB) methodology to account for the fluid solvent at mesoscale level is presented. OPEP is a very efficient, water-free and electrostatic-free force field that reproduces at quasi-atomistic detail processes like peptide folding, structural rearrangements, and aggregation dynamics. The LB method is based on the kinetic description of the solvent in order to solve the fluid mechanics under a wide range of conditions, with the further advantage of being highly scalable on parallel architectures. The capabilities of the approach are presented, and it is shown that the strategy is effective in exploring the role of hydrodynamics on protein relaxation and peptide aggregation. The end result is a strategy for modeling systems of thousands of proteins, such as in the case of dense protein suspensions. The future perspectives of the multiscale approach are also discussed. PMID:26574390

  20. A coarse-grained simulation for the folding of molybdenum disulphide

    NASA Astrophysics Data System (ADS)

    Wang, Cui-Xia; Zhang, Chao; Jiang, Jin-Wu; Rabczuk, Timon

    2016-01-01

    We investigate the folding of molybdenum disulphide (MoS2) using coarse-grained (CG) simulations, in which all the parameters are determined analytically from the Stillinger-Weber atomic potential. Owing to its simplicity, the CG model can be used to derive analytic predictions for the relaxed configuration of the folded MoS2 and the resonant frequency for the breathing-like oscillation. We disclose two interesting phenomena for the breathing-like oscillation in the folded MoS2. First, the breathing-like oscillation is self-actuated, since this oscillation can be actuated by intrinsic thermal vibrations without any external actuation force. Second, the resonant frequency of the breathing-like oscillation is insensitive to the adsorption effect. These two features enable practical applications of the folded MoS2 based nanoresonators, where stable resonant oscillations are desirable.

  1. Coarse-grained simulation reveals key features of HIV-1 capsid self-assembly

    PubMed Central

    Grime, John M. A.; Dama, James F.; Ganser-Pornillos, Barbie K.; Woodward, Cora L.; Jensen, Grant J.; Yeager, Mark; Voth, Gregory A.

    2016-01-01

    The maturation of HIV-1 viral particles is essential for viral infectivity. During maturation, many copies of the capsid protein (CA) self-assemble into a capsid shell to enclose the viral RNA. The mechanistic details of the initiation and early stages of capsid assembly remain to be delineated. We present coarse-grained simulations of capsid assembly under various conditions, considering not only capsid lattice self-assembly but also the potential disassembly of capsid upon delivery to the cytoplasm of a target cell. The effects of CA concentration, molecular crowding, and the conformational variability of CA are described, with results indicating that capsid nucleation and growth is a multi-stage process requiring well-defined metastable intermediates. Generation of the mature capsid lattice is sensitive to local conditions, with relatively subtle changes in CA concentration and molecular crowding influencing self-assembly and the ensemble of structural morphologies. PMID:27174390

  2. CAMELOT: A machine learning approach for coarse-grained simulations of aggregation of block-copolymeric protein sequences

    NASA Astrophysics Data System (ADS)

    Ruff, Kiersten M.; Harmon, Tyler S.; Pappu, Rohit V.

    2015-12-01

    We report the development and deployment of a coarse-graining method that is well suited for computer simulations of aggregation and phase separation of protein sequences with block-copolymeric architectures. Our algorithm, named CAMELOT for Coarse-grained simulations Aided by MachinE Learning Optimization and Training, leverages information from converged all atom simulations that is used to determine a suitable resolution and parameterize the coarse-grained model. To parameterize a system-specific coarse-grained model, we use a combination of Boltzmann inversion, non-linear regression, and a Gaussian process Bayesian optimization approach. The accuracy of the coarse-grained model is demonstrated through direct comparisons to results from all atom simulations. We demonstrate the utility of our coarse-graining approach using the block-copolymeric sequence from the exon 1 encoded sequence of the huntingtin protein. This sequence comprises of 17 residues from the N-terminal end of huntingtin (N17) followed by a polyglutamine (polyQ) tract. Simulations based on the CAMELOT approach are used to show that the adsorption and unfolding of the wild type N17 and its sequence variants on the surface of polyQ tracts engender a patchy colloid like architecture that promotes the formation of linear aggregates. These results provide a plausible explanation for experimental observations, which show that N17 accelerates the formation of linear aggregates in block-copolymeric N17-polyQ sequences. The CAMELOT approach is versatile and is generalizable for simulating the aggregation and phase behavior of a range of block-copolymeric protein sequences.

  3. CAMELOT: A machine learning approach for coarse-grained simulations of aggregation of block-copolymeric protein sequences

    SciTech Connect

    Ruff, Kiersten M.; Harmon, Tyler S.; Pappu, Rohit V.

    2015-12-28

    We report the development and deployment of a coarse-graining method that is well suited for computer simulations of aggregation and phase separation of protein sequences with block-copolymeric architectures. Our algorithm, named CAMELOT for Coarse-grained simulations Aided by MachinE Learning Optimization and Training, leverages information from converged all atom simulations that is used to determine a suitable resolution and parameterize the coarse-grained model. To parameterize a system-specific coarse-grained model, we use a combination of Boltzmann inversion, non-linear regression, and a Gaussian process Bayesian optimization approach. The accuracy of the coarse-grained model is demonstrated through direct comparisons to results from all atom simulations. We demonstrate the utility of our coarse-graining approach using the block-copolymeric sequence from the exon 1 encoded sequence of the huntingtin protein. This sequence comprises of 17 residues from the N-terminal end of huntingtin (N17) followed by a polyglutamine (polyQ) tract. Simulations based on the CAMELOT approach are used to show that the adsorption and unfolding of the wild type N17 and its sequence variants on the surface of polyQ tracts engender a patchy colloid like architecture that promotes the formation of linear aggregates. These results provide a plausible explanation for experimental observations, which show that N17 accelerates the formation of linear aggregates in block-copolymeric N17-polyQ sequences. The CAMELOT approach is versatile and is generalizable for simulating the aggregation and phase behavior of a range of block-copolymeric protein sequences.

  4. A test of systematic coarse-graining of molecular dynamics simulations: Thermodynamic properties

    NASA Astrophysics Data System (ADS)

    Fu, Chia-Chun; Kulkarni, Pandurang M.; Scott Shell, M.; Gary Leal, L.

    2012-10-01

    Coarse-graining (CG) techniques have recently attracted great interest for providing descriptions at a mesoscopic level of resolution that preserve fluid thermodynamic and transport behaviors with a reduced number of degrees of freedom and hence less computational effort. One fundamental question arises: how well and to what extent can a "bottom-up" developed mesoscale model recover the physical properties of a molecular scale system? To answer this question, we explore systematically the properties of a CG model that is developed to represent an intermediate mesoscale model between the atomistic and continuum scales. This CG model aims to reduce the computational cost relative to a full atomistic simulation, and we assess to what extent it is possible to preserve both the thermodynamic and transport properties of an underlying reference all-atom Lennard-Jones (LJ) system. In this paper, only the thermodynamic properties are considered in detail. The transport properties will be examined in subsequent work. To coarse-grain, we first use the iterative Boltzmann inversion (IBI) to determine a CG potential for a (1-ϕ)N mesoscale particle system, where ϕ is the degree of coarse-graining, so as to reproduce the radial distribution function (RDF) of an N atomic particle system. Even though the uniqueness theorem guarantees a one to one relationship between the RDF and an effective pairwise potential, we find that RDFs are insensitive to the long-range part of the IBI-determined potentials, which provides some significant flexibility in further matching other properties. We then propose a reformulation of IBI as a robust minimization procedure that enables simultaneous matching of the RDF and the fluid pressure. We find that this new method mainly changes the attractive tail region of the CG potentials, and it improves the isothermal compressibility relative to pure IBI. We also find that there are optimal interaction cutoff lengths for the CG system, as a function of

  5. Coarse Grained Molecular Dynamics Simulations of Transmembrane Protein-Lipid Systems

    PubMed Central

    Spijker, Peter; van Hoof, Bram; Debertrand, Michel; Markvoort, Albert J.; Vaidehi, Nagarajan; Hilbers, Peter A.J.

    2010-01-01

    Many biological cellular processes occur at the micro- or millisecond time scale. With traditional all-atom molecular modeling techniques it is difficult to investigate the dynamics of long time scales or large systems, such as protein aggregation or activation. Coarse graining (CG) can be used to reduce the number of degrees of freedom in such a system, and reduce the computational complexity. In this paper the first version of a coarse grained model for transmembrane proteins is presented. This model differs from other coarse grained protein models due to the introduction of a novel angle potential as well as a hydrogen bonding potential. These new potentials are used to stabilize the backbone. The model has been validated by investigating the adaptation of the hydrophobic mismatch induced by the insertion of WALP-peptides into a lipid membrane, showing that the first step in the adaptation is an increase in the membrane thickness, followed by a tilting of the peptide. PMID:20640160

  6. Molecular dynamics simulation of coarse-grained poly(L-lysine) dendrimers.

    PubMed

    Rahimi, Ali; Amjad-Iranagh, Sepideh; Modarress, Hamid

    2016-03-01

    Poly(L-lysine) (PLL) dendrimer are amino acid based macromolecules and can be used as drug delivery agents. Their branched structure allows them to be functionalized by various groups to encapsulate drug agents into their structure. In this work, at first, an attempt was made on all-atom simulation of PLL dendrimer of different generations. Based on all-atom results, a course-grained model of this dendrimer was designed and its parameters were determined, to be used for simulation of three generations of PLL dendrimer, at two pHs. Similar to the all-atom, the coarse-grained results indicated that by increasing the generation, the dendrimer becomes more spherical. At pH 7, the dendrimer had larger size, whereas at pH 12, due to back folding of branching chains, they had the tendency to penetrate into the inner layers. The calculated radial probability and radial distribution functions confirm that at pH 7, the PLL dendrimer has more cavities and as a result it can encapsulate more water molecules into its inner structure. By calculating the moment of inertia and the aspect ratio, the formation of spherical structure for PLL dendrimer was confirmed. PMID:26885845

  7. Peroxidised phospholipid bilayers: insight from coarse-grained molecular dynamics simulations.

    PubMed

    Guo, Yachong; Baulin, Vladimir A; Thalmann, Fabrice

    2016-01-01

    An original coarse-grained model for peroxidised phospholipids is presented, based on the MARTINI lipid force field. This model results from a combination of thermodynamic modelling and structural information on the area per lipid, which have been made available recently. The resulting coarse-grained lipid molecules form stable bilayers, and a set of elastic coefficients (compressibility and bending moduli) is obtained. We compare the compressibility coefficient to the experimental values [Weber et al., Soft Matter, 2014, 10, 4241]. Predictions for the mechanical properties, membrane thickness and lateral distribution of hydroperoxide groups in the phospholipid bilayer are presented. PMID:26462464

  8. Connecting Macroscopic Observables and Microscopic Assembly Events in Amyloid Formation Using Coarse Grained Simulations

    PubMed Central

    Bieler, Noah S.; Knowles, Tuomas P. J.; Frenkel, Daan; Vácha, Robert

    2012-01-01

    The pre-fibrillar stages of amyloid formation have been implicated in cellular toxicity, but have proved to be challenging to study directly in experiments and simulations. Rational strategies to suppress the formation of toxic amyloid oligomers require a better understanding of the mechanisms by which they are generated. We report Dynamical Monte Carlo simulations that allow us to study the early stages of amyloid formation. We use a generic, coarse-grained model of an amyloidogenic peptide that has two internal states: the first one representing the soluble random coil structure and the second one the -sheet conformation. We find that this system exhibits a propensity towards fibrillar self-assembly following the formation of a critical nucleus. Our calculations establish connections between the early nucleation events and the kinetic information available in the later stages of the aggregation process that are commonly probed in experiments. We analyze the kinetic behaviour in our simulations within the framework of the theory of classical nucleated polymerisation, and are able to connect the structural events at the early stages in amyloid growth with the resulting macroscopic observables such as the effective nucleus size. Furthermore, the free-energy landscapes that emerge from these simulations allow us to identify pertinent properties of the monomeric state that could be targeted to suppress oligomer formation. PMID:23071427

  9. Algorithm for simulation of quantum many-body dynamics using dynamical coarse-graining

    NASA Astrophysics Data System (ADS)

    Khasin, M.; Kosloff, R.

    2010-04-01

    An algorithm for simulation of quantum many-body dynamics having su(2) spectrum-generating algebra is developed. The algorithm is based on the idea of dynamical coarse-graining. The original unitary dynamics of the target observables—the elements of the spectrum-generating algebra—is simulated by a surrogate open-system dynamics, which can be interpreted as weak measurement of the target observables, performed on the evolving system. The open-system state can be represented by a mixture of pure states, localized in the phase space. The localization reduces the scaling of the computational resources with the Hilbert-space dimension n by factor n3/2(lnn)-1 compared to conventional sparse-matrix methods. The guidelines for the choice of parameters for the simulation are presented and the scaling of the computational resources with the Hilbert-space dimension of the system is estimated. The algorithm is applied to the simulation of the dynamics of systems of 2×104 and 2×106 cold atoms in a double-well trap, described by the two-site Bose-Hubbard model.

  10. Binding of solvated peptide (EPLQLKM) with a graphene sheet via simulated coarse-grained approach.

    PubMed

    Sheikholeslami, Somayyeh; Pandey, R B; Dragneva, Nadiya; Floriano, Wely; Rubel, Oleg; Barr, Stephen A; Kuang, Zhifeng; Berry, Rajiv; Naik, Rajesh; Farmer, Barry

    2014-05-28

    Binding of a solvated peptide A1 ((1)E (2)P (3)L (4)Q (5)L (6)K (7)M) with a graphene sheet is studied by a coarse-grained computer simulation involving input from three independent simulated interaction potentials in hierarchy. A number of local and global physical quantities such as energy, mobility, and binding profiles and radius of gyration of peptides are examined as a function of temperature (T). Quantitative differences (e.g., the extent of binding within a temperature range) and qualitative similarities are observed in results from three simulated potentials. Differences in variations of both local and global physical quantities suggest a need for such analysis with multiple inputs in assessing the reliability of both quantitative and qualitative observations. While all three potentials indicate binding at low T and unbinding at high T, the extent of binding of peptide with the temperature differs. Unlike un-solvated peptides (with little variation in binding among residues), solvation accentuates the differences in residue binding. As a result the binding of solvated peptide at low temperatures is found to be anchored by three residues, (1)E, (4)Q, and (6)K (different from that with the un-solvated peptide). Binding to unbinding transition can be described by the variation of the transverse (with respect to graphene sheet) component of the radius of gyration of the peptide (a potential order parameter) as a function of temperature. PMID:24880319

  11. Multiscale Simulations of Protein Landscapes: Using Coarse Grained Models as Reference Potentials to Full Explicit Models

    PubMed Central

    Messer, Benjamin M.; Roca, Maite; Chu, Zhen T.; Vicatos, Spyridon; Kilshtain, Alexandra Vardi; Warshel, Arieh

    2009-01-01

    Evaluating the free energy landscape of proteins and the corresponding functional aspects presents a major challenge for computer simulation approaches. This challenge is due to the complexity of the landscape and the enormous computer time needed for converging simulations. The use of simplified coarse grained (CG) folding models offers an effective way of sampling the landscape but such a treatment, however, may not give the correct description of the effect of the actual protein residues. A general way around this problem that has been put forward in our early work (Fan et al, Theor Chem Acc (1999) 103:77-80) uses the CG model as a reference potential for free energy calculations of different properties of the explicit model. This method is refined and extended here, focusing on improving the electrostatic treatment and on demonstrating key applications. This application includes: evaluation of changes of folding energy upon mutations, calculations of transition states binding free energies (which are crucial for rational enzyme design), evaluation of catalytic landscape and simulation of the time dependent responses to pH changes. Furthermore, the general potential of our approach in overcoming major challenges in studies of structure function correlation in proteins is discussed. PMID:20052756

  12. Comparing allosteric transitions in the domains of calmodulin through coarse-grained simulations

    NASA Astrophysics Data System (ADS)

    Nandigrami, Prithviraj; Portman, John J.

    2016-03-01

    Calmodulin (CaM) is a ubiquitous Ca2+-binding protein consisting of two structurally similar domains with distinct stabilities, binding affinities, and flexibilities. We present coarse grained simulations that suggest that the mechanism for the domain's allosteric transitions between the open and closed conformations depends on subtle differences in the folded state topology of the two domains. Throughout a wide temperature range, the simulated transition mechanism of the N-terminal domain (nCaM) follows a two-state transition mechanism while domain opening in the C-terminal domain (cCaM) involves unfolding and refolding of the tertiary structure. The appearance of the unfolded intermediate occurs at a higher temperature in nCaM than it does in cCaM consistent with nCaM's higher thermal stability. Under approximate physiological conditions, the simulated unfolded state population of cCaM accounts for 10% of the population with nearly all of the sampled transitions (approximately 95%) unfolding and refolding during the conformational change. Transient unfolding significantly slows the domain opening and closing rates of cCaM, which can potentially influence its Ca2+-binding mechanism.

  13. Hybrid Atomistic and Coarse-Grained Molecular Dynamics Simulations of Polyethylene Glycol (PEG) in Explicit Water.

    PubMed

    Stanzione, Francesca; Jayaraman, Arthi

    2016-05-01

    In-silico design of polymeric biomaterials requires molecular dynamics (MD) simulations that retain essential atomistic/molecular details (e.g., explicit water around the biofunctional macromolecule) while simultaneously achieving large length and time scales pertinent to macroscale function. Such large-scale atomistically detailed macromolecular MD simulations with explicit solvent representation are computationally expensive. One way to overcome this limitation is to use an adaptive resolution scheme (AdResS) in which the explicit solvent molecules dynamically adopt either atomistic or coarse-grained resolution depending on their location (e.g., near or far from the macromolecule) in the system. In this study we present the feasibility and the limitations of AdResS methodology for studying polyethylene glycol (PEG) in adaptive resolution water, for varying PEG length and architecture. We first validate the AdResS methodology for such systems, by comparing PEG and solvent structure with that from all-atom simulations. We elucidate the role of the atomistic zone size and the need for calculating thermodynamic force correction within this AdResS approach to correctly reproduce the structure of PEG and water. Lastly, by varying the PEG length and architecture, we study the hydration of PEG, and the effect of PEG architectures on the structural properties of water. Changing the architecture of PEG from linear to multiarm star, we observe reduction in the solvent accessible surface area of the PEG, and an increase in the order of water molecules in the hydration shells. PMID:27108869

  14. Coarse-grained simulation study of sequence effects on DNA hybridization in a concentrated environment.

    PubMed

    Markegard, Cade B; Fu, Iris W; Reddy, K Anki; Nguyen, Hung D

    2015-02-01

    A novel coarse-grained model is developed to elucidate thermodynamics and kinetic mechanisms of DNA self-assembly. It accounts for sequence and solvent conditions to capture key experimental results such as sequence-dependent thermal property and salt-dependent persistence length of ssDNA and dsDNA. Moreover, constant-temperature simulations on two single strands of a homogeneous sequence show two main mechanisms of hybridization: a slow slithering mechanism and a one-order faster zippering mechanism. Furthermore, large-scale simulations at a high DNA strand concentration demonstrate that DNA self-assembly is a robust and enthalpically driven process in which the formation of double helices is deciphered to occur via multiple self-assembly pathways including the strand displacement mechanism. However, sequence plays an important role in shifting the majority of one pathway over the others and controlling size distribution of self-assembled aggregates. This study yields a complex picture on the role of sequence on programmable self-assembly and demonstrates a promising simulation tool that is suitable for studies in DNA nanotechnology. PMID:25581253

  15. Elastic deformation and failure in protein filament bundles: atomistic simulations and coarse-grained modeling

    PubMed Central

    Hammond, N. A.

    2008-01-01

    The synthetic peptide RAD16-II has shown promise in tissue engineering and drug delivery. It has been studied as a vehicle for cell delivery and controlled release of IGF-1 to repair infarcted cardiac tissue, and as a scaffold to promote capillary formation for an in vitro model of angiogenesis. The structure of RAD16-II is hierarchical, with monomers forming long β-sheets that pair together to form filaments; filaments form bundles approximately 30–60 nm in diameter; branching networks of filament bundles form macroscopic gels. We investigate the mechanics of shearing between the two β-sheets constituting one filament, and between cohered filaments of RAD16-II. This shear loading is found in filament bundle bending or in tensile loading of fibers composed of partial-length filaments. Molecular dynamics simulations show that time to failure is a stochastic function of applied shear stress, and that for a given loading time behavior is elastic for sufficiently small shear loads. We propose a coarse-grained model based on Langevin dynamics that matches molecular dynamics results and facilities extending simulations in space and time. The model treats a filament as an elastic string of particles, each having potential energy that is a periodic function of its position relative to the neighboring filament. With insight from these simulations, we discuss strategies for strengthening RAD16-II and similar materials. PMID:18440063

  16. Coarse-grained simulations of proton-dependent conformational changes in lactose permease.

    PubMed

    Jewel, Yead; Dutta, Prashanta; Liu, Jin

    2016-08-01

    During lactose/H(+) symport, the Escherichia coli lactose permease (LacY) undergoes a series of global conformational transitions between inward-facing (open to cytoplasmic side) and outward-facing (open to periplasmic side) states. However, the exact local interactions and molecular mechanisms dictating those large-scale structural changes are not well understood. All-atom molecular dynamics simulations have been performed to investigate the molecular interactions involved in conformational transitions of LacY, but the simulations can only explore early or partial global structural changes because of the computational limits (< 100 ns). In this work, we implement a hybrid force field that couples the united-atom protein models with the coarse-grained MARTINI water/lipid, to investigate the proton-dependent dynamics and conformational changes of LacY. The effects of the protonation states on two key glutamate residues (Glu325 and Glu269) have been studied. Our results on the salt-bridge dynamics agreed with all-atom simulations at early short time period, validating our simulations. From our microsecond simulations, we were able to observe the complete transition from inward-facing to outward-facing conformations of LacY. Our results showed that all helices have participated during the global conformational transitions and helical movements of LacY. The inter-helical distances measured in our simulations were consistent with the double electron-electron resonance experiments at both cytoplasmic and periplasmic sides. Our simulations indicated that the deprotonation of Glu325 induced the opening of the periplasmics side and partial closure of the cytoplasmic side of LacY, while protonation of the Glu269 caused a stable cross-domain salt-bridge (Glu130-Arg344) and completely closed the cytoplasmic side. Proteins 2016; 84:1067-1074. © 2016 Wiley Periodicals, Inc. PMID:27090495

  17. A coarse-graining approach for molecular simulation that retains the dynamics of the all-atom reference system by implementing hydrodynamic interactions

    SciTech Connect

    Markutsya, Sergiy; Lamm, Monica H

    2014-11-07

    We report on a new approach for deriving coarse-grained intermolecular forces that retains the frictional contribution that is often discarded by conventional coarse-graining methods. The approach is tested for water and an aqueous glucose solution, and the results from the new implementation for coarse-grained molecular dynamics simulation show remarkable agreement with the dynamics obtained from reference all-atom simulations. The agreement between the structural properties observed in the coarse-grained and all-atom simulations is also preserved. We discuss how this approach may be applied broadly to any existing coarse-graining method where the coarse-grained models are rigorously derived from all-atom reference systems.

  18. Coarse-grained simulations of poly(propylene imine) dendrimers in solution.

    PubMed

    Smeijers, A F; Markvoort, A J; Pieterse, K; Hilbers, P A J

    2016-02-21

    The behavior of poly(propylene imine) (PPI) dendrimers in concentrated solutions has been investigated using molecular dynamics simulations containing up to a thousand PPI dendrimers of generation 4 or 5 in explicit water. To deal with large system sizes and time scales required to study the solutions over a wide range of dendrimer concentrations, a previously published coarse-grained model was applied. Simulation results on the radius of gyration, structure factor, intermolecular spacing, dendrimer interpenetration, and water penetration are compared with available experimental data, providing a clear concentration dependent molecular picture of PPI dendrimers. It is shown that with increasing concentration the dendrimer volume diminishes accompanied by a reduction of internalized water, ultimately resulting in solvent filled cavities between stacked dendrimers. Concurrently dendrimer interpenetration increases only slightly, leaving each dendrimer a separate entity also at high concentrations. Moreover, we compare apparent structure factors, as calculated in experimental studies relying on the decoupling approximation and the constant atomic form factor assumption, with directly computed structure factors. We demonstrate that these already diverge at rather low concentrations, not because of small changes in form factor, but rather because the decoupling approximation fails as monomer positions of separate dendrimers become correlated at concentrations well below the overlap concentration. PMID:26896998

  19. Coarse-Grained Simulation of Polycation/DNA-Like Complexes: Role of Neutral Block.

    PubMed

    Zhan, Bicai; Shi, Kaihang; Dong, Zhexi; Lv, Wenjie; Zhao, Shuangliang; Han, Xia; Wang, Hualin; Liu, Honglai

    2015-08-01

    Complexes formed by polycations and DNA are of great research interest because of their prospective application in gene therapy. Whereas the applications of multiblock based polycation generally exhibit promising features, a thorough understanding on the effect of neutral block incorporated in polycation is still lacking. By using coarse-grained dynamics simulation with the help of a simple model for solvent mediated interaction, we perform a theoretical study on the physicochemical properties of various polyplexes composed of a single DNA-like polyanion chain and numbers of linear polycationic chains with different modifications. By analyzing various properties, we find the hydrophobic/hydrophilic modifications of linear polycations may bring an improvement on one aspect of the properties as gene carrier but also involve a trade-off with another one. In particular, polycation with a hydrophobic middle block and a hydrophilic tail block display distinct advantages among di- and triblock linear polycations as gene carrier, while careful design of the hydrophobic block should be made to reduce the zeta potential. The simulation results are compared with available experimental data displaying good agreements. PMID:26076229

  20. Large-scale structural transitions in supercoiled DNA revealed by coarse-grained simulations

    NASA Astrophysics Data System (ADS)

    Krajina, Brad; Spakowitz, Andrew

    Topological constraints, such as DNA supercoiling, play an integral role in genomic regulation and organization in living systems. However, physical understanding of the principles that underlie DNA structure and organization at biologically-relevant length-scales remains a formidable challenge. We develop a coarse-grained simulation approach for predicting equilibrium conformations of supercoiled DNA. With this approach, we study the conformational transitions that arise due to supercoiling across the full range of supercoiling densities that are commonly explored by living systems. Simulations of ring DNA molecules with lengths up to the scale of topological domains in the E. coli chromosome (~10 kilobases) reveal large-scale structural transitions elicited by supercoiling, resulting in 3 supercoiling conformational regimes: chiral coils, extended plectonemes, and branched hyper-supercoils. These results capture the non-monotonic relationship of size versus degree of supercoiling observed in experimental sedimentation studies of supercoiled DNA, and our results provide a physical explanation of the structural transitions underlying this behavior.

  1. Supramolecular assembly of a biomineralizing antimicrobial peptide in coarse-grained Monte Carlo simulations.

    PubMed

    Eby, D Matthew; Johnson, Glenn R; Farmer, Barry L; Pandey, Ras B

    2011-01-21

    Monte Carlo simulations are used to model the self-organizing behavior of the biomineralizing peptide KSL (KKVVFKVKFK) in the presence of phosphate. Originally identified as an antimicrobial peptide, KSL also directs the formation of biosilica through a hypothetical supramolecular template that requires phosphate for assembly. Specificity of each residue and the interactions between the peptide and phosphate are considered in a coarse-grained model. Both local and global physical quantities are calculated as the constituents execute their stochastic motion in the presence and absence of phosphate. Ordered peptide aggregates develop after simulations reach thermodynamic equilibrium, wherein phosphates form bridging ligands with lysines and are found interdigitated between peptide molecules. Results demonstrate that interactions between the lysines and phosphate drive self-organization into lower energy conformations of interconnected peptide scaffolds that resemble the supramolecular structures of polypeptide- and polyamine-mediated silica condensation systems. Furthermore, the specific phosphate-peptide organization appears to mimic the zwitterionic structure of native silaffins (scaffold proteins of diatom shells), suggesting a similar template organization for silica deposition between the in vitro KSL and silaffin systems. PMID:21072418

  2. Prediction and validation of protein intermediate states from structurally rich ensembles and coarse-grained simulations.

    PubMed

    Orellana, Laura; Yoluk, Ozge; Carrillo, Oliver; Orozco, Modesto; Lindahl, Erik

    2016-01-01

    Protein conformational changes are at the heart of cell functions, from signalling to ion transport. However, the transient nature of the intermediates along transition pathways hampers their experimental detection, making the underlying mechanisms elusive. Here we retrieve dynamic information on the actual transition routes from principal component analysis (PCA) of structurally-rich ensembles and, in combination with coarse-grained simulations, explore the conformational landscapes of five well-studied proteins. Modelling them as elastic networks in a hybrid elastic-network Brownian dynamics simulation (eBDIMS), we generate trajectories connecting stable end-states that spontaneously sample the crystallographic motions, predicting the structures of known intermediates along the paths. We also show that the explored non-linear routes can delimit the lowest energy passages between end-states sampled by atomistic molecular dynamics. The integrative methodology presented here provides a powerful framework to extract and expand dynamic pathway information from the Protein Data Bank, as well as to validate sampling methods in general. PMID:27578633

  3. Coarse-grained molecular dynamics simulations of the tensile behavior of a thermosetting polymer

    NASA Astrophysics Data System (ADS)

    Yang, Shaorui; Qu, Jianmin

    2014-07-01

    Using a previously developed coarse-grained model, we conducted large-scale (˜85×85×85nm3) molecular dynamics simulations of uniaxial-strain deformation to study the tensile behavior of an epoxy molding compound, epoxy phenol novolacs (EPN) bisphenol A (BPA). Under the uniaxial-strain deformation, the material is found to exhibit cavity nucleation and growth, followed by stretching of the ligaments separated by the cavities, until the ultimate failure through ligament scissions. The nucleation sites of cavities are rather random and the subsequent cavity growth accounts for much (87%) of the volumetric change during the uniaxial-strain deformation. Ultimate failure of the materials occurs when the cavity volume fraction reaches ˜60%. During the entire deformation process, polymer strands in the network are continuously extended to their linear states and broken in the postyielding strain hardening stage. When most of the strands are stretched to their taut configurations, rapid scission of a large number of strands occurs within a small strain increment, which eventually leads to fracture. Finally, through extensive numerical simulations of various loading conditions in addition to uniaxial strain, we find that yielding of the EPN-BPA can be described by the pressure-modified von Mises yield criterion.

  4. Role of neutral lipids in tear fluid lipid layer: coarse-grained simulation study.

    PubMed

    Telenius, Jelena; Koivuniemi, Artturi; Kulovesi, Pipsa; Holopainen, Juha M; Vattulainen, Ilpo

    2012-12-11

    Tear fluid lipid layer (TFLL) residing at the air-water interface of tears has been recognized to play an important role in the development of dry eye syndrome. Yet, the composition, structure, and mechanical properties of TFLL are only partly known. Here, we report results of coarse-grained simulations of a lipid layer comprising phospholipids, free fatty acids, cholesteryl esters, and triglycerides at the air-water interface to shed light on the properties of TFLL. We consider structural as well as dynamical properties of the lipid layer as a function of surface pressure. Simulations revealed that neutral lipids reside heterogeneously between phospholipids at relatively low pressures but form a separate hydrophobic phase with increasing surface pressure, transforming the initial lipid monolayer to a two-layered structure. When the model of TFLL was compared to a one-component phospholipid monolayer system, we found drastic differences in both structural and dynamical properties that explain the prominent role of neutral lipids as stabilizers of the TFLL. Based on our results, we suggest that neutral lipids are able to increase the stability of the TFLL by modulating its dynamical and structural behavior, which is important for the proper function of tear film. PMID:23151187

  5. Defining the membrane disruption mechanism of kalata B1 via coarse-grained molecular dynamics simulations

    PubMed Central

    Nawae, Wanapinun; Hannongbua, Supa; Ruengjitchatchawalya, Marasri

    2014-01-01

    Kalata B1 has been demonstrated to have bioactivity relating to membrane disruption. In this study, we conducted coarse-grained molecular dynamics simulations to gain further insight into kB1 bioactivity. The simulations were performed at various concentrations of kB1 to capture the overall progression of its activity. Two configurations of kB1 oligomers, termed tower-like and wall-like clusters, were detected. The conjugation between the wall-like oligomers resulted in the formation of a ring-like hollow in the kB1 cluster on the membrane surface. Our results indicated that the molecules of kB1 were trapped at the membrane-water interface. The interfacial membrane binding of kB1 induced a positive membrane curvature, and the lipids were eventually extracted from the membrane through the kB1 ring-like hollow into the space inside the kB1 cluster. These findings provide an alternative view of the mechanism of kB1 bioactivity that corresponds with the concept of an interfacial bioactivity model. PMID:24492660

  6. A coarse-grained model for the simulations of biomolecular interactions in cellular environments

    SciTech Connect

    Xie, Zhong-Ru; Chen, Jiawen; Wu, Yinghao

    2014-02-07

    The interactions of bio-molecules constitute the key steps of cellular functions. However, in vivo binding properties differ significantly from their in vitro measurements due to the heterogeneity of cellular environments. Here we introduce a coarse-grained model based on rigid-body representation to study how factors such as cellular crowding and membrane confinement affect molecular binding. The macroscopic parameters such as the equilibrium constant and the kinetic rate constant are calibrated by adjusting the microscopic coefficients used in the numerical simulations. By changing these model parameters that are experimentally approachable, we are able to study the kinetic and thermodynamic properties of molecular binding, as well as the effects caused by specific cellular environments. We investigate the volumetric effects of crowded intracellular space on bio-molecular diffusion and diffusion-limited reactions. Furthermore, the binding constants of membrane proteins are currently difficult to measure. We provide quantitative estimations about how the binding of membrane proteins deviates from soluble proteins under different degrees of membrane confinements. The simulation results provide biological insights to the functions of membrane receptors on cell surfaces. Overall, our studies establish a connection between the details of molecular interactions and the heterogeneity of cellular environments.

  7. Spreading of a Unilamellar Liposome on Charged Substrates: A Coarse-Grained Molecular Simulation.

    PubMed

    Kong, Xian; Lu, Diannan; Wu, Jianzhong; Liu, Zheng

    2016-04-19

    Supported lipid bilayers (SLBs) are able to accommodate membrane proteins useful for diverse biomimetic applications. Although liposome spreading represents a common procedure for preparation of SLBs, the underlying mechanism is not yet fully understood, particularly from a molecular perspective. The present study examines the effects of the substrate charge on unilamellar liposome spreading on the basis of molecular dynamics simulations for a coarse-grained model of the solvent and lipid molecules. Liposome transformation into a lipid bilayer of different microscopic structures suggests three types of kinetic pathways depending on the substrate charge density, that is, top-receding, parachute, and parachute with wormholes. Each pathway leads to a unique distribution of the lipid molecules and thereby distinctive properties of SLBs. An increase of the substrate charge density results in a magnified asymmetry of the SLBs in terms of the ratio of charged lipids, parallel surface movements, and the distribution of lipid molecules. While the lipid mobility in the proximal layer is strongly correlated with the substrate potential, the dynamics of lipid molecules in the distal monolayer is similar to that of a freestanding lipid bilayer. For liposome spreading on a highly charged surface, wormhole formation promotes lipid exchange between the SLB monolayers thus reduces the asymmetry on the number density of lipid molecules, the lipid order parameter, and the monolayer thickness. The simulation results reveal the important regulatory role of electrostatic interactions on liposome spreading and the properties of SLBs. PMID:27019394

  8. First-principles theory, coarse-grained models, and simulations of ferroelectrics.

    PubMed

    Waghmare, Umesh V

    2014-11-18

    large-scale simulations while capturing the relevant microscopic interactions quantitatively. In this Account, we first summarize the insights obtained into chemical mechanisms of ferroelectricity using first-principles DFT calculations. We then discuss the principles of construction of first-principles model Hamiltonians for ferroelectric phase transitions in perovskite oxides, which involve coarse-graining in time domain by integrating out high frequency phonons. Molecular dynamics simulations of the resulting model are shown to give quantitative predictions of material-specific ferroelectric transition behavior in bulk as well as nanoscale ferroelectric structures. A free energy landscape obtained through coarse-graining in real-space provides deeper understanding of ferroelectric transitions, domains, and states with inhomogeneous order and points out the key role of microscopic coupling between phonons and strain. We conclude with a discussion of the multiscale modeling strategy elucidated here and its application to other materials such as shape memory alloys. PMID:25361389

  9. Simulation of gel phase formation and melting in lipid bilayers using a coarse grained model.

    PubMed

    Marrink, Siewert J; Risselada, Jelger; Mark, Alan E

    2005-06-01

    The transformation between a gel and a fluid phase in dipalmitoyl-phosphatidylcholine (DPPC) bilayers has been simulated using a coarse grained (CG) model by cooling bilayer patches composed of up to 8000 lipids. The critical step in the transformation process is the nucleation of a gel cluster consisting of 20-80 lipids, spanning both monolayers. After the formation of the critical cluster, a fast growth regime is entered. Growth slows when multiple gel domains start interacting, forming a percolating network. Long-lived fluid domains remain trapped and can be metastable on a microsecond time scale. From the temperature dependence of the rate of cluster growth, the line tension of the fluid-gel interface was estimated to be 3+/-2 pN. The reverse process is observed when heating the gel phase. No evidence is found for a hexatic phase as an intermediate stage of melting. The hysteresis observed in the freezing and melting transformation is found to depend both on the system size and on the time scale of the simulation. Extrapolating to macroscopic length and time scales, the transition temperature for heating and cooling converges to 295+/-5 K, in semi-quantitative agreement with the experimental value for DPPC (315 K). The phase transformation is associated with a drop in lateral mobility of the lipids by two orders of magnitude, and an increase in the rotational correlation time of the same order of magnitude. The lipid headgroups, however, remain fluid. These observations are in agreement with experimental findings, and show that the nature of the ordered phase obtained with the CG model is indeed a gel rather than a crystalline phase. Simulations performed at different levels of hydration furthermore show that the gel phase is stabilized at low hydration. A simulation of a small DPPC vesicle reveals that curvature has the opposite effect. PMID:15921980

  10. Computer simulation of strength and ductility of nanotwin-strengthened coarse-grained metals

    NASA Astrophysics Data System (ADS)

    Guo, X.; Ji, R.; Weng, G. J.; Zhu, L. L.; Lu, J.

    2014-10-01

    The superior strength-ductility combination in nanotwin (NT)-strengthened metals has provided a new potential for optimizing the mechanical properties of coarse-grained (CG) metals. In this paper computer simulations based on the mechanism-based strain gradient plasticity and the Johnson-Cook failure criterion have been carried out to uncover the critical factors that serve to provide this dual function. Our results indicate that both the distribution characteristics of the NT regions and the constitutive relations of the NT phase can have a significant impact on the strength and ductility of the CG Cu strengthened by the NT regions. In particular, twin spacing, distribution characteristics such as arrangement, shape and orientation, together with volume fraction of the NT regions, can all have significant effects. Along the way, we also discovered that microcrack initiation, coalescence and deflection constituted the entire failure process. Significant insights into the morphology of NT regions that could deliver superior strength and ductility combination for CG metals have been established.

  11. Dry Martini, a coarse-grained force field for lipid membrane simulations with implicit solvent.

    PubMed

    Arnarez, Clément; Uusitalo, Jaakko J; Masman, Marcelo F; Ingólfsson, Helgi I; de Jong, Djurre H; Melo, Manuel N; Periole, Xavier; de Vries, Alex H; Marrink, Siewert J

    2015-01-13

    Coarse-grained (CG) models allow simulation of larger systems for longer times by decreasing the number of degrees of freedom compared with all-atom models. Here we introduce an implicit-solvent version of the popular CG Martini model, nicknamed "Dry" Martini. To account for the omitted solvent degrees of freedom, the nonbonded interaction matrix underlying the Martini force field was reparametrized. The Dry Martini force field reproduces relatively well a variety of lipid membrane properties such as area per lipid, bilayer thickness, bending modulus, and coexistence of liquid-ordered and disordered domains. Furthermore, we show that the new model can be applied to study membrane fusion and tether formation, with results similar to those of the standard Martini model. Membrane proteins can also be included, but less quantitative results are obtained. The absence of water in Dry Martini leads to a significant speedup for large systems, opening the way to the study of complex multicomponent membranes containing millions of lipids. PMID:26574224

  12. Coarse-grained Brownian dynamics simulations of protein translocation through nanopores

    NASA Astrophysics Data System (ADS)

    Lee, Po-Hsien; Helms, Volkhard; Geyer, Tihamér

    2012-10-01

    A crucial process in biological cells is the translocation of newly synthesized proteins across cell membranes via integral membrane protein pores termed translocons. Recent improved techniques now allow producing artificial membranes with pores of similar dimensions of a few nm as the translocon system. For the translocon system, the protein has to be unfolded, whereas the artificial pores are wide enough so that small proteins can pass through even when folded. To study how proteins permeate through such membrane pores, we used coarse-grained Brownian dynamics simulations where the proteins were modeled as single beads or bead-spring polymers for both folded and unfolded states. The pores were modeled as cylindrical holes through the membrane with various radii and lengths. Diffusion was driven by a concentration gradient created across the porous membrane. Our results for both folded and unfolded configurations show the expected reciprocal relation between the flow rate and the pore length in agreement with an analytical solution derived by Brunn et al. [Q. J. Mech. Appl. Math. 37, 311 (1984)], 10.1093/qjmam/37.2.311. Furthermore, we find that the geometric constriction by the narrow pore leads to an accumulation of proteins at the pore entrance, which in turn compensates for the reduced diffusivity of the proteins inside the pore.

  13. Coarse-grained molecular dynamics simulation of water diffusion in the presence of carbon nanotubes.

    PubMed

    Lado Touriño, Isabel; Naranjo, Arisbel Cerpa; Negri, Viviana; Cerdán, Sebastián; Ballesteros, Paloma

    2015-11-01

    Computational modeling of the translational diffusion of water molecules in anisotropic environments entails vital relevance to understand correctly the information contained in the magnetic resonance images weighted in diffusion (DWI) and of the diffusion tensor images (DTI). In the present work we investigated the validity, strengths and weaknesses of a coarse-grained (CG) model based on the MARTINI force field to simulate water diffusion in a medium containing carbon nanotubes (CNTs) as models of anisotropic water diffusion behavior. We show that water diffusion outside the nanotubes follows Ficḱs law, while water diffusion inside the nanotubes is not described by a Ficḱs behavior. We report on the influence on water diffusion of various parameters such as length and concentration of CNTs, comparing the CG results with those obtained from the more accurate classic force field calculation, like the all-atom approach. Calculated water diffusion coefficients decreased in the presence of nanotubes in a concentration dependent manner. We also observed smaller water diffusion coefficients for longer CNTs. Using the CG methodology we were able to demonstrate anisotropic diffusion of water inside the nanotube scaffold, but we could not prove anisotropy in the surrounding medium, suggesting that grouping several water molecules in a single diffusing unit may affect the diffusional anisotropy calculated. The methodologies investigated in this work represent a first step towards the study of more complex models, including anisotropic cohorts of CNTs or even neuronal axons, with reasonable savings in computation time. PMID:26386454

  14. Curvature Generation and Pressure Profile Modulation in Membrane by Lysolipids: Insights from Coarse-Grained Simulations

    PubMed Central

    Yoo, Jejoong; Cui, Qiang

    2009-01-01

    Abstract Although many membrane additives are known to modulate the activities of membrane proteins via perturbing the properties of lipid membrane, the underlying mechanism is often not precisely understood. In this study, we investigate the impact of asymmetrically incorporating single-tailed lysophosphatidylcholine (LPC) into a membrane bilayer using coarse-grained molecular dynamics simulations. Using a simple computational protocol designed to approximately mimic a micropipette setting, we show that asymmetric incorporation of LPC can lead to significant curvature in a bilayer. Detailed analysis of geometrical and mechanical properties (pressure profile) of the resulting mound structure indicates that the degree of pressure profile perturbation is determined not by the local curvature per se but by the packing of lipid headgroups (i.e., area-per-lipid). The findings help provide a concrete basis for understanding the activation mechanism of mechanosensitive channels by asymmetric incorporation of LPC into membrane patches in patch-clamp experiments. The calculated local pressure profiles are valuable to the construction of realistic membrane models for the analysis of mechanosensation in a continuum mechanics framework. PMID:19843459

  15. Membrane Association of the Diphtheria Toxin Translocation Domain Studied by Coarse-Grained Simulations and Experiment.

    PubMed

    Flores-Canales, Jose C; Vargas-Uribe, Mauricio; Ladokhin, Alexey S; Kurnikova, Maria

    2015-06-01

    Diphtheria toxin translocation (T) domain inserts in lipid bilayers upon acidification of the environment. Computational and experimental studies have suggested that low pH triggers a conformational change of the T-domain in solution preceding membrane binding. The refolded membrane-competent state was modeled to be compact and mostly retain globular structure. In the present work, we investigate how this refolded state interacts with membrane interfaces in the early steps of T-domain's membrane association. Coarse-grained molecular dynamics simulations suggest two distinct membrane-bound conformations of the T-domain in the presence of bilayers composed of a mixture of zwitteronic and anionic phospholipids (POPC:POPG with a 1:3 molar ratio). Both membrane-bound conformations show a common near parallel orientation of hydrophobic helices TH8-TH9 relative to the membrane plane. The most frequently observed membrane-bound conformation is stabilized by electrostatic interactions between the N-terminal segment of the protein and the membrane interface. The second membrane-bound conformation is stabilized by hydrophobic interactions between protein residues and lipid acyl chains, which facilitate deeper protein insertion in the membrane interface. A theoretical estimate of a free energy of binding of a membrane-competent T-domain to the membrane is provided. PMID:25650178

  16. Thermodynamically Consistent Coarse-Graining of Polymers

    NASA Astrophysics Data System (ADS)

    Guenza, Marina

    2015-03-01

    Structural and dynamical properties of macromolecular liquids, melts and mixtures, bridge an extensive range of length- and time-scales. For these systems, the computational limitations of the atomistic description prevent the study of the properties of interest and coarse-grained models remain the only viable approach. In coarse-grained models, structural and thermodynamic consistency across multiple length scales is essential for the predictive role of multi-scale modeling and molecular dynamic simulations that use mesoscale descriptions. This talk presents a coarse-graining approach that conserves structural and thermodynamic quantities independent of the extent of coarse-graining, and describes a model for the reconstruction of the dynamics measured in mesoscale simulations of the coarse-grained system. Some of the general challenges of preserving structural and thermodynamic consistency in coarse-grained models are discussed together with the conditions by which the problem is lessened. This material is based upon work partially supported by the National Science Foundation under Grant No. CHE-1362500.

  17. Coarse-graining methods for computational biology.

    PubMed

    Saunders, Marissa G; Voth, Gregory A

    2013-01-01

    Connecting the molecular world to biology requires understanding how molecular-scale dynamics propagate upward in scale to define the function of biological structures. To address this challenge, multiscale approaches, including coarse-graining methods, become necessary. We discuss here the theoretical underpinnings and history of coarse-graining and summarize the state of the field, organizing key methodologies based on an emerging paradigm for multiscale theory and modeling of biomolecular systems. This framework involves an integrated, iterative approach to couple information from different scales. The primary steps, which coincide with key areas of method development, include developing first-pass coarse-grained models guided by experimental results, performing numerous large-scale coarse-grained simulations, identifying important interactions that drive emergent behaviors, and finally reconnecting to the molecular scale by performing all-atom molecular dynamics simulations guided by the coarse-grained results. The coarse-grained modeling can then be extended and refined, with the entire loop repeated iteratively if necessary. PMID:23451897

  18. Simulating Cellulose Structure, Properties, Thermodynamics, Synthesis, and Deconstruction with Atomistic and Coarse-Grain Models

    SciTech Connect

    Crowley, M. F.; Matthews, J.; Beckham, G.; Bomble, Y.; Hynninen, A. P.; Ciesielski, P. F.

    2012-01-01

    Cellulose is still a mysterious polymer in many ways: structure of microfibrils, thermodynamics of synthesis and degradation, and interactions with other plant cell wall components. Our aim is to uncover the details and mechanisms of cellulose digestion and synthesis. We report the details of the structure of cellulose 1-beta under several temperature conditions and report here the results of these studies and connections to experimental measurements and the measurement in-silico the free energy of decrystallization of several morphologies of cellulose. In spatially large modeling, we show the most recent work of mapping atomistic and coarse-grain models into tomographic images of cellulose and extreme coarse-grain modeling of interactions of large cellulase complexes with microfibrils. We discuss the difficulties of modeling cellulose and suggest future work both experimental and theoretical to increase our understanding of cellulose and our ability to use it as a raw material for fuels and materials.

  19. Modeling Structural Dynamics of Biomolecular Complexes by Coarse-Grained Molecular Simulations.

    PubMed

    Takada, Shoji; Kanada, Ryo; Tan, Cheng; Terakawa, Tsuyoshi; Li, Wenfei; Kenzaki, Hiroo

    2015-12-15

    Due to hierarchic nature of biomolecular systems, their computational modeling calls for multiscale approaches, in which coarse-grained (CG) simulations are used to address long-time dynamics of large systems. Here, we review recent developments and applications of CG modeling methods, focusing on our methods primarily for proteins, DNA, and their complexes. These methods have been implemented in the CG biomolecular simulator, CafeMol. Our CG model has resolution such that ∼10 non-hydrogen atoms are grouped into one CG particle on average. For proteins, each amino acid is represented by one CG particle. For DNA, one nucleotide is simplified by three CG particles, representing sugar, phosphate, and base. The protein modeling is based on the idea that proteins have a globally funnel-like energy landscape, which is encoded in the structure-based potential energy function. We first describe two representative minimal models of proteins, called the elastic network model and the classic Go̅ model. We then present a more elaborate protein model, which extends the minimal model to incorporate sequence and context dependent local flexibility and nonlocal contacts. For DNA, we describe a model developed by de Pablo's group that was tuned to well reproduce sequence-dependent structural and thermodynamic experimental data for single- and double-stranded DNAs. Protein-DNA interactions are modeled either by the structure-based term for specific cases or by electrostatic and excluded volume terms for nonspecific cases. We also discuss the time scale mapping in CG molecular dynamics simulations. While the apparent single time step of our CGMD is about 10 times larger than that in the fully atomistic molecular dynamics for small-scale dynamics, large-scale motions can be further accelerated by two-orders of magnitude with the use of CG model and a low friction constant in Langevin dynamics. Next, we present four examples of applications. First, the classic Go̅ model was used to

  20. Concurrent Multiscale Simulation at Finite Temperature: Coarse-Grained Molecular Dynamics

    SciTech Connect

    Rudd, R E

    2004-01-22

    With the advent of nanotechnology, predictive simulations of nanoscale systems have become in great demand. In some cases nanoscale systems can be simulated directly at the level of atoms. The atomistic techniques used range from models based on a quantum mechanical treatment of the electronic bonds to those based on more empirical descriptions of the interatomic forces. In many cases, however, even nanoscale systems are too big for a purely atomistic approach, typically because the nanoscale device is coupled to its surroundings, and it is necessary to simulate the entire system comprising billions of atoms. A well-known example is the growth of nanoscale epitaxial quantum dots in which the size, shape and location of the dot is affected by the elastic strain developed in a large volume of the substrate as well as the local atomic bonding. The natural solution is to model the surroundings with a more coarse-grained description, suitable for the intrinsically longer length scale. The challenge then is to develop the computational methodology suitable for this kind of concurrent multiscale modeling, one in which the simulated length scale can be changed smoothly and seamlessly from one region of the simulation to another while maintaining the fidelity of the relevant mechanics, dynamics and thermodynamics. The realization that Nature has different relevant length scales goes back at least as far as Democritus. Some 24 centuries ago he put forward the idea that solid matter is comprised ultimately at small scales by a fundamental constituent that he termed an atom. Implicit in his philosophy was the idea that an understanding of the atom would lead to a more robust understanding of the macroscopic world around us. In the intervening period, of course, not only has the science of this atomistic picture been put on a sound footing through the inventions of chemistry, the discovery of the nucleus and the development of quantum mechanics and modern condensed matter

  1. On interfacial properties of tetrahydrofuran: Atomistic and coarse-grained models from molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Garrido, J. M.; Algaba, J.; Míguez, J. M.; Mendiboure, B.; Moreno-Ventas Bravo, A. I.; Piñeiro, M. M.; Blas, F. J.

    2016-04-01

    We have determined the interfacial properties of tetrahydrofuran (THF) from direct simulation of the vapor-liquid interface. The molecules are modeled using six different molecular models, three of them based on the united-atom approach and the other three based on a coarse-grained (CG) approach. In the first case, THF is modeled using the transferable parameters potential functions approach proposed by Chandrasekhar and Jorgensen [J. Chem. Phys. 77, 5073 (1982)] and a new parametrization of the TraPPE force fields for cyclic alkanes and ethers [S. J. Keasler et al., J. Phys. Chem. B 115, 11234 (2012)]. In both cases, dispersive and coulombic intermolecular interactions are explicitly taken into account. In the second case, THF is modeled as a single sphere, a diatomic molecule, and a ring formed from three Mie monomers according to the SAFT-γ Mie top-down approach [V. Papaioannou et al., J. Chem. Phys. 140, 054107 (2014)]. Simulations were performed in the molecular dynamics canonical ensemble and the vapor-liquid surface tension is evaluated from the normal and tangential components of the pressure tensor along the simulation box. In addition to the surface tension, we have also obtained density profiles, coexistence densities, critical temperature, density, and pressure, and interfacial thickness as functions of temperature, paying special attention to the comparison between the estimations obtained from different models and literature experimental data. The simulation results obtained from the three CG models as described by the SAFT-γ Mie approach are able to predict accurately the vapor-liquid phase envelope of THF, in excellent agreement with estimations obtained from TraPPE model and experimental data in the whole range of coexistence. However, Chandrasekhar and Jorgensen model presents significant deviations from experimental results. We also compare the predictions for surface tension as obtained from simulation results for all the models with

  2. On interfacial properties of tetrahydrofuran: Atomistic and coarse-grained models from molecular dynamics simulation.

    PubMed

    Garrido, J M; Algaba, J; Míguez, J M; Mendiboure, B; Moreno-Ventas Bravo, A I; Piñeiro, M M; Blas, F J

    2016-04-14

    We have determined the interfacial properties of tetrahydrofuran (THF) from direct simulation of the vapor-liquid interface. The molecules are modeled using six different molecular models, three of them based on the united-atom approach and the other three based on a coarse-grained (CG) approach. In the first case, THF is modeled using the transferable parameters potential functions approach proposed by Chandrasekhar and Jorgensen [J. Chem. Phys. 77, 5073 (1982)] and a new parametrization of the TraPPE force fields for cyclic alkanes and ethers [S. J. Keasler et al., J. Phys. Chem. B 115, 11234 (2012)]. In both cases, dispersive and coulombic intermolecular interactions are explicitly taken into account. In the second case, THF is modeled as a single sphere, a diatomic molecule, and a ring formed from three Mie monomers according to the SAFT-γ Mie top-down approach [V. Papaioannou et al., J. Chem. Phys. 140, 054107 (2014)]. Simulations were performed in the molecular dynamics canonical ensemble and the vapor-liquid surface tension is evaluated from the normal and tangential components of the pressure tensor along the simulation box. In addition to the surface tension, we have also obtained density profiles, coexistence densities, critical temperature, density, and pressure, and interfacial thickness as functions of temperature, paying special attention to the comparison between the estimations obtained from different models and literature experimental data. The simulation results obtained from the three CG models as described by the SAFT-γ Mie approach are able to predict accurately the vapor-liquid phase envelope of THF, in excellent agreement with estimations obtained from TraPPE model and experimental data in the whole range of coexistence. However, Chandrasekhar and Jorgensen model presents significant deviations from experimental results. We also compare the predictions for surface tension as obtained from simulation results for all the models with

  3. Impact into Coarse Grained Spheres

    NASA Technical Reports Server (NTRS)

    Barnouin-Jha, O. S.; Cintala, M.; Crawford, D. A.

    2005-01-01

    Several experimental studies [1,2,3] indicate that differences in the grain size of the target relative to the projectile could influence the cratering process. Impacts into coarse sand grains of size comparable to the projectile show some discrepancies with existing relationships for crater growth [e.g. 4]. Similarly, targets of ne grained, uniform in diameter glass spheres show differences in crater depth, transient crater diameter, and volume of ejecta excavated as a function of grain size [2,3]. The purpose of this work is to continue investigating how the relative grain size may influence early time coupling between a projectile and target, with implications for subsequent ejecta excavation and crater growth. In previous efforts we used numerical techniques to focus on the propagation of shock waves in coarse, granular media emphasizing the influence of relative grain size on crater growth, ejecta production, cratering efficiency, target strength, and crater shape [5,6,7]. In this study, we use experimental techniques - in part as a reality check for the numerical studies - to report on how coarse grained targets might influence ejecta excavation and crater shape. This body of work possesses important implications for ejecta excavation and cratering efficiency on asteroids that may possess rubble pile-like structures, and on planets that may possess either pre-fractured surfaces or large-scale heterogeneities in shock impedance.

  4. Association, intrinsic shape, and molecular recognition: Elucidating DNA biophysics through coarse-grained simulation

    NASA Astrophysics Data System (ADS)

    Freeman, Gordon Samuel

    DNA is of central importance in biology as it is responsible for carrying, copying, and translating the genetic code into the building blocks that comprise life. In order to accomplish these tasks, the DNA molecule must be versatile and robust. Indeed, the underlying molecular interactions that allow DNA to execute these tasks are complex and their origins are only beginning to be understood. While experiments are able to elucidate many key biophysical phenomena, there remain many unanswered questions. Molecular simulation is able to shed light on phenomena at the molecular scale and provide information that is missing from experimental views of DNA behavior. In this dissertation I use state-of-the-art coarse-grained DNA models to address two key problems. In the first, metadynamics calculations are employed to uncover the free energy surface of two complimentary DNA strands. This free energy surface takes on the appearance of a hybridization funnel and reveals candidates for intermediate states in the hybridization of short DNA oligomers. Such short oligomers are important building blocks for DNA-driven self-assembly and the mechanism of hybridization in this regime is not well understood. The second problem is that of nucleosome formation. Nucleosomes are the fundamental subunit of genome compaction in the nucleus of a cell. As such, nucleosomes are a key epigenetic factor and affect gene expression and the ability of DNA-binding proteins to locate and bind to the appropriate position in the genome. However, the factors that drive nucleosome positioning are not well understood. While DNA sequence is known to affect nucleosome formation, the mechanism by which it does so has not been established and a number of hypotheses explaining this sequence-dependence exist in the literature. I demonstrate that DNA shape dominates this process with contributions arising from both intrinsic DNA curvature as well as DNA-protein interactions driven by sequence

  5. Assembly of Influenza Hemagglutinin Fusion Peptides in a Phospholipid Bilayer by Coarse-grained Computer Simulations

    PubMed Central

    Collu, Francesca; Spiga, Enrico; Lorenz, Christian D.; Fraternali, Franca

    2015-01-01

    Membrane fusion is critical to eukaryotic cellular function and crucial to the entry of enveloped viruses such as influenza and human immunodeficiency virus. Influenza viral entry in the host cell is mediated by a 20–23 amino acid long sequence, called the fusion peptide (FP). Recently, possible structures for the fusion peptide (ranging from an inverted V shaped α-helical structure to an α-helical hairpin, or to a complete α-helix) and their implication in the membrane fusion initiation have been proposed. Despite the large number of studies devoted to the structure of the FP, the mechanism of action of this peptide remains unclear with several mechanisms having been suggested, including the induction of local disorder, promoting membrane curvature, and/or altering local membrane composition. In recent years, several research groups have employed atomistic and/or coarse-grained molecular dynamics (MD) simulations to investigate the matter. In all previous works, the behavior of a single FP monomer was studied, while in this manuscript, we use a simplified model of a tripeptide (TP) monomer of FP (TFP) instead of a single FP monomer because each Influenza Hemagglutinin contains three FP molecules in the biological system. In this manuscript we report findings targeted at understanding the fusogenic properties and the collective behavior of these trimers of FP peptides on a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine model membrane. Here we show how the TFP monomers self-assemble into differently sized oligomers in the presence of the membrane. We measure the perturbation to the structure of the phospholipid membrane caused by the presence of these TFP oligomers. Our work (i) shows how self-assembly of TFP in the presence of the membrane induces non negligible deformation to the membrane and (ii) could be a useful starting point to stimulate discussion and further work targeted to fusion pore formation. PMID:26636093

  6. Why do arginine and lysine organize lipids differently? Insights from coarse-grained and atomistic simulations.

    PubMed

    Wu, Zhe; Cui, Qiang; Yethiraj, Arun

    2013-10-10

    An important puzzle in membrane biophysics is the difference in the behaviors of lysine (Lys) and arginine (Arg) based peptides at the membrane. For example, the translocation of poly-Arg is orders of magnitude faster than that of poly-Lys. Recent experimental work suggests that much of the difference can be inferred from the phase behavior of peptide/lipid mixtures. At similar concentrations, mixtures of phosphatidylethanolamine (PE) and phosphatidylserine (PS) lipids display different phases in the presence of these polypeptides, with a bicontinuous phase observed with poly-Arg peptides and an inverted hexagonal phase observed with poly-Lys peptides. Here we show that simulations with the coarse-grained (CG) BMW-MARTINI model reproduce the experimental results. An analysis using atomistic and CG models reveals that electrostatic and glycerol-peptide interactions play a crucial role in determining the phase behavior of peptide-lipid mixtures, with the difference between Arg and Lys arising from the stronger interactions of the former with lipid glycerols. In other words, the multivalent nature of the guanidinium group allows Arg to simultaneously interact with both phosphate and glycerol groups, while Lys engages solely with phosphate; this feature of amino acid/lipid interactions has not been emphasized in previous studies. The Arg peptides colocalize with PS in regions of high negative Gaussian curvature and stabilize the bicontinuous phase. Decreasing the strength of either the electrostatic interactions or the peptide-glycerol interactions causes the inverted hexagonal phase to become more stable. The results highlight the utility of CG models for the investigation of phase behavior but also emphasize the subtlety of the phenomena, with small changes in specific interactions leading to qualitatively different phases. PMID:24024591

  7. Role of Ionic Clusters in Dynamics of Ionomer Melts: From Atomistic to Coarse Grained Simulations

    NASA Astrophysics Data System (ADS)

    Agrawal, Anupriya

    Ionomers, polymers decorated with ionizable groups, have found application in numerous technologies where ionic transport is required. The ionic groups associate into random clusters resulting in substantial effect on structure, dynamics and transport of these materials. The effects of topology, size and dynamics of these aggregates however remain an open question. Here we probe cluster formation correlated with polymer dynamics through a model system of randomly sulfonated polystyrene (SPS) melts with molecular dynamics (MD) simulations over a broad time and length scales ranging from that within the ionic clusters through polymer segmental dynamics to the motion of the entire molecules. The cluster evolution was probed by fully atomistic studies. We find ladder-like aggregates that transform to globule-like with increasing the dielectric constant of media for sodium neutralized SPS. With increasing dielectric constant, the size of the aggregates decrease and their number increases. Concurrently, the mobility of the polymer increases. The counterion radius and valency affect both morphology and dynamics as is evident in the calculated static and dynamic structure factors. It is further manifested in the results of viscosity obtained through non-equilibrium molecular dynamics technique. Finally, to access larger length scales a three bead coarse-grained model to describe sulfonated styrene that we have developed will be discussed in view of the outstanding challenges in ionic polymers. Supported in part by DOE Grant No. DE-SC007908. This work was carried out in collaboration with Dvora Perahia and Gary Grest while I was a postdoc at Clemson University. I gratefully acknowledge both of them for their support and encouragement.

  8. Shock Simulations of Single-Site Coarse-Grain RDX using the Dissipative Particle Dynamics Method with Reactivity

    NASA Astrophysics Data System (ADS)

    Sellers, Michael; Lisal, Martin; Schweigert, Igor; Larentzos, James; Brennan, John

    2015-06-01

    In discrete particle simulations, when an atomistic model is coarse-grained, a trade-off is made: a boost in computational speed for a reduction in accuracy. Dissipative Particle Dynamics (DPD) methods help to recover accuracy in viscous and thermal properties, while giving back a small amount of computational speed. One of the most notable extensions of DPD has been the introduction of chemical reactivity, called DPD-RX. Today, pairing the current evolution of DPD-RX with a coarse-grained potential and its chemical decomposition reactions allows for the simulation of the shock behavior of energetic materials at a timescale faster than an atomistic counterpart. In 2007, Maillet et al. introduced implicit chemical reactivity in DPD through the concept of particle reactors and simulated the decomposition of liquid nitromethane. We have recently extended the DPD-RX method and have applied it to solid hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) under shock conditions using a recently developed single-site coarse-grain model and a reduced RDX decomposition mechanism. A description of the methods used to simulate RDX and its tranition to hot product gases within DPD-RX will be presented. Additionally, examples of the effect of microstructure on shock behavior will be shown. Approved for public release. Distribution is unlimited.

  9. Tunable Coarse Graining for Monte Carlo Simulations of Proteins via Smoothed Energy Tables: Direct and Exchange Simulations

    PubMed Central

    2015-01-01

    Many commonly used coarse-grained models for proteins are based on simplified interaction sites and consequently may suffer from significant limitations, such as the inability to properly model protein secondary structure without the addition of restraints. Recent work on a benzene fluid (LettieriS.; ZuckermanD. M.J. Comput. Chem.2012, 33, 268−27522120971) suggested an alternative strategy of tabulating and smoothing fully atomistic orientation-dependent interactions among rigid molecules or fragments. Here we report our initial efforts to apply this approach to the polar and covalent interactions intrinsic to polypeptides. We divide proteins into nearly rigid fragments, construct distance and orientation-dependent tables of the atomistic interaction energies between those fragments, and apply potential energy smoothing techniques to those tables. The amount of smoothing can be adjusted to give coarse-grained models that range from the underlying atomistic force field all the way to a bead-like coarse-grained model. For a moderate amount of smoothing, the method is able to preserve about 70–90% of the α-helical structure while providing a factor of 3–10 improvement in sampling per unit computation time (depending on how sampling is measured). For a greater amount of smoothing, multiple folding–unfolding transitions of the peptide were observed, along with a factor of 10–100 improvement in sampling per unit computation time, although the time spent in the unfolded state was increased compared with less smoothed simulations. For a β hairpin, secondary structure is also preserved, albeit for a narrower range of the smoothing parameter and, consequently, for a more modest improvement in sampling. We have also applied the new method in a “resolution exchange” setting, in which each replica runs a Monte Carlo simulation with a different degree of smoothing. We obtain exchange rates that compare favorably to our previous efforts at resolution exchange

  10. Coarse-grained simulation of molecular mechanisms of recovery in thermally activated shape-memory polymers

    NASA Astrophysics Data System (ADS)

    Abberton, Brendan C.; Liu, Wing Kam; Keten, Sinan

    2013-12-01

    Thermally actuated shape-memory polymers (SMPs) are capable of being programmed into a temporary shape and then recovering their permanent reference shape upon exposure to heat, which facilitates a phase transition that allows dramatic increase in molecular mobility. Experimental, analytical, and computational studies have established empirical relations of the thermomechanical behavior of SMPs that have been instrumental in device design. However, the underlying mechanisms of the recovery behavior and dependence on polymer microstructure remain to be fully understood for copolymer systems. This presents an opportunity for bottom-up studies through molecular modeling; however, the limited time-scales of atomistic simulations prohibit the study of key performance metrics pertaining to recovery. In order to elucidate the effects of phase fraction, recovery temperature, and deformation temperature on shape recovery, here we investigate the shape-memory behavior in a copolymer model with coarse-grained potentials using a two-phase molecular model that reproduces physical crosslinking. Our simulation protocol allows observation of upwards of 90% strain recovery in some cases, at time-scales that are on the order of the timescale of the relevant relaxation mechanism (stress relaxation in the unentangled soft-phase). Partial disintegration of the glassy phase during mechanical deformation is found to contribute to irrecoverable strain. Temperature dependence of the recovery indicates nearly full elastic recovery above the trigger temperature, which is near the glass-transition temperature of the rubbery switching matrix. We find that the trigger temperature is also directly correlated with the deformation temperature, indicating that deformation temperature influences the recovery temperatures required to obtain a given amount of shape recovery, until the plateau regions overlap above the transition region. Increasing the fraction of glassy phase results in higher strain

  11. Coarse-grained analysis of stochastically simulated cell populations with a positive feedback genetic network architecture.

    PubMed

    Aviziotis, I G; Kavousanakis, M E; Bitsanis, I A; Boudouvis, A G

    2015-06-01

    Among the different computational approaches modelling the dynamics of isogenic cell populations, discrete stochastic models can describe with sufficient accuracy the evolution of small size populations. However, for a systematic and efficient study of their long-time behaviour over a wide range of parameter values, the performance of solely direct temporal simulations requires significantly high computational time. In addition, when the dynamics of the cell populations exhibit non-trivial bistable behaviour, such an analysis becomes a prohibitive task, since a large ensemble of initial states need to be tested for the quest of possibly co-existing steady state solutions. In this work, we study cell populations which carry the lac operon network exhibiting solution multiplicity over a wide range of extracellular conditions (inducer concentration). By adopting ideas from the so-called "equation-free" methodology, we perform systems-level analysis, which includes numerical tasks such as the computation of coarse steady state solutions, coarse bifurcation analysis, as well as coarse stability analysis. Dynamically stable and unstable macroscopic (population level) steady state solutions are computed by means of bifurcation analysis utilising short bursts of fine-scale simulations, and the range of bistability is determined for different sizes of cell populations. The results are compared with the deterministic cell population balance model, which is valid for large populations, and we demonstrate the increased effect of stochasticity in small size populations with asymmetric partitioning mechanisms. PMID:24929336

  12. All-atom and coarse-grained simulations of the forced unfolding pathways of the SNARE complex.

    PubMed

    Zheng, Wenjun

    2014-07-01

    The SNARE complex, consisting of three proteins (VAMP2, syntaxin, and SNAP-25), is thought to drive membrane fusion by assembling into a four-helix bundle through a zippering process. In support of the above zippering model, a recent single-molecule optical tweezers experiment by Gao et al. revealed a sequential unzipping of SNARE along VAMP2 in the order of the linker domain → the C-terminal domain → the N-terminal domain. To offer detailed structural insights to this unzipping process, we have performed all-atom and coarse-grained steered molecular dynamics (sMD) simulations of the forced unfolding pathways of SNARE using different models and force fields. Our findings are summarized as follows: First, the sMD simulations based on either an all-atom force field (with an implicit solvent model) or a coarse-grained Go model were unable to capture the forced unfolding pathway of SNARE as observed by Gao et al., which may be attributed to insufficient simulation time and inaccurate force fields. Second, the sMD simulations based on a reparameterized coarse-grained model (i.e., modified elastic network model) were able to predict a sequential unzipping of SNARE in good agreement with the findings by Gao et al. The key to this success is to reparameterize the intrahelix and interhelix nonbonded force constants against the pair-wise residue-residue distance fluctuations collected from all-atom MD simulations of SNARE. Therefore, our finding supports the importance of accurately describing the inherent dynamics/flexibility of SNARE (in the absence of force), in order to correctly simulate its unfolding behaviors under force. This study has established a useful computational framework for future studies of the zippering function of SNARE and its perturbations by point mutations with amino-acid level of details, and more generally the forced unfolding pathways of other helix bundle proteins. PMID:24403006

  13. Coarse-graining in peridynamics.

    SciTech Connect

    Silling, Stewart Andrew

    2010-11-01

    The peridynamic theory is an extension of traditional solid mechanics that treats discontinuous media, including the evolution of discontinuities due to fracture, on the same mathematical basis as classically smooth media. A recent advance in the linearized peridynamic theory permits the reduction of the number of degrees of freedom modeled within a body. Under equilibrium conditions, this coarse graining method exactly reproduces the internal forces on the coarsened degrees of freedom, including the effect of the omitted material that is no longer explicitly modeled. The method applies to heterogeneous as well as homogeneous media and accounts for defects in the material. The coarse graining procedure can be repeated over and over, resulting in a hierarchically coarsened description that, at each stage, continues to reproduce the exact internal forces present in the original, detailed model. Each coarsening step results in reduced computational cost. This talk will describe the new peridynamic coarsening method and show computational examples.

  14. An improved fast multipole method for electrostatic potential calculations in a class of coarse-grained molecular simulations

    SciTech Connect

    Poursina, Mohammad; Anderson, Kurt S.

    2014-08-01

    This paper presents a novel algorithm to approximate the long-range electrostatic potential field in the Cartesian coordinates applicable to 3D coarse-grained simulations of biopolymers. In such models, coarse-grained clusters are formed via treating groups of atoms as rigid and/or flexible bodies connected together via kinematic joints. Therefore, multibody dynamic techniques are used to form and solve the equations of motion of such coarse-grained systems. In this article, the approximations for the potential fields due to the interaction between a highly negatively/positively charged pseudo-atom and charged particles, as well as the interaction between clusters of charged particles, are presented. These approximations are expressed in terms of physical and geometrical properties of the bodies such as the entire charge, the location of the center of charge, and the pseudo-inertia tensor about the center of charge of the clusters. Further, a novel substructuring scheme is introduced to implement the presented far-field potential evaluations in a binary tree framework as opposed to the existing quadtree and octree strategies of implementing fast multipole method. Using the presented Lagrangian grids, the electrostatic potential is recursively calculated via sweeping two passes: assembly and disassembly. In the assembly pass, adjacent charged bodies are combined together to form new clusters. Then, the potential field of each cluster due to its interaction with faraway resulting clusters is recursively calculated in the disassembly pass. The method is highly compatible with multibody dynamic schemes to model coarse-grained biopolymers. Since the proposed method takes advantage of constant physical and geometrical properties of rigid clusters, improvement in the overall computational cost is observed comparing to the tradition application of fast multipole method.

  15. Coarse-grained molecular dynamics simulation of the void growth process in the block structure of semicrystalline polymers

    NASA Astrophysics Data System (ADS)

    Higuchi, Yuji; Kubo, Momoji

    2016-06-01

    We study fracture processes of amorphous and semicrystalline polymers with a coarse-grained molecular dynamics simulation. In the amorphous state, the stress caused by strain mainly arises from the loss of the attractive interaction in the voids. However, in semicrystalline polymers, the elongation of bonding is the dominant factor and it causes much more stress than that in an amorphous state. This is because growth of the voids is prevented by the amorphous regions and it is difficult to relax the folded polymers.

  16. A combined coarse-grained and all-atom simulation of TRPV1 channel gating and heat activation

    PubMed Central

    Qin, Feng

    2015-01-01

    The transient receptor potential (TRP) channels act as key sensors of various chemical and physical stimuli in eukaryotic cells. Despite years of study, the molecular mechanisms of TRP channel activation remain unclear. To elucidate the structural, dynamic, and energetic basis of gating in TRPV1 (a founding member of the TRPV subfamily), we performed coarse-grained modeling and all-atom molecular dynamics (MD) simulation based on the recently solved high resolution structures of the open and closed form of TRPV1. Our coarse-grained normal mode analysis captures two key modes of collective motions involved in the TRPV1 gating transition, featuring a quaternary twist motion of the transmembrane domains (TMDs) relative to the intracellular domains (ICDs). Our transition pathway modeling predicts a sequence of structural movements that propagate from the ICDs to the TMDs via key interface domains (including the membrane proximal domain and the C-terminal domain), leading to sequential opening of the selectivity filter followed by the lower gate in the channel pore (confirmed by modeling conformational changes induced by the activation of ICDs). The above findings of coarse-grained modeling are robust to perturbation by lipids. Finally, our MD simulation of the ICD identifies key residues that contribute differently to the nonpolar energy of the open and closed state, and these residues are predicted to control the temperature sensitivity of TRPV1 gating. These computational predictions offer new insights to the mechanism for heat activation of TRPV1 gating, and will guide our future electrophysiology and mutagenesis studies. PMID:25918362

  17. Coarse-grained simulations for organic molecular liquids based on Gay-Berne and electric multipole potentials.

    PubMed

    Xu, Peijun; Shen, Hujun; Yang, Lu; Ding, Yang; Li, Beibei; Shao, Ying; Mao, Yingchen; Li, Guohui

    2013-02-01

    Coarse-grained studies of CH(3)SH, CH(3)CHO and CHCl(3) liquids, based on anisotropic Gay-Berne (GB) and electric multipole potentials (EMP), demonstrate that the coarse-grained model is able to qualitatively reproduce the results obtained from the atomistic model (AMOEBA polarizable force field) and allows for significant saving in computation time. It should be pointed out that the accuracy of the coarse-grained model is very sensitive to how well the anisotropic GB particle is defined and how satisfactorily the EMP sites are chosen. PMID:22961621

  18. Glass Formation of n-Butanol: Coarse-grained Molecular Dynamics Simulations Using Gay-Berne Potential Model

    NASA Astrophysics Data System (ADS)

    Xie, Gui-long; Zhang, Yong-hong; Huang, Shi-ping

    2012-04-01

    Using coarse-grained molecular dynamics simulations based on Gay-Berne potential model, we have simulated the cooling process of liquid n-butanol. A new set of GB parameters are obtained by fitting the results of density functional theory calculations. The simulations are carried out in the range of 290-50 K with temperature decrements of 10 K. The cooling characteristics are determined on the basis of the variations of the density, the potential energy and orientational order parameter with temperature, whose slopes all show discontinuity. Both the radial distribution function curves and the second-rank orientational correlation function curves exhibit splitting in the second peak. Using the discontinuous change of these thermodynamic and structure properties, we obtain the glass transition at an estimate of temperature Tg=120±10 K, which is in good agreement with experimental results 110±1 K.

  19. Coarse-grained modelling of triglyceride crystallisation: a molecular insight into tripalmitin tristearin binary mixtures by molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Pizzirusso, Antonio; Brasiello, Antonio; De Nicola, Antonio; Marangoni, Alejandro G.; Milano, Giuseppe

    2015-12-01

    The first simulation study of the crystallisation of a binary mixture of triglycerides using molecular dynamics simulations is reported. Coarse-grained models of tristearin (SSS) and tripalmitin (PPP) molecules have been considered. The models have been preliminarily tested in the crystallisation of pure SSS and PPP systems. Two different quenching procedures have been tested and their performances have been analysed. The structures obtained from the crystallisation procedures show a high orientation order and a high content of molecules in the tuning fork conformation, comparable with the crystalline α phase. The behaviour of melting temperatures for the α phase of the mixture SSS/PPP obtained from the simulations is in qualitative agreement with the behaviour that was experimentally determined.

  20. Coarse-grained modeling of the intrinsically disordered protein Histatin 5 in solution: Monte Carlo simulations in combination with SAXS.

    PubMed

    Cragnell, Carolina; Durand, Dominique; Cabane, Bernard; Skepö, Marie

    2016-06-01

    Monte Carlo simulations and coarse-grained modeling have been used to analyze Histatin 5, an unstructured short cationic salivary peptide known to have anticandidical properties. The calculated scattering functions have been compared with intensity curves and the distance distribution function P(r) obtained from small angle X-ray scattering (SAXS), at both high and low salt concentrations. The aim was to achieve a molecular understanding and a physico-chemical insight of the obtained SAXS results and to gain information of the conformational changes of Histatin 5 due to altering salt content, charge distribution, and net charge. From a modeling perspective, the accuracy of the electrostatic interactions are of special interest. The used coarse-grained model was based on the primitive model in which charged hard spheres differing in charge and in size represent the ionic particles, and the solvent only enters the model through its relative permittivity. The Hamiltonian of the model comprises three different contributions: (i) excluded volumes, (ii) electrostatic, and (iii) van der Waals interactions. Even though the model can be considered as gross omitting all atomistic details, a great correspondence is obtained with the experimental results. Proteins 2016; 84:777-791. © 2016 Wiley Periodicals, Inc. PMID:26914439

  1. Modeling the Self-Assembly and Stability of DHPC Micelles Using Atomic Resolution and Coarse Grained MD Simulations.

    PubMed

    Kraft, Johan F; Vestergaard, Mikkel; Schiøtt, Birgit; Thøgersen, Lea

    2012-05-01

    Membrane mimics such as micelles and bicelles are widely used in experiments involving membrane proteins. With the aim of being able to carry out molecular dynamics simulations in environments comparable to experimental conditions, we set out to test the ability of both coarse grained and atomistic resolution force fields to model the experimentally observed behavior of the lipid 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC), which is a widely used lipid for biophysical characterization of membrane proteins. It becomes clear from our results that a satisfactory modeling of DHPC aggregates in solution poses different demands to the force field than do the modeling of bilayers. First, the representation of the short tailed lipid DHPC in the coarse grained force field MARTINI is assessed with the intend of successfully self-assemble micelles with structural characteristics comparable to experimental data. Then, the use of the recently presented polarizable water model in MARTINI is shown to be essential for producing micelles that are structurally in accordance with experiments. For the atomistic representations of DHPC micelles in solution the GROMOS96 force field with lipid parameters by A. Kukol fails to maintain stable micelles, whereas the most recent CHARMM36 lipid parameters and GROMOS96 with the so-called Berger lipid parameters both succeed in this regard. PMID:26593649

  2. Structure and dynamics of Ebola virus matrix protein VP40 by a coarse-grained Monte Carlo simulation

    NASA Astrophysics Data System (ADS)

    Pandey, Ras; Farmer, Barry

    Ebola virus matrix protein VP40 (consisting of 326 residues) plays a critical role in viral assembly and its functions such as regulation of viral transcription, packaging, and budding of mature virions into the plasma membrane of infected cells. How does the protein VP40 go through structural evolution during the viral life cycle remains an open question? Using a coarse-grained Monte Carlo simulation we investigate the structural evolution of VP40 as a function of temperature with the input of a knowledge-based residue-residue interaction. A number local and global physical quantities (e.g. mobility profile, contact map, radius of gyration, structure factor) are analyzed with our large-scale simulations. Our preliminary data show that the structure of the protein evolves through different state with well-defined morphologies which can be identified and quantified via a detailed analysis of structure factor.

  3. Coarse-grained molecular-dynamics simulations of the self-assembly of pentablock copolymers into micelles

    NASA Astrophysics Data System (ADS)

    Chushak, Y.; Travesset, A.

    2005-12-01

    Multiblock polymers in aqueous solution, where one or several blocks are hydrophobic, exhibit a rich variety of phases and states of aggregation. In this paper, we investigate a pentablock system ABCBA, where the B block is always hydrophilic and the A and C blocks have varying degrees of hydrophobicity depending on external conditions. We report coarse-grained molecular-dynamics simulations where the solvent is included explicitly and monomers interact via a 6-9 Lennard Jones potential function. The hydrophobic interaction is modeled by tuning the parameter controlling the strength of the interaction between the hydrophobic monomers and the solvent. We investigate the structure and morphology of the micelles for two concrete situations representing changes in temperature and the pH level. The simulated system is directly relevant to a recently synthesized pentablock system consisting of a triblock Pluronic® with an added pH-sensitive end group [B. C. Anderson et al., Macromolecules 36, 1670 (2003)].

  4. Coarse-graining stiff bonds

    NASA Astrophysics Data System (ADS)

    Español, P.; de la Torre, J. A.; Ferrario, M.; Ciccotti, G.

    2011-11-01

    The method of constraints in molecular dynamics is useful because it avoids the resolution of high frequency motions with very small time steps. However, the price to pay is that both the dynamics and the statistics of a constrained system differ from those of the unconstrained one. Instead of using constraints, we propose to dispose of high frequency motions by a coarse-graining procedure in which fast variables are eliminated. These fast variables are thus modeled as friction and thermal fluctuations. We illustrate the methodology with a simple model case, a diatomic molecule in a monoatomic solvent, in which the bond between the atoms of a diatomic molecule is stiff. Although the example is very simple and does not display the interesting effects of "wrong" statistics of the constrained system (i.e. the well-known issue connected to the Fixman potential), it is well suited to give the proof of concept of the whole procedure.

  5. Coarse-graining Landau-Lifshitz damping

    NASA Astrophysics Data System (ADS)

    Feng, Xuebing; Visscher, P. B.

    2001-06-01

    High speed switching in magnetic materials is usually studied with the Landau-Lifshitz (LL) equation, which describes damping through a phenomenological coefficient. The results of micromagnetic calculations based on the LL equation have been observed to depend strongly on the cell size. We take a coarse-graining or renormalization-group approach to this cell size dependence: from a simulation using cell size L, we look at the dynamics of a cell of size 2L and determine an effective damping coefficient that describes the larger-scale dynamics. This can be thought of as a Green-Kubo calculation of the effective damping coefficient. In principle, this makes it possible to coarse grain from the atomic scale to determine the micromagnetic damping coefficient.

  6. A coarse-grained model for DNA-functionalized spherical colloids, revisited: effective pair potential from parallel replica simulations.

    PubMed

    Theodorakis, Panagiotis E; Dellago, Christoph; Kahl, Gerhard

    2013-01-14

    We discuss a coarse-grained model recently proposed by Starr and Sciortino [J. Phys.: Condens. Matter 18, L347 (2006)] for spherical particles functionalized with short single DNA strands. The model incorporates two key aspects of DNA hybridization, i.e., the specificity of binding between DNA bases and the strong directionality of hydrogen bonds. Here, we calculate the effective potential between two DNA-functionalized particles of equal size using a parallel replica protocol. We find that the transition from bonded to unbonded configurations takes place at considerably lower temperatures compared to those that were originally predicted using standard simulations in the canonical ensemble. We put particular focus on DNA-decorations of tetrahedral and octahedral symmetry, as they are promising candidates for the self-assembly into a single-component diamond structure. Increasing colloid size hinders hybridization of the DNA strands, in agreement with experimental findings. PMID:23320725

  7. Dissipative Particle Dynamics Simulations for Phospholipid Membranes Based on a Four-To-One Coarse-Grained Mapping Scheme

    PubMed Central

    Li, Xiaoxu; Gao, Lianghui; Fang, Weihai

    2016-01-01

    In this article, a new set of parameters compatible with the dissipative particle dynamics (DPD) force field is developed for phospholipids. The coarse-grained (CG) models of these molecules are constructed by mapping four heavy atoms and their attached hydrogen atoms to one bead. The beads are divided into types distinguished by charge type, polarizability, and hydrogen-bonding capacity. First, we derive the relationship between the DPD repulsive force and Flory-Huggins χ-parameters based on this four-to-one CG mapping scheme. Then, we optimize the DPD force parameters for phospholipids. The feasibility of this model is demonstrated by simulating the structural and thermodynamic properties of lipid bilayer membranes, including the membrane thickness, the area per lipid, the lipid tail orientation, the bending rigidity, the rupture behavior, and the potential of mean force for lipid flip-flop. PMID:27137463

  8. Dissipative Particle Dynamics Simulations for Phospholipid Membranes Based on a Four-To-One Coarse-Grained Mapping Scheme.

    PubMed

    Li, Xiaoxu; Gao, Lianghui; Fang, Weihai

    2016-01-01

    In this article, a new set of parameters compatible with the dissipative particle dynamics (DPD) force field is developed for phospholipids. The coarse-grained (CG) models of these molecules are constructed by mapping four heavy atoms and their attached hydrogen atoms to one bead. The beads are divided into types distinguished by charge type, polarizability, and hydrogen-bonding capacity. First, we derive the relationship between the DPD repulsive force and Flory-Huggins χ-parameters based on this four-to-one CG mapping scheme. Then, we optimize the DPD force parameters for phospholipids. The feasibility of this model is demonstrated by simulating the structural and thermodynamic properties of lipid bilayer membranes, including the membrane thickness, the area per lipid, the lipid tail orientation, the bending rigidity, the rupture behavior, and the potential of mean force for lipid flip-flop. PMID:27137463

  9. Coarse-grained simulations of the solution-phase self-assembly of poly(3-hexylthiophene) nanostructures

    NASA Astrophysics Data System (ADS)

    Schwarz, Kyra N.; Kee, Tak W.; Huang, David M.

    2013-02-01

    Under certain conditions the conjugated polymer poly(3-hexylthiophene) (P3HT) self-assembles into high-aspect-ratio nanostructures (known as nanofibres, nanowires, or nanoribbons) when cooled below its solubility limit in a marginal solvent such as anisole. Such nanostructures are potentially beneficial for organic photovoltaic device performance. In this work, Langevin dynamics simulations of a coarse-grained model of P3HT in implicit anisole solvent are used to study the self-assembly of P3HT nanostructures for polymer chain lengths and concentrations used experimentally to prepare P3HT nanofibres. The coarse-grained model is parametrised to match the local structure and dynamics of an atomistic model with explicit solvent. Nanofibres are also prepared experimentally and characterised by atomic force microscopy and UV-vis spectroscopy. The simulations match the experimental phase behaviour of P3HT in anisole, showing aggregation of P3HT at 293 and 308 K but not at 323 or 353 K. Single-chain simulations at 293 K reveal two distinct nano-scale aggregate morphologies: hairpins and helices. Hairpin aggregates, which are the precursors of nanofibres, are slightly favoured energetically at 293 K for nuclei of the critical size of ~80 monomers for aggregation. Consequently, chains in multi-chain aggregates adopt the hairpin morphology exclusively in simulations at experimental concentrations at 293 K. The simulated aggregate sizes match experimentally measured nanofibre widths. An estimate of the shift in UV-vis absorption of P3HT due to the change in conjugation length with aggregation in the simulations agrees reasonably well with experiment and shows that most of the spectral red shift that occurs with nanofibre formation is due to increased planarisation of the P3HT chains. In addition to providing insight into the mechanisms of nanofibre formation, the simulations resolve details of the molecular-level organisation of chains in P3HT nanofibres hitherto inaccessible

  10. Dilepton production and reaction dynamics in heavy-ion collisions at SIS energies from coarse-grained transport simulations

    NASA Astrophysics Data System (ADS)

    Endres, Stephan; van Hees, Hendrik; Weil, Janus; Bleicher, Marcus

    2015-07-01

    Dilepton invariant-mass spectra for heavy-ion collisions at GSI Schwerionensynchroton (SIS 18) and LBNL Bevalac energies are calculated using a coarse-grained time evolution from the Ultrarelativistic Quantum Molecular Dynamics (UrQMD) model. The coarse graining of the microscopic UrQMD simulations makes it possible to calculate thermal dilepton-emission rates by the application of in-medium spectral functions from equilibrium quantum-field theoretical calculations. The results show that extremely high baryon chemical potentials dominate the evolution of the created hot and dense fireball. Consequently, a significant modification of the ρ spectral shape becomes visible in the dilepton invariant-mass spectrum, resulting in an enhancement in the low-mass region Me e=200 to 600 MeV/c2. This enhancement, mainly caused by baryonic effects on the ρ spectral shape, can fully describe the experimentally observed excess above the hadronic cocktail contributions in Ar +KCl (Elab=1.76 A GeV) reactions, as measured by the HADES Collaboration and also gives a good explanation of the older DLS Ca +Ca (Elab=1.04 A GeV) data. For the larger Au +Au (Elab=1.23 A GeV ) system, we predict an even stronger excess from our calculations. A systematic comparison of the results for different system sizes from C +C to Au +Au shows that the thermal dilepton yield increases more strongly (∝A4 /3 ) than the hadronic background contributions, which scale with A , owing to its sensitivity on the time evolution of the reaction. We stress that the findings of the present work are consistent with our previous coarse-graining results for dilepton production at the top energy available at the CERN Super Proton Synchrotron (SPS). We argue that it is possible to describe the dilepton results from SIS 18 up to SPS energies by considering the modifications of the ρ spectral function inside a hot and dense medium within the same model.

  11. Coarse-grained simulations of the gating current in the voltage-activated Kv1.2 channel

    PubMed Central

    Kim, Ilsoo; Warshel, Arieh

    2014-01-01

    Quantitative structure-based modeling of voltage activation of ion channels is very challenging. For example, it is very hard to reach converging results, by microscopic simulations while macroscopic treatments involve major uncertainties regarding key features. The current work overcomes some of the above challenges by using our recently developed coarse-grained (CG) model in simulating the activation of the Kv1.2 channel. The CG model has allowed us to explore problems that cannot be fully addressed at present by microscopic simulations, while providing insights on some features that are not usually considered in continuum models, including the distribution of the electrolytes between the membrane and the electrodes during the activation process and thus the physical nature of the gating current. Here, we demonstrate that the CG model yields realistic gating charges and free energy landscapes that allow us to simulate the fluctuating gating current in the activation processes. Our ability to simulate the time dependence of the fast gating current allows us to reproduce the observed trend and provides a clear description of its relationship to the landscape involved in the activation process. PMID:24464485

  12. Molecular Dynamics Simulations of DPPC Bilayers Using “LIME,” a New Coarse-grained Model

    PubMed Central

    Curtis, Emily M.

    2013-01-01

    A new intermediate resolution model for phospholipids, LIME, designed for use with discontinuous molecular dynamics (DMD) simulations is presented. The implicit-solvent model was developed using a multi-scale modeling approach in which the geometric and energetic parameters are obtained by collecting data from atomistic simulations of a system composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) molecules and explicit water. In the model, 14 coarse-grained sites that are classified as 1 of 6 types represent DPPC. DMD simulations performed on a random solution of DPPC resulted in the formation of a defect free bilayer in less than 4 hours. The bilayer formed quantitatively reproduces the main structural properties (e.g. area per lipid, bilayer thickness, bond order parameters) that are observed experimentally. In addition, the bilayer transitions from a liquid-crystalline phase to a tilted gel phase when the temperature is reduced. Transbilayer movement of a lipid from the bottom leaflet to the top leaflet is observed when the temperature is increased. PMID:23521567

  13. Osmolyte Induced Changes in Peptide Conformational Ensemble Correlate with Slower Amyloid Aggregation: A Coarse-Grained Simulation Study.

    PubMed

    Sukenik, Shahar; Sapir, Liel; Harries, Daniel

    2015-12-01

    Stabilizing osmolytes are known to impact the process of amyloid aggregation, often altering aggregation kinetics. Recent evidence further suggests that osmolytes modify the peptide conformational dynamics, as well as change the physical characteristics of assembling amyloid fibrils. To resolve how these variations emerge on the molecular level, we simulated the initial aggregation steps of an amyloid-forming peptide in the presence and absence of the osmolyte sorbitol, a naturally occurring polyol. To this end, a coarse-grained force field was extended and implemented to access larger aggregate sizes and longer time scales. The force field optimization procedure placed emphasis on calibrating the solution thermodynamics of sorbitol, the aggregating peptide in its monomeric form, and the interaction of both of these components with each other and with water. Our simulations show a difference in aggregation kinetics and structural parameters in the presence of sorbitol compared to water, which qualitatively agree well with our experimentally resolved aggregation kinetics of the same peptide. The kinetic changes induced by sorbitol can be traced in our simulations to changes in monomer conformations resulting from osmolyte presence. These translate into changes in peptide conformations within the aggregated clusters and into differences in rates of monomer nucleation and of association to formed fibrils. We find that, compared to pure water as solvent, the presence of sorbitol induces formation of more aggregates each containing fewer peptides, with an increased tendency toward parallel interpeptide contacts. PMID:26587669

  14. Shock Wave Induced Collapse of Arrays of Nanobubbles Located Next to a Lipid Membrane: Coarse-Grained Computer Simulations.

    PubMed

    Santo, Kolattukudy P; Berkowitz, Max L

    2015-07-23

    We used molecular dynamics simulations to study creation of pores in lipid bilayer membranes by inducing shock waves in systems containing arrays of nanobubbles next to these membranes. Shock waves impinged on the bubbles imploding them and produced nanojets that subsequently hit the bilayers making pores in them. Our simulations were performed using the MARTINI coarse-grained force field. The emphasis in our study was on the interaction of shock waves with two-bubble arrays when the bubbles were placed in different alignments. We observed that the largest damage to the bilayer was produced when two bubbles were positioned in a serial alignment and the bubbles touched each other. When two touching each other bubbles were located parallel to the membrane surface and at the same distance from the surface, the membrane damage was reduced, compared to the damage done by explosion of two independent nanobubbles. When two nanobubbles were placed in slanted configurations, the damage was intermediate between damages produced by two bubbles in parallel or serial alignment. Damage to the membrane produced by arrays containing more than two bubbles can be understood as a combination of damage produced by all three alignments of two bubbles. PMID:25117111

  15. Understanding the curvature effect of silica nanoparticles on lysozyme adsorption orientation and conformation: a mesoscopic coarse-grained simulation study.

    PubMed

    Yu, Gaobo; Zhou, Jian

    2016-08-24

    In nanobiotechnology applications, curvature of nanoparticles has a significant effect on protein activities. In this work, lysozyme adsorption on different-sized silica nanoparticles (SNPs) was simulated at the microsecond timescale by using mesoscopic coarse-grained molecular dynamics simulations. It is found that, with the increase of nanoparticle size, which indicates a decrease of surface curvature, adsorbed lysozyme shows a narrower orientation distribution and a greater conformation change, as the electrostatic attraction dominates lysozyme adsorption, and this trend is more pronounced on larger SNPs. Interestingly, the effect induced by different SNP surface curvatures is not related to the direct contact area between lysozyme and SNPs, but to the interfacial hydration layer above the silica surface, since a smaller curvature can lead to a stronger interfacial hydration and make the distribution of interfacial water molecules more ordered. Besides, at higher ionic strength, lysozyme conformation is less affected by strongly negatively charged SNPs, especially for larger nanoparticles. This work might shed some light on how to prepare protein coronas with higher bioactivities in nanobiotechnology. PMID:27465065

  16. Coarse-grained molecular simulation of epidermal growth factor receptor protein tyrosine kinase multi-site self-phosphorylation.

    PubMed

    Koland, John G

    2014-01-01

    Upon the ligand-dependent dimerization of the epidermal growth factor receptor (EGFR), the intrinsic protein tyrosine kinase (PTK) activity of one receptor monomer is activated, and the dimeric receptor undergoes self-phosphorylation at any of eight candidate phosphorylation sites (P-sites) in either of the two C-terminal (CT) domains. While the structures of the extracellular ligand binding and intracellular PTK domains are known, that of the ∼225-amino acid CT domain is not, presumably because it is disordered. Receptor phosphorylation on CT domain P-sites is critical in signaling because of the binding of specific signaling effector molecules to individual phosphorylated P-sites. To investigate how the combination of conventional substrate recognition and the unique topological factors involved in the CT domain self-phosphorylation reaction lead to selectivity in P-site phosphorylation, we performed coarse-grained molecular simulations of the P-site/catalytic site binding reactions that precede EGFR self-phosphorylation events. Our results indicate that self-phosphorylation of the dimeric EGFR, although generally believed to occur in trans, may well occur with a similar efficiency in cis, with the P-sites of both receptor monomers being phosphorylated to a similar extent. An exception was the case of the most kinase-proximal P-site-992, the catalytic site binding of which occurred exclusively in cis via an intramolecular reaction. We discovered that the in cis interaction of P-site-992 with the catalytic site was facilitated by a cleft between the N-terminal and C-terminal lobes of the PTK domain that allows the short CT domain sequence tethering P-site-992 to the PTK core to reach the catalytic site. Our work provides several new mechanistic insights into the EGFR self-phosphorylation reaction, and demonstrates the potential of coarse-grained molecular simulation approaches for investigating the complexities of self-phosphorylation in molecules such as EGFR

  17. Investigation of the bulk modulus of silica aerogel using molecular dynamics simulations of a coarse-grained model.

    PubMed

    Ferreiro-Rangel, Carlos A; Gelb, Lev D

    2013-06-13

    Structural and mechanical properties of silica aerogels are studied using a flexible coarse-grained model and a variety of simulation techniques. The model, introduced in a previous study (J. Phys. Chem. C 2007, 111, 15792-15802), consists of spherical "primary" gel particles that interact through weak nonbonded forces and through microscopically motivated interparticle bonds that may break and form during the simulations. Aerogel models are prepared using a three-stage protocol consisting of separate simulations of gelation, aging, and a final relaxation during which no further bond formation is permitted. Models of varying particle size, density, and size dispersity are considered. These are characterized in terms of fractal dimensions and pore size distributions, and generally good agreement with experimental data is obtained for these metrics. The bulk moduli of these materials are studied in detail. Two different techniques for obtaining the bulk modulus are considered, fluctuation analysis and direct compression/expansion simulations. We find that the fluctuation result can be subject to systematic error due to coupling with the simulation barostat but, if performed carefully, yields results equivalent with those of compression/expansion experiments. The dependence of the bulk modulus on density follows a power law with an exponent between 3.00 and 3.15, in agreement with reported experimental results. The best correlate for the bulk modulus appears to be the volumetric bond density, on which there is also a power law dependence. Polydisperse models exhibit lower bulk moduli than comparable monodisperse models, which is due to lower bond densities in the polydisperse materials. PMID:23631801

  18. Modeling Effects of RNA on Capsid Assembly Pathways via Coarse-Grained Stochastic Simulation

    PubMed Central

    Smith, Gregory R.; Xie, Lu; Schwartz, Russell

    2016-01-01

    The environment of a living cell is vastly different from that of an in vitro reaction system, an issue that presents great challenges to the use of in vitro models, or computer simulations based on them, for understanding biochemistry in vivo. Virus capsids make an excellent model system for such questions because they typically have few distinct components, making them amenable to in vitro and modeling studies, yet their assembly can involve complex networks of possible reactions that cannot be resolved in detail by any current experimental technology. We previously fit kinetic simulation parameters to bulk in vitro assembly data to yield a close match between simulated and real data, and then used the simulations to study features of assembly that cannot be monitored experimentally. The present work seeks to project how assembly in these simulations fit to in vitro data would be altered by computationally adding features of the cellular environment to the system, specifically the presence of nucleic acid about which many capsids assemble. The major challenge of such work is computational: simulating fine-scale assembly pathways on the scale and in the parameter domains of real viruses is far too computationally costly to allow for explicit models of nucleic acid interaction. We bypass that limitation by applying analytical models of nucleic acid effects to adjust kinetic rate parameters learned from in vitro data to see how these adjustments, singly or in combination, might affect fine-scale assembly progress. The resulting simulations exhibit surprising behavioral complexity, with distinct effects often acting synergistically to drive efficient assembly and alter pathways relative to the in vitro model. The work demonstrates how computer simulations can help us understand how assembly might differ between the in vitro and in vivo environments and what features of the cellular environment account for these differences. PMID:27244559

  19. Coarse-grained simulations of vortex dynamics and transition in complex high-Re flows

    SciTech Connect

    Grinstein, Fernando F

    2011-01-21

    Turbulent flow complexity in applications in engineering, geophysics and astrophysics typically requires achieving accurate and dependable large scale predictions of highly nonlinear processes with under-resolved computer simulation models. Laboratory observations typically demonstrate the end outcome of complex non-linear three-dimensional physical processes with many unexplained details and mechanisms. Carefully controlled computational experiments based on the numerical solution of the conservation equations for mass, momentum, and energy, provide insights into the underlying flow dynamics. Relevant computational fluid dynamics issues to be addressed relate to the modeling of the unresolved tlow conditions at the subgrid scale (SGS) level - within a computational cell, and at the supergrid (SPG) scale - at initialization and beyond computational boundaries. SGS and SPG information must be prescribed for closure of the equations solved numerically. SGS models appear explicitly or implicitly as additional source tenns in the modified flow equations solved by the numerical solutions being calculated, while SPG models provide the necessary set of initial and boundary conditions that must be prescribed to ensure unique well-posed solutions. From this perspective, it is clear that the simulation process is inherently determined by the SGS and SPG information prescription process. On the other hand, observables in laboratory experiments are always characterized by the finite scales of the instrumental resolution of measuring/visualizing devices, and subject as well to SPG issues. It is thus important to recognize the inherently intrusive nature of observations based on numerical or laboratory experiments. Ultimately, verification and validation (V & V) frameworks and appropriate metrics for the specific problems at hand are needed to establish predictability of the simulation model. Direct numerical simulation (DNS) - resolving all relevant space/time scales, is

  20. Effect of Backbone Design on Hybridization Thermodynamics of Oligo-nucleic Acids: A Coarse-Grained Molecular Dynamics Simulation Study

    NASA Astrophysics Data System (ADS)

    Ghobadi, Ahmadreza F.; Jayaraman, Arthi

    DNA hybridization is the basis of various bio-nano technologies, such as DNA origami and assembly of DNA-functionalized nanoparticles. A hybridized double stranded (ds) DNA is formed when complementary nucleobases on hybridizing strands exhibit specific and directional hydrogen bonds through canonical Watson-Crick base-pairing interactions. In recent years, the need for cheaper alternatives and significant synthetic advances have driven design of DNA mimics with new backbone chemistries. However, a fundamental understanding of how these backbone modifications in the oligo-nucleic acids impact the hybridization and melting behavior of the duplex is still lacking. In this talk, we present our recent findings on impact of varying backbone chemistry on hybridization of oligo-nucleic acid duplexes. We use coarse-grained molecular dynamics simulations to isolate the effect of strand flexibility, electrostatic interactions and nucleobase spacing on the melting curves for duplexes with various strand sequences and concentrations. Since conjugation of oligo-nucleic acids with polymers serve as building blocks for thermo-responsive polymer networks and gels, we also present the effect of such conjugation on hybridization thermodynamics and polymer conformation.

  1. Molecular dynamics simulations of cholesterol-rich membranes using a coarse-grained force field for cyclic alkanes

    NASA Astrophysics Data System (ADS)

    MacDermaid, Christopher M.; Kashyap, Hemant K.; DeVane, Russell H.; Shinoda, Wataru; Klauda, Jeffery B.; Klein, Michael L.; Fiorin, Giacomo

    2015-12-01

    The architecture of a biological membrane hinges upon the fundamental fact that its properties are determined by more than the sum of its individual components. Studies on model membranes have shown the need to characterize in molecular detail how properties such as thickness, fluidity, and macroscopic bending rigidity are regulated by the interactions between individual molecules in a non-trivial fashion. Simulation-based approaches are invaluable to this purpose but are typically limited to short sampling times and model systems that are often smaller than the required properties. To alleviate both limitations, the use of coarse-grained (CG) models is nowadays an established computational strategy. We here present a new CG force field for cholesterol, which was developed by using measured properties of small molecules, and can be used in combination with our previously developed force field for phospholipids. The new model performs with precision comparable to atomistic force fields in predicting the properties of cholesterol-rich phospholipid bilayers, including area per lipid, bilayer thickness, tail order parameter, increase in bending rigidity, and propensity to form liquid-ordered domains in ternary mixtures. We suggest the use of this model to quantify the impact of cholesterol on macroscopic properties and on microscopic phenomena involving localization and trafficking of lipids and proteins on cellular membranes.

  2. Coarse-grained Molecular Simulation Studies of Complexation of Sulfobetaine-Lysine Copolymer and DNA for Gene Delivery

    NASA Astrophysics Data System (ADS)

    Ghobadi, Ahmadreza F.; Jayaraman, Arthi

    2015-03-01

    Gene delivery involves successful transfection of therapeutic DNA by a vector into target cells and protein expression of that genetic material. Viral vectors are effective at gene delivery but elicit harmful immunogenic responses, thus motivating ongoing research on non-viral transfection agents. Cationic polymers are a promising class of non-viral vectors due to their low immugenic responses and low toxicity, and their ability to bind to the polyanionic DNA backbone to form a polycation-DNA complex (polyplex) that is then internalized in the target cell. While past studies have shown many polycations with differing DNA transfection efficacies, there is a need for general design guidelines that can relate the molecular features of the polycation to its DNA transfection efficiency. Using atomistic and coarse-grained molecular dynamics simulations we connect polycation design to polycation-DNA binding and experimentally observed transfection efficiency. Specifically in this presentation we will discuss our recent work looking into the effect of incorporating zwitterions into lysine based polycations on the resulting polyplex structure, shape, surface charge density and stability of DNA-polycation complexes.

  3. Molecular dynamics simulations of cholesterol-rich membranes using a coarse-grained force field for cyclic alkanes

    SciTech Connect

    MacDermaid, Christopher M. Klein, Michael L.; Fiorin, Giacomo; Kashyap, Hemant K.; DeVane, Russell H.; Shinoda, Wataru; Klauda, Jeffery B.

    2015-12-28

    The architecture of a biological membrane hinges upon the fundamental fact that its properties are determined by more than the sum of its individual components. Studies on model membranes have shown the need to characterize in molecular detail how properties such as thickness, fluidity, and macroscopic bending rigidity are regulated by the interactions between individual molecules in a non-trivial fashion. Simulation-based approaches are invaluable to this purpose but are typically limited to short sampling times and model systems that are often smaller than the required properties. To alleviate both limitations, the use of coarse-grained (CG) models is nowadays an established computational strategy. We here present a new CG force field for cholesterol, which was developed by using measured properties of small molecules, and can be used in combination with our previously developed force field for phospholipids. The new model performs with precision comparable to atomistic force fields in predicting the properties of cholesterol-rich phospholipid bilayers, including area per lipid, bilayer thickness, tail order parameter, increase in bending rigidity, and propensity to form liquid-ordered domains in ternary mixtures. We suggest the use of this model to quantify the impact of cholesterol on macroscopic properties and on microscopic phenomena involving localization and trafficking of lipids and proteins on cellular membranes.

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  5. 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.

  6. CLUB-MARTINI: Selecting Favourable Interactions amongst Available Candidates, a Coarse-Grained Simulation Approach to Scoring Docking Decoys

    PubMed Central

    Hou, Qingzhen; Heringa, Jaap

    2016-01-01

    Large-scale identification of native binding orientations is crucial for understanding the role of protein-protein interactions in their biological context. Measuring binding free energy is the method of choice to estimate binding strength and reveal the relevance of particular conformations in which proteins interact. In a recent study, we successfully applied coarse-grained molecular dynamics simulations to measure binding free energy for two protein complexes with similar accuracy to full-atomistic simulation, but 500-fold less time consuming. Here, we investigate the efficacy of this approach as a scoring method to identify stable binding conformations from thousands of docking decoys produced by protein docking programs. To test our method, we first applied it to calculate binding free energies of all protein conformations in a CAPRI (Critical Assessment of PRedicted Interactions) benchmark dataset, which included over 19000 protein docking solutions for 15 benchmark targets. Based on the binding free energies, we ranked all docking solutions to select the near-native binding modes under the assumption that the native-solutions have lowest binding free energies. In our top 100 ranked structures, for the ‘easy’ targets that have many near-native conformations, we obtain a strong enrichment of acceptable or better quality structures; for the ‘hard’ targets without near-native decoys, our method is still able to retain structures which have native binding contacts. Moreover, in our top 10 selections, CLUB-MARTINI shows a comparable performance when compared with other state-of-the-art docking scoring functions. As a proof of concept, CLUB-MARTINI performs remarkably well for many targets and is able to pinpoint near-native binding modes in the top selections. To the best of our knowledge, this is the first time interaction free energy calculated from MD simulations have been used to rank docking solutions at a large scale. PMID:27166787

  7. Effects of Macromolecular Crowding on Amyloid Beta (16–22) Aggregation Using Coarse-Grained Simulations

    PubMed Central

    2015-01-01

    To examine the effect of crowding on protein aggregation, discontinuous molecular dynamics (DMD) simulations combined with an intermediate resolution protein model, PRIME20, were applied to a peptide/crowder system. The systems contained 192 Aβ(16–22) peptides and crowders of diameters 5, 20, and 40 Å, represented here by simple hard spheres, at crowder volume fractions of 0.00, 0.10, and 0.20. Results show that both crowder volume fraction and crowder diameter have a large impact on fibril and oligomer formation. The addition of crowders to a system of peptides increases the rate of oligomer formation, shifting from a slow ordered formation of oligomers in the absence of crowders, similar to nucleated polymerization, to a fast collapse of peptides and subsequent rearrangement characteristic of nucleated conformational conversion with a high maximum in the number of peptides in oligomers as the total crowder surface area increases. The rate of conversion from oligomers to fibrils also increases with increasing total crowder surface area, giving rise to an increased rate of fibril growth. In all cases, larger volume fractions and smaller crowders provide the greatest aggregation enhancement effects. We also show that the size of the crowders influences the formation of specific oligomer sizes. In our simulations, the 40 Å crowders enhance the number of dimers relative to the numbers of trimers, hexamers, pentamers, and hexamers, while the 5 Å crowders enhance the number of hexamers relative to the numbers of dimers, trimers, tetramers, and pentamers. These results are in qualitative agreement with previous experimental and theoretical work. PMID:25347801

  8. Coarse-Grain Modeling of Energetic Materials

    NASA Astrophysics Data System (ADS)

    Brennan, John

    2015-06-01

    Mechanical and thermal loading of energetic materials can incite responses over a wide range of spatial and temporal scales due to inherent nano- and microscale features. Many energy transfer processes within these materials are atomistically governed, yet the material response is manifested at the micro- and mesoscale. The existing state-of-the-art computational methods include continuum level approaches that rely on idealized field-based formulations that are empirically based. Our goal is to bridge the spatial and temporal modeling regimes while ensuring multiscale consistency. However, significant technical challenges exist, including that the multiscale methods linking the atomistic and microscales for molecular crystals are immature or nonexistent. To begin addressing these challenges, we have implemented a bottom-up approach for deriving microscale coarse-grain models directly from quantum mechanics-derived atomistic models. In this talk, a suite of computational tools is described for particle-based microscale simulations of the nonequilibrium response of energetic solids. Our approach builds upon recent advances both in generating coarse-grain models under high strains and in developing a variant of dissipative particle dynamics that includes chemical reactions.

  9. Coarse-Grained Simulations of Polymer-Grafted Nanoparticles: Structural Stability and Interfacial Behavior.

    PubMed

    Nair, Nitish; Park, Michelle; Handgraaf, Jan-Willem; Cassiola, Flavia M

    2016-09-01

    In the tertiary oil recovery method known as "polymer flooding", the viscosity of the injected water is increased by dissolving partially hydrolyzed polyacrylamide so as to lower the mobility ratio and raise the vertical and areal sweep efficiencies. However, its drawbacks include the degradation of the polymer in the reservoir due to (1) shear while passing through chokes, perforations, and pore throats, (2) morphological changes induced by divalent ions, and (3) complete hydrolysis of the polymer at high temperatures. These factors adversely affect the viscosity of the polymer flood. Past experimental research showed that polymer-grafted nanoparticles (PNPs) could achieve the same viscosity enhancement at lower quantities than traditional linear polymers. The PNPs have the putative advantage of greater stability when confronted with the aforementioned reservoir conditions. In this work, we use dissipative particle dynamics (DPD) to simulate the oil-PNP-water system at the mesoscale and estimate its sensitivity to brine in ways that could serve as guidelines to experiments. We study the effect of salinity on the structure of linear and branched polyelectrolytes before extending the DPD model to PNPs at the oil-water interface. To this end, we parameterize the interactions of the polymer with the oil and water phases, and broadly map out solvent conditions that change the graft's morphology and affect the interfacial behavior of the grafted particle. We find that the equilibrium location of the grafted nanoparticle in an oil-brine system depends on its grafting density and the salinity. PMID:27513884

  10. Restructuring of a model hydrophobic surface: Monte Carlo simulations using a simple coarse-grained model.

    PubMed

    Eun, Changsun; Das, Jhuma; Berkowitz, Max L

    2013-12-12

    A lattice model is proposed to explain the restructuring of an ionic surfactant absorbed on a charged surface. When immersed in water, an ionic mica plate initially covered by a monolayer of surfactants rearranges to a surface inhomogeneously covered by patches of surfactant bilayer and bare mica. The model considers four species that can cover lattice sites of a surface. These species include (i) a surfactant molecule with its headgroup down, (ii) surfactant molecule with the headgroup up, (iii) a surfactant dimer arranged in a tail-to-tail configuration, which is a part of a bilayer, and (iv) a mica lattice site covered by water. We consider that only nearest neighbors on the lattice interact and describe the interactions by an interaction matrix. Using this model, we perform Monte Carlo simulations and study how the structure of the inhomogeneous surface depends on the interaction between water covered lattice site and its neighboring surfactant species covered sites. We observe that when this interaction is absent, the system undergoes phase separation into a bilayer phase and mica surface covered with water. When this interaction is taken into account, patches of surfactant bilayer and water are present in our system. The interaction between mica surfaces covered by patches of ionic surfactants is studied in experiments to understand the nature of long-ranged "hydrophobic" forces. PMID:23962357

  11. Quasiclassical coarse graining and thermodynamic entropy

    SciTech Connect

    Gell-Mann, Murray; Hartle, James B.

    2007-08-15

    Our everyday descriptions of the universe are highly coarse grained, following only a tiny fraction of the variables necessary for a perfectly fine-grained description. Coarse graining in classical physics is made natural by our limited powers of observation and computation. But in the modern quantum mechanics of closed systems, some measure of coarse graining is inescapable because there are no nontrivial, probabilistic, fine-grained descriptions. This essay explores the consequences of that fact. Quantum theory allows for various coarse-grained descriptions, some of which are mutually incompatible. For most purposes, however, we are interested in the small subset of 'quasiclassical descriptions' defined by ranges of values of averages over small volumes of densities of conserved quantities such as energy and momentum and approximately conserved quantities such as baryon number. The near-conservation of these quasiclassical quantities results in approximate decoherence, predictability, and local equilibrium, leading to closed sets of equations of motion. In any description, information is sacrificed through the coarse graining that yields decoherence and gives rise to probabilities for histories. In quasiclassical descriptions, further information is sacrificed in exhibiting the emergent regularities summarized by classical equations of motion. An appropriate entropy measures the loss of information. For a 'quasiclassical realm' this is connected with the usual thermodynamic entropy as obtained from statistical mechanics. It was low for the initial state of our universe and has been increasing since.

  12. An overview of molecular dynamics simulations of oxidized lipid systems, with a comparison of ELBA and MARTINI force fields for coarse grained lipid simulations.

    PubMed

    Siani, P; de Souza, R M; Dias, L G; Itri, R; Khandelia, H

    2016-10-01

    Biological membranes and model lipid systems containing high amounts of unsaturated lipids and sterols are subject to chemical and/or photo-induced lipid oxidation, which leads to the creation of exotic oxidized lipid products (OxPLs). OxPLs are known to have significant physiological impact in cellular systems and also affect physical properties of both biological and model lipid bilayers. In this paper we (i) provide a perspective on the existing literature on simulations of lipid bilayer systems containing oxidized lipid species as well as the main related experimental results, (ii) describe our new data of all-atom and coarse-grained simulations of hydroperoxidized lipid monolayer and bilayer systems and (iii) provide a comparison of the MARTINI and ELBA coarse grained force fields for lipid bilayer systems. We show that the better electrostatic treatment of interactions in ELBA is able to resolve previous conflicts between experiments and simulations. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg. PMID:27058982

  13. Simulating the Radio-Frequency Dielectric Response of Relaxor Ferroelectrics: Combination of Coarse-Grained Hamiltonians and Kinetic Monte Carlo Simulations

    NASA Astrophysics Data System (ADS)

    Geneste, Grégory; Bellaiche, L.; Kiat, Jean-Michel

    2016-06-01

    The radio-frequency dielectric response of the lead-free Ba (Zr0.5Ti0.5)O3 relaxor ferroelectric is simulated using a coarse-grained Hamiltonian. This concept, taken from real-space renormalization group theories, allows us to depict the collective behavior of correlated local modes gathered in blocks. Free-energy barriers for their thermally activated collective hopping are deduced from this ab initio-based approach, and used as input data for kinetic Monte Carlo simulations. The resulting numerical scheme allows us to simulate the dielectric response for external field frequencies ranging from kHz up to a few tens of MHz for the first time and to demonstrate, e.g., that local (electric or elastic) random fields lead to the dielectric relaxation in the radio-frequency range that has been observed in relaxors.

  14. Simulating the Radio-Frequency Dielectric Response of Relaxor Ferroelectrics: Combination of Coarse-Grained Hamiltonians and Kinetic Monte Carlo Simulations.

    PubMed

    Geneste, Grégory; Bellaiche, L; Kiat, Jean-Michel

    2016-06-17

    The radio-frequency dielectric response of the lead-free Ba(Zr_{0.5}Ti_{0.5})O_{3} relaxor ferroelectric is simulated using a coarse-grained Hamiltonian. This concept, taken from real-space renormalization group theories, allows us to depict the collective behavior of correlated local modes gathered in blocks. Free-energy barriers for their thermally activated collective hopping are deduced from this ab initio-based approach, and used as input data for kinetic Monte Carlo simulations. The resulting numerical scheme allows us to simulate the dielectric response for external field frequencies ranging from kHz up to a few tens of MHz for the first time and to demonstrate, e.g., that local (electric or elastic) random fields lead to the dielectric relaxation in the radio-frequency range that has been observed in relaxors. PMID:27367408

  15. Probing the folded state and mechanical unfolding pathways of T4 lysozyme using all-atom and coarse-grained molecular simulation

    NASA Astrophysics Data System (ADS)

    Zheng, Wenjun; Glenn, Paul

    2015-01-01

    The Bacteriophage T4 Lysozyme (T4L) is a prototype modular protein comprised of an N-terminal and a C-domain domain, which was extensively studied to understand the folding/unfolding mechanism of modular proteins. To offer detailed structural and dynamic insights to the folded-state stability and the mechanical unfolding behaviors of T4L, we have performed extensive equilibrium and steered molecular dynamics simulations of both the wild-type (WT) and a circular permutation (CP) variant of T4L using all-atom and coarse-grained force fields. Our all-atom and coarse-grained simulations of the folded state have consistently found greater stability of the C-domain than the N-domain in isolation, which is in agreement with past thermostatic studies of T4L. While the all-atom simulation cannot fully explain the mechanical unfolding behaviors of the WT and the CP variant observed in an optical tweezers study, the coarse-grained simulations based on the Go model or a modified elastic network model (mENM) are in qualitative agreement with the experimental finding of greater unfolding cooperativity in the WT than the CP variant. Interestingly, the two coarse-grained models predict different structural mechanisms for the observed change in cooperativity between the WT and the CP variant—while the Go model predicts minor modification of the unfolding pathways by circular permutation (i.e., preserving the general order that the N-domain unfolds before the C-domain), the mENM predicts a dramatic change in unfolding pathways (e.g., different order of N/C-domain unfolding in the WT and the CP variant). Based on our simulations, we have analyzed the limitations of and the key differences between these models and offered testable predictions for future experiments to resolve the structural mechanism for cooperative folding/unfolding of T4L.

  16. Probing the folded state and mechanical unfolding pathways of T4 lysozyme using all-atom and coarse-grained molecular simulation

    SciTech Connect

    Zheng, Wenjun Glenn, Paul

    2015-01-21

    The Bacteriophage T4 Lysozyme (T4L) is a prototype modular protein comprised of an N-terminal and a C-domain domain, which was extensively studied to understand the folding/unfolding mechanism of modular proteins. To offer detailed structural and dynamic insights to the folded-state stability and the mechanical unfolding behaviors of T4L, we have performed extensive equilibrium and steered molecular dynamics simulations of both the wild-type (WT) and a circular permutation (CP) variant of T4L using all-atom and coarse-grained force fields. Our all-atom and coarse-grained simulations of the folded state have consistently found greater stability of the C-domain than the N-domain in isolation, which is in agreement with past thermostatic studies of T4L. While the all-atom simulation cannot fully explain the mechanical unfolding behaviors of the WT and the CP variant observed in an optical tweezers study, the coarse-grained simulations based on the Go model or a modified elastic network model (mENM) are in qualitative agreement with the experimental finding of greater unfolding cooperativity in the WT than the CP variant. Interestingly, the two coarse-grained models predict different structural mechanisms for the observed change in cooperativity between the WT and the CP variant—while the Go model predicts minor modification of the unfolding pathways by circular permutation (i.e., preserving the general order that the N-domain unfolds before the C-domain), the mENM predicts a dramatic change in unfolding pathways (e.g., different order of N/C-domain unfolding in the WT and the CP variant). Based on our simulations, we have analyzed the limitations of and the key differences between these models and offered testable predictions for future experiments to resolve the structural mechanism for cooperative folding/unfolding of T4L.

  17. Interlaced coarse-graining for the dynamical cluster approximation

    NASA Astrophysics Data System (ADS)

    Haehner, Urs; Staar, Peter; Jiang, Mi; Maier, Thomas; Schulthess, Thomas

    The negative sign problem remains a challenging limiting factor in quantum Monte Carlo simulations of strongly correlated fermionic many-body systems. The dynamical cluster approximation (DCA) makes this problem less severe by coarse-graining the momentum space to map the bulk lattice to a cluster embedded in a dynamical mean-field host. Here, we introduce a new form of an interlaced coarse-graining and compare it with the traditional coarse-graining. We show that it leads to more controlled results with weaker cluster shape and smoother cluster size dependence, which with increasing cluster size converge to the results obtained using the standard coarse-graining. In addition, the new coarse-graining reduces the severity of the fermionic sign problem. Therefore, it enables calculations on much larger clusters and can allow the evaluation of the exact infinite cluster size result via finite size scaling. To demonstrate this, we study the hole-doped two-dimensional Hubbard model and show that the interlaced coarse-graining in combination with the DCA+ algorithm permits the determination of the superconducting Tc on cluster sizes, for which the results can be fitted with the Kosterlitz-Thouless scaling law. This research used resources of the Oak Ridge Leadership Computing Facility (OLCF) awarded by the INCITE program, and of the Swiss National Supercomputing Center. OLCF is a DOE Office of Science User Facility supported under Contract DE-AC05-00OR22725.

  18. Energy-conserving coarse-graining of complex molecules.

    PubMed

    Español, Pep; Serrano, Mar; Pagonabarraga, Ignacio; Zúñiga, Ignacio

    2016-05-25

    Coarse-graining (CG) of complex molecules is a method to reach time scales that would be impossible to access through brute force molecular simulations. In this paper, we formulate a coarse-grained model for complex molecules using first principles caculations that ensures energy conservation. Each molecule is described in a coarse way by a thermal blob characterized by the position and momentum of the center of mass of the molecule, together with its internal energy as an additional degree of freedom. This level of description gives rise to an entropy-based framework instead of the usual one based on the configurational free energy (i.e. potential of mean force). The resulting dynamic equations, which account for an appropriate description of heat transfer at the coarse-grained level, have the structure of the dissipative particle dynamics with energy conservation (DPDE) model but with a clear microscopic underpinning. Under suitable approximations, we provide explicit microscopic expressions for each component (entropy, mean force, friction and conductivity coefficients) appearing in the coarse-grained model. These quantities can be computed directly using MD simulations. The proposed non-isothermal coarse-grained model is thermodynamically consistent and opens up a first principles CG strategy for the study of energy transport issues that are not accessible using current isothermal models. PMID:27127809

  19. A Transferable Coarse-Grained Model for Hydrogen Bonding Liquids

    PubMed Central

    Golubkov, Pavel A.; Wu, Johnny C.; Ren, Pengyu

    2008-01-01

    We present here a recent development of a generalized coarse-grained model for use in molecular simulations. In this model, interactions between coarse-grained particles consist of both van der Waals and explicit electrostatic components. As a result, the coarse-grained model offers the transferability that is lacked by most current effectivepotential based approaches. The previous center-of-mass framework1 is generalized here to include arbitrary off-center interaction sites for both Gay-Berne and multipoles. The new model has been applied to molecular dynamic simulations of neat methanol liquid. By placing a single point multipole at the oxygen atom rather than at the center of mass of methanol, there is a significant improvement in the ability to capture hydrogen-bonding. The critical issue of transferability of the coarse-grained model is verified on methanol-water mixtures, using parameters derived from neat liquids without any modification. The mixture density and internal energy from coarse-grained molecular dynamics simulations show good agreement with experimental measurements, on a par with what has been obtained from more detailed atomic models. By mapping the dynamics trajectory from the coarse-grained simulation into the all-atom counterpart, we are able to investigate atomic .level structure and interaction. Atomic radial distribution functions of neat methanol, neat water and mixtures compare favorably to experimental measurements. Furthermore, hydrogen-bonded 6- and 7-molecule chains of water and methanol observed in the mixture are in agreement with previous atomic simulations. PMID:18688358

  20. Implicit-Solvent Coarse-Grained Simulation with a Fluctuating Interface Reveals a Molecular Mechanism for Peptoid Monolayer Buckling.

    PubMed

    Haxton, Thomas K; Zuckermann, Ronald N; Whitelam, Stephen

    2016-01-12

    Peptoid polymers form extended two-dimensional nanostructures via an interface-mediated assembly process: the amphiphilic peptoids first adsorb to an air-water interface as a monolayer, then buckle and collapse into free-floating bilayer nanosheets when the interface is compressed. Here, we investigate the molecular mechanism of monolayer buckling by developing a method for incorporating interface fluctuations into an implicit-solvent coarse-grained model. Representing the interface with a triangular mesh controlled by surface tension and surfactant adsorption, we predict the direction of buckling for peptoids with a segregated arrangement of charged side chains and predict that peptoids with with an alternating charge pattern should buckle less easily than peptoids with a segregated charge pattern. PMID:26647143

  1. Coarse grained dynamics in the glass phase

    NASA Astrophysics Data System (ADS)

    Smessaert, Anton; Rottler, Jörg

    2013-03-01

    Atomic scale dynamics in glasses is dominated by extended periods of localized vibration, where the crowded surroundings of a particle act as a cage. Collective motion is necessary to escape the cage, and the succession of particle jumps or hops leads to diffusion. Each jump is an elementary relaxation event since the local structure is stable until a jump occurs. The link between local dynamics and structural properties has become of increasing interest in recent years. Aging of the mechanical response has been tied to a power-law distribution of persistence times in the cages, and concentration of hops into dynamical heterogeneities (DH) was observed in granular media and simulations of supercooled liquids in 2D. These studies were limited to small systems or hop detection in subsets, because of the post processing requirements. We present results based on a new algorithm that allows us to detect the hops of all particles during a molecular dynamics simulation. This complete coarse-grained ``map'' of the dynamics allows us to directly investigate temporal and spatial correlations between relaxation events. Furthermore, we can readily identify DH using a cluster algorithm and we explore the impact of aging and deformation on the size and shape of DH.

  2. Phase Separation Behavior of Mixed Lipid Systems at Neutral and Low pH: Coarse-Grained Simulations with DMD/LIME

    PubMed Central

    2015-01-01

    We extend LIME, an intermediate resolution, implicit solvent model for phospholipids previously used in discontinuous molecular dynamics simulations of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayer formation at 325 K, to the description of the geometry and energetics of 1,2-distearoyl-sn-glycero-3-phospho-l-serine (DSPS) and 1,2-dihenarachidoyl-sn-glycero-3-phosphocholine (21PC) and mixtures thereof at both neutral and low pH at 310 K. A multiscale modeling approach is used to calculate the LIME parameters from atomistic simulation data on a mixed DPPC/DSPS system at different pH values. In the model, 17 coarse-grained sites represent DSPS and 18 coarse-grained sites represent 21PC. Each of these coarse-grained sites is classified as 1 of 9 types. LIME/DMD simulations of equimolar bilayers show the following: (1) 21PC/DSPS bilayers with and without surface area restrictions separate faster at low pH than at neutral pH, (2) 21PC/DSPS systems separate at approximately the same rate regardless of whether they are subjected to surface area restrictions, and (3) bilayers with a molar ratio of 9:1 (21PC:DSPS) phase separate to form heterogeneous domains faster at low pH than at neutral pH. Our results are consistent with experimental findings of Sofou and co-workers (Bandekar et al. Mol. Pharmaceutics, 2013, 10, 152–160; Karve et al. Biomaterials, 2010, 31, 4409–4416) that more doxorubicin is released from 21PC/DSPS liposomes at low pH than at neutral pH, presumably because greater phase separation is achieved at low pH than at neutral pH. These are the first molecular-level simulations of the phase separation in mixed lipid bilayers induced by a change in pH. PMID:25549801

  3. HBP Builder: A Tool to Generate Hyperbranched Polymers and Hyperbranched Multi-Arm Copolymers for Coarse-grained and Fully Atomistic Molecular Simulations

    NASA Astrophysics Data System (ADS)

    Yu, Chunyang; Ma, Li; Li, Shanlong; Tan, Haina; Zhou, Yongfeng; Yan, Deyue

    2016-05-01

    Computer simulation has been becoming a versatile tool that can investigate detailed information from the microscopic scale to the mesoscopic scale. However, the crucial first step of molecular simulation is model building, particularly for hyperbranched polymers (HBPs) and hyperbranched multi-arm copolymers (HBMCs) with complex and various topological structures. Unlike well-defined polymers, not only the molar weight of HBPs/HBMCs with polydispersity, but the HBPs/HBMCs with the same degree of polymerization (DP) and degree of branching (DB) also have many possible topological structures, thus making difficulties for user to build model in molecular simulation. In order to build a bridge between model building and molecular simulation of HBPs and HBMCs, we developed HBP Builder, a C language open source HBPs/HBMCs building toolkit. HBP Builder implements an automated protocol to build various coarse-grained and fully atomistic structures of HBPs/HBMCs according to user’s specific requirements. Meanwhile, coarse-grained and fully atomistic output structures can be directly employed in popular simulation packages, including HOOMD, Tinker and Gromacs. Moreover, HBP Builder has an easy-to-use graphical user interface and the modular architecture, making it easy to extend and reuse it as a part of other program.

  4. HBP Builder: A Tool to Generate Hyperbranched Polymers and Hyperbranched Multi-Arm Copolymers for Coarse-grained and Fully Atomistic Molecular Simulations.

    PubMed

    Yu, Chunyang; Ma, Li; Li, Shanlong; Tan, Haina; Zhou, Yongfeng; Yan, Deyue

    2016-01-01

    Computer simulation has been becoming a versatile tool that can investigate detailed information from the microscopic scale to the mesoscopic scale. However, the crucial first step of molecular simulation is model building, particularly for hyperbranched polymers (HBPs) and hyperbranched multi-arm copolymers (HBMCs) with complex and various topological structures. Unlike well-defined polymers, not only the molar weight of HBPs/HBMCs with polydispersity, but the HBPs/HBMCs with the same degree of polymerization (DP) and degree of branching (DB) also have many possible topological structures, thus making difficulties for user to build model in molecular simulation. In order to build a bridge between model building and molecular simulation of HBPs and HBMCs, we developed HBP Builder, a C language open source HBPs/HBMCs building toolkit. HBP Builder implements an automated protocol to build various coarse-grained and fully atomistic structures of HBPs/HBMCs according to user's specific requirements. Meanwhile, coarse-grained and fully atomistic output structures can be directly employed in popular simulation packages, including HOOMD, Tinker and Gromacs. Moreover, HBP Builder has an easy-to-use graphical user interface and the modular architecture, making it easy to extend and reuse it as a part of other program. PMID:27188541

  5. HBP Builder: A Tool to Generate Hyperbranched Polymers and Hyperbranched Multi-Arm Copolymers for Coarse-grained and Fully Atomistic Molecular Simulations

    PubMed Central

    Yu, Chunyang; Ma, Li; Li, Shanlong; Tan, Haina; Zhou, Yongfeng; Yan, Deyue

    2016-01-01

    Computer simulation has been becoming a versatile tool that can investigate detailed information from the microscopic scale to the mesoscopic scale. However, the crucial first step of molecular simulation is model building, particularly for hyperbranched polymers (HBPs) and hyperbranched multi-arm copolymers (HBMCs) with complex and various topological structures. Unlike well-defined polymers, not only the molar weight of HBPs/HBMCs with polydispersity, but the HBPs/HBMCs with the same degree of polymerization (DP) and degree of branching (DB) also have many possible topological structures, thus making difficulties for user to build model in molecular simulation. In order to build a bridge between model building and molecular simulation of HBPs and HBMCs, we developed HBP Builder, a C language open source HBPs/HBMCs building toolkit. HBP Builder implements an automated protocol to build various coarse-grained and fully atomistic structures of HBPs/HBMCs according to user’s specific requirements. Meanwhile, coarse-grained and fully atomistic output structures can be directly employed in popular simulation packages, including HOOMD, Tinker and Gromacs. Moreover, HBP Builder has an easy-to-use graphical user interface and the modular architecture, making it easy to extend and reuse it as a part of other program. PMID:27188541

  6. Measuring Crack Length in Coarse Grain Ceramics

    NASA Technical Reports Server (NTRS)

    Salem, Jonathan A.; Ghosn, Louis J.

    2010-01-01

    Due to a coarse grain structure, crack lengths in precracked spinel specimens could not be measured optically, so the crack lengths and fracture toughness were estimated by strain gage measurements. An expression was developed via finite element analysis to correlate the measured strain with crack length in four-point flexure. The fracture toughness estimated by the strain gaged samples and another standardized method were in agreement.

  7. Critical time scale of coarse-graining entropy production

    NASA Astrophysics Data System (ADS)

    Sohn, Jang-il

    2016-04-01

    We study coarse-grained entropy production in an asymmetric random walk system on a periodic one-dimensional lattice. In coarse-grained systems, the original dynamics are unavoidably destroyed, but the coarse-grained entropy production is not hidden below the critical time-scale separation. The hidden entropy production is rapidly increasing near the critical time-scale separation.

  8. SimRNA: a coarse-grained method for RNA folding simulations and 3D structure prediction.

    PubMed

    Boniecki, Michal J; Lach, Grzegorz; Dawson, Wayne K; Tomala, Konrad; Lukasz, Pawel; Soltysinski, Tomasz; Rother, Kristian M; Bujnicki, Janusz M

    2016-04-20

    RNA molecules play fundamental roles in cellular processes. Their function and interactions with other biomolecules are dependent on the ability to form complex three-dimensional (3D) structures. However, experimental determination of RNA 3D structures is laborious and challenging, and therefore, the majority of known RNAs remain structurally uncharacterized. Here, we present SimRNA: a new method for computational RNA 3D structure prediction, which uses a coarse-grained representation, relies on the Monte Carlo method for sampling the conformational space, and employs a statistical potential to approximate the energy and identify conformations that correspond to biologically relevant structures. SimRNA can fold RNA molecules using only sequence information, and, on established test sequences, it recapitulates secondary structure with high accuracy, including correct prediction of pseudoknots. For modeling of complex 3D structures, it can use additional restraints, derived from experimental or computational analyses, including information about secondary structure and/or long-range contacts. SimRNA also can be used to analyze conformational landscapes and identify potential alternative structures. PMID:26687716

  9. Damage in spherical cellular membrane generated by the shock waves: Coarse-grained molecular dynamics simulation of lipid vesicle

    NASA Astrophysics Data System (ADS)

    Sliozberg, Yelena; Chantawansri, Tanya

    2014-11-01

    Traumatic Brain Injury is a major health issue that is hard to diagnose since it often occurs without signs of external injuries. While it is well known that exposure of biological cells to shock waves causes damage to the cell membrane, it is currently unknown by which mechanisms damage is caused, and how it depends on physical parameters such as shock wave velocity, shock pulse duration, or shock pulse shape. In this computational study, we use a coarse-grained model of the lipid vesicle as a generic model of a cell membrane to elucidate the general principles of the cellular damage induced by the shock wave direct passage through the cranium. Results indicate that the extent of the liposome compression does not strongly depend on the pressure pulse and that liposome extension is very sensitive to the change in the negative pressure phase. The structural integrity of the vesicle is altered as pores form in the lipid membrane at overall pressure impulses generated by supersonic shock waves, which are greater than 5 Pa.s at single or repetitive exposure. Consequently, these permeability changes may lead to changes in the influx of sodium, potassium, and calcium ions.

  10. SimRNA: a coarse-grained method for RNA folding simulations and 3D structure prediction

    PubMed Central

    Boniecki, Michal J.; Lach, Grzegorz; Dawson, Wayne K.; Tomala, Konrad; Lukasz, Pawel; Soltysinski, Tomasz; Rother, Kristian M.; Bujnicki, Janusz M.

    2016-01-01

    RNA molecules play fundamental roles in cellular processes. Their function and interactions with other biomolecules are dependent on the ability to form complex three-dimensional (3D) structures. However, experimental determination of RNA 3D structures is laborious and challenging, and therefore, the majority of known RNAs remain structurally uncharacterized. Here, we present SimRNA: a new method for computational RNA 3D structure prediction, which uses a coarse-grained representation, relies on the Monte Carlo method for sampling the conformational space, and employs a statistical potential to approximate the energy and identify conformations that correspond to biologically relevant structures. SimRNA can fold RNA molecules using only sequence information, and, on established test sequences, it recapitulates secondary structure with high accuracy, including correct prediction of pseudoknots. For modeling of complex 3D structures, it can use additional restraints, derived from experimental or computational analyses, including information about secondary structure and/or long-range contacts. SimRNA also can be used to analyze conformational landscapes and identify potential alternative structures. PMID:26687716

  11. Micro-phase assembly of active sites in a coarse-grained model of chromatin by Monte Carlo simulation

    NASA Astrophysics Data System (ADS)

    Zhang, Yang; Heermann, Dieter; Farmer, Barry; Pandey, Ras

    2011-03-01

    A coarse-grained model is used to study the self-assembly of active sites in a DNA (chromatin) chain. The chromosome is described by a bond-fluctuating chain of two types of nodes A (interacting) and B (non-interacting), distributed randomly with concentration C and 1 - C respectively. Active nodes interact with a Lennard-Jones (LJ) potential and execute their stochastic motion with the Metropolis algorithm. The depth of the LJ potential (f) , a measure of interaction strength and the concentration (C) of the active sites are varied. A number of local and global physical quantities are studied such as mobility (Mn) profile of each node, their local structural profile, root mean square (RMS) displacement (R) , radius of gyration (Rg) , and structure factor S (q) . We find that the chain segments assemble into microphase of blobs which requires higher concentration of active sites at weaker interaction. These findings are consistent with that of a dynamic loop model of chromatin on global (large) scale but differ at small scales. This work is supported in part by the Alexander von Humboldt foundation and AFRL.

  12. COFFDROP: A Coarse-Grained Nonbonded Force Field for Proteins Derived from All-Atom Explicit-Solvent Molecular Dynamics Simulations of Amino Acids

    PubMed Central

    2015-01-01

    We describe the derivation of a set of bonded and nonbonded coarse-grained (CG) potential functions for use in implicit-solvent Brownian dynamics (BD) simulations of proteins derived from all-atom explicit-solvent molecular dynamics (MD) simulations of amino acids. Bonded potential functions were derived from 1 μs MD simulations of each of the 20 canonical amino acids, with histidine modeled in both its protonated and neutral forms; nonbonded potential functions were derived from 1 μs MD simulations of every possible pairing of the amino acids (231 different systems). The angle and dihedral probability distributions and radial distribution functions sampled during MD were used to optimize a set of CG potential functions through use of the iterative Boltzmann inversion (IBI) method. The optimized set of potential functions—which we term COFFDROP (COarse-grained Force Field for Dynamic Representation Of Proteins)—quantitatively reproduced all of the “target” MD distributions. In a first test of the force field, it was used to predict the clustering behavior of concentrated amino acid solutions; the predictions were directly compared with the results of corresponding all-atom explicit-solvent MD simulations and found to be in excellent agreement. In a second test, BD simulations of the small protein villin headpiece were carried out at concentrations that have recently been studied in all-atom explicit-solvent MD simulations by Petrov and Zagrovic (PLoS Comput. Biol.2014, 5, e1003638). The anomalously strong intermolecular interactions seen in the MD study were reproduced in the COFFDROP simulations; a simple scaling of COFFDROP’s nonbonded parameters, however, produced results in better accordance with experiment. Overall, our results suggest that potential functions derived from simulations of pairwise amino acid interactions might be of quite broad applicability, with COFFDROP likely to be especially useful for modeling unfolded or intrinsically

  13. Coarse-Grained and Atomistic Modeling of Polyimides

    NASA Technical Reports Server (NTRS)

    Clancy, Thomas C.; Hinkley, Jeffrey A.

    2004-01-01

    A coarse-grained model for a set of three polyimide isomers is developed. Each polyimide is comprised of BPDA (3,3,4,4' - biphenyltetracarboxylic dianhydride) and one of three APB isomers: 1,3-bis(4-aminophenoxy)benzene, 1,4-bis(4-aminophenoxy)benzene or 1,3-bis(3-aminophenoxy)benzene. The coarse-grained model is constructed as a series of linked vectors following the contour of the polymer backbone. Beads located at the midpoint of each vector define centers for long range interaction energy between monomer subunits. A bulk simulation of each coarse-grained polyimide model is performed with a dynamic Monte Carlo procedure. These coarsegrained models are then reverse-mapped to fully atomistic models. The coarse-grained models show the expected trends in decreasing chain dimensions with increasing meta linkage in the APB section of the repeat unit, although these differences were minor due to the relatively short chains simulated here. Considerable differences are seen among the dynamic Monte Carlo properties of the three polyimide isomers. Decreasing relaxation times are seen with increasing meta linkage in the APB section of the repeat unit.

  14. Wavelets as basis functions to represent the coarse-graining potential in multiscale coarse graining approach

    NASA Astrophysics Data System (ADS)

    Maiolo, M.; Vancheri, A.; Krause, R.; Danani, A.

    2015-11-01

    In this paper, we apply Multiresolution Analysis (MRA) to develop sparse but accurate representations for the Multiscale Coarse-Graining (MSCG) approximation to the many-body potential of mean force. We rigorously framed the MSCG method into MRA so that all the instruments of this theory become available together with a multitude of new basis functions, namely the wavelets. The coarse-grained (CG) force field is hierarchically decomposed at different resolution levels enabling to choose the most appropriate wavelet family for each physical interaction without requiring an a priori knowledge of the details localization. The representation of the CG potential in this new efficient orthonormal basis leads to a compression of the signal information in few large expansion coefficients. The multiresolution property of the wavelet transform allows to isolate and remove the noise from the CG force-field reconstruction by thresholding the basis function coefficients from each frequency band independently. We discuss the implementation of our wavelet-based MSCG approach and demonstrate its accuracy using two different condensed-phase systems, i.e. liquid water and methanol. Simulations of liquid argon have also been performed using a one-to-one mapping between atomistic and CG sites. The latter model allows to verify the accuracy of the method and to test different choices of wavelet families. Furthermore, the results of the computer simulations show that the efficiency and sparsity of the representation of the CG force field can be traced back to the mathematical properties of the chosen family of wavelets. This result is in agreement with what is known from the theory of multiresolution analysis of signals.

  15. Effect of Close-Packed Plane Boundaries in a Bain Zone on the Crack Path in Simulated Coarse-Grained HAZ of Bainitic Steel

    NASA Astrophysics Data System (ADS)

    Terasaki, Hidenori; Shintome, Yutaro; Komizo, Yu-ichi; Ohata, Mitsuru; Moriguchi, Koji; Tomio, Yusaku

    2015-05-01

    Global effect of Bain-zone boundaries and the local effect of close-packed plane (CP) boundaries on the path of secondary cleavage cracks (observed on a fractured V-notch Charpy specimen) were visualized and discussed in simulated coarse-grained HAZ of bainitic steel. Microstructural unit map (Bain-zone map and CP map) was obtained by electron backscatter diffraction method for a prior austenite grain of a few hundred micrometers. Furthermore, a correlation between CP boundaries and sites that favored formation of the blocky martensite-austenite (M-A) constituent was confirmed. It was clarified that two crack deviation/local changing factors (CP boundaries and blocky M-A) are paired.

  16. Coarse-grained models for aqueous polyethylene glycol solutions.

    PubMed

    Choi, Eunsong; Mondal, Jagannath; Yethiraj, Arun

    2014-01-01

    A new coarse-grained force field is developed for polyethylene glycol (PEG) in water. The force field is based on the MARTINI model but with the big multipole water (BMW) model for the solvent. The polymer force field is reparameterized using the MARTINI protocol. The new force field removes the ring-like conformations seen in simulations of short chains with the MARTINI force field; these conformations are not observed in atomistic simulations. We also investigate the effect of using parameters for the end-group that are different from those for the repeat units, with the MARTINI and BMW/MARTINI models. We find that the new BMW/MARTINI force field removes the ring-like conformations seen in the MARTINI models and has more accurate predictions for the density of neat PEG. However, solvent-separated-pairs between chain ends and slow dynamics of the PEG reflect its own artifacts. We also carry out fine-grained simulations of PEG with bundled water clusters and show that the water bundling can lead to ring-like conformations of the polymer molecules. The simulations emphasize the pitfalls of coarse-graining several molecules into one site and suggest that polymer-solvent systems might be a stringent test for coarse-grained force fields. PMID:24350686

  17. Static Recrystallized Grain Size of Coarse-Grained Austenite in an API-X70 Pipeline Steel

    NASA Astrophysics Data System (ADS)

    Sha, Qingyun; Li, Guiyan; Li, Dahang

    2013-12-01

    The effects of initial grain size and strain on the static recrystallized grain size of coarse-grained austenite in an API-X70 steel microalloyed with Nb, V, and Ti were investigated using a Gleeble-3800 thermomechanical simulator. The results indicate that the static recrystallized grain size of coarse-grained austenite decreases with decreasing initial grain size and increasing applied strain. The addition of microalloying elements can lead to a smaller initial grain size for hot deformation due to the grain growth inhibition during reheating, resulting in decreasing of static recrystallized grain size. Based on the experimental data, an equation for the static recrystallized grain size was derived using the least square method. The grain sizes calculated using this equation fit well with the measured ones compared with the equations for fine-grained austenite and for coarse-grained austenite of Nb-V microalloyed steel.

  18. Coarse-grained distributions and superstatistics

    NASA Astrophysics Data System (ADS)

    Chavanis, Pierre-Henri

    2006-01-01

    We show an interesting connection between non-standard (non-Boltzmannian) distribution functions arising in the theory of violent relaxation for collisionless stellar systems [D. Lynden-Bell, Mon. Not. R. Astron. Soc. 136 (1967) 101.] and the notion of superstatistics recently introduced by [Beck and Cohen Physica A 322 (2003) 267]. The common link between these two theories is the emergence of coarse-grained distributions arising out of fine-grained distributions. The coarse-grained distribution functions are written as a superposition of Boltzmann factors weighted by a non-universal function. Even more general distributions can arise in case of incomplete violent relaxation (non-ergodicity). They are stable stationary solutions of the Vlasov equation. We also discuss analogies and differences between the statistical equilibrium state of a multi-components self-gravitating system and the metaequilibrium (or quasi-equilibrium) states of a collisionless stellar system. Finally, we stress the important distinction between entropies, generalized entropies, relative entropies and H-functions. We discuss applications of these ideas in two-dimensional turbulence and for other systems with long-range interactions.

  19. 7 CFR 457.113 - Coarse grains crop insurance provisions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Grains Crop Provisions 1. Definitions Coarse grains. Corn, grain sorghum, and soybeans. Grain sorghum... cash grain price per bushel for the U.S. No. 2 yellow corn, U.S. No. 2 grain sorghum, or U.S. No. 1... yellow corn and grain sorghum, or U.S. No. 1 grade for soybeans. Factors not associated with...

  20. 7 CFR 457.113 - Coarse grains crop insurance provisions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Grains Crop Provisions 1. Definitions Coarse grains. Corn, grain sorghum, and soybeans. Grain sorghum... cash grain price per bushel for the U.S. No. 2 yellow corn, U.S. No. 2 grain sorghum, or U.S. No. 1... yellow corn and grain sorghum, or U.S. No. 1 grade for soybeans. Factors not associated with...

  1. 7 CFR 457.113 - Coarse grains crop insurance provisions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Grains Crop Provisions 1. Definitions Coarse grains. Corn, grain sorghum, and soybeans. Grain sorghum... cash grain price per bushel for the U.S. No. 2 yellow corn, U.S. No. 2 grain sorghum, or U.S. No. 1... yellow corn and grain sorghum, or U.S. No. 1 grade for soybeans. Factors not associated with...

  2. Coarse-grained modelling of supercoiled RNA

    NASA Astrophysics Data System (ADS)

    Matek, Christian; Šulc, Petr; Randisi, Ferdinando; Doye, Jonathan P. K.; Louis, Ard A.

    2015-12-01

    We study the behaviour of double-stranded RNA under twist and tension using oxRNA, a recently developed coarse-grained model of RNA. Introducing explicit salt-dependence into the model allows us to directly compare our results to data from recent single-molecule experiments. The model reproduces extension curves as a function of twist and stretching force, including the buckling transition and the behaviour of plectoneme structures. For negative supercoiling, we predict denaturation bubble formation in plectoneme end-loops, suggesting preferential plectoneme localisation in weak base sequences. OxRNA exhibits a positive twist-stretch coupling constant, in agreement with recent experimental observations.

  3. Coarse grained open system quantum dynamics

    SciTech Connect

    Thanopulos, Ioannis; Brumer, Paul; Shapiro, Moshe

    2008-11-21

    We show that the quantum dynamics of a system comprised of a subspace Q coupled to a larger subspace P can be recast as a reduced set of 'coarse grained' ordinary differential equations with constant coefficients. These equations can be solved by a single diagonalization of a general complex matrix. The method makes no assumptions about the strength of the couplings between the Q and the P subspaces, nor is there any limitation on the initial population in P. The utility of the method is demonstrated via computations in three following areas: molecular compounds, photonic materials, and condensed phases.

  4. Coarse-grained modelling of surface nanobubbles

    NASA Astrophysics Data System (ADS)

    Grosfils, Patrick

    2013-05-01

    Surface nanobubbles are nanoscale gaseous objects that form on hydrophobic surfaces in contact with water. Understanding nanobubble formation and stability remains challenging due to the lack of appropriate theoretical framework and adequate modelling. Here we present a non-equilibrium coarse-grained model for nanobubbles at hydrophobic surfaces. The model is based on a lattice-gas model that has been proposed to understand the hydrophobic effect to which dynamical properties are added. The results presented demonstrate the ability of the model to reproduce the basic features of stable surface nanobubbles, which, thereby, supports the dynamical origin of these objects.

  5. Multiscale coarse graining of liquid-state systems

    NASA Astrophysics Data System (ADS)

    Izvekov, Sergei; Voth, Gregory A.

    2005-10-01

    A methodology is described to systematically derive coarse-grained (CG) force fields for molecular liquids from the underlying atomistic-scale forces. The coarse graining of an interparticle force field is accomplished by the application of a force-matching method to the trajectories and forces obtained from the atomistic trajectory and force data for the CG sites of the targeted system. The CG sites can be associated with the centers of mass of atomic groups because of the simplicity in the evaluation of forces acting on these sites from the atomistic data. The resulting system is called a multiscale coarse-grained (MS-CG) representation. The MS-CG method for liquids is applied here to water and methanol. For both liquids one-site and two-site CG representations without an explicit treatment of the long-ranged electrostatics have been derived. In addition, for water a two-site model having the explicit long-ranged electrostatics has been developed. To improve the thermodynamic properties (e.g., pressure and density) for the MS-CG models, the constraint for the instantaneous virial was included into the force-match procedure. The performance of the resulting models was evaluated against the underlying atomistic simulations and experiment. In contrast with existing approaches for coarse graining of liquid systems, the MS-CG approach is general, relies only on the interatomic interactions in the reference atomistic system.

  6. Using a Péclet number for the translocation of a polymer through a nanopore to tune coarse-grained simulations to experimental conditions

    NASA Astrophysics Data System (ADS)

    de Haan, Hendrick W.; Sean, David; Slater, Gary W.

    2015-02-01

    Coarse-grained simulations are often employed to study the translocation of DNA through a nanopore. The majority of these studies investigate the translocation process in a relatively generic sense and do not endeavor to match any particular set of experimental conditions. In this manuscript, we use the concept of a Péclet number for translocation, Pt, to compare the drift-diffusion balance in a typical experiment vs a typical simulation. We find that the standard coarse-grained approach overestimates diffusion effects by anywhere from a factor of 5 to 50 compared to experimental conditions using double stranded DNA (dsDNA). By defining a Péclet control parameter, λ , we are able to correct this and tune the simulations to replicate the experimental Pt (for dsDNA and other scenarios). To show the effect that a particular Pt can have on the dynamics of translocation, we perform simulations across a wide range of Pt values for two different types of driving forces: a force applied in the pore and a pulling force applied to the end of the polymer. As Pt brings the system from a diffusion dominated to a drift dominated regime, a variety of effects are observed including a non-monotonic dependence of the translocation time τ on Pt and a steep rise in the probability of translocating. Comparing the two force cases illustrates the impact of the crowding effects that occur on the trans side: a non-monotonic dependence of the width of the τ distributions is obtained for the in-pore force but not for the pulling force.

  7. 7 CFR 457.113 - Coarse grains crop insurance provisions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Grains Crop Provisions 1. Definitions Coarse grains— Corn, grain sorghum, and soybeans. Grain sorghum... cash grain price per bushel for the U.S. No. 2 yellow corn, U.S. No. 2 grain sorghum, or U.S. No. 1... yellow corn and grain sorghum, or U.S. No. 1 grade for soybeans. Factors not associated with...

  8. Relative Entropy and Optimization-Driven Coarse-Graining Methods in VOTCA

    PubMed Central

    Mashayak, S. Y.; Jochum, Mara N.; Koschke, Konstantin; Aluru, N. R.; Rühle, Victor; Junghans, Christoph

    2015-01-01

    We discuss recent advances of the VOTCA package for systematic coarse-graining. Two methods have been implemented, namely the downhill simplex optimization and the relative entropy minimization. We illustrate the new methods by coarse-graining SPC/E bulk water and more complex water-methanol mixture systems. The CG potentials obtained from both methods are then evaluated by comparing the pair distributions from the coarse-grained to the reference atomistic simulations. In addition to the newly implemented methods, we have also added a parallel analysis framework to improve the computational efficiency of the coarse-graining process. PMID:26192992

  9. Relative entropy and optimization-driven coarse-graining methods in VOTCA

    SciTech Connect

    Mashayak, S. Y.; Jochum, Mara N.; Koschke, Konstantin; Aluru, N. R.; Rühle, Victor; Junghans, Christoph; Huang, Xuhui

    2015-07-20

    We discuss recent advances of the VOTCA package for systematic coarse-graining. Two methods have been implemented, namely the downhill simplex optimization and the relative entropy minimization. We illustrate the new methods by coarse-graining SPC/E bulk water and more complex water-methanol mixture systems. The CG potentials obtained from both methods are then evaluated by comparing the pair distributions from the coarse-grained to the reference atomistic simulations.We have also added a parallel analysis framework to improve the computational efficiency of the coarse-graining process.

  10. 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.

  11. Translocation Thermodynamics of Linear and Cyclic Nonaarginine into Model DPPC Bilayer via Coarse-Grained Molecular Dynamics Simulation: Implications of Pore Formation and Nonadditivity

    PubMed Central

    2015-01-01

    Structural mechanisms and underlying thermodynamic determinants of efficient internalization of charged cationic peptides (cell-penetrating peptides, CPPs) such as TAT, polyarginine, and their variants, into cells, cellular constructs, and model membrane/lipid bilayers (large and giant unilamellar or multilamelar vesicles) continue to garner significant attention. Two widely held views on the translocation mechanism center on endocytotic and nonendocytotic (diffusive) processes. Espousing the view of a purely diffusive internalization process (supported by recent experimental evidence, [Säälik, P.; et al. J. Controlled Release2011, 153, 117–125]), we consider the underlying free energetics of the translocation of a nonaarginine peptide (Arg9) into a model DPPC bilayer. In the case of the Arg9 cationic peptide, recent experiments indicate a higher internalization efficiency of the cyclic structure (cyclic Arg9) relative to the linear conformer. Furthermore, recent all-atom resolution molecular dynamics simulations of cyclic Arg9 [Huang, K.; et al. Biophys. J., 2013, 104, 412–420] suggested a critical stabilizing role of water- and lipid-constituted pores that form within the bilayer as the charged Arg9 translocates deep into the bilayer center. Herein, we use umbrella sampling molecular dynamics simulations with coarse-grained Martini lipids, polarizable coarse-grained water, and peptide to explore the dependence of translocation free energetics on peptide structure and conformation via calculation of potentials of mean force along preselected reaction paths allowing and preventing membrane deformations that lead to pore formation. Within the context of the coarse-grained force fields we employ, we observe significant barriers for Arg9 translocation from bulk aqueous solution to bilayer center. Moreover, we do not find free-energy minima in the headgroup–water interfacial region, as observed in simulations using all-atom force fields. The pore-forming paths

  12. Coarse-grained modeling of DNA curvature

    NASA Astrophysics Data System (ADS)

    Freeman, Gordon S.; Hinckley, Daniel M.; Lequieu, Joshua P.; Whitmer, Jonathan K.; de Pablo, Juan J.

    2014-10-01

    The interaction of DNA with proteins occurs over a wide range of length scales, and depends critically on its local structure. In particular, recent experimental work suggests that the intrinsic curvature of DNA plays a significant role on its protein-binding properties. In this work, we present a coarse grained model of DNA that is capable of describing base-pairing, hybridization, major and minor groove widths, and local curvature. The model represents an extension of the recently proposed 3SPN.2 description of DNA [D. M. Hinckley, G. S. Freeman, J. K. Whitmer, and J. J. de Pablo, J. Chem. Phys. 139, 144903 (2013)], into which sequence-dependent shape and mechanical properties are incorporated. The proposed model is validated against experimental data including melting temperatures, local flexibilities, dsDNA persistence lengths, and minor groove width profiles.

  13. A nucleotide-level coarse-grained model of RNA

    SciTech Connect

    Šulc, Petr; Ouldridge, Thomas E.; Louis, Ard A.; Romano, Flavio; Doye, Jonathan P. K.

    2014-06-21

    We present a new, nucleotide-level model for RNA, oxRNA, based on the coarse-graining methodology recently developed for the oxDNA model of DNA. The model is designed to reproduce structural, mechanical, and thermodynamic properties of RNA, and the coarse-graining level aims to retain the relevant physics for RNA hybridization and the structure of single- and double-stranded RNA. In order to explore its strengths and weaknesses, we test the model in a range of nanotechnological and biological settings. Applications explored include the folding thermodynamics of a pseudoknot, the formation of a kissing loop complex, the structure of a hexagonal RNA nanoring, and the unzipping of a hairpin motif. We argue that the model can be used for efficient simulations of the structure of systems with thousands of base pairs, and for the assembly of systems of up to hundreds of base pairs. The source code implementing the model is released for public use.

  14. Coarse-graining of proteins based on elastic network models

    NASA Astrophysics Data System (ADS)

    Sinitskiy, Anton V.; Voth, Gregory A.

    2013-08-01

    To simulate molecular processes on biologically relevant length- and timescales, coarse-grained (CG) models of biomolecular systems with tens to even hundreds of residues per CG site are required. One possible way to build such models is explored in this article: an elastic network model (ENM) is employed to define the CG variables. Free energy surfaces are approximated by Taylor series, with the coefficients found by force-matching. CG potentials are shown to undergo renormalization due to roughness of the energy landscape and smoothing of it under coarse-graining. In the case study of hen egg-white lysozyme, the entropy factor is shown to be of critical importance for maintaining the native structure, and a relationship between the proposed ENM-mode-based CG models and traditional CG-bead-based models is discussed. The proposed approach uncovers the renormalizable character of CG models and offers new opportunities for automated and computationally efficient studies of complex free energy surfaces.

  15. A nucleotide-level coarse-grained model of RNA

    NASA Astrophysics Data System (ADS)

    Šulc, Petr; Romano, Flavio; Ouldridge, Thomas E.; Doye, Jonathan P. K.; Louis, Ard A.

    2014-06-01

    We present a new, nucleotide-level model for RNA, oxRNA, based on the coarse-graining methodology recently developed for the oxDNA model of DNA. The model is designed to reproduce structural, mechanical, and thermodynamic properties of RNA, and the coarse-graining level aims to retain the relevant physics for RNA hybridization and the structure of single- and double-stranded RNA. In order to explore its strengths and weaknesses, we test the model in a range of nanotechnological and biological settings. Applications explored include the folding thermodynamics of a pseudoknot, the formation of a kissing loop complex, the structure of a hexagonal RNA nanoring, and the unzipping of a hairpin motif. We argue that the model can be used for efficient simulations of the structure of systems with thousands of base pairs, and for the assembly of systems of up to hundreds of base pairs. The source code implementing the model is released for public use.

  16. Bayesian calibration of coarse-grained forces: Efficiently addressing transferability

    NASA Astrophysics Data System (ADS)

    Patrone, Paul N.; Rosch, Thomas W.; Phelan, Frederick R.

    2016-04-01

    Generating and calibrating forces that are transferable across a range of state-points remains a challenging task in coarse-grained (CG) molecular dynamics. In this work, we present a coarse-graining workflow, inspired by ideas from uncertainty quantification and numerical analysis, to address this problem. The key idea behind our approach is to introduce a Bayesian correction algorithm that uses functional derivatives of CG simulations to rapidly and inexpensively recalibrate initial estimates f0 of forces anchored by standard methods such as force-matching. Taking density-temperature relationships as a running example, we demonstrate that this algorithm, in concert with various interpolation schemes, can be used to efficiently compute physically reasonable force curves on a fine grid of state-points. Importantly, we show that our workflow is robust to several choices available to the modeler, including the interpolation schemes and tools used to construct f0. In a related vein, we also demonstrate that our approach can speed up coarse-graining by reducing the number of atomistic simulations needed as inputs to standard methods for generating CG forces.

  17. Coarse graining of force fields for metal-organic frameworks.

    PubMed

    Dürholt, Johannes P; Galvelis, Raimondas; Schmid, Rochus

    2016-03-14

    We have adapted our genetic algorithm based optimization approach, originally developed to generate force field parameters from quantum mechanic reference data, to derive a first coarse grained force field for a MOF, taking the atomistic MOF-FF as a reference. On the example of the copper paddle-wheel based HKUST-1, a maximally coarse grained model, using a single bead for each three and four coordinated vertex, was developed as a proof of concept. By adding non-bonded interactions with a modified Buckingham potential, the resulting MOF-FF-CGNB is able to predict local deformation energies of the building blocks as well as bulk properties like the tbovs.pto energy difference or elastic constants in a semi-quantitative way. As expected, the negative thermal expansion of HKUST-1 is not reproduced by the maximally coarse grained model. At the expense of atomic resolution, substantially larger systems (up to tens of nanometers in size) can be simulated with respect to structural and mechanical properties, bridging the gap to the mesoscale. As an example the deformation of the [111] surface of HKUST-1 by a "tip" could be computed without artifacts from periodic images. PMID:26732756

  18. Moving Beyond Watson-Crick Models of Coarse Grained DNA

    NASA Astrophysics Data System (ADS)

    Dorfman, Kevin; Linak, Margaret; Tourdot, Richard

    2012-02-01

    DNA structure possesses several levels of complexity, ranging from the sequence of bases (primary structure) to base pairing (secondary structure) to its three-dimensional shape (tertiary structure) and can produce a wide variety of conformations in addition to canonical double stranded DNA. By including non-Watson-Crick interactions in a coarse-grained model, we developed a system that not only can capture the traditional B-form double helix, but also can adopt a wide variety of other DNA conformations. In our experimentally parameterized, coarse-grained DNA model we are able to reproduce the microscopic features of double-stranded DNA without the need for explicit constraints and capture experimental melting curves for a number of short DNA hairpins. We demonstrate the utility of the model by simulating more complex tertiary structures such as the folding of the thrombin aptamer, which includes G-quartets, and strand invasion during triplex formation. Our results highlight the importance of non-canonical interactions in DNA coarse- grained models.

  19. Coarse-Grained Model of SNARE-Mediated Docking

    PubMed Central

    Fortoul, Nicole; Singh, Pankaj; Hui, Chung-Yuen; Bykhovskaia, Maria; Jagota, Anand

    2015-01-01

    Synaptic transmission requires that vesicles filled with neurotransmitter molecules be docked to the plasma membrane by the SNARE protein complex. The SNARE complex applies attractive forces to overcome the long-range repulsion between the vesicle and membrane. To understand how the balance between the attractive and repulsive forces defines the equilibrium docked state we have developed a model that combines the mechanics of vesicle/membrane deformation with an apparently new coarse-grained model of the SNARE complex. The coarse-grained model of the SNARE complex is calibrated by comparison with all-atom molecular dynamics simulations as well as by force measurements in laser tweezer experiments. The model for vesicle/membrane interactions includes the forces produced by membrane deformation and hydration or electrostatic repulsion. Combining these two parts, the coarse-grained model of the SNARE complex with membrane mechanics, we study how the equilibrium docked state varies with the number of SNARE complexes. We find that a single SNARE complex is able to bring a typical synaptic vesicle to within a distance of ∼3 nm from the membrane. Further addition of SNARE complexes shortens this distance, but an overdocked state of >4–6 SNAREs actually increases the equilibrium distance. PMID:25954883

  20. Coarse-Grained Model of SNARE-Mediated Docking.

    PubMed

    Fortoul, Nicole; Singh, Pankaj; Hui, Chung-Yuen; Bykhovskaia, Maria; Jagota, Anand

    2015-05-01

    Synaptic transmission requires that vesicles filled with neurotransmitter molecules be docked to the plasma membrane by the SNARE protein complex. The SNARE complex applies attractive forces to overcome the long-range repulsion between the vesicle and membrane. To understand how the balance between the attractive and repulsive forces defines the equilibrium docked state we have developed a model that combines the mechanics of vesicle/membrane deformation with an apparently new coarse-grained model of the SNARE complex. The coarse-grained model of the SNARE complex is calibrated by comparison with all-atom molecular dynamics simulations as well as by force measurements in laser tweezer experiments. The model for vesicle/membrane interactions includes the forces produced by membrane deformation and hydration or electrostatic repulsion. Combining these two parts, the coarse-grained model of the SNARE complex with membrane mechanics, we study how the equilibrium docked state varies with the number of SNARE complexes. We find that a single SNARE complex is able to bring a typical synaptic vesicle to within a distance of ∼ 3 nm from the membrane. Further addition of SNARE complexes shortens this distance, but an overdocked state of >4-6 SNAREs actually increases the equilibrium distance. PMID:25954883

  1. Interaction of antimicrobial peptides, BP100 and pepR, with model membrane systems as explored by Brownian dynamics simulations on a coarse-grained model.

    PubMed

    Alves, Carla S; Kairys, Visvaldas; Castanho, Miguel A R B; Fernandes, Miguel X

    2012-01-01

    This work focuses on the conformational and dynamic properties of the antimicrobial peptides (AMPs), BP100 and pepR, when confined within model membrane systems. Brownian dynamics (BD) simulations of a coarse-grained model of each respective peptide in an environment reproducing the phospholipid bilayer were carried out. Simple mean-field potentials were used to reproduce three physically different model phosphatidylcholine (PC) membrane systems. Based on the simplicity of the peptide-membrane models used, 1 micros simulations were performed. With the appropriate choice of parameters, the structure and dynamics of each peptide were recovered from each of the simulated BD trajectories. BP100 was observed to adopt a alpha-helical conformation when confined in each PC membrane. For pepR under the same conditions, the formation of an N-terminal alpha-helix was detected, whereas the C-terminus appeared to be less ordered. The dynamic properties of each peptide were characterized in terms of local and global motions. BP100 tended to localize with no preferred orientation approximately halfway across each membrane leaflet, whereas pepR localized near the membrane core with no preferred orientation. Overall, the peptide dynamics were found to vary according to the size of the peptide, as well as the width of the membrane environment. PMID:23193594

  2. SAFT-γ force field for the simulation of molecular fluids: 3. Coarse-grained models of benzene and hetero-group models of n-decylbenzene

    NASA Astrophysics Data System (ADS)

    Lafitte, Thomas; Avendaño, Carlos; Papaioannou, Vasileios; Galindo, Amparo; Adjiman, Claire S.; Jackson, George; Müller, Erich A.

    2012-06-01

    In the first paper of this series [C. Avendaño, T. Lafitte, A. Galindo, C.S. Adjiman, G. Jackson, and E.A. Müller, J. Phys. Chem. B 115, 11154 (2011)] our methodology for the development of accurate coarse-grained (CG) SAFT-γ force fields for the computer simulation of molecular fluids was introduced with carbon dioxide as a particular case study. The procedure involves the use of a molecular-based equation of state to obtain effective intermolecular parameters (from experimental fluid phase equilibrium data) appropriate for molecular simulation over a wide range of fluid conditions. We now extend the methodology to develop coarse-grained models for benzene (C6H6) that can be used in fluid phase simulations. Our SAFT-γ CG force fields for benzene consist of a simple single-segment spherical model, and a rigid three-segment ring structure of tangent spherical groups interacting via Mie (generalized Lennard-Jones) segment-segment interactions. The description of the fluid phase behaviour of benzene with our simplified CG force fields is found to be comparable to that obtained with the more sophisticated models commonly used in the field; a marked improvement is seen with our SAFT-γ models for the vapour pressure, particularly at lower temperatures. These models of benzene together with the previously developed SAFT-γ three-segment chain model of n-decane are used to develop hetero-group force fields for n-decylbenzene, in the spirit of a group contribution methodology. In our approach, the parameters of the phenyl and n-decyl groups are obtained transferably from the individual models of benzene and n-decane, respectively, and the unlike energetic parameters between the phenyl and decyl segments can be obtained from vapour-liquid equilibria data for n-decylbenzene using the SAFT-γ equation of state. The resulting CG hetero-group models are found to describe the fluid properties of n-decylbenzene over a wide range of conditions, exemplifying how our approach

  3. The multiscale coarse-graining method. II. Numerical implementation for coarse-grained molecular models

    PubMed Central

    Noid, W. G.; Liu, Pu; Wang, Yanting; Chu, Jhih-Wei; Ayton, Gary S.; Izvekov, Sergei; Andersen, Hans C.; Voth, Gregory A.

    2008-01-01

    The multiscale coarse-graining (MS-CG) method [S. Izvekov and G. A. Voth, J. Phys. Chem. B 109, 2469 (2005);J. Chem. Phys. 123, 134105 (2005)] employs a variational principle to determine an interaction potential for a CG model from simulations of an atomically detailed model of the same system. The companion paper proved that, if no restrictions regarding the form of the CG interaction potential are introduced and if the equilibrium distribution of the atomistic model has been adequately sampled, then the MS-CG variational principle determines the exact many-body potential of mean force (PMF) governing the equilibrium distribution of CG sites generated by the atomistic model. In practice, though, CG force fields are not completely flexible, but only include particular types of interactions between CG sites, e.g., nonbonded forces between pairs of sites. If the CG force field depends linearly on the force field parameters, then the vector valued functions that relate the CG forces to these parameters determine a set of basis vectors that span a vector subspace of CG force fields. The companion paper introduced a distance metric for the vector space of CG force fields and proved that the MS-CG variational principle determines the CG force force field that is within that vector subspace and that is closest to the force field determined by the many-body PMF. The present paper applies the MS-CG variational principle for parametrizing molecular CG force fields and derives a linear least squares problem for the parameter set determining the optimal approximation to this many-body PMF. Linear systems of equations for these CG force field parameters are derived and analyzed in terms of equilibrium structural correlation functions. Numerical calculations for a one-site CG model of methanol and a molecular CG model of the EMIM+∕NO3− ionic liquid are provided to illustrate the method. PMID:18601325

  4. Structural properties of polymer-brush-grafted gold nanoparticles at the oil-water interface: insights from coarse-grained simulations.

    PubMed

    Quan, Xuebo; Peng, ChunWang; Dong, Jiaqi; Zhou, Jian

    2016-04-14

    In this work, the structural properties of amphiphilic polymer-brush-grafted gold nanoparticles (AuNPs) at the oil-water interface were investigated by coarse-grained simulations. The effects of grafting architecture (diblock, mixed and Janus brush-grafted AuNPs) and hydrophilicity of polymer brushes are discussed. Simulation results indicate that functionalized AuNPs present abundant morphologies including typical core-shell, Janus-type, jellyfish-like, etc., in a water or oil-water solvent environment. It is found that hydrophobic/weak hydrophilic polymer-brush-grafted AuNPs have better phase transfer performance, especially for AuNPs modified with hydrophobic chains as outer blocks and weak hydrophilic chains as inner blocks. This kind of AuNP can cross the interface region and move into the oil phase completely. For hydrophobic/strong hydrophilic polymer-brush-grafted AuNPs, they are trapped in the interface region instead of moving into any phase. The mechanism of phase transfer is ascribed to the flexibility and mobility of outer blocks. Besides, we study the desorption energy by PMF analysis. The results demonstrate that Janus brush-grafted AuNPs show the highest interfacial stability and activity, which can be further strengthened by increasing the hydrophilicity of grafted polymer brushes. This work will promote the industrial applications of polymer-brush-grafted NPs such as phase transfer catalysis and Pickering emulsion catalysis. PMID:26954721

  5. Probability of adsorption of peptide (CR3-1, S2) chains on clay minerals by coarse-grained Monte Carlo simulation

    NASA Astrophysics Data System (ADS)

    Pandey, Ras B.; Heinz, Hendrik; Farmer, Barry L.; Jones, Sharon; Drummy, Lawrence F.; Naik, Rajesh R.

    2009-03-01

    A coarse-grained description is used to study the structure and dynamics of peptide chains (CR3-1, S2) in presence of a clay surface on a cubic lattice. A peptide chain is represented by the specific sequence of amino acids. Specificity of residues is captured via an interaction matrix based on the insight gained from the atomistic simulation, i.e., each residue interacts with surrounding residues, solvent, and the clay surface with a unique interaction potential. We use a standard LJ potential with its coefficient controlled by the interaction matrix. Simulations are performed with a number of peptide chains. Along with the global energy and dynamics of peptides, we keep track of mobility, energy (total and adsorption), and correlation with the local structure from the density profiles of each residue. Based on the analysis of local and global quantities, we are able to assess the probability of adsorption of peptides to clay surface in agreement with experiment. The probability of adsorption of S2 is found to be much higher than that of CR3-1 in which S2 is anchored by Lysine. The procedure is complementary to biopanning experiments since it allows screening a large number of peptides (more than 10E+5) on the surface to estimate their binding potential.

  6. Role of the Electrostatic Interactions in the Stabilization of Ionic Liquid Crystals: Insights from Coarse-Grained MD Simulations of an Imidazolium Model.

    PubMed

    Saielli, Giacomo; Wang, Yanting

    2016-09-01

    In order to investigate the role of the electrostatic interactions in stabilizing various phases of ionic liquids, especially smectic ionic liquid crystals, we have employed a coarse-grained model of 1-hexadecyl-3-methylimidazolium nitrate, [C16mim][NO3], to perform molecular dynamics simulations with the partial charges artificially rescaled by a factor from 0.7 to 1.2. The simulated systems have been characterized by means of orientational and translational order parameters and by distribution functions. We have found that increasing the total charge of the ions strongly stabilizes the ionic smectic phase by shifting the clearing point (melting into the isotropic liquid phase) to higher temperatures, while a smaller effect is observed on the stability of the crystal phase. Our results highlight the importance of the electrostatic interactions in promoting the formation of ionic liquid crystals through microphase segregation. Moreover, as the total charge of the model is increased, we observe a transformation from a homogeneous to a nanosegregated isotropic structure typical of ionic liquids. Therefore, a connection can be established between the degree of nanosegregation of ILs and the stability of ILC phases. All the above can be understood by the competition among electrostatic interactions between charged groups (cationic head groups and anions), van der Waals interactions between nonpolar cationic tail groups, and thermal fluctuations. PMID:27486996

  7. Monte Carlo simulation of ionizing radiation induced DNA strand breaks utilizing coarse grained high-order chromatin structures.

    PubMed

    Liang, Ying; Yang, Gen; Liu, Feng; Wang, Yugang

    2016-01-01

    Ionizing radiation threatens genome integrity by causing DNA damage. Monte Carlo simulation of the interaction of a radiation track structure with DNA provides a powerful tool for investigating the mechanisms of the biological effects. However, the more or less oversimplification of the indirect effect and the inadequate consideration of high-order chromatin structures in current models usually results in discrepancies between simulations and experiments, which undermine the predictive role of the models. Here we present a biophysical model taking into consideration factors that influence indirect effect to simulate radiation-induced DNA strand breaks in eukaryotic cells with high-order chromatin structures. The calculated yields of single-strand breaks and double-strand breaks (DSBs) for photons are in good agreement with the experimental measurements. The calculated yields of DSB for protons and α particles are consistent with simulations by the PARTRAC code, whereas an overestimation is seen compared with the experimental results. The simulated fragment size distributions for (60)Co γ irradiation and α particle irradiation are compared with the measurements accordingly. The excellent agreement with (60)Co irradiation validates our model in simulating photon irradiation. The general agreement found in α particle irradiation encourages model applicability in the high linear energy transfer range. Moreover, we demonstrate the importance of chromatin high-order structures in shaping the spectrum of initial damage. PMID:26675481

  8. Monte Carlo simulation of ionizing radiation induced DNA strand breaks utilizing coarse grained high-order chromatin structures

    NASA Astrophysics Data System (ADS)

    Liang, Ying; Yang, Gen; Liu, Feng; Wang, Yugang

    2016-01-01

    Ionizing radiation threatens genome integrity by causing DNA damage. Monte Carlo simulation of the interaction of a radiation track structure with DNA provides a powerful tool for investigating the mechanisms of the biological effects. However, the more or less oversimplification of the indirect effect and the inadequate consideration of high-order chromatin structures in current models usually results in discrepancies between simulations and experiments, which undermine the predictive role of the models. Here we present a biophysical model taking into consideration factors that influence indirect effect to simulate radiation-induced DNA strand breaks in eukaryotic cells with high-order chromatin structures. The calculated yields of single-strand breaks and double-strand breaks (DSBs) for photons are in good agreement with the experimental measurements. The calculated yields of DSB for protons and α particles are consistent with simulations by the PARTRAC code, whereas an overestimation is seen compared with the experimental results. The simulated fragment size distributions for 60Co γ irradiation and α particle irradiation are compared with the measurements accordingly. The excellent agreement with 60Co irradiation validates our model in simulating photon irradiation. The general agreement found in α particle irradiation encourages model applicability in the high linear energy transfer range. Moreover, we demonstrate the importance of chromatin high-order structures in shaping the spectrum of initial damage.

  9. Coarse-Grained Models for Protein-Cell Membrane Interactions

    PubMed Central

    Bradley, Ryan; Radhakrishnan, Ravi

    2015-01-01

    The physiological properties of biological soft matter are the product of collective interactions, which span many time and length scales. Recent computational modeling efforts have helped illuminate experiments that characterize the ways in which proteins modulate membrane physics. Linking these models across time and length scales in a multiscale model explains how atomistic information propagates to larger scales. This paper reviews continuum modeling and coarse-grained molecular dynamics methods, which connect atomistic simulations and single-molecule experiments with the observed microscopic or mesoscale properties of soft-matter systems essential to our understanding of cells, particularly those involved in sculpting and remodeling cell membranes. PMID:26613047

  10. GPU-Accelerated Molecular Dynamics Simulation to Study Liquid Crystal Phase Transition Using Coarse-Grained Gay-Berne Anisotropic Potential.

    PubMed

    Chen, Wenduo; Zhu, Youliang; Cui, Fengchao; Liu, Lunyang; Sun, Zhaoyan; Chen, Jizhong; Li, Yunqi

    2016-01-01

    Gay-Berne (GB) potential is regarded as an accurate model in the simulation of anisotropic particles, especially for liquid crystal (LC) mesogens. However, its computational complexity leads to an extremely time-consuming process for large systems. Here, we developed a GPU-accelerated molecular dynamics (MD) simulation with coarse-grained GB potential implemented in GALAMOST package to investigate the LC phase transitions for mesogens in small molecules, main-chain or side-chain polymers. For identical mesogens in three different molecules, on cooling from fully isotropic melts, the small molecules form a single-domain smectic-B phase, while the main-chain LC polymers prefer a single-domain nematic phase as a result of connective restraints in neighboring mesogens. The phase transition of side-chain LC polymers undergoes a two-step process: nucleation of nematic islands and formation of multi-domain nematic texture. The particular behavior originates in the fact that the rotational orientation of the mesogenes is hindered by the polymer backbones. Both the global distribution and the local orientation of mesogens are critical for the phase transition of anisotropic particles. Furthermore, compared with the MD simulation in LAMMPS, our GPU-accelerated code is about 4 times faster than the GPU version of LAMMPS and at least 200 times faster than the CPU version of LAMMPS. This study clearly shows that GPU-accelerated MD simulation with GB potential in GALAMOST can efficiently handle systems with anisotropic particles and interactions, and accurately explore phase differences originated from molecular structures. PMID:26986851

  11. GPU-Accelerated Molecular Dynamics Simulation to Study Liquid Crystal Phase Transition Using Coarse-Grained Gay-Berne Anisotropic Potential

    PubMed Central

    Cui, Fengchao; Liu, Lunyang; Sun, Zhaoyan; Chen, Jizhong; Li, Yunqi

    2016-01-01

    Gay-Berne (GB) potential is regarded as an accurate model in the simulation of anisotropic particles, especially for liquid crystal (LC) mesogens. However, its computational complexity leads to an extremely time-consuming process for large systems. Here, we developed a GPU-accelerated molecular dynamics (MD) simulation with coarse-grained GB potential implemented in GALAMOST package to investigate the LC phase transitions for mesogens in small molecules, main-chain or side-chain polymers. For identical mesogens in three different molecules, on cooling from fully isotropic melts, the small molecules form a single-domain smectic-B phase, while the main-chain LC polymers prefer a single-domain nematic phase as a result of connective restraints in neighboring mesogens. The phase transition of side-chain LC polymers undergoes a two-step process: nucleation of nematic islands and formation of multi-domain nematic texture. The particular behavior originates in the fact that the rotational orientation of the mesogenes is hindered by the polymer backbones. Both the global distribution and the local orientation of mesogens are critical for the phase transition of anisotropic particles. Furthermore, compared with the MD simulation in LAMMPS, our GPU-accelerated code is about 4 times faster than the GPU version of LAMMPS and at least 200 times faster than the CPU version of LAMMPS. This study clearly shows that GPU-accelerated MD simulation with GB potential in GALAMOST can efficiently handle systems with anisotropic particles and interactions, and accurately explore phase differences originated from molecular structures. PMID:26986851

  12. Interlaced coarse-graining for the dynamic cluster approximation

    NASA Astrophysics Data System (ADS)

    Staar, P.; Jiang, M.; Hähner, U. R.; Schulthess, T. C.; Maier, T. A.

    2016-04-01

    The dynamical cluster approximation (DCA) and its DCA+ extension use coarse-graining of the momentum space to reduce the complexity of quantum many-body problems, thereby mapping the bulk lattice to a cluster embedded in a dynamical mean-field host. Here, we introduce a new form of an interlaced coarse-graining and compare it with the traditional coarse-graining. While it gives a more localized self-energy for a given cluster size, we show that it leads to more controlled results with weaker cluster shape and smoother cluster size dependence, which converge to the results obtained from the standard coarse-graining with increasing cluster size. Most importantly, the new coarse-graining reduces the severity of the fermionic sign problem of the underlying quantum Monte Carlo cluster solver and thus allows for calculations on larger clusters. This enables the treatment of correlations longer ranged than those accessible with the standard coarse-graining and thus can allow for the evaluation of the exact infinite cluster size result via finite size scaling. As a demonstration, we study the hole-doped two-dimensional Hubbard model and show that the interlaced coarse-graining in combination with the extended DCA+ algorithm permits the determination of the superconducting Tc on cluster sizes for which the results can be fit with a Kosterlitz-Thouless scaling law.

  13. COARSE-GRAINED MODELING OF PROTEIN UNFOLDING DYNAMICS*

    PubMed Central

    DENG, MINGGE

    2014-01-01

    We present a new dynamic elastic network model (DENM) that describes the unfolding process of a force-loaded protein. The protein interaction network and its potentials are constructed based on information of its native-state structure obtained from the Protein Data Bank, with network nodes positioned at the Cα coordinates of the protein backbone. Specifically, to mimic the unfolding process, i.e., to simulate the process of overcoming the local energy barrier on the free energy landscape with force loading, the noncovalent protein network bonds (i.e., hydrogen bonds, salt bridges, hydrophobic contacts, etc.) are broken one-by-one with a certain probability, while the strong covalent bonds along the backbone (i.e., peptide bonds, disulfide bonds, etc.) are kept intact. The jumping event from local energy minima (bonds breaking rate) are chosen according to Kramer’s theory and the Bell model. Moreover, we exploit the self-similar structure of proteins at different scales to design an effective coarse-graining procedure for DENM with optimal parameter selection. The robustness of DENM is validated by coarse-grained molecular dynamics (MD) simulation against atomistic MD simulation of force-extension processes of the Fibrinogen and Titin Immunoglobulin proteins. We observe that the native structure of the proteins determines the total unfolding dynamics (including large deviations) and not just the fluctuations around the native state. PMID:25400515

  14. A quantitative coarse-grain model for lipid bilayers.

    PubMed

    Orsi, Mario; Haubertin, David Y; Sanderson, Wendy E; Essex, Jonathan W

    2008-01-24

    A simplified particle-based computer model for hydrated phospholipid bilayers has been developed and applied to quantitatively predict the major physical features of fluid-phase biomembranes. Compared with available coarse-grain methods, three novel aspects are introduced. First, the main electrostatic features of the system are incorporated explicitly via charges and dipoles. Second, water is accurately (yet efficiently) described, on an individual level, by the soft sticky dipole model. Third, hydrocarbon tails are modeled using the anisotropic Gay-Berne potential. Simulations are conducted by rigid-body molecular dynamics. Our technique proves 2 orders of magnitude less demanding of computational resources than traditional atomic-level methodology. Self-assembled bilayers quantitatively reproduce experimental observables such as electron density, compressibility moduli, dipole potential, lipid diffusion, and water permeability. The lateral pressure profile has been calculated, along with the elastic curvature constants of the Helfrich expression for the membrane bending energy; results are consistent with experimental estimates and atomic-level simulation data. Several of the results presented have been obtained for the first time using a coarse-grain method. Our model is also directly compatible with atomic-level force fields, allowing mixed systems to be simulated in a multiscale fashion. PMID:18085766

  15. Effects of Concentrations on the Transdermal Permeation Enhancing Mechanisms of Borneol: A Coarse-Grained Molecular Dynamics Simulation on Mixed-Bilayer Membranes

    PubMed Central

    Dai, Xingxing; Yin, Qianqian; Wan, Guang; Wang, Ran; Shi, Xinyuan; Qiao, Yanjiang

    2016-01-01

    Borneol is a natural permeation enhancer that is effective in drugs used in traditional clinical practices as well as in modern scientific research. However, its molecular mechanism is not fully understood. In this study, a mixed coarse-grained model of stratum corneum (SC) lipid bilayer comprised of Ceramide-N-sphingosine (CER NS) 24:0, cholesterol (CHOL) and free fatty acids (FFA) 24:0 (2:2:1) was used to examine the permeation enhancing mechanism of borneol on the model drug osthole. We found two different mechanisms that were dependent on concentrations levels of borneol. At low concentrations, the lipid system maintained a bilayer structure. The addition of borneol made the lipid bilayer loosen and improved drug permeation. The “pull” effect of borneol also improved drug permeation. However, for a strongly hydrophobic drug like osthole, the permeation enhancement of borneol was limited. When most borneol molecules permeated into bilayers and were located at the hydrophobic tail region, the spatial competition effect inhibited drug molecules from permeating deeper into the bilayer. At high concentrations, borneol led to the formation of water pores and long-lived reversed micelles. This improved the permeation of osthole and possibly other hydrophobic or hydrophilic drugs through the SC. Our simulation results were supported by Franz diffusion tests and transmission electron microscope (TEM) experiments. PMID:27548141

  16. On the dynamics of molecular self-assembly and the structural analysis of bilayer membranes using coarse-grained molecular dynamics simulations.

    PubMed

    Schindler, Tanja; Kröner, Dietmar; Steinhauser, Martin O

    2016-09-01

    We present a molecular dynamics simulation study of the self-assembly of coarse-grained lipid molecules from unbiased random initial configurations. Our lipid model is based on a well-tried CG polymer model with an additional potential that mimics the hydrophobic properties of lipid tails. We find that several stages of self-organization of lipid clusters are involved in the dynamics of bilayer formation and that the resulting equilibrium structures sensitively depend on the strength of hydrophobic interactions hc of the lipid tails and on temperature T. The obtained stable lipid membranes are quantitatively analyzed with respect to their local structure and their degree of order. At equilibrium, we obtain self-stabilizing bilayer membrane structures that exhibit a bending stiffness κB and compression modulus KC comparable to experimental measurements under physiological conditions. We present a phase diagram of our lipid model which covers a sol-gel transition, a liquid (or gel-like) phase including stable bilayer structures and vesicle formation, as well as a quasi-crystalline phase. We also determine the exact conditions for temperature T and degree of hydrophobicity hc for stable bilayer formation including closed vesicles. PMID:27216316

  17. Electrostatic Interaction between RNA and Protein Capsid in CCMV Simulated by a Coarse-grain RNA model and a Monte Carlo Approach

    PubMed Central

    Zhang, Deqiang; Konecny, Robert; Baker, Nathan A.; McCammon, J. Andrew

    2008-01-01

    Although many viruses have been crystallized and the protein capsid structures have been determined by X-ray crystallography, the nucleic acids often can not be resolved. This is especially true for RNA viruses. The lack of information about the conformation of DNA/RNA greatly hinders our understanding of the assembly mechanism of various viruses. Here we combine a coarse-grain model and a Monte Carlo method to simulate the distribution of viral RNA inside the capsid of Cowpea Chlorotic Mottle Virus (CCMV). Our results show that there is very strong interaction between the N-terminal residues of the capsid proteins, which are highly positive-charged, and the viral RNA. Without these residues, the binding energy disfavors the binding of RNA by the capsid. The RNA forms a shell close to the capsid with the highest densities associated with the capsid dimers. These high-density regions are connected to each other in the shape of a continuous net of triangles. The overall icosahedral shape of the net overlaps with the capsid subunit icosahedral organization. Medium density of RNA is found under the pentamers of the capsid. These findings are consistent with experimental observations. PMID:15386271

  18. Effects of Concentrations on the Transdermal Permeation Enhancing Mechanisms of Borneol: A Coarse-Grained Molecular Dynamics Simulation on Mixed-Bilayer Membranes.

    PubMed

    Dai, Xingxing; Yin, Qianqian; Wan, Guang; Wang, Ran; Shi, Xinyuan; Qiao, Yanjiang

    2016-01-01

    Borneol is a natural permeation enhancer that is effective in drugs used in traditional clinical practices as well as in modern scientific research. However, its molecular mechanism is not fully understood. In this study, a mixed coarse-grained model of stratum corneum (SC) lipid bilayer comprised of Ceramide-N-sphingosine (CER NS) 24:0, cholesterol (CHOL) and free fatty acids (FFA) 24:0 (2:2:1) was used to examine the permeation enhancing mechanism of borneol on the model drug osthole. We found two different mechanisms that were dependent on concentrations levels of borneol. At low concentrations, the lipid system maintained a bilayer structure. The addition of borneol made the lipid bilayer loosen and improved drug permeation. The "pull" effect of borneol also improved drug permeation. However, for a strongly hydrophobic drug like osthole, the permeation enhancement of borneol was limited. When most borneol molecules permeated into bilayers and were located at the hydrophobic tail region, the spatial competition effect inhibited drug molecules from permeating deeper into the bilayer. At high concentrations, borneol led to the formation of water pores and long-lived reversed micelles. This improved the permeation of osthole and possibly other hydrophobic or hydrophilic drugs through the SC. Our simulation results were supported by Franz diffusion tests and transmission electron microscope (TEM) experiments. PMID:27548141

  19. Coarse Grained Simulations of the Electrolytes at the Water-Air Interface from Many Body Dissipative Particle Dynamics.

    PubMed

    Ghoufi, Aziz; Malfreyt, Patrice

    2012-03-13

    Modeling interfacial properties is a major challenge for mesoscopic simulation methods. Many-body dissipative particle dynamics (MDPD) is then a promising method to model heterogeneous systems at long time and length scales. However no rule exists to obtain a set of MDPD parameters capable to reproduce the thermodynamic properties of a molecular system of a specific chemistry. In this letter, we provide a general multiscale method to obtain a set of parameters from atomistic simulations using Flory-Huggins theory (FH) to be used with dissipative particle dynamics. We demonstrate the high quality and the transferability of the resulting parameters on the salt concentration dependence of surface tension. We also show the specificity of inorganic salt at the water-air interface. Our results indicate that the increase of surface tension with the salt concentration cannot be explained in terms of the charge image concept based on the Wagner, Onsager, and Samaras theory but rather in terms of the ion hydration. PMID:26593339

  20. Residue energy and mobility in sequence to global structure and dynamics of a HIV-1 protease (1DIFA) by a coarse-grained Monte Carlo simulation

    NASA Astrophysics Data System (ADS)

    Pandey, R. B.; Farmer, B. L.

    2009-01-01

    Energy, mobility, and structural profiles of residues in a specific sequence of human immunodeficiency virus (HIV)-1 protease chain and its global conformation and dynamics are studied by a coarse-grained computer simulation model on a cubic lattice. HIV-1 protease is described by a chain of 99 residues (nodes) in a specific sequence (1DIFA) with N- and C-terminals on the lattice, where empty lattice sites represent an effective solvent medium. Internal structures of the residues are ignored but their specificities are captured via an interaction (ɛij) matrix (residue-residue, residue-solvent) of the coefficient (fɛij) of the Lennard-Jones potential. Simulations are performed for a range of interaction strength (f ) with the solvent-residue interaction describing the quality of the solvent. Snapshots of the protein show considerable changes in the conformation of the protein on varying the interaction. From the mobility and energy profiles of the residues, it is possible to identify the active (and not so active) segments of the protein and consequently their role in proteolysis. Contrary to interaction thermodynamics, the hydrophobic residues possess higher configurational energy and lower mobility while the electrostatic and polar residues are more mobile despite their lower interaction energy. Segments of hydrophobic core residues, crucial for the structural evolution of the protein are identified—some of which are consistent with recent molecular dynamics simulation in context to possible clinical observations. Global energy and radius of gyration of the protein exhibit nonmonotonic dependence on the interaction strength (f) with opposite trends, e.g., rapid transition into globular structure with higher energy. Variations of the rms displacement of the protein and that of a tracer residue, Gly49, with the time steps show how they slow down on increasing the interaction strength.

  1. Self-assembly behaviours of primitive and modern lipid membrane solutions: a coarse-grained molecular simulation study.

    PubMed

    Arai, Noriyoshi; Yoshimoto, Yuki; Yasuoka, Kenji; Ebisuzaki, Toshikazu

    2016-07-28

    Researchers have studied the origin of life and the process of evolution on early Earth for decades. However, we lack a comprehensive understanding of biogenesis, because there are many stages in the formation and growth of the first cell. We investigate the self-replication processes of coacervate protocells using computer simulations of single-chain lipid and phospholipid aqueous mixtures. Based on a morphological phase diagram, we develop a model of prebiotic self-replication driven by only environmental factors (i.e. temperature and lipid concentrations) without any external force. Moreover, we investigate high concentration structures during the process of self-replication. These structures have an advantage in fusion and repair of cell membranes. Therefore, lipid hot spots may have existed in primordial soup. PMID:27378100

  2. Morphology and mechanical properties of multi-stranded amyloid fibrils probed by atomistic and coarse-grained simulations

    NASA Astrophysics Data System (ADS)

    Yoon, Gwonchan; Lee, Myeongsang; Kim, Kyungwoo; In Kim, Jae; Chang, Hyun Joon; Baek, Inchul; Eom, Kilho; Na, Sungsoo

    2015-12-01

    Amyloid fibrils are responsible for pathogenesis of various diseases and exhibit the structural feature of an ordered, hierarchical structure such as multi-stranded helical structure. As the multi-strandedness of amyloid fibrils has recently been found to be highly correlated with their toxicity and infectivity, it is necessary to study how the hierarchical (i.e. multi-stranded) structure of amyloid fibril is formed. Moreover, although it has recently been reported that the nanomechanics of amyloid proteins plays a key role on the amyloid-induced pathogenesis, a critical role that the multi-stranded helical structure of the fibrils plays in their nanomechanical properties has not fully characterized. In this work, we characterize the morphology and mechanical properties of multi-stranded amyloid fibrils by using equilibrium molecular dynamics simulation and elastic network model. It is shown that the helical pitch of multi-stranded amyloid fibril is linearly proportional to the number of filaments comprising the amyloid fibril, and that multi-strandedness gives rise to improving the bending rigidity of the fibril. Moreover, we have also studied the morphology and mechanical properties of a single protofilament (filament) in order to understand the effect of cross-β structure and mutation on the structures and mechanical properties of amyloid fibrils. Our study sheds light on the underlying design principles showing how the multi-stranded amyloid fibril is formed and how the structure of amyloid fibrils governs their nanomechanical properties.

  3. Potential of mean force analysis of the self-association of leucine-rich transmembrane α-helices: Difference between atomistic and coarse-grained simulations

    NASA Astrophysics Data System (ADS)

    Nishizawa, Manami; Nishizawa, Kazuhisa

    2014-08-01

    Interaction of transmembrane (TM) proteins is important in many biological processes. Large-scale computational studies using coarse-grained (CG) simulations are becoming popular. However, most CG model parameters have not fully been calibrated with respect to lateral interactions of TM peptide segments. Here, we compare the potential of mean forces (PMFs) of dimerization of TM helices obtained using a MARTINI CG model and an atomistic (AT) Berger lipids-OPLS/AA model (ATOPLS). For helical, tryptophan-flanked, leucine-rich peptides (WL15 and WALP15) embedded in a parallel configuration in an octane slab, the ATOPLS PMF profiles showed a shallow minimum (with a depth of approximately 3 kJ/mol; i.e., a weak tendency to dimerize). A similar analysis using the CHARMM36 all-atom model (ATCHARMM) showed comparable results. In contrast, the CG analysis generally showed steep PMF curves with depths of approximately 16-22 kJ/mol, suggesting a stronger tendency to dimerize compared to the AT model. This CG > AT discrepancy in the propensity for dimerization was also seen for dilauroylphosphatidylcholine (DLPC)-embedded peptides. For a WL15 (and WALP15)/DLPC bilayer system, ATOPLS PMF showed a repulsive mean force for a wide range of interhelical distances, in contrast to the attractive forces observed in the octane system. The change from the octane slab to the DLPC bilayer also mitigated the dimerization propensity in the CG system. The dimerization energies of CG (AALALAA)3 peptides in DLPC and dioleoylphosphatidylcholine bilayers were in good agreement with previous experimental data. The lipid headgroup, but not the length of the lipid tails, was a key causative factor contributing to the differences between octane and DLPC. Furthermore, the CG model, but not the AT model, showed high sensitivity to changes in amino acid residues located near the lipid-water interface and hydrophobic mismatch between the peptides and membrane. These findings may help interpret CG and AT

  4. Coarse-Grained Simulations of Topology-Dependent Mechanisms of Protein Unfolding and Translocation Mediated by ClpY ATPase Nanomachines.

    PubMed

    Kravats, Andrea N; Tonddast-Navaei, Sam; Stan, George

    2016-01-01

    Clp ATPases are powerful ring shaped nanomachines which participate in the degradation pathway of the protein quality control system, coupling the energy from ATP hydrolysis to threading substrate proteins (SP) through their narrow central pore. Repetitive cycles of sequential intra-ring ATP hydrolysis events induce axial excursions of diaphragm-forming central pore loops that effect the application of mechanical forces onto SPs to promote unfolding and translocation. We perform Langevin dynamics simulations of a coarse-grained model of the ClpY ATPase-SP system to elucidate the molecular details of unfolding and translocation of an α/β model protein. We contrast this mechanism with our previous studies which used an all-α SP. We find conserved aspects of unfolding and translocation mechanisms by allosteric ClpY, including unfolding initiated at the tagged C-terminus and translocation via a power stroke mechanism. Topology-specific aspects include the time scales, the rate limiting steps in the degradation pathway, the effect of force directionality, and the translocase efficacy. Mechanisms of ClpY-assisted unfolding and translocation are distinct from those resulting from non-allosteric mechanical pulling. Bulk unfolding simulations, which mimic Atomic Force Microscopy-type pulling, reveal multiple unfolding pathways initiated at the C-terminus, N-terminus, or simultaneously from both termini. In a non-allosteric ClpY ATPase pore, mechanical pulling with constant velocity yields larger effective forces for SP unfolding, while pulling with constant force results in simultaneous unfolding and translocation. PMID:26734937

  5. Conformational State Distributions and Catalytically Relevant Dynamics of a Hinge-Bending Enzyme Studied by Single-Molecule FRET and a Coarse-Grained Simulation

    PubMed Central

    Gabba, Matteo; Poblete, Simón; Rosenkranz, Tobias; Katranidis, Alexandros; Kempe, Daryan; Züchner, Tina; Winkler, Roland G.; Gompper, Gerhard; Fitter, Jörg

    2014-01-01

    Over the last few decades, a view has emerged showing that multidomain enzymes are biological machines evolved to harness stochastic kicks of solvent particles into highly directional functional motions. These intrinsic motions are structurally encoded, and Nature makes use of them to catalyze chemical reactions by means of ligand-induced conformational changes and states redistribution. Such mechanisms align reactive groups for efficient chemistry and stabilize conformers most proficient for catalysis. By combining single-molecule Förster resonance energy transfer measurements with normal mode analysis and coarse-grained mesoscopic simulations, we obtained results for a hinge-bending enzyme, namely phosphoglycerate kinase (PGK), which support and extend these ideas. From single-molecule Förster resonance energy transfer, we obtained insight into the distribution of conformational states and the dynamical properties of the domains. The simulations allowed for the characterization of interdomain motions of a compact state of PGK. The data show that PGK is intrinsically a highly dynamic system sampling a wealth of conformations on timescales ranging from nanoseconds to milliseconds and above. Functional motions encoded in the fold are performed by the PGK domains already in its ligand-free form, and substrate binding is not required to enable them. Compared to other multidomain proteins, these motions are rather fast and presumably not rate-limiting in the enzymatic reaction. Ligand binding slightly readjusts the orientation of the domains and feasibly locks the protein motions along a preferential direction. In addition, the functionally relevant compact state is stabilized by the substrates, and acts as a prestate to reach active conformations by means of Brownian motions. PMID:25418172

  6. Electro-optic material design criteria derived from condensed matter simulations using the level-of-detail coarse-graining approach

    NASA Astrophysics Data System (ADS)

    Tillack, Andreas F.

    Electro-optic materials enable a wide variety of photonics applications such as micro-scale optical sensors, terahertz spectroscopy, photonic computing, quantum key distribution, and high speed data transmission for computing as well as global telecommunications. Organic 2nd-order non-linear optical (ONLO) materials offer several key advantages for photonic devices such as intrinsically higher bandwidth on the order of THz, lower power consumption, and smaller device structures compared to currently used inorganic materials such as lithium niobate. ONLO materials consist of electro-optic chromophores arranged such that overall, acentric dipole order is present in the material. Crucial insight into the acentric ordering of an ensemble of electro-optic chromophores can be provided by computational modeling. Presented in this dissertation is a coarse-graining (CG) Monte Carlo approach, the Level-of-Detail (LoD) method, enabling the systematic determination of CG model parameters with no adjustable parameters from ab initio quantum mechanical calculations and fully-atomistic force fields. The LoD method's ability to correctly represent all-atom behavior is demonstrated on a diverse range of condensed molecular systems relevant to different aspects of the simulation of electro-optic materials such as the accurate simulation of pi-pi interactions, the incorporation of flexible molecular linkers, and the prediction of dielectric behavior. Details of molecular interactions that determine the extent of acentric order are investigated and the observations and conclusions derived in this thesis culminate in a set of design criteria for construction of future molecules by experimentalists.

  7. Coarse-Grained Simulations of Topology-Dependent Mechanisms of Protein Unfolding and Translocation Mediated by ClpY ATPase Nanomachines

    PubMed Central

    Kravats, Andrea N.; Tonddast-Navaei, Sam; Stan, George

    2016-01-01

    Clp ATPases are powerful ring shaped nanomachines which participate in the degradation pathway of the protein quality control system, coupling the energy from ATP hydrolysis to threading substrate proteins (SP) through their narrow central pore. Repetitive cycles of sequential intra-ring ATP hydrolysis events induce axial excursions of diaphragm-forming central pore loops that effect the application of mechanical forces onto SPs to promote unfolding and translocation. We perform Langevin dynamics simulations of a coarse-grained model of the ClpY ATPase-SP system to elucidate the molecular details of unfolding and translocation of an α/β model protein. We contrast this mechanism with our previous studies which used an all-α SP. We find conserved aspects of unfolding and translocation mechanisms by allosteric ClpY, including unfolding initiated at the tagged C-terminus and translocation via a power stroke mechanism. Topology-specific aspects include the time scales, the rate limiting steps in the degradation pathway, the effect of force directionality, and the translocase efficacy. Mechanisms of ClpY-assisted unfolding and translocation are distinct from those resulting from non-allosteric mechanical pulling. Bulk unfolding simulations, which mimic Atomic Force Microscopy-type pulling, reveal multiple unfolding pathways initiated at the C-terminus, N-terminus, or simultaneously from both termini. In a non-allosteric ClpY ATPase pore, mechanical pulling with constant velocity yields larger effective forces for SP unfolding, while pulling with constant force results in simultaneous unfolding and translocation. PMID:26734937

  8. Conformational state distributions and catalytically relevant dynamics of a hinge-bending enzyme studied by single-molecule FRET and a coarse-grained simulation.

    PubMed

    Gabba, Matteo; Poblete, Simón; Rosenkranz, Tobias; Katranidis, Alexandros; Kempe, Daryan; Züchner, Tina; Winkler, Roland G; Gompper, Gerhard; Fitter, Jörg

    2014-10-21

    Over the last few decades, a view has emerged showing that multidomain enzymes are biological machines evolved to harness stochastic kicks of solvent particles into highly directional functional motions. These intrinsic motions are structurally encoded, and Nature makes use of them to catalyze chemical reactions by means of ligand-induced conformational changes and states redistribution. Such mechanisms align reactive groups for efficient chemistry and stabilize conformers most proficient for catalysis. By combining single-molecule Förster resonance energy transfer measurements with normal mode analysis and coarse-grained mesoscopic simulations, we obtained results for a hinge-bending enzyme, namely phosphoglycerate kinase (PGK), which support and extend these ideas. From single-molecule Förster resonance energy transfer, we obtained insight into the distribution of conformational states and the dynamical properties of the domains. The simulations allowed for the characterization of interdomain motions of a compact state of PGK. The data show that PGK is intrinsically a highly dynamic system sampling a wealth of conformations on timescales ranging from nanoseconds to milliseconds and above. Functional motions encoded in the fold are performed by the PGK domains already in its ligand-free form, and substrate binding is not required to enable them. Compared to other multidomain proteins, these motions are rather fast and presumably not rate-limiting in the enzymatic reaction. Ligand binding slightly readjusts the orientation of the domains and feasibly locks the protein motions along a preferential direction. In addition, the functionally relevant compact state is stabilized by the substrates, and acts as a prestate to reach active conformations by means of Brownian motions. PMID:25418172

  9. Bayesian parametrization of coarse-grain dissipative dynamics models

    NASA Astrophysics Data System (ADS)

    Dequidt, Alain; Solano Canchaya, Jose G.

    2015-08-01

    We introduce a new bottom-up method for the optimization of dissipative coarse-grain models. The method is based on Bayesian optimization of the likelihood to reproduce a coarse-grained reference trajectory obtained from analysis of a higher resolution molecular dynamics trajectory. This new method is related to force matching techniques, but using the total force on each grain averaged on a coarse time step instead of instantaneous forces. It has the advantage of not being limited to pairwise short-range interactions in the coarse-grain model and also yields an estimation of the friction parameter controlling the dynamics. The theory supporting the method is exposed in a practical perspective, with an analytical solution for the optimal set of parameters. The method was first validated by using it on a system with a known optimum. The new method was then tested on a simple system: n-pentane. The local molecular structure of the optimized model is in excellent agreement with the reference system. An extension of the method allows to get also an excellent agreement for the equilibrium density. As for the dynamic properties, they are also very satisfactory, but more sensitive to the choice of the coarse-grain representation. The quality of the final force field depends on the definition of the coarse grain degrees of freedom and interactions. We consider this method as a serious alternative to other methods like iterative Boltzmann inversion, force matching, and Green-Kubo formulae.

  10. Effective surface coverage of coarse-grained soft matter.

    PubMed

    Craven, Galen T; Popov, Alexander V; Hernandez, Rigoberto

    2014-12-11

    The surface coverage of coarse-grained macromolecules bound to a solid substrate is not simply proportional to the two-dimensional number density because macromolecules can overlap. As a function of the overlap probability δ, we have developed analytical formulas and computational models capable of characterizing this nonlinear relationship. For simplicity, we ignore site-site interactions that would be induced by length-scale mismatches between binding sites and the radius of gyration of the incident coarse-grained macromolecular species. The interactions between macromolecules are modeled with a finite bounded potential that allows multiple macromolecules to occupy the same binding site. The softness of the bounded potential is thereby reduced to the single parameter δ. Through variation of this parameter, completely hard (δ = 0) and completely soft (δ = 1) behavior can be bridged. For soft macromolecular interactions (δ > 0), multiple occupancy reduces the fraction of sites ϕ occupied on the substrate. We derive the exact transition probability between sequential configurations and use this probability to predict ϕ and the distribution of occupied sites. Due to the complexity of the exact ϕ expressions and their analytical intractability at the thermodynamic limit, we apply a simplified mean-field (MF) expression for ϕ. The MF model is found to be in excellent agreement with the exact result. Both the exact and MF models are applied to an example dynamical system with multibody interactions governed by a stochastic bounded potential. Both models show agreement with results measured from simulation. PMID:25059882

  11. A coarse-grained model of microtubule self-assembly

    NASA Astrophysics Data System (ADS)

    Regmi, Chola; Cheng, Shengfeng

    Microtubules play critical roles in cell structures and functions. They also serve as a model system to stimulate the next-generation smart, dynamic materials. A deep understanding of their self-assembly process and biomechanical properties will not only help elucidate how microtubules perform biological functions, but also lead to exciting insight on how microtubule dynamics can be altered or even controlled for specific purposes such as suppressing the division of cancer cells. Combining all-atom molecular dynamics (MD) simulations and the essential dynamics coarse-graining method, we construct a coarse-grained (CG) model of the tubulin protein, which is the building block of microtubules. In the CG model a tubulin dimer is represented as an elastic network of CG sites, the locations of which are determined by examining the protein dynamics of the tubulin and identifying the essential dynamic domains. Atomistic MD modeling is employed to directly compute the tubulin bond energies in the surface lattice of a microtubule, which are used to parameterize the interactions between CG building blocks. The CG model is then used to study the self-assembly pathways, kinetics, dynamics, and nanomechanics of microtubules.

  12. Effects of Concentration and Temperature on DNA Hybridization by Two Closely Related Sequences via Large-Scale Coarse-Grained Simulations.

    PubMed

    Markegard, Cade B; Gallivan, Cameron P; Cheng, Darrell D; Nguyen, Hung D

    2016-08-18

    A newly developed coarse-grained model called BioModi is utilized to elucidate the effects of temperature and concentration on DNA hybridization in self-assembly. Large-scale simulations demonstrate that complementary strands of either the tetrablock sequence or randomized sequence with equivalent number of cytosine or guanine nucleotides can form completely hybridized double helices. Even though the end states are the same for the two sequences, there exist multiple kinetic pathways that are populated with a wider range of transient aggregates of different sizes in the system of random sequences compared to that of the tetrablock sequence. The ability of these aggregates to undergo the strand displacement mechanism to form only double helices depends upon the temperature and DNA concentration. On one hand, low temperatures and high concentrations drive the formation and enhance stability of large aggregating species. On the other hand, high temperatures destabilize base-pair interactions and large aggregates. There exists an optimal range of moderate temperatures and low concentrations that allow minimization of large aggregate formation and maximization of fully hybridized dimers. Such investigation on structural dynamics of aggregating species by two closely related sequences during the self-assembly process demonstrates the importance of sequence design in avoiding the formation of metastable species. Finally, from kinetic modeling of self-assembly dynamics, the activation energy for the formation of double helices was found to be in agreement with experimental results. The framework developed in this work can be applied to the future design of DNA nanostructures in both fields of structural DNA nanotechnology and dynamic DNA nanotechnology wherein equilibrium end states and nonequilibrium dynamics are equally important requiring investigation in cooperation. PMID:27447850

  13. An advanced coarse-grained nucleosome core particle model for computer simulations of nucleosome-nucleosome interactions under varying ionic conditions.

    PubMed

    Fan, Yanping; Korolev, Nikolay; Lyubartsev, Alexander P; Nordenskiöld, Lars

    2013-01-01

    In the eukaryotic cell nucleus, DNA exists as chromatin, a compact but dynamic complex with histone proteins. The first level of DNA organization is the linear array of nucleosome core particles (NCPs). The NCP is a well-defined complex of 147 bp DNA with an octamer of histones. Interactions between NCPs are of paramount importance for higher levels of chromatin compaction. The polyelectrolyte nature of the NCP implies that nucleosome-nucleosome interactions must exhibit a great influence from both the ionic environment as well as the positively charged and highly flexible N-terminal histone tails, protruding out from the NCP. The large size of the system precludes a modelling analysis of chromatin at an all-atom level and calls for coarse-grained approximations. Here, a model of the NCP that include the globular histone core and the flexible histone tails described by one particle per each amino acid and taking into account their net charge is proposed. DNA wrapped around the histone core was approximated at the level of two base pairs represented by one bead (bases and sugar) plus four beads of charged phosphate groups. Computer simulations, using a Langevin thermostat, in a dielectric continuum with explicit monovalent (K(+)), divalent (Mg(2+)) or trivalent (Co(NH(3))(6) (3+)) cations were performed for systems with one or ten NCPs. Increase of the counterion charge results in a switch from repulsive NCP-NCP interaction in the presence of K(+), to partial aggregation with Mg(2+) and to strong mutual attraction of all 10 NCPs in the presence of CoHex(3+). The new model reproduced experimental results and the structure of the NCP-NCP contacts is in agreement with available data. Cation screening, ion-ion correlations and tail bridging contribute to the NCP-NCP attraction and the new NCP model accounts for these interactions. PMID:23418426

  14. SAFT-γ force field for the simulation of molecular fluids: 4. A single-site coarse-grained model of water applicable over a wide temperature range

    NASA Astrophysics Data System (ADS)

    Lobanova, Olga; Avendaño, Carlos; Lafitte, Thomas; Müller, Erich A.; Jackson, George

    2015-05-01

    In this work, we develop coarse-grained (CG) force fields for water, where the effective CG intermolecular interactions between particles are estimated from an accurate description of the macroscopic experimental vapour-liquid equilibria data by means of a molecular-based equation of state. The statistical associating fluid theory for Mie (generalised Lennard-Jones) potentials of variable range (SAFT-VR Mie) is used to parameterise spherically symmetrical (isotropic) force fields for water. The resulting SAFT-γ CG models are based on the Mie (8-6) form with size and energy parameters that are temperature dependent; the latter dependence is a consequence of the angle averaging of the directional polar interactions present in water. At the simplest level of CG where a water molecule is represented as a single bead, it is well known that an isotropic potential cannot be used to accurately reproduce all of the thermodynamic properties of water simultaneously. In order to address this deficiency, we propose two CG potential models of water based on a faithful description of different target properties over a wide range of temperatures: our CGW1-vle model is parameterised to match the saturated-liquid density and vapour pressure; our other CGW1-ift model is parameterised to match the saturated-liquid density and vapour-liquid interfacial tension. A higher level of CG corresponding to two water molecules per CG bead is also considered: the corresponding CGW2-bio model is developed to reproduce the saturated-liquid density and vapour-liquid interfacial tension in the physiological temperature range, and is particularly suitable for the large-scale simulation of bio-molecular systems. A critical comparison of the phase equilibrium and transport properties of the proposed force fields is made with the more traditional atomistic models.

  15. Self-organization of hydrophobic-capped triblock copolymers with a polyelectrolyte midblock: a coarse-grained molecular dynamics simulation study.

    PubMed

    Ghelichi, Mahdi; Qazvini, Nader Taheri

    2016-05-18

    We present the results of a Langevin dynamics simulation study of micellar organization and hydrogel formation in the solutions of coarse-grained ABA copolymer chains. Polymer chains are modeled as bead-spring chains of Lennard-Jones particles by explicit treatment of ionic species in implicit solvent. The studied copolymer is composed of a polyelectrolyte midblock flanked by two hydrophobic endblocks. We explore the self-assembly of copolymer solutions at a fixed polymer concentration and temperature upon systematic variation of the midblock charge fraction, valency of neutralizing counterions, and the stiffness and length of hydrophobic endblocks. Minimization of the surface energy, conformational entropy of the midblock chains, electrostatic repulsion of midblock charges, and the translational entropy of counterions are found to play central roles in controlling the self-organization features of copolymer solutions. Flower-like micelles with A-blocks forming the core of spherical aggregates and B-blocks constituting the micelle corona are established for the neutral midblocks. Increasing the charge content of B chains lowers the fraction of loop conformations and yields a spanning hydrogel network with midblocks bridging the hydrophobic clusters. Counterion valence is shown to exert a strong effect on the micelle size and network structure. The increase in the rigidity of terminal A-blocks increases the fraction of bridging chains and results in the formation of a hydrogel network with bundle-like hydrophobic domains. Longer endblocks are shown to increase the hydrophobic cluster size and enhance the bridged midblock fraction. The qualitative agreement between the experimental and theoretical studies is also discussed. The comprehensive molecular picture provides a framework for the future studies of stimuli-responsive copolymer systems. PMID:27116478

  16. Coarse-grained theory of a realistic tetrahedral liquid model

    NASA Astrophysics Data System (ADS)

    Procaccia, I.; Regev, I.

    2012-02-01

    Tetrahedral liquids such as water and silica-melt show unusual thermodynamic behavior such as a density maximum and an increase in specific heat when cooled to low temperatures. Previous work had shown that Monte Carlo and mean-field solutions of a lattice model can exhibit these anomalous properties with or without a phase transition, depending on the values of the different terms in the Hamiltonian. Here we use a somewhat different approach, where we start from a very popular empirical model of tetrahedral liquids —the Stillinger-Weber model— and construct a coarse-grained theory which directly quantifies the local structure of the liquid as a function of volume and temperature. We compare the theory to molecular-dynamics simulations and show that the theory can rationalize the simulation results and the anomalous behavior.

  17. Nanodomained Nickel Unite Nanocrystal Strength with Coarse-Grain Ductility

    PubMed Central

    Wu, Xiaolei; Yuan, Fuping; Yang, Muxin; Jiang, Ping; Zhang, Chuanxin; Chen, Liu; Wei, Yueguang; Ma, Evan

    2015-01-01

    Conventional metals are routinely hardened by grain refinement or by cold working with the expense of their ductility. Recent nanostructuring strategies have attempted to evade this strength versus ductility trade-off, but the paradox persists. It has never been possible to combine the strength reachable in nanocrystalline metals with the large uniform tensile elongation characteristic of coarse-grained metals. Here a defect engineering strategy on the nanoscale is architected to approach this ultimate combination. For Nickel, spread-out nanoscale domains (average 7 nm in diameter) were produced during electrodeposition, occupying only ~2.4% of the total volume. Yet the resulting Ni achieves a yield strength approaching 1.3 GPa, on par with the strength for nanocrystalline Ni with uniform grains. Simultaneously, the material exhibits a uniform elongation as large as ~30%, at the same level of ductile face-centered-cubic metals. Electron microscopy observations and molecular dynamics simulations demonstrate that the nanoscale domains effectively block dislocations, akin to the role of precipitates for Orowan hardening. In the meantime, the abundant domain boundaries provide dislocation sources and trapping sites of running dislocations for dislocation multiplication, and the ample space in the grain interior allows dislocation storage; a pronounced strain-hardening rate is therefore sustained to enable large uniform elongation. PMID:26122728

  18. Nanodomained Nickel Unite Nanocrystal Strength with Coarse-Grain Ductility

    NASA Astrophysics Data System (ADS)

    Wu, Xiaolei; Yuan, Fuping; Yang, Muxin; Jiang, Ping; Zhang, Chuanxin; Chen, Liu; Wei, Yueguang; Ma, Evan

    2015-06-01

    Conventional metals are routinely hardened by grain refinement or by cold working with the expense of their ductility. Recent nanostructuring strategies have attempted to evade this strength versus ductility trade-off, but the paradox persists. It has never been possible to combine the strength reachable in nanocrystalline metals with the large uniform tensile elongation characteristic of coarse-grained metals. Here a defect engineering strategy on the nanoscale is architected to approach this ultimate combination. For Nickel, spread-out nanoscale domains (average 7 nm in diameter) were produced during electrodeposition, occupying only ~2.4% of the total volume. Yet the resulting Ni achieves a yield strength approaching 1.3 GPa, on par with the strength for nanocrystalline Ni with uniform grains. Simultaneously, the material exhibits a uniform elongation as large as ~30%, at the same level of ductile face-centered-cubic metals. Electron microscopy observations and molecular dynamics simulations demonstrate that the nanoscale domains effectively block dislocations, akin to the role of precipitates for Orowan hardening. In the meantime, the abundant domain boundaries provide dislocation sources and trapping sites of running dislocations for dislocation multiplication, and the ample space in the grain interior allows dislocation storage; a pronounced strain-hardening rate is therefore sustained to enable large uniform elongation.

  19. Coarse-grained dynamics of alignment in animal group models

    NASA Astrophysics Data System (ADS)

    Moon, Sung Joon; Levin, Simon; Kevrekidis, Yannis

    2006-03-01

    Coordinated motion in animal groups, such as bird flocks and fish schools, and their models gives rise to remarkable coherent structures. Using equation-free computational tools we explore the coarse-grained dynamics of a model for the orientational movement decision in animal groups, consisting of a small number of informed "leaders" and a large number of uninformed, nonidentical ``followers.'' The direction in which each group member is headed is characterized by a phase angle of a limit-cycle oscillator, whose dynamics are nonlinearly coupled with those of all the other group members. We identify a small number of proper coarse-grained variables (using uncertainty quantification methods) that describe the collective dynamics, and perform coarse projective integration and equation-free bifurcation analysis of the coarse-grained model behavior in these variables.

  20. SAFT-γ force field for the simulation of molecular fluids: 2. Coarse-grained models of greenhouse gases, refrigerants, and long alkanes.

    PubMed

    Avendaño, Carlos; Lafitte, Thomas; Adjiman, Claire S; Galindo, Amparo; Müller, Erich A; Jackson, George

    2013-03-01

    In the first paper of this series [C. Avendaño, T. Lafitte, A. Galindo, C. S. Adjiman, G. Jackson, and E. A. Müller, J. Phys. Chem. B2011, 115, 11154] we introduced the SAFT-γ force field for molecular simulation of fluids. In our approach, a molecular-based equation of state (EoS) is used to obtain coarse-grained (CG) intermolecular potentials that can then be employed in molecular simulation over a wide range of thermodynamic conditions of the fluid. The macroscopic experimental data for the vapor-liquid equilibria (saturated liquid density and vapor pressure) of a given system are represented with the SAFT-VR Mie EoS and used to estimate effective intermolecular parameters that provide a good description of the thermodynamic properties by exploring a wide parameter space for models based on the Mie (generalized Lennard-Jones) potential. This methodology was first used to develop a simple single-segment CG Mie model of carbon dioxide (CO2) which allows for a reliable representation of the fluid-phase equilibria (for which the model was parametrized), as well as an accurate prediction of other properties such as the enthalpy of vaporization, interfacial tension, supercritical density, and second-derivative thermodynamic properties (thermal expansivity, isothermal compressibility, heat capacity, Joule-Thomson coefficient, and speed of sound). In our current paper, the methodology is further applied and extended to develop effective SAFT-γ CG Mie force fields for some important greenhouse gases including carbon tetrafluoride (CF4) and sulfur hexafluoride (SF6), modeled as simple spherical molecules, and for long linear alkanes including n-decane (n-C10H22) and n-eicosane (n-C20H42), modeled as homonuclear chains of spherical Mie segments. We also apply the SAFT-γ methodology to obtain a CG homonuclear two-segment Mie intermolecular potential for the more challenging polar and asymmetric compound 2,3,3,3-tetrafluoro-1-propene (HFO-1234yf), a novel replacement

  1. Potential of mean force analysis of the self-association of leucine-rich transmembrane α-helices: Difference between atomistic and coarse-grained simulations

    SciTech Connect

    Nishizawa, Manami; Nishizawa, Kazuhisa

    2014-08-21

    Interaction of transmembrane (TM) proteins is important in many biological processes. Large-scale computational studies using coarse-grained (CG) simulations are becoming popular. However, most CG model parameters have not fully been calibrated with respect to lateral interactions of TM peptide segments. Here, we compare the potential of mean forces (PMFs) of dimerization of TM helices obtained using a MARTINI CG model and an atomistic (AT) Berger lipids-OPLS/AA model (AT{sup OPLS}). For helical, tryptophan-flanked, leucine-rich peptides (WL15 and WALP15) embedded in a parallel configuration in an octane slab, the AT{sup OPLS} PMF profiles showed a shallow minimum (with a depth of approximately 3 kJ/mol; i.e., a weak tendency to dimerize). A similar analysis using the CHARMM36 all-atom model (AT{sup CHARMM}) showed comparable results. In contrast, the CG analysis generally showed steep PMF curves with depths of approximately 16–22 kJ/mol, suggesting a stronger tendency to dimerize compared to the AT model. This CG > AT discrepancy in the propensity for dimerization was also seen for dilauroylphosphatidylcholine (DLPC)-embedded peptides. For a WL15 (and WALP15)/DLPC bilayer system, AT{sup OPLS} PMF showed a repulsive mean force for a wide range of interhelical distances, in contrast to the attractive forces observed in the octane system. The change from the octane slab to the DLPC bilayer also mitigated the dimerization propensity in the CG system. The dimerization energies of CG (AALALAA){sub 3} peptides in DLPC and dioleoylphosphatidylcholine bilayers were in good agreement with previous experimental data. The lipid headgroup, but not the length of the lipid tails, was a key causative factor contributing to the differences between octane and DLPC. Furthermore, the CG model, but not the AT model, showed high sensitivity to changes in amino acid residues located near the lipid-water interface and hydrophobic mismatch between the peptides and membrane. These

  2. Coarse-Grained Modeling of Mucus Barrier Properties

    PubMed Central

    Gniewek, Pawel; Kolinski, Andrzej

    2012-01-01

    We designed a simple coarse-grained model of the glycocalyx layer, or adhesive mucus layer (AML), covered by mucus gel (luminal mucus layer) using a polymer lattice model and stochastic sampling (replica exchange Monte Carlo) for canonical ensemble simulations. We assumed that mucin MUC16 is responsible for the structural properties of the AML. Other mucins that are much smaller in size and less relevant for layer structure formation were not included. We further assumed that the system was in quasi-equilibrium. For systems with surface coverage and concentrations of model mucins mimicking physiological conditions, we determined the equilibrium distribution of inert nanoparticles within the mucus layers using an efficient replica exchange Monte Carlo sampling procedure. The results show that the two mucus layers penetrate each other only marginally, and the bilayer imposes a strong barrier for nanoparticles, with the AML layer playing a crucial role in the mucus barrier. PMID:22339855

  3. Entrainment of coarse grains using a discrete particle model

    SciTech Connect

    Valyrakis, Manousos; Arnold, Roger B. Jr.

    2014-10-06

    Conventional bedload transport models and incipient motion theories relying on a time-averaged boundary shear stress are incapable of accounting for the effects of fluctuating near-bed velocity in turbulent flow and are therefore prone to significant errors. Impulse, the product of an instantaneous force magnitude and its duration, has been recently proposed as an appropriate criterion for quantifying the effects of flow turbulence in removing coarse grains from the bed surface. Here, a discrete particle model (DPM) is used to examine the effects of impulse, representing a single idealized turbulent event, on particle entrainment. The results are classified according to the degree of grain movement into the following categories: motion prior to entrainment, initial dislodgement, and energetic displacement. The results indicate that in all three cases the degree of particle motion depends on both the force magnitude and the duration of its application and suggest that the effects of turbulence must be adequately accounted for in order to develop a more accurate method of determining incipient motion. DPM is capable of simulating the dynamics of grain entrainment and is an appropriate tool for further study of the fundamental mechanisms of sediment transport.

  4. Coarse-grained interaction potentials for anisotropic molecules.

    PubMed

    Babadi, M; Everaers, R; Ejtehadi, M R

    2006-05-01

    We have proposed an efficient parametrization method for a recent variant of the Gay Berne potential for dissimilar and biaxial particles [Phys. Rev. E 67, 041710 (2003)] and demonstrated it for a set of small organic molecules. Compared with the previously proposed coarse-grained models, the new potential exhibits a superior performance in close contact and large distant interactions. The repercussions of thermal vibrations and elasticity have been studied through a statistical method. The study justifies that the potential of mean force is representable with the same functional form, extending the application of this coarse-grained description to a broader range of molecules. Moreover, the advantage of employing coarse-grained models over truncated atomistic summations with large distance cutoffs has been briefly studied. PMID:16689591

  5. Polysaccharide-Protein Complexes in a Coarse-Grained Model.

    PubMed

    Poma, Adolfo B; Chwastyk, Mateusz; Cieplak, Marek

    2015-09-10

    We construct two variants of coarse-grained models of three hexaoses: one based on the centers of mass of the monomers and the other associated with the C4 atoms. The latter is found to be better defined and more suitable for studying interactions with proteins described within α-C based models. We determine the corresponding effective stiffness constants through all-atom simulations and two statistical methods. One method is the Boltzmann inversion (BI) and the other, named energy-based (EB), involves direct monitoring of energies as a function of the variables that define the stiffness potentials. The two methods are generally consistent in their account of the stiffness. We find that the elastic constants differ between the hexaoses and are noticeably different from those determined for the crystalline cellulose Iβ. The nonbonded couplings through hydrogen bonds between different sugar molecules are modeled by the Lennard-Jones potentials and are found to be stronger than the hydrogen bonds in proteins. We observe that the EB method agrees with other theoretical and experimental determinations of the nonbonded parameters much better than BI. We then consider the hexaose-Man5B catalytic complexes and determine the contact energies between their the C4-α-C atoms. These interactions are found to be stronger than the proteinic hydrogen bonds: about four times as strong for cellohexaose and two times for mannohexaose. The fluctuational dynamics of the coarse-grained complexes are found to be compatible with previous all-atom studies by Bernardi et al. PMID:26291477

  6. Multiscale dynamics of semiflexible polymers from a universal coarse-graining procedure.

    PubMed

    Koslover, Elena F; Spakowitz, Andrew J

    2014-07-01

    Simulating the dynamics of a semiflexible polymer across time and length scales that bridge the rigid and flexible regimes requires a physically sound method for generating coarse-grained representations of the polymer. Here, we study the dynamic behavior of the discrete stretchable, shearable wormlike chain model, which can be used to coarse-grain a continuous semi-elastic chain at an arbitrary discretization. We show that the dynamics of this universal model match those of the wormlike chain at length scales above the discretization length. The evolution of the stress correlation, as probed through Brownian dynamics simulations, is found to reproduce the predicted behavior in both the rigid and flexible regimes, spanning over six orders of magnitude in time scales. The coarse-graining approach employed here thus enables dynamic simulation of semiflexible polymers at lengths and times that were previously inaccessible with conventional methods. PMID:25122407

  7. Multiscale dynamics of semiflexible polymers from a universal coarse-graining procedure

    NASA Astrophysics Data System (ADS)

    Koslover, Elena F.; Spakowitz, Andrew J.

    2014-07-01

    Simulating the dynamics of a semiflexible polymer across time and length scales that bridge the rigid and flexible regimes requires a physically sound method for generating coarse-grained representations of the polymer. Here, we study the dynamic behavior of the discrete stretchable, shearable wormlike chain model, which can be used to coarse-grain a continuous semi-elastic chain at an arbitrary discretization. We show that the dynamics of this universal model match those of the wormlike chain at length scales above the discretization length. The evolution of the stress correlation, as probed through Brownian dynamics simulations, is found to reproduce the predicted behavior in both the rigid and flexible regimes, spanning over six orders of magnitude in time scales. The coarse-graining approach employed here thus enables dynamic simulation of semiflexible polymers at lengths and times that were previously inaccessible with conventional methods.

  8. Coarse-Grained Molecular Models of Water: A Review

    PubMed Central

    Hadley, Kevin R.; McCabe, Clare

    2012-01-01

    Coarse-grained (CG) models have proven to be very effective tools in the study of phenomena or systems that involve large time- and length-scales. By decreasing the degrees of freedom in the system and using softer interactions than seen in atomistic models, larger timesteps can be used and much longer simulation times can be studied. CG simulations are widely used to study systems of biological importance that are beyond the reach of atomistic simulation, necessitating a computationally efficient and accurate CG model for water. In this review, we discuss the methods used for developing CG water models and the relative advantages and disadvantages of the resulting models. In general, CG water models differ with regards to how many waters each CG group or bead represents, whether analytical or tabular potentials have been used to describe the interactions, and how the model incorporates electrostatic interactions. Finally, how the models are parameterized depends on their application, so, while some are fitted to experimental properties such as surface tension and density, others are fitted to radial distribution functions extracted from atomistic simulations. PMID:22904601

  9. Quantum particles from coarse grained classical probabilities in phase space

    SciTech Connect

    Wetterich, C.

    2010-07-15

    Quantum particles can be obtained from a classical probability distribution in phase space by a suitable coarse graining, whereby simultaneous classical information about position and momentum can be lost. For a suitable time evolution of the classical probabilities and choice of observables all features of a quantum particle in a potential follow from classical statistics. This includes interference, tunneling and the uncertainty relation.

  10. A transferable coarse-grained model for hydrogen-bonding liquids.

    PubMed

    Golubkov, Pavel A; Wu, Johnny C; Ren, Pengyu

    2008-04-21

    We present here a recent development of a generalized coarse-grained model for use in molecular simulations. In this model, interactions between coarse-grained particles consist of both van der Waals and explicit electrostatic components. As a result, the coarse-grained model offers the transferability that is lacked by most current effective-potential based approaches. The previous center-of-mass framework (P. A. Golubkov and P. Ren, J. Chem. Phys., 2006, 125, 64103) is generalized here to include arbitrary off-center interaction sites for both Gay-Berne and multipoles. The new model has been applied to molecular dynamic simulations of neat methanol liquid. By placing a single point multipole at the oxygen atom rather than at the center of mass of methanol, there is a significant improvement in the ability to capture hydrogen-bonding. The critical issue of transferability of the coarse-grained model is verified on methanol-water mixtures, using parameters derived from neat liquids without any modification. The mixture density and internal energy from coarse-grained molecular dynamics simulations show good agreement with experimental measurements, on a par with what has been obtained from more detailed atomic models. By mapping the dynamics trajectory from the coarse-grained simulation into the all-atom counterpart, we are able to investigate atomic-level structure and interaction. Atomic radial distribution functions of neat methanol, neat water and mixtures compare favorably to experimental measurements. Furthermore, hydrogen-bonded 6- and 7-molecule chains of water and methanol observed in the mixture are in agreement with previous atomic simulations. PMID:18688358

  11. Anisotropic Coarse-Grained Model for Proteins Based On Gay–Berne and Electric Multipole Potentials

    PubMed Central

    2015-01-01

    Gay–Berne anisotropic potential has been widely used to evaluate the nonbonded interactions between coarse-grained particles being described as elliptical rigid bodies. In this paper, we are presenting a coarse-grained model for twenty kinds of amino acids and proteins, based on the anisotropic Gay–Berne and point electric multipole (EMP) potentials. We demonstrate that the anisotropic coarse-grained model, namely GBEMP model, is able to reproduce many key features observed from experimental protein structures (Dunbrack Library), as well as from atomistic force field simulations (using AMOEBA, AMBER, and CHARMM force fields), while saving the computational cost by a factor of about 10–200 depending on specific cases and atomistic models. More importantly, unlike other coarse-grained approaches, our framework is based on the fundamental intermolecular forces with explicit treatment of electrostatic and repulsion-dispersion forces. As a result, the coarse-grained protein model presented an accurate description of nonbonded interactions (particularly electrostatic component) between hetero/homodimers (such as peptide–peptide, peptide–water). In addition, the encouraging performance of the model was reflected by the excellent correlation between GBEMP and AMOEBA models in the calculations of the dipole moment of peptides. In brief, the GBEMP model given here is general and transferable, suitable for simulating complex biomolecular systems. PMID:24659927

  12. A Hybrid Coarse-graining Approach for Lipid Bilayers at Large Length and Time Scales

    PubMed Central

    Ayton, Gary S.; Voth, Gregory A.

    2009-01-01

    A hybrid analytic-systematic (HAS) coarse-grained (CG) lipid model is developed and employed in a large-scale simulation of a liposome. The methodology is termed hybrid analyticsystematic as one component of the interaction between CG sites is variationally determined from the multiscale coarse-graining (MS-CG) methodology, while the remaining component utilizes an analytic potential. The systematic component models the in-plane center of mass interaction of the lipids as determined from an atomistic-level MD simulation of a bilayer. The analytic component is based on the well known Gay-Berne ellipsoid of revolution liquid crystal model, and is designed to model the highly anisotropic interactions at a highly coarse-grained level. The HAS CG approach is the first step in an “aggressive” CG methodology designed to model multi-component biological membranes at very large length and timescales. PMID:19281167

  13. Hybrid coarse-graining approach for lipid bilayers at large length and time scales.

    PubMed

    Ayton, Gary S; Voth, Gregory A

    2009-04-01

    A hybrid analytic-systematic (HAS) coarse-grained (CG) lipid model is developed and employed in a large-scale simulation of a liposome. The methodology is termed hybrid analytic-systematic because one component of the interaction between CG sites is variationally determined from the multiscale coarse-graining (MS-CG) methodology, whereas the remaining component utilizes an analytic potential. The systematic component models the in-plane center-of-mass interaction of the lipids as determined from an atomistic-level MD simulation of a bilayer. The analytic component is based on the well-known Gay-Berne ellipsoid-of-revolution liquid-crystal model and is designed to model the highly anisotropic interactions at a highly coarse-grained level. The HAS CG approach is the first step in an "aggressive" CG methodology designed to model multicomponent biological membranes at very large length and time scales. PMID:19281167

  14. Systematic coarse-graining in nucleation theory

    SciTech Connect

    Schweizer, M.; Sagis, L. M. C.

    2015-08-21

    In this work, we show that the standard method to obtain nucleation rate-predictions with the aid of atomistic Monte Carlo simulations leads to nucleation rate predictions that deviate 3 − 5 orders of magnitude from the recent brute-force molecular dynamics simulations [Diemand et al., J. Chem. Phys. 139, 074309 (2013)] conducted in the experimental accessible supersaturation regime for Lennard-Jones argon. We argue that this is due to the truncated state space the literature mostly relies on, where the number of atoms in a nucleus is considered the only relevant order parameter. We here formulate the nonequilibrium statistical mechanics of nucleation in an extended state space, where the internal energy and momentum of the nuclei are additionally incorporated. We show that the extended model explains the lack in agreement between the molecular dynamics simulations by Diemand et al. and the truncated state space. We demonstrate additional benefits of using the extended state space; in particular, the definition of a nucleus temperature arises very naturally and can be shown without further approximation to obey the fluctuation law of McGraw and LaViolette. In addition, we illustrate that our theory conveniently allows to extend existing theories to richer sets of order parameters.

  15. Systematic coarse-graining in nucleation theory.

    PubMed

    Schweizer, M; Sagis, L M C

    2015-08-21

    In this work, we show that the standard method to obtain nucleation rate-predictions with the aid of atomistic Monte Carlo simulations leads to nucleation rate predictions that deviate 3 - 5 orders of magnitude from the recent brute-force molecular dynamics simulations [Diemand et al., J. Chem. Phys. 139, 074309 (2013)] conducted in the experimental accessible supersaturation regime for Lennard-Jones argon. We argue that this is due to the truncated state space the literature mostly relies on, where the number of atoms in a nucleus is considered the only relevant order parameter. We here formulate the nonequilibrium statistical mechanics of nucleation in an extended state space, where the internal energy and momentum of the nuclei are additionally incorporated. We show that the extended model explains the lack in agreement between the molecular dynamics simulations by Diemand et al. and the truncated state space. We demonstrate additional benefits of using the extended state space; in particular, the definition of a nucleus temperature arises very naturally and can be shown without further approximation to obey the fluctuation law of McGraw and LaViolette. In addition, we illustrate that our theory conveniently allows to extend existing theories to richer sets of order parameters. PMID:26298141

  16. Systematic coarse-graining in nucleation theory

    NASA Astrophysics Data System (ADS)

    Schweizer, M.; Sagis, L. M. C.

    2015-08-01

    In this work, we show that the standard method to obtain nucleation rate-predictions with the aid of atomistic Monte Carlo simulations leads to nucleation rate predictions that deviate 3 - 5 orders of magnitude from the recent brute-force molecular dynamics simulations [Diemand et al., J. Chem. Phys. 139, 074309 (2013)] conducted in the experimental accessible supersaturation regime for Lennard-Jones argon. We argue that this is due to the truncated state space the literature mostly relies on, where the number of atoms in a nucleus is considered the only relevant order parameter. We here formulate the nonequilibrium statistical mechanics of nucleation in an extended state space, where the internal energy and momentum of the nuclei are additionally incorporated. We show that the extended model explains the lack in agreement between the molecular dynamics simulations by Diemand et al. and the truncated state space. We demonstrate additional benefits of using the extended state space; in particular, the definition of a nucleus temperature arises very naturally and can be shown without further approximation to obey the fluctuation law of McGraw and LaViolette. In addition, we illustrate that our theory conveniently allows to extend existing theories to richer sets of order parameters.

  17. Coarse-grained mechanics of viral shells

    NASA Astrophysics Data System (ADS)

    Klug, William S.; Gibbons, Melissa M.

    2008-03-01

    We present an approach for creating three-dimensional finite element models of viral capsids from atomic-level structural data (X-ray or cryo-EM). The models capture heterogeneous geometric features and are used in conjunction with three-dimensional nonlinear continuum elasticity to simulate nanoindentation experiments as performed using atomic force microscopy. The method is extremely flexible; able to capture varying levels of detail in the three-dimensional structure. Nanoindentation simulations are presented for several viruses: Hepatitis B, CCMV, HK97, and φ29. In addition to purely continuum elastic models a multiscale technique is developed that combines finite-element kinematics with MD energetics such that large-scale deformations are facilitated by a reduction in degrees of freedom. Simulations of these capsid deformation experiments provide a testing ground for the techniques, as well as insight into the strength-determining mechanisms of capsid deformation. These methods can be extended as a framework for modeling other proteins and macromolecular structures in cell biology.

  18. Coarse-Grained Clustering Dynamics of Heterogeneously Coupled Neurons.

    PubMed

    Moon, Sung Joon; Cook, Katherine A; Rajendran, Karthikeyan; Kevrekidis, Ioannis G; Cisternas, Jaime; Laing, Carlo R

    2015-12-01

    The formation of oscillating phase clusters in a network of identical Hodgkin-Huxley neurons is studied, along with their dynamic behavior. The neurons are synaptically coupled in an all-to-all manner, yet the synaptic coupling characteristic time is heterogeneous across the connections. In a network of N neurons where this heterogeneity is characterized by a prescribed random variable, the oscillatory single-cluster state can transition-through [Formula: see text] (possibly perturbed) period-doubling and subsequent bifurcations-to a variety of multiple-cluster states. The clustering dynamic behavior is computationally studied both at the detailed and the coarse-grained levels, and a numerical approach that can enable studying the coarse-grained dynamics in a network of arbitrarily large size is suggested. Among a number of cluster states formed, double clusters, composed of nearly equal sub-network sizes are seen to be stable; interestingly, the heterogeneity parameter in each of the double-cluster components tends to be consistent with the random variable over the entire network: Given a double-cluster state, permuting the dynamical variables of the neurons can lead to a combinatorially large number of different, yet similar "fine" states that appear practically identical at the coarse-grained level. For weak heterogeneity we find that correlations rapidly develop, within each cluster, between the neuron's "identity" (its own value of the heterogeneity parameter) and its dynamical state. For single- and double-cluster states we demonstrate an effective coarse-graining approach that uses the Polynomial Chaos expansion to succinctly describe the dynamics by these quickly established "identity-state" correlations. This coarse-graining approach is utilized, within the equation-free framework, to perform efficient computations of the neuron ensemble dynamics. PMID:26458901

  19. Generic Coarse-Grained Model for Protein Folding and Aggregation

    NASA Astrophysics Data System (ADS)

    Bereau, Tristan; Deserno, Markus

    2009-03-01

    The complexity involved in protein structure is not only due to the rich variety of amino acids, but also the inherent weak interactions, comparable to thermal energy, and important cooperative phenomena. This presents a challenge in atomistic simulations, as it is associated with high-dimensionality and ruggedness of the energy landscape as well as long equilibration times. We have recently developed a coarse-grained (CG) implicit solvent peptide model which has been designed to reproduce key consequences of the abovementioned weak interactions. Its intermediate level of resolution, four beads per amino acid, allows for accurate sampling of local conformations by designing a force field that relies on simple interactions. A realistic ratio of α-helix to β-sheet content is achieved by mimicking a nearest-neighbor dipole interaction. We tune the model in order to fold helical proteins while systematically comparing the structure with NMR data. Very good agreement is achieved for proteins that have simple tertiary structures. We further probe the effects of cooperativity between amino acids by looking at peptide aggregation, where hydrophobic peptide fragments cooperatively form large-scale β-sheet structures. The model is able to reproduce features from atomistic simulations on a qualitative basis.

  20. Thermal response of proteins (histone H2AX, H3.1) by a coarse-grained Monte Carlo simulation with a knowledge-based phenomenological potential

    NASA Astrophysics Data System (ADS)

    Fritsche, Miriam; Heermann, Dieter; Pandey, Ras; Farmer, Barry

    2012-02-01

    Using a coarse-grained bond fluctuating model, we investigate structure and dynamics of two histones, H2AX (143 residues) and H3.1 (136 residues) as a function of temperature (T). A knowledged based contact matrix is used as an input for a phenomenological residue-residue interaction in a generalized Lennard-Jones potential. Metropolis algorithm is used to execute stochastic movement of each residue. A number of local and global physical quantities are analyzed. Despite unique energy and mobility profiles of its residues in a specific sequence, the histone H3.1 appears to undergo a structural transformation from a random coil to a globular conformation on reducing the temperature. The radius of gyration of the histone H2AX, in contrast, exhibits a non-monotonic dependence on temperature with a maximum at a characteristic temperature (Tc) where crossover occurs from a positive (stretching below Tc) to negative (contraction above Tc) thermal response on increasing T. Multi-scale structures of the proteins are examined by a detailed analysis of their structure functions.

  1. Coarse-grained DNA modeling: Hybridization and ionic effects

    NASA Astrophysics Data System (ADS)

    Hinckley, Daniel M.

    Deoxyribonucleic acid (DNA) is a biopolymer of enormous significance in living systems. The utility of DNA in such systems is derived from the programmable nature of DNA and its unique mechanical properties. Recently, material scientists have harnessed these properties in order to create systems that spontaneous self-assemble on the nanoscale. Both biologists and material scientists are hindered by an incomplete understanding of the physical interactions that together govern DNA's behavior. Computer simulations, especially those at the coarse-grained (CG) level, can potentially complete this understanding by resolving details indiscernible with current experimental techniques. In this thesis, we advance the state-of-the-art of DNA CG simulations by first reviewing the relevant theory and the evolution of CG DNA models since their inception. Then we present 3SPN.2, an improved CG model for DNA that should provide new insights into biological and nanotechnological systems which incorporate DNA. We perform forward flux sampling simulations in order to examine the effect of sequence, oligomer length, and ionic strength on DNA oligomer hybridization. Due to the limitations inherent in continuum treatments of electrostatic interactions in biological systems, we generate a CG model of biological ions for use with 3SPN.2 and other CG models. Lastly, we illustrate the potential of 3SPN.2 and CG ions by using the models in simulations of viral capsid packaging experiments. The models and results described in this thesis will be useful in future modeling efforts that seek to identify the fundamental physics that govern behavior such as nucleosome positioning, DNA hybridization, and DNA nanoassembly.

  2. Bottom-up coarse-graining of a simple graphene model: the blob picture.

    PubMed

    Kauzlarić, David; Meier, Julia T; Español, Pep; Succi, Sauro; Greiner, Andreas; Korvink, Jan G

    2011-02-14

    The coarse-graining of a simple all-atom 2D microscopic model of graphene, in terms of "blobs" described by center of mass variables, is presented. The equations of motion of the coarse-grained variables take the form of dissipative particle dynamics (DPD). The coarse-grained conservative forces and the friction of the DPD model are obtained via a bottom-up procedure from molecular dynamics (MD) simulations. The separation of timescales for blobs of 24 and 96 carbon atoms is sufficiently pronounced for the Markovian assumption, inherent to the DPD model, to provide satisfactory results. In particular, the MD velocity autocorrelation function of the blobs is well reproduced by the DPD model, provided that the effect of friction and noise is taken into account. However, DPD cross-correlations between neighbor blobs show appreciable discrepancies with respect to the MD results. Possible extensions to mend these discrepancies are briefly outlined. PMID:21322660

  3. Coarse-grained force field; general folding theory

    PubMed Central

    Liwo, Adam; He, Yi; Scheraga, Harold A.

    2012-01-01

    We review the coarse-grained UNited RESidue (UNRES) force field for the simulations of protein structure and dynamics, which is being developed in our laboratory over the last several years. UNRES is a physics-based force field, the prototype of which is defined as a potential of mean force of polypeptide chains in water, where all the degrees of freedom except the coordinates of α-carbon atoms and side-chain centers have been integrated out. We describe the initial implementation of UNRES to protein-structure prediction formulated as a search for the global minimum of the potential-energy function and its subsequent molecular dynamics and extensions of molecular-dynamics implementation, which enabled us to study protein-folding pathways and thermodynamics, as well as to reformulate the protein-structure prediction problem as a search for the conformational ensemble with the lowest free energy at temperatures below the folding-transition temperature. Applications of UNRES to study biological problems are also described. PMID:21643583

  4. Coarse-Grained Model for Water Involving a Virtual Site.

    PubMed

    Deng, Mingsen; Shen, Hujun

    2016-02-01

    In this work, we propose a new coarse-grained (CG) model for water by combining the features of two popular CG water models (BMW and MARTINI models) as well as by adopting a topology similar to that of the TIP4P water model. In this CG model, a CG unit, representing four real water molecules, consists of a virtual site, two positively charged particles, and a van der Waals (vdW) interaction center. Distance constraint is applied to the bonds formed between the vdW interaction center and the positively charged particles. The virtual site, which carries a negative charge, is determined by the locations of the two positively charged particles and the vdW interaction center. For the new CG model of water, we coined the name "CAVS" (charge is attached to a virtual site) due to the involvment of the virtual site. After being tested in molecular dynamic (MD) simulations of bulk water at various time steps, under different temperatures and in different salt (NaCl) concentrations, the CAVS model offers encouraging predictions for some bulk properties of water (such as density, dielectric constant, etc.) when compared to experimental ones. PMID:26747089

  5. Free-energy coarse-grained potential for C{sub 60}

    SciTech Connect

    Edmunds, D. M. Tangney, P.; Vvedensky, D. D.; Foulkes, W. M. C.

    2015-10-28

    We propose a new deformable free energy method for generating a free-energy coarse-graining potential for C{sub 60}. Potentials generated from this approach exhibit a strong temperature dependence and produce excellent agreement with benchmark fully atomistic molecular dynamics simulations. Parameter sets for analytical fits to this potential are provided at four different temperatures.

  6. Deformation Behaviour of Coarse Grain Alumina under Shock Loading

    NASA Astrophysics Data System (ADS)

    Gupta, Satish

    2013-06-01

    To develop better understanding of the shock wave induced deformation behavior of coarse grain alumina ceramics, and for measurement of its Hugoniot Elastic Limit (HEL), in-situ and recovery gas gun experiments have been carried out on coarse grain alumina (grain size ~ 10 μm), prepared in the form of discs (>99.9% TMD) by pressure-less sintering of alpha alumina powder at 1583 K. The HEL value of 1.9 GPa has been determined from the kink in the pressure history recorded using piezoresistance gauge and also from the free surface velocity history of the sample shocked to 9 GPa. The nano-indentation measurements on the alumina samples shocked to 6.5 GPa showed hardness value 15% lower than 21.3 GPa for unshocked alumina, and strong Indentation Size Effect (ISE); the hardness value was still lower and the ISE was stronger for the sample shocked to 12 GPa. The XRD measurements showed reduced particle size and increased microstrains in the shocked alumina fragments. SEM, FESEM and TEM measurements on shock treated samples showed presence of grain localized micro- and nano-scale deformations, micro-cleavages, grain-boundary microcracks, extensive shear induced deformations, and localized micro-fractures, etc. These observations led to the development of a qualitative model for the damage initiation and its subsequent growth mechanisms in shocked alumina. The work performed in collaboration with K.D. Joshi of BARC and A.K. Mukhopadhyay of CGCRI.

  7. High capacitance of coarse-grained carbide derived carbon electrodes

    NASA Astrophysics Data System (ADS)

    Dyatkin, Boris; Gogotsi, Oleksiy; Malinovskiy, Bohdan; Zozulya, Yuliya; Simon, Patrice; Gogotsi, Yury

    2016-02-01

    We report exceptional electrochemical properties of supercapacitor electrodes composed of large, granular carbide-derived carbon (CDC) particles. Using a titanium carbide (TiC) precursor, we synthesized 70-250 μm sized particles with high surface area and a narrow pore size distribution. Electrochemical cycling of these coarse-grained powders defied conventional wisdom that a small particle size is strictly required for supercapacitor electrodes and allowed high charge storage densities, rapid transport, and good rate handling ability. The material showcased capacitance above 100 F g-1 at sweep rates as high as 250 mV s-1 in organic electrolyte. 250-1000 micron thick dense CDC films with up to 80 mg cm-2 loading showed superior areal capacitances. The material significantly outperformed its activated carbon counterpart in organic electrolytes and ionic liquids. Furthermore, large internal/external surface ratio of coarse-grained carbons allowed the resulting electrodes to maintain high electrochemical stability up to 3.1 V in ionic liquid electrolyte. In addition to presenting novel insights into the electrosorption process, these coarse-grained carbons offer a pathway to low-cost, high-performance implementation of supercapacitors in automotive and grid-storage applications.

  8. The Theory of Ultra-Coarse-Graining. 2. Numerical Implementation.

    PubMed

    Davtyan, Aram; Dama, James F; Sinitskiy, Anton V; Voth, Gregory A

    2014-12-01

    The increasing interest in the modeling of complex macromolecular systems in recent years has spurred the development of numerous coarse-graining (CG) techniques. However, many of the CG models are constructed assuming that all details beneath the resolution of CG degrees of freedom are fast and average out, which sets limits on the resolution of feasible coarse-grainings and on the range of applications of the CG models. Ultra-coarse-graining (UCG) makes it possible to construct models at any desired resolution while accounting for discrete conformational or chemical changes within the CG sites that can modulate the interactions between them. Here, we discuss the UCG methodology and its numerical implementation. We pay particular attention to the numerical mechanism for including state transitions between different conformations within CG sites because this has not been discussed previously. Using a simple example of 1,2-dichloroethane, we demonstrate the ability of the UCG model to reproduce the multiconfigurational behavior of this molecular liquid, even when each molecule is modeled with only one CG site. The methodology can also be applied to other molecular liquids and macromolecular systems with time scale separation between conformational transitions and other intramolecular motions and rotations. PMID:26583210

  9. Coarse-graining the electrostatic potential via distributed multipole expansions

    PubMed Central

    Gramada, Apostol; Bourne, Philip E.

    2011-01-01

    Multipole expansions offer a natural path to coarse-graining the electrostatic potential. However, the validity of the expansion is restricted to regions outside a spherical enclosure of the distribution of charge and, therefore, not suitable for most applications that demand accurate representation at arbitrary positions around the molecule. We propose and demonstrate a distributed multipole expansion approach that resolves this limitation. We also provide a practical algorithm for the computational implementation of this approach. The method allows the partitioning of the charge distribution into subsystems so that the multipole expansion of each component of the partition, and therefore of their superposition, is valid outside an enclosing surface of the molecule of arbitrary shape. The complexity of the resulting coarse-grained model of electrostatic potential is dictated by the area of the molecular surface and therefore, for a typical three-dimensional molecule, it scale as N2/3 with N, the number of charges in the system. This makes the method especially useful for coarse-grained studies of biological systems consisting of many large macromolecules provided that the configuration of the individual molecules can be approximated as fixed. PMID:21572587

  10. Insights on protein-DNA recognition by coarse grain modelling

    PubMed Central

    Poulain, Pierre; Saladin, Adrien; Hartmann, Brigitte; Prévost, Chantal

    2008-01-01

    Coarse grain modelling of macromolecules is a new approach potentially well adapted to answer numerous issues, ranging from physics to biology. We propose here an original DNA coarse grain model specifically dedicated to protein–DNA docking, a crucial, but still largely unresolved, question in molecular biology. Using a representative set of protein–DNA complexes, we first show that our model is able to predict the interaction surface between the macromolecular partners taken in their bound form. In a second part, the impact of the DNA sequence and electrostatics, together with the DNA and protein conformations on docking is investigated. Our results strongly suggest that the overall DNA structure mainly contributes in discriminating the interaction site on cognate proteins. Direct electrostatic interactions between phosphate groups and amino acids side chains strengthen the binding. Overall, this work demonstrates that coarse grain modelling can reveal itself a precious auxiliary for a general and complete description and understanding of protein–DNA association mechanisms. PMID:18478582

  11. High capacitance of coarse-grained carbide derived carbon electrodes

    DOE PAGESBeta

    Dyatkin, Boris; Gogotsi, Oleksiy; Malinovskiy, Bohdan; Zozulya, Yuliya; Simon, Patrice; Gogotsi, Yury

    2016-01-01

    Here, we report exceptional electrochemical properties of supercapacitor electrodes composed of large, granular carbide-derived carbon (CDC) particles. We synthesized 70–250 μm sized particles with high surface area and a narrow pore size distribution, using a titanium carbide (TiC) precursor. Electrochemical cycling of these coarse-grained powders defied conventional wisdom that a small particle size is strictly required for supercapacitor electrodes and allowed high charge storage densities, rapid transport, and good rate handling ability. Moreover, the material showcased capacitance above 100 F g-1 at sweep rates as high as 250 mV s-1 in organic electrolyte. 250–1000 micron thick dense CDC films withmore » up to 80 mg cm-2 loading showed superior areal capacitances. The material significantly outperformed its activated carbon counterpart in organic electrolytes and ionic liquids. Furthermore, large internal/external surface ratio of coarse-grained carbons allowed the resulting electrodes to maintain high electrochemical stability up to 3.1 V in ionic liquid electrolyte. In addition to presenting novel insights into the electrosorption process, these coarse-grained carbons offer a pathway to low-cost, high-performance implementation of supercapacitors in automotive and grid-storage applications.« less

  12. High capacitance of coarse-grained carbide derived carbon electrodes

    SciTech Connect

    Dyatkin, Boris; Gogotsi, Oleksiy; Malinovskiy, Bohdan; Zozulya, Yuliya; Simon, Patrice; Gogotsi, Yury

    2016-01-01

    Here, we report exceptional electrochemical properties of supercapacitor electrodes composed of large, granular carbide-derived carbon (CDC) particles. We synthesized 70–250 μm sized particles with high surface area and a narrow pore size distribution, using a titanium carbide (TiC) precursor. Electrochemical cycling of these coarse-grained powders defied conventional wisdom that a small particle size is strictly required for supercapacitor electrodes and allowed high charge storage densities, rapid transport, and good rate handling ability. Moreover, the material showcased capacitance above 100 F g-1 at sweep rates as high as 250 mV s-1 in organic electrolyte. 250–1000 micron thick dense CDC films with up to 80 mg cm-2 loading showed superior areal capacitances. The material significantly outperformed its activated carbon counterpart in organic electrolytes and ionic liquids. Furthermore, large internal/external surface ratio of coarse-grained carbons allowed the resulting electrodes to maintain high electrochemical stability up to 3.1 V in ionic liquid electrolyte. In addition to presenting novel insights into the electrosorption process, these coarse-grained carbons offer a pathway to low-cost, high-performance implementation of supercapacitors in automotive and grid-storage applications.

  13. Optimization of Analytical Potentials for Coarse-Grained Biopolymer Models.

    PubMed

    Mereghetti, Paolo; Maccari, Giuseppe; Spampinato, Giulia Lia Beatrice; Tozzini, Valentina

    2016-08-25

    The increasing trend in the recent literature on coarse grained (CG) models testifies their impact in the study of complex systems. However, the CG model landscape is variegated: even considering a given resolution level, the force fields are very heterogeneous and optimized with very different parametrization procedures. Along the road for standardization of CG models for biopolymers, here we describe a strategy to aid building and optimization of statistics based analytical force fields and its implementation in the software package AsParaGS (Assisted Parameterization platform for coarse Grained modelS). Our method is based on the use and optimization of analytical potentials, optimized by targeting internal variables statistical distributions by means of the combination of different algorithms (i.e., relative entropy driven stochastic exploration of the parameter space and iterative Boltzmann inversion). This allows designing a custom model that endows the force field terms with a physically sound meaning. Furthermore, the level of transferability and accuracy can be tuned through the choice of statistical data set composition. The method-illustrated by means of applications to helical polypeptides-also involves the analysis of two and three variable distributions, and allows handling issues related to the FF term correlations. AsParaGS is interfaced with general-purpose molecular dynamics codes and currently implements the "minimalist" subclass of CG models (i.e., one bead per amino acid, Cα based). Extensions to nucleic acids and different levels of coarse graining are in the course. PMID:27150459

  14. Parameterization of backbone flexibility in a coarse-grained force field for proteins (COFFDROP) derived from all-atom explicit-solvent molecular dynamics simulations of all possible two-residue peptides

    PubMed Central

    Frembgen-Kesner, Tamara; Andrews, Casey T.; Li, Shuxiang; Ngo, Nguyet Anh; Shubert, Scott A.; Jain, Aakash; Olayiwola, Oluwatoni; Weishaar, Mitch R.; Elcock, Adrian H.

    2015-01-01

    Recently, we reported the parameterization of a set of coarse-grained (CG) nonbonded potential functions, derived from all-atom explicit-solvent molecular dynamics (MD) simulations of amino acid pairs, and designed for use in (implicit-solvent) Brownian dynamics (BD) simulations of proteins; this force field was named COFFDROP (COarse-grained Force Field for Dynamic Representations Of Proteins). Here, we describe the extension of COFFDROP to include bonded backbone terms derived from fitting to results of explicit-solvent MD simulations of all possible two-residue peptides containing the 20 standard amino acids, with histidine modeled in both its protonated and neutral forms. The iterative Boltzmann inversion (IBI) method was used to optimize new CG potential functions for backbone-related terms by attempting to reproduce angle, dihedral and distance probability distributions generated by the MD simulations. In a simple test of the transferability of the extended force field, the angle, dihedral and distance probability distributions obtained from BD simulations of 56 three-residue peptides were compared to results from corresponding explicit-solvent MD simulations. In a more challenging test of the COFFDROP force field, it was used to simulate eight intrinsically disordered proteins and was shown to quite accurately reproduce the experimental hydrodynamic radii (Rhydro), provided that the favorable nonbonded interactions of the force field were uniformly scaled downwards in magnitude. Overall, the results indicate that the COFFDROP force field is likely to find use in modeling the conformational behavior of intrinsically disordered proteins and multi-domain proteins connected by flexible linkers. PMID:26574429

  15. A Coarse-Grained Elastic Network Atom Contact Model and Its Use in the Simulation of Protein Dynamics and the Prediction of the Effect of Mutations

    PubMed Central

    Frappier, Vincent; Najmanovich, Rafael J.

    2014-01-01

    Normal mode analysis (NMA) methods are widely used to study dynamic aspects of protein structures. Two critical components of NMA methods are coarse-graining in the level of simplification used to represent protein structures and the choice of potential energy functional form. There is a trade-off between speed and accuracy in different choices. In one extreme one finds accurate but slow molecular-dynamics based methods with all-atom representations and detailed atom potentials. On the other extreme, fast elastic network model (ENM) methods with Cα−only representations and simplified potentials that based on geometry alone, thus oblivious to protein sequence. Here we present ENCoM, an Elastic Network Contact Model that employs a potential energy function that includes a pairwise atom-type non-bonded interaction term and thus makes it possible to consider the effect of the specific nature of amino-acids on dynamics within the context of NMA. ENCoM is as fast as existing ENM methods and outperforms such methods in the generation of conformational ensembles. Here we introduce a new application for NMA methods with the use of ENCoM in the prediction of the effect of mutations on protein stability. While existing methods are based on machine learning or enthalpic considerations, the use of ENCoM, based on vibrational normal modes, is based on entropic considerations. This represents a novel area of application for NMA methods and a novel approach for the prediction of the effect of mutations. We compare ENCoM to a large number of methods in terms of accuracy and self-consistency. We show that the accuracy of ENCoM is comparable to that of the best existing methods. We show that existing methods are biased towards the prediction of destabilizing mutations and that ENCoM is less biased at predicting stabilizing mutations. PMID:24762569

  16. The multiscale coarse-graining method. XI. Accurate interactions based on the centers of charge of coarse-grained sites

    SciTech Connect

    Cao, Zhen; Voth, Gregory A.

    2015-12-28

    It is essential to be able to systematically construct coarse-grained (CG) models that can efficiently and accurately reproduce key properties of higher-resolution models such as all-atom. To fulfill this goal, a mapping operator is needed to transform the higher-resolution configuration to a CG configuration. Certain mapping operators, however, may lose information related to the underlying electrostatic properties. In this paper, a new mapping operator based on the centers of charge of CG sites is proposed to address this issue. Four example systems are chosen to demonstrate this concept. Within the multiscale coarse-graining framework, CG models that use this mapping operator are found to better reproduce the structural correlations of atomistic models. The present work also demonstrates the flexibility of the mapping operator and the robustness of the force matching method. For instance, important functional groups can be isolated and emphasized in the CG model.

  17. Microcanonical thermostatistics of coarse-grained proteins with amyloidogenic propensity

    NASA Astrophysics Data System (ADS)

    Frigori, Rafael B.; Rizzi, Leandro G.; Alves, Nelson A.

    2013-01-01

    The formation of fibrillar aggregates seems to be a common characteristic of polypeptide chains, although the observation of these aggregates may depend on appropriate experimental conditions. Partially folded intermediates seem to have an important role in the generation of protein aggregates, and a mechanism for this fibril formation considers that these intermediates also correspond to metastable states with respect to the fibrillar ones. Here, using a coarse-grained (CG) off-lattice model, we carry out a comparative analysis of the thermodynamic aspects characterizing the folding transition with respect to the propensity for aggregation of four different systems: two isoforms of the amyloid β-protein, the Src SH3 domain, and the human prion proteins (hPrP). Microcanonical analysis of the data obtained from replica exchange method is conducted to evaluate the free-energy barrier and latent heat in these models. The simulations of the amyloid β isoforms and Src SH3 domain indicated that the folding process described by this CG model is related to a negative specific heat, a phenomenon that can only be verified in the microcanonical ensemble in first-order phase transitions. The CG simulation of the hPrP heteropolymer yielded a continuous folding transition. The absence of a free-energy barrier and latent heat favors the presence of partially unfolded conformations, and in this context, this thermodynamic aspect could explain the reason why the hPrP heteropolymer is more aggregation-prone than the other heteropolymers considered in this study. We introduced the hydrophobic radius of gyration as an order parameter and found that it can be used to obtain reliable information about the hydrophobic packing and the transition temperatures in the folding process.

  18. Microcanonical thermostatistics of coarse-grained proteins with amyloidogenic propensity.

    PubMed

    Frigori, Rafael B; Rizzi, Leandro G; Alves, Nelson A

    2013-01-01

    The formation of fibrillar aggregates seems to be a common characteristic of polypeptide chains, although the observation of these aggregates may depend on appropriate experimental conditions. Partially folded intermediates seem to have an important role in the generation of protein aggregates, and a mechanism for this fibril formation considers that these intermediates also correspond to metastable states with respect to the fibrillar ones. Here, using a coarse-grained (CG) off-lattice model, we carry out a comparative analysis of the thermodynamic aspects characterizing the folding transition with respect to the propensity for aggregation of four different systems: two isoforms of the amyloid β-protein, the Src SH3 domain, and the human prion proteins (hPrP). Microcanonical analysis of the data obtained from replica exchange method is conducted to evaluate the free-energy barrier and latent heat in these models. The simulations of the amyloid β isoforms and Src SH3 domain indicated that the folding process described by this CG model is related to a negative specific heat, a phenomenon that can only be verified in the microcanonical ensemble in first-order phase transitions. The CG simulation of the hPrP heteropolymer yielded a continuous folding transition. The absence of a free-energy barrier and latent heat favors the presence of partially unfolded conformations, and in this context, this thermodynamic aspect could explain the reason why the hPrP heteropolymer is more aggregation-prone than the other heteropolymers considered in this study. We introduced the hydrophobic radius of gyration as an order parameter and found that it can be used to obtain reliable information about the hydrophobic packing and the transition temperatures in the folding process. PMID:23298062

  19. Chemically transferable coarse-grained potentials from conditional reversible work calculations.

    PubMed

    Brini, E; van der Vegt, N F A

    2012-10-21

    The representability and transferability of effective pair potentials used in multiscale simulations of soft matter systems is ill understood. In this paper, we study liquid state systems composed of n-alkanes, the coarse-grained (CG) potential of which may be assumed pairwise additive and has been obtained using the conditional reversible work (CRW) method. The CRW method is a free-energy-based coarse-graining procedure, which, by means of performing the coarse graining at pair level, rigorously provides a pair potential that describes the interaction free energy between two mapped atom groups (beads) embedded in their respective chemical environments. The pairwise nature of the interactions combined with their dependence on the chemically bonded environment makes CRW potentials ideally suited in studies of chemical transferability. We report CRW potentials for hexane using a mapping scheme that merges two heavy atoms in one CG bead. It is shown that the model is chemically and thermodynamically transferable to alkanes of different chain lengths in the liquid phase at temperatures between the melting and the boiling point under atmospheric (1 atm) pressure conditions. It is further shown that CRW-CG potentials may be readily obtained from a single simulation of the liquid state using the free energy perturbation method, thereby providing a fast and versatile molecular coarse graining method for aliphatic molecules. PMID:23083154

  20. Hierarchical coarse-graining strategy for protein-membrane systems to access mesoscopic scales

    PubMed Central

    Ayton, Gary S.; Lyman, Edward

    2014-01-01

    An overall multiscale simulation strategy for large scale coarse-grain simulations of membrane protein systems is presented. The protein is modeled as a heterogeneous elastic network, while the lipids are modeled using the hybrid analytic-systematic (HAS) methodology, where in both cases atomistic level information obtained from molecular dynamics simulation is used to parameterize the model. A feature of this approach is that from the outset liposome length scales are employed in the simulation (i.e., on the order of ½ a million lipids plus protein). A route to develop highly coarse-grained models from molecular-scale information is proposed and results for N-BAR domain protein remodeling of a liposome are presented. PMID:20158037

  1. Heterogeneous lamella structure unites ultrafine-grain strength with coarse-grain ductility

    PubMed Central

    Wu, Xiaolei; Yang, Muxin; Yuan, Fuping; Wu, Guilin; Wei, Yujie; Huang, Xiaoxu; Zhu, Yuntian

    2015-01-01

    Grain refinement can make conventional metals several times stronger, but this comes at dramatic loss of ductility. Here we report a heterogeneous lamella structure in Ti produced by asymmetric rolling and partial recrystallization that can produce an unprecedented property combination: as strong as ultrafine-grained metal and at the same time as ductile as conventional coarse-grained metal. It also has higher strain hardening than coarse-grained Ti, which was hitherto believed impossible. The heterogeneous lamella structure is characterized with soft micrograined lamellae embedded in hard ultrafine-grained lamella matrix. The unusual high strength is obtained with the assistance of high back stress developed from heterogeneous yielding, whereas the high ductility is attributed to back-stress hardening and dislocation hardening. The process discovered here is amenable to large-scale industrial production at low cost, and might be applicable to other metal systems. PMID:26554017

  2. Heterogeneous lamella structure unites ultrafine-grain strength with coarse-grain ductility.

    PubMed

    Wu, Xiaolei; Yang, Muxin; Yuan, Fuping; Wu, Guilin; Wei, Yujie; Huang, Xiaoxu; Zhu, Yuntian

    2015-11-24

    Grain refinement can make conventional metals several times stronger, but this comes at dramatic loss of ductility. Here we report a heterogeneous lamella structure in Ti produced by asymmetric rolling and partial recrystallization that can produce an unprecedented property combination: as strong as ultrafine-grained metal and at the same time as ductile as conventional coarse-grained metal. It also has higher strain hardening than coarse-grained Ti, which was hitherto believed impossible. The heterogeneous lamella structure is characterized with soft micrograined lamellae embedded in hard ultrafine-grained lamella matrix. The unusual high strength is obtained with the assistance of high back stress developed from heterogeneous yielding, whereas the high ductility is attributed to back-stress hardening and dislocation hardening. The process discovered here is amenable to large-scale industrial production at low cost, and might be applicable to other metal systems. PMID:26554017

  3. Vapor Pressure of Aqueous Solutions of Electrolytes Reproduced with Coarse-Grained Models without Electrostatics.

    PubMed

    Perez Sirkin, Yamila A; Factorovich, Matías H; Molinero, Valeria; Scherlis, Damian A

    2016-06-14

    The vapor pressure of water is a key property in a large class of applications from the design of membranes for fuel cells and separations to the prediction of the mixing state of atmospheric aerosols. Molecular simulations have been used to compute vapor pressures, and a few studies on liquid mixtures and solutions have been reported on the basis of the Gibbs Ensemble Monte Carlo method in combination with atomistic force fields. These simulations are costly, making them impractical for the prediction of the vapor pressure of complex materials. The goal of the present work is twofold: (1) to demonstrate the use of the grand canonical screening approach ( Factorovich , M. H. J. Chem. Phys. 2014 , 140 , 064111 ) to compute the vapor pressure of solutions and to extend the methodology for the treatment of systems without a liquid-vapor interface and (2) to investigate the ability of computationally efficient high-resolution coarse-grained models based on the mW monatomic water potential and ions described exclusively with short-range interactions to reproduce the relative vapor pressure of aqueous solutions. We find that coarse-grained models of LiCl and NaCl solutions faithfully reproduce the experimental relative pressures up to high salt concentrations, despite the inability of these models to predict cohesive energies of the solutions or the salts. A thermodynamic analysis reveals that the coarse-grained models achieve the experimental activity coefficients of water in solution through a compensation of severely underestimated hydration and vaporization free energies of the salts. Our results suggest that coarse-grained models developed to replicate the hydration structure and the effective ion-ion attraction in solution may lead to this compensation. Moreover, they suggest an avenue for the design of coarse-grained models that accurately reproduce the activity coefficients of solutions. PMID:27196963

  4. Statistical coarse-graining of molecular dynamics into peridynamics.

    SciTech Connect

    Silling, Stewart Andrew; Lehoucq, Richard B.

    2007-10-01

    This paper describes an elegant statistical coarse-graining of molecular dynamics at finite temperature into peridynamics, a continuum theory. Peridynamics is an efficient alternative to molecular dynamics enabling dynamics at larger length and time scales. In direct analogy with molecular dynamics, peridynamics uses a nonlocal model of force and does not employ stress/strain relationships germane to classical continuum mechanics. In contrast with classical continuum mechanics, the peridynamic representation of a system of linear springs and masses is shown to have the same dispersion relation as the original spring-mass system.

  5. Molecular Dynamics Trajectory Compression with a Coarse-Grained Model

    PubMed Central

    Cheng, Yi-Ming; Gopal, Srinivasa Murthy; Law, Sean M.; Feig, Michael

    2012-01-01

    Molecular dynamics trajectories are very data-intensive thereby limiting sharing and archival of such data. One possible solution is compression of trajectory data. Here, trajectory compression based on conversion to the coarse-grained model PRIMO is proposed. The compressed data is about one third of the original data and fast decompression is possible with an analytical reconstruction procedure from PRIMO to all-atom representations. This protocol largely preserves structural features and to a more limited extent also energetic features of the original trajectory. PMID:22025759

  6. Coarse-grained molecular dynamics: Nonlinear finite elements and finite temperature

    SciTech Connect

    Rudd, R E; Broughton, J Q

    2005-05-30

    Coarse-grained molecular dynamics (CGMD) is a technique developed as a concurrent multiscale model that couples conventional molecular dynamics (MD) to a more coarse-grained description of the periphery. The coarse-grained regions are modeled on a mesh in a formulation that generalizes conventional finite element modeling (FEM) of continuum elasticity. CGMD is derived solely from the MD model, however, and has no continuum parameters. As a result, it provides a coupling that is smooth and provides control of errors that arise at the coupling between the atomistic and coarse-grained regions. In this article, we elaborate on the formulation of CGMD, describing in detail how CGMD is applied to anharmonic solids and finite temperature simulations. As tests of CGMD, we present in detail the calculation of the phonon spectra for solid argon and tantalum in 3D, demonstrating how CGMD provides a better description of the elastic waves than that provided by FEM. We also present elastic wave scattering calculations that show the elastic wave scattering is more benign in CGMD than FEM. We also discuss the dependence of scattering on the properties of the mesh. We introduce a rigid approximation to CGMD that eliminates internal relaxation, similar to the Quasicontinuum technique, and compare it to the full CGMD.

  7. Coarse-grained cosmological perturbation theory: Stirring up the dust model

    NASA Astrophysics Data System (ADS)

    Uhlemann, Cora; Kopp, Michael

    2015-04-01

    We study the effect of coarse graining the dynamics of a pressureless self-gravitating fluid (coarse-grained dust) in the context of cosmological perturbation theory, in both the Eulerian and Lagrangian frameworks. We obtain recursion relations for the Eulerian perturbation kernels of the coarse-grained dust model by relating them to those of the standard pressureless fluid model. The effect of the coarse graining is illustrated by means of power and cross spectra for the density and velocity, which are computed up to one-loop order. In particular, the large-scale vorticity power spectrum that arises naturally from a mass-weighted velocity is derived from first principles. We find qualitatively good agreement for the magnitude, shape, and spectral index of the vorticity power spectrum with recent measurements from N -body simulations and results from the effective field theory of large-scale structure. To lay the ground for applications in the context of Lagrangian perturbation theory, we finally describe how the kernels obtained in Eulerian space can be mapped to Lagrangian ones.

  8. Path-space variational inference for non-equilibrium coarse-grained systems

    NASA Astrophysics Data System (ADS)

    Harmandaris, Vagelis; Kalligiannaki, Evangelia; Katsoulakis, Markos; Plecháč, Petr

    2016-06-01

    In this paper we discuss information-theoretic tools for obtaining optimized coarse-grained molecular models for both equilibrium and non-equilibrium molecular simulations. The latter are ubiquitous in physicochemical and biological applications, where they are typically associated with coupling mechanisms, multi-physics and/or boundary conditions. In general the non-equilibrium steady states are not known explicitly as they do not necessarily have a Gibbs structure. The presented approach can compare microscopic behavior of molecular systems to parametric and non-parametric coarse-grained models using the relative entropy between distributions on the path space and setting up a corresponding path-space variational inference problem. The methods can become entirely data-driven when the microscopic dynamics are replaced with corresponding correlated data in the form of time series. Furthermore, we present connections and generalizations of force matching methods in coarse-graining with path-space information methods. We demonstrate the enhanced transferability of information-based parameterizations to different observables, at a specific thermodynamic point, due to information inequalities. We discuss methodological connections between information-based coarse-graining of molecular systems and variational inference methods primarily developed in the machine learning community. However, we note that the work presented here addresses variational inference for correlated time series due to the focus on dynamics. The applicability of the proposed methods is demonstrated on high-dimensional stochastic processes given by overdamped and driven Langevin dynamics of interacting particles.

  9. Insights into DNA-mediated interparticle interactions from a coarse-grained model.

    PubMed

    Ding, Yajun; Mittal, Jeetain

    2014-11-14

    DNA-functionalized particles have great potential for the design of complex self-assembled materials. The major hurdle in realizing crystal structures from DNA-functionalized particles is expected to be kinetic barriers that trap the system in metastable amorphous states. Therefore, it is vital to explore the molecular details of particle assembly processes in order to understand the underlying mechanisms. Molecular simulations based on coarse-grained models can provide a convenient route to explore these details. Most of the currently available coarse-grained models of DNA-functionalized particles ignore key chemical and structural details of DNA behavior. These models therefore are limited in scope for studying experimental phenomena. In this paper, we present a new coarse-grained model of DNA-functionalized particles which incorporates some of the desired features of DNA behavior. The coarse-grained DNA model used here provides explicit DNA representation (at the nucleotide level) and complementary interactions between Watson-Crick base pairs, which lead to the formation of single-stranded hairpin and double-stranded DNA. Aggregation between multiple complementary strands is also prevented in our model. We study interactions between two DNA-functionalized particles as a function of DNA grafting density, lengths of the hybridizing and non-hybridizing parts of DNA, and temperature. The calculated free energies as a function of pair distance between particles qualitatively resemble experimental measurements of DNA-mediated pair interactions. PMID:25399156

  10. Characteristics of energy exchange between inter- and intramolecular degrees of freedom in crystalline 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) with implications for coarse-grained simulations of shock waves in polyatomic molecular crystals

    NASA Astrophysics Data System (ADS)

    Kroonblawd, Matthew P.; Sewell, Thomas D.; Maillet, Jean-Bernard

    2016-02-01

    In this report, we characterize the kinetics and dynamics of energy exchange between intramolecular and intermolecular degrees of freedom (DoF) in crystalline 1,3,5-triamino-2,4,6-trinitrobenzene (TATB). All-atom molecular dynamics (MD) simulations are used to obtain predictions for relaxation from certain limiting initial distributions of energy between the intra- and intermolecular DoF. The results are used to parameterize a coarse-grained Dissipative Particle Dynamics at constant Energy (DPDE) model for TATB. Each TATB molecule in the DPDE model is represented as an all-atom, rigid-molecule mesoparticle, with explicit external (molecular translational and rotational) DoF and coarse-grained implicit internal (vibrational) DoF. In addition to conserving linear and angular momentum, the DPDE equations of motion conserve the total system energy provided that particles can exchange energy between their external and internal DoF. The internal temperature of a TATB molecule is calculated using an internal equation of state, which we develop here, and the temperatures of the external and internal DoF are coupled using a fluctuation-dissipation relation. The DPDE force expression requires specification of the input parameter σ that determines the rate at which energy is exchanged between external and internal DoF. We adjusted σ based on the predictions for relaxation processes obtained from MD simulations. The parameterized DPDE model was employed in large-scale simulations of shock compression of TATB. We show that the rate of energy exchange governed by σ can significantly influence the transient behavior of the system behind the shock.

  11. Characteristics of energy exchange between inter- and intramolecular degrees of freedom in crystalline 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) with implications for coarse-grained simulations of shock waves in polyatomic molecular crystals.

    PubMed

    Kroonblawd, Matthew P; Sewell, Thomas D; Maillet, Jean-Bernard

    2016-02-14

    In this report, we characterize the kinetics and dynamics of energy exchange between intramolecular and intermolecular degrees of freedom (DoF) in crystalline 1,3,5-triamino-2,4,6-trinitrobenzene (TATB). All-atom molecular dynamics (MD) simulations are used to obtain predictions for relaxation from certain limiting initial distributions of energy between the intra- and intermolecular DoF. The results are used to parameterize a coarse-grained Dissipative Particle Dynamics at constant Energy (DPDE) model for TATB. Each TATB molecule in the DPDE model is represented as an all-atom, rigid-molecule mesoparticle, with explicit external (molecular translational and rotational) DoF and coarse-grained implicit internal (vibrational) DoF. In addition to conserving linear and angular momentum, the DPDE equations of motion conserve the total system energy provided that particles can exchange energy between their external and internal DoF. The internal temperature of a TATB molecule is calculated using an internal equation of state, which we develop here, and the temperatures of the external and internal DoF are coupled using a fluctuation-dissipation relation. The DPDE force expression requires specification of the input parameter σ that determines the rate at which energy is exchanged between external and internal DoF. We adjusted σ based on the predictions for relaxation processes obtained from MD simulations. The parameterized DPDE model was employed in large-scale simulations of shock compression of TATB. We show that the rate of energy exchange governed by σ can significantly influence the transient behavior of the system behind the shock. PMID:26874491

  12. Systematic coarse-grained modeling of complexation between small interfering RNA and polycations

    NASA Astrophysics Data System (ADS)

    Wei, Zonghui; Luijten, Erik

    2015-12-01

    All-atom molecular dynamics simulations can provide insight into the properties of polymeric gene-delivery carriers by elucidating their interactions and detailed binding patterns with nucleic acids. However, to explore nanoparticle formation through complexation of these polymers and nucleic acids and study their behavior at experimentally relevant time and length scales, a reliable coarse-grained model is needed. Here, we systematically develop such a model for the complexation of small interfering RNA (siRNA) and grafted polyethyleneimine copolymers, a promising candidate for siRNA delivery. We compare the predictions of this model with all-atom simulations and demonstrate that it is capable of reproducing detailed binding patterns, charge characteristics, and water release kinetics. Since the coarse-grained model accelerates the simulations by one to two orders of magnitude, it will make it possible to quantitatively investigate nanoparticle formation involving multiple siRNA molecules and cationic copolymers.

  13. Systematic coarse-grained modeling of complexation between small interfering RNA and polycations

    SciTech Connect

    Wei, Zonghui; Luijten, Erik

    2015-12-28

    All-atom molecular dynamics simulations can provide insight into the properties of polymeric gene-delivery carriers by elucidating their interactions and detailed binding patterns with nucleic acids. However, to explore nanoparticle formation through complexation of these polymers and nucleic acids and study their behavior at experimentally relevant time and length scales, a reliable coarse-grained model is needed. Here, we systematically develop such a model for the complexation of small interfering RNA (siRNA) and grafted polyethyleneimine copolymers, a promising candidate for siRNA delivery. We compare the predictions of this model with all-atom simulations and demonstrate that it is capable of reproducing detailed binding patterns, charge characteristics, and water release kinetics. Since the coarse-grained model accelerates the simulations by one to two orders of magnitude, it will make it possible to quantitatively investigate nanoparticle formation involving multiple siRNA molecules and cationic copolymers.

  14. Improved Coarse-Grained Modeling of Cholesterol-Containing Lipid Bilayers

    PubMed Central

    2015-01-01

    Cholesterol trafficking, which is an essential function in mammalian cells, is intimately connected to molecular-scale interactions through cholesterol modulation of membrane structure and dynamics and interaction with membrane receptors. Since these effects of cholesterol occur on micro- to millisecond time scales, it is essential to develop accurate coarse-grained simulation models that can reach these time scales. Cholesterol has been shown experimentally to thicken the membrane and increase phospholipid tail order between 0 and 40% cholesterol, above which these effects plateau or slightly decrease. Here, we showed that the published MARTINI coarse-grained force-field for phospholipid (POPC) and cholesterol fails to capture these effects. Using reference atomistic simulations, we systematically modified POPC and cholesterol bonded parameters in MARTINI to improve its performance. We showed that the corrections to pseudobond angles between glycerol and the lipid tails and around the oleoyl double bond particle (the “angle-corrected model”) slightly improves the agreement of MARTINI with experimentally measured thermal, elastic, and dynamic properties of POPC membranes. The angle-corrected model improves prediction of the thickening and ordering effects up to 40% cholesterol but overestimates these effects at higher cholesterol concentration. In accordance with prior work that showed the cholesterol rough face methyl groups are important for limiting cholesterol self-association, we revised the coarse-grained representation of these methyl groups to better match cholesterol-cholesterol radial distribution functions from atomistic simulations. In addition, by using a finer-grained representation of the branched cholesterol tail than MARTINI, we improved predictions of lipid tail order and bilayer thickness across a wide range of concentrations. Finally, transferability testing shows that a model incorporating our revised parameters into DOPC outperforms other

  15. Minimizing memory as an objective for coarse-graining

    NASA Astrophysics Data System (ADS)

    Guttenberg, Nicholas; Dama, James F.; Saunders, Marissa G.; Voth, Gregory A.; Weare, Jonathan; Dinner, Aaron R.

    2013-03-01

    Coarse-graining a molecular model is the process of integrating over degrees of freedom to obtain a reduced representation. This process typically involves two separate but related steps, selection of the coordinates comprising the reduced system and modeling their interactions. Both the coordinate selection and the modeling procedure present challenges. Here, we focus on the former. Typically, one seeks to integrate over the fast degrees of freedom and retain the slow degrees of freedom. Failure to separate timescales results in memory. With this motivation, we introduce a heuristic measure of memory and show that it can be used to compare competing coordinate selections for a given modeling procedure. We numerically explore the utility of this heuristic for three systems of increasing complexity. The first example is a four-particle linear model, which is exactly solvable. The second example is a sixteen-particle nonlinear model; this system has interactions that are characteristic of molecular force fields but is still sufficiently simple to permit exhaustive numerical treatment. The third example is an atomic-resolution representation of a protein, the class of models most often treated by relevant coarse-graining approaches; we specifically study an actin monomer. In all three cases, we find that the heuristic suggests coordinate selections that are physically intuitive and reflect molecular structure. The memory heuristic can thus serve as an objective codification of expert knowledge and a guide to sites within a model that requires further attention.

  16. Effective mobility of dislocations from systematic coarse-graining

    NASA Astrophysics Data System (ADS)

    Kooiman, M.; Hütter, M.; Geers, MGD

    2015-06-01

    The dynamics of large amounts of dislocations governs the plastic response of crystalline materials. In this contribution we discuss the relation between the mobility of discrete dislocations and the resulting flow rule for coarse-grained dislocation densities. The mobilities used in literature on these levels are quite different, for example in terms of their intrinsic the stress dependence. To establish the relation across the scales, we have derived the macroscopic evolution equations of dislocation densities from the equations of motion of individual dislocations by means of systematic coarse-graining. From this, we can identify a memory kernel relating the driving force and the flux of dislocations. This kernel can be considered as an effective macroscopic mobility with two contributions; a direct contribution related to the overdamped motion of individual dislocations, and an emergent contribution that arises from time correlations of fluctuations in the Peach-Koehler force. Scaling analysis shows that the latter contribution is dominant for dislocations in metals at room temperature. We also discuss several concerns related to the separation of timescales.

  17. An exactly solvable coarse-grained model for species diversity

    NASA Astrophysics Data System (ADS)

    Suweis, Samir; Rinaldo, Andrea; Maritan, Amos

    2012-07-01

    We present novel analytical results concerning ecosystem species diversity that stem from a proposed coarse-grained neutral model based on birth-death processes. The relevance of the problem lies in the urgency for understanding and synthesizing both theoretical results from ecological neutral theory and empirical evidence on species diversity preservation. The neutral model of biodiversity deals with ecosystems at the same trophic level, where per capita vital rates are assumed to be species independent. Closed-form analytical solutions for the neutral theory are obtained within a coarse-grained model, where the only input is the species persistence time distribution. Our results pertain to: the probability distribution function of the number of species in the ecosystem, both in transient and in stationary states; the n-point connected time correlation function; and the survival probability, defined as the distribution of time spans to local extinction for a species randomly sampled from the community. Analytical predictions are also tested on empirical data from an estuarine fish ecosystem. We find that emerging properties of the ecosystem are very robust and do not depend on specific details of the model, with implications for biodiversity and conservation biology.

  18. Million atom DFT calculations using coarse graining and petascale computing

    NASA Astrophysics Data System (ADS)

    Nicholson, Don; Odbadrakh, Kh.; Samolyuk, G. D.; Stoller, R. E.; Zhang, X. G.; Stocks, G. M.

    2014-03-01

    Researchers performing classical Molecular Dynamics (MD) on defect structures often find it necessary to use millions of atoms in their models. It would be useful to perform density functional calculations on these large configurations in order to observe electron-based properties such as local charge and spin and the Helmann-Feynman forces on the atoms. The great number of atoms usually requires that a subset be ``carved'' from the configuration and terminated in a less that satisfactory manner, e.g. free space or inappropriate periodic boundary conditions. Coarse graining based on the Locally Self-consistent Multiple Scattering method (LSMS) and petascale computing can circumvent this problem by treating the whole system but dividing the atoms into two groups. In Coarse Grained LSMS (CG-LSMS) one group of atoms has its charge and scattering determined prescriptively based on neighboring atoms while the remaining group of atoms have their charge and scattering determined according to DFT as implemented in the LSMS. The method will be demonstrated for a one-million-atom model of a displacement cascade in Fe for which 24,130 atoms are treated with full DFT and the remaining atoms are treated prescriptively. Work supported as part of Center for Defect Physics, an Energy Frontier Research Center funded by the U.S. DOE, Office of Science, Basic Energy Sciences, used Oak Ridge Leadership Computing Facility, Oak Ridge National Lab, of DOE Office of Science.

  19. Coarse-graining the structure of polycyclic aromatic hydrocarbons clusters.

    PubMed

    Hernández-Rojas, J; Calvo, F; Wales, D J

    2016-05-18

    Clusters of polycyclic aromatic hydrocarbons (PAHs) are essential components of soot and may concentrate a significant fraction of carbon matter in the interstellar medium. In this contribution, coarse-grained potentials are parameterized using all-atom reference data to model PAH molecules, such as coronene (C24H12) or circumcoronene (C54H18), and their aggregates. Low-energy structures of pure coronene or circumcoronene clusters obtained using basin-hopping global optimization are found to agree with atomistic results, and consist of finite 1D columnar motifs, sometimes juxtaposed in larger clusters. The structures are only weakly perturbed when quadrupolar interactions are included. π-Stacking also dominates in binary coronene/circumcoronene aggregates, although intriguing motifs are predicted in which one or more molecules are sandwiched between the other PAH species. The coarse-grained model is also extended to account for interaction with a flat graphitic substrate. In this case, binding is stronger with the substrate than with other molecules, and the PAHs are predicted to arrange into a flat triangular monolayer. PMID:27055581

  20. Theoretical reconstruction of realistic dynamics of highly coarse-grained cis-1,4-polybutadiene melts

    NASA Astrophysics Data System (ADS)

    Lyubimov, I. Y.; Guenza, M. G.

    2013-03-01

    The theory to reconstruct the atomistic-level chain diffusion from the accelerated dynamics that is measured in mesoscale simulations of the coarse-grained system, is applied here to the dynamics of cis-1,4-polybutadiene melts where each chain is described as a soft interacting colloidal particle. The rescaling formalism accounts for the corrections in the dynamics due to the change in entropy and the change in friction that are a consequence of the coarse-graining procedure. By including these two corrections the dynamics is rescaled to reproduce the realistic dynamics of the system described at the atomistic level. The rescaled diffusion coefficient obtained from mesoscale simulations of coarse-grained cis-1,4-polybutadiene melts shows good agreement with data from united atom simulations performed by Tsolou et al. [Macromolecules 38, 1478 (2005)], 10.1021/ma0491210. The derived monomer friction coefficient is used as an input to the theory for cooperative dynamics that describes the internal dynamics of a polymer moving in a transient regions of slow cooperative motion in a liquid of macromolecules. Theoretically predicted time correlation functions show good agreement with simulations in the whole range of length and time scales in which data are available.

  1. Premelting, fluctuations, and coarse-graining of water-ice interfaces

    SciTech Connect

    Limmer, David T.; Chandler, David

    2014-11-14

    Using statistical field theory supplemented with molecular dynamics simulations, we consider premelting on the surface of ice as a generic consequence of broken hydrogen bonds at the boundary between the condensed and gaseous phases. A procedure for coarse-graining molecular configurations onto a continuous scalar order parameter field is discussed, which provides a convenient representation of the interface between locally crystal-like and locally liquid-like regions. A number of interfacial properties are straightforwardly evaluated using this procedure such as the average premelting thickness and surface tension. The temperature and system size dependence of the premelting layer thickness calculated in this way confirms the characteristic logarithmic growth expected for the scalar field theory that the system is mapped onto through coarse-graining, though remains finite due to long-ranged interactions. Finally, from explicit simulations the existence of a premelting layer is shown to be insensitive to bulk lattice geometry, exposed crystal face, and curvature.

  2. Fused coarse-grained model of aromatic ionic liquids and their behaviour at electrodes.

    PubMed

    Li, Bin; Ma, Ke; Wang, Yong-Lei; Turesson, Martin; Woodward, Clifford E; Forsman, Jan

    2016-03-01

    A fused coarse-grained model of aromatic ionic liquids 1-alkyl-3-methylimidazoliums tetrafluoroborate ([CnMIM(+)][BF4(-)]) has been constructed. Structural and dynamical properties calculated from our model are compared with experimental data as well as with corresponding results from simulations of other suggested models. Specifically, we adopt a fused-sphere coarse-grained model for cations and anions. This model is utilized to study structure and differential capacitance in models of flat and porous carbon electrodes. We find that the capacitance varies with pore size, in a manner that is related to the packing of ions inside the pore. For very narrow pores, diffusion is slow and the establishment of thermodynamic equilibrium may exceed the practical limits for our molecular dynamics simulations. PMID:26928079

  3. Coarse Graining and Localized Plasticity between Sliding Nanocrystalline Metals

    NASA Astrophysics Data System (ADS)

    Romero, Pedro A.; Järvi, Tommi T.; Beckmann, Nils; Mrovec, Matous; Moseler, Michael

    2014-07-01

    Tribological shearing of polycrystalline metals typically leads to grain refinement at the sliding interface. This study, however, shows that nanocrystalline metals exhibit qualitatively different behavior. Using large-scale atomistic simulations, we demonstrate that during sliding, contact interface nanocrystalline grains self-organize through extensive grain coarsening and lattice rotation until the optimal plastic slip orientation is established. Subsequently, plastic deformation is frequently confined to localized nanoshear bands aligned with the shearing direction and emanating from voids and other defects in the vicinity of the sliding interface.

  4. A coarse grained stochastic particle interacting system for tropical convection

    NASA Astrophysics Data System (ADS)

    Khouider, B.

    2012-12-01

    Climate models (GCMs) fail to represent adequately the variability associated with organized convection in the tropics. This deficiency is believed to hinder medium and long range weather forecasts, over weeks to months. GCMs use very complex sub-grid models, known as cumulus parameterizations, to represent the effects of clouds and convection as well as other unresolved processes. Cumulus parameterizations are intrinsically deterministic and are typically based on the quasi-equilibrium theory, which assumes that convection instantaneously consumes the atmospheric instability produced by radiation. In this talk, I will discuss a stochastic model for organized tropical convection based on a particle interacting system defined on a microscopic lattice. An order parameter is assumed to take the values 0,1,2,3 at a any given lattice site according to whether it is a clear site or it is occupied by a cloud of a one of the three types: congestus, deep, or stratiform, following intuitive rules motivated by recent satellite observations and various field campaigns conducted over the Indian Ocean and Western Pacific. The microscopic Markov process is coarse-grained systematically to obtain a multidimensional birth-death process with immigration, following earlier work done by Katsoulakis, Majda, and Vlachos (JCP 2003) for the case of the Ising model where the order parameter takes the values 0 and 1. The coarse grained birth-death process is a stochastic model, intermediate between the microscopic lattice model and the deterministic mean field limit, that is used to represent the sub-grid scale variability of the underlying physical process (here the cloud cover) with a negligible computational overhead and yet permits both local interactions between lattice sites and two-way interactions between the cloud cover and the large-scale climate dynamics. The new systematic coarse-graining, developed here for the multivalued order parameter, provides a unifying framework

  5. Using Atomistic Molecular Dynamics Simulations to Guide Development of Coarse-Grained Models of Polyethylene glycol (PEG), Elastic-like peptides (ELP) and Collagen-like peptides (CMP) For Biomaterial Design

    NASA Astrophysics Data System (ADS)

    Stanzione, Francesca; Jayaraman, Arthi

    Molecular dynamics (MD) is a well established technique to study the structure and dynamics of biomolecular systems. While atomistic simulations maintain chemical details, they are computationally intensive, thus limiting the accessible time, the length scales and the sampling. To overcome these limitations, coarse-grained (CG) models have proven to be successful in reproducing experimentally relevant length and time scales with reasonable computational expense. CG models can be developed to be phenomenological by effectively reproducing experimental results or can be developed by mapping rigorously to structural information provided by atomistic MD simulations. The latter method is recommended for biomolecules and biomaterials since atomistic simulations capture the detailed effect of the medium on interactions that affect the structure, dynamics and functional properties of the biomolecules, and that can be programmed into the CG models. In this poster we highlight three different cases where atomistic MD simulations provide such essential information to guide CG models: Polyethylene glycol, Elastic-like peptides and Collagen-like peptides based biomaterials.

  6. Peridynamics as a rigorous coarse-graining of atomistics for multiscale materials design.

    SciTech Connect

    Lehoucq, Richard B.; Aidun, John Bahram; Silling, Stewart Andrew; Sears, Mark P.; Kamm, James R.; Parks, Michael L.

    2010-09-01

    This report summarizes activities undertaken during FY08-FY10 for the LDRD Peridynamics as a Rigorous Coarse-Graining of Atomistics for Multiscale Materials Design. The goal of our project was to develop a coarse-graining of finite temperature molecular dynamics (MD) that successfully transitions from statistical mechanics to continuum mechanics. The goal of our project is to develop a coarse-graining of finite temperature molecular dynamics (MD) that successfully transitions from statistical mechanics to continuum mechanics. Our coarse-graining overcomes the intrinsic limitation of coupling atomistics with classical continuum mechanics via the FEM (finite element method), SPH (smoothed particle hydrodynamics), or MPM (material point method); namely, that classical continuum mechanics assumes a local force interaction that is incompatible with the nonlocal force model of atomistic methods. Therefore FEM, SPH, and MPM inherit this limitation. This seemingly innocuous dichotomy has far reaching consequences; for example, classical continuum mechanics cannot resolve the short wavelength behavior associated with atomistics. Other consequences include spurious forces, invalid phonon dispersion relationships, and irreconcilable descriptions/treatments of temperature. We propose a statistically based coarse-graining of atomistics via peridynamics and so develop a first of a kind mesoscopic capability to enable consistent, thermodynamically sound, atomistic-to-continuum (AtC) multiscale material simulation. Peridynamics (PD) is a microcontinuum theory that assumes nonlocal forces for describing long-range material interaction. The force interactions occurring at finite distances are naturally accounted for in PD. Moreover, PDs nonlocal force model is entirely consistent with those used by atomistics methods, in stark contrast to classical continuum mechanics. Hence, PD can be employed for mesoscopic phenomena that are beyond the realms of classical continuum mechanics and

  7. Investigating the impact of representation upon coarse-grained models

    NASA Astrophysics Data System (ADS)

    Foley, Thomas; Shell, M. Scott; Noid, William

    The first step in building a coarse-grained (CG) model is choosing a representation or `mapping' of the original system at a reduced resolution. In practice, the mapping is often chosen on the basis of `physical intuition.' Consequently this crucial step would greatly benefit from the development of systematic and principled methodologies. Accordingly, we have studied the relationship between the mapping and the resulting CG model. As a starting point, we have analytically derived, as a function of the CG mapping, the exact many-body potential of mean force (PMF) for the simple Gaussian Network Model (GNM) of protein fluctuations. We use this as a simple model for investigating the effect of the CG mapping upon the information loss and quality of the CG model. Moreover, by considering the GNM's for different proteins, we investigate the significance of high resolution structural features for the quality of the CG model. We acknowledge support from the NSF, Alfred P. Sloan Foundation, and KITP.

  8. Supramolecular polymerization: a coarse grained molecular dynamics study.

    PubMed

    Bejagam, Karteek K; Balasubramanian, Sundaram

    2015-04-30

    A coarse-grained (CG) force field to model the self-assembly of benzene-1,3,5-tricarboxamide (BTA) class of compounds in nonpolar solvents has been developed. The model includes an intrinsic point dipole embedded on one of the CG beads so as to impart a macrodipole moment to the oligomer, one of its characteristic feature. Chemical specificity has been preserved by benchmarking against results, including dimerization and solvation free energies, obtained from an all-atom representation. Starting from a well-dispersed configuration in n-nonane, BTA molecules self-assemble to form one-dimensional stacks. Free energy (FE) changes for the various manner in which short oligomers can exchange between the assembled and the dispersed states have been calculated. These calculations show BTA to self-assemble via a downhill cooperative mechanism with a nucleus size of three. PMID:25853485

  9. Coarse grained modeling of transport properties in monoclonal antibody solution

    NASA Astrophysics Data System (ADS)

    Swan, James; Wang, Gang

    Monoclonal antibodies and their derivatives represent the fastest growing segment of the bio pharmaceutical industry. For many applications such as novel cancer therapies, high concentration, sub-cutaneous injections of these protein solutions are desired. However, depending on the peptide sequence within the antibody, such high concentration formulations can be too viscous to inject via human derived force alone. Understanding how heterogenous charge distribution and hydrophobicity within the antibodies leads to high viscosities is crucial to their future application. In this talk, we explore a coarse grained computational model of therapeutically relevant monoclonal antibodies that accounts for electrostatic, dispersion and hydrodynamic interactions between suspended antibodies to predict assembly and transport properties in concentrated antibody solutions. We explain the high viscosities observed in many experimental studies of the same biologics.

  10. Coarse-grained kinetic equations for quantum systems

    NASA Astrophysics Data System (ADS)

    Petrov, E. G.

    2013-01-01

    The nonequilibrium density matrix method is employed to derive a master equation for the averaged state populations of an open quantum system subjected to an external high frequency stochastic field. It is shown that if the characteristic time τstoch of the stochastic process is much lower than the characteristic time τsteady of the establishment of the system steady state populations, then on the time scale Δ t ˜ τsteady, the evolution of the system populations can be described by the coarse-grained kinetic equations with the averaged transition rates. As an example, the exact averaging is carried out for the dichotomous Markov process of the kangaroo type.

  11. Short-range, overpressure-driven methane migration in coarse-grained gas hydrate reservoirs

    DOE PAGESBeta

    Nole, Michael; Daigle, Hugh; Cook, Ann E.; Malinverno, Alberto

    2016-08-31

    Two methane migration mechanisms have been proposed for coarse-grained gas hydrate reservoirs: short-range diffusive gas migration and long-range advective fluid transport from depth. Herein we demonstrate that short-range fluid flow due to overpressure in marine sediments is a significant additional methane transport mechanism that allows hydrate to precipitate in large quantities in thick, coarse-grained hydrate reservoirs. Two-dimensional simulations demonstrate that this migration mechanism, short-range advective transport, can supply significant amounts of dissolved gas and is unencumbered by limitations of the other two end-member mechanisms. Here, short-range advective migration can increase the amount of methane delivered to sands as compared tomore » the slow process of diffusion, yet it is not necessarily limited by effective porosity reduction as is typical of updip advection from a deep source.« less

  12. Moving beyond Watson-Crick models of coarse grained DNA dynamics

    NASA Astrophysics Data System (ADS)

    Linak, Margaret C.; Tourdot, Richard; Dorfman, Kevin D.

    2011-11-01

    DNA produces a wide range of structures in addition to the canonical B-form of double-stranded DNA. Some of these structures are stabilized by Hoogsteen bonds. We developed an experimentally parameterized, coarse-grained model that incorporates such bonds. The model reproduces many of the microscopic features of double-stranded DNA and captures the experimental melting curves for a number of short DNA hairpins, even when the open state forms complicated secondary structures. We demonstrate the utility of the model by simulating the folding of a thrombin aptamer, which contains G-quartets, and strand invasion during triplex formation. Our results highlight the importance of including Hoogsteen bonding in coarse-grained models of DNA.

  13. Folding of small knotted proteins: Insights from a mean field coarse-grained model

    SciTech Connect

    Najafi, Saeed; Potestio, Raffaello

    2015-12-28

    A small but relevant number of proteins whose native structure is known features nontrivial topology, i.e., they are knotted. Understanding the process of folding from a swollen unknotted state to the biologically relevant native conformation is, for these proteins, particularly difficult, due to their rate-limiting topological entanglement. To shed some light into this conundrum, we introduced a structure-based coarse-grained model of the protein, where the information about the folded conformation is encoded in bonded angular interactions only, which do not favor the formation of native contacts. A stochastic search scheme in parameter space is employed to identify a set of interactions that maximizes the probability to attain the knotted state. The optimal knotting pathways of the two smallest knotted proteins, obtained through this approach, are consistent with the results derived by means of coarse-grained as well as full atomistic simulations.

  14. Proximal distributions from angular correlations: A measure of the onset of coarse-graining

    PubMed Central

    Dyer, Kippi M.; Pettitt, B. Montgomery

    2013-01-01

    In this work we examine and extend the theory of proximal radial distribution functions for molecules in solution. We point out two formal extensions, the first of which generalizes the proximal distribution function hierarchy approach to the complete, angularly dependent molecular pair distribution function. Second, we generalize from the traditional right-handed solute-solvent proximal distribution functions to the left-handed distributions. The resulting neighbor hierarchy convergence is shown to provide a measure of the coarse-graining of the internal solute sites with respect to the solvent. Simulation of the test case of a deca-alanine peptide shows that this coarse-graining measure converges at a length scale of approximately 5 amino acids for the system considered. PMID:24320368

  15. Proximal distributions from angular correlations: A measure of the onset of coarse-graining

    NASA Astrophysics Data System (ADS)

    Dyer, Kippi M.; Pettitt, B. Montgomery

    2013-12-01

    In this work we examine and extend the theory of proximal radial distribution functions for molecules in solution. We point out two formal extensions, the first of which generalizes the proximal distribution function hierarchy approach to the complete, angularly dependent molecular pair distribution function. Second, we generalize from the traditional right-handed solute-solvent proximal distribution functions to the left-handed distributions. The resulting neighbor hierarchy convergence is shown to provide a measure of the coarse-graining of the internal solute sites with respect to the solvent. Simulation of the test case of a deca-alanine peptide shows that this coarse-graining measure converges at a length scale of approximately 5 amino acids for the system considered.

  16. Gene expression dynamics with stochastic bursts: Construction and exact results for a coarse-grained model

    NASA Astrophysics Data System (ADS)

    Lin, Yen Ting; Doering, Charles R.

    2016-02-01

    We present a theoretical framework to analyze the dynamics of gene expression with stochastic bursts. Beginning with an individual-based model which fully accounts for the messenger RNA (mRNA) and protein populations, we propose an expansion of the master equation for the joint process. The resulting coarse-grained model reduces the dimensionality of the system, describing only the protein population while fully accounting for the effects of discrete and fluctuating mRNA population. Closed form expressions for the stationary distribution of the protein population and mean first-passage times of the coarse-grained model are derived and large-scale Monte Carlo simulations show that the analysis accurately describes the individual-based process accounting for mRNA population, in contrast to the failure of commonly proposed diffusion-type models.

  17. A Hybrid Approach for Highly Coarse-grained Lipid Bilayer Models

    PubMed Central

    Srivastava, Anand; Voth, Gregory A.

    2012-01-01

    We present a systematic methodology to develop highly coarse-grained (CG) lipid models for large scale bio-membrane simulations, in which we derive CG interactions using a powerful combination of the multiscale coarse-graining (MS-CG) method, and an analytical form of the CG potential to model interactions at short range. The resulting hybrid coarse-graining (HCG) methodology is used to develop a three-site solvent-free model for 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and a 1:1 mixture of 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS) and DOPC. In addition, we developed a four-site model of DOPC, demonstrating the capability of the HCG methodology in designing model lipid systems of a desired resolution. We carried out microsecond-scale molecular dynamics (MD) simulations of large vesicles, highlighting the ability of the model to study systems at mesoscopic length and time scales. The models of DLPC, DOPC and DOPC-DOPS have elastic properties consistent with experiment and structural properties such as the radial distribution functions (RDF), bond and angle distributions, and the z-density distributions that compare well with reference all-atom systems. PMID:25100925

  18. Classical predictability and coarse-grained evolution of the quantum baker's map

    SciTech Connect

    Scherer, Artur; Soklakov, Andrei N.; Schack, Ruediger

    2006-06-15

    We investigate how classical predictability of the coarse-grained evolution of the quantum baker's map depends on the character of the coarse-graining. Our analysis extends earlier work by Brun and Hartle [Phys. Rev. D 60, 123503 (1999)] to the case of a chaotic map. To quantify predictability, we compare the rate of entropy increase for a family of coarse-grainings in the decoherent histories formalism. We find that the rate of entropy increase is dominated by the number of scales characterizing the coarse-graining.

  19. Coarse graining the distribution function of cold dark matter - II

    NASA Astrophysics Data System (ADS)

    Henriksen, R. N.

    2004-12-01

    We study analytically the coarse- and fine-grained distribution function (DF) established by the self-similar infall of collisionless matter. We find this function explicitly for isotropic and spherically symmetric systems in terms of cosmological initial conditions. The coarse-grained function is structureless and steady but the familiar phase-space sheet substructure is recovered in the fine-grained limit. By breaking the self-similarity of the halo infall we are able to argue for a central density flattening. In addition there will be an edge steepening. The best-fitting analytic density function is likely to be provided by a high-order polytrope fit smoothly to an outer power law of index -3 for isolated systems. There may be a transition to a -4 power law in the outer regions of tidally truncated systems. As we find that the central flattening is progressive in time, dynamically young systems such as galaxy clusters may well possess a Navarro, Frenk and White type density profile, while primordial dwarf galaxies, for example, are expected to have cores. This progressive flattening is expected to end either in the non-singular isothermal sphere, or in the non-singular metastable polytropic cores; as the DFs associated with each of these arise naturally in the bulk halo during the infall. We suggest, based on previous studies of the evolution of de-stabilized polytropes, that a collisionless system may pass through a family of polytropes of increasing order, finally approaching the limit of the non-singular isothermal sphere, if the `violent' collective relaxation is frequently re-excited by `merger' events. Thus central dominant (cD) galaxies, and indeed all bright galaxies that have grown in this fashion, should be in polytropic states. Our results suggest that no physics beyond that of wave-particle scattering is necessary to explain the nature of dark matter density profiles. However, this may be assisted by the scattering of particles from the centre of the

  20. Coupling a nano-particle with isothermal fluctuating hydrodynamics: Coarse-graining from microscopic to mesoscopic dynamics

    NASA Astrophysics Data System (ADS)

    Español, Pep; Donev, Aleksandar

    2015-12-01

    We derive a coarse-grained description of the dynamics of a nanoparticle immersed in an isothermal simple fluid by performing a systematic coarse graining of the underlying microscopic dynamics. As coarse-grained or relevant variables, we select the position of the nanoparticle and the total mass and momentum density field of the fluid, which are locally conserved slow variables because they are defined to include the contribution of the nanoparticle. The theory of coarse graining based on the Zwanzing projection operator leads us to a system of stochastic ordinary differential equations that are closed in the relevant variables. We demonstrate that our discrete coarse-grained equations are consistent with a Petrov-Galerkin finite-element discretization of a system of formal stochastic partial differential equations which resemble previously used phenomenological models based on fluctuating hydrodynamics. Key to this connection between our "bottom-up" and previous "top-down" approaches is the use of the same dual orthogonal set of linear basis functions familiar from finite element methods (FEMs), both as a way to coarse-grain the microscopic degrees of freedom and as a way to discretize the equations of fluctuating hydrodynamics. Another key ingredient is the use of a "linear for spiky" weak approximation which replaces microscopic "fields" with a linear FE interpolant inside expectation values. For the irreversible or dissipative dynamics, we approximate the constrained Green-Kubo expressions for the dissipation coefficients with their equilibrium averages. Under suitable approximations, we obtain closed approximations of the coarse-grained dynamics in a manner which gives them a clear physical interpretation and provides explicit microscopic expressions for all of the coefficients appearing in the closure. Our work leads to a model for dilute nanocolloidal suspensions that can be simulated effectively using feasibly short molecular dynamics simulations as input

  1. Coupling a nano-particle with isothermal fluctuating hydrodynamics: Coarse-graining from microscopic to mesoscopic dynamics

    SciTech Connect

    Español, Pep; Donev, Aleksandar

    2015-12-21

    We derive a coarse-grained description of the dynamics of a nanoparticle immersed in an isothermal simple fluid by performing a systematic coarse graining of the underlying microscopic dynamics. As coarse-grained or relevant variables, we select the position of the nanoparticle and the total mass and momentum density field of the fluid, which are locally conserved slow variables because they are defined to include the contribution of the nanoparticle. The theory of coarse graining based on the Zwanzing projection operator leads us to a system of stochastic ordinary differential equations that are closed in the relevant variables. We demonstrate that our discrete coarse-grained equations are consistent with a Petrov-Galerkin finite-element discretization of a system of formal stochastic partial differential equations which resemble previously used phenomenological models based on fluctuating hydrodynamics. Key to this connection between our “bottom-up” and previous “top-down” approaches is the use of the same dual orthogonal set of linear basis functions familiar from finite element methods (FEMs), both as a way to coarse-grain the microscopic degrees of freedom and as a way to discretize the equations of fluctuating hydrodynamics. Another key ingredient is the use of a “linear for spiky” weak approximation which replaces microscopic “fields” with a linear FE interpolant inside expectation values. For the irreversible or dissipative dynamics, we approximate the constrained Green-Kubo expressions for the dissipation coefficients with their equilibrium averages. Under suitable approximations, we obtain closed approximations of the coarse-grained dynamics in a manner which gives them a clear physical interpretation and provides explicit microscopic expressions for all of the coefficients appearing in the closure. Our work leads to a model for dilute nanocolloidal suspensions that can be simulated effectively using feasibly short molecular dynamics

  2. Coupling a nano-particle with isothermal fluctuating hydrodynamics: Coarse-graining from microscopic to mesoscopic dynamics.

    PubMed

    Español, Pep; Donev, Aleksandar

    2015-12-21

    We derive a coarse-grained description of the dynamics of a nanoparticle immersed in an isothermal simple fluid by performing a systematic coarse graining of the underlying microscopic dynamics. As coarse-grained or relevant variables, we select the position of the nanoparticle and the total mass and momentum density field of the fluid, which are locally conserved slow variables because they are defined to include the contribution of the nanoparticle. The theory of coarse graining based on the Zwanzing projection operator leads us to a system of stochastic ordinary differential equations that are closed in the relevant variables. We demonstrate that our discrete coarse-grained equations are consistent with a Petrov-Galerkin finite-element discretization of a system of formal stochastic partial differential equations which resemble previously used phenomenological models based on fluctuating hydrodynamics. Key to this connection between our "bottom-up" and previous "top-down" approaches is the use of the same dual orthogonal set of linear basis functions familiar from finite element methods (FEMs), both as a way to coarse-grain the microscopic degrees of freedom and as a way to discretize the equations of fluctuating hydrodynamics. Another key ingredient is the use of a "linear for spiky" weak approximation which replaces microscopic "fields" with a linear FE interpolant inside expectation values. For the irreversible or dissipative dynamics, we approximate the constrained Green-Kubo expressions for the dissipation coefficients with their equilibrium averages. Under suitable approximations, we obtain closed approximations of the coarse-grained dynamics in a manner which gives them a clear physical interpretation and provides explicit microscopic expressions for all of the coefficients appearing in the closure. Our work leads to a model for dilute nanocolloidal suspensions that can be simulated effectively using feasibly short molecular dynamics simulations as input

  3. A simple and transferable all-atom/coarse-grained hybrid model to study membrane processes.

    PubMed

    Genheden, Samuel; Essex, Jonathan W

    2015-10-13

    We present an efficient all-atom/coarse-grained hybrid model and apply it to membrane processes. This model is an extension of the all-atom/ELBA model applied previously to processes in water. Here, we improve the efficiency of the model by implementing a multiple-time step integrator that allows the atoms and the coarse-grained beads to be propagated at different timesteps. Furthermore, we fine-tune the interaction between the atoms and the coarse-grained beads by computing the potential of mean force of amino acid side chain analogs along the membrane normal and comparing to atomistic simulations. The model was independently validated on the calculation of small-molecule partition coefficients. Finally, we apply the model to membrane peptides. We studied the tilt angle of the Walp23 and Kalp23 helices in two different model membranes and the stability of the glycophorin A dimer. The model is efficient, accurate, and straightforward to use, as it does not require any extra interaction particles, layers of atomistic solvent molecules or tabulated potentials, thus offering a novel, simple approach to study membrane processes. PMID:26574264

  4. Generalized coarse-grained model based on point multipole and Gay-Berne potentials

    NASA Astrophysics Data System (ADS)

    Golubkov, Pavel A.; Ren, Pengyu

    2006-08-01

    This paper presents a general coarse-grained molecular mechanics model based on electric point multipole expansion and Gay-Berne [J. Chem. Phys. 74, 3316 (1981)] potential. Coarse graining of van der Waals potential is achieved by treating molecules as soft uniaxial ellipsoids interacting via a generalized anisotropic Gay-Berne function. The charge distribution is represented by point multipole expansion, including point charge, dipole, and quadrupole moments placed at the center of mass. The Gay-Berne and point multipole potentials are combined in the local reference frame defined by the inertial frame of the all-atom counterpart. The coarse-grained model has been applied to rigid-body molecular dynamics simulations of molecular liquids including benzene and methanol. The computational efficiency is improved by several orders of magnitude, while the results are in reasonable agreement with all-atom models and experimental data. We also discuss the implications of using point multipole for polar molecules capable of hydrogen bonding and the applicability of this model to a broad range of molecular systems including highly charged biopolymers.

  5. Generalized coarse-grained model based on point multipole and Gay-Berne potentials.

    PubMed

    Golubkov, Pavel A; Ren, Pengyu

    2006-08-14

    This paper presents a general coarse-grained molecular mechanics model based on electric point multipole expansion and Gay-Berne [J. Chem. Phys. 74, 3316 (1981)] potential. Coarse graining of van der Waals potential is achieved by treating molecules as soft uniaxial ellipsoids interacting via a generalized anisotropic Gay-Berne function. The charge distribution is represented by point multipole expansion, including point charge, dipole, and quadrupole moments placed at the center of mass. The Gay-Berne and point multipole potentials are combined in the local reference frame defined by the inertial frame of the all-atom counterpart. The coarse-grained model has been applied to rigid-body molecular dynamics simulations of molecular liquids including benzene and methanol. The computational efficiency is improved by several orders of magnitude, while the results are in reasonable agreement with all-atom models and experimental data. We also discuss the implications of using point multipole for polar molecules capable of hydrogen bonding and the applicability of this model to a broad range of molecular systems including highly charged biopolymers. PMID:16942269

  6. An Anisotropic Coarse-Grained Model for Proteins Based On Gay-Berne and Electric Multipole Potentials.

    PubMed

    Shen, Hujun; Li, Yan; Ren, Pengyu; Zhang, Dinglin; Li, Guohui

    2014-02-10

    Gay-Berne anisotropic potential has been widely used to evaluate the non-bonded interactions between coarse-grained particles being described as elliptical rigid bodies. In this paper, we are presenting a coarse-grained model for twenty kinds of amino acids and proteins, based on the anisotropic Gay-Berne and point electric multipole (EMP) potentials. We demonstrate that the anisotropic coarse-grained model, namely GBEMP model, is able to reproduce many key features observed from experimental protein structures (Dunbrack Library) as well as from atomistic force field simulations (using AMOEBA, AMBER and CHARMM force fields) while saving the computational cost by a factor of about 10~200 depending on specific cases and atomistic models. More importantly, unlike other coarse-grained approaches, our framework is based on the fundamental intermolecular forces with explicit treatment of electrostatic and repulsion-dispersion forces. As a result, the coarse-grained protein model presented an accurate description of non-bonded interactions (particularly electrostatic component) between hetero-/homo-dimers (such as peptide-peptide, peptide-water). In addition, the encouraging performance of the model was reflected by the excellent correlation between GBEMP and AMOEBA models in the calculations of the dipole moment of peptides. In brief, the GBEMP model given here is general and transferable, suitable for simulating complex biomolecular systems. PMID:24659927

  7. Perspective: Coarse-grained models for biomolecular systems

    NASA Astrophysics Data System (ADS)

    Noid, W. G.

    2013-09-01

    By focusing on essential features, while averaging over less important details, coarse-grained (CG) models provide significant computational and conceptual advantages with respect to more detailed models. Consequently, despite dramatic advances in computational methodologies and resources, CG models enjoy surging popularity and are becoming increasingly equal partners to atomically detailed models. This perspective surveys the rapidly developing landscape of CG models for biomolecular systems. In particular, this review seeks to provide a balanced, coherent, and unified presentation of several distinct approaches for developing CG models, including top-down, network-based, native-centric, knowledge-based, and bottom-up modeling strategies. The review summarizes their basic philosophies, theoretical foundations, typical applications, and recent developments. Additionally, the review identifies fundamental inter-relationships among the diverse approaches and discusses outstanding challenges in the field. When carefully applied and assessed, current CG models provide highly efficient means for investigating the biological consequences of basic physicochemical principles. Moreover, rigorous bottom-up approaches hold great promise for further improving the accuracy and scope of CG models for biomolecular systems.

  8. Coarse-grained potentials of single-walled carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Zhao, Junhua; Jiang, Jin-Wu; Wang, Lifeng; Guo, Wanlin; Rabczuk, Timon

    2014-11-01

    We develop the coarse-grained (CG) potentials of single-walled carbon nanotubes (SWCNTs) in CNT bundles and buckypaper for the study of the static and dynamic behaviors. The explicit expressions of the CG stretching, bending and torsion potentials for the nanotubes are obtained by the stick-spiral and the beam models, respectively. The non-bonded CG potentials between two different CG beads are derived from analytical results based on the cohesive energy between two parallel and crossing SWCNTs from the van der Waals interactions. We show that the CG model is applicable to large deformations of complex CNT systems by combining the bonded potentials with non-bonded potentials. Checking against full atom molecular dynamics calculations and our analytical results shows that the present CG potentials have high accuracy. The established CG potentials are used to study the mechanical properties of the CNT bundles and buckypaper efficiently at minor computational cost, which shows great potential for the design of micro- and nanomechanical devices and systems.

  9. Anatomy of an Allende coarse-grained inclusion

    NASA Astrophysics Data System (ADS)

    El Gorsey, A.; Armstrong, J. T.; Wasserburg, G. J.

    1985-11-01

    The petrology, mineralogy, and mineral chemistry of a coarse-grained calcium-aluminum-rich inclusion from Allende are studied. The inclusion consists of a spinel-fassaite-melilite core surrounded by a melilite mantle. The zoning, chemical variation between crystals, and concentration of molecules in the melilite and fassaite of the spinel-free island, spinel-rich area, and melilite mantle are examined. The possible formation of the inclusion by gas-solid condensation, crystallization from a homogeneous refractory silicate melt, and evaporative loss due to distillation is analyzed. These processes, however, do not explain the textural relations and mineral chemistries of the spinel-free island, spinel-rich areas, and melilite mantle. The formation of the inclusion by spinel-free islands forming by crystallization from a spinel deficient liquid, the capture of solid clasts and Fremdlinge in a more refractory spinel-saturated liquid, and formation of the outer melilite veneer mantle from two refractory liquid layers is proposed.

  10. Improving the treatment of coarse-grain electrostatics: CVCEL.

    PubMed

    Ceres, N; Lavery, R

    2015-12-28

    We propose an analytic approach for calculating the electrostatic energy of proteins or protein complexes in aqueous solution. This method, termed CVCEL (Circular Variance Continuum ELectrostatics), is fitted to Poisson calculations and is able to reproduce the corresponding energies for different choices of solute dielectric constant. CVCEL thus treats both solute charge interactions and charge self-energies, and it can also deal with salt solutions. Electrostatic damping notably depends on the degree of solvent exposure of the charges, quantified here in terms of circular variance, a measure that reflects the vectorial distribution of the neighbors around a given center. CVCEL energies can be calculated rapidly and have simple analytical derivatives. This approach avoids the need for calculating effective atomic volumes or Born radii. After describing how the method was developed, we present test results for coarse-grain proteins of different shapes and sizes, using different internal dielectric constants and different salt concentrations and also compare the results with those from simple distance-dependent models. We also show that the CVCEL approach can be used successfully to calculate the changes in electrostatic energy associated with changes in protein conformation or with protein-protein binding. PMID:26723603

  11. Improving the treatment of coarse-grain electrostatics: CVCEL

    SciTech Connect

    Ceres, N.; Lavery, R.

    2015-12-28

    We propose an analytic approach for calculating the electrostatic energy of proteins or protein complexes in aqueous solution. This method, termed CVCEL (Circular Variance Continuum ELectrostatics), is fitted to Poisson calculations and is able to reproduce the corresponding energies for different choices of solute dielectric constant. CVCEL thus treats both solute charge interactions and charge self-energies, and it can also deal with salt solutions. Electrostatic damping notably depends on the degree of solvent exposure of the charges, quantified here in terms of circular variance, a measure that reflects the vectorial distribution of the neighbors around a given center. CVCEL energies can be calculated rapidly and have simple analytical derivatives. This approach avoids the need for calculating effective atomic volumes or Born radii. After describing how the method was developed, we present test results for coarse-grain proteins of different shapes and sizes, using different internal dielectric constants and different salt concentrations and also compare the results with those from simple distance-dependent models. We also show that the CVCEL approach can be used successfully to calculate the changes in electrostatic energy associated with changes in protein conformation or with protein-protein binding.

  12. Coarse-grained, foldable, physical model of the polypeptide chain

    PubMed Central

    Chakraborty, Promita; Zuckermann, Ronald N.

    2013-01-01

    Although nonflexible, scaled molecular models like Pauling–Corey’s and its descendants have made significant contributions in structural biology research and pedagogy, recent technical advances in 3D printing and electronics make it possible to go one step further in designing physical models of biomacromolecules: to make them conformationally dynamic. We report here the design, construction, and validation of a flexible, scaled, physical model of the polypeptide chain, which accurately reproduces the bond rotational degrees of freedom in the peptide backbone. The coarse-grained backbone model consists of repeating amide and α-carbon units, connected by mechanical bonds (corresponding to φ and ψ) that include realistic barriers to rotation that closely approximate those found at the molecular scale. Longer-range hydrogen-bonding interactions are also incorporated, allowing the chain to readily fold into stable secondary structures. The model is easily constructed with readily obtainable parts and promises to be a tremendous educational aid to the intuitive understanding of chain folding as the basis for macromolecular structure. Furthermore, this physical model can serve as the basis for linking tangible biomacromolecular models directly to the vast array of existing computational tools to provide an enhanced and interactive human–computer interface. PMID:23898168

  13. Cellulose microfibril formation within a coarse grained molecular dynamics

    NASA Astrophysics Data System (ADS)

    Nili, Abdolmadjid; Shklyaev, Oleg; Crespi, Vincent; Zhao, Zhen; Zhong, Linghao; CLSF Collaboration

    2014-03-01

    Cellulose in biomass is mostly in the form of crystalline microfibrils composed of 18 to 36 parallel chains of polymerized glucose monomers. A single chain is produced by cellular machinery (CesA) located on the preliminary cell wall membrane. Information about the nucleation stage can address important questions about intermediate region between cell wall and the fully formed crystalline microfibrils. Very little is known about the transition from isolated chains to protofibrils up to a full microfibril, in contrast to a large body of studies on both CesA and the final crystalline microfibril. In addition to major experimental challenges in studying this transient regime, the length and time scales of microfibril nucleation are inaccessible to atomistic molecular dynamics. We have developed a novel coarse grained model for cellulose microfibrils which accounts for anisotropic interchain interactions. The model allows us to study nucleation, kinetics, and growth of cellulose chains/protofibrils/microfibrils. This work is supported by the US Department of Energy, Office of Basic Energy Sciences as part of The Center for LignoCellulose Structure and Formation, an Energy Frontier Research Center.

  14. Studying the Enhanced Ductility of Bimodal Nanocrystalline Copper Using a Coarse-Grained Model

    NASA Astrophysics Data System (ADS)

    Gao, Guo-Jie Jason; Wang, Yun-Jiang; Ogata, Shigenobu

    Viewing a bimodal configuration of nanocrystalline copper as composed of soft grains containing stiff cores, we proposed a coarse-grained model with systematically tunable stiffness of grains to study the enhanced ductility of bimodal nanocrystalline copper [Y. Wang, M. Chen, F. Zhou, and E. Ma, Nature 419 (2002) 912]. Using molecular dynamics simulations, we shear our model quasistatically. Our results not only qualitatively confirms that a bimodal configuration could behave more ductile than a monomodal one but also predicts there exists a range of ratio of soft/stiff domains that best minimizes shear localization. Moreover, our model indicates that a bimodal configuration could sometimes exacerbate shear localization and therefore jeopardize ductility if the ratio of soft/stiff domains is not properly chosen. This may explain why some experimental results are hard to be reproduced.

  15. An anisotropic coarse-grained model based on Gay-Berne and electric multipole potentials and its application to simulate a DMPC bilayer in an implicit solvent model.

    PubMed

    Shen, Hujun; Li, Yan; Xu, Peijun; Li, Xiaofang; Chu, Huiying; Zhang, Dinglin; Li, Guohui

    2015-06-01

    In this work, we aim at optimizing the performance of the anisotropic GBEMP model, which adopts a framework by combining a Gay-Berne (GB) anisotropic potential with an electric multipole (EMP) potential, in simulating a DMPC lipid bilayer in an implicit solvent model. First, the Gay-Berne parameters were initially obtained by fitting to atomistic profiles of van der Waals interactions between homodimers of molecular fragments while EMP parameters was directly derived from the expansion of point multipoles at predefined EMP sites. Second, the GB and EMP parameters for DMPC molecule were carefully optimized to be comparable to AMBER atomistic model in the calculations of the dipole moments of DMPC monomers adopting different conformations as well as the nonbonded interactions between two DMPC molecules adopting different conformations and separated at various distances. Finally, the GB parameters for DMPC were slightly adjusted in simulating a 72 DMPC bilayer system so that our GBEMP model would be able to reproduce a few important structural properties, namely, thickness (DHH), area per lipid ( AL) and volume per lipid ( VL). Meanwhile, the atomistic and experimental results for electron density profiles and order parameters were reproduced reasonably well by the GBEMP model, demonstrating the promising feature of GBEMP model in modeling lipid systems. Finally, we have shown that current GBEMP model is more efficient by a factor of about 25 than AMBER atomistic point charge model. PMID:25788250

  16. Combining a polarizable force-field and a coarse-grained polarizable solvent model: application to long dynamics simulations of bovine pancreatic trypsin inhibitor.

    PubMed

    Masella, Michel; Borgis, Daniel; Cuniasse, Philippe

    2008-08-01

    The dynamic coupling between a polarizable protein force field and a particle-based implicit solvent model is described. The polarizable force field, TCPEp, developed recently to simulate protein systems, is characterized by a reduced number of polarizable sites, with a substantial gain in efficiency for an equal chemical accuracy. The Polarizable Pseudo-Particle (PPP) solvent model represents the macroscopic solvent polarization by induced dipoles placed on mobile Lennard-Jones pseudo-particles. The solvent-induced dipoles are sensitive to the solute electric field, but not to each other, so that the computational cost of solvent-solvent interactions is basically negligible. The solute and solvent induced dipoles are determined self-consistently and the equations of motion are solved using an efficient iterative multiple time step procedure. The solvation cost with respect to vacuum simulations is shown to decrease with solute size: the estimated multiplicative factor is 2.5 for a protein containing about 1000 atoms, and as low as 1.15 for 8000 atoms. The model is tested for six 20 ns molecular dynamics trajectories of a traditional benchmark system: the hydrated Bovine Pancreatic Trypsin Inhibitor (BPTI). Even though the TCPEp parameters have not been refined to be used with the solvent PPP model, we observe a good conservation of the BPTI structure along the trajectories. Moreover, our approach is able to provide a description of the protein solvation thermodynamic at the same accuracy as the standard Poisson-Boltzman continuum methods. It provides in addition a good description of the microscopic structural aspects concerning the solute/solvent interaction. PMID:18351600

  17. Dynamic force matching: A method for constructing dynamical coarse-grained models with realistic time dependence

    SciTech Connect

    Davtyan, Aram; Dama, James F.; Voth, Gregory A.; Andersen, Hans C.

    2015-04-21

    Coarse-grained (CG) models of molecular systems, with fewer mechanical degrees of freedom than an all-atom model, are used extensively in chemical physics. It is generally accepted that a coarse-grained model that accurately describes equilibrium structural properties (as a result of having a well constructed CG potential energy function) does not necessarily exhibit appropriate dynamical behavior when simulated using conservative Hamiltonian dynamics for the CG degrees of freedom on the CG potential energy surface. Attempts to develop accurate CG dynamic models usually focus on replacing Hamiltonian motion by stochastic but Markovian dynamics on that surface, such as Langevin or Brownian dynamics. However, depending on the nature of the system and the extent of the coarse-graining, a Markovian dynamics for the CG degrees of freedom may not be appropriate. In this paper, we consider the problem of constructing dynamic CG models within the context of the Multi-Scale Coarse-graining (MS-CG) method of Voth and coworkers. We propose a method of converting a MS-CG model into a dynamic CG model by adding degrees of freedom to it in the form of a small number of fictitious particles that interact with the CG degrees of freedom in simple ways and that are subject to Langevin forces. The dynamic models are members of a class of nonlinear systems interacting with special heat baths that were studied by Zwanzig [J. Stat. Phys. 9, 215 (1973)]. The properties of the fictitious particles can be inferred from analysis of the dynamics of all-atom simulations of the system of interest. This is analogous to the fact that the MS-CG method generates the CG potential from analysis of equilibrium structures observed in all-atom simulation data. The dynamic models generate a non-Markovian dynamics for the CG degrees of freedom, but they can be easily simulated using standard molecular dynamics programs. We present tests of this method on a series of simple examples that demonstrate that

  18. Multiscale design of coarse-grained elastic network-based potentials for the μ opioid receptor.

    PubMed

    Fossépré, Mathieu; Leherte, Laurence; Laaksonen, Aatto; Vercauteren, Daniel P

    2016-09-01

    Despite progress in computer modeling, most biological processes are still out of reach when using all-atom (AA) models. Coarse-grained (CG) models allow classical molecular dynamics (MD) simulations to be accelerated. Although simplification of spatial resolution at different levels is often investigated, simplification of the CG potential in itself has been less common. CG potentials are often similar to AA potentials. In this work, we consider the design and reliability of purely mechanical CG models of the μ opioid receptor (μOR), a G protein-coupled receptor (GPCR). In this sense, CG force fields (FF) consist of a set of holonomic constraints guided by an elastic network model (ENM). Even though ENMs are used widely to perform normal mode analysis (NMA), they are not often implemented as a single FF in the context of MD simulations. In this work, various ENM-like potentials were investigated by varying their force constant schemes and connectivity patterns. A method was established to systematically parameterize ENM-like potentials at different spatial resolutions by using AA data. To do so, new descriptors were introduced. The choice of conformation descriptors that also include flexibility information is important for a reliable parameterization of ENMs with different degrees of sensitivity. Hence, ENM-like potentials, with specific parameters, can be sufficient to accurately reproduce AA MD simulations of μOR at highly coarse-grained resolutions. Therefore, the essence of the flexibility properties of μOR can be captured with simple models at different CG spatial resolutions, opening the way to mechanical approaches to understanding GPCR functions. Graphical Abstract All atom structure, residue interaction network and coarse-grained elastic network models of the μ opioid receptor (μOR). PMID:27566318

  19. Topological coarse graining of polymer chains using wavelet-accelerated Monte Carlo. II. Self-avoiding chains.

    PubMed

    Ismail, Ahmed E; Stephanopoulos, George; Rutledge, Gregory C

    2005-06-15

    In the preceding paper [A. E. Ismail, G. C. Rutledge, and G. Stephanopoulos J. Chem. Phys. (in press)] we introduced wavelet-accelerated Monte Carlo (WAMC), a coarse-graining methodology based on the wavelet transform, as a method for sampling polymer chains. In the present paper, we extend our analysis to consider excluded-volume effects by studying self-avoiding chains. We provide evidence that the coarse-grained potentials developed using the WAMC method obey phenomenological scaling laws, and use simple physical arguments for freely jointed chains to motivate these laws. We show that coarse-grained self-avoiding random walks can reproduce results obtained from simulations of the original, more-detailed chains to a high degree of accuracy, in orders of magnitude less time. PMID:16008482

  20. Gay-Berne and electrostatic multipole based coarse-grain potential in implicit solvent

    NASA Astrophysics Data System (ADS)

    Wu, Johnny; Zhen, Xia; Shen, Hujun; Li, Guohui; Ren, Pengyu

    2011-10-01

    A general, transferable coarse-grain (CG) framework based on the Gay-Berne potential and electrostatic point multipole expansion is presented for polypeptide simulations. The solvent effect is described by the Generalized Kirkwood theory. The CG model is calibrated using the results of all-atom simulations of model compounds in solution. Instead of matching the overall effective forces produced by atomic models, the fundamental intermolecular forces such as electrostatic, repulsion-dispersion, and solvation are represented explicitly at a CG level. We demonstrate that the CG alanine dipeptide model is able to reproduce quantitatively the conformational energy of all-atom force fields in both gas and solution phases, including the electrostatic and solvation components. Replica exchange molecular dynamics and microsecond dynamic simulations of polyalanine of 5 and 12 residues reveal that the CG polyalanines fold into "alpha helix" and "beta sheet" structures. The 5-residue polyalanine displays a substantial increase in the "beta strand" fraction relative to the 12-residue polyalanine. The detailed conformational distribution is compared with those reported from recent all-atom simulations and experiments. The results suggest that the new coarse-graining approach presented in this study has the potential to offer both accuracy and efficiency for biomolecular modeling.

  1. Gay-Berne and electrostatic multipole based coarse-grain potential in implicit solvent

    PubMed Central

    Wu, Johnny; Zhen, Xia; Shen, Hujun; Li, Guohui; Ren, Pengyu

    2011-01-01

    A general, transferable coarse-grain (CG) framework based on the Gay-Berne potential and electrostatic point multipole expansion is presented for polypeptide simulations. The solvent effect is described by the Generalized Kirkwood theory. The CG model is calibrated using the results of all-atom simulations of model compounds in solution. Instead of matching the overall effective forces produced by atomic models, the fundamental intermolecular forces such as electrostatic, repulsion-dispersion, and solvation are represented explicitly at a CG level. We demonstrate that the CG alanine dipeptide model is able to reproduce quantitatively the conformational energy of all-atom force fields in both gas and solution phases, including the electrostatic and solvation components. Replica exchange molecular dynamics and microsecond dynamic simulations of polyalanine of 5 and 12 residues reveal that the CG polyalanines fold into “alpha helix” and “beta sheet” structures. The 5-residue polyalanine displays a substantial increase in the “beta strand” fraction relative to the 12-residue polyalanine. The detailed conformational distribution is compared with those reported from recent all-atom simulations and experiments. The results suggest that the new coarse-graining approach presented in this study has the potential to offer both accuracy and efficiency for biomolecular modeling. PMID:22029338

  2. Gay-Berne and electrostatic multipole based coarse-grain potential in implicit solvent.

    PubMed

    Wu, Johnny; Zhen, Xia; Shen, Hujun; Li, Guohui; Ren, Pengyu

    2011-10-21

    A general, transferable coarse-grain (CG) framework based on the Gay-Berne potential and electrostatic point multipole expansion is presented for polypeptide simulations. The solvent effect is described by the Generalized Kirkwood theory. The CG model is calibrated using the results of all-atom simulations of model compounds in solution. Instead of matching the overall effective forces produced by atomic models, the fundamental intermolecular forces such as electrostatic, repulsion-dispersion, and solvation are represented explicitly at a CG level. We demonstrate that the CG alanine dipeptide model is able to reproduce quantitatively the conformational energy of all-atom force fields in both gas and solution phases, including the electrostatic and solvation components. Replica exchange molecular dynamics and microsecond dynamic simulations of polyalanine of 5 and 12 residues reveal that the CG polyalanines fold into "alpha helix" and "beta sheet" structures. The 5-residue polyalanine displays a substantial increase in the "beta strand" fraction relative to the 12-residue polyalanine. The detailed conformational distribution is compared with those reported from recent all-atom simulations and experiments. The results suggest that the new coarse-graining approach presented in this study has the potential to offer both accuracy and efficiency for biomolecular modeling. PMID:22029338

  3. PRAM C:a new programming environment for fine-grain and coarse-grain parallelism.

    SciTech Connect

    Brown, Jonathan Leighton; Wen, Zhaofang.

    2004-11-01

    In the search for ''good'' parallel programming environments for Sandia's current and future parallel architectures, they revisit a long-standing open question. Can the PRAM parallel algorithms designed by theoretical computer scientists over the last two decades be implemented efficiently? This open question has co-existed with ongoing efforts in the HPC community to develop practical parallel programming models that can simultaneously provide ease of use, expressiveness, performance, and scalability. Unfortunately, no single model has met all these competing requirements. Here they propose a parallel programming environment, PRAM C, to bridge the gap between theory and practice. This is an attempt to provide an affirmative answer to the PRAM question, and to satisfy these competing practical requirements. This environment consists of a new thin runtime layer and an ANSI C extension. The C extension has two control constructs and one additional data type concept, ''shared''. This C extension should enable easy translation from PRAM algorithms to real parallel programs, much like the translation from sequential algorithms to C programs. The thin runtime layer bundles fine-grained communication requests into coarse-grained communication to be served by message-passing. Although the PRAM represents SIMD-style fine-grained parallelism, a stand-alone PRAM C environment can support both fine-grained and coarse-grained parallel programming in either a MIMD or SPMD style, interoperate with existing MPI libraries, and use existing hardware. The PRAM C model can also be integrated easily with existing models. Unlike related efforts proposing innovative hardware with the goal to realize the PRAM, ours can be a pure software solution with the purpose to provide a practical programming environment for existing parallel machines; it also has the potential to perform well on future parallel architectures.

  4. Gravitational dynamics of an infinite shuffled lattice: Particle coarse-graining, nonlinear clustering, and the continuum limit.

    PubMed

    Baertschiger, T; Joyce, M; Gabrielli, A; Sylos Labini, F

    2007-07-01

    We study the evolution under their self-gravity of particles evolving from infinite "shuffled lattice" initial conditions. We focus here specifically on the comparison between the evolution of such a system and that of "daughter" coarse-grained particle distributions. These are sparser (i.e., lower density) particle distributions, defined by a simple coarse-graining procedure, which share the same large-scale mass fluctuations. We consider both the case that such coarse-grainings are performed (i) on the initial conditions, and (ii) at a finite time with a specific additional prescription. In numerical simulations we observe that, to a first approximation, these coarse-grainings represent well the evolution of the two-point correlation properties over a significant range of scales. We note, in particular, that the form of the two-point correlation function in the original system, when it is evolving in the asymptotic "self-similar" regime, may be reproduced well in a daughter coarse-grained system in which the dynamics are still dominated by two-body (nearest neighbor) interactions. This provides a simple physical description of the origin of the form of part of the asymptotic nonlinear correlation function. Using analytical results on the early time evolution of these systems, however, we show that small observed differences between the evolved system and its coarse-grainings at the initial time will in fact diverge as the ratio of the coarse-graining scale to the original interparticle distance increases. The second coarse-graining studied, performed at a finite time in a specified manner, circumvents this problem. It also makes it more physically transparent why gravitational dynamics from these initial conditions tends toward a self-similar evolution. We finally discuss the precise definition of a limit in which a continuum (specifically Vlasov-type) description of the observed linear and nonlinear evolution should be applicable. This requires the introduction

  5. Markov state modeling and dynamical coarse-graining via discrete relaxation path sampling.

    PubMed

    Fačkovec, B; Vanden-Eijnden, E; Wales, D J

    2015-07-28

    A method is derived to coarse-grain the dynamics of complex molecular systems to a Markov jump process (MJP) describing how the system jumps between cells that fully partition its state space. The main inputs are relaxation times for each pair of cells, which are shown to be robust with respect to positioning of the cell boundaries. These relaxation times can be calculated via molecular dynamics simulations performed in each cell separately and are used in an efficient estimator for the rate matrix of the MJP. The method is illustrated through applications to Sinai billiards and a cluster of Lennard-Jones discs. PMID:26233119

  6. Development and application of coarse-grained models for lipids

    NASA Astrophysics Data System (ADS)

    Cui, Qiang

    2013-03-01

    I'll discuss a number of topics that represent our efforts in developing reliable molecular models for describing chemical and physical processes involving biomembranes. This is an exciting yet challenging research area because of the multiple length and time scales that are present in the relevant problems. Accordingly, we attempt to (1) understand the value and limitation of popular coarse-grained (CG) models for lipid membranes with either a particle or continuum representation; (2) develop new CG models that are appropriate for the particular problem of interest. As specific examples, I'll discuss (1) a comparison of atomistic, MARTINI (a particle based CG model) and continuum descriptions of a membrane fusion pore; (2) the development of a modified MARTINI model (BMW-MARTINI) that features a reliable description of membrane/water interfacial electrostatics and its application to cell-penetration peptides and membrane-bending proteins. Motivated specifically by the recent studies of Wong and co-workers, we compare the self-assembly behaviors of lipids with cationic peptides that include either Arg residues or a combination of Lys and hydrophobic residues; in particular, we attempt to reveal factors that stabilize the cubic ``double diamond'' Pn3m phase over the inverted hexagonal HII phase. For example, to explicitly test the importance of the bidentate hydrogen-bonding capability of Arg to the stabilization of negative Gaussian curvature, we also compare results using variants of the BMW-MARTINI model that treat the side chain of Arg with different levels of details. Collectively, the results suggest that both the bidentate feature of Arg and the overall electrostatic properties of cationic peptides are important to the self-assembly behavior of these peptides with lipids. The results are expected to have general implications to the mechanism of peptides and proteins that stimulate pore formation in biomembranes. Work in collaboration with Zhe Wu, Leili Zhang

  7. Hydrodynamic interactions and Brownian forces in colloidal suspensions: Coarse-graining over time and length scales

    NASA Astrophysics Data System (ADS)

    Padding, J. T.; Louis, A. A.

    2006-09-01

    We describe in detail how to implement a coarse-grained hybrid molecular dynamics and stochastic rotation dynamics simulation technique that captures the combined effects of Brownian and hydrodynamic forces in colloidal suspensions. The importance of carefully tuning the simulation parameters to correctly resolve the multiple time and length scales of this problem is emphasized. We systematically analyze how our coarse-graining scheme resolves dimensionless hydrodynamic numbers such as the Reynolds number Re, which indicates the importance of inertial effects, the Schmidt number Sc, which indicates whether momentum transport is liquidlike or gaslike, the Mach number, which measures compressibility effects, the Knudsen number, which describes the importance of noncontinuum molecular effects, and the Peclet number, which describes the relative effects of convective and diffusive transport. With these dimensionless numbers in the correct regime the many Brownian and hydrodynamic time scales can be telescoped together to maximize computational efficiency while still correctly resolving the physically relevant processes. We also show how to control a number of numerical artifacts, such as finite-size effects and solvent-induced attractive depletion interactions. When all these considerations are properly taken into account, the measured colloidal velocity autocorrelation functions and related self-diffusion and friction coefficients compare quantitatively with theoretical calculations. By contrast, these calculations demonstrate that, notwithstanding its seductive simplicity, the basic Langevin equation does a remarkably poor job of capturing the decay rate of the velocity autocorrelation function in the colloidal regime, strongly underestimating it at short times and strongly overestimating it at long times. Finally, we discuss in detail how to map the parameters of our method onto physical systems and from this extract more general lessons—keeping in mind that there

  8. Hydration Properties and Solvent Effects for All-Atom Solutes in Polarizable Coarse-Grained Water.

    PubMed

    Yan, Xin Cindy; Tirado-Rives, Julian; Jorgensen, William L

    2016-08-25

    Due to the importance of water in chemical and biological systems, a coarse-grained representation of the solvent can greatly simplify the description of the system while retaining key thermodynamic properties of the medium. A multiscale solvation model that couples all-atom solutes and polarizable Martini coarse-grained water (AAX/CGS) is developed to reproduce free energies of hydration of organic solutes. Using Monte Carlo/free energy perturbation (MC/FEP) calculations, results from multiscale and all-atom simulations are compared. Improved accuracy is obtained with the AAX/CGS approach for hydrophobic and sulfur- or halogen-containing solutes, but larger deviations are found for polar solute molecules where hydrogen bonding is featured. Furthermore, solvent effects on conformational and tautomeric equilibria of AA solutes were investigated using AA, CG, and GB/SA solvent models. It is found that the CG solvent model can reproduce well the medium effects from experiment and AA simulations; however, the GB/SA solvent model fails in some cases. A 7-30-fold reduction in computational cost is found for the present AAX/CGS multiscale simulations compared to the AA alternative. PMID:26901452

  9. The ELBA Force Field for Coarse-Grain Modeling of Lipid Membranes

    PubMed Central

    Orsi, Mario; Essex, Jonathan W.

    2011-01-01

    A new coarse-grain model for molecular dynamics simulation of lipid membranes is presented. Following a simple and conventional approach, lipid molecules are modeled by spherical sites, each representing a group of several atoms. In contrast to common coarse-grain methods, two original (interdependent) features are here adopted. First, the main electrostatics are modeled explicitly by charges and dipoles, which interact realistically through a relative dielectric constant of unity (). Second, water molecules are represented individually through a new parametrization of the simple Stockmayer potential for polar fluids; each water molecule is therefore described by a single spherical site embedded with a point dipole. The force field is shown to accurately reproduce the main physical properties of single-species phospholipid bilayers comprising dioleoylphosphatidylcholine (DOPC) and dioleoylphosphatidylethanolamine (DOPE) in the liquid crystal phase, as well as distearoylphosphatidylcholine (DSPC) in the liquid crystal and gel phases. Insights are presented into fundamental properties and phenomena that can be difficult or impossible to study with alternative computational or experimental methods. For example, we investigate the internal pressure distribution, dipole potential, lipid diffusion, and spontaneous self-assembly. Simulations lasting up to 1.5 microseconds were conducted for systems of different sizes (128, 512 and 1058 lipids); this also allowed us to identify size-dependent artifacts that are expected to affect membrane simulations in general. Future extensions and applications are discussed, particularly in relation to the methodology's inherent multiscale capabilities. PMID:22194874

  10. On the representability problem and the physical meaning of coarse-grained models.

    PubMed

    Wagner, Jacob W; Dama, James F; Durumeric, Aleksander E P; Voth, Gregory A

    2016-07-28

    In coarse-grained (CG) models where certain fine-grained (FG, i.e., atomistic resolution) observables are not directly represented, one can nonetheless identify indirect the CG observables that capture the FG observable's dependence on CG coordinates. Often, in these cases it appears that a CG observable can be defined by analogy to an all-atom or FG observable, but the similarity is misleading and significantly undermines the interpretation of both bottom-up and top-down CG models. Such problems emerge especially clearly in the framework of the systematic bottom-up CG modeling, where a direct and transparent correspondence between FG and CG variables establishes precise conditions for consistency between CG observables and underlying FG models. Here we present and investigate these representability challenges and illustrate them via the bottom-up conceptual framework for several simple analytically tractable polymer models. The examples provide special focus on the observables of configurational internal energy, entropy, and pressure, which have been at the root of controversy in the CG literature, as well as discuss observables that would seem to be entirely missing in the CG representation but can nonetheless be correlated with CG behavior. Though we investigate these problems in the framework of systematic coarse-graining, the lessons apply to top-down CG modeling also, with crucial implications for simulation at constant pressure and surface tension and for the interpretations of structural and thermodynamic correlations for comparison to experiment. PMID:27475349

  11. Majorization approach to entropic uncertainty relations for coarse-grained observables

    NASA Astrophysics Data System (ADS)

    Rudnicki, Łukasz

    2015-03-01

    We improve the entropic uncertainty relations for position and momentum coarse-grained measurements. We derive the continuous, coarse-grained counterparts of the discrete uncertainty relations based on the concept of majorization. The entropic inequalities obtained involve two Rényi entropies of the same order, and thus go beyond the standard scenario with conjugated parameters. In a special case describing the sum of two Shannon entropies, the majorization-based bounds significantly outperform the currently known results in the regime of larger coarse graining, and might thus be useful for entanglement detection in continuous variables.

  12. Quantum Mechanics/Molecular Mechanics Method Combined with Hybrid All-Atom and Coarse-Grained Model: Theory and Application on Redox Potential Calculations.

    PubMed

    Shen, Lin; Yang, Weitao

    2016-04-12

    We developed a new multiresolution method that spans three levels of resolution with quantum mechanical, atomistic molecular mechanical, and coarse-grained models. The resolution-adapted all-atom and coarse-grained water model, in which an all-atom structural description of the entire system is maintained during the simulations, is combined with the ab initio quantum mechanics and molecular mechanics method. We apply this model to calculate the redox potentials of the aqueous ruthenium and iron complexes by using the fractional number of electrons approach and thermodynamic integration simulations. The redox potentials are recovered in excellent accordance with the experimental data. The speed-up of the hybrid all-atom and coarse-grained water model renders it computationally more attractive. The accuracy depends on the hybrid all-atom and coarse-grained water model used in the combined quantum mechanical and molecular mechanical method. We have used another multiresolution model, in which an atomic-level layer of water molecules around redox center is solvated in supramolecular coarse-grained waters for the redox potential calculations. Compared with the experimental data, this alternative multilayer model leads to less accurate results when used with the coarse-grained polarizable MARTINI water or big multipole water model for the coarse-grained layer. PMID:26930454

  13. Modeling of Ultrasonic Propagation in a Coarse Grain Structure

    NASA Astrophysics Data System (ADS)

    Jenson, F.; Fortuna, T.; Doudet, L.

    2009-03-01

    The metallurgical structure of centrifugally cast stainless steel components makes it difficult to ultrasonically inspect them. The centimeter-size grains forming the macrostructure strongly affect the transmitted field and thus limit inspection capabilities. Such macrostructures can be computed using an algorithm based on the Voronoi diagrams. This mathematical tool provides good qualitative representations of equiaxed and columnar structures. By combining the Voronoi diagrams with existing CIVA functionalities such as the transmitted field computation in a heterogeneous medium using the so-called pencil method, it is shown that some important physical phenomena responsible for inspection difficulties may be reproduced. For instance, the field distortions in phase and amplitude due to the velocity fluctuations that are caused by the large grain structures of these materials are properly described thanks to this approach. These distortions represent deviations from quantities that are usually described by existing theories, such as the mean field attenuation. Comparisons of simulated results with experimental data are also presented and discussed in this paper.

  14. Incorporation of memory effects in coarse-grained modeling via the Mori-Zwanzig formalism

    SciTech Connect

    Li, Zhen; Bian, Xin; Karniadakis, George Em; Li, Xiantao

    2015-12-28

    The Mori-Zwanzig formalism for coarse-graining a complex dynamical system typically introduces memory effects. The Markovian assumption of delta-correlated fluctuating forces is often employed to simplify the formulation of coarse-grained (CG) models and numerical implementations. However, when the time scales of a system are not clearly separated, the memory effects become strong and the Markovian assumption becomes inaccurate. To this end, we incorporate memory effects into CG modeling by preserving non-Markovian interactions between CG variables, and the memory kernel is evaluated directly from microscopic dynamics. For a specific example, molecular dynamics (MD) simulations of star polymer melts are performed while the corresponding CG system is defined by grouping many bonded atoms into single clusters. Then, the effective interactions between CG clusters as well as the memory kernel are obtained from the MD simulations. The constructed CG force field with a memory kernel leads to a non-Markovian dissipative particle dynamics (NM-DPD). Quantitative comparisons between the CG models with Markovian and non-Markovian approximations indicate that including the memory effects using NM-DPD yields similar results as the Markovian-based DPD if the system has clear time scale separation. However, for systems with small separation of time scales, NM-DPD can reproduce correct short-time properties that are related to how the system responds to high-frequency disturbances, which cannot be captured by the Markovian-based DPD model.

  15. Systematic hierarchical coarse-graining with the inverse Monte Carlo method.

    PubMed

    Lyubartsev, Alexander P; Naômé, Aymeric; Vercauteren, Daniel P; Laaksonen, Aatto

    2015-12-28

    We outline our coarse-graining strategy for linking micro- and mesoscales of soft matter and biological systems. The method is based on effective pairwise interaction potentials obtained in detailed ab initio or classical atomistic Molecular Dynamics (MD) simulations, which can be used in simulations at less accurate level after scaling up the size. The effective potentials are obtained by applying the inverse Monte Carlo (IMC) method [A. P. Lyubartsev and A. Laaksonen, Phys. Rev. E 52(4), 3730-3737 (1995)] on a chosen subset of degrees of freedom described in terms of radial distribution functions. An in-house software package MagiC is developed to obtain the effective potentials for arbitrary molecular systems. In this work we compute effective potentials to model DNA-protein interactions (bacterial LiaR regulator bound to a 26 base pairs DNA fragment) at physiological salt concentration at a coarse-grained (CG) level. Normally the IMC CG pair-potentials are used directly as look-up tables but here we have fitted them to five Gaussians and a repulsive wall. Results show stable association between DNA and the model protein as well as similar position fluctuation profile. PMID:26723605

  16. Parameterizing the Morse potential for coarse-grained modeling of blood plasma

    SciTech Connect

    Zhang, Na; Zhang, Peng; Kang, Wei; Bluestein, Danny; Deng, Yuefan

    2014-01-15

    Multiscale simulations of fluids such as blood represent a major computational challenge of coupling the disparate spatiotemporal scales between molecular and macroscopic transport phenomena characterizing such complex fluids. In this paper, a coarse-grained (CG) particle model is developed for simulating blood flow by modifying the Morse potential, traditionally used in Molecular Dynamics for modeling vibrating structures. The modified Morse potential is parameterized with effective mass scales for reproducing blood viscous flow properties, including density, pressure, viscosity, compressibility and characteristic flow dynamics of human blood plasma fluid. The parameterization follows a standard inverse-problem approach in which the optimal micro parameters are systematically searched, by gradually decoupling loosely correlated parameter spaces, to match the macro physical quantities of viscous blood flow. The predictions of this particle based multiscale model compare favorably to classic viscous flow solutions such as Counter-Poiseuille and Couette flows. It demonstrates that such coarse grained particle model can be applied to replicate the dynamics of viscous blood flow, with the advantage of bridging the gap between macroscopic flow scales and the cellular scales characterizing blood flow that continuum based models fail to handle adequately.

  17. A Coarse-Grained Protein Model in a Water-like Solvent

    NASA Astrophysics Data System (ADS)

    Sharma, Sumit; Kumar, Sanat K.; Buldyrev, Sergey V.; Debenedetti, Pablo G.; Rossky, Peter J.; Stanley, H. Eugene

    2013-05-01

    Simulations employing an explicit atom description of proteins in solvent can be computationally expensive. On the other hand, coarse-grained protein models in implicit solvent miss essential features of the hydrophobic effect, especially its temperature dependence, and have limited ability to capture the kinetics of protein folding. We propose a free space two-letter protein (``H-P'') model in a simple, but qualitatively accurate description for water, the Jagla model, which coarse-grains water into an isotropically interacting sphere. Using Monte Carlo simulations, we design protein-like sequences that can undergo a collapse, exposing the ``Jagla-philic'' monomers to the solvent, while maintaining a ``hydrophobic'' core. This protein-like model manifests heat and cold denaturation in a manner that is reminiscent of proteins. While this protein-like model lacks the details that would introduce secondary structure formation, we believe that these ideas represent a first step in developing a useful, but computationally expedient, means of modeling proteins.

  18. Parameterizing the Morse Potential for Coarse-Grained Modeling of Blood Plasma

    PubMed Central

    Zhang, Na; Zhang, Peng; Kang, Wei; Bluestein, Danny; Deng, Yuefan

    2014-01-01

    Multiscale simulations of fluids such as blood represent a major computational challenge of coupling the disparate spatiotemporal scales between molecular and macroscopic transport phenomena characterizing such complex fluids. In this paper, a coarse-grained (CG) particle model is developed for simulating blood flow by modifying the Morse potential, traditionally used in Molecular Dynamics for modeling vibrating structures. The modified Morse potential is parameterized with effective mass scales for reproducing blood viscous flow properties, including density, pressure, viscosity, compressibility and characteristic flow dynamics of human blood plasma fluid. The parameterization follows a standard inverse-problem approach in which the optimal micro parameters are systematically searched, by gradually decoupling loosely correlated parameter spaces, to match the macro physical quantities of viscous blood flow. The predictions of this particle based multiscale model compare favorably to classic viscous flow solutions such as Counter-Poiseuille and Couette flows. It demonstrates that such coarse grained particle model can be applied to replicate the dynamics of viscous blood flow, with the advantage of bridging the gap between macroscopic flow scales and the cellular scales characterizing blood flow that continuum based models fail to handle adequately. PMID:24910470

  19. Systematic hierarchical coarse-graining with the inverse Monte Carlo method

    NASA Astrophysics Data System (ADS)

    Lyubartsev, Alexander P.; Naômé, Aymeric; Vercauteren, Daniel P.; Laaksonen, Aatto

    2015-12-01

    We outline our coarse-graining strategy for linking micro- and mesoscales of soft matter and biological systems. The method is based on effective pairwise interaction potentials obtained in detailed ab initio or classical atomistic Molecular Dynamics (MD) simulations, which can be used in simulations at less accurate level after scaling up the size. The effective potentials are obtained by applying the inverse Monte Carlo (IMC) method [A. P. Lyubartsev and A. Laaksonen, Phys. Rev. E 52(4), 3730-3737 (1995)] on a chosen subset of degrees of freedom described in terms of radial distribution functions. An in-house software package MagiC is developed to obtain the effective potentials for arbitrary molecular systems. In this work we compute effective potentials to model DNA-protein interactions (bacterial LiaR regulator bound to a 26 base pairs DNA fragment) at physiological salt concentration at a coarse-grained (CG) level. Normally the IMC CG pair-potentials are used directly as look-up tables but here we have fitted them to five Gaussians and a repulsive wall. Results show stable association between DNA and the model protein as well as similar position fluctuation profile.

  20. Incorporation of memory effects in coarse-grained modeling via the Mori-Zwanzig formalism.

    PubMed

    Li, Zhen; Bian, Xin; Li, Xiantao; Karniadakis, George Em

    2015-12-28

    The Mori-Zwanzig formalism for coarse-graining a complex dynamical system typically introduces memory effects. The Markovian assumption of delta-correlated fluctuating forces is often employed to simplify the formulation of coarse-grained (CG) models and numerical implementations. However, when the time scales of a system are not clearly separated, the memory effects become strong and the Markovian assumption becomes inaccurate. To this end, we incorporate memory effects into CG modeling by preserving non-Markovian interactions between CG variables, and the memory kernel is evaluated directly from microscopic dynamics. For a specific example, molecular dynamics (MD) simulations of star polymer melts are performed while the corresponding CG system is defined by grouping many bonded atoms into single clusters. Then, the effective interactions between CG clusters as well as the memory kernel are obtained from the MD simulations. The constructed CG force field with a memory kernel leads to a non-Markovian dissipative particle dynamics (NM-DPD). Quantitative comparisons between the CG models with Markovian and non-Markovian approximations indicate that including the memory effects using NM-DPD yields similar results as the Markovian-based DPD if the system has clear time scale separation. However, for systems with small separation of time scales, NM-DPD can reproduce correct short-time properties that are related to how the system responds to high-frequency disturbances, which cannot be captured by the Markovian-based DPD model. PMID:26723613

  1. Incorporation of memory effects in coarse-grained modeling via the Mori-Zwanzig formalism

    NASA Astrophysics Data System (ADS)

    Li, Zhen; Bian, Xin; Li, Xiantao; Karniadakis, George Em

    2015-12-01

    The Mori-Zwanzig formalism for coarse-graining a complex dynamical system typically introduces memory effects. The Markovian assumption of delta-correlated fluctuating forces is often employed to simplify the formulation of coarse-grained (CG) models and numerical implementations. However, when the time scales of a system are not clearly separated, the memory effects become strong and the Markovian assumption becomes inaccurate. To this end, we incorporate memory effects into CG modeling by preserving non-Markovian interactions between CG variables, and the memory kernel is evaluated directly from microscopic dynamics. For a specific example, molecular dynamics (MD) simulations of star polymer melts are performed while the corresponding CG system is defined by grouping many bonded atoms into single clusters. Then, the effective interactions between CG clusters as well as the memory kernel are obtained from the MD simulations. The constructed CG force field with a memory kernel leads to a non-Markovian dissipative particle dynamics (NM-DPD). Quantitative comparisons between the CG models with Markovian and non-Markovian approximations indicate that including the memory effects using NM-DPD yields similar results as the Markovian-based DPD if the system has clear time scale separation. However, for systems with small separation of time scales, NM-DPD can reproduce correct short-time properties that are related to how the system responds to high-frequency disturbances, which cannot be captured by the Markovian-based DPD model.

  2. Two-Component Coarse-Grained Molecular-Dynamics Model for the Human Erythrocyte Membrane

    PubMed Central

    Li, He; Lykotrafitis, George

    2012-01-01

    We present a two-component coarse-grained molecular-dynamics model for simulating the erythrocyte membrane. The proposed model possesses the key feature of combing the lipid bilayer and the erythrocyte cytoskeleton, thus showing both the fluidic behavior of the lipid bilayer and the elastic properties of the erythrocyte cytoskeleton. In this model, three types of coarse-grained particles are introduced to represent clusters of lipid molecules, actin junctions, and band-3 complexes, respectively. The proposed model facilitates simulations that span large length scales (approximately micrometers) and timescales (approximately milliseconds). By tuning the interaction potential parameters, we were able to control the diffusivity and bending rigidity of the membrane model. We studied the membrane under shearing and found that at a low shear strain rate, the developed shear stress was due mainly to the spectrin network, whereas the viscosity of the lipid bilayer contributed to the resulting shear stress at higher strain rates. In addition, we investigated the effects of a reduced spectrin network connectivity on the shear modulus of the membrane. PMID:22225800

  3. Systematic hierarchical coarse-graining with the inverse Monte Carlo method

    SciTech Connect

    Lyubartsev, Alexander P.; Naômé, Aymeric; Vercauteren, Daniel P.; Laaksonen, Aatto

    2015-12-28

    We outline our coarse-graining strategy for linking micro- and mesoscales of soft matter and biological systems. The method is based on effective pairwise interaction potentials obtained in detailed ab initio or classical atomistic Molecular Dynamics (MD) simulations, which can be used in simulations at less accurate level after scaling up the size. The effective potentials are obtained by applying the inverse Monte Carlo (IMC) method [A. P. Lyubartsev and A. Laaksonen, Phys. Rev. E 52(4), 3730–3737 (1995)] on a chosen subset of degrees of freedom described in terms of radial distribution functions. An in-house software package MagiC is developed to obtain the effective potentials for arbitrary molecular systems. In this work we compute effective potentials to model DNA-protein interactions (bacterial LiaR regulator bound to a 26 base pairs DNA fragment) at physiological salt concentration at a coarse-grained (CG) level. Normally the IMC CG pair-potentials are used directly as look-up tables but here we have fitted them to five Gaussians and a repulsive wall. Results show stable association between DNA and the model protein as well as similar position fluctuation profile.

  4. Properties of Coarse-Grained Polymer Models: Statics, Dynamics, and Crystallinity

    NASA Astrophysics Data System (ADS)

    Grest, Gary; Salerno, K. Michael; Agrawal, Anupriya; Perahia, Dvora

    2015-03-01

    To capture large length and time scales, coarse-grained (CG) models that combine multiple atoms into one bead have been developed to model polymer melts. In the process microscopic detail is discarded in exchange for computational efficiency. However it is not well-understood how the scale of coarse-graining affects the polymer structure and dynamics. We compare results of atomistic simulations with CG models in which each CG bead represents three, four, or six methylene groups for C96H194, C480H962,andC960H1922. The CG potential is developed at 500K by iterative Boltzmann inversion. While static properties such as end-to-end distance and radius of gyration are captured by all CG models, the entanglement length deviates from experimental results with increased CG scale. The mean squared displacement of CG models is used to determine scale factors between the atomistic and CG models. During cooling to low temperature, the three and four-carbon models form a semi-crystalline structure while the six-carbon model and a four-carbon model based on the MARTINI force field remain amorphous at all temperatures. These findings show that the level of coarse-graining and CG interactions can strongly affect model temperature transferability. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's NNSA under Contract DE-AC04-94AL85000.

  5. Global- and local-scale characterisation of bed surface structure in coarse-grained alluvial rivers

    NASA Astrophysics Data System (ADS)

    Powell, Mark; Ockelford, Annie; Nguyen, Thao; Wood, Jo; Rice, Steve; Reid, Ian; Tate, Nick

    2013-04-01

    It is widely recognised that adjustments in bed surface grain size (texture) and grain arrangement (structure) exert significant controls on the stability of coarse-grained alluvial rivers. Modifications to bed surface texture and structure occur during active sediment transport and are mediated by the process of mobile armouring which concentrates coarser-than-average particles on the surface and organises them into a variety of grain- and bedform-scale configurations. Textural aspects of surface armouring are well understood to the extent that sediment transport models can be used to predict the size distribution of armours that develop under different sediment supply regimes and shear stresses. Research has also found that the adjustment of bed surface grain size is often patchy and that the development of finer-grained and coarser-grained areas of the bed has important implications for both the rate and grain size of transported sediment. The structural aspects of stream-bed armouring, however, are less well understood, largely because of the difficulty of recognising and characterising bedforms and bed-structures that have dimensions similar to their constituent particles. Moreover, bed structure is generally parameterised using global scale descriptors of the bed surface such that information on the spatial heterogeneity of the structure is lost. The aim of this poster is to characterise the structural characteristics of water-worked river gravels, paying particular attention to quantifying the spatial heterogeneity of those characteristics using local scale descriptors. Results reported from a number of flume experiments designed to simulate the spatio-temporal evolution of bed configurations (surface texture and structure) as the system adjusts to a condition of equilibrium transport are used to evaluate the spatial variability of bed surface structure and explore its significance for modelling sediment transport rates in gravel-bed rivers. Keywords: bed

  6. A temperature-dependent coarse-grained model for the thermoresponsive polymer poly(N-isopropylacrylamide)

    SciTech Connect

    Abbott, Lauren J.; Stevens, Mark J.

    2015-12-22

    In this study, a coarse-grained (CG) model is developed for the thermoresponsive polymer poly(N-isopropylacrylamide) (PNIPAM), using a hybrid top-down and bottom-up approach. Nonbonded parameters are fit to experimental thermodynamic data following the procedures of the SDK (Shinoda, DeVane, and Klein) CG force field, with minor adjustments to provide better agreement with radial distribution functions from atomistic simulations. Bonded parameters are fit to probability distributions from atomistic simulations using multi-centered Gaussian-based potentials. The temperature-dependent potentials derived for the PNIPAM CG model in this work properly capture the coil–globule transition of PNIPAM single chains and yield a chain-length dependence consistent with atomistic simulations.

  7. A temperature-dependent coarse-grained model for the thermoresponsive polymer poly(N-isopropylacrylamide)

    NASA Astrophysics Data System (ADS)

    Abbott, Lauren J.; Stevens, Mark J.

    2015-12-01

    A coarse-grained (CG) model is developed for the thermoresponsive polymer poly(N-isopropylacrylamide) (PNIPAM), using a hybrid top-down and bottom-up approach. Nonbonded parameters are fit to experimental thermodynamic data following the procedures of the SDK (Shinoda, DeVane, and Klein) CG force field, with minor adjustments to provide better agreement with radial distribution functions from atomistic simulations. Bonded parameters are fit to probability distributions from atomistic simulations using multi-centered Gaussian-based potentials. The temperature-dependent potentials derived for the PNIPAM CG model in this work properly capture the coil-globule transition of PNIPAM single chains and yield a chain-length dependence consistent with atomistic simulations.

  8. A temperature-dependent coarse-grained model for the thermoresponsive polymer poly(N-isopropylacrylamide).

    PubMed

    Abbott, Lauren J; Stevens, Mark J

    2015-12-28

    A coarse-grained (CG) model is developed for the thermoresponsive polymer poly(N-isopropylacrylamide) (PNIPAM), using a hybrid top-down and bottom-up approach. Nonbonded parameters are fit to experimental thermodynamic data following the procedures of the SDK (Shinoda, DeVane, and Klein) CG force field, with minor adjustments to provide better agreement with radial distribution functions from atomistic simulations. Bonded parameters are fit to probability distributions from atomistic simulations using multi-centered Gaussian-based potentials. The temperature-dependent potentials derived for the PNIPAM CG model in this work properly capture the coil-globule transition of PNIPAM single chains and yield a chain-length dependence consistent with atomistic simulations. PMID:26723705

  9. A temperature-dependent coarse-grained model for the thermoresponsive polymer poly(N-isopropylacrylamide)

    SciTech Connect

    Abbott, Lauren J.; Stevens, Mark J.

    2015-12-28

    A coarse-grained (CG) model is developed for the thermoresponsive polymer poly(N-isopropylacrylamide) (PNIPAM), using a hybrid top-down and bottom-up approach. Nonbonded parameters are fit to experimental thermodynamic data following the procedures of the SDK (Shinoda, DeVane, and Klein) CG force field, with minor adjustments to provide better agreement with radial distribution functions from atomistic simulations. Bonded parameters are fit to probability distributions from atomistic simulations using multi-centered Gaussian-based potentials. The temperature-dependent potentials derived for the PNIPAM CG model in this work properly capture the coil–globule transition of PNIPAM single chains and yield a chain-length dependence consistent with atomistic simulations.

  10. A temperature-dependent coarse-grained model for the thermoresponsive polymer poly(N-isopropylacrylamide)

    DOE PAGESBeta

    Abbott, Lauren J.; Stevens, Mark J.

    2015-12-22

    In this study, a coarse-grained (CG) model is developed for the thermoresponsive polymer poly(N-isopropylacrylamide) (PNIPAM), using a hybrid top-down and bottom-up approach. Nonbonded parameters are fit to experimental thermodynamic data following the procedures of the SDK (Shinoda, DeVane, and Klein) CG force field, with minor adjustments to provide better agreement with radial distribution functions from atomistic simulations. Bonded parameters are fit to probability distributions from atomistic simulations using multi-centered Gaussian-based potentials. The temperature-dependent potentials derived for the PNIPAM CG model in this work properly capture the coil–globule transition of PNIPAM single chains and yield a chain-length dependence consistent with atomisticmore » simulations.« less

  11. The role of inertia and coarse-graining on the transverse modes of lipid bilayers

    NASA Astrophysics Data System (ADS)

    Hömberg, M.; Müller, M.

    2012-03-01

    We determine the transverse dispersion relations of a lipid bilayer by generalizing the Seifert-Langer theory to include the bilayer's inertia and its surface tension. Thereby we extend the applicability of the original theory to computer simulations of lipid bilayers with and without solvent, as well as to simulations with and without momentum conservation. We calculate the asymptotic dispersion relations and identify conditions under which propagating modes occur. The theory is compared with simulations of a coarse-grained, solvent-free model, where we extract the transverse dispersion relations by fitting the intermediate scattering function of bilayer undulations. An estimate of the intermonolayer friction is obtained and compared with the result of a Green-Kubo relation.

  12. Membrane-Protein Interactions in a Generic Coarse-Grained Model for Lipid Bilayers

    PubMed Central

    West, Beate; Brown, Frank L.H.; Schmid, Friederike

    2009-01-01

    Abstract We study membrane-protein interactions and membrane-mediated protein-protein interactions by Monte Carlo simulations of a generic coarse-grained model for lipid bilayers with cylindrical hydrophobic inclusions. The strength of the hydrophobic force and the hydrophobic thickness of the proteins are systematically varied. The results are compared with analytical predictions of two popular analytical theories: The Landau-de Gennes theory and the elastic theory. The elastic theory provides an excellent description of the fluctuation spectra of pure membranes and successfully reproduces the deformation profiles of membranes around single proteins. However, its prediction for the potential of mean force between proteins is not compatible with the simulation data for large distances. The simulations show that the lipid-mediated interactions are governed by five competing factors: direct interactions; lipid-induced depletion interactions; lipid bridging; lipid packing; and a smooth long-range contribution. The mechanisms leading to hydrophobic mismatch interactions are critically analyzed. PMID:18835907

  13. Coarse-grained description of polymer blends as chains of interacting soft particles

    NASA Astrophysics Data System (ADS)

    Walton, Kevin; Guenza, Marina

    We present an analytic pair potential in a coarse grain description of a polymer blend where each chain is represented as a chain of soft-colloidal particles. This coarse grain model is based on integral theory that can represent the chains at variable levels.The particles have soft repulsion at separation less than the size of each coarse grain unit and a long repulsive tail with small attractive portion. While the short range pieces of the potential dominates the liquid structure, the long range tail dominate the thermodynamics of the system. So an accurate potential in both the short and long range distances is need to keep give correct structure and thermodynamical properties in the coarse grain description.

  14. Impact of coarse-grained measurement with finite range on continuous-variable quantum key distribution

    NASA Astrophysics Data System (ADS)

    Wang, Tianyi; Yu, Song; Gu, Wanyi

    2016-03-01

    In continuous-variable quantum key distribution, detectors are necessarily coarse grained and of finite range. We analyze the impact of both features and demonstrate that while coarse graining adds a fixed error to the estimated excess noise, finite range degrades the estimation accuracy of both transmission and excess noise. Moreover, the inaccurate estimation due to finite range may results in secret key rate underestimation, even misjudgment of security. To compensate these consequences, tuning the modulation variance is a possible way.

  15. A comparative study of coarse-graining methods for polymeric fluids: Mori-Zwanzig vs. iterative Boltzmann inversion vs. stochastic parametric optimization.

    PubMed

    Li, Zhen; Bian, Xin; Yang, Xiu; Karniadakis, George Em

    2016-07-28

    We construct effective coarse-grained (CG) models for polymeric fluids by employing two coarse-graining strategies. The first one is a forward-coarse-graining procedure by the Mori-Zwanzig (MZ) projection while the other one applies a reverse-coarse-graining procedure, such as the iterative Boltzmann inversion (IBI) and the stochastic parametric optimization (SPO). More specifically, we perform molecular dynamics (MD) simulations of star polymer melts to provide the atomistic fields to be coarse-grained. Each molecule of a star polymer with internal degrees of freedom is coarsened into a single CG particle and the effective interactions between CG particles can be either evaluated directly from microscopic dynamics based on the MZ formalism, or obtained by the reverse methods, i.e., IBI and SPO. The forward procedure has no free parameters to tune and recovers the MD system faithfully. For the reverse procedure, we find that the parameters in CG models cannot be selected arbitrarily. If the free parameters are properly defined, the reverse CG procedure also yields an accurate effective potential. Moreover, we explain how an aggressive coarse-graining procedure introduces the many-body effect, which makes the pairwise potential invalid for the same system at densities away from the training point. From this work, general guidelines for coarse-graining of polymeric fluids can be drawn. PMID:27475343

  16. A comparative study of coarse-graining methods for polymeric fluids: Mori-Zwanzig vs. iterative Boltzmann inversion vs. stochastic parametric optimization

    NASA Astrophysics Data System (ADS)

    Li, Zhen; Bian, Xin; Yang, Xiu; Karniadakis, George Em

    2016-07-01

    We construct effective coarse-grained (CG) models for polymeric fluids by employing two coarse-graining strategies. The first one is a forward-coarse-graining procedure by the Mori-Zwanzig (MZ) projection while the other one applies a reverse-coarse-graining procedure, such as the iterative Boltzmann inversion (IBI) and the stochastic parametric optimization (SPO). More specifically, we perform molecular dynamics (MD) simulations of star polymer melts to provide the atomistic fields to be coarse-grained. Each molecule of a star polymer with internal degrees of freedom is coarsened into a single CG particle and the effective interactions between CG particles can be either evaluated directly from microscopic dynamics based on the MZ formalism, or obtained by the reverse methods, i.e., IBI and SPO. The forward procedure has no free parameters to tune and recovers the MD system faithfully. For the reverse procedure, we find that the parameters in CG models cannot be selected arbitrarily. If the free parameters are properly defined, the reverse CG procedure also yields an accurate effective potential. Moreover, we explain how an aggressive coarse-graining procedure introduces the many-body effect, which makes the pairwise potential invalid for the same system at densities away from the training point. From this work, general guidelines for coarse-graining of polymeric fluids can be drawn.

  17. A Direct Method for Incorporating Experimental Data into Multiscale Coarse-Grained Models.

    PubMed

    Dannenhoffer-Lafage, Thomas; White, Andrew D; Voth, Gregory A

    2016-05-10

    To extract meaningful data from molecular simulations, it is necessary to incorporate new experimental observations as they become available. Recently, a new method was developed for incorporating experimental observations into molecular simulations, called experiment directed simulation (EDS), which utilizes a maximum entropy argument to bias an existing model to agree with experimental observations while changing the original model by a minimal amount. However, there is no discussion in the literature of whether or not the minimal bias systematically and generally improves the model by creating agreement with the experiment. In this work, we show that the relative entropy of the biased system with respect to an ideal target is always reduced by the application of a minimal bias, such as the one utilized by EDS. Using all-atom simulations that have been biased with EDS, one can then easily and rapidly improve a bottom-up multiscale coarse-grained (MS-CG) model without the need for a time-consuming reparametrization of the underlying atomistic force field. Furthermore, the improvement given by the many-body interactions introduced by the EDS bias can be maintained after being projected down to effective two-body MS-CG interactions. The result of this analysis is a new paradigm in coarse-grained modeling and simulation in which the "bottom-up" and "top-down" approaches are combined within a single, rigorous formalism based on statistical mechanics. The utility of building the resulting EDS-MS-CG models is demonstrated on two molecular systems: liquid methanol and ethylene carbonate. PMID:27045328

  18. Coarse-graining to the meso and continuum scales with molecular-dynamics-like models

    NASA Astrophysics Data System (ADS)

    Plimpton, Steve

    Many engineering-scale problems that industry or the national labs try to address with particle-based simulations occur at length and time scales well beyond the most optimistic hopes of traditional coarse-graining methods for molecular dynamics (MD), which typically start at the atomic scale and build upward. However classical MD can be viewed as an engine for simulating particles at literally any length or time scale, depending on the models used for individual particles and their interactions. To illustrate I'll highlight several coarse-grained (CG) materials models, some of which are likely familiar to molecular-scale modelers, but others probably not. These include models for water droplet freezing on surfaces, dissipative particle dynamics (DPD) models of explosives where particles have internal state, CG models of nano or colloidal particles in solution, models for aspherical particles, Peridynamics models for fracture, and models of granular materials at the scale of industrial processing. All of these can be implemented as MD-style models for either soft or hard materials; in fact they are all part of our LAMMPS MD package, added either by our group or contributed by collaborators. Unlike most all-atom MD simulations, CG simulations at these scales often involve highly non-uniform particle densities. So I'll also discuss a load-balancing method we've implemented for these kinds of models, which can improve parallel efficiencies. From the physics point-of-view, these models may be viewed as non-traditional or ad hoc. But because they are MD-style simulations, there's an opportunity for physicists to add statistical mechanics rigor to individual models. Or, in keeping with a theme of this session, to devise methods that more accurately bridge models from one scale to the next.

  19. Bridging scales: from atoms to coarse-grained models for soft matter systems

    NASA Astrophysics Data System (ADS)

    Peter, Christine

    2015-03-01

    Molecular simulation has extended to increasingly complex soft matter systems, and time-scale and system-size requirements have instigated the use of simulation models on multiple levels of resolution. On the classical particle-based level, a large variety of methods to develop coarse grained (CG) simulation models has emerged, an important subgroup being those scale-bridging methods where the CG model is derived from and systematically linked to an underlying atomistic description. In my talk, I will introduce a few of these methods, address the underlying concepts as well as some of the ongoing challenges that are inherent to coarse graining. A natural consequence of reducing the level of resolution in a simulation model is a loss of transferability, i.e. a decreasing ability to correctly describe a system at several thermodynamic state points. Intimately linked to this is a loss of the ability to correctly represent all structural, thermodynamic and dynamic properties of the system. Examples for these limitations are easily found in all CG simulations of multicomponent or multiphase soft matter systems - ranging from liquid crystals, biomolecular aggregates, biomaterials to hard/soft nanocomposites. A correct representation of phase transitions, phase coexistence, environment-induced conformational transitions, or effects due to surfaces and interfaces is a severe challenge for bottom-up CG models. Addressing this challenge requires both a method of generating CG potentials as well as finding and rationalizing an appropriate reference state point to start out from. I will illustrate several of these aspects using examples from the biomolecular and (biomimetic-) materials world.

  20. Coarse Graining to Investigate Membrane Induced Peptide Folding of Anticancer Peptides

    NASA Astrophysics Data System (ADS)

    Ganesan, Sai; Xu, Hongcheng; Matysiak, Silvina

    Information about membrane induced peptide folding mechanisms using all-atom molecular dynamics simulations is a challenge due to time and length scale issues.We recently developed a low resolution Water Explicit Polarizable PROtein coarse-grained Model by adding oppositely charged dummy particles inside protein backbone beads.These two dummy particles represent a fluctuating dipole,thus introducing structural polarization into the coarse-grained model.With this model,we were able to achieve significant α- β secondary structure content de novo,without any added bias.We extended the model to zwitterionic and anionic lipids,by adding oppositely charged dummy particles inside polar beads, to capture the ability of the head group region to form hydrogen bonds.We use zwitterionic POPC and anionic POPS as our model lipids, and a cationic anticancer peptide,SVS1,as our model peptide.We have characterized the driving forces for SVS1 folding on lipid bilayers with varying anionic and zwitterionic lipid compositions.Based on our results, dipolar interactions between peptide backbone and lipid head groups contribute to stabilize folded conformations.Cooperativity in folding is induced by both intra peptide and membrane-peptide interaction.

  1. A Coarse-Grained Molecular Model for Glycosaminoglycans: Application to Chondroitin, Chondroitin Sulfate, and Hyaluronic Acid

    PubMed Central

    Bathe, Mark; Rutledge, Gregory C.; Grodzinsky, Alan J.; Tidor, Bruce

    2005-01-01

    A coarse-grained molecular model is presented for the study of the equilibrium conformation and titration behavior of chondroitin (CH), chondroitin sulfate (CS), and hyaluronic acid (HA)—glycosaminoglycans (GAGs) that play a central role in determining the structure and biomechanical properties of the extracellular matrix of articular cartilage. Systematic coarse-graining from an all-atom description of the disaccharide building blocks retains the polyelectrolytes' specific chemical properties while enabling the simulation of high molecular weight chains that are inaccessible to all-atom representations. Results are presented for the characteristic ratio, the ionic strength-dependent persistence length, the pH-dependent expansion factor for the end-to-end distance, and the titration behavior of the GAGs. Although 4-sulfation of the N-acetyl-D-galactosamine residue is found to increase significantly the intrinsic stiffness of CH with respect to 6-sulfation, only small differences in the titration behavior of the two sulfated forms of CH are found. Persistence length expressions are presented for each type of GAG using a macroscopic (wormlike chain-based) and a microscopic (bond vector correlation-based) definition. Model predictions agree quantitatively with experimental conformation and titration measurements, which support use of the model in the investigation of equilibrium solution properties of GAGs. PMID:15805173

  2. Contrasting Polymer Behavior Under Nanoconfinement using Thermomechanically Consistent Coarse-Grained Models

    NASA Astrophysics Data System (ADS)

    Keten, Sinan; Xia, Wenjie; Hsu, David

    2015-03-01

    We present a systematic, two-bead per monomer coarse graining strategy that simulates the thermomechanical behavior of polymers several hundred times faster than all-atom MD (Hsu et al. JCTC, 2014). The predictive capability of the technique is illustrated here for 5 different methacrylate monomers and polystyrene stereoisomers. The approach involves optimization of analytical bonded potentials from atomistic bonded distributions to emulate local structure, as validated by chain end-to-end length and the radius of gyration comparisons with experiments and random coil theory. Nonbonded Lennard-Jones potentials are tuned to reproduce the elastic modulus (E) and glass transition temperature (Tg) at a single thermodynamic state. Density-corrected parameters capture temperature-modulus dependence in the 150-600 K range. Flory-Fox constants of the CG models are commensurate with all atomistic and experimental results, even though all calibrations are done at a single molecular weight. Finally, we further demonstrate the predictive capabilities of the models by examining thin film nanoconfinement effects for different polymers, film thicknesses, interfacial energies, and molecular weights. Our technique, called thermomechanically consistent coarse graining (TCCG), is demonstrated, using polystyrene and poly(methylmethacrylate) as universal benchmarks, to be a robust and effective technique to understand the thermomechanical behavior of polymers thin films and nanocomposites.

  3. Coarse-grained electrostatic interactions of coronene: Towards the crystalline phase

    NASA Astrophysics Data System (ADS)

    Heinemann, Thomas; Palczynski, Karol; Dzubiella, Joachim; Klapp, Sabine H. L.

    2015-11-01

    In this article, we present and compare two different, coarse-grained approaches to model electrostatic interactions of disc-shaped aromatic molecules, specifically coronene. Our study builds on our previous work [T. Heinemann et al., J. Chem. Phys. 141, 214110 (2014)], where we proposed, based on a systematic coarse-graining procedure starting from the atomistic level, an anisotropic effective (Gay-Berne-like) potential capable of describing van der Waals contributions to the interaction energy. To take into account electrostatics, we introduce, first, a linear quadrupole moment along the symmetry axis of the coronene disc. The second approach takes into account the fact that the partial charges within the molecules are distributed in a ring-like fashion. We then reparametrize the effective Gay-Berne-like potential such that it matches, at short distances, the ring-ring potential. To investigate the validity of these two approaches, we perform many-particle molecular dynamics simulations, focusing on the crystalline phase (karpatite) where electrostatic interaction effects are expected to be particularly relevant for the formation of tilted stacked columns. Specifically, we investigate various structural parameters as well as the melting transition. We find that the second approach yields consistent results with those from experiments despite the fact that the underlying potential decays with the wrong distance dependence at large molecule separations. Our strategy can be transferred to a broader class of molecules, such as benzene or hexabenzocoronene.

  4. Coarse Grained Approach to First Principles Modeling of Radiation Cascade in Large Fe Supercells

    NASA Astrophysics Data System (ADS)

    Odbadrakh, Kh; Nicholson, D. M.; Rusanu, A.; Samolyuk, G. D.; Stoller, R. E.; Zhang, X.-G.; Stocks, G. M.

    2012-12-01

    Classical Molecular Dynamics (MD) simulations characterizing dislocations and radiation damage typically treat 105-107 atoms. First principles techniques employed to understand systems at an atomistic level are not practical for such large systems consisting of millions of atoms. We present an efficient coarse grained (CG) approach to calculate local electronic and magnetic properties of large MD-generated structures from the first principles. Local atomic magnetic moments in crystalline Fe are perturbed by the presence of radiation generated vacancies and interstitials. The effects are most pronounced near the defect cores and decay slowly as the strain field of the defects decrease with distance. We develop the CG technique based on the Locally Self-consistent Multiple Scattering (LSMS) method that exploits the near-sightedness of the electron Green function. The atomic positions were determined by MD with an embedded atom force field. The local moments in the neighborhood of the defect cores are calculated with first-principles based on full local structure information. Atoms in the rest of the system are modeled by representative atoms with approximated properties. The calculations result in local moments near the defect centers with first-principles accuracy, while capturing coarse-grained details of local moments at greater length scales. This CG approach makes these large scale structures amenable to first principles study.

  5. A coarse-grained model to study calcium activation of the cardiac thin filament

    NASA Astrophysics Data System (ADS)

    Zhang, Jing; Schwartz, Steven

    2015-03-01

    Familial hypertrophic cardiomyopathy (FHC) is one of the most common heart disease caused by genetic mutations. Cardiac muscle contraction and relaxation involve regulation of crossbridge binding to the cardiac thin filament, which regulates actomyosin interactions through calcium-dependent alterations in the dynamics of cardiac troponin (cTn) and tropomyosin (Tm). An atomistic model of cTn complex interacting with Tm has been studied by our group. A more realistic model requires the inclusion of the dynamics of actin filament, which is almost 6 times larger than cTn and Tm in terms of atom numbers, and extensive sampling of the model becomes very resource-demanding. By using physics-based protein united-residue force field, we introduce a coarse-grained model to study the calcium activation of the thin filament resulting from cTn's allosteric regulation of Tm dynamics on actin. The time scale is much longer than that of all-atom molecular dynamics simulation because of the reduction of the degrees of freedom. The coarse-grained model is a good template for studying cardiac thin filament mutations that cause FHC, and reduces the cost of computational resources.

  6. Coarse-grained model for the interconversion between different crystalline cellulose allomorphs

    SciTech Connect

    Langan, Paul

    2012-01-01

    We present the results of Langevin dynamics simulations on a coarse grained model for crystalline cellulose. In particular, we analyze two different cellulose crystalline forms: cellulose I (the natural form of cellulose) and cellulose IIII (obtained after cellulose I is treated with anhydrous liquid ammonia). Cellulose IIII has been the focus of wide interest in the field of cellulosic biofuels as it can be efficiently hydrolyzed to glucose (its enzymatic degradation rates are up to 5 fold higher than those of cellulose I ). In turn, glucose can eventually be fermented into fuels. The coarse-grained model presented in this study is based on a simplified geometry and on an effective potential mimicking the changes in both intracrystalline hydrogen bonds and stacking interactions during the transition from cellulose I to cellulose IIII. The model accurately reproduces both structural and thermomechanical properties of cellulose I and IIII. The work presented herein describes the structural transition from cellulose I to cellulose IIII as driven by the change in the equilibrium state of two degrees of freedom in the cellulose chains. The structural transition from cellulose I to cellulose IIII is essentially reduced to a search for optimal spatial arrangement of the cellulose chains.

  7. Predicting Themomechanical Responses of Polymer Thin Films and Nanocomposites via an Innovative Coarse-grained Approach

    NASA Astrophysics Data System (ADS)

    Xia, Wenjie; Hsu, David; Keten, Sinan

    Understanding and predicting the thermomechanical responses of nanoscale polymer systems are very challenging as their responses are greatly influenced by many factors, such as interfacial energy, filler volume fraction and molecule weight, giving rise to the presence of nanoscale interface and free surface. To overcome these issues, here we employ a novel atomistically informed coarse-grained computational technique, called thermomechanically consistent coarse graining (TCCG), to investigate how the nanoscale interface and free surface influence the elastic modulus (E) and glass transition temperature (Tg) of polymer films and nanocomposites. By performing tensile tests and nanoindentation simulations, we are able to predict the size dependent elastic properties of polymer films and quantify the length scale of the local mechanical interphase. Finally, taking cellulose nanocrystal (CNC) and poly(methyl-methacrylate) (PMMA) nanocomposites as a relevant model system, we present a multi-scale framework built upon our CG approach to allow the prediction of Tg of nanocomposite as a function of interfacial energy and filler volume fractions by drawing the analogy between thin film and nanocomposites. Our established multi-scale framework is validated by recent experiments and breaks new ground in predicting, without any empirical parameters, key structure-property relationships for polymer nanomaterials.

  8. Coarse-grained electrostatic interactions of coronene: Towards the crystalline phase.

    PubMed

    Heinemann, Thomas; Palczynski, Karol; Dzubiella, Joachim; Klapp, Sabine H L

    2015-11-01

    In this article, we present and compare two different, coarse-grained approaches to model electrostatic interactions of disc-shaped aromatic molecules, specifically coronene. Our study builds on our previous work [T. Heinemann et al., J. Chem. Phys. 141, 214110 (2014)], where we proposed, based on a systematic coarse-graining procedure starting from the atomistic level, an anisotropic effective (Gay-Berne-like) potential capable of describing van der Waals contributions to the interaction energy. To take into account electrostatics, we introduce, first, a linear quadrupole moment along the symmetry axis of the coronene disc. The second approach takes into account the fact that the partial charges within the molecules are distributed in a ring-like fashion. We then reparametrize the effective Gay-Berne-like potential such that it matches, at short distances, the ring-ring potential. To investigate the validity of these two approaches, we perform many-particle molecular dynamics simulations, focusing on the crystalline phase (karpatite) where electrostatic interaction effects are expected to be particularly relevant for the formation of tilted stacked columns. Specifically, we investigate various structural parameters as well as the melting transition. We find that the second approach yields consistent results with those from experiments despite the fact that the underlying potential decays with the wrong distance dependence at large molecule separations. Our strategy can be transferred to a broader class of molecules, such as benzene or hexabenzocoronene. PMID:26547161

  9. Necessity of high-resolution for coarse-grained modeling of flexible proteins.

    PubMed

    Jia, Zhiguang; Chen, Jianhan

    2016-07-01

    The popular MARTINI coarse-grained (CG) force field requires the protein structure to be fixed, and is unsuitable for simulating dynamic processes such as protein folding. Here, we examine the feasibility of developing a flexible protein model within the MARTINI framework. The results demonstrate that the MARTINI CG scheme does not properly describe the volume and packing of protein backbone and side chains and leads to excessive collapse without structural restraints in explicit CG water. Combining atomistic protein representation with the MARTINI CG solvent, such as in the PACE model, dramatically improves description of flexible protein conformations. Yet, the CG solvent is insufficient to capture the conformational dependence of protein-solvent interactions, and PACE is unable to properly model context dependent conformational transitions. Taken together, high physical resolution at or near the atomistic level is likely necessary for flexible protein models with explicit, microscopic solvents, and the coarse-graining needs to focus on possible simplification in interaction potentials. © 2016 Wiley Periodicals, Inc. PMID:27130454

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  11. Coarse-grained electrostatic interactions of coronene: Towards the crystalline phase

    SciTech Connect

    Heinemann, Thomas Klapp, Sabine H. L.; Palczynski, Karol Dzubiella, Joachim

    2015-11-07

    In this article, we present and compare two different, coarse-grained approaches to model electrostatic interactions of disc-shaped aromatic molecules, specifically coronene. Our study builds on our previous work [T. Heinemann et al., J. Chem. Phys. 141, 214110 (2014)], where we proposed, based on a systematic coarse-graining procedure starting from the atomistic level, an anisotropic effective (Gay-Berne-like) potential capable of describing van der Waals contributions to the interaction energy. To take into account electrostatics, we introduce, first, a linear quadrupole moment along the symmetry axis of the coronene disc. The second approach takes into account the fact that the partial charges within the molecules are distributed in a ring-like fashion. We then reparametrize the effective Gay-Berne-like potential such that it matches, at short distances, the ring-ring potential. To investigate the validity of these two approaches, we perform many-particle molecular dynamics simulations, focusing on the crystalline phase (karpatite) where electrostatic interaction effects are expected to be particularly relevant for the formation of tilted stacked columns. Specifically, we investigate various structural parameters as well as the melting transition. We find that the second approach yields consistent results with those from experiments despite the fact that the underlying potential decays with the wrong distance dependence at large molecule separations. Our strategy can be transferred to a broader class of molecules, such as benzene or hexabenzocoronene.

  12. Effects of Surface Water on Protein Dynamics Studied by a Novel Coarse-Grained Normal Mode Approach

    PubMed Central

    Zhou, Lei; Siegelbaum, Steven A.

    2008-01-01

    Normal mode analysis (NMA) has received much attention as a direct approach to extract the collective motions of macromolecules. However, the stringent requirement of computational resources by classical all-atom NMA limits the size of the macromolecules to which the method is normally applied. We implemented a novel coarse-grained normal mode approach based on partitioning the all-atom Hessian matrix into relevant and nonrelevant parts. It is interesting to note that, using classical all-atom NMA results as a reference, we found that this method generates more accurate results than do other coarse-grained approaches, including elastic network model and block normal mode approaches. Moreover, this new method is effective in incorporating the energetic contributions from the nonrelevant atoms, including surface water molecules, into the coarse-grained protein motions. The importance of such improvements is demonstrated by the effect of surface water to shift vibrational modes to higher frequencies and by an increase in overlap of the coarse-grained eigenvector space (the motion directions) with that obtained from molecular dynamics simulations of solvated protein in a water box. These results not only confirm the quality of our method but also point out the importance of incorporating surface structural water in studying protein dynamics. PMID:18212016

  13. Modeling the self-assembly of peptide amphiphiles into fibers using coarse-grained molecular dynamics.

    PubMed

    Lee, One-Sun; Cho, Vince; Schatz, George C

    2012-09-12

    We have studied the self-assembly of peptide amphiphiles (PAs) into a cylindrical micelle fiber starting from a homogeneous mixture of PAs in water using coarse-grained molecular dynamics simulations. Nine independent 16 μs runs all show spontaneous fiber formation in which the PA molecules first form spherical micelles, and then micelles form a three-dimensional network via van der Waals interactions. As the hydrophobic core belonging to the different micelles merge, the three-dimensional network disappears and a fiber having a diameter of ∼80 Å appears. In agreement with atomistic simulation results, water molecules are excluded from the hydrophobic core and penetrate to ∼15 Å away from the axis of fiber. About 66% of the surface of fiber is covered with the IKVAV epitope, and ∼92% of the epitope is exposed to water molecules. PMID:22924639

  14. Lipid Bilayer Vesicle extrusion through nanopores: a coarse grained molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Bertrand, Martin; Joos, Bela

    2011-03-01

    We conducted Coarse-Grained Molecular Dynamics simulations of the pressure extrusion of vesicles in nanopores that confirm and help explain prior experimental observations (Patty, P. and Frisken, B., Biophys. J., 85, 2003). We demonstrate that, to a first approximation, the final size of extruded vesicles can be obtained by considering an invariable inner vesicle volume enclosed by a finitely extensible lipid bilayer. Using our data, we also describe in details the mechanics of vesicle rupture in a nanopore when pushed by various pressure gradients. This is made possible by tracking local variations of the stress in the lipid membrane via changes in surface area using a triangulation algorithm. The simulations are executed using state of the art GPU accelerated software. Our findings could potentially be useful in the design of liposome based drug delivery systems and in getting a better understanding of how the cell nucleus and the cell as a whole react in similar conditions. Work supported by NSERC and FQRNT.

  15. Calibration and validation of coarse-grained models of atomic systems: application to semiconductor manufacturing

    NASA Astrophysics Data System (ADS)

    Farrell, Kathryn; Oden, J. Tinsley

    2014-07-01

    Coarse-grained models of atomic systems, created by aggregating groups of atoms into molecules to reduce the number of degrees of freedom, have been used for decades in important scientific and technological applications. In recent years, interest in developing a more rigorous theory for coarse graining and in assessing the predictivity of coarse-grained models has arisen. In this work, Bayesian methods for the calibration and validation of coarse-grained models of atomistic systems in thermodynamic equilibrium are developed. For specificity, only configurational models of systems in canonical ensembles are considered. Among major challenges in validating coarse-grained models are (1) the development of validation processes that lead to information essential in establishing confidence in the model's ability predict key quantities of interest and (2), above all, the determination of the coarse-grained model itself; that is, the characterization of the molecular architecture, the choice of interaction potentials and thus parameters, which best fit available data. The all-atom model is treated as the "ground truth," and it provides the basis with respect to which properties of the coarse-grained model are compared. This base all-atom model is characterized by an appropriate statistical mechanics framework in this work by canonical ensembles involving only configurational energies. The all-atom model thus supplies data for Bayesian calibration and validation methods for the molecular model. To address the first challenge, we develop priors based on the maximum entropy principle and likelihood functions based on Gaussian approximations of the uncertainties in the parameter-to-observation error. To address challenge (2), we introduce the notion of model plausibilities as a means for model selection. This methodology provides a powerful approach toward constructing coarse-grained models which are most plausible for given all-atom data. We demonstrate the theory and

  16. 7 CFR 457.113 - Coarse grains crop insurance provisions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... in accordance with 7 CFR part 400, subpart G, by the coverage level percentage you elect. Silage— A... planted aceage. if you have limited or additional levels of coverage, as specified in 7 CFR part 400... grains— Corn, grain sorghum, and soybeans. Grain sorghum— The crop defined as sorghum under the...

  17. Coupling multiscale phenomena in systems with mobile chemical species through first principles coarse graining

    NASA Astrophysics Data System (ADS)

    van der Ven, Anton

    2004-03-01

    Many multiscale solid state phenomena involve the transport of chemical species over large distances. This is true of crack growth in corrosive environments as well as diffusional phase transformations. Often these phenomena occur over time scales that are too long for a direct atomistic simulation. Instead continuum methods that draw on phenomenological kinetic parameters such as diffusion coefficients or thermodynamic response functions such as informed cohesive zone models are necessary. A link between first principles atomistic methods and macroscopic kinetic parameters or response functions can be made with statistical mechanical coarse-graining techniques. For multicomponent crystalline solids, this involves integrating out fast degrees of freedom to generate a coarse-grained first-principles lattice model Hamiltonian that is suited for calculating both thermodynamic and kinetic properties, the latter with the help of Green-Kubo methods. We illustrate this approach by describing (i) a first principles calculation of diffusion coefficients in non-dilute alloys, essential input for continuum simulations of diffusional phase transformations and (ii) a first principles derivation of a cohesive zone model in the presence of highly mobile impurities. Cohesive zone models are used to describe the response of a solid ahead of the crack tip in continuum simulations of crack growth. We will show that for some systems, stress induced phase transformations can occur along the cohesive zone above a critical impurity chemical potential. The stress-induced transformation is accompanied by a saturation of the cohesive zone region with impurities and leads to a dramatic reduction of critical stress for decohesion.

  18. Web-based computational chemistry education with CHARMMing II: Coarse-grained protein folding.

    PubMed

    Pickard, Frank C; Miller, Benjamin T; Schalk, Vinushka; Lerner, Michael G; Woodcock, H Lee; Brooks, Bernard R

    2014-07-01

    A lesson utilizing a coarse-grained (CG) Gō-like model has been implemented into the CHARMM INterface and Graphics (CHARMMing) web portal (www.charmming.org) to the Chemistry at HARvard Macromolecular Mechanics (CHARMM) molecular simulation package. While widely used to model various biophysical processes, such as protein folding and aggregation, CG models can also serve as an educational tool because they can provide qualitative descriptions of complex biophysical phenomena for a relatively cheap computational cost. As a proof of concept, this lesson demonstrates the construction of a CG model of a small globular protein, its simulation via Langevin dynamics, and the analysis of the resulting data. This lesson makes connections between modern molecular simulation techniques and topics commonly presented in an advanced undergraduate lecture on physical chemistry. It culminates in a straightforward analysis of a short dynamics trajectory of a small fast folding globular protein; we briefly describe the thermodynamic properties that can be calculated from this analysis. The assumptions inherent in the model and the data analysis are laid out in a clear, concise manner, and the techniques used are consistent with those employed by specialists in the field of CG modeling. One of the major tasks in building the Gō-like model is determining the relative strength of the nonbonded interactions between coarse-grained sites. New functionality has been added to CHARMMing to facilitate this process. The implementation of these features into CHARMMing helps automate many of the tedious aspects of constructing a CG Gō model. The CG model builder and its accompanying lesson should be a valuable tool to chemistry students, teachers, and modelers in the field. PMID:25058338

  19. Web-Based Computational Chemistry Education with CHARMMing II: Coarse-Grained Protein Folding

    PubMed Central

    Schalk, Vinushka; Lerner, Michael G.; Woodcock, H. Lee; Brooks, Bernard R.

    2014-01-01

    A lesson utilizing a coarse-grained (CG) G-like model has been implemented into the CHARMM INterface and Graphics (CHARMMing) web portal (www.charmming.org) to the Chemistry at HARvard Macromolecular Mechanics (CHARMM) molecular simulation package. While widely used to model various biophysical processes, such as protein folding and aggregation, CG models can also serve as an educational tool because they can provide qualitative descriptions of complex biophysical phenomena for a relatively cheap computational cost. As a proof of concept, this lesson demonstrates the construction of a CG model of a small globular protein, its simulation via Langevin dynamics, and the analysis of the resulting data. This lesson makes connections between modern molecular simulation techniques and topics commonly presented in an advanced undergraduate lecture on physical chemistry. It culminates in a straightforward analysis of a short dynamics trajectory of a small fast folding globular protein; we briefly describe the thermodynamic properties that can be calculated from this analysis. The assumptions inherent in the model and the data analysis are laid out in a clear, concise manner, and the techniques used are consistent with those employed by specialists in the field of CG modeling. One of the major tasks in building the G-like model is determining the relative strength of the nonbonded interactions between coarse-grained sites. New functionality has been added to CHARMMing to facilitate this process. The implementation of these features into CHARMMing helps automate many of the tedious aspects of constructing a CG G model. The CG model builder and its accompanying lesson should be a valuable tool to chemistry students, teachers, and modelers in the field. PMID:25058338

  20. PACSAB: Coarse-Grained Force Field for the Study of Protein-Protein Interactions and Conformational Sampling in Multiprotein Systems.

    PubMed

    Emperador, Agustí; Sfriso, Pedro; Villarreal, Marcos Ariel; Gelpí, Josep Lluis; Orozco, Modesto

    2015-12-01

    Molecular dynamics simulations of proteins are usually performed on a single molecule, and coarse-grained protein models are calibrated using single-molecule simulations, therefore ignoring intermolecular interactions. We present here a new coarse-grained force field for the study of many protein systems. The force field, which is implemented in the context of the discrete molecular dynamics algorithm, is able to reproduce the properties of folded and unfolded proteins, in both isolation, complexed forming well-defined quaternary structures, or aggregated, thanks to its proper evaluation of protein-protein interactions. The accuracy and computational efficiency of the method makes it a universal tool for the study of the structure, dynamics, and association/dissociation of proteins. PMID:26597989

  1. Multi-scale morphology in self-assembly of peptides to proteins via a coarse-grain model

    NASA Astrophysics Data System (ADS)

    Pandey, Ras; Farmer, Barry

    2015-03-01

    Self-organizing structures of short peptides (6-7 residues) and proteins (136 residues) are studied by a coarse-grained Monte Carlo simulation. Peptides and proteins are described by coarse-grained chains of residues whose interactions are described by a knowledge-based residue-residue interaction potential that captures the compositional specificity. Large-scale computer simulations are performed to study the structural evolution e.g. aggregation, network, etc. at a range of temperatures and concentrations. A number of local and global physical quantities including structure factor are examined. We find that the residue interactions, concentration, and size of chains are very important in modulating the structure of emerging morphologies in the specified temperature range. Estimates are provided for the effective (fractal) dimension of the assembly over various length scales as a function of temperature. This work is supported by the Air Force Research Laboratory.

  2. On a Primal Coarse Projective Integration Method for Multiscale Simulations

    NASA Astrophysics Data System (ADS)

    Skoric, Milos; Ishiguro, Seiji; Maluckov, Sandra

    2006-10-01

    A novel simulation framework called Equation-Free Projective Integration (EFPI) was recently applied to nonlinear plasmas by M. Shay [1] to study propagation and steepening of a 1D ion sound (IS) with a PIC code as a microscopic simulator. To initialize, macro plasma variables are ``lifted'' to a fine micro-representation. PIC code is stepped forward for a short time, and the results are ``restricted'' or smoothed back to macro space. By extrapolation, time derivative is estimated and projected with a large step; the process is repeated. As a simple alternative, we propose a sort of a primal EPFI scheme to simulate nonlinear plasmas including kinetic effects. The micro-simulator is a standard 1D ES PIC code. Ions are assumed inherently coarse grained or ``smoothed'' and tracked to extrapolate in time and project. The potential is averaged over the electron plasma period to extrapolate and project. No adiabatic approximation for electrons is used [2], instead, self-consistently find the non-uniform electron distribution from the Poisson equation and ion density. Preliminary results for nonlinear IS as well as for the IS double layer paradigm are presented and some limitations on the EPFI discussed. [1] M. Shay, J. Drake, W. Dorland, J. of Comp. Phys (APS DPP 2005) [2] G. Stanchev, A. Maluckov et al., in EPS Fusion (Rome, 2006).

  3. A coarse-grained model of the 10-23 DNAzyme

    NASA Astrophysics Data System (ADS)

    Dorfman, Kevin; Kenward, Martin

    2010-03-01

    DNAzymes are single-stranded DNA that catalyze nucleic acid biochemistry. We have adopted a simple bead-spring model that captures, in a coarse-grained manner, the diffusive motion and self-interactions of single-stranded DNA. We used this model to investigate the structure and dynamics of the RNA cleaving 10-23 DNAzyme over long time scales via Brownian dynamics simulations. We start from an unfolded state where the DNAzyme is bound to its substrate and allow the system to relax. The structural data thus obtained agree well with FRET measurements and provide a connection between the proposed structure of the DNAzyme and chemical rate data appearing in the literature. We have also investigated the changes in the structure of the DNAzyme/substrate complex following the cleavage of the substrate. In agreement with single-molecule FRET data, we find that the DNAzyme rapidly unwinds into an extended structure.

  4. Robotic action acquisition with cognitive biases in coarse-grained state space.

    PubMed

    Uragami, Daisuke; Kohno, Yu; Takahashi, Tatsuji

    2016-07-01

    Some of the authors have previously proposed a cognitively inspired reinforcement learning architecture (LS-Q) that mimics cognitive biases in humans. LS-Q adaptively learns under uniform, coarse-grained state division and performs well without parameter tuning in a giant-swing robot task. However, these results were shown only in simulations. In this study, we test the validity of the LS-Q implemented in a robot in a real environment. In addition, we analyze the learning process to elucidate the mechanism by which the LS-Q adaptively learns under the partially observable environment. We argue that the LS-Q may be a versatile reinforcement learning architecture, which is, despite its simplicity, easily applicable and does not require well-prepared settings. PMID:27195484

  5. Coarse-grained model of conformation-dependent electrophoretic mobility and its influence on DNA dynamics.

    PubMed

    Pandey, Harsh; Underhill, Patrick T

    2015-11-01

    The electrophoretic mobility of molecules such as λ-DNA depends on the conformation of the molecule. It has been shown that electrohydrodynamic interactions between parts of the molecule lead to a mobility that depends on conformation and can explain some experimental observations. We have developed a new coarse-grained model that incorporates these changes of mobility into a bead-spring chain model. Brownian dynamics simulations have been performed using this model. The model reproduces the cross-stream migration that occurs in capillary electrophoresis when pressure-driven flow is applied parallel or antiparallel to the electric field. The model also reproduces the change of mobility when the molecule is stretched significantly in an extensional field. We find that the conformation-dependent mobility can lead to a new type of unraveling of the molecule in strong fields. This occurs when different parts of the molecule have different mobilities and the electric field is large. PMID:26651689

  6. Coarse-Grained Structural Modeling of Molecular Motors Using Multibody Dynamics

    PubMed Central

    Parker, David; Bryant, Zev; Delp, Scott L.

    2010-01-01

    Experimental and computational approaches are needed to uncover the mechanisms by which molecular motors convert chemical energy into mechanical work. In this article, we describe methods and software to generate structurally realistic models of molecular motor conformations compatible with experimental data from different sources. Coarse-grained models of molecular structures are constructed by combining groups of atoms into a system of rigid bodies connected by joints. Contacts between rigid bodies enforce excluded volume constraints, and spring potentials model system elasticity. This simplified representation allows the conformations of complex molecular motors to be simulated interactively, providing a tool for hypothesis building and quantitative comparisons between models and experiments. In an example calculation, we have used the software to construct atomically detailed models of the myosin V molecular motor bound to its actin track. The software is available at www.simtk.org. PMID:20428469

  7. Development of DPD coarse-grained models: From bulk to interfacial properties

    NASA Astrophysics Data System (ADS)

    Solano Canchaya, José G.; Dequidt, Alain; Goujon, Florent; Malfreyt, Patrice

    2016-08-01

    A new Bayesian method was recently introduced for developing coarse-grain (CG) force fields for molecular dynamics. The CG models designed for dissipative particle dynamics (DPD) are optimized based on trajectory matching. Here we extend this method to improve transferability across thermodynamic conditions. We demonstrate the capability of the method by developing a CG model of n-pentane from constant-NPT atomistic simulations of bulk liquid phases and we apply the CG-DPD model to the calculation of the surface tension of the liquid-vapor interface over a large range of temperatures. The coexisting densities, vapor pressures, and surface tensions calculated with different CG and atomistic models are compared to experiments. Depending on the database used for the development of the potentials, it is possible to build a CG model which performs very well in the reproduction of the surface tension on the orthobaric curve.

  8. Development of DPD coarse-grained models: From bulk to interfacial properties.

    PubMed

    Solano Canchaya, José G; Dequidt, Alain; Goujon, Florent; Malfreyt, Patrice

    2016-08-01

    A new Bayesian method was recently introduced for developing coarse-grain (CG) force fields for molecular dynamics. The CG models designed for dissipative particle dynamics (DPD) are optimized based on trajectory matching. Here we extend this method to improve transferability across thermodynamic conditions. We demonstrate the capability of the method by developing a CG model of n-pentane from constant-NPT atomistic simulations of bulk liquid phases and we apply the CG-DPD model to the calculation of the surface tension of the liquid-vapor interface over a large range of temperatures. The coexisting densities, vapor pressures, and surface tensions calculated with different CG and atomistic models are compared to experiments. Depending on the database used for the development of the potentials, it is possible to build a CG model which performs very well in the reproduction of the surface tension on the orthobaric curve. PMID:27497539

  9. Generalization of the DLA process with different immiscible components by time-scale coarse graining

    NASA Astrophysics Data System (ADS)

    Postnikov, E. B.; Ryabov, A. B.; Loskutov, A.

    2007-10-01

    In the framework of the mean-field approximation we propose a new approach to the description of the growth of fractal structures which are formed as a result of the process of diffusion limited aggregation. Our approach is based on the coarse graining of the time scale which takes into account the property of discreteness of such structures. The obtained system of partial differential equations allows us to evaluate numerically the fractal dimension and the cluster density depending on the distance from the cluster center. The results are in a quite good agreement with values found by the direct numerical simulations. The proposed approach is generalized for the case of the cluster description with different immiscible particles.

  10. Coarse-grained model of conformation-dependent electrophoretic mobility and its influence on DNA dynamics

    NASA Astrophysics Data System (ADS)

    Pandey, Harsh; Underhill, Patrick T.

    2015-11-01

    The electrophoretic mobility of molecules such as λ -DNA depends on the conformation of the molecule. It has been shown that electrohydrodynamic interactions between parts of the molecule lead to a mobility that depends on conformation and can explain some experimental observations. We have developed a new coarse-grained model that incorporates these changes of mobility into a bead-spring chain model. Brownian dynamics simulations have been performed using this model. The model reproduces the cross-stream migration that occurs in capillary electrophoresis when pressure-driven flow is applied parallel or antiparallel to the electric field. The model also reproduces the change of mobility when the molecule is stretched significantly in an extensional field. We find that the conformation-dependent mobility can lead to a new type of unraveling of the molecule in strong fields. This occurs when different parts of the molecule have different mobilities and the electric field is large.

  11. Boltzmann rovibrational collisional coarse-grained model for internal energy excitation and dissociation in hypersonic flows.

    PubMed

    Munafò, A; Panesi, M; Magin, T E

    2014-02-01

    A Boltzmann rovibrational collisional coarse-grained model is proposed to reduce a detailed kinetic mechanism database developed at NASA Ames Research Center for internal energy transfer and dissociation in N(2)-N interactions. The coarse-grained model is constructed by lumping the rovibrational energy levels of the N(2) molecule into energy bins. The population of the levels within each bin is assumed to follow a Boltzmann distribution at the local translational temperature. Excitation and dissociation rate coefficients for the energy bins are obtained by averaging the elementary rate coefficients. The energy bins are treated as separate species, thus allowing for non-Boltzmann distributions of their populations. The proposed coarse-grained model is applied to the study of nonequilibrium flows behind normal shock waves and within converging-diverging nozzles. In both cases, the flow is assumed inviscid and steady. Computational results are compared with those obtained by direct solution of the master equation for the rovibrational collisional model and a more conventional multitemperature model. It is found that the proposed coarse-grained model is able to accurately resolve the nonequilibrium dynamics of internal energy excitation and dissociation-recombination processes with only 20 energy bins. Furthermore, the proposed coarse-grained model provides a superior description of the nonequilibrium phenomena occurring in shock heated and nozzle flows when compared with the conventional multitemperature models. PMID:25353565

  12. Symmetry-adapted digital modeling III. Coarse-grained icosahedral viruses.

    PubMed

    Janner, A

    2016-05-01

    Considered is the coarse-grained modeling of icosahedral viruses in terms of a three-dimensional lattice (the digital modeling lattice) selected among the projected points in space of a six-dimensional icosahedral lattice. Backbone atomic positions (Cα's for the residues of the capsid and phosphorus atoms P for the genome nucleotides) are then indexed by their nearest lattice point. This leads to a fine-grained lattice point characterization of the full viral chains in the backbone approximation (denoted as digital modeling). Coarse-grained models then follow by a proper selection of the indexed backbone positions, where for each chain one can choose the desired coarseness. This approach is applied to three viruses, the Satellite tobacco mosaic virus, the bacteriophage MS2 and the Pariacoto virus, on the basis of structural data from the Brookhaven Protein Data Bank. In each case the various stages of the procedure are illustrated for a given coarse-grained model and the corresponding indexed positions are listed. Alternative coarse-grained models have been derived and compared. Comments on related results and approaches, found among the very large set of publications in this field, conclude this article. PMID:27126109

  13. Boltzmann rovibrational collisional coarse-grained model for internal energy excitation and dissociation in hypersonic flows

    NASA Astrophysics Data System (ADS)

    Munafò, A.; Panesi, M.; Magin, T. E.

    2014-02-01

    A Boltzmann rovibrational collisional coarse-grained model is proposed to reduce a detailed kinetic mechanism database developed at NASA Ames Research Center for internal energy transfer and dissociation in N2-N interactions. The coarse-grained model is constructed by lumping the rovibrational energy levels of the N2 molecule into energy bins. The population of the levels within each bin is assumed to follow a Boltzmann distribution at the local translational temperature. Excitation and dissociation rate coefficients for the energy bins are obtained by averaging the elementary rate coefficients. The energy bins are treated as separate species, thus allowing for non-Boltzmann distributions of their populations. The proposed coarse-grained model is applied to the study of nonequilibrium flows behind normal shock waves and within converging-diverging nozzles. In both cases, the flow is assumed inviscid and steady. Computational results are compared with those obtained by direct solution of the master equation for the rovibrational collisional model and a more conventional multitemperature model. It is found that the proposed coarse-grained model is able to accurately resolve the nonequilibrium dynamics of internal energy excitation and dissociation-recombination processes with only 20 energy bins. Furthermore, the proposed coarse-grained model provides a superior description of the nonequilibrium phenomena occurring in shock heated and nozzle flows when compared with the conventional multitemperature models.

  14. Effective rates from thermodynamically consistent coarse-graining of models for molecular motors with probe particles

    NASA Astrophysics Data System (ADS)

    Zimmermann, Eva; Seifert, Udo

    2015-02-01

    Many single-molecule experiments for molecular motors comprise not only the motor but also large probe particles coupled to it. The theoretical analysis of these assays, however, often takes into account only the degrees of freedom representing the motor. We present a coarse-graining method that maps a model comprising two coupled degrees of freedom which represent motor and probe particle to such an effective one-particle model by eliminating the dynamics of the probe particle in a thermodynamically and dynamically consistent way. The coarse-grained rates obey a local detailed balance condition and reproduce the net currents. Moreover, the average entropy production as well as the thermodynamic efficiency is invariant under this coarse-graining procedure. Our analysis reveals that only by assuming unrealistically fast probe particles, the coarse-grained transition rates coincide with the transition rates of the traditionally used one-particle motor models. Additionally, we find that for multicyclic motors the stall force can depend on the probe size. We apply this coarse-graining method to specific case studies of the F1-ATPase and the kinesin motor.

  15. Coarse-graining and phase behavior of model star polymer-colloid mixtures in solvents of varying quality

    NASA Astrophysics Data System (ADS)

    Nikoubashman, Arash; Mahynski, Nathan A.; Capone, Barbara; Panagiotopoulos, Athanassios Z.; Likos, Christos N.

    2015-12-01

    We study the effective interactions and phase behavior of star polymer-colloid mixtures through theory and Monte Carlo simulations. We extend previous theoretical approaches for calculating the effective star-colloid pair potential to take into account attractive contributions, which become significant at worsening solvent conditions. In order to assess the validity of our simulation and theory, we compute the effective interactions via virtual move parallel tempering Monte Carlo simulations using a microscopic bead-spring model for the star polymer and achieve excellent agreement. Finally, we perform grand canonical Monte Carlo simulations of the coarse-grained systems to study the effect of solvent quality on the phase behavior.

  16. Formational Mechanisms and Morphology of Windblown Coarse-Grained Sand Ripples at White Sands, New Mexico

    NASA Astrophysics Data System (ADS)

    Glade, R.; Jerolmack, D. J.; Pelletier, J. D.

    2014-12-01

    Coarse-grained ripples, also known as "megaripples," are large sand ripples found in both aeolian and aquatic environments on Earth, and are common on Mars. The formation and morphology of coarse-grained ripples are not as well understood as more common splash ripples. Current understanding suggests that formative wind speeds are above the saltation threshold for the fine grains, but below this threshold for coarse grains found on the crests, such that they creep. Based on this idea, we hypothesize that wind speeds above this coarse-grain saltation threshold will destroy the ripples. We further hypothesize that these ripples do not have an equilibrium size; rather, their size is related to the persistence of formative winds in a given direction. To test this model, we studied windblown coarse-grained ripples in White Sands, New Mexico. Terrestrial LiDAR was used to obtain high resolution ripple morphology and migration over a three month period. Wind velocity profiles and concurrent saltating grain size data were collected during a wind storm to directly relate modes of transport to particle size and wind stress. These local data were used to calibrate wind records from a nearby meteorological station to estimate local fluid stress using a long-term record. LiDAR data indicate that these ripples were destroyed and reoriented between March and June 2013, while the wind record shows that the coarse-grain saltation threshold was indeed exceeded during this time. Morphological analysis indicates that the lee slope of these ripples is set by saltation impact - similar to splash ripples - but that height, wavelength and stoss slope are not related to instantaneous transport conditions. The historical wind record also shows that the range of wind directions decreases rapidly with increasing speed, restricting strong winds to a narrow range of direction. From these results we explore the idea that coarse-grained ripples are typically larger and less frequently destroyed

  17. Polarizable Water Model for the Coarse-Grained MARTINI Force Field

    PubMed Central

    Sengupta, Durba; Marrink, Siewert J.

    2010-01-01

    Coarse-grained (CG) simulations have become an essential tool to study a large variety of biomolecular processes, exploring temporal and spatial scales inaccessible to traditional models of atomistic resolution. One of the major simplifications of CG models is the representation of the solvent, which is either implicit or modeled explicitly as a van der Waals particle. The effect of polarization, and thus a proper screening of interactions depending on the local environment, is absent. Given the important role of water as a ubiquitous solvent in biological systems, its treatment is crucial to the properties derived from simulation studies. Here, we parameterize a polarizable coarse-grained water model to be used in combination with the CG MARTINI force field. Using a three-bead model to represent four water molecules, we show that the orientational polarizability of real water can be effectively accounted for. This has the consequence that the dielectric screening of bulk water is reproduced. At the same time, we parameterized our new water model such that bulk water density and oil/water partitioning data remain at the same level of accuracy as for the standard MARTINI force field. We apply the new model to two cases for which current CG force fields are inadequate. First, we address the transport of ions across a lipid membrane. The computed potential of mean force shows that the ions now naturally feel the change in dielectric medium when moving from the high dielectric aqueous phase toward the low dielectric membrane interior. In the second application we consider the electroporation process of both an oil slab and a lipid bilayer. The electrostatic field drives the formation of water filled pores in both cases, following a similar mechanism as seen with atomistically detailed models. PMID:20548957

  18. A unified data representation theory for network visualization, ordering and coarse-graining

    NASA Astrophysics Data System (ADS)

    Kovács, István A.; Mizsei, Réka; Csermely, Péter

    2015-09-01

    Representation of large data sets became a key question of many scientific disciplines in the last decade. Several approaches for network visualization, data ordering and coarse-graining accomplished this goal. However, there was no underlying theoretical framework linking these problems. Here we show an elegant, information theoretic data representation approach as a unified solution of network visualization, data ordering and coarse-graining. The optimal representation is the hardest to distinguish from the original data matrix, measured by the relative entropy. The representation of network nodes as probability distributions provides an efficient visualization method and, in one dimension, an ordering of network nodes and edges. Coarse-grained representations of the input network enable both efficient data compression and hierarchical visualization to achieve high quality representations of larger data sets. Our unified data representation theory will help the analysis of extensive data sets, by revealing the large-scale structure of complex networks in a comprehensible form.

  19. A unified data representation theory for network visualization, ordering and coarse-graining

    PubMed Central

    Kovács, István A.; Mizsei, Réka; Csermely, Péter

    2015-01-01

    Representation of large data sets became a key question of many scientific disciplines in the last decade. Several approaches for network visualization, data ordering and coarse-graining accomplished this goal. However, there was no underlying theoretical framework linking these problems. Here we show an elegant, information theoretic data representation approach as a unified solution of network visualization, data ordering and coarse-graining. The optimal representation is the hardest to distinguish from the original data matrix, measured by the relative entropy. The representation of network nodes as probability distributions provides an efficient visualization method and, in one dimension, an ordering of network nodes and edges. Coarse-grained representations of the input network enable both efficient data compression and hierarchical visualization to achieve high quality representations of larger data sets. Our unified data representation theory will help the analysis of extensive data sets, by revealing the large-scale structure of complex networks in a comprehensible form. PMID:26348923

  20. A Coarse Grained Model for Methylcellulose: Spontaneous Ring Formation at Elevated Temperature

    NASA Astrophysics Data System (ADS)

    Huang, Wenjun; Larson, Ronald

    Methylcellulose (MC) is widely used as food additives and pharma applications, where its thermo-reversible gelation behavior plays an important role. To date the gelation mechanism is not well understood, and therefore attracts great research interest. In this study, we adopted coarse-grained (CG) molecular dynamics simulations to model the MC chains, including the homopolymers and random copolymers that models commercial METHOCEL A, in an implicit water environment, where each MC monomer modeled with a single bead. The simulations are carried using a LAMMPS program. We parameterized our CG model using the radial distribution functions from atomistic simulations of short MC oligomers, extrapolating the results to long chains. We used dissociation free energy to validate our CG model against the atomistic model. The CG model captured the effects of monomer substitution type and temperature from the atomistic simulations. We applied this CG model to simulate single chains up to 1000 monomers long and obtained persistence lengths that are close to those determined from experiment. We observed the chain collapse transition for random copolymer at 600 monomers long at 50C. The chain collapsed into a stable ring structure with outer diameter around 14nm, which appears to be a precursor to the fibril structure observed in the methylcellulose gel observed by Lodge et al. in the recent studies. Our CG model can be extended to other MC derivatives for studying the interaction between these polymers and small molecules, such as hydrophobic drugs.

  1. Characterization of a potent antimicrobial lipopeptide via coarse-grained molecular dynamics

    PubMed Central

    Horn, Joshua N.; Sengillo, Jesse D.; Lin, Dejun; Romo, Tod D.; Grossfield, Alan

    2013-01-01

    The prevalence of antibiotic-resistant pathogens is a major medical concern, prompting increased interest in the development of novel antimicrobial compounds. One such set of naturally occurring compounds, known as antimicrobial peptides (AMPs), have broad-spectrum activity, but come with many limitations for clinical use. Recent work has resulted in a set of antimicrobial lipopeptides (AMLPs) with micromolar minimum inhibitory concentrations and excellent selectivity for bacterial membranes. To characterize a potent, synthetic lipopeptide, C16-KGGK, we used multi-microsecond coarse-grained simulations with the MARTINI forcefield, with a total simulation time of nearly 46 microseconds. These simulations show rapid binding of C16-KGGK, which forms micelles in solution, to model bacterial lipid bilayers. Furthermore, upon binding to the surface of the bilayer, these lipopeptides alter the local lipid organization by recruiting negatively charged POPG lipids to the site of binding. It is likely that this drastic reorganization of the bilayer has major effects on bilayer dynamics and cellular processes that depend on specific bilayer compositions. By contrast, the simulations revealed no association between the lipopeptides and model mammalian bilayers. These simulations provide biophysical insights into lipopeptide selectivity and suggest a possible mechanism for antimicrobial action. PMID:21819964

  2. Thermal dileptons from coarse-grained transport as fireball probes at SIS energies

    NASA Astrophysics Data System (ADS)

    Galatyuk, Tetyana; Hohler, Paul M.; Rapp, Ralf; Seck, Florian; Stroth, Joachim

    2016-05-01

    Utilizing a coarse-graining method to convert hadronic transport simulations of Au+Au collisions at SIS energies into local temperature, baryon and pion densities, we compute the pertinent radiation of thermal dileptons based on an in-medium ρ spectral function that describes available spectra at ultrarelativistic collision energies. In particular, we analyze how far the resulting yields and slopes of the invariant-mass spectra can probe the lifetime and temperatures of the fireball. We find that dilepton radiation sets in after the initial overlap phase of the colliding nuclei of about 7fm/ c, and lasts for about 13fm/ c. This duration closely coincides with the development of the transverse collectivity of the baryons, thus establishing a direct correlation between hadronic collective effects and thermal EM radiation, and supporting a near local equilibration of the system. This fireball "lifetime" is substantially smaller than the typical 20-30fm/ c that naive considerations of the density evolution alone would suggest. We furthermore find that the total dilepton yield radiated into the invariant-mass window of M=0.3 -0.7GeV/ c^2 normalized to the number of charged pions, follows a relation to the lifetime found earlier in the (ultra-) relativistic regime of heavy-ion collisions, and thus corroborates the versatility of this tool. The spectral slopes of the invariant-mass spectra above the φ -meson mass provide a thermometer of the hottest phases of the collision, and agree well with the maximal temperatures extracted from the coarse-grained hadron spectra.

  3. Atomistic simulations of dislocation pileup: Grain boundaries interaction

    SciTech Connect

    Wang, Jian

    2015-05-27

    Here, using molecular dynamics (MD) simulations, we studied the dislocation pileup–grain boundary (GB) interactions. Two Σ11 asymmetrical tilt grain boundaries in Al are studied to explore the influence of orientation relationship and interface structure on dislocation activities at grain boundaries. To mimic the reality of a dislocation pileup in a coarse-grained polycrystalline, we optimized the dislocation population in MD simulations and developed a predict-correct method to create a dislocation pileup in MD simulations. MD simulations explored several kinetic processes of dislocations–GB reactions: grain boundary sliding, grain boundary migration, slip transmission, dislocation reflection, reconstruction of grain boundary, and the correlation of these kinetic processes with the available slip systems across the GB and atomic structures of the GB.

  4. Atomistic simulations of dislocation pileup: Grain boundaries interaction

    DOE PAGESBeta

    Wang, Jian

    2015-05-27

    Here, using molecular dynamics (MD) simulations, we studied the dislocation pileup–grain boundary (GB) interactions. Two Σ11 asymmetrical tilt grain boundaries in Al are studied to explore the influence of orientation relationship and interface structure on dislocation activities at grain boundaries. To mimic the reality of a dislocation pileup in a coarse-grained polycrystalline, we optimized the dislocation population in MD simulations and developed a predict-correct method to create a dislocation pileup in MD simulations. MD simulations explored several kinetic processes of dislocations–GB reactions: grain boundary sliding, grain boundary migration, slip transmission, dislocation reflection, reconstruction of grain boundary, and the correlation ofmore » these kinetic processes with the available slip systems across the GB and atomic structures of the GB.« less

  5. Coarse-grained description of cosmic structure from Szekeres models

    NASA Astrophysics Data System (ADS)

    Sussman, Roberto A.; Delgado Gaspar, I.; Hidalgo, Juan Carlos

    2016-03-01

    We show that the full dynamical freedom of the well known Szekeres models allows for the description of elaborated 3-dimensional networks of cold dark matter structures (over-densities and/or density voids) undergoing ``pancake'' collapse. By reducing Einstein's field equations to a set of evolution equations, which themselves reduce in the linear limit to evolution equations for linear perturbations, we determine the dynamics of such structures, with the spatial comoving location of each structure uniquely specified by standard early Universe initial conditions. By means of a representative example we examine in detail the density contrast, the Hubble flow and peculiar velocities of structures that evolved, from linear initial data at the last scattering surface, to fully non-linear 10-20 Mpc scale configurations today. To motivate further research, we provide a qualitative discussion on the connection of Szekeres models with linear perturbations and the pancake collapse of the Zeldovich approximation. This type of structure modelling provides a coarse grained—but fully relativistic non-linear and non-perturbative —description of evolving large scale cosmic structures before their virialisation, and as such it has an enormous potential for applications in cosmological research.

  6. Experimental study on coarse grain saltation dynamics in bedrock channels

    NASA Astrophysics Data System (ADS)

    Chatanantavet, Phairot; Whipple, Kelin X.; Adams, Mark A.; Lamb, Michael P.

    2013-06-01

    of bed load particles on bedrock surfaces is important for landscape evolution and bedrock incision in steep landscapes. However, few studies have investigated saltation in bedrock channels where, unlike alluvial channels, the bed roughness height and the sediment size may be independent. To address this data gap, we measured the saltation hop height, hop length, and velocity of gravel saltating over a planar bed using 80-160 readings from high-speed photography and direct measurements. Two separate dimensional analyses are used: one leading to a bed shear stress scaling and another leading to a Froude number (Fr) scaling. Our new saltation data coupled with numerous data from previous studies suggest that both shear stress and Fr-scaling analyses are valid in characterizing bed load saltation dynamics with bed roughness ranging from smooth to alluvial beds. However, the Fr approach has the advantages that (1) there is no need to estimate a critical Shields stress τc*, which alone can vary up to 2 orders of magnitude (e.g., 0.001-0.1) due to changes in relative bed roughness and slope and (2) the Fr-based scaling fits the saltation data set better in a least squares sense. Results show that the saltation velocity of bed load is independent of grain density and grain size and is linearly proportional to flow velocity. Saltation height has a nonlinear dependence on grain size. Saltation length increases primarily with flow velocity, and it is inversely proportional to submerged specific density. Our results suggest that either τc* or bed roughness coefficient must be properly estimated to yield accurate results in saltation-abrasion models.

  7. A Coarse-Grained Model for Thermoresponsive Poly(N-isopropylacrylamide)

    NASA Astrophysics Data System (ADS)

    Abbott, Lauren J.; Stevens, Mark J.

    Poly(N-isopropylacrylamide) (PNIPAM) is a thermoresponsive polymer that undergoes a phase transition at its lower critical solution temperature (LCST). Although atomistic simulations have been effective to study PNIPAM single chains in solution, they are limited in reaching longer length- and time-scales. In this work, a coarse-grained (CG) model is developed for PNIPAM that captures its thermoresponsive behavior. Nonbonded parameters are fit to experimental thermodynamic data, with minor adjustments to provide better agreement with radial distribution functions from atomistic simulations. Bonded parameters are fit to probability distributions from atomistic simulations using multi-centered Gaussian-based potentials. The temperature-dependent potentials derived for the CG model in this work properly capture the coil-globule transition of PNIPAM single chains and yield a chain-length dependence consistent with atomistic simulations and experiment. The self-assembly of PNIPAM surfactants is also explored. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

  8. Segregation anisotropy of Sn on different crystallographic orientation surfaces of coarse-grained Zircaloy-4

    NASA Astrophysics Data System (ADS)

    Xie, Shijing; Zhou, Bangxin; Chen, Chuanming; Wang, Boyang; Jiang, Dong

    2016-02-01

    X-ray photoelectron spectroscopy (XPS) technique was utilized to study the correlation between the tendency of Sn surface segregation and the crystallographic orientation of grain surface in coarse-grained (0.2-0.8 mm in diameter) Zircaloy-4 specimen. The results indicated that the intensity of Sn surface segregation was in an order of (0001) < (1 bar 2 1 bar 0) ≈ (01 1 bar 0) , and it was in agreement with the prediction from bond-breaking theory.

  9. Improved Coarse-Grained Modeling of Cholesterol-Containing Lipid Bilayers

    SciTech Connect

    Daily, Michael D.; Olsen, Brett N.; Schlesinger, Paul H.; Ory, Daniel S.; Baker, Nathan A.

    2014-03-24

    In mammalian cells cholesterol is essential for membrane function, but in excess can be cytototoxic. The cellular response to acute cholesterol loading involves biophysical-based mechanisms that regulate cholesterol levels, through modulation of the “activity” or accessibility of cholesterol to extra-membrane acceptors. Experiments and united atom (UA) simulations show that at high concentrations of cholesterol, lipid bilayers thin significantly and cholesterol availability to external acceptors increases substantially. Such cholesterol activation is critical to its trafficking within cells. Here we aim to reduce the computational cost to enable simulation of large and complex systems involved in cholesterol regulation, such as those including oxysterols and cholesterol-sensing proteins. To accomplish this, we have modified the published MARTINI coarse-grained force field to improve its predictions of cholesterol-induced changes in both macroscopic and microscopic properties of membranes. Most notably, MARTINI fails to capture both the (macroscopic) area condensation and membrane thickening seen at less than 30% cholesterol and the thinning seen above 40% cholesterol. The thinning at high concentration is critical to cholesterol activation. Microscopic properties of interest include cholesterol-cholesterol radial distribution functions (RDFs), tilt angle, and accessible surface area. First, we develop an “angle-corrected” model wherein we modify the coarse-grained bond angle potentials based on atomistic simulations. This modification significantly improves prediction of macroscopic properties, most notably the thickening/thinning behavior, and also slightly improves microscopic property prediction relative to MARTINI. Second, we add to the angle correction a “volume correction” by also adjusting phospholipid bond lengths to achieve a more accurate volume per molecule. The angle + volume correction substantially further improves the quantitative

  10. Chondrule remelting: Evidence from coarse-grained chondrule rims and compound chondrules

    NASA Technical Reports Server (NTRS)

    Rubin, A. E.; Krot, A. N.

    1994-01-01

    The meteorites that best preserve the nebular record are the type 3 ordinary (OC) and carbonaceous chondrites; their major components include chondrules and chondrule fragments, refractory and mafic inclusions, FeO-rich silicate matrix material. Many chondrules are surrounded by nms; these can be divided into two major types: (1) fine-grained rims, which are composed of matrix material; and (2) igneous or coarse-grained rims, which have igneous textures and larger, less-ferroan mafic silicate grains. Fine-grained rims surround most of the chondrules in the least-equilibrated type 3 ordinary and carbonaceous chondrites. They were most likely derived via collapse of clumps of nebular dust that accreted around coarse objects such as chondrules and inclusions. Coarse-grined or igneous rims surround approximately 10% of the chondrules in type 3 OC and approximately 50% of the chondrules in CV3 chondrites as well as some chondrule fragments and isolated mineral grains. They probably formed by partly melting finer-grained dust-rich precursors and admixed chondrule fragments.

  11. A coarse grained protein model with internal degrees of freedom. Application to α-synuclein aggregation

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

    Particles in simulations are traditionally endowed with fixed interactions. While this is appropriate for particles representing atoms or molecules, objects with significant internal dynamics—like sequences of amino acids or even an entire protein—are poorly modelled by invariable particles. We develop a highly coarse grained polymorph patchy particle with the ultimate aim of simulating proteins as chains of particles at the secondary structure level. Conformational changes, e.g., a transition between disordered and β-sheet states, are accommodated by internal coordinates that determine the shape and interaction characteristics of the particles. The internal coordinates, as well as the particle positions and orientations, are propagated by Brownian Dynamics in response to their local environment. As an example of the potential offered by polymorph particles, we model the amyloidogenic intrinsically disordered protein α-synuclein, involved in Parkinson's disease, as a single particle with two internal states. The simulations yield oligomers of particles in the disordered state and fibrils of particles in the "misfolded" cross-β-sheet state. The aggregation dynamics is complex, as aggregates can form by a direct nucleation-and-growth mechanism and by two-step-nucleation through conversions between the two cluster types. The aggregation dynamics is complex, with fibrils formed by direct nucleation-and-growth, by two-step-nucleation through the conversion of an oligomer and by auto-catalysis of this conversion.

  12. Coarse-grained model of water diffusion and proton conductivity in hydrated polyelectrolyte membrane

    NASA Astrophysics Data System (ADS)

    Lee, Ming-Tsung; Vishnyakov, Aleksey; Neimark, Alexander V.

    2016-01-01

    Using dissipative particle dynamics (DPD), we simulate nanoscale segregation, water diffusion, and proton conductivity in hydrated sulfonated polystyrene (sPS). We employ a novel model [Lee et al. J. Chem. Theory Comput. 11(9), 4395-4403 (2015)] that incorporates protonation/deprotonation equilibria into DPD simulations. The polymer and water are modeled by coarse-grained beads interacting via short-range soft repulsion and smeared charge electrostatic potentials. The proton is introduced as a separate charged bead that forms dissociable Morse bonds with the base beads representing water and sulfonate anions. Morse bond formation and breakup artificially mimics the Grotthuss mechanism of proton hopping between the bases. The DPD model is parameterized by matching the proton mobility in bulk water, dissociation constant of benzenesulfonic acid, and liquid-liquid equilibrium of water-ethylbenzene solutions. The DPD simulations semi-quantitatively predict nanoscale segregation in the hydrated sPS into hydrophobic and hydrophilic subphases, water self-diffusion, and proton mobility. As the hydration level increases, the hydrophilic subphase exhibits a percolation transition from isolated water clusters to a 3D network. The analysis of hydrophilic subphase connectivity and water diffusion demonstrates the importance of the dynamic percolation effect of formation and breakup of temporary junctions between water clusters. The proposed DPD model qualitatively predicts the ratio of proton to water self-diffusion and its dependence on the hydration level that is in reasonable agreement with experiments.

  13. Coarse-grained model of water diffusion and proton conductivity in hydrated polyelectrolyte membrane.

    PubMed

    Lee, Ming-Tsung; Vishnyakov, Aleksey; Neimark, Alexander V

    2016-01-01

    Using dissipative particle dynamics (DPD), we simulate nanoscale segregation, water diffusion, and proton conductivity in hydrated sulfonated polystyrene (sPS). We employ a novel model [Lee et al. J. Chem. Theory Comput. 11(9), 4395-4403 (2015)] that incorporates protonation/deprotonation equilibria into DPD simulations. The polymer and water are modeled by coarse-grained beads interacting via short-range soft repulsion and smeared charge electrostatic potentials. The proton is introduced as a separate charged bead that forms dissociable Morse bonds with the base beads representing water and sulfonate anions. Morse bond formation and breakup artificially mimics the Grotthuss mechanism of proton hopping between the bases. The DPD model is parameterized by matching the proton mobility in bulk water, dissociation constant of benzenesulfonic acid, and liquid-liquid equilibrium of water-ethylbenzene solutions. The DPD simulations semi-quantitatively predict nanoscale segregation in the hydrated sPS into hydrophobic and hydrophilic subphases, water self-diffusion, and proton mobility. As the hydration level increases, the hydrophilic subphase exhibits a percolation transition from isolated water clusters to a 3D network. The analysis of hydrophilic subphase connectivity and water diffusion demonstrates the importance of the dynamic percolation effect of formation and breakup of temporary junctions between water clusters. The proposed DPD model qualitatively predicts the ratio of proton to water self-diffusion and its dependence on the hydration level that is in reasonable agreement with experiments. PMID:26747818

  14. Preface: Special Topic on Coarse Graining of Macromolecules, Biopolymers, and Membranes.

    PubMed

    Holm, Christian; Gompper, Gerhard; Dill, Ken A

    2015-12-28

    This special issue highlights new developments in theory and coarse-graining in biological and synthetic macromolecules and membranes. Such approaches give unique insights into the principles and design of the structures, dynamics, and assembly processes of these complex fluids and soft materials, where the length and time scales are often prohibitively long for fully atomistic modeling. PMID:26723585

  15. Preface: Special Topic on Coarse Graining of Macromolecules, Biopolymers, and Membranes

    NASA Astrophysics Data System (ADS)

    Holm, Christian; Gompper, Gerhard; Dill, Ken A.

    2015-12-01

    This special issue highlights new developments in theory and coarse-graining in biological and synthetic macromolecules and membranes. Such approaches give unique insights into the principles and design of the structures, dynamics, and assembly processes of these complex fluids and soft materials, where the length and time scales are often prohibitively long for fully atomistic modeling.

  16. Preface: Special Topic on Coarse Graining of Macromolecules, Biopolymers, and Membranes

    SciTech Connect

    Holm, Christian; Gompper, Gerhard; Dill, Ken A.

    2015-12-28

    This special issue highlights new developments in theory and coarse-graining in biological and synthetic macromolecules and membranes. Such approaches give unique insights into the principles and design of the structures, dynamics, and assembly processes of these complex fluids and soft materials, where the length and time scales are often prohibitively long for fully atomistic modeling.

  17. On the Investigation of Coarse-Grained Models for Water: Balancing Computational Efficiency and the Retention of Structural Properties

    PubMed Central

    Hadley, Kevin R.; McCabe, Clare

    2010-01-01

    Developing accurate models of water for use in computer simulations is important for the study of many chemical and biological systems, including lipid bilayer self-assembly. The large temporal and spatial scales needed to study such self-assembly have led to the development and application of coarse-grained models for the lipid-lipid, lipid-solvent and solvent-solvent interactions. Unfortunately, popular center-of-mass-based coarse-graining techniques are limited to modeling water with one-water per bead. In this work, we have utilized the K-means algorithm to determine the optimal clustering of waters to allow the mapping of multiple waters to single coarse-grained beads. Through the study of a simple mixture between water and an amphiphilic solute (1-pentanol), we find a 4-water bead model has the optimal balance between computational efficiency and accurate solvation and structural properties when compared to water models ranging from 1 to 9 waters per bead. The 4-water model was subsequently utilized in studies of the solvation of hexadecanoic acid and the structure, as measured via radial distribution functions, for the hydrophobic tails and the bulk water phase were found to agree well with experimental data and their atomistic targets. PMID:20230012

  18. Coarse-grained models using local-density potentials optimized with the relative entropy: Application to implicit solvation

    NASA Astrophysics Data System (ADS)

    Sanyal, Tanmoy; Shell, M. Scott

    2016-07-01

    Bottom-up multiscale techniques are frequently used to develop coarse-grained (CG) models for simulations at extended length and time scales but are often limited by a compromise between computational efficiency and accuracy. The conventional approach to CG nonbonded interactions uses pair potentials which, while computationally efficient, can neglect the inherently multibody contributions of the local environment of a site to its energy, due to degrees of freedom that were coarse-grained out. This effect often causes the CG potential to depend strongly on the overall system density, composition, or other properties, which limits its transferability to states other than the one at which it was parameterized. Here, we propose to incorporate multibody effects into CG potentials through additional nonbonded terms, beyond pair interactions, that depend in a mean-field manner on local densities of different atomic species. This approach is analogous to embedded atom and bond-order models that seek to capture multibody electronic effects in metallic systems. We show that the relative entropy coarse-graining framework offers a systematic route to parameterizing such local density potentials. We then characterize this approach in the development of implicit solvation strategies for interactions between model hydrophobes in an aqueous environment.

  19. Coarse-grained models using local-density potentials optimized with the relative entropy: Application to implicit solvation.

    PubMed

    Sanyal, Tanmoy; Shell, M Scott

    2016-07-21

    Bottom-up multiscale techniques are frequently used to develop coarse-grained (CG) models for simulations at extended length and time scales but are often limited by a compromise between computational efficiency and accuracy. The conventional approach to CG nonbonded interactions uses pair potentials which, while computationally efficient, can neglect the inherently multibody contributions of the local environment of a site to its energy, due to degrees of freedom that were coarse-grained out. This effect often causes the CG potential to depend strongly on the overall system density, composition, or other properties, which limits its transferability to states other than the one at which it was parameterized. Here, we propose to incorporate multibody effects into CG potentials through additional nonbonded terms, beyond pair interactions, that depend in a mean-field manner on local densities of different atomic species. This approach is analogous to embedded atom and bond-order models that seek to capture multibody electronic effects in metallic systems. We show that the relative entropy coarse-graining framework offers a systematic route to parameterizing such local density potentials. We then characterize this approach in the development of implicit solvation strategies for interactions between model hydrophobes in an aqueous environment. PMID:27448876

  20. Experimental Verification of a Critical Condition for the Formation of As-Cast Coarse Columnar Austenite Grain Structure in a Hyperperitectic Carbon Steel

    NASA Astrophysics Data System (ADS)

    Ohno, Munekazu; Maruyama, Masato; Matsuura, Kiyotaka

    2015-11-01

    Experimental verification of a critical condition for the formation of coarse columnar γ grain (CCG) structure in as-cast hyperperitectic carbon steels, which was put forward based on theories of grain growth and phase-field simulations in early studies, is carried out by means of a Bridgman-type directional solidification experiment. The occurrence of the discontinuous and continuous grain growth processes and the resulting formation of CCG and equiaxed γ grain structures, respectively, are demonstrated. Importantly, these changes of the as-cast microstructures and the grain growth modes are in excellent agreement with the previously proposed critical condition of the CCG formation.

  1. Bed Surface Characterisation in Coarse-Grained Alluvial Rivers

    NASA Astrophysics Data System (ADS)

    Nguyen, T. T.; Powell, M.; Tate, N.; Wood, J.; Rice, S. P.; Reid, I.; Ockelford, A.; Chorus

    2011-12-01

    Rivers are active agents of erosion and deposition, and the movement of sediment represents a logistic and sometimes strategic nuisance that affects road and rail communications, channel stability and river ecosystems. The processes of sediment transport are, however, still unclear to the extent that sediment transport rates are often greatly under- or over-predicted by existing predictive equations. Much of the uncertainty derives from the fact that the river bed is a complex arrangement of grains that is difficult to characterise. Quantifying the structural properties, or fabric, of water worked gravels and their topographic signatures in ways that can interface with quantitative analyses of flow and sediment transport is a particular problem. It remains a difficult modelling challenge that has yet to be fully solved. This paper presents some preliminary results from a flume study investigating the dynamics of bed surface structuring in gravel-bed rivers. The evolution of the bed during the experiments was characterised using measurements of surface microtopography extracted from high resolution bed elevation data collected using a Faro measuring arm laser scanner. The objective of the paper is to discuss the utility of a variety of aspatial and scale-based spatial and morphometric metrics which are used to quantify the developing microtopography and structure of the water-worked gravel surfaces.

  2. Application of electromagnetic acoustic transducers to coarse-grained material

    SciTech Connect

    Alers, G.A. )

    1991-07-01

    Electromagnetic Acoustic Transducers (EMATs) have certain advantages over piezoelectric transducers because they do not require a coupling medium between the part and the transducer and they can be designed to generate and detect focused sound waves of types unavailable to conventional probes. This program investigated a 500 kHz EMAT designed to focus Shear Horizontal ultrasonic waves onto the interior of centrifugally cast stainless steel (CCSS) in the hope that the large attenuation caused by scattering from the large grains could be minimized and reflections from small defects could be more easily detected. The results demonstrated that synthetic aperture focusing had to be used to distinguish flaw echoes from backscattered noise'' but that flaw detection by a pulse-echo technique was still difficult because of the attenuation of the signal as it propagated to and from the focal point. The ability to control the angle of injection of the sound beam by simply changing the frequency was demonstrated. 4 refs., 10 figs.

  3. Computational Study of Uniaxial Deformations in Silica Aerogel Using a Coarse-Grained Model.

    PubMed

    Ferreiro-Rangel, Carlos A; Gelb, Lev D

    2015-07-01

    Simulations of a flexible coarse-grained model are used to study silica aerogels. This model, introduced in a previous study (J. Phys. Chem. C 2007, 111, 15792), consists of spherical particles which interact through weak nonbonded forces and strong interparticle bonds that may form and break during the simulations. Small-deformation simulations are used to determine the elastic moduli of a wide range of material models, and large-deformation simulations are used to probe structural evolution and plastic deformation. Uniaxial deformation at constant transverse pressure is simulated using two methods: a hybrid Monte Carlo approach combining molecular dynamics for the motion of individual particles and stochastic moves for transverse stress equilibration, and isothermal molecular dynamics simulations at fixed Poisson ratio. Reasonable agreement on elastic moduli is obtained except at very low densities. The model aerogels exhibit Poisson ratios between 0.17 and 0.24, with higher-density gels clustered around 0.20, and Young's moduli that vary with aerogel density according to a power-law dependence with an exponent near 3.0. These results are in agreement with reported experimental values. The models are shown to satisfy the expected homogeneous isotropic linear-elastic relationship between bulk and Young's moduli at higher densities, but there are systematic deviations at the lowest densities. Simulations of large compressive and tensile strains indicate that these materials display a ductile-to-brittle transition as the density is increased, and that the tensile strength varies with density according to a power law, with an exponent in reasonable agreement with experiment. Auxetic behavior is observed at large tensile strains in some models. Finally, at maximum tensile stress very few broken bonds are found in the materials, in accord with the theory that only a small fraction of the material structure is actually load-bearing. PMID:26039801

  4. The role of Domain:Domain Interactions Vs Domain:Water Interactions in the coarse-grained simulations of the E1P to E2P transitions in Ca-ATPase (SERCA)

    PubMed Central

    Andersen, Jens Peter; Woolf, Thomas B.

    2012-01-01

    SERCA is an important model system for understanding the molecular details of conformational change in membrane transport systems. This reflects the large number of solved x-ray structures and the equally large database of mutations that have been assayed. In this computational study we provide a molecular dynamics description of the conformational changes during the E1P -> E2P transitions. This set of states further changes with insertion mutants in the A-M3 linker region. These mutants were experimentally shown to lead to significant shifts in rates between the E1P -> E2P states. Using the population shift framework and dynamic importance sampling method along with coarse-grained representations of the protein, lipid and water, we suggest why these changes are found. The calculations sample on intermediates and suggest that changes in interactions, individual helix interactions and water behavior are key elements in the molecular compositions that underlie shifts in kinetics. In particular, as the insertion length grows, it attracts more water and disrupts domain interactions, creating changes as well at the sites of key helix interactions between the A-Domain and the P-Domain. This provides a conceptual picture that aids understanding of the experimental results. PMID:22422644

  5. Photon and dilepton production at the Facility for Proton and Anti-Proton Research and beam-energy scan at the Relativistic Heavy-Ion Collider using coarse-grained microscopic transport simulations

    NASA Astrophysics Data System (ADS)

    Endres, Stephan; van Hees, Hendrik; Bleicher, Marcus

    2016-05-01

    We present calculations of dilepton and photon spectra for the energy range Elab=2 A to35 A GeV which will be available for the Compressed Baryonic Matter (CBM) experiment at the future Facility for Proton and Anti-Proton Research (FAIR). The same energy regime will also be covered by phase II of the beam-energy scan at the Relativistic Heavy-Ion Collider (RHIC-BES). Coarse-grained dynamics from microscopic transport calculations of the Ultrarelativistic Quantum Molecular Dynamics (UrQMD) model is used to determine temperature and chemical potentials, which allows for the use of dilepton and photon-emission rates from equilibrium quantum-field-theory calculations. The results indicate that nonequilibrium effects, the presence of baryonic matter, and the creation of a deconfined phase might show up in specific manners in the measurable dilepton invariant-mass spectra and in the photon transverse-momentum spectra. However, as the many influences are difficult to disentangle, we argue that the challenge for future measurements of electromagnetic probes will be to provide a high precision with uncertainties much lower than in previous experiments. Furthermore, a systematic study of the whole energy range covered by CBM at FAIR and RHIC-BES is necessary to discriminate between different effects, which influence the spectra, and to identify possible signatures of a phase transition.

  6. An experimentally-informed coarse-grained 3-Site-Per-Nucleotide model of DNA: structure, thermodynamics, and dynamics of hybridization.

    PubMed

    Hinckley, Daniel M; Freeman, Gordon S; Whitmer, Jonathan K; de Pablo, Juan J

    2013-10-14

    A new 3-Site-Per-Nucleotide coarse-grained model for DNA is presented. The model includes anisotropic potentials between bases involved in base stacking and base pair interactions that enable the description of relevant structural properties, including the major and minor grooves. In an improvement over available coarse-grained models, the correct persistence length is recovered for both ssDNA and dsDNA, allowing for simulation of non-canonical structures such as hairpins. DNA melting temperatures, measured for duplexes and hairpins by integrating over free energy surfaces generated using metadynamics simulations, are shown to be in quantitative agreement with experiment for a variety of sequences and conditions. Hybridization rate constants, calculated using forward-flux sampling, are also shown to be in good agreement with experiment. The coarse-grained model presented here is suitable for use in biological and engineering applications, including nucleosome positioning and DNA-templated engineering. PMID:24116642

  7. An experimentally-informed coarse-grained 3-site-per-nucleotide model of DNA: Structure, thermodynamics, and dynamics of hybridization

    PubMed Central

    Hinckley, Daniel M.; Freeman, Gordon S.; Whitmer, Jonathan K.; de Pablo, Juan J.

    2013-01-01

    A new 3-Site-Per-Nucleotide coarse-grained model for DNA is presented. The model includes anisotropic potentials between bases involved in base stacking and base pair interactions that enable the description of relevant structural properties, including the major and minor grooves. In an improvement over available coarse-grained models, the correct persistence length is recovered for both ssDNA and dsDNA, allowing for simulation of non-canonical structures such as hairpins. DNA melting temperatures, measured for duplexes and hairpins by integrating over free energy surfaces generated using metadynamics simulations, are shown to be in quantitative agreement with experiment for a variety of sequences and conditions. Hybridization rate constants, calculated using forward-flux sampling, are also shown to be in good agreement with experiment. The coarse-grained model presented here is suitable for use in biological and engineering applications, including nucleosome positioning and DNA-templated engineering. PMID:24116642

  8. Penetration strength of coarse granular materials from DEM simulations

    NASA Astrophysics Data System (ADS)

    Quezada, Juan Carlos; Saussine, Gilles; Breul, Pierre; Radjai, Farhang

    2013-06-01

    Field tests are widely used for soil characterization in geotechnical applications in spite of implementation difficulties. The light penetrometer test is a well-known testing tool for fine soils, but the physical interpretation of the output data in the case of coarse granular materials is far less evident. In fact, the data are considerably more sensitive to various parameters such as fabric structure, particles shape or the applied impact energy. In order to achieve a better understanding of the underlying phenomena, we performed a numerical study by means contact dynamics DEM simulations. We consider the penetration of a moving tip into a sample composed of irregular grain shapes and we analyze the influence of the driving velocity and applied energy on the penetration strength. We find that the latter grows with both the penetration rate and energy. Force fluctuations on the tip involve a jamming-unjamming process. The typology of contact network and inter-granular friction play a major role in the fluctuations and measured values of the cone penetration strength.

  9. Coarse-graining of cellular automata, emergence, and the predictability of complex systems

    NASA Astrophysics Data System (ADS)

    Israeli, Navot; Goldenfeld, Nigel

    2006-02-01

    We study the predictability of emergent phenomena in complex systems. Using nearest-neighbor, one-dimensional cellular automata (CA) as an example, we show how to construct local coarse-grained descriptions of CA in all classes of Wolfram’s classification. The resulting coarse-grained CA that we construct are capable of emulating the large-scale behavior of the original systems without accounting for small-scale details. Several CA that can be coarse-grained by this construction are known to be universal Turing machines; they can emulate any CA or other computing devices and are therefore undecidable. We thus show that because in practice one only seeks coarse-grained information, complex physical systems can be predictable and even decidable at some level of description. The renormalization group flows that we construct induce a hierarchy of CA rules. This hierarchy agrees well with apparent rule complexity and is therefore a good candidate for a complexity measure and a classification method. Finally we argue that the large-scale dynamics of CA can be very simple, at least when measured by the Kolmogorov complexity of the large-scale update rule, and moreover exhibits a novel scaling law. We show that because of this large-scale simplicity, the probability of finding a coarse-grained description of CA approaches unity as one goes to increasingly coarser scales. We interpret this large-scale simplicity as a pattern formation mechanism in which large-scale patterns are forced upon the system by the simplicity of the rules that govern the large-scale dynamics.

  10. An analytical coarse-graining method which preserves the free energy, structural correlations, and thermodynamic state of polymer melts from the atomistic to the mesoscale

    SciTech Connect

    McCarty, J.; Clark, A. J.; Copperman, J.; Guenza, M. G.

    2014-05-28

    Structural and thermodynamic consistency of coarse-graining models across multiple length scales is essential for the predictive role of multi-scale modeling and molecular dynamic simulations that use mesoscale descriptions. Our approach is a coarse-grained model based on integral equation theory, which can represent polymer chains at variable levels of chemical details. The model is analytical and depends on molecular and thermodynamic parameters of the system under study, as well as on the direct correlation function in the k → 0 limit, c{sub 0}. A numerical solution to the PRISM integral equations is used to determine c{sub 0}, by adjusting the value of the effective hard sphere diameter, d{sub HS}, to agree with the predicted equation of state. This single quantity parameterizes the coarse-grained potential, which is used to perform mesoscale simulations that are directly compared with atomistic-level simulations of the same system. We test our coarse-graining formalism by comparing structural correlations, isothermal compressibility, equation of state, Helmholtz and Gibbs free energies, and potential energy and entropy using both united atom and coarse-grained descriptions. We find quantitative agreement between the analytical formalism for the thermodynamic properties, and the results of Molecular Dynamics simulations, independent of the chosen level of representation. In the mesoscale description, the potential energy of the soft-particle interaction becomes a free energy in the coarse-grained coordinates which preserves the excess free energy from an ideal gas across all levels of description. The structural consistency between the united-atom and mesoscale descriptions means the relative entropy between descriptions has been minimized without any variational optimization parameters. The approach is general and applicable to any polymeric system in different thermodynamic conditions.

  11. Laser Processing of Coarse Grain Polycrystalline Diamond (PCD) Cutting Tool Inserts using Picosecond Laser Pulses

    NASA Astrophysics Data System (ADS)

    Dold, C.; Henerichs, M.; Gilgen, P.; Wegener, K.

    Manufacturing of cutting edges in PCD cutting tool inserts (CTI) using picosecond pulsewidth laser sources is presented. Cutting edge radii of redge = 5 to 6 μm are achieved. Validation experiments are carried out on a turning lathe using lasered and ground CTI on machining carbon fibre reinforced plastics (CFRP) which is mainly used for aircraft structures. Experiments are done on fine and coarse grain PCD structures (average grain sizes are 2-4 μm and 25 μm resepectively) which are not economical in the latter case if manufactured conventionally, e.g. using grinding processes. Wear resistance, tool lifetime and process forces can be improved if laser processed coarse grain cutting tools are employed.

  12. Coarse grain modeling of imperfect networks and gels

    NASA Astrophysics Data System (ADS)

    Sliozberg, Yelena; Chantawansri, Tanya; Sirk, Timothy; Andzelm, Jan; Mrozek, Randy; Lenhart, Joseph

    2013-03-01

    There is a strong interest in chemically and physically cross-linked entangled polymer networks and gels due to their tailorability in respect to both mechanical and structural properties. Even so, these properties are sensitive to imperfections in the polymer networks, such as dangling ends and loops. Computational modeling is a viable tool to understand the effects of these imperfections on properties in a controlled environment, in which specific defects can be systematically created and varied. In this study, we have employed generic bead-spring models of flexible chains to study a chemically and physically cross-linked network. Our results will show the importance defects, such as dangling ends and loops, on the mechanical and structural properties of these networks. We will also discuss the effects of these defects on the time-dependent elastic modulus. The simulation results qualitatively agree with experimental results and the other theoretical predictions.

  13. Coarse-grained molecular dynamics modeling of the kinetics of lamellar block copolymer defect annealing

    NASA Astrophysics Data System (ADS)

    Peters, Andrew J.; Lawson, Richard A.; Nation, Benjamin D.; Ludovice, Peter J.; Henderson, Clifford L.

    2016-01-01

    State-of-the-art block copolymer (BCP)-directed self-assembly (DSA) methods still yield defect densities orders of magnitude higher than is necessary in semiconductor fabrication despite free-energy calculations that suggest equilibrium defect densities are much lower than is necessary for economic fabrication. This disparity suggests that the main problem may lie in the kinetics of defect removal. This work uses a coarse-grained model to study the rates, pathways, and dependencies of healing a common defect to give insight into the fundamental processes that control defect healing and give guidance on optimal process conditions for BCP-DSA. It is found that bulk simulations yield an exponential drop in defect heal rate above χN˜30. Thin films show no change in rate associated with the energy barrier below χN˜50, significantly higher than the χN values found previously for self-consistent field theory studies that neglect fluctuations. Above χN˜50, the simulations show an increase in energy barrier scaling with 1/2 to 1/3 of the bulk systems. This is because thin films always begin healing at the free interface or the BCP-underlayer interface, where the increased A-B contact area associated with the transition state is minimized, while the infinitely thick films cannot begin healing at an interface.

  14. PaLaCe: A Coarse-Grain Protein Model for Studying Mechanical Properties.

    PubMed

    Pasi, Marco; Lavery, Richard; Ceres, Nicoletta

    2013-01-01

    We present a coarse-grain protein model PaLaCe (Pasi-Lavery-Ceres) that has been developed principally to allow fast computational studies of protein mechanics and to clarify the links between mechanics and function. PaLaCe uses a two-tier protein representation with one to three pseudoatoms representing each amino acid for the main nonbonded interactions, combined with atomic-scale peptide groups and some side chain atoms to allow the explicit representation of backbone hydrogen bonds and to simplify the treatment of bonded interactions. The PaLaCe force field is composed of physics-based terms, parametrized using Boltzmann inversion of conformational probability distributions derived from a protein structure data set, and iteratively refined to reproduce the experimental distributions. PaLaCe has been implemented in the MMTK simulation package and can be used for energy minimization, normal mode calculations, and molecular or stochastic dynamics. We present simulations with PaLaCe that test its ability to maintain stable structures for folded proteins, reproduce their dynamic fluctuations, and correctly model large-scale, force-induced conformational changes. PMID:26589071

  15. Self-assembly of Spherical Macroions in Solution: A Coarse-grained Molecular Dynamics Study

    NASA Astrophysics Data System (ADS)

    Liu, Zhuonan; Liu, Tianbo; Tsige, Mesfin

    2015-03-01

    Macroions (such as polyoxometalates) in solution can form a stable hollow spherical super-molecular structure called blackberry when they have moderate surface charge density and size (1-10 nm). Depending on the surface charge density of macroions, the size of the blackberry can be from 20 to more than 100 nm. Other macroions such as dendrimers can also self-assemble into similar super-molecular structure in solution. Existing theories such as Debye-Hückel and DLVO theories cannot explain this phenomenon and we are not aware of any other theory that can explain this. Previous studies using all-atom Molecular Dynamics simulations have shown identical macroions forming oligomers mediated by counterions. Due to the limitations in all-atom simulation and available computational capabilities, these studies handled only small systems with simple macroions, leading to less conclusive but still relevant results on the self-assembly behavior. To overcome these limitations, in this work large-scale coarse-grained modeling of macroions in solution is used. In order to understand the origin of the attractive force that is responsible for the self-assembly of macroions, different types of macroions in different solution conditions are studied. This work was supported by NSF Grant DMR0847580.

  16. Freezing Transitions of Nanoconfined Coarse-Grained Water Show Subtle Dependence on Confining Environment.

    PubMed

    Lu, Qing; Straub, John E

    2016-03-10

    The solid-to-liquid phase transition in water nanofilms confined between plates, with varying separations and water-plate interactions ranging from strongly hydrophobic to strongly hydrophilic, was simulated using a coarse-grained monatomic water model (mW) and the generalized replica exchange method (gREM). Extensive gREM simulations combined with the statistical temperature weighted histogram analysis method (ST-WHAM) provide a detailed description of the thermodynamic properties intrinsic to the phase transition, including the transition temperature, isobaric heat capacity, phase change enthalpy, entropy, and their dependence on the interplate distance and the plate-water interaction. The ice structure of water nanofilms was characterized at various conditions using the transverse density profile and the distribution of angles formed by hydrogen-bonded neighboring molecules. Flat bilayer ice was observed to be the dominant solid phase at close interplate distance, while puckered bilayer ice, similar to a slab of ice Ih, is the predominant structure at larger interplates. Stable puckered bilayer ice, previously observed to have a low melting point, is observed to have enhanced stability with high melting temperature when confined between hydrophilic plates. These results demonstrate the strong dependence of phase stability and coexistence in nanoconfined systems on the geometry and physical properties of the confining environment. PMID:26906259

  17. Combining coarse-grained nonbonded and atomistic bonded interactions for protein modeling.

    PubMed

    Zacharias, Martin

    2013-01-01

    A hybrid coarse-grained (CG) and atomistic (AT) model for protein simulations and rapid searching and refinement of peptide-protein complexes has been developed. In contrast to other hybrid models that typically represent spatially separate parts of a protein by either a CG or an AT force field model, the present approach simultaneously represents the protein by an AT (united atom) and a CG model. The interactions of the protein main chain are described based on the united atom force field allowing a realistic representation of protein secondary structures. In addition, the AT description of all other bonded interactions keeps the protein compatible with a realistic bonded geometry. Nonbonded interactions between side chains and side chains and main chain are calculated at the level of a CG model using a knowledge-based potential. Unrestrained molecular dynamics simulations on several test proteins resulted in trajectories in reasonable agreement with the corresponding experimental structures. Applications to the refinement of docked peptide-protein complexes resulted in improved complex structures. Application to the rapid refinement of docked protein-protein complex is also possible but requires further optimization of force field parameters. PMID:22911567

  18. A systematic procedure to build a relaxed dense-phase atomistic representation of a complex amorphous polymer using a coarse-grained modeling approach

    PubMed Central

    Li, Xianfeng; Latour, Robert A.

    2009-01-01

    A systematic procedure has been developed to construct a relaxed dense-phase atomistic structure of a complex amorphous polymer. The numerical procedure consists of (1) coarse graining the atomistic model of the polymer into a mesoscopic model based on an iterative algorithm for potential inversion from distribution functions of the atomistic model, (2) relaxation of the coarse grained chain using a molecular dynamics scheme, and (3) recovery of the atomistic structure by reverse mapping based on the superposition of atomistic counterparts on the corresponding coarse grained coordinates. These methods are demonstrated by their application to construct a relaxed, dense-phase model of poly(DTB succinate), which is an amorphous tyrosine-derived biodegradable polymer that is being developed for biomedical applications. Both static and dynamic properties from the coarse-grained and atomistic simulations are analyzed and compared. The coarse-grained model, which contains the essential features of the DTB succinate structure, successfully described both local and global structural properties of the atomistic chain. The effective speedup compared to the corresponding atomistic simulation is substantially above 102, thus enabling simulation times to reach well into the characteristic experimental regime. The computational approach for reversibly bridging between coarse-grained and atomistic models provides an efficient method to produce relaxed dense-phase all-atom molecular models of complex amorphous polymers that can subsequently be used to study and predict the atomistic-level behavior of the polymer under different environmental conditions in order to optimally design polymers for targeted applications. PMID:20161121

  19. A Coarse-Grained Model for Polyglutamine Aggregation Modulated by Amphipathic Flanking Sequences

    PubMed Central

    Ruff, Kiersten M.; Khan, Siddique J.; Pappu, Rohit V.

    2014-01-01

    The aggregation of proteins with expanded polyglutamine (polyQ) tracts is directly relevant to the formation of neuronal intranuclear inclusions in Huntington’s disease. In vitro studies have uncovered the effects of flanking sequences as modulators of the driving forces and mechanisms of polyQ aggregation in sequence segments associated with HD. Specifically, a seventeen-residue amphipathic stretch (N17) that is directly N-terminal to the polyQ tract in huntingtin decreases the overall solubility, destabilizes nonfibrillar aggregates, and accelerates fibril formation. Published results from atomistic simulations showed that the N17 module reduces the frequency of intermolecular association. Our reanalysis of these simulation results demonstrates that the N17 module also reduces interchain entanglements between polyQ domains. These two effects, which are observed on the smallest lengthscales, are incorporated into phenomenological pair potentials and used in coarse-grained Brownian dynamics simulations to investigate their impact on large-scale aggregation. We analyze the results from Brownian dynamics simulations using the framework of diffusion-limited cluster aggregation. When entanglements prevail, which is true in the absence of N17, small spherical clusters and large linear aggregates form on distinct timescales, in accord with in vitro experiments. Conversely, when entanglements are quenched and a barrier to intermolecular associations is introduced, both of which are attributable to N17, the timescales for forming small species and large linear aggregates become similar. Therefore, the combination of a reduction of interchain entanglements through homopolymeric polyQ and barriers to intermolecular associations appears to be sufficient for providing a minimalist phenomenological rationalization of in vitro observations regarding the effects of N17 on polyQ aggregation. PMID:25185558

  20. Thermodynamic and structural signatures of water-driven methane-methane attraction in coarse-grained mW water

    NASA Astrophysics Data System (ADS)

    Song, Bin; Molinero, Valeria

    2013-08-01

    Hydrophobic interactions are responsible for water-driven processes such as protein folding and self-assembly of biomolecules. Microscopic theories and molecular simulations have been used to study association of a pair of methanes in water, the paradigmatic example of hydrophobic attraction, and determined that entropy is the driving force for the association of the methane pair, while the enthalpy disfavors it. An open question is to which extent coarse-grained water models can still produce correct thermodynamic and structural signatures of hydrophobic interaction. In this work, we investigate the hydrophobic interaction between a methane pair in water at temperatures from 260 to 340 K through molecular dynamics simulations with the coarse-grained monatomic water model mW. We find that the coarse-grained model correctly represents the free energy of association of the methane pair, the temperature dependence of free energy, and the positive change in entropy and enthalpy upon association. We investigate the relationship between thermodynamic signatures and structural order of water through the analysis of the spatial distribution of the density, energy, and tetrahedral order parameter Qt of water. The simulations reveal an enhancement of tetrahedral order in the region between the first and second hydration shells of the methane molecules. The increase in tetrahedral order, however, is far from what would be expected for a clathrate-like or ice-like shell around the solutes. This work shows that the mW water model reproduces the key signatures of hydrophobic interaction without long ranged electrostatics or the need to be re-parameterized for different thermodynamic states. These characteristics, and its hundred-fold increase in efficiency with respect to atomistic models, make mW a promising water model for studying water-driven hydrophobic processes in more complex systems.

  1. Coarse-Grained Molecular Dynamics Study of the Curing and Properties of Highly Cross-Linked Epoxy Polymers.

    PubMed

    Aramoon, Amin; Breitzman, Timothy D; Woodward, Christopher; El-Awady, Jaafar A

    2016-09-01

    In this work, a coarse-grained model is developed for highly cross-linked bisphenol A diglycidyl ether epoxy resin with diaminobutane hardener. In this model, all conformationally relevant coarse-grained degrees of freedom are accounted for by sampling over the free-energy surfaces of the atomic structures using quantum mechanical simulations. The interaction potentials between nonbonded coarse-grained particles are optimized to accurately predict the experimentally measured density and glass-transition temperature of the system. In addition, a new curing algorithm is also developed to model the creation of highly cross-linked epoxy networks. In this algorithm, to create a highly cross-linked network, the reactants are redistributed from regions with an excessive number of reactive molecules to regions with a lower number of reactants to increase the chances of cross-linking. This new algorithm also dynamically controls the rate of cross-linking at each local region to ensure uniformity of the resulting network. The curing simulation conducted using this algorithm is able to develop polymeric networks having a higher average degree of cross-linking, which is more uniform throughout the simulation cell as compared to that in the networks cured using other curing algorithms. The predicted gel point from the current curing algorithm is in the acceptable theoretical and experimental range of measured values. Also, the resulting cross-linked microstructure shows a volume shrinkage of 5%, which is close to the experimentally measured volume shrinkage of the cured epoxy. Finally, the thermal expansion coefficients of materials in the glassy and rubbery states show good agreement with the experimental values. PMID:27504803

  2. A stochastic thermostat algorithm for coarse-grained thermomechanical modeling of large-scale soft matters: Theory and application to microfilaments

    SciTech Connect

    Li, Tong; Gu, YuanTong

    2014-04-15

    As all-atom molecular dynamics method is limited by its enormous computational cost, various coarse-grained strategies have been developed to extend the length scale of soft matters in the modeling of mechanical behaviors. However, the classical thermostat algorithm in highly coarse-grained molecular dynamics method would underestimate the thermodynamic behaviors of soft matters (e.g. microfilaments in cells), which can weaken the ability of materials to overcome local energy traps in granular modeling. Based on all-atom molecular dynamics modeling of microfilament fragments (G-actin clusters), a new stochastic thermostat algorithm is developed to retain the representation of thermodynamic properties of microfilaments at extra coarse-grained level. The accuracy of this stochastic thermostat algorithm is validated by all-atom MD simulation. This new stochastic thermostat algorithm provides an efficient way to investigate the thermomechanical properties of large-scale soft matters.

  3. Characterizing DNA Star-Tile-Based Nanostructures Using a Coarse-Grained Model.

    PubMed

    Schreck, John S; Romano, Flavio; Zimmer, Matthew H; Louis, Ard A; Doye, Jonathan P K

    2016-04-26

    We use oxDNA, a coarse-grained model of DNA at the nucleotide level, to simulate large nanoprisms that are composed of multi-arm star tiles, in which the size of bulge loops that have been incorporated into the tile design is used to control the flexibility of the tiles. The oxDNA model predicts equilibrium structures for several different nanoprism designs that are in excellent agreement with the experimental structures as measured by cryoTEM. In particular we reproduce the chiral twisting of the top and bottom faces of the nanoprisms, as the bulge sizes in these structures are varied due to the greater flexibility of larger bulges. We are also able to follow how the properties of the star tiles evolve as the prisms are assembled. Individual star tiles are very flexible, but their structures become increasingly well-defined and rigid as they are incorporated into larger assemblies. oxDNA also finds that the experimentally observed prisms are more stable than their inverted counterparts, but interestingly this preference for the arms of the tiles to bend in a given direction only emerges after they are part of larger assemblies. These results show the potential for oxDNA to provide detailed structural insight as well as to predict the properties of DNA nanostructures and hence to aid rational design in DNA nanotechnology. PMID:27010928

  4. Coarse-Grained Antibody Models for "Weak" Protein-Protein Interactions from Low to High Concentrations.

    PubMed

    Calero-Rubio, Cesar; Saluja, Atul; Roberts, Christopher J

    2016-07-14

    So-called "weak" protein-protein interactions are important for the control of solution properties and stability at elevated protein concentrations (c2) but are not practical to capture in atomistic simulations. This report focuses on a series of coarse-grained models for predicting second osmotic virial coefficients (B22) and high-concentration Rayleigh scattering (osmotic compressibility) as a function of c2 for monoclonal antibodies (MAbs) that are of interest in biotechnology. B22 and molecular volume along with c2-dependent osmotic compressibility were calculated for a series of models with increasing structural detail. Models were refined to include contributions from sterics, short-ranged van der Waals and hydrophobic attractions, screened electrostatics, and the flexibility of the mAb hinge region. The results highlight shortcomings for spherical models of MAbs and a useful balance between numerical accuracy and computational burden offered by models based on 6 or 12 spherical, partly overlapping domains. The results provide bounds for realistic values of effective charges on variable domains in order for MAbs to be stable in solution and more generally illustrate semiquantitative bounds for the space of model parameters that can reproduce experimental behavior and provide a basis for future development of computationally efficient and accurate CG mAb models to predict both low- and high-c2 behavior. PMID:27314827

  5. A transferable coarse-grained model for diphenylalanine: How to represent an environment driven conformational transition

    SciTech Connect

    Dalgicdir, Cahit; Sensoy, Ozge; Sayar, Mehmet; Peter, Christine

    2013-12-21

    One of the major challenges in the development of coarse grained (CG) simulation models that aim at biomolecular structure formation processes is the correct representation of an environment-driven conformational change, for example, a folding/unfolding event upon interaction with an interface or upon aggregation. In the present study, we investigate this transferability challenge for a CG model using the example of diphenylalanine. This dipeptide displays a transition from a trans-like to a cis-like conformation upon aggregation as well as upon transfer from bulk water to the cyclohexane/water interface. Here, we show that one can construct a single CG model that can reproduce both the bulk and interface conformational behavior and the segregation between hydrophobic/hydrophilic medium. While the general strategy to obtain nonbonded interactions in the present CG model is to reproduce solvation free energies of small molecules representing the CG beads in the respective solvents, the success of the model strongly depends on nontrivial decisions one has to make to capture the delicate balance between the bonded and nonbonded interactions. In particular, we found that the peptide's conformational behavior is qualitatively affected by the cyclohexane/water interaction potential, an interaction that does not directly involve the peptide at all but merely influences the properties of the hydrophobic/hydrophilic interface. Furthermore, we show that a small modification to improve the structural/conformational properties of the CG model could dramatically alter the thermodynamic properties.

  6. A transferable coarse-grained model for diphenylalanine: how to represent an environment driven conformational transition.

    PubMed

    Dalgicdir, Cahit; Sensoy, Ozge; Peter, Christine; Sayar, Mehmet

    2013-12-21

    One of the major challenges in the development of coarse grained (CG) simulation models that aim at biomolecular structure formation processes is the correct representation of an environment-driven conformational change, for example, a folding/unfolding event upon interaction with an interface or upon aggregation. In the present study, we investigate this transferability challenge for a CG model using the example of diphenylalanine. This dipeptide displays a transition from a trans-like to a cis-like conformation upon aggregation as well as upon transfer from bulk water to the cyclohexane/water interface. Here, we show that one can construct a single CG model that can reproduce both the bulk and interface conformational behavior and the segregation between hydrophobic/hydrophilic medium. While the general strategy to obtain nonbonded interactions in the present CG model is to reproduce solvation free energies of small molecules representing the CG beads in the respective solvents, the success of the model strongly depends on nontrivial decisions one has to make to capture the delicate balance between the bonded and nonbonded interactions. In particular, we found that the peptide's conformational behavior is qualitatively affected by the cyclohexane/water interaction potential, an interaction that does not directly involve the peptide at all but merely influences the properties of the hydrophobic/hydrophilic interface. Furthermore, we show that a small modification to improve the structural/conformational properties of the CG model could dramatically alter the thermodynamic properties. PMID:24359360

  7. A transferable coarse-grained model for diphenylalanine: How to represent an environment driven conformational transition

    NASA Astrophysics Data System (ADS)

    Dalgicdir, Cahit; Sensoy, Ozge; Peter, Christine; Sayar, Mehmet

    2013-12-01

    One of the major challenges in the development of coarse grained (CG) simulation models that aim at biomolecular structure formation processes is the correct representation of an environment-driven conformational change, for example, a folding/unfolding event upon interaction with an interface or upon aggregation. In the present study, we investigate this transferability challenge for a CG model using the example of diphenylalanine. This dipeptide displays a transition from a trans-like to a cis-like conformation upon aggregation as well as upon transfer from bulk water to the cyclohexane/water interface. Here, we show that one can construct a single CG model that can reproduce both the bulk and interface conformational behavior and the segregation between hydrophobic/hydrophilic medium. While the general strategy to obtain nonbonded interactions in the present CG model is to reproduce solvation free energies of small molecules representing the CG beads in the respective solvents, the success of the model strongly depends on nontrivial decisions one has to make to capture the delicate balance between the bonded and nonbonded interactions. In particular, we found that the peptide's conformational behavior is qualitatively affected by the cyclohexane/water interaction potential, an interaction that does not directly involve the peptide at all but merely influences the properties of the hydrophobic/hydrophilic interface. Furthermore, we show that a small modification to improve the structural/conformational properties of the CG model could dramatically alter the thermodynamic properties.

  8. In-medium Spectral Functions in a Coarse-Graining Approach

    NASA Astrophysics Data System (ADS)

    Endres, Stephan; van Hees, Hendrik; Weil, Janus; Bleicher, Marcus

    2015-04-01

    We use a coarse-graining approach to extract local thermodynamic properties from simulations with a microscopic transport model by averaging over a large ensemble of events. Setting up a grid of small space-time cells and going into each cell's rest frame allows to determine baryon and energy density. With help of an equation of state we get the corresponding temperature T and baryon-chemical potential μB. These results are used for the calculation of the thermal dilepton yield. We apply and compare two different spectral functions for the ρ meson, firstly a calculation from hadronic many-body theory and secondly a calculation from experimental scattering amplitudes. The results obtained with our approach are compared to measurements of the NA60 Collaboration. A relatively good description of the data is achieved with both spectral functions. However, the hadronic many-body calculation is found to be closer to the experimental data with regard to the in-medium broadening of the spectral shape.

  9. Concurrent parametrization against static and kinetic information leads to more robust coarse-grained force fields

    NASA Astrophysics Data System (ADS)

    Rudzinski, J. F.; Bereau, T.

    2016-07-01

    The parametrization of coarse-grained (CG) simulation models for molecular systems often aims at reproducing static properties alone. The reduced molecular friction of the CG representation usually results in faster, albeit inconsistent, dynamics. In this work, we rely on Markov state models to simultaneously characterize the static and kinetic properties of two CG peptide force fields—one top-down and one bottom-up. Instead of a rigorous evolution of CG dynamics (e.g., using a generalized Langevin equation), we attempt to improve the description of kinetics by simply altering the existing CG models, which employ standard Langevin dynamics. By varying masses and relevant force-field parameters, we can improve the timescale separation of the slow kinetic processes, achieve a more consistent ratio of mean-first-passage times between metastable states, and refine the relative free-energies between these states. Importantly, we show that the incorporation of kinetic information into a structure-based parametrization improves the description of the helix-coil transition sampled by a minimal CG model. While structure-based models understabilize the helical state, kinetic constraints help identify CG models that improve the ratio of forward/backward timescales by effectively hindering the sampling of spurious conformational intermediate states.

  10. Stretching and twisting of the DNA duplexes in coarse-grained dynamical models.

    PubMed

    Niewieczerzał, Szymon; Cieplak, Marek

    2009-11-25

    Three coarse-grained molecular dynamics models of the double-stranded DNA are proposed and compared in the context of single molecule mechanical manipulation such as twisting and various schemes of stretching-unzipping, shearing, two-strand stretching and stretching of only one strand. The models differ in the number of effective beads (between two and five) representing each nucleotide. They all show similar behaviour, but the bigger the resolution, the more details in the force patterns. The models incorporate the effective Lennard-Jones potentials in the couplings between two strands and harmonic potentials to describe the structure of a single strand. The force patterns are shown to depend on the sequence studied. In particular, both shearing and unzipping for an all-AT sequence lead to lower forces than for an all-CG sequence. The unzipping patterns and the corresponding scenario diagrams for the contact rupture events are found to reflect the sequential information if the temperature is moderate and initial transients are discarded. The derived torque-force phase diagram is found to be qualitatively consistent with experiments and all-atom simulations. PMID:21832500

  11. Stretching and twisting of the DNA duplexes in coarse-grained dynamical models

    NASA Astrophysics Data System (ADS)

    Niewieczerzał, Szymon; Cieplak, Marek

    2009-11-01

    Three coarse-grained molecular dynamics models of the double-stranded DNA are proposed and compared in the context of single molecule mechanical manipulation such as twisting and various schemes of stretching—unzipping, shearing, two-strand stretching and stretching of only one strand. The models differ in the number of effective beads (between two and five) representing each nucleotide. They all show similar behaviour, but the bigger the resolution, the more details in the force patterns. The models incorporate the effective Lennard-Jones potentials in the couplings between two strands and harmonic potentials to describe the structure of a single strand. The force patterns are shown to depend on the sequence studied. In particular, both shearing and unzipping for an all-AT sequence lead to lower forces than for an all-CG sequence. The unzipping patterns and the corresponding scenario diagrams for the contact rupture events are found to reflect the sequential information if the temperature is moderate and initial transients are discarded. The derived torque-force phase diagram is found to be qualitatively consistent with experiments and all-atom simulations.

  12. Introducing improved structural properties and salt dependence into a coarse-grained model of DNA

    SciTech Connect

    Snodin, Benedict E. K. Mosayebi, Majid; Schreck, John S.; Romano, Flavio; Doye, Jonathan P. K.; Randisi, Ferdinando; Šulc, Petr; Ouldridge, Thomas E.; Tsukanov, Roman; Nir, Eyal; Louis, Ard A.

    2015-06-21

    We introduce an extended version of oxDNA, a coarse-grained model of deoxyribonucleic acid (DNA) designed to capture the thermodynamic, structural, and mechanical properties of single- and double-stranded DNA. By including explicit major and minor grooves and by slightly modifying the coaxial stacking and backbone-backbone interactions, we improve the ability of the model to treat large (kilobase-pair) structures, such as DNA origami, which are sensitive to these geometric features. Further, we extend the model, which was previously parameterised to just one salt concentration ([Na{sup +}] = 0.5M), so that it can be used for a range of salt concentrations including those corresponding to physiological conditions. Finally, we use new experimental data to parameterise the oxDNA potential so that consecutive adenine bases stack with a different strength to consecutive thymine bases, a feature which allows a more accurate treatment of systems where the flexibility of single-stranded regions is important. We illustrate the new possibilities opened up by the updated model, oxDNA2, by presenting results from simulations of the structure of large DNA objects and by using the model to investigate some salt-dependent properties of DNA.

  13. Derivation of coarse-grained potentials via multistate iterative Boltzmann inversion

    PubMed Central

    Moore, Timothy C.; Iacovella, Christopher R.; McCabe, Clare

    2014-01-01

    In this work, an extension is proposed to the standard iterative Boltzmann inversion (IBI) method used to derive coarse-grained potentials. It is shown that the inclusion of target data from multiple states yields a less state-dependent potential, and is thus better suited to simulate systems over a range of thermodynamic states than the standard IBI method. The inclusion of target data from multiple states forces the algorithm to sample regions of potential phase space that match the radial distribution function at multiple state points, thus producing a derived potential that is more representative of the underlying interactions. It is shown that the algorithm is able to converge to the true potential for a system where the underlying potential is known. It is also shown that potentials derived via the proposed method better predict the behavior of n-alkane