Science.gov

Sample records for coarse-grained structural modeling

  1. 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.

  2. 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.

  3. 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.

  4. Predicting RNA 3D structure using a coarse-grain helix-centered model

    PubMed Central

    Kerpedjiev, Peter; Höner zu Siederdissen, Christian; Hofacker, Ivo L.

    2015-01-01

    A 3D model of RNA structure can provide information about its function and regulation that is not possible with just the sequence or secondary structure. Current models suffer from low accuracy and long running times and either neglect or presume knowledge of the long-range interactions which stabilize the tertiary structure. Our coarse-grained, helix-based, tertiary structure model operates with only a few degrees of freedom compared with all-atom models while preserving the ability to sample tertiary structures given a secondary structure. It strikes a balance between the precision of an all-atom tertiary structure model and the simplicity and effectiveness of a secondary structure representation. It provides a simplified tool for exploring global arrangements of helices and loops within RNA structures. We provide an example of a novel energy function relying only on the positions of stems and loops. We show that coupling our model to this energy function produces predictions as good as or better than the current state of the art tools. We propose that given the wide range of conformational space that needs to be explored, a coarse-grain approach can explore more conformations in less iterations than an all-atom model coupled to a fine-grain energy function. Finally, we emphasize the overarching theme of providing an ensemble of predicted structures, something which our tool excels at, rather than providing a handful of the lowest energy structures. PMID:25904133

  5. 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

  6. Protein secondary-structure description with a coarse-grained model.

    PubMed

    Kneller, Gerald R; Hinsen, Konrad

    2015-07-01

    A coarse-grained geometrical model for protein secondary-structure description and analysis is presented which uses only the positions of the C(α) atoms. A space curve connecting these positions by piecewise polynomial interpolation is constructed and the folding of the protein backbone is described by a succession of screw motions linking the Frenet frames at consecutive C(α) positions. Using the ASTRAL subset of the SCOPe database of protein structures, thresholds are derived for the screw parameters of secondary-structure elements and demonstrate that the latter can be reliably assigned on the basis of a C(α) model. For this purpose, a comparative study with the widely used DSSP (Define Secondary Structure of Proteins) algorithm was performed and it was shown that the parameter distribution corresponding to the ensemble of all pure C(α) structures in the RCSB Protein Data Bank matches that of the ASTRAL database. It is expected that this approach will be useful in the development of structure-refinement techniques for low-resolution data. PMID:26143913

  7. 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.

  8. Tetrahedrality and structural order for hydrophobic interactions in a coarse-grained water model

    NASA Astrophysics Data System (ADS)

    Chaimovich, Aviel; Shell, M. Scott

    2014-02-01

    The hydrophobic interaction manifests two separate regimes in terms of size: Small nonpolar bodies exhibit a weak oscillatory force (versus distance) while large nonpolar surfaces exhibit a strong monotonic one. This crossover in hydrophobic behavior is typically explained in terms of water's tetrahedral structure: Its tetrahedrality is enhanced near small solutes and diminished near large planar ones. Here, we demonstrate that water's tetrahedral correlations signal this switch even in a highly simplified, isotropic, "core-softened" water model. For this task, we introduce measures of tetrahedrality based on the angular distribution of water's nearest neighbors. On a quantitative basis, the coarse-grained model of course is only approximate: (1) While greater than simple Lennard-Jones liquids, its bulk tetrahedrality remains lower than that of fully atomic models; and (2) the decay length of the large-scale hydrophobic interaction is less than has been found in experiments. Even so, the qualitative behavior of the model is surprisingly rich and exhibits numerous waterlike hydrophobic behaviors, despite its simplicity. We offer several arguments for the manner in which it should be able to (at least partially) reproduce tetrahedral correlations underlying these effects.

  9. 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.

  10. Probing the structural dynamics of the SNARE recycling machine based on coarse-grained modeling.

    PubMed

    Zheng, Wenjun

    2016-08-01

    Membrane fusion in eukaryotes is driven by the formation of a four-helix bundle by three SNARE proteins. To recycle the SNARE proteins, they must be disassembled by the ATPase NSF and four SNAP proteins which together form a 20S supercomplex. Recently, the first high-resolution structures of the NSF (in both ATP and ADP state) and 20S (in four distinct states termed I, II, IIIa, and IIIb) were solved by cryo-electron microscopy (cryo-EM), which have paved the way for structure-driven studies of the SNARE recycling mechanism. To probe the structural dynamics of SNARE disassembly at amino-acid level of details, a systematic coarse-grained modeling based on an elastic network model and related analyses were performed. Our normal mode analysis of NSF, SNARE, and 20S predicted key modes of collective motions that partially account for the observed structural changes, and illuminated how the SNARE complex can be effectively destabilized by untwisting and bending motions of the SNARE complex driven by the amino-terminal domains of NSF in state II. Our flexibility analysis identified regions with high/low flexibility that coincide with key functional sites (such as the NSF-SNAPs-SNARE binding sites). A subset of hotspot residues that control the above collective motions, which will make promising targets for future mutagenesis studies were also identified. Finally, the conformational changes in 20S as induced by the transition of NSF from ATP to ADP state were modeled, and a concerted untwisting motion of SNARE/SNAPs and a sideway flip of two amino-terminal domains were observed. In sum, the findings have offered new structural and dynamic details relevant to the SNARE disassembly mechanism, and will guide future functional studies of the SNARE recycling machinery. Proteins 2016; 84:1055-1066. © 2016 Wiley Periodicals, Inc. PMID:27090373

  11. Nucleotide-induced conformational dynamics in ABC transporters from structure-based coarse grained modelling.

    NASA Astrophysics Data System (ADS)

    Flechsig, Holger

    2016-02-01

    ATP-binding cassette (ABC) transporters are integral membrane proteins which mediate the exchange of diverse substrates across membranes powered by ATP molecules. Our understanding of their activity is still hampered since the conformational dynamics underlying the operation of such proteins cannot yet be resolved in detailed molecular dynamics studies. Here a coarse grained model which allows to mimic binding of nucleotides and follow subsequent conformational motions of full-length transporter structures in computer simulations is proposed and implemented. To justify its explanatory quality, the model is first applied to the maltose transporter system for which multiple conformations are known and we find that the model predictions agree remarkably well with the experimental data. For the MalK subunit the switching from open to the closed dimer configuration upon ATP binding is reproduced and, moreover, for the full-length maltose transporter, progression from inward-facing to the outward-facing state is correctly obtained. For the heme transporter HmuUV, for which only the free structure could yet be determined, the model was then applied to predict nucleotide-induced conformational motions. Upon binding of ATP-mimicking ligands the structure changed from a conformation in which the nucleotide-binding domains formed an open shape, to a conformation in which they were found in tight contact, while, at the same time, a pronounced rotation of the transmembrane domains was observed. This finding is supported by normal mode analysis, and, comparison with structural data of the homologous vitamin B12 transporter BtuCD suggests that the observed rotation mechanism may contribute a common functional aspect for this class of ABC transporters. Although in HmuuV noticeable rearrangement of essential transmembrane helices was detected, there are no indications from our simulations that ATP binding alone may facilitate propagation of substrate molecules in this transporter

  12. 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

  13. Bottom-up coarse-grained models that accurately describe the structure, pressure, and compressibility of molecular liquids

    SciTech Connect

    Dunn, Nicholas J. H.; Noid, W. G.

    2015-12-28

    The present work investigates the capability of bottom-up coarse-graining (CG) methods for accurately modeling both structural and thermodynamic properties of all-atom (AA) models for molecular liquids. In particular, we consider 1, 2, and 3-site CG models for heptane, as well as 1 and 3-site CG models for toluene. For each model, we employ the multiscale coarse-graining method to determine interaction potentials that optimally approximate the configuration dependence of the many-body potential of mean force (PMF). We employ a previously developed “pressure-matching” variational principle to determine a volume-dependent contribution to the potential, U{sub V}(V), that approximates the volume-dependence of the PMF. We demonstrate that the resulting CG models describe AA density fluctuations with qualitative, but not quantitative, accuracy. Accordingly, we develop a self-consistent approach for further optimizing U{sub V}, such that the CG models accurately reproduce the equilibrium density, compressibility, and average pressure of the AA models, although the CG models still significantly underestimate the atomic pressure fluctuations. Additionally, by comparing this array of models that accurately describe the structure and thermodynamic pressure of heptane and toluene at a range of different resolutions, we investigate the impact of bottom-up coarse-graining upon thermodynamic properties. In particular, we demonstrate that U{sub V} accounts for the reduced cohesion in the CG models. Finally, we observe that bottom-up coarse-graining introduces subtle correlations between the resolution, the cohesive energy density, and the “simplicity” of the model.

  14. 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

  15. 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.

  16. A coarse-grained model with implicit salt for RNAs: Predicting 3D structure, stability and salt effect

    SciTech Connect

    Shi, Ya-Zhou; Wang, Feng-Hua; Wu, Yuan-Yan; Tan, Zhi-Jie

    2014-09-14

    To bridge the gap between the sequences and 3-dimensional (3D) structures of RNAs, some computational models have been proposed for predicting RNA 3D structures. However, the existed models seldom consider the conditions departing from the room/body temperature and high salt (1M NaCl), and thus generally hardly predict the thermodynamics and salt effect. In this study, we propose a coarse-grained model with implicit salt for RNAs to predict 3D structures, stability, and salt effect. Combined with Monte Carlo simulated annealing algorithm and a coarse-grained force field, the model folds 46 tested RNAs (≤45 nt) including pseudoknots into their native-like structures from their sequences, with an overall mean RMSD of 3.5 Å and an overall minimum RMSD of 1.9 Å from the experimental structures. For 30 RNA hairpins, the present model also gives the reliable predictions for the stability and salt effect with the mean deviation ∼ 1.0 °C of melting temperatures, as compared with the extensive experimental data. In addition, the model could provide the ensemble of possible 3D structures for a short RNA at a given temperature/salt condition.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. Native state dynamics and mechanical properties of human topoisomerase I within a structure-based coarse-grained model.

    PubMed

    Szklarczyk, Oliwia; Staroń, Krzysztof; Cieplak, Marek

    2009-11-01

    A coarse grained molecular dynamics model with an implicit solvent is used to elucidate properties of the human topoisomerase I. The model is defined through the native structure and it allows covering significantly longer time scales than in all atom simulations. Single residue and double residue motional characteristics are studied. The results are consistent with all atom simulations reported in the literature indicating usefulness of the model in further studies of this protein. Novel findings include broadening of the description of the dynamic behavior of the lip and hinge regions and a characterization of the motional properties of the RRM binding site of the enzyme. We also consider mechanical stretching of the protein and identify sources of the force peaks. The elastic properties of topoisomerase I are predicted to be average in comparison to other proteins, yielding a maximum force of resistance to pulling which should be of order 120 pN. The contact unraveling pattern is consistent with the understanding of the structure and function of the protein. We find supporting evidence for the hypothesis that the C-terminal domain acquires an ordered structure upon binding with the core enzyme even though it forms a molten globule when in isolation. PMID:19452556

  8. 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.

  9. 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.

  10. Coarse-grained modeling of the structural states and transition underlying the powerstroke of dynein motor domain.

    PubMed

    Zheng, Wenjun

    2012-04-21

    This study aims to model a minimal dynein motor domain capable of motor function, which consists of the linker domain, six AAA+ modules (AAA1-AAA6), coiled coil stalk, and C-terminus domain. To this end, we have used the newly solved X-ray structures of dynein motor domain to perform a coarse-grained modeling of dynein's post- and pre-powerstroke conformation and the conformational transition between them. First, we have used normal mode analysis to identify a single normal mode that captures the coupled motions of AAA1-AAA2 closing and linker domain rotation, which enables the ATP-driven recovery stroke of dynein. Second, based on the post-powerstroke conformation solved crystallographically, we have modeled dynein's pre-powerstroke conformation by computationally inducing AAA1-AAA2 closing and sliding of coiled coil stalk, and the resulting model features a linker domain near the pre-powerstroke position and a slightly tilted stalk. Third, we have modeled the conformational transition from pre- to post-powerstroke conformation, which predicts a clear sequence of structural events that couple microtubule binding, powerstroke and product release, and supports a signaling path from stalk to AAA1 via AAA3 and AAA4. Finally, we have found that a closed AAA3-AAA4 interface (compatible with nucleotide binding) is essential to the mechano-chemical coupling in dynein. Our modeling not only offers unprecedented structural insights to the motor function of dynein as described by past single-molecule, fluorescence resonance energy transfer, and electron microscopy studies, but also provides new predictions for future experiments to test. PMID:22519354

  11. 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

  12. Coarse grained models, bond orientational order, and the structural characterization of residue networks

    NASA Astrophysics Data System (ADS)

    Ortiz, Carlos Pompeyo

    Rigidity emerges in a broad class of soft matter systems, relevant to many industrial and biological processes. In our experiments, we study a model soft matter system, hard-sphere Brownian suspensions of submicron particles. Brownian suspensions lack rigidity in the absence of external driving, but form flow-stabilized solid-like microsphere heaps under the influence of hydrodynamic forces. The overarching question driving my dissertation is "What is the nature of the rigidity of these microsphere heaps?" Does the rigidity of the heaps follow from mechanical stability driven by a sufficiently interconnected network of particle contacts? Or, does the rigidity of the heaps follow from a kinetic glass transition characterized by a diverging resistance to flow such that the time necessary to observe rearrangements grows prohibitively large? We expect that insights into the mechanism of rigidity of Brownian microsphere heaps are applicable to a wide class of soft matter systems. In this thesis,we have overcome the limitations of previous experimental approaches. Namely, we show that the rigidity of our heaps does not emerge from the effects of gravity, inertia, static friction, or van der Waals sticking. In Chapter 1 of thesis, we review the background literature. In Chapter 2, we present the experimental, analytical, and computational methods used in the remainder of the thesis. In Chapter 3, we investigate the onset of rigidity by characterizing the steady-state size of the heap versus the imposed flow conditions. We show that thermal fluctuations and repulsive interparticle interactions, the dominant forces at the single-particle scale, suppress the development of a rigid phase. These conditions imply that the onset of rigidity in involves many-body collective interactions. In Chapter 4, we measure the response of the heap to external perturbations, which allows us to measure their elastic modulus and compare our results to hard sphere theoretical expectations. We

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. 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.

  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. 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.

  4. 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

  5. A Model for Structure and Thermodynamics of ssDNA and dsDNA Near a Surface: A Coarse Grained Approach

    SciTech Connect

    Ambia Garrido, Joaquin; Vainrub, Arnold; Pettitt, Bernard M.

    2010-12-01

    New methods based on surfaces or beads have allowed measurement of properties of single DNA molecules in very accurate ways. Theoretical coarse grained models have been developed to understand the behavior of single stranded and double stranded DNA. These models have been shown to be accurate and relatively simple for very short systems of 6–8 base pairs near surfaces. Comparatively less is known about the influence of a surface on the secondary structures of longer molecules important to many technologies. Surface fields due to either applied potentials and/or dielectric boundaries are not in current surface mounted coarse grained models. To gain insight into longer and surface mounted sequences we parameterized a discretized worm-like chain model. Each link is considered a sphere of 6 base pairs in length for dsDNA, and 1.5 bases for ssDNA (requiring an always even number of spheres). For this demonstration of the model, the chain is tethered to a surface by a fixed length, non-interacting 0.536 nm linker. Configurational sampling was achieved via Monte Carlo simulation. Our model successfully reproduces end to end distance averages from experimental results, in agreement with polymer theory and all-atom simulations. Our average tilt results are also in agreement with allatom simulations for the case of dense systems.

  6. A model for Structure and Thermodynamics of ssDNA and dsDNA Near a Surface: a Coarse Grained Approach

    PubMed Central

    Ambia-Garrido, J.; Vainrub, Arnold; Pettitt, B. Montgomery

    2010-01-01

    New methods based on surfaces or beads have allowed measurement of properties of single DNA molecules in very accurate ways. Theoretical coarse grained models have been developed to understand the behavior of single stranded and double stranded DNA. These models have been shown to be accurate and relatively simple for very short systems of 6–8 base pairs near surfaces. Comparatively less is known about the influence of a surface on the secondary structures of longer molecules important to many technologies. Surface fields due to either applied potentials and/or dielectric boundaries are not in current surface mounted coarse grained models. To gain insight into longer and surface mounted sequences we parameterized a discretized worm-like chain model. Each link is considered a sphere of 6 base pairs in length for dsDNA, and 1.5 bases for ssDNA (requiring an always even number of spheres). For this demonstration of the model, the chain is tethered to a surface by a fixed length, non-interacting 0.536 nm linker. Configurational sampling was achieved via Monte-Carlo simulation. Our model successfully reproduces end to end distance averages from experimental results, in agreement with polymer theory and all atom simulations. Our average tilt results are also in agreement with all atom simulations for the case of dense systems. PMID:20957064

  7. A model for structure and thermodynamics of ssDNA and dsDNA near a surface: A coarse grained approach

    NASA Astrophysics Data System (ADS)

    Ambia-Garrido, J.; Vainrub, Arnold; Pettitt, B. Montgomery

    2010-12-01

    New methods based on surfaces or beads have allowed measurement of properties of single DNA molecules in very accurate ways. Theoretical coarse grained models have been developed to understand the behavior of single stranded and double stranded DNA. These models have been shown to be accurate and relatively simple for very short systems of 6-8 base pairs near surfaces. Comparatively less is known about the influence of a surface on the secondary structures of longer molecules important to many technologies. Surface fields due to either applied potentials and/or dielectric boundaries are not in current surface mounted coarse grained models. To gain insight into longer and surface mounted sequences we parameterized a discretized worm-like chain model. Each link is considered a sphere of 6 base pairs in length for dsDNA, and 1.5 bases for ssDNA (requiring an always even number of spheres). For this demonstration of the model, the chain is tethered to a surface by a fixed length, non-interacting 0.536 nm linker. Configurational sampling was achieved via Monte Carlo simulation. Our model successfully reproduces end to end distance averages from experimental results, in agreement with polymer theory and all-atom simulations. Our average tilt results are also in agreement with all-atom simulations for the case of dense systems.

  8. 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.

  9. 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.

  10. 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

    methods through applications to representative atomic structures and we discuss extensions to the validation process for molecular models of polymer structures encountered in certain semiconductor nanomanufacturing processes. The powerful method of model plausibility as a means for selecting interaction potentials for coarse-grained models is discussed in connection with a coarse-grained hexane molecule. Discussions of how all-atom information is used to construct priors are contained in an appendix.

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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.

  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. 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

  18. 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.

  19. 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}.

  20. 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

  1. 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

  2. Bridging between NMA and Elastic Network Models: Preserving All-Atom Accuracy in Coarse-Grained Models

    PubMed Central

    Na, Hyuntae; Jernigan, Robert L.; Song, Guang

    2015-01-01

    Dynamics can provide deep insights into the functional mechanisms of proteins and protein complexes. For large protein complexes such as GroEL/GroES with more than 8,000 residues, obtaining a fine-grained all-atom description of its normal mode motions can be computationally prohibitive and is often unnecessary. For this reason, coarse-grained models have been used successfully. However, most existing coarse-grained models use extremely simple potentials to represent the interactions within the coarse-grained structures and as a result, the dynamics obtained for the coarse-grained structures may not always be fully realistic. There is a gap between the quality of the dynamics of the coarse-grained structures given by all-atom models and that by coarse-grained models. In this work, we resolve an important question in protein dynamics computations—how can we efficiently construct coarse-grained models whose description of the dynamics of the coarse-grained structures remains as accurate as that given by all-atom models? Our method takes advantage of the sparseness of the Hessian matrix and achieves a high efficiency with a novel iterative matrix projection approach. The result is highly significant since it can provide descriptions of normal mode motions at an all-atom level of accuracy even for the largest biomolecular complexes. The application of our method to GroEL/GroES offers new insights into the mechanism of this biologically important chaperonin, such as that the conformational transitions of this protein complex in its functional cycle are even more strongly connected to the first few lowest frequency modes than with other coarse-grained models. PMID:26473491

  3. 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

  4. 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.

  5. 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

  6. Bottom-up coarse-grained models with predictive accuracy and transferability for both structural and thermodynamic properties of heptane-toluene mixtures

    NASA Astrophysics Data System (ADS)

    Dunn, Nicholas J. H.; Noid, W. G.

    2016-05-01

    This work investigates the promise of a "bottom-up" extended ensemble framework for developing coarse-grained (CG) models that provide predictive accuracy and transferability for describing both structural and thermodynamic properties. We employ a force-matching variational principle to determine system-independent, i.e., transferable, interaction potentials that optimally model the interactions in five distinct heptane-toluene mixtures. Similarly, we employ a self-consistent pressure-matching approach to determine a system-specific pressure correction for each mixture. The resulting CG potentials accurately reproduce the site-site rdfs, the volume fluctuations, and the pressure equations of state that are determined by all-atom (AA) models for the five mixtures. Furthermore, we demonstrate that these CG potentials provide similar accuracy for additional heptane-toluene mixtures that were not included their parameterization. Surprisingly, the extended ensemble approach improves not only the transferability but also the accuracy of the calculated potentials. Additionally, we observe that the required pressure corrections strongly correlate with the intermolecular cohesion of the system-specific CG potentials. Moreover, this cohesion correlates with the relative "structure" within the corresponding mapped AA ensemble. Finally, the appendix demonstrates that the self-consistent pressure-matching approach corresponds to minimizing an appropriate relative entropy.

  7. Size and chain length effects on structural behaviors of biphenylcyclohexane-based liquid crystal nanoclusters by a coarse-grained model.

    PubMed

    Liao, Ming-Liang; Ju, Shin-Pon; Chang, Chun-Yi; Huang, Wei-Lin

    2012-06-01

    Size and chain length effects on structural behaviors of liquid crystal nanoclusters were examined by a coarse-grained model and the configurational-bias Monte Carlo (CBMC) simulation. The nanoclusters investigated in this study are composed of the biphenylcyclohexane-based BCH5H liquid crystal molecule and its derivatives. Results of the study show that the average energy decreases (i.e., more negative) as the cluster size (i.e., the number of molecules) increases. With the increasing cluster size, the equilibrium conformation of the nanocluster changes gradually from a pipe-like structure (for the smaller systems) to a ball-like cluster (for the larger systems). The order parameter of the system reduces with the transition of the equilibrium conformation. Regarding the chain length effect, the pipe-like equilibrium conformation (for the smaller systems) was observed more close to a pipe as the length of the tail alkyl chain of the derivatives extended. However, due to the flexibility of the tail alkyl chain, the pipe conformation of the system deflects slightly about its cyclohexyl group as the tail extends further. PMID:21975541

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. Capturing mechanical properties of biological cells using coarse-grained modeling

    NASA Astrophysics Data System (ADS)

    Mao, Wenbin; Chang, Monique; Alexeev, Alexander

    2013-11-01

    Understanding cell mechanics is important for a variety of biomedical applications. Our goal is to develop a coarse-grained computational model that can properly capture the micromechanics of biological cells. The coarse-grained cell model includes an elastic shell enclosing a cross-linked polymer network and a viscous fluid representing, respectively, cell membrane, cytoskeleton, and cytoplasm. We use this model to investigate the mechanical response of cells to external forces and compare the results with the experimental AFM measurements. We systematically vary the properties and structure of the internal polymer network and the outer membrane to assess their influence on the cell mechanical responses. This model not only reveals interesting insights into the cell mechanics, but also provides a promising tool for investigation of motile and multicellular systems. Acknowledge financial support from NSF under Award No. 0932510.

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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

  9. A coarse-grained model for amorphous and crystalline fatty acids

    NASA Astrophysics Data System (ADS)

    Hadley, K. R.; McCabe, C.

    2010-04-01

    Fatty acids constitute one of the main components of the lipid lamellae in the top layer of the skin, known as the stratum corneum, which acts as a barrier to foreign substances entering the body and to water leaving the body. To better understand the mechanics of the skin, a molecular-level understanding of the structure of the lamellae needs to be investigated. As a first step toward this goal, the current work involves the development of a coarse-grained model for fatty acids in an amorphous and a crystalline state. In order to retain the structural details of the atomistic molecules, radial distribution functions have been used to provide target data against which the coarse-grained force field is optimized. The optimization was achieved using the method developed by Reith, Pütz, and Müller-Plathe with a damping factor introduced into the updating scheme to facilitate the convergence against the crystalline radial distribution functions. Using this approach, a transferable force field has been developed for both crystalline and amorphous systems that can be used to describe fatty acids of different chain lengths. We are unaware of any other coarse-grained model in the literature that has been developed to study solid phases. Additionally, the amorphous force field has been shown to accurately model mixtures of different free fatty acids based on the potentials derived from pure lipid systems.

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. A polarizable coarse-grained protein model for dissipative particle dynamics.

    PubMed

    Peter, Emanuel K; Lykov, Kirill; Pivkin, Igor V

    2015-10-01

    We present a new coarse-grained polarizable protein model for dissipative particle dynamics (DPD) method. This method allows large timesteps in particle-based systems and speeds up sampling by many orders of magnitude. Our new model is based on the electrostatic polarization of the protein backbone and a detailed representation of the sidechains in combination with a polarizable water model. We define our model parameters using the experimental structures of two proteins, TrpZip2 and TrpCage. Backmapping and subsequent short replica-exchange molecular dynamics runs verify our approach and show convergence to the experimental structures on the atomistic level. We validate our model on five different proteins: GB1, the WW-domain, the B-domain of Protein A, the peripheral binding subunit and villin headpiece. PMID:26339692

  15. 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

  16. Coarse-grained modeling of protein second osmotic virial coefficients: sterics and short-ranged attractions.

    PubMed

    Grünberger, Alexander; Lai, Pin-Kuang; Blanco, Marco A; Roberts, Christopher J

    2013-01-24

    A series of coarse-grained models, with different levels of structural resolution, were tested to calculate the steric contributions to protein osmotic second virial coefficients (B(22,S)) for proteins ranging from small single-domain molecules to large multidomain molecules, using the recently developed Mayer sampling method. B(22,S) was compared for different levels of coarse-graining: four-beads-per-amino-acid (4bAA), one-bead-per-amino-acid (1bAA), one-sphere-per-domain (1sD), and one-sphere-per-protein (1sP). Values for the 1bAA and 4bAA models were quantitatively indistinguishable for both spherical and nonspherical proteins, and the agreement with values from all-atom models improved with increasing protein size, making the CG approach attractive for large proteins of biotechnological interest. Interestingly, in the absence of detailed structural information, the hydrodynamic radius (R(h)) along with a simple 1sP approximation provided reasonably accurate values for B(22,S) for both globular and highly asymmetric protein structures, while other 1sP approximations gave poorer agreement; this helps to justify the currently empirical practice of estimating B(22,S) from R(h) for large proteins such as antibodies. The results also indicate that either 1bAA or 4bAA CG models may be good starting points for incorporating short-range attractions. Comparison of gD-crystallin B(22) values including both sterics and short-range attractions shows that 1bAA and 4bAA models give equivalent results when properly scaled to account for differences in the number of surface beads in the two CG descriptions. This provides a basis for future work that will also incorporate long-ranged electrostatic attractions and repulsions. PMID:23245189

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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).

  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. 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

  4. Coarse-Grained Models Reveal Functional Dynamics - I. Elastic Network Models – Theories, Comparisons and Perspectives

    PubMed Central

    Yang, Lee-Wei; Chng, Choon-Peng

    2008-01-01

    In this review, we summarize the progress on coarse-grained elastic network models (CG-ENMs) in the past decade. Theories were formulated to allow study of conformational dynamics in time/space frames of biological interest. Several highlighted models and their underlined hypotheses are introduced in physical depth. Important ENM offshoots, motivated to reproduce experimental data as well as to address the slow-mode-encoded configurational transitions, are also introduced. With the theoretical developments, computational cost is significantly reduced due to simplified potentials and coarse-grained schemes. Accumulating wealth of data suggest that ENMs agree equally well with experiment in describing equilibrium dynamics despite their distinct potentials and levels of coarse-graining. They however do differ in the slowest motional components that are essential to address large conformational changes of functional significance. The difference stems from the dissimilar curvatures of the harmonic energy wells described for each model. We also provide our views on the predictability of ‘open to close’ (open→close) transitions of biomolecules on the basis of conformational selection theory. Lastly, we address the limitations of the ENM formalism which are partially alleviated by the complementary CG-MD approach, to be introduced in the second paper of this two-part series. PMID:19812764

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Coarse-Grained Modeling of Nucleic Acids Using Anisotropic Gay-Berne and Electric Multipole Potentials.

    PubMed

    Li, Guohui; Shen, Hujun; Zhang, Dinglin; Li, Yan; Wang, Honglei

    2016-02-01

    In this work, we attempt to apply a coarse-grained (CG) model, which is based on anisotropic Gay-Berne and electric multipole (EMP) potentials, to the modeling of nucleic acids. First, a comparison has been made between the CG and atomistic models (AMBER point-charge model) in the modeling of DNA and RNA hairpin structures. The CG results have demonstrated a good quality in maintaining the nucleic acid hairpin structures, in reproducing the dynamics of backbone atoms of nucleic acids, and in describing the hydrogen-bonding interactions between nucleic acid base pairs. Second, the CG and atomistic AMBER models yield comparable results in modeling double-stranded DNA and RNA molecules. It is encouraging that our CG model is capable of reproducing many elastic features of nucleic acid base pairs in terms of the distributions of the interbase pair step parameters (such as shift, slide, tilt, and twist) and the intrabase pair parameters (such as buckle, propeller, shear, and stretch). Finally, The GBEMP model has shown a promising ability to predict the melting temperatures of DNA duplexes with different lengths. PMID:26717419

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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

  3. Coarse-graining polymer solutions: A critical appraisal of single- and multi-site models

    NASA Astrophysics Data System (ADS)

    D'Adamo, G.; Menichetti, R.; Pelissetto, A.; Pierleoni, C.

    2015-09-01

    We critically discuss and review the general ideas behind single- and multi-site coarse-grained (CG) models as applied to macromolecular solutions in the dilute and semi-dilute regime. We first consider single-site models with zero-density and density-dependent pair potentials. We highlight advantages and limitations of each option in reproducing the thermodynamic behavior and the large-scale structure of the underlying reference model. As a case study we consider solutions of linear homopolymers in a solvent of variable quality. Secondly, we extend the discussion to multi-component systems presenting, as a test case, results for mixtures of colloids and polymers. Specifically, we found the CG model with zero-density potentials to be unable to predict fluid-fluid demixing in a reasonable range of densities for mixtures of colloids and polymers of equal size. For larger colloids, the polymer volume fractions at which phase separation occurs are largely overestimated. CG models with density-dependent potentials are somewhat less accurate than models with zero-density potentials in reproducing the thermodynamics of the system and, although they present a phase separation, they significantly underestimate the polymer volume fractions along the binodal. Finally, we discuss a general multi-site strategy, which is thermodynamically consistent and fully transferable with the number of sites, and that allows us to overcome most of the limitations discussed for single-site models.

  4. Hierarchical coarse-graining model for photosystem II including electron and excitation-energy transfer processes.

    PubMed

    Matsuoka, Takeshi; Tanaka, Shigenori; Ebina, Kuniyoshi

    2014-03-01

    We propose a hierarchical reduction scheme to cope with coupled rate equations that describe the dynamics of multi-time-scale photosynthetic reactions. To numerically solve nonlinear dynamical equations containing a wide temporal range of rate constants, we first study a prototypical three-variable model. Using a separation of the time scale of rate constants combined with identified slow variables as (quasi-)conserved quantities in the fast process, we achieve a coarse-graining of the dynamical equations reduced to those at a slower time scale. By iteratively employing this reduction method, the coarse-graining of broadly multi-scale dynamical equations can be performed in a hierarchical manner. We then apply this scheme to the reaction dynamics analysis of a simplified model for an illuminated photosystem II, which involves many processes of electron and excitation-energy transfers with a wide range of rate constants. We thus confirm a good agreement between the coarse-grained and fully (finely) integrated results for the population dynamics. PMID:24418347

  5. Coarse-grained models of stripe forming systems: Phase diagrams, anomalies, and scaling hypothesis

    NASA Astrophysics Data System (ADS)

    Mendoza-Coto, Alejandro; Stariolo, Daniel A.

    2012-11-01

    Two coarse-grained models which capture some universal characteristics of stripe forming systems are studied. At high temperatures, the structure factors of both models attain their maxima on a circle in reciprocal space, as a consequence of generic isotropic competing interactions. Although this is known to lead to some universal properties, we show that the phase diagrams have important differences, which are a consequence of the particular k⃗ dependence of the fluctuation spectrum in each model. The phase diagrams are computed in a mean field approximation and also after inclusion of small fluctuations, which are shown to modify drastically the mean field behavior. Observables like the modulation length and magnetization profiles are computed for the whole temperature range accessible to both models and some important differences in behavior are observed. A stripe compression modulus is computed, showing an anomalous behavior with temperature as recently reported in related models. Also, a recently proposed scaling hypothesis for modulated systems is tested and found to be valid for both models studied.

  6. 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.

  7. 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

  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. 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

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. A generalized-Yvon-Born-Green method for coarse-grained modeling. Advances, Challenges, and Insight

    NASA Astrophysics Data System (ADS)

    Rudzinski, J. F.; Noid, W. G.

    2015-09-01

    The Yvon-Born-Green (YBG) integral equation is a basic result of liquid state theory that relates the pair potential of a simple fluid to the resulting equilibrium two- and three-body correlation functions. Quite recently, we derived a more general form that can be applied to complex molecular systems. This generalized-YBG (g-YBG) theory provides not only an exact relation between a given potential and the resulting equilibrium correlation functions, but also a remarkably powerful framework for directly solving the statistical mechanics inverse problem of determining potentials from equilibrium structure ensembles. In the context of coarse-grained (CG) modeling, the g-YBG theory determines a variationally optimal approximation to the many-body potential of mean force directly (i.e., noniteratively) from structural correlation functions and, in particular, allows "force-matching" without forces. While our initial efforts numerically validated the g-YBG theory with relatively simple systems, our more recent efforts have considered increasingly complex systems, such as peptides and polymers. This minireview summarizes this progress and the resulting insight, as well as discusses the outstanding challenges and future directions for the g-YBG theory.

  15. 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.

  16. 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.

  17. A coarse-grained transport model for neutral particles in turbulent plasmas

    SciTech Connect

    Mekkaoui, A.; Reiter, D.; Boerner, P.; Marandet, Y.; Genesio, P.; Rosato, J.; Capes, H.; Koubiti, M.; Godbert-Mouret, L.; Stamm, R.

    2012-12-15

    The transport of neutral particles in turbulent plasmas is addressed from the prospect of developing coarse-grained transport models which can be implemented in code suites like B2-EIRENE, currently used for designing the ITER divertor. The statistical properties of turbulent fluctuations are described by a multivariate Gamma distribution able to retain space and time correlations through a proper choice of covariance function. We show that in the scattering free case, relevant for molecules and impurity atoms, the average neutral particle density obeys a Boltzmann equation with an ionization rate renormalized by fluctuations. This result lends itself to a straightforward implementation in the EIRENE Monte Carlo solver for neutral particles. Special emphasis is put on the inclusion of time correlations, and in particular on the ballistic motion of coherent turbulent structures. The role of these time dependent effects is discussed for D{sub 2} molecules and beryllium atoms. The sensitivity of our results to the assumptions on the statistical properties of fluctuations is investigated.

  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 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

  20. Optimization of an Elastic Network Augmented Coarse Grained Model to Study CCMV Capsid Deformation

    PubMed Central

    Globisch, Christoph; Krishnamani, Venkatramanan; Deserno, Markus; Peter, Christine

    2013-01-01

    The major protective coat of most viruses is a highly symmetric protein capsid that forms spontaneously from many copies of identical proteins. Structural and mechanical properties of such capsids, as well as their self-assembly process, have been studied experimentally and theoretically, including modeling efforts by computer simulations on various scales. Atomistic models include specific details of local protein binding but are limited in system size and accessible time, while coarse grained (CG) models do get access to longer time and length scales but often lack the specific local interactions. Multi-scale models aim at bridging this gap by systematically connecting different levels of resolution. Here, a CG model for CCMV (Cowpea Chlorotic Mottle Virus), a virus with an icosahedral shell of 180 identical protein monomers, is developed, where parameters are derived from atomistic simulations of capsid protein dimers in aqueous solution. In particular, a new method is introduced to combine the MARTINI CG model with a supportive elastic network based on structural fluctuations of individual monomers. In the parametrization process, both network connectivity and strength are optimized. This elastic-network optimized CG model, which solely relies on atomistic data of small units (dimers), is able to correctly predict inter-protein conformational flexibility and properties of larger capsid fragments of 20 and more subunits. Furthermore, it is shown that this CG model reproduces experimental (Atomic Force Microscopy) indentation measurements of the entire viral capsid. Thus it is shown that one obvious goal for hierarchical modeling, namely predicting mechanical properties of larger protein complexes from models that are carefully parametrized on elastic properties of smaller units, is achievable. PMID:23613730

  1. 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

  2. Accurate coarse-grained models for mixtures of colloids and linear polymers under good-solvent conditions

    SciTech Connect

    D’Adamo, Giuseppe; Pelissetto, Andrea; Pierleoni, Carlo

    2014-12-28

    A coarse-graining strategy, previously developed for polymer solutions, is extended here to mixtures of linear polymers and hard-sphere colloids. In this approach, groups of monomers are mapped onto a single pseudoatom (a blob) and the effective blob-blob interactions are obtained by requiring the model to reproduce some large-scale structural properties in the zero-density limit. We show that an accurate parametrization of the polymer-colloid interactions is obtained by simply introducing pair potentials between blobs and colloids. For the coarse-grained (CG) model in which polymers are modelled as four-blob chains (tetramers), the pair potentials are determined by means of the iterative Boltzmann inversion scheme, taking full-monomer (FM) pair correlation functions at zero-density as targets. For a larger number n of blobs, pair potentials are determined by using a simple transferability assumption based on the polymer self-similarity. We validate the model by comparing its predictions with full-monomer results for the interfacial properties of polymer solutions in the presence of a single colloid and for thermodynamic and structural properties in the homogeneous phase at finite polymer and colloid density. The tetramer model is quite accurate for q ≲ 1 (q=R{sup ^}{sub g}/R{sub c}, where R{sup ^}{sub g} is the zero-density polymer radius of gyration and R{sub c} is the colloid radius) and reasonably good also for q = 2. For q = 2, an accurate coarse-grained description is obtained by using the n = 10 blob model. We also compare our results with those obtained by using single-blob models with state-dependent potentials.

  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. C -IBI: Targeting cumulative coordination within an iterative protocol to derive coarse-grained models of (multi-component) complex fluids

    NASA Astrophysics Data System (ADS)

    de Oliveira, Tiago E.; Netz, Paulo A.; Kremer, Kurt; Junghans, Christoph; Mukherji, Debashish

    2016-05-01

    We present a coarse-graining strategy that we test for aqueous mixtures. The method uses pair-wise cumulative coordination as a target function within an iterative Boltzmann inversion (IBI) like protocol. We name this method coordination iterative Boltzmann inversion ( C -IBI). While the underlying coarse-grained model is still structure based and, thus, preserves pair-wise solution structure, our method also reproduces solvation thermodynamics of binary and/or ternary mixtures. Additionally, we observe much faster convergence within C -IBI compared to IBI. To validate the robustness, we apply C -IBI to study test cases of solvation thermodynamics of aqueous urea and a triglycine solvation in aqueous urea.

  5. The impact of resolution upon entropy and information in coarse-grained models

    NASA Astrophysics Data System (ADS)

    Foley, Thomas T.; Shell, M. Scott; Noid, W. G.

    2015-12-01

    By eliminating unnecessary degrees of freedom, coarse-grained (CG) models tremendously facilitate numerical calculations and theoretical analyses of complex phenomena. However, their success critically depends upon the representation of the system and the effective potential that governs the CG degrees of freedom. This work investigates the relationship between the CG representation and the many-body potential of mean force (PMF), W, which is the appropriate effective potential for a CG model that exactly preserves the structural and thermodynamic properties of a given high resolution model. In particular, we investigate the entropic component of the PMF and its dependence upon the CG resolution. This entropic component, SW, is a configuration-dependent relative entropy that determines the temperature dependence of W. As a direct consequence of eliminating high resolution details from the CG model, the coarsening process transfers configurational entropy and information from the configuration space into SW. In order to further investigate these general results, we consider the popular Gaussian Network Model (GNM) for protein conformational fluctuations. We analytically derive the exact PMF for the GNM as a function of the CG representation. In the case of the GNM, -TSW is a positive, configuration-independent term that depends upon the temperature, the complexity of the protein interaction network, and the details of the CG representation. This entropic term demonstrates similar behavior for seven model proteins and also suggests, in each case, that certain resolutions provide a more efficient description of protein fluctuations. These results may provide general insight into the role of resolution for determining the information content, thermodynamic properties, and transferability of CG models. Ultimately, they may lead to a rigorous and systematic framework for optimizing the representation of CG models.

  6. The impact of resolution upon entropy and information in coarse-grained models

    SciTech Connect

    Foley, Thomas T.; Shell, M. Scott; Noid, W. G.

    2015-12-28

    By eliminating unnecessary degrees of freedom, coarse-grained (CG) models tremendously facilitate numerical calculations and theoretical analyses of complex phenomena. However, their success critically depends upon the representation of the system and the effective potential that governs the CG degrees of freedom. This work investigates the relationship between the CG representation and the many-body potential of mean force (PMF), W, which is the appropriate effective potential for a CG model that exactly preserves the structural and thermodynamic properties of a given high resolution model. In particular, we investigate the entropic component of the PMF and its dependence upon the CG resolution. This entropic component, S{sub W}, is a configuration-dependent relative entropy that determines the temperature dependence of W. As a direct consequence of eliminating high resolution details from the CG model, the coarsening process transfers configurational entropy and information from the configuration space into S{sub W}. In order to further investigate these general results, we consider the popular Gaussian Network Model (GNM) for protein conformational fluctuations. We analytically derive the exact PMF for the GNM as a function of the CG representation. In the case of the GNM, −TS{sub W} is a positive, configuration-independent term that depends upon the temperature, the complexity of the protein interaction network, and the details of the CG representation. This entropic term demonstrates similar behavior for seven model proteins and also suggests, in each case, that certain resolutions provide a more efficient description of protein fluctuations. These results may provide general insight into the role of resolution for determining the information content, thermodynamic properties, and transferability of CG models. Ultimately, they may lead to a rigorous and systematic framework for optimizing the representation of CG models.

  7. Coarse-grained particle model for pedestrian flow using diffusion maps

    NASA Astrophysics Data System (ADS)

    Marschler, Christian; Starke, Jens; Liu, Ping; Kevrekidis, Ioannis G.

    2014-01-01

    Interacting particle systems constitute the dynamic model of choice in a variety of application areas. A prominent example is pedestrian dynamics, where good design of escape routes for large buildings and public areas can improve evacuation in emergency situations, avoiding exit blocking and the ensuing panic. Here we employ diffusion maps to study the coarse-grained dynamics of two pedestrian crowds trying to pass through a door from opposite sides. These macroscopic variables and the associated smooth embeddings lead to a better description and a clearer understanding of the nature of the transition to oscillatory dynamics. We also compare the results to those obtained through intuitively chosen macroscopic variables.

  8. Coarse Grained Modeling of The Interface BetweenWater and Heterogeneous Surfaces

    SciTech Connect

    Willard, Adam; Chandler, David

    2008-06-23

    Using coarse grained models we investigate the behavior of water adjacent to an extended hydrophobic surface peppered with various fractions of hydrophilic patches of different sizes. We study the spatial dependence of the mean interface height, the solvent density fluctuations related to drying the patchy substrate, and the spatial dependence of interfacial fluctuations. We find that adding small uniform attractive interactions between the substrate and solvent cause the mean position of the interface to be very close to the substrate. Nevertheless, the interfacial fluctuations are large and spatially heterogeneous in response to the underlying patchy substrate. We discuss the implications of these findings to the assembly of heterogeneous surfaces.

  9. Validating a Coarse-Grained Potential Energy Function through Protein Loop Modelling

    PubMed Central

    MacDonald, James T.; Kelley, Lawrence A.; Freemont, Paul S.

    2013-01-01

    Coarse-grained (CG) methods for sampling protein conformational space have the potential to increase computational efficiency by reducing the degrees of freedom. The gain in computational efficiency of CG methods often comes at the expense of non-protein like local conformational features. This could cause problems when transitioning to full atom models in a hierarchical framework. Here, a CG potential energy function was validated by applying it to the problem of loop prediction. A novel method to sample the conformational space of backbone atoms was benchmarked using a standard test set consisting of 351 distinct loops. This method used a sequence-independent CG potential energy function representing the protein using -carbon positions only and sampling conformations with a Monte Carlo simulated annealing based protocol. Backbone atoms were added using a method previously described and then gradient minimised in the Rosetta force field. Despite the CG potential energy function being sequence-independent, the method performed similarly to methods that explicitly use either fragments of known protein backbones with similar sequences or residue-specific /-maps to restrict the search space. The method was also able to predict with sub-Angstrom accuracy two out of seven loops from recently solved crystal structures of proteins with low sequence and structure similarity to previously deposited structures in the PDB. The ability to sample realistic loop conformations directly from a potential energy function enables the incorporation of additional geometric restraints and the use of more advanced sampling methods in a way that is not possible to do easily with fragment replacement methods and also enable multi-scale simulations for protein design and protein structure prediction. These restraints could be derived from experimental data or could be design restraints in the case of computational protein design. C++ source code is available for download from http

  10. Multiscale coarse-grained modelling of chromatin components: DNA and the nucleosome.

    PubMed

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

    2016-06-01

    To model large biomolecular systems, such as cell and organelles an atomistic description is not currently achievable and is not generally practical. Therefore, simplified coarse-grained (CG) modelling becomes a necessity. One of the most important cellular components is chromatin, a large DNA-protein complex where DNA is highly compacted. Recent progress in coarse graining modelling of the major chromatin components, double helical DNA and the nucleosome core particle (NCP) is presented. First, general principles and approaches allowing rigorous bottom-to-top generation of interaction potentials in the CG models are presented. Then, recent CG models of DNA are reviewed and their adequacy is benchmarked against experimental data on the salt dependence of DNA flexibility (persistence length). Furthermore, a few recent CG models of the NCP are described and their application for studying salt-dependent NCP-NCP interaction is discussed. An example of a multiscale approach to CG modelling of chromatin is presented where interactions and self-assembly of thousands of NCPs in solution are observed. PMID:26956528

  11. 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.

  12. 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

  13. Coding coarse grained polymer model for LAMMPS and its application to polymer crystallization

    NASA Astrophysics Data System (ADS)

    Luo, Chuanfu; Sommer, Jens-Uwe

    2009-08-01

    We present a patch code for LAMMPS to implement a coarse grained (CG) model of poly(vinyl alcohol) (PVA). LAMMPS is a powerful molecular dynamics (MD) simulator developed at Sandia National Laboratories. Our patch code implements tabulated angular potential and Lennard-Jones-9-6 (LJ96) style interaction for PVA. Benefited from the excellent parallel efficiency of LAMMPS, our patch code is suitable for large-scale simulations. This CG-PVA code is used to study polymer crystallization, which is a long-standing unsolved problem in polymer physics. By using parallel computing, cooling and heating processes for long chains are simulated. The results show that chain-folded structures resembling the lamellae of polymer crystals are formed during the cooling process. The evolution of the static structure factor during the crystallization transition indicates that long-range density order appears before local crystalline packing. This is consistent with some experimental observations by small/wide angle X-ray scattering (SAXS/WAXS). During the heating process, it is found that the crystalline regions are still growing until they are fully melted, which can be confirmed by the evolution both of the static structure factor and average stem length formed by the chains. This two-stage behavior indicates that melting of polymer crystals is far from thermodynamic equilibrium. Our results concur with various experiments. It is the first time that such growth/reorganization behavior is clearly observed by MD simulations. Our code can be easily used to model other type of polymers by providing a file containing the tabulated angle potential data and a set of appropriate parameters. Program summaryProgram title: lammps-cgpva Catalogue identifier: AEDE_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEDE_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: GNU's GPL No. of lines in distributed program

  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. 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

  16. 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.

  17. Virtual ultrasound sources for inspecting nuclear components of coarse-grained structure

    SciTech Connect

    Brizuela, J.; Katchadjian, P.; Desimone, C.; Garcia, A.

    2014-02-18

    This work describes an ultrasonic inspection procedure designed for verifying coarse-grained structure materials, which are commonly used on nuclear reactors. In this case, conventional phased array techniques cannot be used due to attenuating characteristics and backscattered noise from microstructures inside the material. Thus, synthetic aperture ultrasonic imaging (SAFT) is used for this approach in contact conditions. In order to increase energy transferred to the medium, synthetic transmit aperture is formed by several elements which generate a diverging wavefront equivalent to a virtual ultrasound source behind the transducer. On the other hand, the phase coherence technique has been applied to reduce more structural noise and improve the image quality. The beamforming process has been implemented over a GPU platform to reduce computing time.

  18. 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

  19. Coarse-graining molecular dynamics models using an extended Galerkin method

    NASA Astrophysics Data System (ADS)

    Li, Xiantao

    2013-03-01

    I will present a systematic approach to coarse-grain molecular dynamics models for solids. The coarse-grained models are derived by Galerkin projection to a sequence of Krylov subspaces. On the coarsest space, the model corresponds to a finite element discretization of the continuum elasto-dynamics model. On the other hand, the projection to the finest space yields the full molecular dynamics description. The models in between serve as a smooth transition between the two scales. We start with a molecular dynamics (MD) model, mix¨i = -∂V/∂xi . First, let Y0 be the approximation space for the continuum model. By projecting the MD model onto the subspace, we obtain a coarse-grained model, M q ¨ = F (q) . Using the Cauchy-Born approximation, this model can be shown to coincide with the finite element representation of the continuum elastodynamics model. This model has limited accuracy near lattice defects. One natural idea is to switch to the MD model in regions surround local defect. As a result, one creates an interface between the continuum and atomistic description, where coupling conditions are needed. Direct coupling methods may involve enforcing constraints or mixing the energy or forces. Such an approach may suffer from large phonon reflections at the interface, and introduce large modeling error. In order to seamlessly couple this model to MD, we successively expand the approximation space to the Krylov spaces, Kl =Y0 + AY0 + ⋯ +AlY0 . Here A is the force constant matrix, computed from the atomistic model. Due to the translational invariance, only a smaller number of such matrices need to be computed. By projecting the MD model onto this new subspace, we obtain an extended system, M q .. =F0 (q ,ξ1 , ... ,ξl) ,ξ̈1 =F1 (q ,ξ1 , ... ,ξl) , ... ... ,ξ̈l =Fl (q ,ξ1 , ... ,ξl) . The additional variables ξj represent the coefficients in the extended approximation space. Using this systematic approach, one can build a hierarchy of models with

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. Systematic coarse-graining of spectrin-level red blood cell models

    PubMed Central

    Fedosov, Dmitry A.; Caswell, Bruce; Karniadakis, George Em

    2013-01-01

    We present a rigorous procedure to derive coarse-grained red blood cell (RBC) models, which yield accurate mechanical response. Based on a semi-analytic theory the linear and nonlinear elastic properties of healthy and infected RBCs in malaria can be matched with those obtained in optical tweezers stretching experiments. The present analysis predicts correctly the membrane Young’s modulus in contrast to about 50% error in predictions by previous models. In addition, we develop a stress-free model which avoids a number of pitfalls of existing RBC models, such as non-smooth or poorly controlled equilibrium shape and dependence of the mechanical properties on the initial triangulation quality. Here we employ dissipative particle dynamics for the implementation but the proposed model is general and suitable for use in many existing continuum and particle-based numerical methods. PMID:24353352

  7. SIRAH: a structurally unbiased coarse-grained force field for proteins with aqueous solvation and long-range electrostatics.

    PubMed

    Darré, Leonardo; Machado, Matías Rodrigo; Brandner, Astrid Febe; González, Humberto Carlos; Ferreira, Sebastián; Pantano, Sergio

    2015-02-10

    Modeling of macromolecular structures and interactions represents an important challenge for computational biology, involving different time and length scales. However, this task can be facilitated through the use of coarse-grained (CG) models, which reduce the number of degrees of freedom and allow efficient exploration of complex conformational spaces. This article presents a new CG protein model named SIRAH, developed to work with explicit solvent and to capture sequence, temperature, and ionic strength effects in a topologically unbiased manner. SIRAH is implemented in GROMACS, and interactions are calculated using a standard pairwise Hamiltonian for classical molecular dynamics simulations. We present a set of simulations that test the capability of SIRAH to produce a qualitatively correct solvation on different amino acids, hydrophilic/hydrophobic interactions, and long-range electrostatic recognition leading to spontaneous association of unstructured peptides and stable structures of single polypeptides and protein-protein complexes. PMID:26575407

  8. Automated Optimization of Water–Water Interaction Parameters for a Coarse-Grained Model

    PubMed Central

    2015-01-01

    We have developed an automated parameter optimization software framework (ParOpt) that implements the Nelder–Mead simplex algorithm and applied it to a coarse-grained polarizable water model. The model employs a tabulated, modified Morse potential with decoupled short- and long-range interactions incorporating four water molecules per interaction site. Polarizability is introduced by the addition of a harmonic angle term defined among three charged points within each bead. The target function for parameter optimization was based on the experimental density, surface tension, electric field permittivity, and diffusion coefficient. The model was validated by comparison of statistical quantities with experimental observation. We found very good performance of the optimization procedure and good agreement of the model with experiment. PMID:24460506

  9. Automated optimization of water-water interaction parameters for a coarse-grained model.

    PubMed

    Fogarty, Joseph C; Chiu, See-Wing; Kirby, Peter; Jakobsson, Eric; Pandit, Sagar A

    2014-02-13

    We have developed an automated parameter optimization software framework (ParOpt) that implements the Nelder-Mead simplex algorithm and applied it to a coarse-grained polarizable water model. The model employs a tabulated, modified Morse potential with decoupled short- and long-range interactions incorporating four water molecules per interaction site. Polarizability is introduced by the addition of a harmonic angle term defined among three charged points within each bead. The target function for parameter optimization was based on the experimental density, surface tension, electric field permittivity, and diffusion coefficient. The model was validated by comparison of statistical quantities with experimental observation. We found very good performance of the optimization procedure and good agreement of the model with experiment. PMID:24460506

  10. 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

  11. 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.

  12. 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

  13. Coarse-graining intermittent intracellular transport: Two- and three-dimensional models

    NASA Astrophysics Data System (ADS)

    Lawley, Sean D.; Tuft, Marie; Brooks, Heather A.

    2015-10-01

    Viruses and other cellular cargo that lack locomotion must rely on diffusion and cellular transport systems to navigate through a biological cell. Indeed, advances in single particle tracking have revealed that viral motion alternates between (a) diffusion in the cytoplasm and (b) active transport along microtubules. This intermittency makes quantitative analysis of trajectories difficult. Therefore, the purpose of this paper is to construct mathematical methods to approximate intermittent dynamics by effective stochastic differential equations. The coarse-graining method that we develop is more accurate than existing techniques and applicable to a wide range of intermittent transport models. In particular, we apply our method to two- and three-dimensional cell geometries (disk, sphere, and cylinder) and demonstrate its accuracy. In addition to these specific applications, we also explain our method in full generality for use on future intermittent models.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. Cooperativity, Local-Nonlocal Coupling, and Nonnative Interactions: Principles of Protein Folding from Coarse-Grained Models

    NASA Astrophysics Data System (ADS)

    Chan, Hue Sun; Zhang, Zhuqing; Wallin, Stefan; Liu, Zhirong

    2011-05-01

    Coarse-grained, self-contained polymer models are powerful tools in the study of protein folding. They are also essential to assess predictions from less rigorous theoretical approaches that lack an explicit-chain representation. Here we review advances in coarse-grained modeling of cooperative protein folding, noting in particular that the Levinthal paradox was raised in response to the experimental discovery of two-state-like folding in the late 1960s, rather than to the problem of conformational search per se. Comparisons between theory and experiment indicate a prominent role of desolvation barriers in cooperative folding, which likely emerges generally from a coupling between local conformational preferences and nonlocal packing interactions. Many of these principles have been elucidated by native-centric models, wherein nonnative interactions may be treated perturbatively. We discuss these developments as well as recent applications of coarse-grained chain modeling to knotted proteins and to intrinsically disordered proteins.

  20. Cooperativity, local-nonlocal coupling, and nonnative interactions: principles of protein folding from coarse-grained models.

    PubMed

    Chan, Hue Sun; Zhang, Zhuqing; Wallin, Stefan; Liu, Zhirong

    2011-01-01

    Coarse-grained, self-contained polymer models are powerful tools in the study of protein folding. They are also essential to assess predictions from less rigorous theoretical approaches that lack an explicit-chain representation. Here we review advances in coarse-grained modeling of cooperative protein folding, noting in particular that the Levinthal paradox was raised in response to the experimental discovery of two-state-like folding in the late 1960s, rather than to the problem of conformational search per se. Comparisons between theory and experiment indicate a prominent role of desolvation barriers in cooperative folding, which likely emerges generally from a coupling between local conformational preferences and nonlocal packing interactions. Many of these principles have been elucidated by native-centric models, wherein nonnative interactions may be treated perturbatively. We discuss these developments as well as recent applications of coarse-grained chain modeling to knotted proteins and to intrinsically disordered proteins. PMID:21453060

  1. AWSEM-MD: Protein Structure Prediction Using Coarse-grained Physical Potentials and Bioinformatically Based Local Structure Biasing

    PubMed Central

    Davtyan, Aram; Schafer, Nicholas P.; Zheng, Weihua; Clementi, Cecilia; Wolynes, Peter G.; Papoian, Garegin A.

    2012-01-01

    The Associative memory, Water mediated, Structure and Energy Model (AWSEM) is a coarse-grained protein force field. AWSEM contains physically motivated terms, such as hydrogen bonding, as well as a bioinformatically based local structure biasing term, which efficiently takes into account many-body effects that are modulated by the local sequence. When combined with appropriate local or global alignments to choose memories, AWSEM can be used to perform de novo protein structure prediction. Herein we present structure prediction results for a particular choice of local sequence alignment method based on short residue sequences called fragments. We demonstrate the model’s structure prediction capabilities for three levels of global homology between the target sequence and those proteins used for local structure biasing, all of which assume that the structure of the target sequence is not known. When there are no homologs in the database of structures used for local structure biasing, AWSEM calculations produce structural predictions that are somewhat improved compared with prior works using related approaches. The inclusion of a small number of structures from homologous sequences improves structure prediction only marginally but when the fragment search is restricted to only homologous sequences, AWSEM can perform high resolution structure prediction and can be used for kinetics and dynamics studies. PMID:22545654

  2. Coarse-grained model of adsorption of blood plasma proteins onto nanoparticles

    NASA Astrophysics Data System (ADS)

    Lopez, Hender; Lobaskin, Vladimir

    2015-12-01

    We present a coarse-grained model for evaluation of interactions of globular proteins with nanoparticles (NPs). The protein molecules are represented by one bead per aminoacid and the nanoparticle by a homogeneous sphere that interacts with the aminoacids via a central force that depends on the nanoparticle size. The proposed methodology is used to predict the adsorption energies for six common human blood plasma proteins on hydrophobic charged or neutral nanoparticles of different sizes as well as the preferred orientation of the molecules upon adsorption. Our approach allows one to rank the proteins by their binding affinity to the nanoparticle, which can be used for predicting the composition of the NP-protein corona. The predicted ranking is in good agreement with known experimental data for protein adsorption on surfaces.

  3. 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

  4. Proteins at air-water interfaces: a coarse-grained model.

    PubMed

    Cieplak, Marek; Allan, Daniel B; Leheny, Robert L; Reich, Daniel H

    2014-11-01

    We present a coarse-grained model to describe the adsorption and deformation of proteins at an air-water interface. The interface is introduced empirically in the form of a localized field that couples to a hydropathy scale of amino acids. We consider three kinds of proteins: protein G, egg-white lysozyme, and hydrophobin. We characterize the nature of the deformation and the orientation of the proteins induced by their proximity to and association with the interface. We also study protein diffusion in the layer formed at the interface and show that the diffusion slows with increasing concentration in a manner similar to that for a colloidal suspension approaching the glass transition. PMID:25310625

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. Coarse-grained red blood cell model with accurate mechanical properties, rheology and dynamics.

    PubMed

    Fedosov, Dmitry A; Caswell, Bruce; Karniadakis, George E

    2009-01-01

    We present a coarse-grained red blood cell (RBC) model with accurate and realistic mechanical properties, rheology and dynamics. The modeled membrane is represented by a triangular mesh which incorporates shear inplane energy, bending energy, and area and volume conservation constraints. The macroscopic membrane elastic properties are imposed through semi-analytic theory, and are matched with those obtained in optical tweezers stretching experiments. Rheological measurements characterized by time-dependent complex modulus are extracted from the membrane thermal fluctuations, and compared with those obtained from the optical magnetic twisting cytometry results. The results allow us to define a meaningful characteristic time of the membrane. The dynamics of RBCs observed in shear flow suggests that a purely elastic model for the RBC membrane is not appropriate, and therefore a viscoelastic model is required. The set of proposed analyses and numerical tests can be used as a complete model testbed in order to calibrate the modeled viscoelastic membranes to accurately represent RBCs in health and disease. PMID:19965026

  10. A coarse-grained α-carbon protein model with anisotropic hydrogen-bonding

    PubMed Central

    Yap, Eng-Hui; Fawzi, Nicolas Lux; Head-Gordon, Teresa

    2012-01-01

    We develop a sequence based α-carbon model to incorporate a mean field estimate of the orientation dependence of the polypeptide chain that gives rise to specific hydrogen bond pairing to stabilize α-helices and β-sheets. We illustrate the success of the new protein model in capturing thermodynamic measures and folding mechanism of proteins L and G. Compared to our previous coarse-grained model, the new model shows greater folding cooperativity and improvements in designability of protein sequences, as well as predicting correct trends for kinetic rates and mechanism for proteins L and G. We believe the model is broadly applicable to other protein folding and protein–protein co-assembly processes, and does not require experimental input beyond the topology description of the native state. Even without tertiary topology information, it can also serve as a mid-resolution protein model for more exhaustive conformational search strategies that can bridge back down to atomic descriptions of the polypeptide chain. PMID:17879350

  11. 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.

  12. 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

  13. Vibrational solvatochromism and electrochromism: Coarse-grained models and their relationships

    NASA Astrophysics Data System (ADS)

    Cho, Minhaeng

    2009-03-01

    A theoretical description of vibrational solvatochromism and electrochromism is presented by using a coarse-grained model based on a distributed charge and multipole interaction theory. Solvatochromic frequency shift has been described by considering the interaction between distributed charges of a solute and electrostatic potential due to distributed charges of solvent molecules. Another approach was based on the expansion of the solvatochromic frequency shift in terms of solvent electric field and its gradient at distributed sites on solute. The relationship between these two approaches is elucidated and their validities are discussed. It is also shown that the distributed charge and multipole model for solvatochromism developed here can be used to describe vibrational Stark effects on frequency and transition dipole moment. The relationship between the vibrational Stark tuning rate and the parameters obtained from recent vibrational solvatochromism studies is clarified and used to determine the vibrational Stark tuning rates of a few stretching modes, which are then directly compared with experimentally measured values. We anticipate that the present theoretical model can be used to study a variety of vibrational solvatochromic and electrochromic phenomena and to extract critical information on local electrostatic environment around a small IR probe in solution or protein from linear and nonlinear IR spectroscopic studies.

  14. 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.

  15. 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.

  16. 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.

  17. A multiscale coarse-grained polarizable solvent model for handling long tail bulk electrostatics.

    PubMed

    Masella, Michel; Borgis, Daniel; Cuniasse, Philippe

    2013-05-15

    A multiscale coarse-grained approach able to handle efficiently the solvation of microscopic solutes in extended chemical environment is described. That approach is able to compute readily and efficiently very long-range solute/solvent electrostatic microscopic interactions, up to the 1-μm scale, by considering a reduced amount of computational resources. All the required parameters are assigned to reproduce available data concerning the solvation of single ions. Such a strategy makes it possible to reproduce with good accuracy the solvation properties concerning simple ion pairs in solution (in particular, the asymptotic behavior of the ion pair potentials of mean force). This new method represents an extension of the polarizable pseudoparticle solvent model, which has been recently improved to account for the main features of hydrophobic effects in liquid water (Masella et al., J. Comput. Chem. 2011, 32, 2664). This multiscale approach is well suited to be used for computing the impact of charge changes in free energy computations, in terms of both accuracy and efficiency. PMID:23382002

  18. 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

  19. 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

  20. Coarse-grained models reveal functional dynamics--I. Elastic network models--theories, comparisons and perspectives.

    PubMed

    Yang, Lee-Wei; Chng, Choon-Peng

    2008-01-01

    In this review, we summarize the progress on coarse-grained elastic network models (CG-ENMs) in the past decade. Theories were formulated to allow study of conformational dynamics in time/space frames of biological interest. Several highlighted models and their underlined hypotheses are introduced in physical depth. Important ENM offshoots, motivated to reproduce experimental data as well as to address the slow-mode-encoded configurational transitions, are also introduced. With the theoretical developments, computational cost is significantly reduced due to simplified potentials and coarse-grained schemes. Accumulating wealth of data suggest that ENMs agree equally well with experiment in describing equilibrium dynamics despite their distinct potentials and levels of coarse-graining. They however do differ in the slowest motional components that are essential to address large conformational changes of functional significance. The difference stems from the dissimilar curvatures of the harmonic energy wells described for each model. We also provide our views on the predictability of 'open to close' (open-->close) transitions of biomolecules on the basis of conformational selection theory. Lastly, we address the limitations of the ENM formalism which are partially alleviated by the complementary CG-MD approach, to be introduced in the second paper of this two-part series. PMID:19812764

  1. Mechanism of the formation of peripheral coarse grain structure in hot extrusion of Al-4.5Zn-1Mg

    NASA Astrophysics Data System (ADS)

    Eivani, A. R.; Zhou, J.; Duszczyk, J.

    2016-04-01

    Microstructural evolution leading to peripheral coarse grain (PCG) structure in hot extruded Al-4.5Zn-1Mg rods is investigated. The extent of dynamic recrystallization (DRX) in the as-extruded product falls not in line with the basis over which the existing mechanisms for interpretation of PCG formation are built. A new mechanism is therefore proposed based on partial DRX during extrusion and nucleation and abnormal growth of statically recrsystallised grains.

  2. Applying Ultrasonic Phased Array Technology to Examine Austenitic Coarse-Grained Structures for Light Water Reactor Piping

    SciTech Connect

    Anderson, Michael T.; Cumblidge, Stephen E.; Doctor, Steven R.

    2003-12-18

    Pacific Northwest Laboratory is evaluating the capabilities and limitations of phased array (PA) technology to detect service-type flaws in coarse-grained austenitic piping structures. The work is being sponsored by the U.S. Nuclear Regulatory Commission, Office of Research. This paper presents initial work involving the use of PA technology to determine the effectiveness of detecting and accurately characterizing flaws on the far-side of austenitic piping welds.

  3. C–IBI: Targeting cumulative coordination within an iterative protocol to derive coarse-grained models of (multi-component) complex fluids

    DOE PAGESBeta

    de Oliveira, Tiago E.; Netz, Paulo A.; Kremer, Kurt; Junghans, Christoph; Mukherji, Debashish

    2016-05-03

    We present a coarse-graining strategy that we test for aqueous mixtures. The method uses pair-wise cumulative coordination as a target function within an iterative Boltzmann inversion (IBI) like protocol. We name this method coordination iterative Boltzmann inversion (C–IBI). While the underlying coarse-grained model is still structure based and, thus, preserves pair-wise solution structure, our method also reproduces solvation thermodynamics of binary and/or ternary mixtures. In addition, we observe much faster convergence within C–IBI compared to IBI. To validate the robustness, we apply C–IBI to study test cases of solvation thermodynamics of aqueous urea and a triglycine solvation in aqueous urea.

  4. Coarse-Grained Molecular Dynamics for Computer Modeling of Nanomechanical Systems

    SciTech Connect

    Rudd, R E

    2003-11-02

    Unique challenges for computer modeling and simulation arise in the course of the development and design of nanoscale mechanical systems. Materials often exhibit unconventional behavior at the nanoscale that can affect device operation and failure. This uncertainty poses a problem because of the limited experimental characterization at these ultra-small length scales. In this Article we give an overview of how we have used concurrent multiscale modeling techniques to address some of these issues. Of particular interest are the dynamic and temperature-dependent processes found in nanomechanical systems. We focus on the behavior of sub-micron mechanical components of Micro-Electro-Mechanical Systems (MEMS) and Nano-Electro-Mechanical Systems (NEMS), especially flexural-mode resonators. The concurrent multiscale methodology we have developed for NEMS employs an atomistic description of millions of atoms in relatively small but key regions of the system, coupled to, and run concurrently with, a generalized finite element model of the periphery. We describe two such techniques. The more precise model, Coarse-Grained Molecular Dynamics (CGMD), describes the dynamics on a mesh of elements, but the equations of motion are built up from the underlying atomistic physics to ensure a smooth coupling between regions governed by different length scales. In many cases the degrees of smoothness of the coupling provided by CGMD is not necessary. The hybrid Coupling of Length Scales (CLS) methodology, combining molecular dynamics with conventional finite element modeling, provides a suitable technique for these cases at a greatly reduced computation expense. We review these models and some of the results we have obtained regarding size effects in the elasticity and dissipation of nanomechanical systems.

  5. 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.

  6. Coarse-Grained Model for Colloidal Protein Interactions, B22, and Protein Cluster Formation

    PubMed Central

    Blanco, Marco A.; Sahin, Eric; Robinson, Anne S.; Roberts, Christopher J.

    2014-01-01

    Reversible protein cluster formation is an important initial step in the processes of native and non-native protein aggregation, but involves relatively long time and length scales for detailed atomistic simulations and extensive mapping of free energy landscapes. A coarse-grained (CG) model is presented to semi-quantitatively characterize the thermodynamics and key configurations involved in the landscape for protein oligomerization, as well as experimental measures of interactions such as the osmotic second virial coefficient (B22). Based on earlier work, this CG model treats proteins as rigid bodies composed of one bead per amino acid, with each amino acid having specific parameters for its size, hydrophobicity, and charge. The net interactions are a combination of steric repulsions, short-range attractions, and screened long-range charge-charge interactions. Model parametrization was done by fitting simulation results against experimental values of the B22 as a function of solution ionic strength for α-chymotrypsinogen A and γD-crystallin (gD-Crys). The CG model is applied to characterize the pairwise interactions and dimerization of gD-Crys and the dependance on temperature, protein concentration, and ionic strength. The results illustrate that at experimentally relevant conditions where stable dimers do not form, the entropic contributions are predominant in the free-energy of protein cluster formation and colloidal protein interactions, arguing against interpretations that treat B22 primarily from energetic considerations alone. Additionally, the results suggest that electrostatic interactions help to modulate the population of the different stable configurations for protein nearest-neighbor pairs, while short-range attractions determine the relative orientations of proteins within these configurations. Finally, simulation results are combined with Principal Component Analysis to identify those amino-acids / surface patches that form inter-protein contacts

  7. A Coarse Grained Model for a Lipid Membrane with Physiological Composition and Leaflet Asymmetry

    PubMed Central

    Sharma, Satyan; Kim, Brian N.; Stansfeld, Phillip J.; Sansom, Mark S. P.; Lindau, Manfred

    2015-01-01

    The resemblance of lipid membrane models to physiological membranes determines how well molecular dynamics (MD) simulations imitate the dynamic behavior of cell membranes and membrane proteins. Physiological lipid membranes are composed of multiple types of phospholipids, and the leaflet compositions are generally asymmetric. Here we describe an approach for self-assembly of a Coarse-Grained (CG) membrane model with physiological composition and leaflet asymmetry using the MARTINI force field. An initial set-up of two boxes with different types of lipids according to the leaflet asymmetry of mammalian cell membranes stacked with 0.5 nm overlap, reliably resulted in the self-assembly of bilayer membranes with leaflet asymmetry resembling that of physiological mammalian cell membranes. Self-assembly in the presence of a fragment of the plasma membrane protein syntaxin 1A led to spontaneous specific positioning of phosphatidylionositol(4,5)bisphosphate at a positively charged stretch of syntaxin consistent with experimental data. An analogous approach choosing an initial set-up with two concentric shells filled with different lipid types results in successful assembly of a spherical vesicle with asymmetric leaflet composition. Self-assembly of the vesicle in the presence of the synaptic vesicle protein synaptobrevin 2 revealed the correct position of the synaptobrevin transmembrane domain. This is the first CG MD method to form a membrane with physiological lipid composition as well as leaflet asymmetry by self-assembly and will enable unbiased studies of the incorporation and dynamics of membrane proteins in more realistic CG membrane models. PMID:26659855

  8. 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

  9. TOPICAL REVIEW Coarse-grained models to study dynamics of nanoscale biomolecules and their applications to the ribosome

    NASA Astrophysics Data System (ADS)

    Trylska, Joanna

    2010-11-01

    Biopolymers are of dynamic nature and undergo functional motions spanning a large spectrum of timescales. To study the internal dynamics of nano-sized molecular complexes that exceed hundred thousands of atoms with atomic detail is computationally inefficient. Therefore, to achieve both the spatial and temporal scales of biological interest coarse-grained models of macromolecules are often used. By uniting groups of atoms into single interacting centers one decreases the resolution of the system and gets rid of the irrelevant degrees of freedom. This simplification, even though it requires parameterization, makes the studies of biomolecular dynamics computationally tractable and allows us to reach beyond the microsecond time frame. Here, I review the coarse-grained models of macromolecules composed of proteins and nucleic acids. I give examples of one-bead models that were developed to investigate the internal dynamics and focus on their applications to the ribosome—the nanoscale protein synthesis machine.

  10. Coarse-grained molecular dynamics modeling of the kinetics of lamellar BCP defect annealing

    NASA Astrophysics Data System (ADS)

    Peters, Andrew J.; Lawson, Richard A.; Nation, Benjamin D.; Ludovice, Peter J.; Henderson, Clifford L.

    2015-03-01

    Directed self-assembly of block copolymers (BCPs) is a process that has received great interest in the field of nanomanufacturing in the past decade, and great strides towards forming high quality aligned patterns have been made. But state of the art methods still yield defectivities orders of magnitude higher than is necessary in semi-conductor fabrication even though free energy calculations suggest that equilibrium defectivities are much lower than is necessary for economic semi-conductor 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 infinitely thick films yield an exponential drop in defect heal rate above χN ~ 30. Below χN ~ 30, the rate of transport was similar to the rate at which the transition state was reached so that the overall rate changed only slightly. The energy barrier in periodic simulations increased with 0.31 χN on average. Thin film simulations show no change in rate associated with the energy barrier below χN ~ 50, and then show an increase in energy barrier scaling with 0.16χN. Thin film simulations always begin to heal at either the free interface or the BCP-underlayer interface where the increased A-B contact area associated with the transition state will be minimized, while the infinitely thick films must start healing in the bulk where the A-B contact area is increased. It is also found that cooperative chain movement is required for the defect to start healing.

  11. 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

  12. 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

  13. N-Body interactions in soft-sphere coarse-grained models of star polymers.

    PubMed

    Pelissetto, Andrea

    2012-02-01

    We consider the coarse-grained approach in which star polymers are mapped onto atoms located at the centers of the stars interacting by means of ultrasoft potentials. We generalize the Witten-Pincus formula to all n-body potentials: in the good-solvent regime all potentials show an ultrasoft logarithmic divergence when the relative distance of all n stars goes to zero, with coefficients that can be related to the partition-function exponents γ(f). PMID:22463232

  14. 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.

  15. 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

  16. Understanding the apparent stator-rotor connections in the rotary ATPase family using coarse-grained computer modeling.

    PubMed

    Richardson, Robin A; Papachristos, Konstantinos; Read, Daniel J; Harlen, Oliver G; Harrison, Michael; Paci, Emanuele; Muench, Stephen P; Harris, Sarah A

    2014-12-01

    Advances in structural biology, such as cryo-electron microscopy (cryo-EM) have allowed for a number of sophisticated protein complexes to be characterized. However, often only a static snapshot of a protein complex is visualized despite the fact that conformational change is frequently inherent to biological function, as is the case for molecular motors. Computer simulations provide valuable insights into the different conformations available to a particular system that are not accessible using conventional structural techniques. For larger proteins and protein complexes, where a fully atomistic description would be computationally prohibitive, coarse-grained simulation techniques such as Elastic Network Modeling (ENM) are often employed, whereby each atom or group of atoms is linked by a set of springs whose properties can be customized according to the system of interest. Here we compare ENM with a recently proposed continuum model known as Fluctuating Finite Element Analysis (FFEA), which represents the biomolecule as a viscoelastic solid subject to thermal fluctuations. These two complementary computational techniques are used to answer a critical question in the rotary ATPase family; implicit within these motors is the need for a rotor axle and proton pump to rotate freely of the motor domain and stator structures. However, current single particle cryo-EM reconstructions have shown an apparent connection between the stators and rotor axle or pump region, hindering rotation. Both modeling approaches show a possible role for this connection and how it would significantly constrain the mobility of the rotary ATPase family. PMID:25174610

  17. Coarse-grained ions without charges: Reproducing the solvation structure of NaCl in water using short-ranged potentials

    NASA Astrophysics Data System (ADS)

    DeMille, Robert C.; Molinero, Valeria

    2009-07-01

    A coarse-grained model of NaCl in water is presented where the ions are modeled without charge to avoid computationally challenging electrostatics. A monatomic model of water [V. Molinero and E. B. Moore, J. Phys. Chem. B 113, 4008 (2009)] is used as the basis for this coarse-grain approach. The ability of Na+ to disrupt the native tetrahedral arrangement of water molecules, and of Cl- to integrate within this organization, is preserved in this mW-ion model through parametrization focused on water's solvation of these ions. This model successfully reproduces the structural effect of ions on water, referenced to observations from experiments and atomistic molecular dynamics simulations, while using extremely short-ranged potentials. Without Coulomb interactions the model replicates details of the ion-water structure such as distinguishing contact and solvent-separated ion pairs and the free energy barriers between them. The approach of mimicking ionic effects with short-ranged interactions results in performance gains of two orders of magnitude compared to Ewald methods. Explored over a broad range of salt concentration, the model reproduces the solvation structure and trends of diffusion relative to atomistic simulations and experimental results. The functional form of the mW-ion model can be parametrized to represent other electrolytes. With increased computational efficiency and reliable structural fidelity, this model promises to be an asset for accessing significantly longer simulation time scales with an explicit solvent in a coarse-grained system involving, for example, polyelectrolytes such as proteins, nucleic acids, and fuel-cell membranes.

  18. Coarse-grained model for colloidal protein interactions, B(22), and protein cluster formation.

    PubMed

    Blanco, Marco A; Sahin, Erinc; Robinson, Anne S; Roberts, Christopher J

    2013-12-19

    Reversible protein cluster formation is an important initial step in the processes of native and non-native protein aggregation, but involves relatively long time and length scales for detailed atomistic simulations and extensive mapping of free energy landscapes. A coarse-grained (CG) model is presented to semiquantitatively characterize the thermodynamics and key configurations involved in the landscape for protein oligomerization, as well as experimental measures of interactions such as the osmotic second virial coefficient (B22). Based on earlier work (Grüenberger et al., J. Phys. Chem. B 2013, 117, 763), this CG model treats proteins as rigid bodies composed of one bead per amino acid, with each amino acid having specific parameters for its size, hydrophobicity, and charge. The net interactions are a combination of steric repulsions, short-range attractions, and screened long-range charge-charge interactions. Model parametrization was done by fitting simulation results against experimental value of B22 as a function of solution ionic strength for α-chymotrypsinogen A and γD-Crystallin (gD-Crys). The CG model is applied to characterize the pairwise interactions and dimerization of gD-Crys and the dependence on temperature, protein concentration, and ionic strength. The results illustrate that at experimentally relevant conditions where stable dimers do not form, the entropic contributions are predominant in the free-energy of protein cluster formation and colloidal protein interactions, arguing against interpretations that treat B22 primarily from energetic considerations alone. Additionally, the results suggest that electrostatic interactions help to modulate the population of the different stable configurations for protein nearest-neighbor pairs, while short-range attractions determine the relative orientations of proteins within these configurations. Finally, simulation results are combined with Principal Component Analysis to identify those amino

  19. Discriminating binding mechanisms of an intrinsically disordered protein via a multi-state coarse-grained model

    SciTech Connect

    Knott, Michael; Best, Robert B.

    2014-05-07

    Many proteins undergo a conformational transition upon binding to their cognate binding partner, with intrinsically disordered proteins (IDPs) providing an extreme example in which a folding transition occurs. However, it is often not clear whether this occurs via an “induced fit” or “conformational selection” mechanism, or via some intermediate scenario. In the first case, transient encounters with the binding partner favour transitions to the bound structure before the two proteins dissociate, while in the second the bound structure must be selected from a subset of unbound structures which are in the correct state for binding, because transient encounters of the incorrect conformation with the binding partner are most likely to result in dissociation. A particularly interesting situation involves those intrinsically disordered proteins which can bind to different binding partners in different conformations. We have devised a multi-state coarse-grained simulation model which is able to capture the binding of IDPs in alternate conformations, and by applying it to the binding of nuclear coactivator binding domain (NCBD) to either ACTR or IRF-3 we are able to determine the binding mechanism. By all measures, the binding of NCBD to either binding partner appears to occur via an induced fit mechanism. Nonetheless, we also show how a scenario closer to conformational selection could arise by choosing an alternative non-binding structure for NCBD.

  20. Discriminating binding mechanisms of an intrinsically disordered protein via a multi-state coarse-grained model

    PubMed Central

    Knott, Michael; Best, Robert B.

    2014-01-01

    Many proteins undergo a conformational transition upon binding to their cognate binding partner, with intrinsically disordered proteins (IDPs) providing an extreme example in which a folding transition occurs. However, it is often not clear whether this occurs via an “induced fit” or “conformational selection” mechanism, or via some intermediate scenario. In the first case, transient encounters with the binding partner favour transitions to the bound structure before the two proteins dissociate, while in the second the bound structure must be selected from a subset of unbound structures which are in the correct state for binding, because transient encounters of the incorrect conformation with the binding partner are most likely to result in dissociation. A particularly interesting situation involves those intrinsically disordered proteins which can bind to different binding partners in different conformations. We have devised a multi-state coarse-grained simulation model which is able to capture the binding of IDPs in alternate conformations, and by applying it to the binding of nuclear coactivator binding domain (NCBD) to either ACTR or IRF-3 we are able to determine the binding mechanism. By all measures, the binding of NCBD to either binding partner appears to occur via an induced fit mechanism. Nonetheless, we also show how a scenario closer to conformational selection could arise by choosing an alternative non-binding structure for NCBD. PMID:24811666

  1. 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

  2. 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.

  3. Combining a polarizable force-field and a coarse-grained polarizable solvent model. II. Accounting for hydrophobic effects.

    PubMed

    Masella, Michel; Borgis, Daniel; Cuniasse, Philippe

    2011-09-01

    A revised and improved version of our efficient polarizable force-field/coarse grained solvent combined approach (Masella, Borgis, and Cuniasse, J. Comput. Chem. 2008, 29, 1707) is described. The polarizable pseudo-particle solvent model represents the macroscopic solvent polarization by induced dipoles placed on mobile pseudo-particles. In this study, we propose a new formulation of the energy term handling the nonelectrostatic interactions among the pseudo-particles. This term is now able to reproduce the energetic and structural response of liquid water due to the presence of a hydrophobic spherical cavity. Accordingly, the parameters of the energy term handling the nonpolar solute/solvent interactions have been refined to reproduce the free-solvation energy of small solutes, based on a standard thermodynamic integration scheme. The reliability of this new approach has been checked for the properties of solvated methane and of the solvated methane dimer, as well as by performing 10 × 20 ns molecular dynamics (MD) trajectories for three solvated proteins. A long-time stability of the protein structures along the trajectories is observed. Moreover, our method still provides a measure of the protein solvation thermodynamic at the same accuracy as standard Poisson-Boltzman continuum methods. These results show the relevance of our approach and its applicability to massively coupled MD schemes to accurately and intensively explore solvated macromolecule potential energy surfaces. PMID:21647929

  4. 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

  5. Sliding of Proteins Non-specifically Bound to DNA: Brownian Dynamics Studies with Coarse-Grained Protein and DNA Models

    PubMed Central

    Ando, Tadashi; Skolnick, Jeffrey

    2014-01-01

    DNA binding proteins efficiently search for their cognitive sites on long genomic DNA by combining 3D diffusion and 1D diffusion (sliding) along the DNA. Recent experimental results and theoretical analyses revealed that the proteins show a rotation-coupled sliding along DNA helical pitch. Here, we performed Brownian dynamics simulations using newly developed coarse-grained protein and DNA models for evaluating how hydrodynamic interactions between the protein and DNA molecules, binding affinity of the protein to DNA, and DNA fluctuations affect the one dimensional diffusion of the protein on the DNA. Our results indicate that intermolecular hydrodynamic interactions reduce 1D diffusivity by 30%. On the other hand, structural fluctuations of DNA give rise to steric collisions between the CG-proteins and DNA, resulting in faster 1D sliding of the protein. Proteins with low binding affinities consistent with experimental estimates of non-specific DNA binding show hopping along the CG-DNA. This hopping significantly increases sliding speed. These simulation studies provide additional insights into the mechanism of how DNA binding proteins find their target sites on the genome. PMID:25504215

  6. A coarse-grained model of thermally activated damage in heterogeneous media: Time evolution of the creep rate

    NASA Astrophysics Data System (ADS)

    Baxevanis, Th.

    2008-08-01

    A coarse-grained mean-field model is proposed where the damage enhanced creep of heterogeneous materials is described by the theory of absolute reaction rates. The dynamics of the proposed model, below a critical load, is characterized by an intensive precursor activity in the form of avalanches of microscopic breaking events that leads to a final catastrophic cascade occurring at a finite strain. Above the critical load, failure is instantaneous. The critical load is the static (elastic) fracture strength; thus the model is consistent with its time-independent analogue. Finally, the proposed model reproduces the experimental observations on the time evolution of the creep rate.

  7. THE OPEP COARSE-GRAINED PROTEIN MODEL: FROM SINGLE MOLECULES, AMYLOID FORMATION, ROLE OF MACROMOLECULAR CROWDING AND HYDRODYNAMICS TO RNA/DNA COMPLEXES

    PubMed Central

    Sterpone, Fabio; Melchionna, Simone; Tuffery, Pierre; Pasquali, Samuela; Mousseau, Normand; Cragnolini, Tristan; Chebaro, Yassmine; Saint-Pierre, Jean-Francois; Kalimeri, Maria; Barducci, Alessandro; Laurin, Yohan; Tek, Alex; Baaden, Marc; Nguyen, Phuong Hoang; Derreumaux, Philippe

    2015-01-01

    The OPEP coarse-grained protein model has been applied to a wide range of applications since its first release 15 years ago. The model, which combines energetic and structural accuracy and chemical specificity, allows studying single protein properties, DNA/RNA complexes, amyloid fibril formation and protein suspensions in a crowded environment. Here we first review the current state of the model and the most exciting applications using advanced conformational sampling methods. We then present the current limitations and a perspective on the on-going developments. PMID:24759934

  8. Reconciling Structural and Thermodynamic Predictions Using All-Atom and Coarse-Grain Force Fields: The Case of Charged Oligo-Arginine Translocation into DMPC Bilayers

    PubMed Central

    2015-01-01

    Using the translocation of short, charged cationic oligo-arginine peptides (mono-, di-, and triarginine) from bulk aqueous solution into model DMPC bilayers, we explore the question of the similarity of thermodynamic and structural predictions obtained from molecular dynamics simulations using all-atom and Martini coarse-grain force fields. Specifically, we estimate potentials of mean force associated with translocation using standard all-atom (CHARMM36 lipid) and polarizable and nonpolarizable Martini force fields, as well as a series of modified Martini-based parameter sets. We find that we are able to reproduce qualitative features of potentials of mean force of single amino acid side chain analogues into model bilayers. In particular, modifications of peptide–water and peptide–membrane interactions allow prediction of free energy minima at the bilayer–water interface as obtained with all-atom force fields. In the case of oligo-arginine peptides, the modified parameter sets predict interfacial free energy minima as well as free energy barriers in almost quantitative agreement with all-atom force field based simulations. Interfacial free energy minima predicted by a modified coarse-grained parameter set are −2.51, −4.28, and −5.42 for mono-, di-, and triarginine; corresponding values from all-atom simulations are −0.83, −3.33, and −3.29, respectively, all in units of kcal/mol. We found that a stronger interaction between oligo-arginine and the membrane components and a weaker interaction between oligo-arginine and water are crucial for producing such minima in PMFs using the polarizable CG model. The difference between bulk aqueous and bilayer center states predicted by the modified coarse-grain force field are 11.71, 14.14, and 16.53 kcal/mol, and those by the all-atom model are 6.94, 8.64, and 12.80 kcal/mol; those are of almost the same order of magnitude. Our simulations also demonstrate a remarkable similarity in the structural aspects of

  9. Conformational Properties of Sodium Polystyrenesulfonate in Water: Insights from a Coarse-Grained Model with Explicit Solvent.

    PubMed

    Mantha, Sriteja; Yethiraj, Arun

    2015-08-27

    Polymer solutions present a significant computational challenge because chemical realism on small length scales can be important, but the polymer molecules are very large. In polyelectrolyte solutions, there is often the additional complexity that the molecules consist of hydrophobic and charged groups, which makes an accurate treatment of the solvent, water, crucial. One route to achieve this balance is through coarse-grained models where several atoms on a monomer are grouped into one interaction site. In this work, we develop a coarse grained (CG) model for sodium polystyrenesulfonate (NaPSS) in water using a methodology consistent with the MARTINI coarse-graining philosophy, where four heavy atoms are grouped into one CG site. We consider two models for water: polarizable MARTINI (POL) and big multipole water (BMW). In each case, interaction parameters for the polymer sites are obtained by matching the potential of mean force between two monomers to results of atomistic simulations. The force field based on the POL water provides a more reasonable description of polymer properties than that based on the BMW water. We study the properties of single chains using the POL force field. Fully sulfonated chains are rodlike (i.e., the root-mean-square radius of gyration, Rg, scales linearly with degree of polymerization, N). When the fraction of sulfonation, f, is 0.25 or less, the chain collapses into a cylindrical globule. For f = 0.5, pearl-necklace conformations are observed when every second monomer is sulfonated. The lifetime of a counterion around a polymer is on the order of 100 ps, suggesting that there is no counterion condensation. The model is computationally feasible and should allow one to study the effect of local chemistry on the properties of polymers in aqueous solution. PMID:26047770

  10. 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