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Sample records for coarse-grained structural modeling

  1. Coarse-grained modeling of RNA 3D structure.

    PubMed

    Dawson, Wayne K; Maciejczyk, Maciej; Jankowska, Elzbieta J; Bujnicki, Janusz M

    2016-07-01

    Functional RNA molecules depend on three-dimensional (3D) structures to carry out their tasks within the cell. Understanding how these molecules interact to carry out their biological roles requires a detailed knowledge of RNA 3D structure and dynamics as well as thermodynamics, which strongly governs the folding of RNA and RNA-RNA interactions as well as a host of other interactions within the cellular environment. Experimental determination of these properties is difficult, and various computational methods have been developed to model the folding of RNA 3D structures and their interactions with other molecules. However, computational methods also have their limitations, especially when the biological effects demand computation of the dynamics beyond a few hundred nanoseconds. For the researcher confronted with such challenges, a more amenable approach is to resort to coarse-grained modeling to reduce the number of data points and computational demand to a more tractable size, while sacrificing as little critical information as possible. This review presents an introduction to the topic of coarse-grained modeling of RNA 3D structures and dynamics, covering both high- and low-resolution strategies. We discuss how physics-based approaches compare with knowledge based methods that rely on databases of information. In the course of this review, we discuss important aspects in the reasoning process behind building different models and the goals and pitfalls that can result.

  2. Coarse graining approach to First principles modeling of structural materials

    SciTech Connect

    Odbadrakh, Khorgolkhuu; Nicholson, Don M; Rusanu, Aurelian; Samolyuk, German D; Wang, Yang; Stoller, Roger E; Zhang, X.-G.; Stocks, George Malcolm

    2013-01-01

    Classical Molecular Dynamic (MD) simulations characterizing extended defects typically require millions of atoms. First principles calculations employed to understand these defect systems at an electronic level cannot, and should not deal with such large numbers of atoms. We present an e cient coarse graining (CG) approach to calculate local electronic properties of large MD-generated structures from the rst principles. We used the Locally Self-consistent Multiple Scattering (LSMS) method for two types of iron defect structures 1) screw-dislocation dipoles and 2) radiation cascades. The multiple scattering equations are solved at fewer sites using the CG. The atomic positions were determined by MD with an embedded atom force eld. The local moments in the neighborhood of the defect cores are calculated with rst-principles based on full local structure information, while atoms in the rest of the system are modeled by representative atoms with approximated properties. This CG approach reduces computational costs signi cantly and makes large-scale structures amenable to rst principles study. Work is sponsored by the USDoE, O ce of Basic Energy Sciences, Center for Defect Physics, an Energy Frontier Research Center. This research used resources of the Oak Ridge Leadership Computing Facility at the ORNL, which is supported by the O ce of Science of the USDoE under Contract No. DE-AC05-00OR22725.

  3. Coarse-grained description of cosmic structure from Szekeres models

    SciTech Connect

    Sussman, Roberto A.; Gaspar, I. Delgado; Hidalgo, Juan Carlos E-mail: ismael.delgadog@uaem.edu.mx

    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.

  4. 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.

  5. 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.

  6. 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

  7. Computational methods toward accurate RNA structure prediction using coarse-grained and all-atom models.

    PubMed

    Krokhotin, Andrey; Dokholyan, Nikolay V

    2015-01-01

    Computational methods can provide significant insights into RNA structure and dynamics, bridging the gap in our understanding of the relationship between structure and biological function. Simulations enrich and enhance our understanding of data derived on the bench, as well as provide feasible alternatives to costly or technically challenging experiments. Coarse-grained computational models of RNA are especially important in this regard, as they allow analysis of events occurring in timescales relevant to RNA biological function, which are inaccessible through experimental methods alone. We have developed a three-bead coarse-grained model of RNA for discrete molecular dynamics simulations. This model is efficient in de novo prediction of short RNA tertiary structure, starting from RNA primary sequences of less than 50 nucleotides. To complement this model, we have incorporated additional base-pairing constraints and have developed a bias potential reliant on data obtained from hydroxyl probing experiments that guide RNA folding to its correct state. By introducing experimentally derived constraints to our computer simulations, we are able to make reliable predictions of RNA tertiary structures up to a few hundred nucleotides. Our refined model exemplifies a valuable benefit achieved through integration of computation and experimental methods.

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

    PubMed

    Kerpedjiev, Peter; Höner Zu Siederdissen, Christian; Hofacker, Ivo L

    2015-06-01

    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. © 2015 Kerpedjiev et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  9. Coarse-Grained Structural Modeling of Molecular Motors Using Multibody Dynamics.

    PubMed

    Parker, David; Bryant, Zev; Delp, Scott L

    2009-09-01

    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.

  10. A unified approach to preserve structure and thermodynamics in a coarse-grained model of aqueous mixtures

    NASA Astrophysics Data System (ADS)

    Ganguly, Pritam; Mukherji, Debashish; Junghans, Christoph; van der Vegt, Nico

    2012-02-01

    Biological organizations depend on a sensitive balance of noncovalent interactions, in particular also those involving interactions of small molecules, including inorganic salts and urea, with biomolecules in aqueous solution. Computer simulations of these types of systems require simple-yet-specific models in order to cover all relevant time and length scales. We present a method to systematically coarse-grain liquid mixtures using Kirkwood-Buff theory of solution combined with an iterative Boltzmann inversion technique that infers single-site interaction potentials for the solution components from the pair correlation functions. Our method preserves both the solution structure at pair level and variations of solution components' chemical potentials with compositions within a unified coarse-graining framework. To test the robustness of our approach, we simulated urea-water and benzene-water systems over a wide-range of concentrations. We also observe the coarse-grained potentials to be reasonably transferable with varying concentrations.

  11. 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.

  12. Introducing improved structural properties and salt dependence into a coarse-grained model of DNA

    NASA Astrophysics Data System (ADS)

    Snodin, Benedict E. K.; Randisi, Ferdinando; Mosayebi, Majid; Šulc, Petr; Schreck, John S.; Romano, Flavio; Ouldridge, Thomas E.; Tsukanov, Roman; Nir, Eyal; Louis, Ard A.; Doye, Jonathan P. K.

    2015-06-01

    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+] = 0.5M), so that it can be used for a range of salt concentrations including those corresponding to physiological conditions. Finally, we use new experimental data to parameterise the oxDNA potential so that consecutive adenine bases stack with a different strength to consecutive thymine bases, a feature which allows a more accurate treatment of systems where the flexibility of single-stranded regions is important. We illustrate the new possibilities opened up by the updated model, oxDNA2, by presenting results from simulations of the structure of large DNA objects and by using the model to investigate some salt-dependent properties of DNA.

  13. Introducing improved structural properties and salt dependence into a coarse-grained model of DNA.

    PubMed

    Snodin, Benedict E K; Randisi, Ferdinando; Mosayebi, Majid; Šulc, Petr; Schreck, John S; Romano, Flavio; Ouldridge, Thomas E; Tsukanov, Roman; Nir, Eyal; Louis, Ard A; Doye, Jonathan P K

    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(+)] = 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.

  14. Structural, mechanical, and thermodynamic properties of a coarse-grained DNA model

    NASA Astrophysics Data System (ADS)

    Ouldridge, Thomas E.; Louis, Ard A.; Doye, Jonathan P. K.

    2011-02-01

    We explore in detail the structural, mechanical, and thermodynamic properties of a coarse-grained model of DNA similar to that recently introduced in a study of DNA nanotweezers [T. E. Ouldridge, A. A. Louis, and J. P. K. Doye, Phys. Rev. Lett. 134, 178101 (2010)]. Effective interactions are used to represent chain connectivity, excluded volume, base stacking, and hydrogen bonding, naturally reproducing a range of DNA behavior. The model incorporates the specificity of Watson-Crick base pairing, but otherwise neglects sequence dependence of interaction strengths, resulting in an "average base" description of DNA. We quantify the relation to experiment of the thermodynamics of single-stranded stacking, duplex hybridization, and hairpin formation, as well as structural properties such as the persistence length of single strands and duplexes, and the elastic torsional and stretching moduli of double helices. We also explore the model's representation of more complex motifs involving dangling ends, bulged bases and internal loops, and the effect of stacking and fraying on the thermodynamics of the duplex formation transition.

  15. 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

  16. 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

  17. 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.

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

    PubMed

    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, UV(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 UV, 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 UV 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.

  19. 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

  20. Multi-Body Coarse-Grained Potentials for Native Structure Recognition and Quality Assessment of Protein Models

    PubMed Central

    Gniewek, Pawel; Leelananda, Sumudu P.; Kolinski, Andrzej; Jernigan, Robert L.; Kloczkowski, Andrzej

    2011-01-01

    Summary Multi-body potentials have been of much interest recently because they take into account three dimensional interactions related to residue packing and capture the cooperativity of these interactions in protein structures. Our goal was to combine long range multi-body potentials and short range potentials to improve recognition of native structure among misfolded decoys. We optimized the weights for four-body non-sequential, four-body sequential and short range potentials in order to obtain optimal model ranking results for threading and have compared these data against results obtained with other potentials. (Twenty six different coarse-grained potentials from the Potentials ‘R’Us web server have been used.) Our optimized multi-body potentials outperform all other contact potentials in the recognition of the native structure among decoys, both for models from homology template-based modeling and from template-free modeling in CASP8 decoy sets. We have compared the results obtained for this optimized coarse-grained potentials, where each residue is represented by a single point, with results obtained by using the DFIRE potential, which takes into account atomic level information of proteins. We found that for all proteins larger than 80 amino acids our optimized coarse-grained potentials yield results comparable to those obtained with the atomic DFIRE potential. PMID:21560165

  1. Structurally detailed coarse-grained model for Sec-facilitated co-translational protein translocation and membrane integration

    PubMed Central

    Miller, Thomas F.

    2017-01-01

    We present a coarse-grained simulation model that is capable of simulating the minute-timescale dynamics of protein translocation and membrane integration via the Sec translocon, while retaining sufficient chemical and structural detail to capture many of the sequence-specific interactions that drive these processes. The model includes accurate geometric representations of the ribosome and Sec translocon, obtained directly from experimental structures, and interactions parameterized from nearly 200 μs of residue-based coarse-grained molecular dynamics simulations. A protocol for mapping amino-acid sequences to coarse-grained beads enables the direct simulation of trajectories for the co-translational insertion of arbitrary polypeptide sequences into the Sec translocon. The model reproduces experimentally observed features of membrane protein integration, including the efficiency with which polypeptide domains integrate into the membrane, the variation in integration efficiency upon single amino-acid mutations, and the orientation of transmembrane domains. The central advantage of the model is that it connects sequence-level protein features to biological observables and timescales, enabling direct simulation for the mechanistic analysis of co-translational integration and for the engineering of membrane proteins with enhanced membrane integration efficiency. PMID:28328943

  2. 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.

  3. 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.

  4. Coarse grained normal mode analysis vs. refined Gaussian Network Model for protein residue-level structural fluctuations.

    PubMed

    Park, Jun-Koo; Jernigan, Robert; Wu, Zhijun

    2013-01-01

    We investigate several approaches to coarse grained normal mode analysis on protein residual-level structural fluctuations by choosing different ways of representing the residues and the forces among them. Single-atom representations using the backbone atoms C(α), C, N, and C(β) are considered. Combinations of some of these atoms are also tested. The force constants between the representative atoms are extracted from the Hessian matrix of the energy function and served as the force constants between the corresponding residues. The residue mean-square-fluctuations and their correlations with the experimental B-factors are calculated for a large set of proteins. The results are compared with all-atom normal mode analysis and the residue-level Gaussian Network Model. The coarse-grained methods perform more efficiently than all-atom normal mode analysis, while their B-factor correlations are also higher. Their B-factor correlations are comparable with those estimated by the Gaussian Network Model and in many cases better. The extracted force constants are surveyed for different pairs of residues with different numbers of separation residues in sequence. The statistical averages are used to build a refined Gaussian Network Model, which is able to predict residue-level structural fluctuations significantly better than the conventional Gaussian Network Model in many test cases.

  5. 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.

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

    PubMed

    Poulain, P; Saladin, A; Hartmann, B; Prévost, C

    2008-11-30

    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 acid side chains strengthen the binding. Overall, this work demonstrates that coarse grain modeling can reveal itself a precious auxiliary for a general and complete description and understanding of protein-DNA association mechanisms.

  7. Structure-based coarse-graining in liquid slabs.

    PubMed

    Jochum, Mara; Andrienko, Denis; Kremer, Kurt; Peter, Christine

    2012-08-14

    Structure-based coarse-graining relies on matching the pair correlation functions of a reference (atomistic) and a coarse-grained system. As such, it is designed for systems with uniform density distributions. Here, we demonstrate how it can be generalized for inhomogeneous systems by coarse-graining slabs of liquid water and methanol in vacuum, as well as a single benzene molecule at the water-vacuum interface. Our conclusion is that coarse-graining performed in inhomogeneous systems improves thermodynamic properties and the structure of interfaces without significant alterations to the local structure of the bulk liquid.

  8. An experimentally-informed coarse-grained 3-site-per-nucleotide model of DNA: Structure, thermodynamics, and dynamics of hybridization

    NASA Astrophysics Data System (ADS)

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

    2013-10-01

    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.

  9. Coarse-grained model of glycosaminoglycans.

    PubMed

    Samsonov, Sergey A; Bichmann, Leon; Pisabarro, M Teresa

    2015-01-26

    Glycosaminoglycans (GAGs) represent a class of anionic periodic linear polysaccharides, which mediate cell communication processes by interactions with their protein targets in the extracellular matrix. Due to their high flexibility, charged nature, periodicity, and polymeric nature, GAGs are challenging systems for computational approaches. To deal with the length challenge, coarse-grained (CG) modeling could be a promising approach. In this work, we develop AMBER-compatible CG parameters for GAGs using all-atomic (AA) molecular dynamics (MD) simulations in explicit solvent and the Boltzmann conversion approach. We compare both global and local properties of GAGs obtained in the simulations with AA and CG approaches, and we conclude that our CG model is appropriate for the MD approach of long GAG molecules at long time scales.

  10. 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.

  11. 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.

  12. Recent Advances in Transferable Coarse-Grained Modeling of Proteins

    PubMed Central

    Kar, Parimal; Feig, Michael

    2017-01-01

    Computer simulations are indispensable tools for studying the structure and dynamics of biological macromolecules. Biochemical processes occur on different scales of length and time. Atomistic simulations cannot cover the relevant spatiotemporal scales at which the cellular processes occur. To address this challenge, coarse-grained (CG) modeling of the biological systems are employed. Over the last few years, many CG models for proteins continue to be developed. However, many of them are not transferable with respect to different systems and different environments. In this review, we discuss those CG protein models that are transferable and that retain chemical specificity. We restrict ourselves to CG models of soluble proteins only. We also briefly review recent progress made in the multi-scale hybrid all-atom/coarse-grained simulations of proteins. PMID:25443957

  13. 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

  14. Analytical structure, dynamics, and coarse graining of a kinetic model of an active fluid

    NASA Astrophysics Data System (ADS)

    Gao, Tong; Betterton, Meredith D.; Jhang, An-Sheng; Shelley, Michael J.

    2017-09-01

    We analyze one of the simplest active suspensions with complex dynamics: a suspension of immotile "extensor" particles that exert active extensile dipolar stresses on the fluid in which they are immersed. This is relevant to several experimental systems, such as recently studied tripartite rods that create extensile flows by consuming a chemical fuel. We first describe the system through a Doi-Onsager kinetic theory based on microscopic modeling. This theory captures the active stresses produced by the particles that can drive hydrodynamic instabilities, as well as the steric interactions of rodlike particles that lead to nematic alignment. This active nematic system yields complex flows and disclination defect dynamics very similar to phenomenological Landau-deGennes Q -tensor theories for active nematic fluids, as well as by more complex Doi-Onsager theories for polar microtubule-motor-protein systems. We apply the quasiequilibrium Bingham closure, used to study suspensions of passive microscopic rods, to develop a nonstandard Q -tensor theory. We demonstrate through simulation that this B Q -tensor theory gives an excellent analytical and statistical accounting of the suspension's complex dynamics, at a far reduced computational cost. Finally, we apply the B Q -tensor model to study the dynamics of extensor suspensions in circular and biconcave domains. In circular domains, we reproduce previous results for systems with weak nematic alignment, but for strong alignment we find unusual dynamics with activity-controlled defect production and absorption at the boundaries of the domain. In biconcave domains, a Fredericks-like transition occurs as the width of the neck connecting the two disks is varied.

  15. A coarse-grained model for PETN crystals

    SciTech Connect

    Gee, R; Wu, C; Maiti, A

    2006-02-10

    Using the energetic material Pentaerythritol Tetranitrate (PETN) as a specific example of molecular crystal, we describe the development of a simple coarse-graining procedure by grouping several atoms or whole functional groups into single charge-neutral beads. As compared to fully atomistic calculations the coarse-grained model speeds up simulations by more than two orders of magnitude. Yet, by adjusting only two parameters in the coarse-grained interaction, the model accurately predicts the lattice constants, sublimation energy, pressure-volume curve up to P=10 GPa, and energetically the most stable facets. Computed surface and desorption energies, bulk modulus, and equilibrium morphology are reported as well.

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

    PubMed

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

    2008-06-28

    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(+)NO(3) (-) ionic liquid are provided to illustrate the method.

  17. Dynamical coarse grained models with realistic time dependence

    NASA Astrophysics Data System (ADS)

    Andersen, Hans

    2015-03-01

    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. 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 an 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 was studied by Zwanzig [R. Zwanzig, J. Stat. Phys. 9, 215 (1973)]. The dynamic models generate a non-Markovian dynamics for the CG degrees of freedom, but they can be easily simulated using standard molecular dynamics simulation programs. We present tests of this method on a series of simple examples that demonstrate that the method provides realistic dynamical CG models that have non-Markovian or close to Markovian behavior that is consistent with the actual dynamical behavior of the all-atom system used to construct the CG model. The dynamic CG models have computational requirements that are similar to

  18. 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

  19. 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

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

    DOE PAGES

    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

  1. 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.

  2. A coarse grain model for protein-surface interactions.

    PubMed

    Wei, Shuai; Knotts, Thomas A

    2013-09-07

    The interaction of proteins with surfaces is important in numerous applications in many fields-such as biotechnology, proteomics, sensors, and medicine--but fundamental understanding of how protein stability and structure are affected by surfaces remains incomplete. Over the last several years, molecular simulation using coarse grain models has yielded significant insights, but the formalisms used to represent the surface interactions have been rudimentary. We present a new model for protein surface interactions that incorporates the chemical specificity of both the surface and the residues comprising the protein in the context of a one-bead-per-residue, coarse grain approach that maintains computational efficiency. The model is parameterized against experimental adsorption energies for multiple model peptides on different types of surfaces. The validity of the model is established by its ability to quantitatively and qualitatively predict the free energy of adsorption and structural changes for multiple biologically-relevant proteins on different surfaces. The validation, done with proteins not used in parameterization, shows that the model produces remarkable agreement between simulation and experiment.

  3. A coarse grain model for protein-surface interactions

    NASA Astrophysics Data System (ADS)

    Wei, Shuai; Knotts, Thomas A.

    2013-09-01

    The interaction of proteins with surfaces is important in numerous applications in many fields—such as biotechnology, proteomics, sensors, and medicine—but fundamental understanding of how protein stability and structure are affected by surfaces remains incomplete. Over the last several years, molecular simulation using coarse grain models has yielded significant insights, but the formalisms used to represent the surface interactions have been rudimentary. We present a new model for protein surface interactions that incorporates the chemical specificity of both the surface and the residues comprising the protein in the context of a one-bead-per-residue, coarse grain approach that maintains computational efficiency. The model is parameterized against experimental adsorption energies for multiple model peptides on different types of surfaces. The validity of the model is established by its ability to quantitatively and qualitatively predict the free energy of adsorption and structural changes for multiple biologically-relevant proteins on different surfaces. The validation, done with proteins not used in parameterization, shows that the model produces remarkable agreement between simulation and experiment.

  4. 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.

  5. Obtaining fully dynamic coarse-grained models from MD.

    PubMed

    Español, Pep; Zúñiga, Ignacio

    2011-06-14

    We present a general method to obtain parametrised models for the drift and diffusion terms of the Fokker-Planck equation of a coarse-grained description of molecular systems. The method is based on the minimisation of the relative entropy defined in terms of the two-time joint probability and thus captures the full dynamics of the coarse-grained description. In addition, we show an alternative Bayesian argument that starts from the path probability of a diffusion process which allows one to obtain the best parametrised model that fits an actual observed path of the coarse-grained variables. Both approaches lead to exactly the same optimisation function giving strong support to the methodology. We provide an heuristic argument that explains how both approaches are connected.

  6. MARTINI Coarse-Grained Models of Polyethylene and Polypropylene.

    PubMed

    Panizon, Emanuele; Bochicchio, Davide; Monticelli, Luca; Rossi, Giulia

    2015-06-25

    The understanding of the interaction of nanoplastics with living organisms is crucial both to assess the health hazards of degraded plastics and to design functional polymer nanoparticles with biomedical applications. In this paper, we develop two coarse-grained models of everyday use polymers, polyethylene (PE) and polypropylene (PP), aimed at the study of the interaction of hydrophobic plastics with lipid membranes. The models are compatible with the popular MARTINI force field for lipids, and they are developed using both structural and thermodynamic properties as targets in the parametrization. The models are then validated by showing their reliability at reproducing structural properties of the polymers, both linear and branched, in dilute conditions, in the melt, and in a PE-PP blend. PE and PP radius of gyration is correctly reproduced in all conditions, while PE-PP interactions in the blend are slightly overestimated. Partitioning of PP and PE oligomers in phosphatidylcholine membranes as obtained at CG level reproduces well atomistic data.

  7. 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.

  8. 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.

  9. One-bead coarse-grained model for RNA dynamics.

    PubMed

    Villada-Balbuena, Mario; Carbajal-Tinoco, Mauricio D

    2017-01-28

    We present a revised version of a coarse-grained model for RNA dynamics. In such approach, the description of nucleotides is reduced to single points that interact between them through a series of effective pair potentials that were obtained from an improved analysis of RNA structures from the Protein Data Bank. These interaction potentials are the main constituents of a Brownian dynamics simulation algorithm that allows to perform a variety of tasks by taking advantage of the reduced number of variables. Such tasks include the prediction of the three-dimensional configuration of a series of test molecules. Moreover, the model permits the inclusion of effective magnesium ions and the ends of the RNA chains can be pulled with an external force to study the process of unfolding. In spite of the simplicity of the model, we obtain a good agreement with the experimental results.

  10. One-bead coarse-grained model for RNA dynamics

    NASA Astrophysics Data System (ADS)

    Villada-Balbuena, Mario; Carbajal-Tinoco, Mauricio D.

    2017-01-01

    We present a revised version of a coarse-grained model for RNA dynamics. In such approach, the description of nucleotides is reduced to single points that interact between them through a series of effective pair potentials that were obtained from an improved analysis of RNA structures from the Protein Data Bank. These interaction potentials are the main constituents of a Brownian dynamics simulation algorithm that allows to perform a variety of tasks by taking advantage of the reduced number of variables. Such tasks include the prediction of the three-dimensional configuration of a series of test molecules. Moreover, the model permits the inclusion of effective magnesium ions and the ends of the RNA chains can be pulled with an external force to study the process of unfolding. In spite of the simplicity of the model, we obtain a good agreement with the experimental results.

  11. 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

  12. 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.

  13. Coarse-Grained and Atomistic Modeling of Polyimides

    NASA Technical Reports Server (NTRS)

    Clancy, Thomas C.; Hinkley, Jeffrey A.

    2004-01-01

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

  14. CG2AA: backmapping protein coarse-grained structures.

    PubMed

    Lombardi, Leandro E; Martí, Marcelo A; Capece, Luciana

    2016-04-15

    Coarse grain (CG) models allow long-scale simulations with a much lower computational cost than that of all-atom simulations. However, the absence of atomistic detail impedes the analysis of specific atomic interactions that are determinant in most interesting biomolecular processes. In order to study these phenomena, it is necessary to reconstruct the atomistic structure from the CG representation. This structure can be analyzed by itself or be used as an onset for atomistic molecular dynamics simulations. In this work, we present a computer program that accurately reconstructs the atomistic structure from a CG model for proteins, using a simple geometrical algorithm. The software is free and available online at http://www.ic.fcen.uba.ar/cg2aa/cg2aa.py Supplementary data are available at Bioinformatics online. lula@qi.fcen.uba.ar. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. A coarse grain model for DNA.

    PubMed

    Knotts, Thomas A; Rathore, Nitin; Schwartz, David C; de Pablo, Juan J

    2007-02-28

    Understanding the behavior of DNA at the molecular level is of considerable fundamental and engineering importance. While adequate representations of DNA exist at the atomic and continuum level, there is a relative lack of models capable of describing the behavior of DNA at mesoscopic length scales. We present a mesoscale model of DNA that reduces the complexity of a nucleotide to three interactions sites, one each for the phosphate, sugar, and base, thereby rendering the investigation of DNA up to a few microns in length computationally tractable. The charges on these sites are considered explicitly. The model is parametrized using thermal denaturation experimental data at a fixed salt concentration. The validity of the model is established by its ability to predict several aspects of DNA behavior, including salt-dependent melting, bubble formation and rehybridization, and the mechanical properties of the molecule as a function of salt concentration.

  16. A coarse grain model for DNA

    NASA Astrophysics Data System (ADS)

    Knotts, Thomas A.; Rathore, Nitin; Schwartz, David C.; de Pablo, Juan J.

    2007-02-01

    Understanding the behavior of DNA at the molecular level is of considerable fundamental and engineering importance. While adequate representations of DNA exist at the atomic and continuum level, there is a relative lack of models capable of describing the behavior of DNA at mesoscopic length scales. We present a mesoscale model of DNA that reduces the complexity of a nucleotide to three interactions sites, one each for the phosphate, sugar, and base, thereby rendering the investigation of DNA up to a few microns in length computationally tractable. The charges on these sites are considered explicitly. The model is parametrized using thermal denaturation experimental data at a fixed salt concentration. The validity of the model is established by its ability to predict several aspects of DNA behavior, including salt-dependent melting, bubble formation and rehybridization, and the mechanical properties of the molecule as a function of salt concentration.

  17. 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

  18. 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.

  19. Coarse-Grained Model of SNARE-Mediated Docking

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Choi, Eunsong; Mondal, Jagannath; Yethiraj, Arun

    2014-01-09

    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.

  1. Coarse Grained Model for Biological Simulations: Recent Refinements and Validation

    PubMed Central

    Vicatos, Spyridon; Rychkova, Anna; Mukherjee, Shayantani; Warshel, Arieh

    2014-01-01

    Exploring the free energy landscape of proteins and modeling 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 various simplified coarse grained (CG) models offers an effective way of sampling the landscape, but most current models are not expected to give a reliable description of protein stability and functional aspects. The main problem is associated with insufficient focus on the electrostatic features of the model. In this respect our recent CG model offers significant advantage as it has been refined while focusing on its electrostatic free energy. Here we review the current state of our model, describing recent refinement, extensions and validation studies while focusing on demonstrating key applications. These include studies of protein stability, extending the model to include membranes and electrolytes and electrodes as well as studies of voltage activated proteins, protein insertion trough the translocon, the action of molecular motors and even the coupling of the stalled ribosome and the translocon. Our example illustrates the general potential of our approach in overcoming major challenges in studies of structure function correlation in proteins and large macromolecular complexes. PMID:25050439

  2. Parametrizing coarse grained models for molecular systems at equilibrium

    NASA Astrophysics Data System (ADS)

    Kalligiannaki, E.; Chazirakis, A.; Tsourtis, A.; Katsoulakis, M. A.; Plecháč, P.; Harmandaris, V.

    2016-10-01

    Hierarchical coarse graining of atomistic molecular systems at equilibrium has been an intensive research topic over the last few decades. In this work we (a) review theoretical and numerical aspects of different parametrization methods (structural-based, force matching and relative entropy) to derive the effective interaction potential between coarse-grained particles. All methods approximate the many body potential of mean force; resulting, however, in different optimization problems. (b) We also use a reformulation of the force matching method by introducing a generalized force matching condition for the local mean force in the sense that allows the approximation of the potential of mean force under both linear and non-linear coarse graining mappings (E. Kalligiannaki, et al., J. Chem. Phys. 2015). We apply and compare these methods to: (a) a benchmark system of two isolated methane molecules; (b) methane liquid; (c) water; and (d) an alkane fluid. Differences between the effective interactions, derived from the various methods, are found that depend on the actual system under study. The results further reveal the relation of the various methods and the sensitivities that may arise in the implementation of numerical methods used in each case.

  3. 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

  4. A coarse grained protein-lipid model with application to lipoprotein particles

    PubMed Central

    Shih, Amy Y.; Arkhipov, Anton; Freddolino, Peter L.; Schulten, Klaus

    2008-01-01

    A coarse-grained model for molecular dynamics simulations is extended from lipids to proteins. In the framework of such models pioneered by Klein, atoms are described group-wise by beads, with the interactions between beads governed by effective potentials. The extension developed here is based on a coarse-grained lipid model previously developed by Marrink et al., though further versions will reconcile the approach taken with the systematic approach of Klein and other authors. Each amino acid of the protein is represented by two coarse-grained beads, one for the backbone (identical for all residues) and one for the side-chain (which differs depending on the residue type). The coarse-graining reduces system size about ten-fold and allows integration time steps of 25 to 50 fs. The model is applied to simulations of discoidal high-density lipoprotein particles, involving water, lipids, and two primarily helical proteins. These particles are an ideal test system for the extension of coarse-grained models. Our model proved reliable in maintaining the shape of pre-assembled particles and in accurately reproducing overall structural features of high-density lipoproteins. Microsecond simulations of lipoprotein assembly revealed formation of a protein-lipid complex in which two proteins are attached to either side of a discoidal lipid bilayer. PMID:16494423

  5. Transferable coarse-grained model for perfluorosulfonic acid polymer membranes

    NASA Astrophysics Data System (ADS)

    Kuo, An-Tsung; Okazaki, Susumu; Shinoda, Wataru

    2017-09-01

    Perfluorosulfonic acid (PFSA) polymer membranes are widely used as proton exchange membranes. Because the structure of the aqueous domain within the PFSA membrane is expected to directly influence proton conductance, many coarse-grained (CG) simulation studies have been performed to investigate the membrane morphology; these studies mostly used phenomenological models, such as dissipative particle dynamics. However, a chemically accurate CG model is required to investigate the morphology in realistic membranes and to provide a concrete molecular design. Here, we attempt to construct a predictive CG model for the structure and morphology of PFSA membranes that is compatible with the Sinoda-DeVane-Klein (SDK) CG water model [Shinoda et al., Mol. Simul. 33, 27 (2007)]. First, we extended the parameter set for the SDK CG force field to examine a hydrated PFSA membrane based on thermodynamic and structural data from experiments and all-atom (AA) molecular dynamics (MD) simulations. However, a noticeable degradation of the morphology motivated us to improve the structural properties by using the iterative Boltzmann inversion (IBI) approach. Thus, we explored a possible combination of the SDK and IBI approaches to describe the nonbonded interaction. The hybrid SDK/IBI model improved the structural issues of SDK, showing a better agreement with AA-MD in the radial distribution functions. The hybrid SDK/IBI model was determined to reasonably reproduce both the thermodynamic and structural properties of the PFSA membrane for all examined water contents. In addition, the model demonstrated good transferability and has considerable potential for application to realistic long-chained PFSA membranes.

  6. Transferable coarse-grained model for perfluorosulfonic acid polymer membranes.

    PubMed

    Kuo, An-Tsung; Okazaki, Susumu; Shinoda, Wataru

    2017-09-07

    Perfluorosulfonic acid (PFSA) polymer membranes are widely used as proton exchange membranes. Because the structure of the aqueous domain within the PFSA membrane is expected to directly influence proton conductance, many coarse-grained (CG) simulation studies have been performed to investigate the membrane morphology; these studies mostly used phenomenological models, such as dissipative particle dynamics. However, a chemically accurate CG model is required to investigate the morphology in realistic membranes and to provide a concrete molecular design. Here, we attempt to construct a predictive CG model for the structure and morphology of PFSA membranes that is compatible with the Sinoda-DeVane-Klein (SDK) CG water model [Shinoda et al., Mol. Simul. 33, 27 (2007)]. First, we extended the parameter set for the SDK CG force field to examine a hydrated PFSA membrane based on thermodynamic and structural data from experiments and all-atom (AA) molecular dynamics (MD) simulations. However, a noticeable degradation of the morphology motivated us to improve the structural properties by using the iterative Boltzmann inversion (IBI) approach. Thus, we explored a possible combination of the SDK and IBI approaches to describe the nonbonded interaction. The hybrid SDK/IBI model improved the structural issues of SDK, showing a better agreement with AA-MD in the radial distribution functions. The hybrid SDK/IBI model was determined to reasonably reproduce both the thermodynamic and structural properties of the PFSA membrane for all examined water contents. In addition, the model demonstrated good transferability and has considerable potential for application to realistic long-chained PFSA membranes.

  7. Resolution-Adapted All-Atomic and Coarse-Grained Model for Biomolecular Simulations.

    PubMed

    Shen, Lin; Hu, Hao

    2014-06-10

    We develop here an adaptive multiresolution method for the simulation of complex heterogeneous systems such as the protein molecules. The target molecular system is described with the atomistic structure while maintaining concurrently a mapping to the coarse-grained models. The theoretical model, or force field, used to describe the interactions between two sites is automatically adjusted in the simulation processes according to the interaction distance/strength. Therefore, all-atomic, coarse-grained, or mixed all-atomic and coarse-grained models would be used together to describe the interactions between a group of atoms and its surroundings. Because the choice of theory is made on the force field level while the sampling is always carried out in the atomic space, the new adaptive method preserves naturally the atomic structure and thermodynamic properties of the entire system throughout the simulation processes. The new method will be very useful in many biomolecular simulations where atomistic details are critically needed.

  8. 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}.

  9. Capturing the essence of folding and functions of biomolecules using coarse-grained models.

    PubMed

    Hyeon, Changbong; Thirumalai, D

    2011-09-27

    The distances over which biological molecules and their complexes can function range from a few nanometres, in the case of folded structures, to millimetres, for example, during chromosome organization. Describing phenomena that cover such diverse length, and also time, scales requires models that capture the underlying physics for the particular length scale of interest. Theoretical ideas, in particular, concepts from polymer physics, have guided the development of coarse-grained models to study folding of DNA, RNA and proteins. More recently, such models and their variants have been applied to the functions of biological nanomachines. Simulations using coarse-grained models are now poised to address a wide range of problems in biology.

  10. 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

  11. A multiscale approach to triglycerides simulations: from atomistic to coarse-grained models and back.

    PubMed

    Brasiello, Antonio; Crescitelli, Silvestro; Milano, Giuseppe

    2012-01-01

    The aim of this paper is to provide a simulation strategy to study the liquid-solid transition of triglycerides. The strategy is based on a multiscale approach. A coarse-grained model, parameterized on the basis of reference atomistic simulations, has been used to model the liquid-solid transition. A reverse mapping procedure has been proposed to reconstruct atomistic models from coarse-grained configurations and validated against experimental structural properties. The nucleation and growth of the crystalline order have been analysed in terms of several properties.

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

    PubMed

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

    2015-10-01

    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.

  13. 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.

  14. A Framework for Dynamic Modeling of Surface-Structure Patches on Bed Load Transport in Coarse Grained Reaches

    NASA Astrophysics Data System (ADS)

    Strom, K. B.

    2010-12-01

    Mountain streams are the first link in the fluvial system and often have complex bed morphologies which make it difficult to develop simple quantitative expressions for sediment mass flux and stream flow resistance. Such expressions are important for landscape evolution modeling as well as stream management and restoration practices and efforts. Part of the difficulty lies in the fact that stream beds can have large variations in particle size and structural organization - both of which lead to variations in bed strength that can change as a function of time. This study presents a mathematical framework to account for the dynamic impact of surface-structure patches on bed strength and bed load transport under simplified conditions. The framework is based on conservation principles for tracking the exchange of mass between structured and unstructured surface patches in the bed during structure formation and breakup. Two main transport equations are solved for the mobile and stationary phases, and the exchange between the two is modeled using particle collision theory and a simple breakup model (figure 1). The experiments of Strom et al. (2004) are used to parameterize the model initial conditions, and calculated and experimentally observed transport rates are compared as a function of time. Conceptual sketch of the modeling framework for: (A) a gravel bed, and (B) an idealized bed of uniform spherical particles. Mass conservation equations are written for each phase (structured and unstructured) and then solved with time under varying conditions.

  15. Impact of Thermostats on Folding and Aggregation Properties of Peptides Using the Optimized Potential for Efficient Structure Prediction Coarse-Grained Model.

    PubMed

    Spill, Yannick G; Pasquali, Samuela; Derreumaux, Philippe

    2011-05-10

    The simulation of amyloid fibril formation is impossible if one takes into account all chemical details of the amino acids and their detailed interactions with the solvent. We investigate the folding and aggregation of two model peptides using the optimized potential for efficient structure prediction (OPEP) coarse-grained model and replica exchange molecular dynamics (REMD) simulations coupled with either the Langevin or the Berendsen thermostat. For both the monomer of blocked penta-alanine and the trimer of the 25-35 fragment of the Alzheimer's amyloid β protein, we find little variations in the equilibrium structures and heat capacity curves using the two thermostats. Despite this high similarity, we detect significant differences in the populations of the dominant conformations at low temperatures, whereas the configurational distributions remain the same in proximity of the melting temperature. Aβ25-35 trimers at 300 K have an averaged β-sheet content of 12% and are primarily characterized by fully disordered peptides or a small curved two-stranded β-sheet stabilized by a disordered peptide. In addition, OPEP molecular dynamics simulations of Aβ25-35 hexamers at 300 K with a small curved six-stranded antiparallel β-sheet do not show any extension of the β-sheet content. These data support the idea that the mechanism of Aβ25-35 amyloid formation does not result from a high fraction of extended β-sheet-rich trimers and hexamers.

  16. 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.

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

    NASA Astrophysics Data System (ADS)

    Ding, Yajun; Mittal, Jeetain

    2014-11-01

    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.

  18. 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.

  19. Sequence transferable coarse-grained model of amphiphilic copolymers

    NASA Astrophysics Data System (ADS)

    De Silva, Chathuranga C.; Leophairatana, Porakrit; Ohkuma, Takahiro; Koberstein, Jeffrey T.; Kremer, Kurt; Mukherji, Debashish

    2017-08-01

    Polymer properties are inherently multi-scale in nature, where delicate local interaction details play a key role in describing their global conformational behavior. In this context, deriving coarse-grained (CG) multi-scale models for polymeric liquids is a non-trivial task. Further complexities arise when dealing with copolymer systems with varying microscopic sequences, especially when they are of amphiphilic nature. In this work, we derive a segment-based generic CG model for amphiphilic copolymers consisting of repeat units of hydrophobic (methylene) and hydrophilic (ethylene oxide) monomers. The system is a simulation analogue of polyacetal copolymers [S. Samanta et al., Macromolecules 49, 1858 (2016)]. The CG model is found to be transferable over a wide range of copolymer sequences and also to be consistent with existing experimental data.

  20. Probing the structural dynamics of the CRISPR-Cas9 RNA-guided DNA-cleavage system by coarse-grained modeling.

    PubMed

    Zheng, Wenjun

    2017-02-01

    In the adaptive immune systems of many bacteria and archaea, the Cas9 endonuclease forms a complex with specific guide/scaffold RNA to identify and cleave complementary target sequences in foreign DNA. This DNA targeting machinery has been exploited in numerous applications of genome editing and transcription control. However, the molecular mechanism of the Cas9 system is still obscure. Recently, high-resolution structures have been solved for Cas9 in different structural forms (e.g., unbound forms, RNA-bound binary complexes, and RNA-DNA-bound tertiary complexes, corresponding to an inactive state, a pre-target-bound state, and a cleavage-competent or product state), which offered key structural insights to the Cas9 mechanism. To further probe the structural dynamics of Cas9 interacting with RNA and DNA at the amino-acid level of details, we have performed systematic coarse-grained modeling using an elastic network model and related analyses. Our normal mode analysis predicted a few key modes of collective motions that capture the observed conformational changes featuring large domain motions triggered by binding of RNA and DNA. Our flexibility analysis identified specific regions with high or low flexibility that coincide with key functional sites (such as DNA/RNA-binding sites, nuclease cleavage sites, and key hinges). We also identified a small set of hotspot residues that control the energetics of functional motions, which overlap with known functional sites and offer promising targets for future mutagenesis efforts to improve the specificity of Cas9. Finally, we modeled the conformational transitions of Cas9 from the unbound form to the binary complex and then the tertiary complex, and predicted a distinct sequence of domain motions. In sum, our findings have offered rich structural and dynamic details relevant to the Cas9 machinery, and will guide future investigation and engineering of the Cas9 systems. Proteins 2017; 85:342-353. © 2016 Wiley Periodicals

  1. 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.

  2. 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.

  3. Coarse-Grained Lattice Model Simulations of Sequence-Structure Fitness of a Ribosome-Inactivating Protein

    DTIC Science & Technology

    2007-11-05

    109, 6722–6731. 26. McQuarrie , D. A. Statistical Mechanics . Harper and Row: New York, 1976. 27. Angell, C. A. Proc Natl Acad Sci USA 1995, 92, 6675...favorable. While there are many computational methods that apply force fields or statistical potentials to assess compara- bility of sequences fitted to...sequence-de- pendent, and restraint components. The sequence-specific poten- tial was derived through geometric statistics of known protein structures

  4. 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.

  5. Solvation free energies and partition coefficients with the coarse-grained and hybrid all-atom/coarse-grained MARTINI models

    NASA Astrophysics Data System (ADS)

    Genheden, Samuel

    2017-09-01

    We present the estimation of solvation free energies of small solutes in water, n-octanol and hexane using molecular dynamics simulations with two MARTINI models at different resolutions, viz. the coarse-grained (CG) and the hybrid all-atom/coarse-grained (AA/CG) models. From these estimates, we also calculate the water/hexane and water/octanol partition coefficients. More than 150 small, organic molecules were selected from the Minnesota solvation database and parameterized in a semi-automatic fashion. Using either the CG or hybrid AA/CG models, we find considerable deviations between the estimated and experimental solvation free energies in all solvents with mean absolute deviations larger than 10 kJ/mol, although the correlation coefficient is between 0.55 and 0.75 and significant. There is also no difference between the results when using the non-polarizable and polarizable water model, although we identify some improvements when using the polarizable model with the AA/CG solutes. In contrast to the estimated solvation energies, the estimated partition coefficients are generally excellent with both the CG and hybrid AA/CG models, giving mean absolute deviations between 0.67 and 0.90 log units and correlation coefficients larger than 0.85. We analyze the error distribution further and suggest avenues for improvements.

  6. 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.

  7. Multisequence algorithm for coarse-grained biomolecular simulations: Exploring the sequence-structure relationship of proteins

    NASA Astrophysics Data System (ADS)

    Aina, A.; Wallin, S.

    2017-09-01

    We consider a generalized-ensemble algorithm for coarse-grained simulations of biomolecules which allows the thermodynamic behavior of two or more sequences to be determined in a single multisequence run. By carrying out a random walk in sequence space, the method also enhances conformational sampling. Escape from local energy minima is accelerated by visiting sequences for which the minima are more shallow or absent. We test the method on an intermediate-resolution coarse-grained model for protein folding with 3 amino acid types and explore the potential for a large-scale coverage of sequence space by applying the method to sets of more than 1000 sequences. The resulting thermodynamic data are used to analyze the structures and stability properties of sequences covering the space between folds with different secondary structures.

  8. Multisequence algorithm for coarse-grained biomolecular simulations: Exploring the sequence-structure relationship of proteins.

    PubMed

    Aina, A; Wallin, S

    2017-09-07

    We consider a generalized-ensemble algorithm for coarse-grained simulations of biomolecules which allows the thermodynamic behavior of two or more sequences to be determined in a single multisequence run. By carrying out a random walk in sequence space, the method also enhances conformational sampling. Escape from local energy minima is accelerated by visiting sequences for which the minima are more shallow or absent. We test the method on an intermediate-resolution coarse-grained model for protein folding with 3 amino acid types and explore the potential for a large-scale coverage of sequence space by applying the method to sets of more than 1000 sequences. The resulting thermodynamic data are used to analyze the structures and stability properties of sequences covering the space between folds with different secondary structures.

  9. 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.

  10. 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.

  11. 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

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

    PubMed

    Deng, Mingsen; Shen, Hujun

    2016-02-04

    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.

  13. Coarse-graining away electronic structure: a rigorous route to accurate condensed phase interaction potentials

    NASA Astrophysics Data System (ADS)

    Knight, Chris; Voth, Gregory A.

    2012-05-01

    The molecular simulation of condensed phase systems with electronic structure methods can be prohibitively expensive if the length and time scales necessary to observe the desired chemical phenomena are too large. One solution is to map the results of a representative electronic structure simulation onto a computationally more efficient model that reproduces the original calculation, while allowing for statistical sampling relevant to the required length and time scales. The statistical mechanical multiscale coarse-graining procedure is one methodology in which a model can be developed by integrating over the subset of fast degrees of freedom to construct a reduced representation of the original system that reproduces thermodynamic, and in some instances dynamic, properties. The coarse-graining away of electronic structure is one application of this general method, wherein the electronic degrees of freedom are integrated out and the full dimensionality of the system is mapped to that of only the nuclei. The forces on the nuclei in this reduced representation are obtained from a variational force-matching procedure applied to the Hellman-Feynman forces of the original full electron + nuclear system. This work discusses the coarse-graining procedure and its application to ab initio molecular dynamics simulations of the aqueous hydroxide ion.

  14. Coarse-grained modeling of polyethylene melts: Effect on dynamics

    DOE PAGES

    Peters, Brandon L.; Salerno, K. Michael; Agrawal, Anupriya; ...

    2017-05-23

    The distinctive viscoelastic behavior of polymers results from a coupled interplay of motion on multiple length and time scales. Capturing the broad time and length scales of polymer motion remains a challenge. Using polyethylene (PE) as a model macromolecule, we construct coarse-grained (CG) models of PE with three to six methyl groups per CG bead and probe two critical aspects of the technique: pressure corrections required after iterative Boltzmann inversion (IBI) to generate CG potentials that match the pressure of reference fully atomistic melt simulations and the transferability of CG potentials across temperatures. While IBI produces nonbonded pair potentials thatmore » give excellent agreement between the atomistic and CG pair correlation functions, the resulting pressure for the CG models is large compared with the pressure of the atomistic system. We find that correcting the potential to match the reference pressure leads to nonbonded interactions with much deeper minima and slightly smaller effective bead diameter. However, simulations with potentials generated by IBI and pressure-corrected IBI result in similar mean-square displacements (MSDs) and stress autocorrelation functions G(t) for PE melts. While the time rescaling factor required to match CG and atomistic models is the same for pressure- and non-pressure-corrected CG models, it strongly depends on temperature. Furthermore, transferability was investigated by comparing the MSDs and stress autocorrelation functions for potentials developed at different temperatures.« less

  15. A coarse-grain three-site-per-nucleotide model for DNA with explicit ions

    NASA Astrophysics Data System (ADS)

    Freeman, Gordon S.; Hinckley, Daniel M.; de Pablo, Juan J.

    2011-10-01

    The "three sites per nucleotide" (3SPN) model provides a coarse-grained representation of nucleic acids for simulation of molecular processes. Previously, this model has relied on an implicit representation of the surrounding ionic environment at the level of Debye-Hückel theory. In this work, we eliminate this limitation and present an explicit representation of ions, both monovalent and divalent. The coarse-grain ion-ion and ion-phosphate potential energy functions are inferred from all-atom simulations and parameterized to reproduce key features of the local structure and organization of ions in bulk water and in the presence of DNA. The resulting model, 3SPN.1-I, is capable of reproducing the local structure observed in detailed atomistic simulations, as well as the experimental melting temperature of DNA for a range of DNA oligonucleotide lengths, CG-content, Na+ concentration, and Mg2 + concentration.

  16. Thermodynamics of atomistic and coarse-grained models of water on nonpolar surfaces

    NASA Astrophysics Data System (ADS)

    Ardham, Vikram Reddy; Leroy, Frédéric

    2017-08-01

    In order to study the phenomena where interfaces play a dominant role through molecular simulations, the proper representation of the interfacial thermodynamic properties of a given model is of crucial importance. The use of coarse-grained rather than atomistic models makes it possible to simulate interfacial systems with larger time and length scales. In the present work, we compare the structure and thermodynamic behavior of one atomistic and two single-site coarse-grained models of water on nonpolar surfaces, namely, graphite and the basal plane of molybdenum disulfide. The three models interact with the surfaces through Lennard-Jones potentials parametrized to reproduce recent experimental contact angle measurements. The models form a layered structure close to the surface, which is usually observed on sufficiently attractive nonpolar substrates. However, differences in the structure and thermodynamic behavior are observed between the models. These differences are explained by certain features of the water models, such as short range tetrahedral order and liquid density fluctuations. Besides these results, the approach employed in the present study may be used to assess the ability of coarse-grained models for solid-liquid systems to represent consistent interfacial thermodynamics.

  17. Coarse-grained modeling of protein unspecifically bound to DNA

    NASA Astrophysics Data System (ADS)

    Guardiani, Carlo; Cencini, Massimo; Cecconi, Fabio

    2014-04-01

    There is now a certain consensus that transcription factors (TFs) reach their target sites, where they regulate gene transcription, via a mechanism dubbed facilitated diffusion (FD). In FD, the TF cycles between events of 3D diffusion in solution (jumps), 1D diffusion along DNA (sliding), and small jumps (hopping), achieving association rates higher than for 3D diffusion alone. We investigate the FD phenomenology through molecular dynamics simulations in the framework of coarse-grained modeling. We show that, despite the crude approximations, the model generates, upon varying the equilibrium distance of the DNA-TF interaction, a phenomenology matching a number of experimental and numerical results obtained with more refined models. In particular, focusing on the kinematics of the process, we characterize the geometrical properties of TF trajectories during sliding. We find that sliding occurs via helical paths around the DNA helix, leading to a coupling of translation along the DNA axis with rotation around it. The 1D diffusion constant measured in simulations is found to be interwoven with the geometrical properties of sliding and we develop a simple argument that can be used to quantitatively reproduce the measured values.

  18. Diblock copolymer bilayers as model for polymersomes: A coarse grain approach.

    PubMed

    Grillo, Damián A; Albano, Juan M R; Mocskos, Esteban E; Facelli, Julio C; Pickholz, Mónica; Ferraro, Marta B

    2017-06-28

    This paper presents a new model for polymersomes developed using a poly(ethylene oxide)-poly(butadiene) diblock copolymer bilayer. The model is based on a coarse-grained approach using the MARTINI force field. Since no MARTINI parameters exist for poly(butadiene), we have refined these parameters using quantum mechanical calculations and molecular dynamics simulations. The model has been validated using extensive molecular dynamics simulations in systems with several hundred polymer units and reaching up to 6 μs. These simulations show that the copolymer coarse grain model self-assemble into bilayers and that NPT and NPNγT ensemble runs reproduce key structural and mechanical experimental properties for different copolymer length chains with a similar hydrophilic weight fraction.

  19. Diblock copolymer bilayers as model for polymersomes: A coarse grain approach

    NASA Astrophysics Data System (ADS)

    Grillo, Damián A.; Albano, Juan M. R.; Mocskos, Esteban E.; Facelli, Julio C.; Pickholz, Mónica; Ferraro, Marta B.

    2017-06-01

    This paper presents a new model for polymersomes developed using a poly(ethylene oxide)-poly(butadiene) diblock copolymer bilayer. The model is based on a coarse-grained approach using the MARTINI force field. Since no MARTINI parameters exist for poly(butadiene), we have refined these parameters using quantum mechanical calculations and molecular dynamics simulations. The model has been validated using extensive molecular dynamics simulations in systems with several hundred polymer units and reaching up to 6 μ s. These simulations show that the copolymer coarse grain model self-assemble into bilayers and that NPT and NPNγT ensemble runs reproduce key structural and mechanical experimental properties for different copolymer length chains with a similar hydrophilic weight fraction.

  20. 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.

  1. Folding and stability of helical bundle proteins from coarse-grained models.

    PubMed

    Kapoor, Abhijeet; Travesset, Alex

    2013-07-01

    We develop a coarse-grained model where solvent is considered implicitly, electrostatics are included as short-range interactions, and side-chains are coarse-grained to a single bead. The model depends on three main parameters: hydrophobic, electrostatic, and side-chain hydrogen bond strength. The parameters are determined by considering three level of approximations and characterizing the folding for three selected proteins (training set). Nine additional proteins (containing up to 126 residues) as well as mutated versions (test set) are folded with the given parameters. In all folding simulations, the initial state is a random coil configuration. Besides the native state, some proteins fold into an additional state differing in the topology (structure of the helical bundle). We discuss the stability of the native states, and compare the dynamics of our model to all atom molecular dynamics simulations as well as some general properties on the interactions governing folding dynamics. Copyright © 2013 Wiley Periodicals, Inc.

  2. Coarse grained model for calculating the ion mobility of hydrocarbons

    NASA Astrophysics Data System (ADS)

    Kuroboshi, Y.; Takemura, K.

    2016-12-01

    Hydrocarbons are widely used as insulating compounds. However, their fundamental characteristics in conduction phenomena are not completely understood. A great deal of effort is required to determine reasonable ionic behavior from experiments because of their complicated procedures and tight controls of the temperature and the purity of the liquids. In order to understand the conduction phenomena, we have theoretically calculated the ion mobilities of hydrocarbons and investigated their characteristics using the coarse grained model in molecular dynamics simulations. We assumed a molecule of hydrocarbons to be a bead and simulated its dependence on the viscosity, electric field, and temperature. Furthermore, we verified the suitability of the conformation, scale size, and long-range interactions for the ion mobility. The results of the simulations show that the ion mobility values agree reasonably well with the values from Walden's rule and depend on the viscosity but not on the electric field. The ion mobility and self-diffusion coefficient exponentially increase with increasing temperature, while the activation energy decreases with increasing molecular size. These values and characteristics of the ion mobility are in reasonable agreement with experimental results. In the future, we can understand not only the ion mobilies of hydrocarbons in conduction, but also we can predict general phenomena in electrochemistry with molecular dynamics simulations.

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

    NASA Astrophysics Data System (ADS)

    Najafi, Saeed; Potestio, Raffaello

    2015-12-01

    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. 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.

  5. 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

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

    PubMed Central

    Hadley, K. R.; McCabe, C.

    2010-01-01

    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. PMID:20387939

  8. 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

  9. 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.

  10. Asymmetric folding pathways and transient misfolding in a coarse-grained model of proteins

    NASA Astrophysics Data System (ADS)

    Wolff, K.; Vendruscolo, M.; Porto, M.

    2011-05-01

    Coarse-grained approaches to study the protein folding process provide the possibility to explore timescales longer than those accessible to all-atom models and thus provide access, albeit in less detail, to larger regions of the conformational space. Here, we investigate the behaviour of a coarse-grained model whose two primary characteristics are a tube-like geometry to describe the self-avoidance effects of the polypeptide chain, and an energy function based on a one-dimensional structural representation that specifies the sequence's connectivity in a given conformation. Such an energy function, rather than favouring the formation of specific native pairwise contacts, promotes the establishment of a specific target connectivity for each amino acid. We illustrate the use of this model by showing that it enables to follow the complete process of folding and to efficiently determine the free energy landscapes of two small α-helical proteins, the villin headpiece domain and the ubiquitin associated domain, providing results that closely resemble those found in extensive molecular dynamics studies. These results support the idea that the use of coarse-grained models that capture the self-avoidance and the connectivity of a polypeptide chain represents a promising approach for obtaining effective descriptions of many aspects of the behaviour of proteins.

  11. Coarse-grained modeling of hybrid block copolymer system

    NASA Astrophysics Data System (ADS)

    Su, Yongrui

    This thesis is comprised of three major projects of my research. In the first project, I proposed a nanoparticle model and combined it with the Theoretically Informed Coarse Grained (TICG) model for pure polymer systems and the grand canonical slip springs model developed in our group to build a new model for entangled nanocomposites. With Molecule Dynamics(MD) simulation, I studied the mechanic properties of the nanocomposites, for example the influence of nanoparticles size and volume fraction on entanglements, the diffusion of polymers and nanoparticles, and the influence of nanoparticles size and volume fraction on viscosity et al.. We found that the addition of small-size nanoparticles reduces the viscosity of the nanocomposites, which is in contrary to what Einstein predicted a century ago. However, when particle increases its size to micrometers the Einstein predictions is recovered. From our simulation, we believe that small-size nanoparticles can more effectively decrease the entanglements of nanocomposites than larger particles. The free volume effect introduced by small-size nanoparticles also helps decrease the viscosity of the whole system. In the second project, I combined the Ohta-Kawasaki (OK) model [3] and the Covariance Matrix Adaptation Evolutionary Strategy(CMA-ES) to optimize the block copolymer blends self-assembly in the hole-shrink process. The aim is to predict the optimal composition and the optimal surface energy to direct the block copolymer blends self-assembly process in the confined hole. After optimization in the OK model, we calibrated the optimal results by the more reliable TICG model and got the same morphology. By comparing different optimization process, we found that the homopolymers which are comprised of the same monomers as either block of the block copolymer can form a perfect perforated hole and might have better performance than the pure block copolymer. While homopolymers which are comprised of a third-party monomers

  12. Coarse Grained Model for Exploring Voltage Dependent Ion Channels

    PubMed Central

    Dryga, Anatoly; Chakrabarty, Suman; Vicatos, Spyridon; Warshel, Arieh

    2011-01-01

    The relationship between the membrane voltage and the gating of voltage activated ion channels and other systems have been a problem of great current interest. Unfortunately, reliable molecular simulations of external voltage effects present a major challenge, since meaningful converging microscopic simulations are not yet available and macroscopic treatments involve major uncertainties in terms of the dielectric used and other key features. This work extends our coarse grained (CG) model to simulations of membrane/protein systems under external potential. Special attention has been devoted to a consistent modeling of the effect of external potential due to the electrodes, emphasizing semimacroscopic description of the electrolytes in the solution regions between the membranes and the electrodes, as well as the coupling between the combined potential from the electrodes and electrolytes, and the protein ionization states. We also provide a clear connection to microscopic treatment of the electrolytes and thus can explore possible conceptual problems that are hard to resolve by other current approaches. For example, we obtain a clear description of the charge distribution in the entire electrolyte system, including near the electrodes in membrane/electrodes systems (where continuum models do not seem to provide the relevant results). Furthermore, the present treatment provides an insight on the distribution of the electrolyte charges before and after equilibration across the membrane, and thus on the nature of the gating charge. The different aspects of the model have been carefully validated by considering problems ranging for the simple Debye-Huckel, Gouy-Chapman models to the evaluation of the electrolyte distribution between two electrodes, as well as the effect of extending the simulation system by periodic replicas. Overall the clear connection to microscopic descriptions combined with the power of the CG modeling seems to offer a powerful tool for exploring

  13. Coarse graining from variationally enhanced sampling applied to the Ginzburg–Landau model

    PubMed Central

    Invernizzi, Michele; Valsson, Omar; Parrinello, Michele

    2017-01-01

    A powerful way to deal with a complex system is to build a coarse-grained model capable of catching its main physical features, while being computationally affordable. Inevitably, such coarse-grained models introduce a set of phenomenological parameters, which are often not easily deducible from the underlying atomistic system. We present a unique approach to the calculation of these parameters, based on the recently introduced variationally enhanced sampling method. It allows us to obtain the parameters from atomistic simulations, providing thus a direct connection between the microscopic and the mesoscopic scale. The coarse-grained model we consider is that of Ginzburg–Landau, valid around a second-order critical point. In particular, we use it to describe a Lennard–Jones fluid in the region close to the liquid–vapor critical point. The procedure is general and can be adapted to other coarse-grained models. PMID:28292890

  14. Coarse graining from variationally enhanced sampling applied to the Ginzburg-Landau model.

    PubMed

    Invernizzi, Michele; Valsson, Omar; Parrinello, Michele

    2017-03-28

    A powerful way to deal with a complex system is to build a coarse-grained model capable of catching its main physical features, while being computationally affordable. Inevitably, such coarse-grained models introduce a set of phenomenological parameters, which are often not easily deducible from the underlying atomistic system. We present a unique approach to the calculation of these parameters, based on the recently introduced variationally enhanced sampling method. It allows us to obtain the parameters from atomistic simulations, providing thus a direct connection between the microscopic and the mesoscopic scale. The coarse-grained model we consider is that of Ginzburg-Landau, valid around a second-order critical point. In particular, we use it to describe a Lennard-Jones fluid in the region close to the liquid-vapor critical point. The procedure is general and can be adapted to other coarse-grained models.

  15. REACH Coarse-Grained Biomolecular Simulation: Transferability between Different Protein Structural Classes

    PubMed Central

    Moritsugu, Kei; Smith, Jeremy C.

    2008-01-01

    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 α), plastocyanin (all β), and dihydrofolate reductase (α/β) 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

  16. Dynamic force matching: A method for constructing dynamical coarse-grained models with realistic time dependence

    NASA Astrophysics Data System (ADS)

    Davtyan, Aram; Dama, James F.; Voth, Gregory A.; Andersen, Hans C.

    2015-04-01

    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

  17. Dynamic force matching: A method for constructing dynamical coarse-grained models with realistic time dependence

    SciTech Connect

    Davtyan, Aram; Dama, James F.; Voth, Gregory A.; Andersen, Hans C.

    2015-04-21

    Coarse-grained (CG) models of molecular systems, with fewer mechanical degrees of freedom than an all-atom model, are used extensively in chemical physics. It is generally accepted that a coarse-grained model that accurately describes equilibrium structural properties (as a result of having a well constructed CG potential energy function) does not necessarily exhibit appropriate dynamical behavior when simulated using conservative Hamiltonian dynamics for the CG degrees of freedom on the CG potential energy surface. Attempts to develop accurate CG dynamic models usually focus on replacing Hamiltonian motion by stochastic but Markovian dynamics on that surface, such as Langevin or Brownian dynamics. However, depending on the nature of the system and the extent of the coarse-graining, a Markovian dynamics for the CG degrees of freedom may not be appropriate. In this paper, we consider the problem of constructing dynamic CG models within the context of the Multi-Scale Coarse-graining (MS-CG) method of Voth and coworkers. We propose a method of converting a MS-CG model into a dynamic CG model by adding degrees of freedom to it in the form of a small number of fictitious particles that interact with the CG degrees of freedom in simple ways and that are subject to Langevin forces. The dynamic models are members of a class of nonlinear systems interacting with special heat baths that were studied by Zwanzig [J. Stat. Phys. 9, 215 (1973)]. The properties of the fictitious particles can be inferred from analysis of the dynamics of all-atom simulations of the system of interest. This is analogous to the fact that the MS-CG method generates the CG potential from analysis of equilibrium structures observed in all-atom simulation data. The dynamic models generate a non-Markovian dynamics for the CG degrees of freedom, but they can be easily simulated using standard molecular dynamics programs. We present tests of this method on a series of simple examples that demonstrate that

  18. 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.

  19. 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

  20. 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.

  1. Autocorrelation study of the Θ transition for a coarse-grained polymer model.

    PubMed

    Qi, Kai; Bachmann, Michael

    2014-08-21

    By means of Metropolis Monte Carlo simulations of a coarse-grained model for flexible polymers, we investigate how the integrated autocorrelation times of different energetic and structural quantities depend on the temperature. We show that, due to critical slowing down, an extremal autocorrelation time can also be considered as an indicator for the collapse transition that helps to locate the transition point. This is particularly useful for finite systems, where response quantities such as the specific heat do not necessarily exhibit clear indications for pronounced thermal activity.

  2. Coarse-grained models of protein folding: toy models or predictive tools?

    PubMed

    Clementi, Cecilia

    2008-02-01

    Coarse-grained models are emerging as a practical alternative to all-atom simulations for the characterization of protein folding mechanisms over long time scales. While a decade ago minimalist toy models were mainly designed to test general hypotheses on the principles regulating protein folding, the latest coarse-grained models are increasingly realistic and can be used to characterize quantitatively the detailed folding mechanism of specific proteins. The ability of such models to reproduce the essential features of folding dynamics suggests that each single atomic degree of freedom is not by itself particularly relevant to folding and supports a statistical mechanical approach to characterize folding transitions. When combined with more refined models and with experimental studies, the systematic investigation of protein systems and complexes using coarse-grained models can advance our theoretical understanding of the actual organizing principles that emerge from the complex network of interactions among protein atomic constituents.

  3. Free energies for coarse-grained proteins by integrating multibody statistical contact potentials with entropies from elastic network models

    PubMed Central

    Zimmermann, Michael T.; Leelananda, Sumudu P.; Gniewek, Pawel; Feng, Yaping; Jernigan, Robert L.; Kloczkowski, Andrzej

    2011-01-01

    We propose a novel method of calculation of free energy for coarse grained models of proteins by combining our newly developed multibody potentials with entropies computed from elastic network models of proteins. Multi-body potentials have been of much interest recently because they take into account three dimensional interactions related to residue packing and capture the cooperativity of these interactions in protein structures. Combining four-body non-sequential, four-body sequential and pairwise short range potentials with optimized weights for each term, our coarse-grained potential improved recognition of native structure among misfolded decoys, outperforming all other contact potentials for CASP8 decoy sets and performance comparable to the fully atomic empirical DFIRE potentials. By combing statistical contact potentials with entropies from elastic network models of the same structures we can compute free energy changes and improve coarse-grained modeling of protein structure and dynamics. The consideration of protein flexibility and dynamics should improve protein structure prediction and refinement of computational models. This work is the first to combine coarse-grained multibody potentials with an entropic model that takes into account contributions of the entire structure, investigating native-like decoy selection. PMID:21674234

  4. Structural Investigation of MscL Gating Using Experimental Data and Coarse Grained MD Simulations

    PubMed Central

    Deplazes, Evelyne; Louhivuori, Martti; Jayatilaka, Dylan; Marrink, Siewert J.; Corry, Ben

    2012-01-01

    The mechanosensitive channel of large conductance (MscL) has become a model system in which to understand mechanosensation, a process involved in osmoregulation and many other physiological functions. While a high resolution closed state structure is available, details of the open structure and the gating mechanism remain unknown. In this study we combine coarse grained simulations with restraints from EPR and FRET experiments to study the structural changes involved in gating with much greater level of conformational sampling than has previously been possible. We generated a set of plausible open pore structures that agree well with existing open pore structures and gating models. Most interestingly, we found that membrane thinning induces a kink in the upper part of TM1 that causes an outward motion of the periplasmic loop away from the pore centre. This previously unobserved structural change might present a new mechanism of tension sensing and might be related to a functional role in osmoregulation. PMID:23028281

  5. Extending the range and physical accuracy of coarse-grained models: Order parameter dependent interactions

    NASA Astrophysics Data System (ADS)

    Wagner, Jacob W.; Dannenhoffer-Lafage, Thomas; Jin, Jaehyeok; Voth, Gregory A.

    2017-07-01

    Order parameters (i.e., collective variables) are often used to describe the behavior of systems as they capture different features of the free energy surface. Yet, most coarse-grained (CG) models only employ two- or three-body non-bonded interactions between the CG particles. In situations where these interactions are insufficient for the CG model to reproduce the structural distributions of the underlying fine-grained (FG) model, additional interactions must be included. In this paper, we introduce an approach to expand the basis sets available in the multiscale coarse-graining (MS-CG) methodology by including order parameters. Then, we investigate the ability of an additive local order parameter (e.g., density) and an additive global order parameter (i.e., distance from a hard wall) to improve the description of CG models in interfacial systems. Specifically, we study methanol liquid-vapor coexistence, acetonitrile liquid-vapor coexistence, and acetonitrile liquid confined by hard-wall plates, all using single site CG models. We find that the use of order parameters dramatically improves the reproduction of structural properties of interfacial CG systems relative to the FG reference as compared with pairwise CG interactions alone.

  6. Coarse-grained model for the interconversion between different crystalline cellulose allomorphs

    SciTech Connect

    Langan, Paul

    2012-01-01

    We present the results of Langevin dynamics simulations on a coarse grained model for crystalline cellulose. In particular, we analyze two different cellulose crystalline forms: cellulose I (the natural form of cellulose) and cellulose IIII (obtained after cellulose I is treated with anhydrous liquid ammonia). Cellulose IIII has been the focus of wide interest in the field of cellulosic biofuels as it can be efficiently hydrolyzed to glucose (its enzymatic degradation rates are up to 5 fold higher than those of cellulose I ). In turn, glucose can eventually be fermented into fuels. The coarse-grained model presented in this study is based on a simplified geometry and on an effective potential mimicking the changes in both intracrystalline hydrogen bonds and stacking interactions during the transition from cellulose I to cellulose IIII. The model accurately reproduces both structural and thermomechanical properties of cellulose I and IIII. The work presented herein describes the structural transition from cellulose I to cellulose IIII as driven by the change in the equilibrium state of two degrees of freedom in the cellulose chains. The structural transition from cellulose I to cellulose IIII is essentially reduced to a search for optimal spatial arrangement of the cellulose chains.

  7. A coarse-grained protein force field for folding and structure prediction.

    PubMed

    Maupetit, Julien; Tuffery, P; Derreumaux, Philippe

    2007-11-01

    We have revisited the protein coarse-grained optimized potential for efficient structure prediction (OPEP). The training and validation sets consist of 13 and 16 protein targets. Because optimization depends on details of how the ensemble of decoys is sampled, trial conformations are generated by molecular dynamics, threading, greedy, and Monte Carlo simulations, or taken from publicly available databases. The OPEP parameters are varied by a genetic algorithm using a scoring function which requires that the native structure has the lowest energy, and the native-like structures have energy higher than the native structure but lower than the remote conformations. Overall, we find that OPEP correctly identifies 24 native or native-like states for 29 targets and has very similar capability to the all-atom discrete optimized protein energy model (DOPE), found recently to outperform five currently used energy models.

  8. 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.

  9. Coarse-grained model of glycosaminoglycans in aqueous salt solutions. A field-theoretical approach.

    PubMed

    Kolesnikov, Andrei L; Budkov, Yurij A; Nogovitsyn, Evgenij A

    2014-11-20

    We present results of self-consistent field calculations of thermodynamic and structural properties of glycosaminoglycans (chondroitin sulfate, hyaluronic acid, and heparin) in aqueous solutions with added monovalent and divalent salts. A semiphenomenological coarse-grained model for semiflexible polyelectrolyte chains in solution is proposed. The coarse-grained model permits one to focus on the essential features of these systems and provides significant computational advantages with respect to more detailed models. Our approach relies on the method of Gaussian equivalent representation for the calculation of the partition functions in the form of functional integrals. This method provides reliable thermodynamic information for polyelectrolyte solutions over wide ranges of monomer concentrations. In the present work, we use the comparison and fitting of the experimental osmotic pressure with a theoretical equation of state within the Gaussian equivalent representation. The degrees of ionization, radii of gyration, persistence lengths, and structure factors of chondroitin sulfate, hyaluronic acid, and heparin in aqueous solutions with added monovalent and divalent salts are calculated and discussed.

  10. 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.

  11. Boltzmann rovibrational collisional coarse-grained model for internal energy excitation and dissociation in hypersonic flows.

    PubMed

    Munafò, A; Panesi, M; Magin, T E

    2014-02-01

    A Boltzmann rovibrational collisional coarse-grained model is proposed to reduce a detailed kinetic mechanism database developed at NASA Ames Research Center for internal energy transfer and dissociation in N(2)-N interactions. The coarse-grained model is constructed by lumping the rovibrational energy levels of the N(2) molecule into energy bins. The population of the levels within each bin is assumed to follow a Boltzmann distribution at the local translational temperature. Excitation and dissociation rate coefficients for the energy bins are obtained by averaging the elementary rate coefficients. The energy bins are treated as separate species, thus allowing for non-Boltzmann distributions of their populations. The proposed coarse-grained model is applied to the study of nonequilibrium flows behind normal shock waves and within converging-diverging nozzles. In both cases, the flow is assumed inviscid and steady. Computational results are compared with those obtained by direct solution of the master equation for the rovibrational collisional model and a more conventional multitemperature model. It is found that the proposed coarse-grained model is able to accurately resolve the nonequilibrium dynamics of internal energy excitation and dissociation-recombination processes with only 20 energy bins. Furthermore, the proposed coarse-grained model provides a superior description of the nonequilibrium phenomena occurring in shock heated and nozzle flows when compared with the conventional multitemperature models.

  12. Coarse graining approach to First principles modeling of radiation cascade in large Fe super-cells

    NASA Astrophysics Data System (ADS)

    Odbadrakh, Khorgolkhuu; Nicholson, Don; Rusanu, Aurelian; Wang, Yang; Stoller, Roger; Zhang, Xiaoguang; Stocks, George

    2012-02-01

    First principles techniques employed to understand systems at an atomistic level are not practical for large systems consisting of millions of atoms. We present an efficient coarse graining approach to bridge the first principles calculations of local electronic properties to classical Molecular Dynamics (MD) simulations of large structures. Local atomic magnetic moments in crystalline Fe are perturbed by radiation generated defects. The effects are most pronounced near the defect core and decay with distance. We develop a coarse grained 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. This work was supported by the Center for Defect Physics, an Energy Frontier Research Center funded by the US Department of Energy, Office of Science, Office of Basic Energy Sciences.

  13. Integral equation analysis of single-site coarse-grained models for polymer-colloid mixtures

    NASA Astrophysics Data System (ADS)

    Menichetti, Roberto; D'Adamo, Giuseppe; Pelissetto, Andrea; Pierleoni, Carlo

    2015-09-01

    We discuss the reliability of integral equation methods based on several commonly used closure relations in determining the phase diagram of coarse-grained models of soft-matter systems characterised by mutually interacting soft- and hard-core particles. Specifically, we consider a set of potentials appropriate to describe a system of hard-sphere colloids and linear homopolymers in good solvent, and investigate the behaviour when the soft particles are smaller than the colloids, which is the regime of validity of the coarse-grained models. Using computer-simulation results as a benchmark, we find that the hypernetted-chain approximation provides accurate estimates of thermodynamics and structure in the colloid-gas phase in which the density of colloids is small. On the other hand, all closures considered appear to be unable to describe the behaviour of the mixture in the colloid-liquid phase, as they cease to converge at polymer densities significantly smaller than those at the binodal. As a consequence, integral equations appear to be unable to predict a quantitatively correct phase diagram.

  14. 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.

  15. Effective rates from thermodynamically consistent coarse-graining of models for molecular motors with probe particles.

    PubMed

    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 F(1)-ATPase and the kinesin motor.

  16. Construction of ultra-coarse-grained model of protein with a Gō-like potential

    NASA Astrophysics Data System (ADS)

    Zhang, Yuwei; Cao, Zexing; Xia, Fei

    2017-08-01

    Ultra-Coarse-Grained (UCG) model whose resolution is less than residue-based coarse-grained model, is being developed in recent years. In this work, we attempt to construct a UCG model with a classical Gō-like potential. The heterogeneous parameters of local and nonlocal interactions in the energy potential function are derived by using fluctuation matching method. The simulated results with UCG models indicate that it could reproduce the root mean square fluctuations as accurate as that of long-time all-atom simulations. Therefore, the UCG model has great potential in the simulation of huge biological systems such as biomaterials.

  17. 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

  18. Lipid Bilayer Membrane Elasticity and Hydrodynamics : Insights from Dynamic Implicit-Solvent Coarse-Grained Models

    NASA Astrophysics Data System (ADS)

    Atzberger, Paul

    2014-03-01

    Lipid bilayer membranes have been widely studied using fully atomistic molecular dynamics and continuum mechanics descriptions. To bridge this gap many mesoscale implicit-solvent models have been developed to capture at equilibrium essential features of lipid bilayer membrane formation and internal structure, while at the same time providing enough simplification in simulations to allow access to large spatial scales. To study dynamic processes in such implicit solvent models requires further advances to account for important kinetic effects mediated by the solvent. We discuss our recent progress on developing thermostats for dynamic processes based on continuum fluctuating hydrodynamics for implicit-solvent coarse-grained models of lipid bilayer membranes. We present results for vesicle bilayers making comparisons with explicit solvent simulations and continuum theory.

  19. A Coarse-grained Model of Stratum Corneum Lipids: Free Fatty Acids and Ceramide NS

    PubMed Central

    Moore, Timothy C.; Iacovella, Christopher R.; Hartkamp, Remco; Bunge, Annette L.; McCabe, Clare

    2017-01-01

    Ceramide (CER)-based biological membranes are used both experimentally and in simulations as simplified model systems of the skin barrier. Molecular dynamics studies have generally focused on simulating preassembled structures using atomistically detailed models of CERs, which limit the system sizes and timescales that can practically be probed, rendering them ineffective for studying particular phenomena, including self-assembly into bilayer and lamellar superstructures. Here, we report on the development of a coarse-grained (CG) model for CER NS, the most abundant CER in human stratum corneum. Multistate iterative Boltzmann inversion is used to derive the intermolecular pair potentials, resulting in a force field that is applicable over a range of state points and suitable for studying ceramide self-assembly. The chosen CG mapping, which includes explicit interaction sites for hydroxyl groups, captures the directional nature of hydrogen bonding and allows for accurate predictions of several key structural properties of CER NS bilayers. Simulated wetting experiments allow the hydrophobicity of CG beads to be accurately tuned to match atomistic wetting behavior, which affects the whole system since inaccurate hydrophobic character is found to unphysically alter the lipid packing in hydrated lamellar states. We find that CER NS can self-assemble into multilamellar structures, enabling the study of lipid systems more representative of the multilamellar lipid structures present in the skin barrier. The coarse-grained force field derived herein represents an important step in using molecular dynamics to study the human skin barrier, which gives a resolution not available through experiment alone. PMID:27564869

  20. Multi-scale simulations of biological systems using the OPEP coarse-grained model.

    PubMed

    Sterpone, Fabio; Doutreligne, Sébastien; Tran, Thanh Thuy; Melchionna, Simone; Baaden, Marc; Nguyen, Phuong H; Derreumaux, Philippe

    2017-09-13

    Biomolecules are complex machines that are optimized by evolution to properly fulfill or contribute to a variety of biochemical tasks in the cellular environment. Computer simulations based on quantum mechanics and atomistic force fields have been proven to be a powerful microscope for obtaining valuable insights into many biological, physical, and chemical processes. Many interesting phenomena involve, however, a time scale and a number of degrees of freedom, notably if crowding is considered, that cannot be explored at an atomistic resolution. To bridge the gap between reality and simulation, many different advanced computational techniques and coarse-grained (CG) models have been developed. Here, we report some applications of the CG OPEP protein model to amyloid fibril formation, the response of catch-bond proteins to two types of fluid flow, and interactive simulations to fold peptides with well-defined 3D structures or with intrinsic disorder. Copyright © 2017. Published by Elsevier Inc.

  1. Combining coarse-grained protein models with replica-exchange all-atom molecular dynamics.

    PubMed

    Wabik, Jacek; Kmiecik, Sebastian; Gront, Dominik; Kouza, Maksim; Koliński, Andrzej

    2013-05-10

    We describe a combination of all-atom simulations with CABS, a well-established coarse-grained protein modeling tool, into a single multiscale protocol. The simulation method has been tested on the C-terminal beta hairpin of protein G, a model system of protein folding. After reconstructing atomistic details, conformations derived from the CABS simulation were subjected to replica-exchange molecular dynamics simulations with OPLS-AA and AMBER99sb force fields in explicit solvent. Such a combination accelerates system convergence several times in comparison with all-atom simulations starting from the extended chain conformation, demonstrated by the analysis of melting curves, the number of native-like conformations as a function of time and secondary structure propagation. The results strongly suggest that the proposed multiscale method could be an efficient and accurate tool for high-resolution studies of protein folding dynamics in larger systems.

  2. Toward Quantitative Coarse-Grained Models of Lipids with Fluids Density Functional Theory.

    PubMed

    Frink, Laura J Douglas; Frischknecht, Amalie L; Heroux, Michael A; Parks, Michael L; Salinger, Andrew G

    2012-04-10

    We describe methods to determine optimal coarse-grained models of lipid bilayers for use in fluids density functional theory (fluids-DFT) calculations. Both coarse-grained lipid architecture and optimal parametrizations of the models based on experimental measures are discussed in the context of dipalmitoylphosphatidylcholine (DPPC) lipid bilayers in water. The calculations are based on a combination of the modified-iSAFT theory for bonded systems and an accurate fundamental measures theory (FMT) for hard sphere reference fluids. We furthermore discuss a novel approach for pressure control in the fluids-DFT calculations that facilitates both partitioning studies and zero tension control for the bilayer studies. A detailed discussion of the numerical implementations for both solvers and pressure control capabilities are provided. We show that it is possible to develop a coarse-grained lipid bilayer model that is consistent with experimental properties (thickness and area per lipid) of DPPC provided that the coarse-graining is not too extreme. As a final test of the model, we find that the predicted area compressibility moduli and lateral pressure profiles of the optimized models are in reasonable agreement with prior results.

  3. Multiscale Modeling at Nanointerfaces: Polymer Thin Film Materials Discovery via Thermomechanically Consistent Coarse Graining

    NASA Astrophysics Data System (ADS)

    Hsu, David D.

    Due to high nanointerfacial area to volume ratio, the properties of "nanoconfined" polymer thin films, blends, and composites become highly altered compared to their bulk homopolymer analogues. Understanding the structure-property mechanisms underlying this effect is an active area of research. However, despite extensive work, a fundamental framework for predicting the local and system-averaged thermomechanical properties as a function of configuration and polymer species has yet to be established. Towards bridging this gap, here, we present a novel, systematic coarse-graining (CG) method which is able to capture quantitatively, the thermomechanical properties of real polymer systems in bulk and in nanoconfined geometries. This method, which we call thermomechanically consistent coarse-graining (TCCG), is a two-bead-per-monomer CG hybrid approach through which bonded interactions are optimized to match the atomistic structure via the Iterative Boltzmann Inversion method (IBI), and nonbonded interactions are tuned to macroscopic targets through parametric studies. We validate the TCCG method by systematically developing coarse-grain models for a group of five specialized methacrylate-based polymers including poly(methyl methacrylate) (PMMA). Good correlation with bulk all-atom (AA) simulations and experiments is found for the temperature-dependent glass transition temperature (Tg) Flory-Fox scaling relationships, self-diffusion coefficients of liquid monomers, and modulus of elasticity. We apply this TCCG method also to bulk polystyrene (PS) using a comparable coarse-grain CG bead mapping strategy. The model demonstrates chain stiffness commensurate with experiments, and we utilize a density-correction term to improve the transferability of the elastic modulus over a 500 K range. Additionally, PS and PMMA models capture the unexplained, characteristically dissimilar scaling of Tg with the thickness of free-standing films as seen in experiments. Using vibrational

  4. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

  6. 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

  7. 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.

  8. 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).

  9. 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).

  10. A comparison of coarse-grained and continuum models for membrane bending in lipid bilayer fusion pores.

    PubMed

    Yoo, Jejoong; Jackson, Meyer B; Cui, Qiang

    2013-02-19

    To establish the validity of continuum mechanics models quantitatively for the analysis of membrane remodeling processes, we compare the shape and energies of the membrane fusion pore predicted by coarse-grained (MARTINI) and continuum mechanics models. The results at these distinct levels of resolution give surprisingly consistent descriptions for the shape of the fusion pore, and the deviation between the continuum and coarse-grained models becomes notable only when the radius of curvature approaches the thickness of a monolayer. Although slow relaxation beyond microseconds is observed in different perturbative simulations, the key structural features (e.g., dimension and shape of the fusion pore near the pore center) are consistent among independent simulations. These observations provide solid support for the use of coarse-grained and continuum models in the analysis of membrane remodeling. The combined coarse-grained and continuum analysis confirms the recent prediction of continuum models that the fusion pore is a metastable structure and that its optimal shape is neither toroidal nor catenoidal. Moreover, our results help reveal a new, to our knowledge, bowing feature in which the bilayers close to the pore axis separate more from one another than those at greater distances from the pore axis; bowing helps reduce the curvature and therefore stabilizes the fusion pore structure. The spread of the bilayer deformations over distances of hundreds of nanometers and the substantial reduction in energy of fusion pore formation provided by this spread indicate that membrane fusion can be enhanced by allowing a larger area of membrane to participate and be deformed. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  11. A Comparison of Coarse-Grained and Continuum Models for Membrane Bending in Lipid Bilayer Fusion Pores

    PubMed Central

    Yoo, Jejoong; Jackson, Meyer B.; Cui, Qiang

    2013-01-01

    To establish the validity of continuum mechanics models quantitatively for the analysis of membrane remodeling processes, we compare the shape and energies of the membrane fusion pore predicted by coarse-grained (MARTINI) and continuum mechanics models. The results at these distinct levels of resolution give surprisingly consistent descriptions for the shape of the fusion pore, and the deviation between the continuum and coarse-grained models becomes notable only when the radius of curvature approaches the thickness of a monolayer. Although slow relaxation beyond microseconds is observed in different perturbative simulations, the key structural features (e.g., dimension and shape of the fusion pore near the pore center) are consistent among independent simulations. These observations provide solid support for the use of coarse-grained and continuum models in the analysis of membrane remodeling. The combined coarse-grained and continuum analysis confirms the recent prediction of continuum models that the fusion pore is a metastable structure and that its optimal shape is neither toroidal nor catenoidal. Moreover, our results help reveal a new, to our knowledge, bowing feature in which the bilayers close to the pore axis separate more from one another than those at greater distances from the pore axis; bowing helps reduce the curvature and therefore stabilizes the fusion pore structure. The spread of the bilayer deformations over distances of hundreds of nanometers and the substantial reduction in energy of fusion pore formation provided by this spread indicate that membrane fusion can be enhanced by allowing a larger area of membrane to participate and be deformed. PMID:23442963

  12. Coarse-Grained Descriptions of Dynamics for Networks with Both Intrinsic and Structural Heterogeneities

    PubMed Central

    Bertalan, Tom; Wu, Yan; Laing, Carlo; Gear, C. William; Kevrekidis, Ioannis G.

    2017-01-01

    Finding accurate reduced descriptions for large, complex, dynamically evolving networks is a crucial enabler to their simulation, analysis, and ultimately design. Here, we propose and illustrate a systematic and powerful approach to obtaining good collective coarse-grained observables—variables successfully summarizing the detailed state of such networks. Finding such variables can naturally lead to successful reduced dynamic models for the networks. The main premise enabling our approach is the assumption that the behavior of a node in the network depends (after a short initial transient) on the node identity: a set of descriptors that quantify the node properties, whether intrinsic (e.g., parameters in the node evolution equations) or structural (imparted to the node by its connectivity in the particular network structure). The approach creates a natural link with modeling and “computational enabling technology” developed in the context of Uncertainty Quantification. In our case, however, we will not focus on ensembles of different realizations of a problem, each with parameters randomly selected from a distribution. We will instead study many coupled heterogeneous units, each characterized by randomly assigned (heterogeneous) parameter value(s). One could then coin the term Heterogeneity Quantification for this approach, which we illustrate through a model dynamic network consisting of coupled oscillators with one intrinsic heterogeneity (oscillator individual frequency) and one structural heterogeneity (oscillator degree in the undirected network). The computational implementation of the approach, its shortcomings and possible extensions are also discussed. PMID:28659781

  13. Toward multiscale modeling of the chromatin fiber: a coarse grain model for DNA

    NASA Astrophysics Data System (ADS)

    Savelyev, Alexey; Papoian, Garegin

    2008-03-01

    In eukaryotic cells DNA is compacted a million-fold into a chromatin. Understanding the mechanism of chromatin folding is of great biological importance. All-atom Molecular Dynamics (MD) simulations could provide crucial insights into the electrostatic and structural mechanisms of chromatin folding. However, because of the enormous size of even short chromatin fiber segment and long folding time-scales, atomistic simulations are computationally impractical. Our long-term aim is to build an accurate coarse-grain (CG) model of the chromatin, derived systematically from all-atom simulations of its smaller parts. Here we report the development of the CG model for a linear DNA chain, playing the role of a linker DNA segment in the chromatin. We derived CG inter-DNA electrostatic potential from atomistic simulations with explicit solvent and mobile ions, instead of relying on the standard models of continuum electrostatics, which are inadequate at small intermolecular distances. In addition, we used the ideas of renormalization group theory to construct an optimization scheme for parameterizing the CG force field. This novel approach is designed to accurately reproduce correlations among various CG degrees of freedom. The implementation of these correlations was left as an open question in the prior studies of CG polymer models.

  14. Fast coarse-grained model for RNA titration

    NASA Astrophysics Data System (ADS)

    Barroso da Silva, Fernando Luís; Derreumaux, Philippe; Pasquali, Samuela

    2017-01-01

    A new numerical scheme for RNA (ribonucleic acid) titration based on the Debye-Hückel framework for the salt description is proposed in an effort to reduce the computational costs for further applications to study protein-RNA systems. By means of different sets of Monte Carlo simulations, we demonstrated that this new scheme is able to correctly reproduce the experimental titration behavior and salt pKa shifts. In comparison with other theoretical approaches, similar or even better outcomes are achieved at much lower computational costs. The model was tested on the lead-dependent ribozyme, the branch-point helix, and the domain 5 from Azotobacter vinelandii Intron 5.

  15. Representing environment-induced helix-coil transitions in a coarse grained peptide model

    NASA Astrophysics Data System (ADS)

    Dalgicdir, Cahit; Globisch, Christoph; Sayar, Mehmet; Peter, Christine

    2016-10-01

    Coarse grained (CG) models are widely used in studying peptide self-assembly and nanostructure formation. One of the recurrent challenges in CG modeling is the problem of limited transferability, for example to different thermodynamic state points and system compositions. Understanding transferability is generally a prerequisite to knowing for which problems a model can be reliably used and predictive. For peptides, one crucial transferability question is whether a model reproduces the molecule's conformational response to a change in its molecular environment. This is of particular importance since CG peptide models often have to resort to auxiliary interactions that aid secondary structure formation. Such interactions take care of properties of the real system that are per se lost in the coarse graining process such as dihedral-angle correlations along the backbone or backbone hydrogen bonding. These auxiliary interactions may then easily overstabilize certain conformational propensities and therefore destroy the ability of the model to respond to stimuli and environment changes, i.e. they impede transferability. In the present paper we have investigated a short peptide with amphiphilic EALA repeats which undergoes conformational transitions between a disordered and a helical state upon a change in pH value or due to the presence of a soft apolar/polar interface. We designed a base CG peptide model that does not carry a specific (backbone) bias towards a secondary structure. This base model was combined with two typical approaches of ensuring secondary structure formation, namely a C α -C α -C α -C α pseudodihedral angle potential or a virtual site interaction that mimics hydrogen bonding. We have investigated the ability of the two resulting CG models to represent the environment-induced conformational changes in the helix-coil equilibrium of EALA. We show that with both approaches a CG peptide model can be obtained that is environment-transferable and that

  16. 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

  17. Coarse-grained models for interacting, flapping swimmers

    NASA Astrophysics Data System (ADS)

    Oza, Anand; Ristroph, Leif; Shelley, Michael; Courant Institute Applied Math Lab Collaboration

    2016-11-01

    We present the results of a theoretical investigation into the dynamics of interacting flapping swimmers. Our study is motivated by ongoing experiments in the NYU Applied Math Lab, in which freely-translating, heaving airfoils interact hydrodynamically to choose their relative positions and velocities. We develop a discrete dynamical system in which flapping swimmers shed point vortices during each flapping cycle, which in turn exert forces on the swimmers. We present a framework for finding exact solutions to the evolution equations and for assessing their stability, giving physical insight into the preference for certain observed "schooling states". The model may be extended to arrays of flapping swimmers, and configurations in which the swimmers' flapping frequencies are incommensurate. Generally, our results indicate how hydrodynamics may mediate schooling and flocking behavior in biological contexts. A. Oza acknowledges the support of the NSF Mathematical Sciences Postdoctoral Fellowship.

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

    PubMed Central

    Wei, Zonghui

    2015-01-01

    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. PMID:26723631

  19. 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.

  20. A coarse-grained DNA model for the prediction of current signals in DNA translocation experiments

    NASA Astrophysics Data System (ADS)

    Weik, Florian; Kesselheim, Stefan; Holm, Christian

    2016-11-01

    We present an implicit solvent coarse-grained double-stranded DNA (dsDNA) model confined to an infinite cylindrical pore that reproduces the experimentally observed current modulations of a KaCl solution at various concentrations. Our model extends previous coarse-grained and mean-field approaches by incorporating a position dependent friction term on the ions, which Kesselheim et al. [Phys. Rev. Lett. 112, 018101 (2014)] identified as an essential ingredient to correctly reproduce the experimental data of Smeets et al. [Nano Lett. 6, 89 (2006)]. Our approach reduces the computational effort by orders of magnitude compared with all-atom simulations and serves as a promising starting point for modeling the entire translocation process of dsDNA. We achieve a consistent description of the system's electrokinetics by using explicitly parameterized ions, a friction term between the DNA beads and the ions, and a lattice-Boltzmann model for the solvent.

  1. Simulating protein unfolding under pressure with a coarse-grained model.

    PubMed

    Perezzan, Ramiro; Rey, Antonio

    2012-11-14

    We describe and test a coarse-grained molecular model for the simulation of the effects of pressure on the folding/unfolding transition of proteins. The model is a structure-based one, which takes into account the desolvation barrier for the formation of the native contacts. The pressure is taken into account in a qualitative, mean field approach, acting on the parameters describing the native stabilizing interactions. The model has been tested by simulating the thermodynamic and structural behavior of protein GB1 with a parallel tempering Monte Carlo algorithm. At low effective pressures, the model reproduces the standard two-state thermal transition between the native and denatured states. However, at large pressures a new state appears. Its structural characteristics have been analyzed, showing that it corresponds to a swollen version of the native structure. This swollen state is at equilibrium with the native state at low temperatures, but gradually transforms into the thermally denatured state as temperature is increased. Therefore, our model predicts a downhill transition between the swollen and the denatured states. The analysis of the model permits us to obtain a phase diagram for the pressure-temperature behavior of the simulated system, which is compatible with the known elliptical shape of this diagram for real proteins.

  2. Protein simulation using coarse-grained two-bead multipole force field with polarizable water models

    NASA Astrophysics Data System (ADS)

    Li, Min; Zhang, John Z. H.

    2017-02-01

    A recently developed two-bead multipole force field (TMFF) is employed in coarse-grained (CG) molecular dynamics (MD) simulation of proteins in combination with polarizable CG water models, the Martini polarizable water model, and modified big multipole water model. Significant improvement in simulated structures and dynamics of proteins is observed in terms of both the root-mean-square deviations (RMSDs) of the structures and residue root-mean-square fluctuations (RMSFs) from the native ones in the present simulation compared with the simulation result with Martini's non-polarizable water model. Our result shows that TMFF simulation using CG water models gives much stable secondary structures of proteins without the need for adding extra interaction potentials to constrain the secondary structures. Our result also shows that by increasing the MD time step from 2 fs to 6 fs, the RMSD and RMSF results are still in excellent agreement with those from all-atom simulations. The current study demonstrated clearly that the application of TMFF together with a polarizable CG water model significantly improves the accuracy and efficiency for CG simulation of proteins.

  3. A simple and transferable all-atom/coarse-grained hybrid model to study membrane processes.

    PubMed

    Genheden, Samuel; Essex, Jonathan W

    2015-10-13

    We present an efficient all-atom/coarse-grained hybrid model and apply it to membrane processes. This model is an extension of the all-atom/ELBA model applied previously to processes in water. Here, we improve the efficiency of the model by implementing a multiple-time step integrator that allows the atoms and the coarse-grained beads to be propagated at different timesteps. Furthermore, we fine-tune the interaction between the atoms and the coarse-grained beads by computing the potential of mean force of amino acid side chain analogs along the membrane normal and comparing to atomistic simulations. The model was independently validated on the calculation of small-molecule partition coefficients. Finally, we apply the model to membrane peptides. We studied the tilt angle of the Walp23 and Kalp23 helices in two different model membranes and the stability of the glycophorin A dimer. The model is efficient, accurate, and straightforward to use, as it does not require any extra interaction particles, layers of atomistic solvent molecules or tabulated potentials, thus offering a novel, simple approach to study membrane processes.

  4. 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.

  5. 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

    2016-02-09

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

    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.

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

    PubMed Central

    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

  8. 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

    2016-08-31

    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.

  9. 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.

  10. 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.

  11. A multi-state coarse grained modeling approach for an intrinsically disordered peptide.

    PubMed

    Ramezanghorbani, Farhad; Dalgicdir, Cahit; Sayar, Mehmet

    2017-09-07

    Many proteins display a marginally stable tertiary structure, which can be altered via external stimuli. Since a majority of coarse grained (CG) models are aimed at structure prediction, their success for an intrinsically disordered peptide's conformational space with marginal stability and sensitivity to external stimuli cannot be taken for granted. In this study, by using the LKα14 peptide as a test system, we demonstrate a bottom-up approach for constructing a multi-state CG model, which can capture the conformational behavior of this peptide in three distinct environments with a unique set of interaction parameters. LKα14 is disordered in dilute solutions; however, it strictly adopts the α-helix conformation upon aggregation or when in contact with a hydrophobic/hydrophilic interface. Our bottom-up approach combines a generic base model, that is unbiased for any particular secondary structure, with nonbonded interactions which represent hydrogen bonds, electrostatics, and hydrophobic forces. We demonstrate that by using carefully designed all atom potential of mean force calculations from all three states of interest, one can get a balanced representation of the nonbonded interactions. Our CG model behaves intrinsically disordered in bulk water, folds into an α-helix in the presence of an interface or a neighboring peptide, and is stable as a tetrameric unit, successfully reproducing the all atom molecular dynamics simulations and experimental results.

  12. A multi-state coarse grained modeling approach for an intrinsically disordered peptide

    NASA Astrophysics Data System (ADS)

    Ramezanghorbani, Farhad; Dalgicdir, Cahit; Sayar, Mehmet

    2017-09-01

    Many proteins display a marginally stable tertiary structure, which can be altered via external stimuli. Since a majority of coarse grained (CG) models are aimed at structure prediction, their success for an intrinsically disordered peptide's conformational space with marginal stability and sensitivity to external stimuli cannot be taken for granted. In this study, by using the LKα 14 peptide as a test system, we demonstrate a bottom-up approach for constructing a multi-state CG model, which can capture the conformational behavior of this peptide in three distinct environments with a unique set of interaction parameters. LKα 14 is disordered in dilute solutions; however, it strictly adopts the α -helix conformation upon aggregation or when in contact with a hydrophobic/hydrophilic interface. Our bottom-up approach combines a generic base model, that is unbiased for any particular secondary structure, with nonbonded interactions which represent hydrogen bonds, electrostatics, and hydrophobic forces. We demonstrate that by using carefully designed all atom potential of mean force calculations from all three states of interest, one can get a balanced representation of the nonbonded interactions. Our CG model behaves intrinsically disordered in bulk water, folds into an α -helix in the presence of an interface or a neighboring peptide, and is stable as a tetrameric unit, successfully reproducing the all atom molecular dynamics simulations and experimental results.

  13. 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

  14. Structure and properties of composites based chitosan and carbon nanostructures: atomistic and coarse-grained simulation

    NASA Astrophysics Data System (ADS)

    Glukhova, O. E.; Kolesnikova, A. S.; Grishina, O. A.; Slepchenkov, M. M.

    2015-03-01

    At the present time actual task of the modern materials is the creation of biodegradable biocompatible composite materials possessing high strength properties for medical purposes. One of the most promising biomaterials from a position of creation on their basis super strong nanofibres is chitosan. The aim of this work is a theoretical study of the structural features and physico-mechanical properties of biocomposite materials based on chitosan and carbon nanostructures. As matrix nanocomposite we considered various carbon nano-objects, namely carbon nanotubes and graphene. Using the developed original software complex KVAZAR we built atomistic and coarse-grained models of the biocomposite material. To identify regularities of influence of the configuration of the carbon matrix on the mechanical and electronic properties of biocomposite we carried out a series of numerical experiments using a classical algorithm of molecular dynamics and semi-empirical methods. The obtained results allow us to suggest that the generated biocomposite based on chitosan and carbon nanostructures has high stability and strength characteristics. Such materials can be used in biomedicine as a base material for creating of artificial limbs.

  15. Coarse-Grained Modeling of the Mechanical Properties of Entangled Polymer Systems

    NASA Astrophysics Data System (ADS)

    Pasquini, Brian; Escobedo, Fernando; Joo, Yong L.

    2006-03-01

    The complexity of entangled polymer interactions is a promising area for simulation studies to build upon polymer physics theories; however, it is necessary to use a coarse-grained approach to simulate the dynamic response of large polymer systems. Such studies have been done by treating the entanglement interactions as a set of entanglement points, which serve as the ends for the coarse-grained simulation unit. One method from literature (Smith and Termonia) formulates the free energy of an entanglement network based exclusively on neighboring entanglement points and uses temporary bonds which break as the simulation progresses. Another method (Terzis, Theodorou and Stroeks) treats the coarse-grained units as delocalized polymer density clouds, and formulates an expression for the free energy based on local polymer density. The first method has been extended to three dimensions for direct comparison to the second in tensile strain experiments. These models also show promise to understanding microstructure effects on mechanical properties in materials such as spider silk.

  16. 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.

  17. 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

  18. Coarse-grained empirical potential structure refinement: Application to a reverse aqueous micelle.

    PubMed

    Soper, A K; Edler, K J

    2017-06-01

    Conventional atomistic computer simulations, involving perhaps up to 10(6)atoms, can achieve length-scales on the order of a few 10s of nm. Yet many heterogeneous systems, such as colloids, nano-structured materials, or biological systems, can involve correlations over distances up 100s of nm, perhaps even 1μm in some instances. For such systems it is necessary to invoke coarse-graining, where single atoms are replaced by agglomerations of atoms, usually represented as spheres, in order for the simulation to be performed within a practical computer memory and time scale. Small angle scattering and reflectivity measurements, both X-ray and neutron, are routinely used to investigate structure in these systems, and traditionally the data have been interpreted in terms of discrete objects, such as spheres, sheets, and cylinders, and combinations thereof. Here we combine the coarse-grained computer simulation approach with neutron small angle scattering to refine the structure of a heterogeneous system, in the present case a reverse aqueous micelle of sodium-dioctyl sulfosuccinate (AOT) and iso-octane. The method closely follows empirical potential structure refinement and involves deriving an empirical interaction potential from the scattering data. As in traditional coarse-grained methods, individual atoms are replaced by spherical density profiles, which, unlike real atoms, can inter-penetrate to a significant extent. The method works over an arbitrary range of length-scales, but is limited to around 2 orders of magnitude in distance above a specified dimension. The smallest value for this dimension is of order 1nm, but the largest dimension is arbitrary. This article is part of a Special Issue entitled "Recent Advances in Bionanomaterials" Guest Editor: Dr. Marie-Louise Saboungi and Dr. Samuel D. Bader. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. A systematically coarse-grained solvent-free model for quantitative phospholipid bilayer simulations.

    PubMed

    Wang, Zun-Jing; Deserno, Markus

    2010-09-02

    We present an implicit solvent coarse-grained (CG) model for quantitative simulations of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers. The absence of explicit solvent enables membrane simulations on large length and time scales at moderate computational expense. Despite improved computational efficiency, the model preserves chemical specificity and quantitative accuracy. The bonded and nonbonded interactions together with the effective cohesion mimicking the hydrophobic effect were systematically tuned by matching structural and mechanical properties from experiments and all-atom bilayer simulations, such as saturated area per lipid, radial distribution functions, density and pressure profiles across the bilayer, P(2) order, etc. The CG lipid model is shown to self-assemble into a bilayer starting from a random dispersion. Its line tension and elastic properties, such as bending and stretching modulus, are semiquantitatively consistent with experiments. The effects of (i) reduced molecular friction and (ii) more efficient integration combine to an overall speed-up of 3-4 orders of magnitude compared to all-atom bilayer simulations. Our CG lipid model is especially useful for studies of large-scale phenomena in membranes that nevertheless require a fair description of chemical specificity, e.g., membrane patches interacting with movable and transformable membrane proteins and peptides.

  20. Structure and stability of chiral beta-tapes: a computational coarse-grained approach.

    PubMed

    Bellesia, Giovanni; Fedorov, Maxim V; Kuznetsov, Yuri A; Timoshenko, Edward G

    2005-04-01

    We present two coarse-grained models of different levels of detail for the description of beta-sheet tapes obtained from equilibrium self-assembly of short rationally designed oligopeptides in solution. Here we only consider the case of the homopolymer oligopeptides with the identical sidegroups attached, in which the tapes have a helicoid surface with two equivalent sides. The influence of the chirality parameter on the geometrical characteristics, namely the diameter, interstrand distance, and pitch, of the tapes has been investigated. The two models are found to produce equivalent results suggesting a considerable degree of universality in conformations of the tapes.

  1. 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.

  2. An analytical coarse-graining method which preserves the free energy, structural correlations, and thermodynamic state of polymer melts from the atomistic to the mesoscale

    NASA Astrophysics Data System (ADS)

    McCarty, J.; Clark, A. J.; Copperman, J.; Guenza, M. G.

    2014-05-01

    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, c0. A numerical solution to the PRISM integral equations is used to determine c0, by adjusting the value of the effective hard sphere diameter, dHS, 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.

  3. 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.

  4. 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.

  5. A systematic procedure to build a relaxed dense-phase atomistic representation of a complex amorphous polymer using a coarse-grained modeling approach.

    PubMed

    Li, Xianfeng; Latour, Robert A

    2009-07-31

    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 10(2), 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.

  6. 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.

  7. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

    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 D2 molecules and beryllium atoms. The sensitivity of our results to the assumptions on the statistical properties of fluctuations is investigated.

  9. RedMDStream: Parameterization and Simulation Toolbox for Coarse-Grained Molecular Dynamics Models

    PubMed Central

    Leonarski, Filip; Trylska, Joanna

    2015-01-01

    Coarse-grained (CG) models in molecular dynamics (MD) are powerful tools to simulate the dynamics of large biomolecular systems on micro- to millisecond timescales. However, the CG model, potential energy terms, and parameters are typically not transferable between different molecules and problems. So parameterizing CG force fields, which is both tedious and time-consuming, is often necessary. We present RedMDStream, a software for developing, testing, and simulating biomolecules with CG MD models. Development includes an automatic procedure for the optimization of potential energy parameters based on metaheuristic methods. As an example we describe the parameterization of a simple CG MD model of an RNA hairpin. PMID:25902423

  10. Coarse-grain model for natural cellulose fibrils in explicit water

    SciTech Connect

    Srinivas, Goundla; Cheng, Xiaolin; Smith, Jeremy C.

    2014-02-24

    Understanding biomass structure and dynamics on multiple time and length scales is important for the development of cellulosic biofuels. To this aim, we have developed a coarse-grain (CG) model for molecular dynamics (MD) simulations of cellulose fibrils in explicit water based on target observables from fully atomistic simulations. This model examines the significance of the presence of explicit solvent and compares results with the previous, implicit solvent CG cellulose models. The present, constraint-free CG model is used to generate a series of noncrystalline fibril structures using a coupling parameter, λ, between fully crystalline and fully amorphous potentials. By exploring various structural parameters, including the root-mean-square deviation, root-mean-square fluctuations, radius of gyration, and persistence length, we find the crystalline-to-amorphous state transition takes place at λ ≈ 0.386. The persistence length of cellulose fibril in the transition region corresponds to that of native cellulose fibrils. The transition between crystalline and amorphous fibrils occurs at larger values of λ in explicit water than in the implicit case. Detailed analysis of individual energetic contribution to the transition reveals that the nonbonded interactions, in particular, that of cellulose water interaction, plays a significant role in the observed crystalline to amorphous transition of cellulose fibril. The present study thus highlights the importance of solvent presence that cannot be adequately described with the previous implicit solvent model. In conclusion, the present method provides an accurate and constraint-free approach for deriving a variety of structures of cellulose in water, with a wide range of crystallinity, suitable for incorporation into large-scale models of lignocellulosic biomass.

  11. 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

  12. Communication: Constructing an implicit quantum mechanical/molecular mechanics solvent model by coarse-graining explicit solvent.

    PubMed

    Theel, Kelly L; Wen, Shuhao; Beran, Gregory J O

    2013-08-28

    To avoid repeated, computationally expensive QM solute calculations while sampling MM solvent in QM/MM simulations, a new approach for constructing an implicit solvent model by coarse-graining the solvent properties over many explicit solvent configurations is proposed. The solvent is modeled using a polarizable force field that is parameterized in terms of distributed multipoles (electrostatics), polarizabilities (induction), and frequency-dependent polarizabilities (dispersion). The coarse-graining procedure exploits the ability to translate these properties to the center of each coarse-graining cell and average them over many solvent configurations before interacting them with the solute. A single coarse-grained QM/MM calculation of the interaction between a formamide solute and aqueous solvent reproduces the much more expensive average over many explicit QM/MM calculations with kJ/mol accuracy.

  13. Communication: Constructing an implicit quantum mechanical/molecular mechanics solvent model by coarse-graining explicit solvent

    NASA Astrophysics Data System (ADS)

    Theel, Kelly L.; Wen, Shuhao; Beran, Gregory J. O.

    2013-08-01

    To avoid repeated, computationally expensive QM solute calculations while sampling MM solvent in QM/MM simulations, a new approach for constructing an implicit solvent model by coarse-graining the solvent properties over many explicit solvent configurations is proposed. The solvent is modeled using a polarizable force field that is parameterized in terms of distributed multipoles (electrostatics), polarizabilities (induction), and frequency-dependent polarizabilities (dispersion). The coarse-graining procedure exploits the ability to translate these properties to the center of each coarse-graining cell and average them over many solvent configurations before interacting them with the solute. A single coarse-grained QM/MM calculation of the interaction between a formamide solute and aqueous solvent reproduces the much more expensive average over many explicit QM/MM calculations with kJ/mol accuracy.

  14. 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.

  15. 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.

  16. Computational Study of Uniaxial Deformations in Silica Aerogel Using a Coarse-Grained Model.

    PubMed

    Ferreiro-Rangel, Carlos A; Gelb, Lev D

    2015-07-09

    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.

  17. 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.

  18. Biophysical Coarse-Grained Modeling Provides Insights into Transport through the Nuclear Pore Complex

    PubMed Central

    Moussavi-Baygi, R.; Jamali, Y.; Karimi, R.; Mofrad, M.R.K.

    2011-01-01

    The nuclear pore complex (NPC) is the gatekeeper of the nucleus, capable of actively discriminating between the active and inert cargo while accommodating a high rate of translocations. The biophysical mechanisms underlying transport, however, remain unclear due to the lack of information about biophysical factors playing role in transport. Based on published experimental data, we have established a coarse-grained model of an intact NPC structure to examine nucleocytoplasmic transport with refined spatial and temporal resolutions. Using our model, we estimate the transport time versus cargo sizes. Our findings suggest that the mean transport time of cargos smaller than 15 nm is independent of size, while beyond this size, there is a sharp increase in the mean transport time. The model confirms that kap-FG hydrophobicity is sufficient for active cargo transport. Moreover, our model predicts that during translocation, small and large cargo-complexes are hydrophobically attached to FG-repeat domains for 86 and 96% of their transport time, respectively. Inside the central channel FG-repeats form a thick layer on the wall leaving an open tube. The cargo-complex is almost always attached to this layer and diffuses back and forth, regardless of the cargo size. Finally, we propose a plausible model for transport in which the NPC can be viewed as a lubricated gate. This model incorporates basic assumptions underlying virtual-gate and reduction-of-dimensionality models with the addition of the FG-layer inside the central channel acting as a lubricant. PMID:21402022

  19. 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.

  20. Modeling the Formation of Alkali Aluminosilicate Gels at the Mesoscale Using Coarse-Grained Monte Carlo.

    PubMed

    Yang, Kengran; White, Claire E

    2016-11-08

    Alkali-activated materials (AAMs) are currently being pursued as viable alternatives to conventional ordinary Portland cement because of their lower carbon footprint and established mechanical performance. However, our understanding of the mesoscale morphology (∼1 to 100 nm) of AAMs and related amorphous aluminosilicate gels, including the development of the three-dimensional aluminosilicate network and nanoscale porosity, is severely limited. This study investigates the structural changes that occur during the formation of AAM gels at the mesoscale by utilizing a coarse-grained Monte Carlo (CGMC) modeling technique that exploits density functional theory calculations. The model is capable of simulating the reaction of an aluminosilicate particle in a highly alkaline solution (sodium hydroxide or sodium silicate). Two precursor morphologies have been investigated (layered alumina and silica sheets mimicking metakaolin and spherical aluminosilicate particles reminiscent of coal-derived fly ash) to determine if the precursor morphology has an impact on the structural evolution of the resulting alkali-activated aluminosilicate gel. The CGMC model can capture the three major stages of the alkali-activation process-dissolution, polycondensation, and reorganization-revealing that the dissolved silicate and aluminate species, ranging from monomers to nanoprecipitates (100s of monomers in size), exist in the pore solution of the hardened gel. The model also reveals that the silica concentration of the activating solution controls the extent of dissolution of the precursor particle. From the analysis of the aluminosilicate cluster size distributions, the mechanisms of AAM gel growth have been elucidated, revealing that Ostwald ripening occurs in systems containing free silica at the start of the reaction. On the other hand, growth of the hydroxide-activated systems (metakaolin and fly ash) occurs via the formation of intermediate-sized clusters in addition to continual

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

    PubMed

    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 [Formula: see text]-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 [Formula: see text]/[Formula: see text]-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

  2. 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

  3. Refining the Treatment of Membrane Proteins by Coarse-Grained Models

    PubMed Central

    Vorobyov, Igor; Kim, Ilsoo; Chu, Zhen T.; Warshel, Arieh

    2015-01-01

    Obtaining a quantitative description of the membrane proteins stability is crucial for understanding many biological processes. However the advance in this direction has remained a major challenge for both experimental studies and molecular modeling. One of the possible directions is the use of coarse-grained models but such models must be carefully calibrated and validated. Here we use a recent progress in benchmark studies on the energetics of amino acid residue and peptide membrane insertion and membrane protein stability in refining our previously developed coarse-grained model (Vicatos et al Proteins 2014; 82: 1168). Our refined model parameters were fitted and/or tested to reproduce water/membrane partitioning energetics of amino acid side chains and a couple of model peptides. This new model provides a reasonable agreement with experiment for absolute folding free energies of several β-barrel membrane proteins as well as effects of point mutations on a relative stability for one of those proteins, OmpLA. The consideration and ranking of different rotameric states for a mutated residue was found to be essential to achieve satisfactory agreement with the reference data. PMID:26531155

  4. Refining the treatment of membrane proteins by coarse-grained models.

    PubMed

    Vorobyov, Igor; Kim, Ilsoo; Chu, Zhen T; Warshel, Arieh

    2016-01-01

    Obtaining a quantitative description of the membrane proteins stability is crucial for understanding many biological processes. However the advance in this direction has remained a major challenge for both experimental studies and molecular modeling. One of the possible directions is the use of coarse-grained models but such models must be carefully calibrated and validated. Here we use a recent progress in benchmark studies on the energetics of amino acid residue and peptide membrane insertion and membrane protein stability in refining our previously developed coarse-grained model (Vicatos et al., Proteins 2014;82:1168). Our refined model parameters were fitted and/or tested to reproduce water/membrane partitioning energetics of amino acid side chains and a couple of model peptides. This new model provides a reasonable agreement with experiment for absolute folding free energies of several β-barrel membrane proteins as well as effects of point mutations on a relative stability for one of those proteins, OmpLA. The consideration and ranking of different rotameric states for a mutated residue was found to be essential to achieve satisfactory agreement with the reference data. © 2015 Wiley Periodicals, Inc.

  5. Capturing the multiscale dynamics of membrane protein complexes with all-atom, mixed-resolution, and coarse-grained models.

    PubMed

    Liao, Chenyi; Zhao, Xiaochuan; Liu, Jiyuan; Schneebeli, Severin T; Shelley, John C; Li, Jianing

    2017-03-20

    The structures and dynamics of protein complexes are often challenging to model in heterogeneous environments such as biological membranes. Herein, we meet this fundamental challenge at attainable cost with all-atom, mixed-resolution, and coarse-grained models of vital membrane proteins. We systematically simulated five complex models formed by two distinct G protein-coupled receptors (GPCRs) in the lipid-bilayer membrane on the ns-to-μs timescales. These models, which suggest the swinging motion of an intracellular loop, for the first time, provide the molecular details for the regulatory role of such a loop. For the models at different resolutions, we observed consistent structural stability but various levels of speed-ups in protein dynamics. The mixed-resolution and coarse-grained models show two and four times faster protein diffusion than the all-atom models, in addition to a 4- and 400-fold speed-up in the simulation performance. Furthermore, by elucidating the strengths and challenges of combining all-atom models with reduced resolution models, this study can serve as a guide to simulating other complex systems in heterogeneous environments efficiently.

  6. 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.

  7. Two-component coarse-grained molecular-dynamics model for the human erythrocyte membrane.

    PubMed

    Li, He; Lykotrafitis, George

    2012-01-04

    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.

  8. SAFT-γ force field for the simulation of molecular fluids. 1. A single-site coarse grained model of carbon dioxide.

    PubMed

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

    2011-09-29

    An application of the "top-down" concept for the development of accurate coarse-grained intermolecular potentials of complex fluids is presented. With the more common "bottom-up" procedure, coarse-grained models are constructed from a suitable simplification of a detailed atomistic representation, and small adjustments to the intermolecular parameters are made by comparison with limited experimental data where necessary. In contrast, in the top-down approach, a molecular-based equation of state is used to obtain an effective coarse-grained intermolecular potential that reproduces the macroscopic experimental thermophysical properties over a wide range of conditions. These coarse-grained intermolecular potentials can then be used in conventional molecular simulation to obtain properties (such as structure or dynamics) that are not directly accessible from the equation of state or at extreme conditions where the theory is expected to fail. To demonstrate our procedure, a coarse-grained model for carbon dioxide (CO(2)) is obtained from a recent implementation of the statistical associating fluid theory of variable range (SAFT-VR) employing a Mie (generalized Lennard-Jones) potential; the parameters of this single-site Mie model of CO(2) are estimated by optimizing the equation of state's description of the experimental vapor-pressure and saturated liquid density data. This approach is only viable because of the excellent agreement of the SAFT-VR Mie EoS with simulation data. Our single-site SAFT-γ coarse-grained model for CO(2) is used in Monte Carlo molecular simulation to assess the adequacy of the description of the fluid-phase behavior and properties that were not used to develop the potential model such as the enthalpy of vaporization, interfacial tension, density profiles, supercritical densities, and second-derivative thermodynamic properties (thermal expansivity, isothermal compressibility, heat capacity, Joule-Thompson coefficient, and speed of sound). The

  9. Coarse-grain simulations of skin ceramide NS with newly derived parameters clarify structure of melted phase.

    PubMed

    Sovová, Žofie; Berka, Karel; Otyepka, Michal; Jurečka, Petr

    2015-03-12

    Ceramides are lipids that are involved in numerous biologically important structures (e.g., the stratum corneum and ceramide-rich platforms) and processes (e.g., signal transduction and membrane fusion), but their behavior is not fully understood. We report coarse-grain force field parameters for N-lignocerylsphingosine (ceramide NS, also known as ceramide 2) that are consistent with the Martini force field. These parameters were optimized for simulations in the gel phase and validated against atomistic simulations. Coarse-grained simulations with our parameters provide areas per lipid, membrane thicknesses, and electron density profiles that are in good agreement with atomistic simulations. Properties of the simulated membranes are compared with available experimental data. The obtained parameters were used to model the phase behavior of ceramide NS as a function of temperature and hydration. At low water content and above the main phase transition temperature, the bilayer melts into an irregular phase, which may correspond to the unstructured melted-chain phase observed in X-ray diffraction experiments. The developed parameters also reproduce the extended conformation of ceramide, which may occur in the stratum corneum. The parameters presented herein will facilitate studies on important complex functional structures such as the uppermost layer of the skin and ceramide-rich platforms in phospholipid membranes.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Coarse graining of NN inelastic interactions up to 3 GeV: Repulsive versus structural core

    NASA Astrophysics Data System (ADS)

    Fernández-Soler, P.; Ruiz Arriola, E.

    2017-07-01

    The repulsive short-distance core is one of the main paradigms of nuclear physics which even seems confirmed by QCD lattice calculations. On the other hand nuclear potentials at short distances are motivated by high energy behavior where inelasticities play an important role. We analyze NN interactions up to 3 GeV in terms of simple coarse grained complex and energy dependent interactions. We discuss two possible and conflicting scenarios which share the common feature of a vanishing wave function at the core location in the particular case of S waves. We find that the optical potential with a repulsive core exhibits a strong energy dependence whereas the optical potential with the structural core is characterized by a rather adiabatic energy dependence which allows one to treat inelasticity perturbatively. We discuss the possible implications for nuclear structure calculations of both alternatives.

  16. 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

    2012-05-08

    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.

  17. 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

  18. Multi-layer coarse-graining polarization model for treating electrostatic interactions of solvated α-conotoxin peptides

    NASA Astrophysics Data System (ADS)

    Jiang, Nan; Ma, Jing

    2012-04-01

    A multi-layer coarse-graining (CG) model is presented for treating the electrostatic interactions of solvated α-conotoxin peptides. According to the sensitivity to the electrostatic environment, a hybrid set of electrostatic parameters, such as secondary-structure- and residue-based dipoles, and atom-centered partial charges, are adopted. For the polarization "inert" secondary-structures and residues, the fragment dipole moments are distributed within narrow ranges with the magnitude close to zero. The coarse-graining fragment dipoles are parameterized from a large training set (10 000 configurations) to reproduce the electrostatic features of molecular fragments. In contrast, the electrostatically "sensitive" atoms exhibit large fluctuations of charges with the varied environments. The environment-dependent variable charges are updated in each energetic calculation. The electrostatic interaction of the whole chemical system is hence partitioned into several sub-terms coming from the fragment dipole-dipole, (fragment) dipole-(atom) charge, and atom charge-charge interactions. A large number of test calculations on the relative energies of cyclo-peptide conformers have demonstrated that the multi-layer CG electrostatic model presents better performance than the non-polarized force fields, in comparison with the density-functional theory and the fully polarized force field model. The selection of CG fragment centers, mass or geometric center, has little influence on the fragment-based dipole-dipole interactions. The multi-layer partition of electrostatic polarization is expected to be applied to many biologically interesting and complicated phenomena.

  19. A transferable coarse-grained potential to study the structure of confined, supercritical Lennard-Jones fluids.

    PubMed

    Sanghi, T; Aluru, N R

    2010-01-28

    In this paper, we develop a transferable coarse-grained interatomic potential to study the structure of simple (spherical and nonpolar) Lennard-Jones (LJ) fluids confined at supercritical temperatures. The potential is used in empirical potential based quasicontinuum theory, [A. V. Raghunathan et al., J. Chem. Phys. 127, 174701 (2007)] to study the structure of three simple LJ fluids (oxygen, methane, and argon) confined in slitlike geometries. The results obtained using the coarse-grained interatomic potential are found to be in good agreement with those predicted by equilibrium molecular dynamics simulations.

  20. Predictive coarse-graining

    NASA Astrophysics Data System (ADS)

    Schöberl, Markus; Zabaras, Nicholas; Koutsourelakis, Phaedon-Stelios

    2017-03-01

    We propose a data-driven, coarse-graining formulation in the context of equilibrium statistical mechanics. In contrast to existing techniques which are based on a fine-to-coarse map, we adopt the opposite strategy by prescribing a probabilistic coarse-to-fine map. This corresponds to a directed probabilistic model where the coarse variables play the role of latent generators of the fine scale (all-atom) data. From an information-theoretic perspective, the framework proposed provides an improvement upon the relative entropy method [1] and is capable of quantifying the uncertainty due to the information loss that unavoidably takes place during the coarse-graining process. Furthermore, it can be readily extended to a fully Bayesian model where various sources of uncertainties are reflected in the posterior of the model parameters. The latter can be used to produce not only point estimates of fine-scale reconstructions or macroscopic observables, but more importantly, predictive posterior distributions on these quantities. Predictive posterior distributions reflect the confidence of the model as a function of the amount of data and the level of coarse-graining. The issues of model complexity and model selection are seamlessly addressed by employing a hierarchical prior that favors the discovery of sparse solutions, revealing the most prominent features in the coarse-grained model. A flexible and parallelizable Monte Carlo - Expectation-Maximization (MC-EM) scheme is proposed for carrying out inference and learning tasks. A comparative assessment of the proposed methodology is presented for a lattice spin system and the SPC/E water model.

  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. 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.

  3. 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

  4. Development of DPD coarse-grained models: From bulk to interfacial properties.

    PubMed

    Solano Canchaya, José G; Dequidt, Alain; Goujon, Florent; Malfreyt, Patrice

    2016-08-07

    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.

  5. An improved coarse-grained model of solvation and the hydrophobic effect

    PubMed Central

    Varilly, Patrick; Patel, Amish J.; Chandler, David

    2011-01-01

    We present a coarse-grained lattice model of solvation thermodynamics and the hydrophobic effect that implements the ideas of Lum–Chandler–Weeks theory [J. Phys. Chem. B 134, 4570 (1999)] and improves upon previous lattice models based on it. Through comparison with molecular simulation, we show that our model captures the length-scale and curvature dependence of solvation free energies with near-quantitative accuracy and 2–3 orders of magnitude less computational effort, and further, correctly describes the large but rare solvent fluctuations that are involved in dewetting, vapor tube formation, and hydrophobic assembly. Our model is intermediate in detail and complexity between implicit-solvent models and explicit-water simulations. PMID:21341830

  6. 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.

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

    PubMed Central

    Chng, Choon-Peng; Yang, Lee-Wei

    2008-01-01

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

  8. Role of surface ligands in nanoparticle permeation through a model membrane: a coarse-grained molecular dynamics simulations study

    NASA Astrophysics Data System (ADS)

    Song, Bo; Yuan, Huajun; Jameson, Cynthia J.; Murad, Sohail

    2012-09-01

    How nanoparticles interact with biological membranes is of significant importance in determining the toxicity of nanoparticles as well as their potential applications in phototherapy, imaging and gene/drug delivery. It has been shown that such interactions are often determined by nanoparticle physicochemical factors such as size, shape, hydrophobicity and surface charge density. Surface modification of the nanoparticle offers the possibility of creating site-specific carriers for both drug delivery and diagnostic purposes. In this work, we use coarse-grained molecular dynamic simulations to explore the permeation characteristics of ligand-coated nanoparticles through a model membrane. We compare permeation behaviors of ligand-coated nanoparticles with bare nanoparticles to provide insights into how the ligands affect the permeation process. A series of simulations is carried out to validate a coarse-grained model for nanoparticles and a lipid membrane system. The minimum driving force for nanoparticles to penetrate the membrane and the mechanism of nanoparticle-membrane interaction were investigated. The potential of the mean force profile, nanoparticle velocity profile, force profile and density profiles (planar and radial) were obtained to explore the nanoparticle permeation process. The structural properties of both nanoparticles and lipid membrane during the permeation, which are of considerable fundamental interest, are also studied in our work. The findings described in our work will lead to a better understanding of nanoparticle-lipid membrane interactions and cell cytotoxicity and help develop more efficient nanocarrier systems for intracellular delivery of therapeutics.

  9. 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

  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. Insights from Coarse-GrainedModels for Protein Folding and Dynamics

    PubMed Central

    Hills, Ronald D.; Brooks, Charles L.

    2009-01-01

    Exploring the landscape of large scale conformational changes such as protein folding at atomistic detail poses a considerable computational challenge. Coarse-grained representations of the peptide chain have therefore been developed and over the last decade have proved extremely valuable. These include topology-based Gō models, which constitute a smooth and funnel-like approximation to the folding landscape. We review the many variations of the Gō model that have been employed to yield insight into folding mechanisms. Their success has been interpreted as a consequence of the dominant role of the native topology in folding. The role of local contact density in determining protein dynamics is also discussed and is used to explain the ability of Gō-like models to capture sequence effects in folding and elucidate conformational transitions. PMID:19399227

  12. Coarse-Grained Molecular Dynamics and Multiscale Modeling of NEMS Resonators

    SciTech Connect

    Rudd, R E

    2001-12-21

    We review concurrent multiscale simulations of dynamic and temperature-dependent processes found in nanomechanical systems coupled to larger scale surroundings. We focus on the behavior of sub-micron Micro-Electro-Mechanical Systems (MEMS), especially microresonators. These systems are often called NEMS, for Nano-Electro-Mechanical Systems. The coupling of length scales methodology we have developed for MEMS employs an atomistic description of small but key regions of the system, consisting of millions of atoms, coupled concurrently to a finite element model of the periphery. The model, Coarse-Grained Molecular Dynamics (CGMD), builds a generalized finite element formalism from the underlying atomistic physics in order to ensure a smooth coupling between regions governed by different length scales. The result is a model that accurately describes the behavior of the mechanical components of MEMS down to the atomic scale.

  13. A coarse-grained model for synergistic action of multiple enzymes on cellulose

    SciTech Connect

    Asztalos, Andrea; Daniels, Marcus; Sethi, Anurag; Shen, Tongye; Langan, Paul; Redondo, Antonio; Gnanakaran, Sandrasegaram

    2012-08-01

    In this study, degradation of cellulose to glucose requires the cooperative action of three classes of enzymes, collectively known as cellulases. Endoglucanases randomly bind to cellulose surfaces and generate new chain ends by hydrolyzing -1,4-D-glycosidic bonds. Exoglucanases bind to free chain ends and hydrolyze glycosidic bonds in a processive manner releasing cellobiose units. Then, -glucosidases hydrolyze soluble cellobiose to glucose. Optimal synergistic action of these enzymes is essential for efficient digestion of cellulose. Experiments show that as hydrolysis proceeds and the cellulose substrate becomes more heterogeneous, the overall degradation slows down. As catalysis occurs on the surface of crystalline cellulose, several factors affect the overall hydrolysis. Therefore, spatial models of cellulose degradation must capture effects such as enzyme crowding and surface heterogeneity, which have been shown to lead to a reduction in hydrolysis rates. As a result, we present a coarse-grained stochastic model for capturing the key events associated with the enzymatic degradation of cellulose at the mesoscopic level. This functional model accounts for the mobility and action of a single cellulase enzyme as well as the synergy of multiple endo- and exo-cellulases on a cellulose surface. The quantitative description of cellulose degradation is calculated on a spatial model by including free and bound states of both endo- and exo-cellulases with explicit reactive surface terms (e.g., hydrogen bond breaking, covalent bond cleavages) and corresponding reaction rates. The dynamical evolution of the system is simulated by including physical interactions between cellulases and cellulose. In conclusion, our coarse-grained model reproduces the qualitative behavior of endoglucanases and exoglucanases by accounting for the spatial heterogeneity of the cellulose surface as well as other spatial factors such as enzyme crowding. Importantly, it captures the endo

  14. 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.

  15. A temperature-dependent coarse-grained model for the thermoresponsive polymer poly(N-isopropylacrylamide)

    DOE PAGES

    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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2017-05-01

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

  3. The origin of coarse grain structure in friction-stir welded AA5083 after heat treatment

    NASA Astrophysics Data System (ADS)

    Chen, Ke

    Friction stir welding (FSW) takes place in the solid state, thus providing potential advantages of welds of high strength and ductility with fine microstructures. However, post-FSW heat treatment can produce very coarse grains, potentially reducing mechanical properties. AA5083-H18 sheets were friction-stir butt-welded using three sets of welding parameters representing a wide range of heat input. They were then heat treated for 5 minutes at 738 K (465°C), producing grain sizes exceeding 100 mum near the top weld surfaces, and proceeding toward the bottom surface to various degrees depending on the welding parameters. Electron backscatter diffraction (EBSD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), optical metallography, Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and Vickers hardness testing were used to characterize the regions within welds. The mechanism responsible for forming the large grains was identified as abnormal grain growth (AGG). Based on a simple model of grain growth, the heat treatment is found to be near the critical condition for AGG to occur, with the principal determinants being the post-FSW grain size and fraction of low angle boundaries. Other possible factors (second-phase particle volume fractions and sizes, textures, dislocation content, and Mg solute distribution) were not significantly different in AGG and non-AGG regions. Based on these results, recommendations for changes in alloy, FSW conditions, and post-FSW heat treatment were identified to eliminate AGG.

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

    NASA Astrophysics Data System (ADS)

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

    2013-01-01

    We discuss a coarse-grained model recently proposed by Starr and Sciortino [J. Phys.: Condens. Matter 18, L347 (2006), 10.1088/0953-8984/18/26/L02] 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.

  5. 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.

  6. A unified coarse-grained model of biological macromolecules based on mean-field multipole-multipole interactions.

    PubMed

    Liwo, Adam; Baranowski, Maciej; Czaplewski, Cezary; Gołaś, Ewa; He, Yi; Jagieła, Dawid; Krupa, Paweł; Maciejczyk, Maciej; Makowski, Mariusz; Mozolewska, Magdalena A; Niadzvedtski, Andrei; Ołdziej, Stanisław; Scheraga, Harold A; Sieradzan, Adam K; Slusarz, Rafał; Wirecki, Tomasz; Yin, Yanping; Zaborowski, Bartłomiej

    2014-08-01

    A unified coarse-grained model of three major classes of biological molecules--proteins, nucleic acids, and polysaccharides--has been developed. It is based on the observations that the repeated units of biopolymers (peptide groups, nucleic acid bases, sugar rings) are highly polar and their charge distributions can be represented crudely as point multipoles. The model is an extension of the united residue (UNRES) coarse-grained model of proteins developed previously in our laboratory. The respective force fields are defined as the potentials of mean force of biomacromolecules immersed in water, where all degrees of freedom not considered in the model have been averaged out. Reducing the representation to one center per polar interaction site leads to the representation of average site-site interactions as mean-field dipole-dipole interactions. Further expansion of the potentials of mean force of biopolymer chains into Kubo's cluster-cumulant series leads to the appearance of mean-field dipole-dipole interactions, averaged in the context of local interactions within a biopolymer unit. These mean-field interactions account for the formation of regular structures encountered in biomacromolecules, e.g., α-helices and β-sheets in proteins, double helices in nucleic acids, and helicoidally packed structures in polysaccharides, which enables us to use a greatly reduced number of interacting sites without sacrificing the ability to reproduce the correct architecture. This reduction results in an extension of the simulation timescale by more than four orders of magnitude compared to the all-atom representation. Examples of the performance of the model are presented.

  7. Transferability of a coarse-grained atactic polystyrene model: the non-bonded potential effect.

    PubMed

    Xiao, Qiang; Guo, Hongxia

    2016-11-02

    In this paper, we construct an efficient and simple coarse grained (CG) model for atactic polystyrene (PS) by using a 1 : 1 mapping scheme at 463 K and 1 atm pressure and derive the corresponding bonded and non-bonded potentials in the CG force field (FF) via a direct Boltzmann inversion approach and a combined structure-based and thermodynamic quantities-based CG method, respectively. For computational considerations, the non-bonded interaction between CG particles is described by Lennard-Jones (LJ) type potentials, and both the radial distribution function (RDF) and the bulk density of the atomistic simulations are taken as target properties in the parameterization of the two LJ parameters. To shed light on the choice of LJ forms of CG non-bonded potentials when designing the CG models, a series of CG models with different LJ potentials are constructed and compared in order to understand how the quality of a CG model in reproducing the structure and thermodynamic properties of chemically realistic systems is affected by the choice of non-bonded potentials. We find that with our structural and thermodynamics combined CG method to construct the CG FF at a single thermodynamic state point without any temperature dependent LJ potential correction and/or pressure optimization, the resulting CG models possess good temperature transferability in a wide range of temperatures 300-600 K, where both the target properties and several other static properties (such as thermal expansion coefficient and mean-square radius of gyration) are generally reproduced. Furthermore, the non-bonded LJ potential influences the density response of CG models to the temperature change, i.e., CG models with harder LJ potentials show better temperature transferability than the softer ones. Meanwhile, the derived Tg increases with increasing LJ repulsion strength while thermal expansion coefficients in both melt and glass states are lowered as the LJ potential hardens. With regard to the

  8. A coarse-grained model for synergistic action of multiple enzymes on cellulose

    DOE PAGES

    Asztalos, Andrea; Daniels, Marcus; Sethi, Anurag; ...

    2012-08-01

    In this study, degradation of cellulose to glucose requires the cooperative action of three classes of enzymes, collectively known as cellulases. Endoglucanases randomly bind to cellulose surfaces and generate new chain ends by hydrolyzing -1,4-D-glycosidic bonds. Exoglucanases bind to free chain ends and hydrolyze glycosidic bonds in a processive manner releasing cellobiose units. Then, -glucosidases hydrolyze soluble cellobiose to glucose. Optimal synergistic action of these enzymes is essential for efficient digestion of cellulose. Experiments show that as hydrolysis proceeds and the cellulose substrate becomes more heterogeneous, the overall degradation slows down. As catalysis occurs on the surface of crystalline cellulose,more » several factors affect the overall hydrolysis. Therefore, spatial models of cellulose degradation must capture effects such as enzyme crowding and surface heterogeneity, which have been shown to lead to a reduction in hydrolysis rates. As a result, we present a coarse-grained stochastic model for capturing the key events associated with the enzymatic degradation of cellulose at the mesoscopic level. This functional model accounts for the mobility and action of a single cellulase enzyme as well as the synergy of multiple endo- and exo-cellulases on a cellulose surface. The quantitative description of cellulose degradation is calculated on a spatial model by including free and bound states of both endo- and exo-cellulases with explicit reactive surface terms (e.g., hydrogen bond breaking, covalent bond cleavages) and corresponding reaction rates. The dynamical evolution of the system is simulated by including physical interactions between cellulases and cellulose. In conclusion, our coarse-grained model reproduces the qualitative behavior of endoglucanases and exoglucanases by accounting for the spatial heterogeneity of the cellulose surface as well as other spatial factors such as enzyme crowding. Importantly, it captures the endo

  9. Coarse-Grained Modeling of the Actin Filament Derived from Atomistic-Scale Simulations

    PubMed Central

    Chu, Jhih-Wei; Voth, Gregory A.

    2006-01-01

    A coarse-grained (CG) procedure that incorporates the information obtained from all-atom molecular dynamics (MD) simulations is presented and applied to actin filaments (F-actin). This procedure matches the averaged values and fluctuations of the effective internal coordinates that are used to define a CG model to the values extracted from atomistic MD simulations. The fluctuations of effective internal coordinates in a CG model are computed via normal-mode analysis (NMA), and the computed fluctuations are matched with the atomistic MD results in a self-consistent manner. Each actin monomer (G-actin) is coarse-grained into four sites, and each site corresponds to one of the subdomains of G-actin. The potential energy of a CG G-actin contains three bonds, two angles, and one dihedral angle; effective harmonic bonds are used to describe the intermonomer interactions in a CG F-actin. The persistence length of a CG F-actin was found to be sensitive to the cut-off distance of assigning intermonomer bonds. Effective harmonic bonds for a monomer with its third nearest neighboring monomers are found to be necessary to reproduce the values of persistence length obtained from all-atom MD simulations. Compared to the elastic network model, incorporating the information of internal coordinate fluctuations enhances the accuracy and robustness for a CG model to describe the shapes of low-frequency vibrational modes. Combining the fluctuation-matching CG procedure and NMA, the achievable time- and length scales of modeling actin filaments can be greatly enhanced. In particular, a method is described to compute the force-extension curve using the CG model developed in this work and NMA. It was found that F-actin is easily buckled under compressive deformation, and a writhing mode is developed as a result. In addition to the bending and twisting modes, this novel writhing mode of F-actin could also play important roles in the interactions of F-actin with actin-binding proteins and

  10. Extension of CAVS coarse-grained model to phospholipid membranes: The importance of electrostatics.

    PubMed

    Shen, Hujun; Deng, Mingsen; Zhang, Yachao

    2017-05-15

    It is evident from experiment that electrostatic potential (or dipole potential) is positive inside PC or PE lipid bilayers in the absence of ions. MARTINI coarse-grained (CG) model, which has been widely used in simulating physical properties of lipid bilayers, fails to reproduce the positive value for the dipole potential in the membrane interior. Although the total dipole potential can be correctly described by the BMW/MARTINI model, the contribution from the ester dipoles, playing a nontrivial role in the electrostatic potential across lipid membranes, is neglected by this hybrid approach. In the ELBA CG model, the role of the ester dipoles is considered, but it is overweighed because various atomistic models have consistently shown that water is actually the leading contributor of dipole potential. Here, we present a CG approach by combining the BMW-like water model (namely CAVS model) with the ELBA-like lipid model proposed in this work. Our CG model was designed not only to correctly reproduce the positive values for the dipole potential inside PC and PE lipid bilayers but also to properly balance the individual contributions from the ester dipoles and water, surmounting the limitations of current CG models in the calculations of dipole potential. © 2017 Wiley Periodicals, Inc.

  11. 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.

  12. Multiscale crystal defect dynamics: A coarse-grained lattice defect model based on crystal microstructure

    NASA Astrophysics Data System (ADS)

    Lyu, Dandan; Li, Shaofan

    2017-10-01

    Crystal defects have microstructure, and this microstructure should be related to the microstructure of the original crystal. Hence each type of crystals may have similar defects due to the same failure mechanism originated from the same microstructure, if they are under the same loading conditions. In this work, we propose a multiscale crystal defect dynamics (MCDD) model that models defects by considering its intrinsic microstructure derived from the microstructure or material genome of the original perfect crystal. The main novelties of present work are: (1) the discrete exterior calculus and algebraic topology theory are used to construct a scale-up (coarse-grained) dual lattice model for crystal defects, which may represent all possible defect modes inside a crystal; (2) a higher order Cauchy-Born rule (up to the fourth order) is adopted to construct atomistic-informed constitutive relations for various defect process zones, and (3) an hierarchical strain gradient theory based finite element formulation is developed to support an hierarchical multiscale cohesive (process) zone model for various defects in a unified formulation. The efficiency of MCDD computational algorithm allows us to simulate dynamic defect evolution at large scale while taking into account atomistic interaction. The MCDD model has been validated by comparing of the results of MCDD simulations with that of molecular dynamics (MD) in the cases of nanoindentation and uniaxial tension. Numerical simulations have shown that MCDD model can predict dislocation nucleation induced instability and inelastic deformation, and thus it may provide an alternative solution to study crystal plasticity.

  13. Universal and non-universal features in coarse-grained models of flow in disordered solids.

    PubMed

    Nicolas, Alexandre; Martens, Kirsten; Bocquet, Lydéric; Barrat, Jean-Louis

    2014-07-14

    We study the two-dimensional (2D) shear flow of amorphous solids within variants of an elastoplastic model, paying particular attention to spatial correlations and time fluctuations of, e.g., local stresses. The model is based on the local alternation between an elastic regime and plastic events during which the local stress is redistributed. The importance of a fully tensorial description of the stress and of the inclusion of (coarse-grained) convection in the model is investigated; scalar and tensorial models yield similar results, while convection enhances fluctuations and breaks the spurious symmetry between the flow and velocity gradient directions, for instance when shear localisation is observed. Besides, correlation lengths measured with diverse protocols are discussed. One class of such correlation lengths simply scale with the spacing between homogeneously distributed, simultaneous plastic events. This leads to a scaling of the correlation length with the shear rate as γ̇(-1/2) in 2D in the athermal regime, regardless of the details of the model. The radius of the cooperative disk, defined as the near-field region in which plastic events induce a stress redistribution that is not amenable to a mean-field treatment, notably follows this scaling. On the other hand, the cooperative volume measured from the four-point stress susceptibility and its dependence on the system size and the shear rate are model-dependent.

  14. 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.

  15. Comparison of thermodynamic properties of coarse-grained and atomic-level simulation models.

    PubMed

    Baron, Riccardo; Trzesniak, Daniel; de Vries, Alex H; Elsener, Andreas; Marrink, Siewert J; van Gunsteren, Wilfred F

    2007-02-19

    Thermodynamic data are often used to calibrate or test amomic-level (AL) force fields for molecular dynamics (MD) simulations. In contrast, the majority of coarse-grained (CG) force fields do not rely extensively on thermodynamic quantities. Recently, a CG force field for lipids, hydrocarbons, ions, and water, in which approximately four non-hydrogen atoms are mapped onto one interaction site, has been proposed and applied to study various aspects of lipid systems. To date, no extensive investigation of its capability to describe salvation thermodynamics has been undertaken. In the present study, a detailed picture of vaporization, solvation, and phase-partitioning thermodynamics for liquid hydrocarbons and water was obtained at CG and AL resolutions, in order to compare the two types or models and evaluate their ability to describe thermodynamic properties in the temperature range between 263 and 343 K. Both CG and AL models capture the experimental dependence of the thermodynamic properties on the temperature, albeit a systematically weaker dependence is found for the CG model. Moreover, deviations are found for solvation thermodynamics and for the corresponding enthalpy-entropy compensation for the CG model. Particularly water/oil repulsion seems to be overestimated. However, the results suggest that the thermodynamic properties considered should be reproducible by a CG model provided it is reparametrized on the basis of these liquid-phase properties.

  16. Coarse-grained model of water diffusion and proton conductivity in hydrated polyelectrolyte membrane

    SciTech Connect

    Lee, Ming-Tsung; Vishnyakov, Aleksey; Neimark, Alexander V.

    2016-01-07

    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.

  17. PyCGTOOL: Automated Generation of Coarse-Grained Molecular Dynamics Models from Atomistic Trajectories.

    PubMed

    Graham, James A; Essex, Jonathan W; Khalid, Syma

    2017-04-24

    Development of coarse-grained (CG) molecular dynamics models is often a laborious process which commonly relies upon approximations to similar models, rather than systematic parametrization. PyCGTOOL automates much of the construction of CG models via calculation of both equilibrium values and force constants of internal coordinates directly from atomistic molecular dynamics simulation trajectories. The derivation of bespoke parameters from atomistic simulations improves the quality of the CG model compared to the use of generic parameters derived from other molecules, while automation greatly reduces the time required. The ease of configuration of PyCGTOOL enables the rapid investigation of multiple atom-to-bead mappings and topologies. Although we present PyCGTOOL used in combination with the GROMACS molecular dynamics engine its use of standard trajectory input libraries means that it is in principle compatible with other software. The software is available from the URL https://github.com/jag1g13/pycgtool as the following doi: 10.5281/zenodo.259330 .

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. Predicting Partition Coefficients with a Simple All-Atom/Coarse-Grained Hybrid Model.

    PubMed

    Genheden, Samuel

    2016-01-12

    The solvation free energy is an essential quantity in force field development and in numerous applications. Here, we present the estimation of solvation free energies in polar (water, hexanol, octanol, and nonanol) and in apolar (hexane, octane, and nonane) media. The estimates are produced using molecular dynamics simulations employing a simple all-atom/coarse-grained hybrid model (AA/ELBA) and are therefore very efficient. More than 150 solutes were taken from the Minnesota solvation database and represent small, organic molecules. The mean absolute deviation for the different solvents ranges between 2.0 and 4.1 kJ/mol, and the correlation coefficient ranges between 0.78 and 0.99, indicating that the predictions are accurate. Outliers are identified, and potential avenues for improvements are discussed. Furthermore, partition coefficients between water and the organic solvents were estimated, and the percentage of the predictions that has the correct sign ranges between 74% (for octane) and 92% (for octanol and hexanol). Finally, membrane/water partition coefficients are replaced with hexane/water and octanol/water partition coefficients, and the latter is found to be as accurate as the expensive membrane calculations, indicating a wider application area.

  4. 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.

  5. Derivation of free energy expressions for tube models from coarse-grained slip-link models.

    PubMed

    Steenbakkers, Rudi J A; Schieber, Jay D

    2012-07-21

    We present the free energy of a single-chain mean-field model for polymer melt dynamics, which uses a continuous (tube-like) approximation to the discrete entanglements with surrounding chains, but, in contrast to previous tube models, includes fluctuations in the number density of Kuhn steps along the primitive path and in the degree of entanglement. The free energy is obtained from that of the slip-link model with fluctuating entanglement positions [J. D. Schieber and K. Horio, J. Chem. Phys. 132, 074905 (2010)] by taking the continuous limit of (functions of) the discrete Kuhn-step numbers and end-to-end vectors of the strands between entanglements. This coarse-graining from a more-detailed level of description has the advantage that no ad hoc arguments need to be introduced. Moreover, the thermodynamic consistency of the slip-link model [J. D. Schieber, J. Non-Equilib. Thermodyn. 28, 179 (2003)] can be preserved. Fluctuations in the positions of entanglements lead to a harmonic bending term in the free energy of the continuous chain, similar to that derived by Read et al. [Macromolecules 41, 6843 (2008)] starting from a modified GLaMM model [R. S. Graham, A. E. Likhtman, T. C. B. McLeish, and S. T. Milner, J. Rheol. 47, 1171 (2003)]. If these fluctuations are set to zero, the free energy becomes purely Gaussian and corresponds to the continuous limit of the original slip-link model, with affinely moving entanglements [J. D. Schieber, J. Chem. Phys. 118, 5162 (2003)]. The free energy reduces to that of Read et al. under their assumptions of a homogeneous Kuhn-step number density and a constant degree of entanglement. Finally, we show how a transformation of the primitive-path coordinate can be applied to make the degree of entanglement an outcome of the model instead of a variable. In summary, this paper constitutes a first step towards a unified mathematical formulation of tube models. The next step will be to formulate the dynamics of the primitive

  6. Derivation of free energy expressions for tube models from coarse-grained slip-link models

    NASA Astrophysics Data System (ADS)

    Steenbakkers, Rudi J. A.; Schieber, Jay D.

    2012-07-01

    We present the free energy of a single-chain mean-field model for polymer melt dynamics, which uses a continuous (tube-like) approximation to the discrete entanglements with surrounding chains, but, in contrast to previous tube models, includes fluctuations in the number density of Kuhn steps along the primitive path and in the degree of entanglement. The free energy is obtained from that of the slip-link model with fluctuating entanglement positions [J. D. Schieber and K. Horio, J. Chem. Phys. 132, 074905 (2010)], 10.1063/1.3314727 by taking the continuous limit of (functions of) the discrete Kuhn-step numbers and end-to-end vectors of the strands between entanglements. This coarse-graining from a more-detailed level of description has the advantage that no ad hoc arguments need to be introduced. Moreover, the thermodynamic consistency of the slip-link model [J. D. Schieber, J. Non-Equilib. Thermodyn. 28, 179 (2003)], 10.1515/JNETDY.2003.010 can be preserved. Fluctuations in the positions of entanglements lead to a harmonic bending term in the free energy of the continuous chain, similar to that derived by Read et al. [Macromolecules 41, 6843 (2008)], 10.1021/ma8009855 starting from a modified GLaMM model [R. S. Graham, A. E. Likhtman, T. C. B. McLeish, and S. T. Milner, J. Rheol. 47, 1171 (2003)], 10.1122/1.1595099. If these fluctuations are set to zero, the free energy becomes purely Gaussian and corresponds to the continuous limit of the original slip-link model, with affinely moving entanglements [J. D. Schieber, J. Chem. Phys. 118, 5162 (2003)], 10.1063/1.1553764. The free energy reduces to that of Read et al. under their assumptions of a homogeneous Kuhn-step number density and a constant degree of entanglement. Finally, we show how a transformation of the primitive-path coordinate can be applied to make the degree of entanglement an outcome of the model instead of a variable. In summary, this paper constitutes a first step towards a unified mathematical

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

    DOE PAGES

    de Oliveira, Tiago E.; Netz, Paulo A.; Kremer, Kurt; ...

    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.

  8. A Bayesian framework for adaptive selection, calibration, and validation of coarse-grained models of atomistic systems

    SciTech Connect

    Farrell, Kathryn Oden, J. Tinsley Faghihi, Danial

    2015-08-15

    A general adaptive modeling algorithm for selection and validation of coarse-grained models of atomistic systems is presented. A Bayesian framework is developed to address uncertainties in parameters, data, and model selection. Algorithms for computing output sensitivities to parameter variances, model evidence and posterior model plausibilities for given data, and for computing what are referred to as Occam Categories in reference to a rough measure of model simplicity, make up components of the overall approach. Computational results are provided for representative applications.

  9. A Coarse-Grained Model Based on Morse Potential for Water and n-Alkanes.

    PubMed

    Chiu, See-Wing; Scott, H Larry; Jakobsson, Eric

    2010-03-09

    In order to extend the time and distance scales of molecular dynamics simulations, it is essential to create accurate coarse-grained force fields, in which each particle contains several atoms. Coarse-grained force fields that utilize the Lennard-Jones potential form for pairwise nonbonded interactions have been shown to suffer from serious inaccuracy, notably with respect to describing the behavior of water. In this paper, we describe a coarse-grained force field for water, in which each particle contains four water molecules, based on the Morse potential form. By molecular dynamics simulations, we show that our force field closely replicates important water properties. We also describe a Morse potential force field for alkanes and a simulation method for alkanes in which individual particles may have variable size, providing flexibility in constructing complex molecules comprised partly or solely of alkane groups. We find that, in addition to being more accurate, the Morse potential also provides the ability to take larger time steps than the Lennard-Jones, because the short distance repulsion potential profile is less steep. We suggest that the Morse potential form should be considered as an alternative for the Lennard-Jones form for coarse-grained molecular dynamics simulations.

  10. 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.

  11. 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

  12. 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

  13. HIGH-FIDELITY SIMULATION-DRIVEN MODEL DEVELOPMENT FOR COARSE-GRAINED COMPUTATIONAL FLUID DYNAMICS

    SciTech Connect

    Hanna, Botros N.; Dinh, Nam T.; Bolotnov, Igor A.

    2016-06-01

    Nuclear reactor safety analysis requires identifying various credible accident scenarios and determining their consequences. For a full-scale nuclear power plant system behavior, it is impossible to obtain sufficient experimental data for a broad range of risk-significant accident scenarios. In single-phase flow convective problems, Direct Numerical Simulation (DNS) and Large Eddy Simulation (LES) can provide us with high fidelity results when physical data are unavailable. However, these methods are computationally expensive and cannot be afforded for simulation of long transient scenarios in nuclear accidents despite extraordinary advances in high performance scientific computing over the past decades. The major issue is the inability to make the transient computation parallel, thus making number of time steps required in high-fidelity methods unaffordable for long transients. In this work, we propose to apply a high fidelity simulation-driven approach to model sub-grid scale (SGS) effect in Coarse Grained Computational Fluid Dynamics CG-CFD. This approach aims to develop a statistical surrogate model instead of the deterministic SGS model. We chose to start with a turbulent natural convection case with volumetric heating in a horizontal fluid layer with a rigid, insulated lower boundary and isothermal (cold) upper boundary. This scenario of unstable stratification is relevant to turbulent natural convection in a molten corium pool during a severe nuclear reactor accident, as well as in containment mixing and passive cooling. The presented approach demonstrates how to create a correction for the CG-CFD solution by modifying the energy balance equation. A global correction for the temperature equation proves to achieve a significant improvement to the prediction of steady state temperature distribution through the fluid layer.

  14. Conformational Properties of a Polymer in an Ionic Liquid: Computer Simulations and Integral Equation Theory of a Coarse-Grained Model.

    PubMed

    Choi, Eunsong; Yethiraj, Arun

    2015-07-23

    We study the conformational properties of polymers in room temperature ionic liquids using theory and simulations of a coarse-grained model. Atomistic simulations have shown that single poly(ethylene oxide) (PEO) molecules in the ionic liquid 1-butyl 3-methyl imidazolium tetrafluoroborate ([BMIM][BF4]) are expanded at room temperature (i.e., the radius of gyration, Rg), scales with molecular weight, Mw, as Rg ∼ Mw(0.9), instead of the expected self-avoiding walk behavior. The simulations were restricted to fairly short chains, however, which might not be in the true scaling regime. In this work, we investigate a coarse-grained model for the behavior of PEO in [BMIM][BF4]. We use existing force fields for PEO and [BMIM][BF4] and Lorentz–Berthelot mixing rules for the cross interactions. The coarse-grained model predicts that PEO collapses in the ionic liquid. We also present an integral equation theory for the structure of the ionic liquid and the conformation properties of the polymer. The theory is in excellent agreement with the simulation results. We conclude that the properties of polymers in ionic liquids are unusually sensitive to the details of the intermolecular interactions. The integral equation theory is sufficiently accurate to be a useful guide to computational work.

  15. 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.

  16. A comparison of united atom, explicit atom, and coarse-grained simulation models for poly(ethylene oxide).

    PubMed

    Chen, Chunxia; Depa, Praveen; Sakai, Victoria García; Maranas, Janna K; Lynn, Jeffrey W; Peral, Inmaculada; Copley, John R D

    2006-06-21

    We compare static and dynamic properties obtained from three levels of modeling for molecular dynamics simulation of poly(ethylene oxide) (PEO). Neutron scattering data are used as a test of each model's accuracy. The three simulation models are an explicit atom (EA) model (all the hydrogens are taken into account explicitly), a united atom (UA) model (CH(2) and CH(3) groups are considered as a single unit), and a coarse-grained (CG) model (six united atoms are taken as one bead). All three models accurately describe the PEO static structure factor as measured by neutron diffraction. Dynamics are assessed by comparison to neutron time of flight data, which follow self-motion of protons. Hydrogen atom motion from the EA model and carbon/oxygen atom motion from the UA model closely follow the experimental hydrogen motion, while hydrogen atoms reinserted in the UA model are too fast. The EA and UA models provide a good description of the orientation properties of C-H vectors measured by nuclear magnetic resonance experiments. Although dynamic observables in the CG model are in excellent agreement with their united atom counterparts, they cannot be compared to neutron data because the time after which the CG model is valid is greater than the neutron decay times.

  17. Coarse-Graining of TIP4P/2005, TIP4P-Ew, SPC/E, and TIP3P to Monatomic Anisotropic Water Models Using Relative Entropy Minimization.

    PubMed

    Lu, Jibao; Qiu, Yuqing; Baron, Riccardo; Molinero, Valeria

    2014-09-09

    Coarse-grained models are becoming a competitive alternative for modeling processes that occur over time and length scales beyond the reach of fully atomistic molecular simulations. Ideally, coarse-grained models should not only achieve high computational efficiency but also provide accurate predictions and fundamental insight into the role of molecular interactions, the characteristic behavior, and properties of the system they model. In this work we derive a series of monatomic coarse-grained water models mX(REM) from the most popular atomistic water models X = TIP3P, SPC/E, TIP4P-Ew, and TIP4P/2005, using the relative entropy minimization (REM) method. Each coarse-grained water molecule is represented by a single particle that interacts through short-ranged anisotropic interactions that encourage the formation of "hydrogen-bonded" structures. We systematically investigate the features of the coarse-grained models in reproducing over 20 structural, dynamic, and thermodynamic properties of the reference atomistic water models-including the existence and locus of the characteristic density anomaly. The mX(REM) coarse-grained models reproduce quite faithfully the radial and angular distribution function of water, produce a temperature of maximum density (TMD), and stabilize the ice I crystal. Moreover, the ratio between the TMD and the melting temperature of the crystal in the mX(REM) models and liquid-ice equilibrium properties show reasonable agreement with the results of the corresponding atomistic models. The mX(REM) models, however, severely underestimate the cohesive energy of the condensed water phases. We investigate which specific limitations of the coarse-grained models arise from the REM methodology, from the monatomic nature of the models, and from the Stillinger-Weber interaction potential form. Our analysis indicates that a small compromise in the accuracy of structural properties can result in a significant increase of the overall accuracy and

  18. The susceptibility of α-helical secondary structure to steric strain: Coarse-grained simulation of dendronized polypeptides.

    PubMed

    Browne, William; Geissler, Phillip L

    2010-10-14

    The propensity of a peptide chain for adopting helical secondary structure can be modulated not only through the solvation properties of its side chains but also through their size and shape. Here we examine a coarse-grained model for dendronized polypeptides that focuses on the susceptibility of α-helical structure to the steric strain exerted by hydrophilic pendant groups. Undecorated molecules exhibit a pronounced transition from random coil to helix upon cooling [J. P. Kemp and J. Z. Y. Chen, Biomacromolecules 2, 389 (2001)]. As gauged by specific heat and by order parameters characterizing helicity at several length scales, this transition is quite robust to the introduction of first- and second-generation dendron side chains. More highly branched side chains, however, reduce the entropy of compact states so severely that helical ordering is undetectable over the entire temperature range accessible to our importance sampling methods. Consistent with experimental observations for side chains comparable to those of our model in volume-excluding size and shape, we find the backbone of these third-generation molecules to assume a distended rodlike state that is both stiff and achiral.

  19. 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.

  20. Structure-based design of carbon nanotubes as HIV-1 protease inhibitors: atomistic and coarse-grained simulations.

    PubMed

    Cheng, Yuan; Li, Dechang; Ji, Baohua; Shi, Xinghua; Gao, Huajian

    2010-09-01

    Nanoparticles such as fullerenes and carbon nanotubes have been extensively studied for biomedical applications. In this paper, we report the design of carbon nanotubes as HIV-1 protease inhibitors. Docking and molecular dynamics calculations are performed using an atomistic model to explore the optimal interaction structure and free energy between the nanotube and HIV-1 protease. A coarse-grained model is then developed based on the atomistic model, allowing us to investigate the dynamic behaviors of the protease in the bound and unbound states. The dynamic process reveals that the carbon nanotube is able to bind to the active site of the protease and prevent the active flaps from opening up, thus blocking the function of the protease. This process is strongly influenced by the size of the nanotube. The binding of carbon nanotubes to an alternative binding site other than the active site is also explored. Therefore, carbon nanotube-based inhibitors have great potential for application as HIV-1 protease inhibitors.

  1. Molecular dynamics simulation of protein adsorption at fluid interfaces: a comparison of all-atom and coarse-grained models.

    PubMed

    Euston, Stephen R

    2010-10-11

    The adsorption of LTP at the decane-water interface was modeled using all-atom and coarse-grained (CG) molecular dynamics simulations. The CG model (300 ns simulation, 1200 ns scaled time) generates equilibrium adsorbed conformations in about 12 h, whereas the equivalent 1200 ns simulation would take about 300 days for the all-atom model. In both models the LTP molecule adsorbs with α-helical regions parallel to the interface with an average tilt angle normal to the interface of 73° for the all-atom model and 62° for the CG model. In the all-atom model, the secondary structure of the LTP is conserved upon adsorption. A considerable proportion of the N-terminal loop of LTP can be found in the decane phase for the all-atom model, whereas in the CG model the protein only penetrates as far as the mixed water-decane interfacial region. This difference may arise due to the different schemes used to parametrize force field parameters in the two models.

  2. Hierarchical Coarse-Graining Via a Generalized Yvon-Born Green Framework: Many-Body Correlations, Mappings, and Structural Accuracy

    NASA Astrophysics Data System (ADS)

    Rudzinski, Joseph F.

    Atomically-detailed molecular dynamics simulations have emerged as one of the most powerful theoretic tools for studying complex, condensed-phase systems. Despite their ability to provide incredible molecular insight, these simulations are insufficient for investigating complex biological processes, e.g., protein folding or molecular aggregation, on relevant length and time scales. The increasing scope and sophistication of atomically-detailed models has motivated the development of "hierarchical" approaches, which parameterize a low resolution, coarse-grained (CG) model based on simulations of an atomically-detailed model. The utility of hierarchical CG models depends on their ability to accurately incorporate the correct physics of the underlying model. One approach for ensuring this "consistency" between the models is to parameterize the CG model to reproduce the structural ensemble generated by the high resolution model. The many-body potential of mean force is the proper CG energy function for reproducing all structural distributions of the atomically-detailed model, at the CG level of resolution. However, this CG potential is a configuration-dependent free energy function that is generally too complicated to represent or simulate. The multiscale coarse-graining (MS-CG) method employs a generalized Yvon-Born-Green (g-YBG) relation to directly determine a variationally optimal approximation to the many-body potential of mean force. The MS-CG/g-YBG method provides a convenient and transparent framework for investigating the equilibrium structure of the system, at the CG level of resolution. In this work, we investigate the fundamental limitations and approximations of the MS-CG/g-YBG method. Throughout the work, we propose several theoretic constructs to directly relate the MS-CG/g-YBG method to other popular structure-based CG approaches. We investigate the physical interpretation of the MS-CG/g-YBG correlation matrix, the quantity responsible for disentangling

  3. 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

  4. 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

  5. Highly Coarse-Grained Representations of Transmembrane Proteins

    PubMed Central

    2017-01-01

    Numerous biomolecules and biomolecular complexes, including transmembrane proteins (TMPs), are symmetric or at least have approximate symmetries. Highly coarse-grained models of such biomolecules, aiming at capturing the essential structural and dynamical properties on resolution levels coarser than the residue scale, must preserve the underlying symmetry. However, making these models obey the correct physics is in general not straightforward, especially at the highly coarse-grained resolution where multiple (∼3–30 in the current study) amino acid residues are represented by a single coarse-grained site. In this paper, we propose a simple and fast method of coarse-graining TMPs obeying this condition. The procedure involves partitioning transmembrane domains into contiguous segments of equal length along the primary sequence. For the coarsest (lowest-resolution) mappings, it turns out to be most important to satisfy the symmetry in a coarse-grained model. As the resolution is increased to capture more detail, however, it becomes gradually more important to match modular repeats in the secondary structure (such as helix-loop repeats) instead. A set of eight TMPs of various complexity, functionality, structural topology, and internal symmetry, representing different classes of TMPs (ion channels, transporters, receptors, adhesion, and invasion proteins), has been examined. The present approach can be generalized to other systems possessing exact or approximate symmetry, allowing for reliable and fast creation of multiscale, highly coarse-grained mappings of large biomolecular assemblies. PMID:28043122

  6. Coarse Grained Models Reveal Essential Contributions of Topological Constraints to the Conformational Free Energy of RNA Bulges

    PubMed Central

    2015-01-01

    Recent studies have shown that simple stereochemical constraints encoded at the RNA secondary structure level significantly restrict the orientation of RNA helices across two-way junctions and yield physically reasonable distributions of RNA 3D conformations. Here we develop a new coarse-grain model, TOPRNA, that is optimized for exploring detailed aspects of these topological constraints in complex RNA systems. Unlike prior models, TOPRNA effectively treats RNAs as collections of semirigid helices linked by freely rotatable single strands, allowing us to isolate the effects of secondary structure connectivity and sterics on 3D structure. Simulations of bulge junctions show that TOPRNA captures new aspects of topological constraints, including variations arising from deviations in local A-form structure, translational displacements of the helices, and stereochemical constraints imposed by bulge-linker nucleotides. Notably, these aspects of topological constraints define free energy landscapes that coincide with the distribution of bulge conformations in the PDB. Our simulations also quantitatively reproduce NMR RDC measurements made on HIV-1 TAR at low salt concentrations, although not for different TAR mutants or at high salt concentrations. Our results confirm that topological constraints are an important determinant of bulge conformation and dynamics and demonstrate the utility of TOPRNA for studying the topological constraints of complex RNAs. PMID:24547945

  7. 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.

  8. Folding 19 proteins to their native state and stability of large proteins from a coarse-grained model.

    PubMed

    Kapoor, Abhijeet; Travesset, Alex

    2014-03-01

    We develop an intermediate resolution model, where the backbone is modeled with atomic resolution but the side chain with a single bead, by extending our previous model (Proteins (2013) DOI: 10.1002/prot.24269) to properly include proline, preproline residues and backbone rigidity. Starting from random configurations, the model properly folds 19 proteins (including a mutant 2A3D sequence) into native states containing β sheet, α helix, and mixed α/β. As a further test, the stability of H-RAS (a 169 residue protein, critical in many signaling pathways) is investigated: The protein is stable, with excellent agreement with experimental B-factors. Despite that proteins containing only α helices fold to their native state at lower backbone rigidity, and other limitations, which we discuss thoroughly, the model provides a reliable description of the dynamics as compared with all atom simulations, but does not constrain secondary structures as it is typically the case in more coarse-grained models. Further implications are described. Copyright © 2013 Wiley Periodicals, Inc.

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

    NASA Astrophysics Data System (ADS)

    Knott, Michael; Best, Robert B.

    2014-05-01

    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.

  10. 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.

  11. 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

  12. Brownian Dynamics Simulation of Nucleocytoplasmic Transport: A Coarse-Grained Model for the Functional State of the Nuclear Pore Complex

    PubMed Central

    Moussavi-Baygi, Ruhollah; Jamali, Yousef; Karimi, Reza; Mofrad, Mohammad R. K.

    2011-01-01

    The nuclear pore complex (NPC) regulates molecular traffic across the nuclear envelope (NE). Selective transport happens on the order of milliseconds and the length scale of tens of nanometers; however, the transport mechanism remains elusive. Central to the transport process is the hydrophobic interactions between karyopherins (kaps) and Phe-Gly (FG) repeat domains. Taking into account the polymeric nature of FG-repeats grafted on the elastic structure of the NPC, and the kap-FG hydrophobic affinity, we have established a coarse-grained model of the NPC structure that mimics nucleocytoplasmic transport. To establish a foundation for future works, the methodology and biophysical rationale behind the model is explained in details. The model predicts that the first-passage time of a 15 nm cargo-complex is about 2.6±0.13 ms with an inverse Gaussian distribution for statistically adequate number of independent Brownian dynamics simulations. Moreover, the cargo-complex is primarily attached to the channel wall where it interacts with the FG-layer as it passes through the central channel. The kap-FG hydrophobic interaction is highly dynamic and fast, which ensures an efficient translocation through the NPC. Further, almost all eight hydrophobic binding spots on kap-β are occupied simultaneously during transport. Finally, as opposed to intact NPCs, cytoplasmic filaments-deficient NPCs show a high degree of permeability to inert cargos, implying the defining role of cytoplasmic filaments in the selectivity barrier. PMID:21673865

  13. As Simple As Possible, but Not Simpler: Exploring the Fidelity of Coarse-Grained Protein Models for Simulated Force Spectroscopy

    PubMed Central

    Rottler, Jörg; Plotkin, Steven S.

    2016-01-01

    Mechanical unfolding of a single domain of loop-truncated superoxide dismutase protein has been simulated via force spectroscopy techniques with both all-atom (AA) models and several coarse-grained models having different levels of resolution: A Gō model containing all heavy atoms in the protein (HA-Gō), the associative memory, water mediated, structure and energy model (AWSEM) which has 3 interaction sites per amino acid, and a Gō model containing only one interaction site per amino acid at the Cα position (Cα-Gō). To systematically compare results across models, the scales of time, energy, and force had to be suitably renormalized in each model. Surprisingly, the HA-Gō model gives the softest protein, exhibiting much smaller force peaks than all other models after the above renormalization. Clustering to render a structural taxonomy as the protein unfolds showed that the AA, HA-Gō, and Cα-Gō models exhibit a single pathway for early unfolding, which eventually bifurcates repeatedly to multiple branches only after the protein is about half-unfolded. The AWSEM model shows a single dominant unfolding pathway over the whole range of unfolding, in contrast to all other models. TM alignment, clustering analysis, and native contact maps show that the AWSEM pathway has however the most structural similarity to the AA model at high nativeness, but the least structural similarity to the AA model at low nativeness. In comparison to the AA model, the sequence of native contact breakage is best predicted by the HA-Gō model. All models consistently predict a similar unfolding mechanism for early force-induced unfolding events, but diverge in their predictions for late stage unfolding events when the protein is more significantly disordered. PMID:27898663

  14. Structural variation of alpha-synuclein with temperature by a coarse-grained approach with knowledge-based interactions

    NASA Astrophysics Data System (ADS)

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

    2015-09-01

    Despite enormous efforts, our understanding the structure and dynamics of α-synuclein (ASN), a disordered protein (that plays a key role in neurodegenerative disease) is far from complete. In order to better understand sequence-structure-property relationships in α-SYNUCLEIN we have developed a coarse-grained model using knowledge-based residue-residue interactions and used it to study the structure of free ASN as a function of temperature (T) with a large-scale Monte Carlo simulation. Snapshots of the simulation and contour contact maps show changes in structure formation due to self-assembly as a function of temperature. Variations in the residue mobility profiles reveal clear distinction among three segments along the protein sequence. The N-terminal (1-60) and C-terminal (96-140) regions contain the least mobile residues, which are separated by the higher mobility non-amyloid component (NAC) (61-95). Our analysis of the intra-protein contact profile shows a higher frequency of residue aggregation (clumping) in the N-terminal region relative to that in the C-terminal region, with little or no aggregation in the NAC region. The radius of gyration (Rg) of ASN decays monotonically with decreasing the temperature, consistent with the finding of Allison et al. (JACS, 2009). Our analysis of the structure function provides an insight into the mass (N) distribution of ASN, and the dimensionality (D) of the structure as a function of temperature. We find that the globular structure with D ≈ 3 at low T, a random coil, D ≈ 2 at high T and in between (2 ≤ D ≤ 3) at the intermediate temperatures. The magnitudes of D are in agreement with experimental estimates (J. Biological Chem 2002).

  15. A coarse-grained computational model of the nuclear pore complex predicts Phe-Gly nucleoporin dynamics

    DOE PAGES

    Pulupa, Joan; Rachh, Manas; Tomasini, Michael D.; ...

    2017-09-08

    The phenylalanine-glycine–repeat nucleoporins (FG-Nups), which occupy the lumen of the nuclear pore complex (NPC), are critical for transport between the nucleus and cytosol. Although NPCs differ in composition across species, they are largely conserved in organization and function. Transport through the pore is on the millisecond timescale. Here, to explore the dynamics of nucleoporins on this timescale, we use coarse-grained computational simulations. These simulations generate predictions that can be experimentally tested to distinguish between proposed mechanisms of transport. Our model reflects the conserved structure of the NPC, in which FG-Nup filaments extend into the lumen and anchor along the interiormore » of the channel. The lengths of the filaments in our model are based on the known characteristics of yeast FG-Nups. The FG-repeat sites also bind to each other, and we vary this association over several orders of magnitude and run 100-ms simulations for each value. The autocorrelation functions of the orientation of the simulated FG-Nups are compared with in vivo anisotropy data. We observe that FG-Nups reptate back and forth through the NPC at timescales commensurate with experimental measurements of the speed of cargo transport through the NPC. Our results are consistent with models of transport where FG-Nup filaments are free to move across the central channel of the NPC, possibly informing how cargo might transverse the NPC.« less

  16. Predicting the morphology of sickle red blood cells using coarse-grained models of intracellular aligned hemoglobin polymers.

    PubMed

    Lei, Huan; Karniadakis, George Em

    2012-04-28

    Sickle red blood cells (SS-RBCs) exhibit heterogeneous cell morphologies (sickle, holly leaf, granular, etc.) in the deoxygenated state due to the polymerization of the sickle hemoglobin. Experimental evidence points to a close relationship between SS-RBC morphology and intracellular aligned hemoglobin polymers. Here, we develop a coarse-grained (CG) stochastic model to represent the growth of the intracellular aligned hemoglobin polymer domain. The CG model is calibrated based on the mechanical properties (Young's modulus, bending rigidity) of the sickle hemoglobin fibers reported in experiments. The process of the cell membrane transition is simulated for physiologic aligned hemoglobin polymer configurations and mean corpuscular hemoglobin concentration. Typical SS-RBC morphologies observed in experiments can be obtained from the current model as a result of the intracellular aligned hemoglobin polymer development without introducing any further ad hoc assumptions. It is found that the final shape of SS-RBCs is primarily determined by the angular width of the aligned hemoglobin polymer domain, but it also depends, to a lesser degree, on the polymer growth rate and the cell membrane rigidity. Cell morphologies are quantified by structural shape factors, which agree well with experimental results from medical images.

  17. Predicting the morphology of sickle red blood cells using coarse-grained models of intracellular aligned hemoglobin polymers†

    PubMed Central

    Lei, Huan; Karniadakis, George Em

    2013-01-01

    Sickle red blood cells (SS-RBCs) exhibit heterogeneous cell morphologies (sickle, holly leaf, granular, etc.) in the deoxygenated state due to the polymerization of the sickle hemoglobin. Experimental evidence points to a close relationship between SS-RBC morphology and intracellular aligned hemoglobin polymers. Here, we develop a coarse-grained (CG) stochastic model to represent the growth of the intracellular aligned hemoglobin polymer domain. The CG model is calibrated based on the mechanical properties (Young’s modulus, bending rigidity) of the sickle hemoglobin fibers reported in experiments. The process of the cell membrane transition is simulated for physiologic aligned hemoglobin polymer configurations and mean corpuscular hemoglobin concentration. Typical SS-RBC morphologies observed in experiments can be obtained from the current model as a result of the intracellular aligned hemoglobin polymer development without introducing any further ad hoc assumptions. It is found that the final shape of SS-RBCs is primarily determined by the angular width of the aligned hemoglobin polymer domain, but it also depends, to a lesser degree, on the polymer growth rate and the cell membrane rigidity. Cell morphologies are quantified by structural shape factors, which agree well with experimental results from medical images. PMID:24307912

  18. A coarse-grained computational model of the nuclear pore complex predicts Phe-Gly nucleoporin dynamics.

    PubMed

    Pulupa, Joan; Rachh, Manas; Tomasini, Michael D; Mincer, Joshua S; Simon, Sanford M

    2017-10-02

    The phenylalanine-glycine-repeat nucleoporins (FG-Nups), which occupy the lumen of the nuclear pore complex (NPC), are critical for transport between the nucleus and cytosol. Although NPCs differ in composition across species, they are largely conserved in organization and function. Transport through the pore is on the millisecond timescale. Here, to explore the dynamics of nucleoporins on this timescale, we use coarse-grained computational simulations. These simulations generate predictions that can be experimentally tested to distinguish between proposed mechanisms of transport. Our model reflects the conserved structure of the NPC, in which FG-Nup filaments extend into the lumen and anchor along the interior of the channel. The lengths of the filaments in our model are based on the known characteristics of yeast FG-Nups. The FG-repeat sites also bind to each other, and we vary this association over several orders of magnitude and run 100-ms simulations for each value. The autocorrelation functions of the orientation of the simulated FG-Nups are compared with in vivo anisotropy data. We observe that FG-Nups reptate back and forth through the NPC at timescales commensurate with experimental measurements of the speed of cargo transport through the NPC. Our results are consistent with models of transport where FG-Nup filaments are free to move across the central channel of the NPC, possibly informing how cargo might transverse the NPC. © 2017 Pulupa et al.

  19. Markov state modeling and dynamical coarse-graining via discrete relaxation path sampling

    NASA Astrophysics Data System (ADS)

    Fačkovec, B.; Vanden-Eijnden, E.; Wales, D. J.

    2015-07-01

    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.

  20. 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

  1. Sliding of proteins non-specifically bound to DNA: Brownian dynamics studies with coarse-grained protein and DNA models.

    PubMed

    Ando, Tadashi; Skolnick, Jeffrey

    2014-12-01

    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.

  2. 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

  3. A hybrid all-atom/coarse grain model for multiscale simulations of DNA.

    PubMed

    Machado, Matías Rodrigo; Dans, Pablo Daniel; Pantano, Sergio

    2011-10-28

    Hybrid simulations of molecular systems, which combine all-atom (AA) with simplified (or coarse grain, CG) representations, propose an advantageous alternative to gain atomistic details on relevant regions while getting profit from the speedup of treating a bigger part of the system at the CG level. Here we present a reduced set of parameters derived to treat a hybrid interface in DNA simulations. Our method allows us to forthrightly link a state-of-the-art force field for AA simulations of DNA with a CG representation developed by our group. We show that no modification is needed for any of the existing residues (neither AA nor CG). Only the bonding parameters at the hybrid interface are enough to produce a smooth transition of electrostatic, mechanic and dynamic features in different AA/CG systems, which are studied by molecular dynamics simulations using an implicit solvent. The simplicity of the approach potentially permits us to study the effect of mutations/modifications as well as DNA binding molecules at the atomistic level within a significantly larger DNA scaffold considered at the CG level. Since all the interactions are computed within the same classical Hamiltonian, the extension to a quantum/classical/coarse-grain multilayer approach using QM/MM modules implemented in widely used simulation packages is straightforward.

  4. Spectral coarse grained controllability of complex networks

    NASA Astrophysics Data System (ADS)

    Wang, Pei; Xu, Shuang

    2017-07-01

    With the accumulation of interaction data from various systems, a fundamental question in network science is how to reduce the sizes while keeping certain properties of complex networks. Combined the spectral coarse graining theory and the structural controllability of complex networks, we explore the structural controllability of undirected complex networks during coarse graining processes. We evidence that the spectral coarse grained controllability (SCGC) properties for the Erdös-Rényi (ER) random networks, the scale-free (SF) random networks and the small-world (SW) random networks are distinct from each other. The SW networks are very robust, while the SF networks are sensitive during the coarse graining processes. As an emergent properties for the dense ER networks, during the coarse graining processes, there exists a threshold value of the coarse grained sizes, which separates the controllability of the reduced networks into robust and sensitive to coarse graining. Investigations on some real-world complex networks indicate that the SCGC properties are varied among different categories and different kinds of networks, some highly organized social or biological networks are more difficult to be controlled, while many man-made power networks and infrastructure networks can keep the controllability properties during the coarse graining processes. Furthermore, we speculate that the SCGC properties of complex networks may depend on their degree distributions. The associated investigations have potential implications in the control of large-scale complex networks, as well as in the understanding of the organization of complex networks.

  5. Reconciling structural and thermodynamic predictions using all-atom and coarse-grain force fields: the case of charged oligo-arginine translocation into DMPC bilayers.

    PubMed

    Hu, Yuan; Sinha, Sudipta Kumar; Patel, Sandeep

    2014-10-16

    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 the ensemble of

  6. 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

  7. 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.

  8. Dynamic force matching: Construction of dynamic coarse-grained models with realistic short time dynamics and accurate long time dynamics

    NASA Astrophysics Data System (ADS)

    Davtyan, Aram; Voth, Gregory A.; Andersen, Hans C.

    2016-12-01

    We recently developed a dynamic force matching technique for converting a coarse-grained (CG) model of a molecular system, with a CG potential energy function, into a dynamic CG model with realistic dynamics [A. Davtyan et al., J. Chem. Phys. 142, 154104 (2015)]. This is done by supplementing the model with additional degrees of freedom, called "fictitious particles." In that paper, we tested the method on CG models in which each molecule is coarse-grained into one CG point particle, with very satisfactory results. When the method was applied to a CG model of methanol that has two CG point particles per molecule, the results were encouraging but clearly required improvement. In this paper, we introduce a new type (called type-3) of fictitious particle that exerts forces on the center of mass of two CG sites. A CG model constructed using type-3 fictitious particles (as well as type-2 particles previously used) gives a much more satisfactory dynamic model for liquid methanol. In particular, we were able to construct a CG model that has the same self-diffusion coefficient and the same rotational relaxation time as an all-atom model of liquid methanol. Type-3 particles and generalizations of it are likely to be useful in converting more complicated CG models into dynamic CG models.

  9. Paramaterization of a coarse-grained model for linear alkylbenzene sulfonate surfactants and molecular dynamics studies of their self-assembly in aqueous solution

    NASA Astrophysics Data System (ADS)

    He, Xibing; Shinoda, Wataru; DeVane, Russell; Anderson, Kelly L.; Klein, Michael L.

    2010-02-01

    A coarse-grained (CG) forcefield for linear alkylbenzene sulfonates (LAS) was systematically parameterized. Thermodynamic data from experiments and structural data obtained from all-atom molecular dynamics were used as targets to parameterize CG potentials for the bonded and non-bonded interactions. The added computational efficiency permits one to employ computer simulation to probe the self-assembly of LAS aqueous solutions into different morphologies starting from a random configuration. The present CG model is shown to accurately reproduce the phase behavior of solutions of pure isomers of sodium dodecylbenzene sulfonate, despite the fact that phase behavior was not directly taken into account in the forcefield parameterization.

  10. Multiscale Particle-Based Modeling of Flowing Platelets in Blood Plasma Using Dissipative Particle Dynamics and Coarse Grained Molecular Dynamics

    PubMed Central

    Zhang, Peng; Gao, Chao; Zhang, Na; Slepian, Marvin J.; Deng, Yuefan; Bluestein, Danny

    2014-01-01

    We developed a multiscale particle-based model of platelets, to study the transport dynamics of shear stresses between the surrounding fluid and the platelet membrane. This model facilitates a more accurate prediction of the activation potential of platelets by viscous shear stresses - one of the major mechanisms leading to thrombus formation in cardiovascular diseases and in prosthetic cardiovascular devices. The interface of the model couples coarse-grained molecular dynamics (CGMD) with dissipative particle dynamics (DPD). The CGMD handles individual platelets while the DPD models the macroscopic transport of blood plasma in vessels. A hybrid force field is formulated for establishing a functional interface between the platelet membrane and the surrounding fluid, in which the microstructural changes of platelets may respond to the extracellular viscous shear stresses transferred to them. The interaction between the two systems preserves dynamic properties of the flowing platelets, such as the flipping motion. Using this multiscale particle-based approach, we have further studied the effects of the platelet elastic modulus by comparing the action of the flow-induced shear stresses on rigid and deformable platelet models. The results indicate that neglecting the platelet deformability may overestimate the stress on the platelet membrane, which in turn may lead to erroneous predictions of the platelet activation under viscous shear flow conditions. This particle-based fluid-structure interaction multiscale model offers for the first time a computationally feasible approach for simulating deformable platelets interacting with viscous blood flow, aimed at predicting flow induced platelet activation by using a highly resolved mapping of the stress distribution on the platelet membrane under dynamic flow conditions. PMID:25530818

  11. Multiscale Particle-Based Modeling of Flowing Platelets in Blood Plasma Using Dissipative Particle Dynamics and Coarse Grained Molecular Dynamics.

    PubMed

    Zhang, Peng; Gao, Chao; Zhang, Na; Slepian, Marvin J; Deng, Yuefan; Bluestein, Danny

    2014-12-01

    We developed a multiscale particle-based model of platelets, to study the transport dynamics of shear stresses between the surrounding fluid and the platelet membrane. This model facilitates a more accurate prediction of the activation potential of platelets by viscous shear stresses - one of the major mechanisms leading to thrombus formation in cardiovascular diseases and in prosthetic cardiovascular devices. The interface of the model couples coarse-grained molecular dynamics (CGMD) with dissipative particle dynamics (DPD). The CGMD handles individual platelets while the DPD models the macroscopic transport of blood plasma in vessels. A hybrid force field is formulated for establishing a functional interface between the platelet membrane and the surrounding fluid, in which the microstructural changes of platelets may respond to the extracellular viscous shear stresses transferred to them. The interaction between the two systems preserves dynamic properties of the flowing platelets, such as the flipping motion. Using this multiscale particle-based approach, we have further studied the effects of the platelet elastic modulus by comparing the action of the flow-induced shear stresses on rigid and deformable platelet models. The results indicate that neglecting the platelet deformability may overestimate the stress on the platelet membrane, which in turn may lead to erroneous predictions of the platelet activation under viscous shear flow conditions. This particle-based fluid-structure interaction multiscale model offers for the first time a computationally feasible approach for simulating deformable platelets interacting with viscous blood flow, aimed at predicting flow induced platelet activation by using a highly resolved mapping of the stress distribution on the platelet membrane under dynamic flow conditions.

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

    NASA Astrophysics Data System (ADS)

    Pandey, Ras; Farmer, Barry

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

  13. On the application of the MARTINI coarse-grained model to immersion of a protein in a phospholipid bilayer

    NASA Astrophysics Data System (ADS)

    Mustafa, Ghulam; Nandekar, Prajwal P.; Yu, Xiaofeng; Wade, Rebecca C.

    2015-12-01

    An important step in the simulation of a membrane protein in a phospholipid bilayer is the correct immersion of the protein in the bilayer. Crystal structures are determined without the bilayer. Particularly for proteins with monotopic domains, it can be unclear how deeply and in which orientation the protein is being inserted in the membrane. We have previously developed a procedure combining coarse-grain (CG) with all-atom (AA) molecular dynamics (MD) simulations to insert and simulate a cytochrome P450 (CYP) possessing an N-terminal transmembrane helix connected by a flexible linker region to a globular domain that dips into the membrane. The CG simulations provide a computationally efficient means to explore different orientations and conformations of the CYP in the membrane. Converged configurations obtained in the CG simulations are then refined in AA simulations. Here, we tested different variants of the MARTINI CG model, differing in the water model, the treatment of long-range non-bonded interactions, and the implementation (GROMACS 4.5.5 vs 5.0.4), for this purpose. We examined the behavior of the models for simulating a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer in water and for the immersion of CYP3A4 in a POPC bilayer, and compared the CG-MD results with the previously reported experimental and simulation results. We also tested the methodology on a set of four other CYPs. Finally, we propose an optimized protocol for modeling such protein-membrane systems that provides the most plausible configurations and is computationally efficient; this incorporates the standard non-polar water model and the GROMACS 5.0.4 implementation with a reaction field treatment of long-range interactions.

  14. On the application of the MARTINI coarse-grained model to immersion of a protein in a phospholipid bilayer.

    PubMed

    Mustafa, Ghulam; Nandekar, Prajwal P; Yu, Xiaofeng; Wade, Rebecca C

    2015-12-28

    An important step in the simulation of a membrane protein in a phospholipid bilayer is the correct immersion of the protein in the bilayer. Crystal structures are determined without the bilayer. Particularly for proteins with monotopic domains, it can be unclear how deeply and in which orientation the protein is being inserted in the membrane. We have previously developed a procedure combining coarse-grain (CG) with all-atom (AA) molecular dynamics (MD) simulations to insert and simulate a cytochrome P450 (CYP) possessing an N-terminal transmembrane helix connected by a flexible linker region to a globular domain that dips into the membrane. The CG simulations provide a computationally efficient means to explore different orientations and conformations of the CYP in the membrane. Converged configurations obtained in the CG simulations are then refined in AA simulations. Here, we tested different variants of the MARTINI CG model, differing in the water model, the treatment of long-range non-bonded interactions, and the implementation (GROMACS 4.5.5 vs 5.0.4), for this purpose. We examined the behavior of the models for simulating a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer in water and for the immersion of CYP3A4 in a POPC bilayer, and compared the CG-MD results with the previously reported experimental and simulation results. We also tested the methodology on a set of four other CYPs. Finally, we propose an optimized protocol for modeling such protein-membrane systems that provides the most plausible configurations and is computationally efficient; this incorporates the standard non-polar water model and the GROMACS 5.0.4 implementation with a reaction field treatment of long-range interactions.

  15. On the application of the MARTINI coarse-grained model to immersion of a protein in a phospholipid bilayer

    SciTech Connect

    Mustafa, Ghulam E-mail: rebecca.wade@h-its.org; Nandekar, Prajwal P.; Yu, Xiaofeng; Wade, Rebecca C. E-mail: rebecca.wade@h-its.org

    2015-12-28

    An important step in the simulation of a membrane protein in a phospholipid bilayer is the correct immersion of the protein in the bilayer. Crystal structures are determined without the bilayer. Particularly for proteins with monotopic domains, it can be unclear how deeply and in which orientation the protein is being inserted in the membrane. We have previously developed a procedure combining coarse-grain (CG) with all-atom (AA) molecular dynamics (MD) simulations to insert and simulate a cytochrome P450 (CYP) possessing an N-terminal transmembrane helix connected by a flexible linker region to a globular domain that dips into the membrane. The CG simulations provide a computationally efficient means to explore different orientations and conformations of the CYP in the membrane. Converged configurations obtained in the CG simulations are then refined in AA simulations. Here, we tested different variants of the MARTINI CG model, differing in the water model, the treatment of long-range non-bonded interactions, and the implementation (GROMACS 4.5.5 vs 5.0.4), for this purpose. We examined the behavior of the models for simulating a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer in water and for the immersion of CYP3A4 in a POPC bilayer, and compared the CG-MD results with the previously reported experimental and simulation results. We also tested the methodology on a set of four other CYPs. Finally, we propose an optimized protocol for modeling such protein-membrane systems that provides the most plausible configurations and is computationally efficient; this incorporates the standard non-polar water model and the GROMACS 5.0.4 implementation with a reaction field treatment of long-range interactions.

  16. On using a too large integration time step in molecular dynamics simulations of coarse-grained molecular models.

    PubMed

    Winger, Moritz; Trzesniak, Daniel; Baron, Riccardo; van Gunsteren, Wilfred F

    2009-03-28

    The use of a coarse-grained (CG) model that is widely used in molecular dynamics simulations of biomolecular systems is investigated with respect to the dependence of a variety of quantities upon the size of the used integration time step and cutoff radius. The results suggest that when using a non-bonded interaction-cutoff radius of 1.4 nm a time step of maximally 10 fs should be used, in order not to produce energy sinks or wells. Using a too-large time step, e.g. 50 fs with a cutoff of 1.2 nm, as is done in the coarse-grained model of Marrink et al. (J. Phys. Chem. B, 2004, 108, 250 and 2007, 111, 7812), induces errors due to the linear approximation of the integrators that are commonly used to integrate the equations of motion. As a spin-off of the investigation of the mentioned CG models, we found that the parameters of the CG water model place it at physiological temperatures well into the solid phase of the phase diagram.

  17. Non-Markovian coarse-grained modeling of polymeric fluids based on the Mori-Zwanzig formalism

    NASA Astrophysics Data System (ADS)

    Li, Zhen; Bian, Xin; Li, Xiantao; Karniadakis, George

    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 based on the Mori-Zwanzig formalism. 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 on both static and dynamic properties between the CG models with Markovian and non-Markovian approximations will be presented. Supported by the DOE Center on Mathematics for Mesoscopic Modeling of Materials (CM4) and an INCITE grant.

  18. Coarse-grained protein molecular dynamics simulations.

    PubMed

    Derreumaux, Philippe; Mousseau, Normand

    2007-01-14

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

  19. Coarse-grained protein molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Derreumaux, Philippe; Mousseau, Normand

    2007-01-01

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

  20. Shock simulations of a single-site coarse-grain RDX model using the dissipative particle dynamics method with reactivity

    NASA Astrophysics Data System (ADS)

    Sellers, Michael S.; Lísal, Martin; Schweigert, Igor; Larentzos, James P.; Brennan, John K.

    2017-01-01

    In discrete particle simulations, when an atomistic model is coarse-grained, a tradeoff is made: a boost in computational speed for a reduction in accuracy. The Dissipative Particle Dynamics (DPD) methods help to recover lost accuracy of the viscous and thermal properties, while giving back a relatively small amount of computational speed. Since its initial development for polymers, one of the most notable extensions of DPD has been the introduction of chemical reactivity, called DPD-RX. In 2007, Maillet, Soulard, and Stoltz introduced implicit chemical reactivity in DPD through the concept of particle reactors and simulated the decomposition of liquid nitromethane. We present an extended and generalized version of the DPD-RX method, and have applied it to solid hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). Demonstration simulations of reacting RDX are performed under shock conditions using a recently developed single-site coarse-grain model and a reduced RDX decomposition mechanism. A description of the methods used to simulate RDX and its transition to hot product gases within DPD-RX is presented. Additionally, we discuss several examples of the effect of shock speed and microstructure on the corresponding material chemistry.

  1. A coarse-grained biophysical model of sequence evolution and the population size dependence of the speciation rate

    PubMed Central

    Khatri, Bhavin S.; Goldstein, Richard A.

    2015-01-01

    Speciation is fundamental to understanding the huge diversity of life on Earth. Although still controversial, empirical evidence suggests that the rate of speciation is larger for smaller populations. Here, we explore a biophysical model of speciation by developing a simple coarse-grained theory of transcription factor-DNA binding and how their co-evolution in two geographically isolated lineages leads to incompatibilities. To develop a tractable analytical theory, we derive a Smoluchowski equation for the dynamics of binding energy evolution that accounts for the fact that natural selection acts on phenotypes, but variation arises from mutations in sequences; the Smoluchowski equation includes selection due to both gradients in fitness and gradients in sequence entropy, which is the logarithm of the number of sequences that correspond to a particular binding energy. This simple consideration predicts that smaller populations develop incompatibilities more quickly in the weak mutation regime; this trend arises as sequence entropy poises smaller populations closer to incompatible regions of phenotype space. These results suggest a generic coarse-grained approach to evolutionary stochastic dynamics, allowing realistic modelling at the phenotypic level. PMID:25936759

  2. A coarse-grained biophysical model of sequence evolution and the population size dependence of the speciation rate.

    PubMed

    Khatri, Bhavin S; Goldstein, Richard A

    2015-08-07

    Speciation is fundamental to understanding the huge diversity of life on Earth. Although still controversial, empirical evidence suggests that the rate of speciation is larger for smaller populations. Here, we explore a biophysical model of speciation by developing a simple coarse-grained theory of transcription factor-DNA binding and how their co-evolution in two geographically isolated lineages leads to incompatibilities. To develop a tractable analytical theory, we derive a Smoluchowski equation for the dynamics of binding energy evolution that accounts for the fact that natural selection acts on phenotypes, but variation arises from mutations in sequences; the Smoluchowski equation includes selection due to both gradients in fitness and gradients in sequence entropy, which is the logarithm of the number of sequences that correspond to a particular binding energy. This simple consideration predicts that smaller populations develop incompatibilities more quickly in the weak mutation regime; this trend arises as sequence entropy poises smaller populations closer to incompatible regions of phenotype space. These results suggest a generic coarse-grained approach to evolutionary stochastic dynamics, allowing realistic modelling at the phenotypic level. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. The Renormalization Group and Its Applications to Generating Coarse-Grained Models of Large Biological Molecular Systems.

    PubMed

    Koehl, Patrice; Poitevin, Frédéric; Navaza, Rafael; Delarue, Marc

    2017-03-14

    Understanding the dynamics of biomolecules is the key to understanding their biological activities. Computational methods ranging from all-atom molecular dynamics simulations to coarse-grained normal-mode analyses based on simplified elastic networks provide a general framework to studying these dynamics. Despite recent successes in studying very large systems with up to a 100,000,000 atoms, those methods are currently limited to studying small- to medium-sized molecular systems due to computational limitations. One solution to circumvent these limitations is to reduce the size of the system under study. In this paper, we argue that coarse-graining, the standard approach to such size reduction, must define a hierarchy of models of decreasing sizes that are consistent with each other, i.e., that each model contains the information of the dynamics of its predecessor. We propose a new method, Decimate, for generating such a hierarchy within the context of elastic networks for normal-mode analysis. This method is based on the concept of the renormalization group developed in statistical physics. We highlight the details of its implementation, with a special focus on its scalability to large systems of up to millions of atoms. We illustrate its application on two large systems, the capsid of a virus and the ribosome translation complex. We show that highly decimated representations of those systems, containing down to 1% of their original number of atoms, still capture qualitatively and quantitatively their dynamics. Decimate is available as an OpenSource resource.

  4. Coarse-grained component concurrency in Earth system modeling: parallelizing atmospheric radiative transfer in the GFDL AM3 model using the Flexible Modeling System coupling framework

    NASA Astrophysics Data System (ADS)

    Balaji, V.; Benson, Rusty; Wyman, Bruce; Held, Isaac

    2016-10-01

    Climate models represent a large variety of processes on a variety of timescales and space scales, a canonical example of multi-physics multi-scale modeling. Current hardware trends, such as Graphical Processing Units (GPUs) and Many Integrated Core (MIC) chips, are based on, at best, marginal increases in clock speed, coupled with vast increases in concurrency, particularly at the fine grain. Multi-physics codes face particular challenges in achieving fine-grained concurrency, as different physics and dynamics components have different computational profiles, and universal solutions are hard to come by. We propose here one approach for multi-physics codes. These codes are typically structured as components interacting via software frameworks. The component structure of a typical Earth system model consists of a hierarchical and recursive tree of components, each representing a different climate process or dynamical system. This recursive structure generally encompasses a modest level of concurrency at the highest level (e.g., atmosphere and ocean on different processor sets) with serial organization underneath. We propose to extend concurrency much further by running more and more lower- and higher-level components in parallel with each other. Each component can further be parallelized on the fine grain, potentially offering a major increase in the scalability of Earth system models. We present here first results from this approach, called coarse-grained component concurrency, or CCC. Within the Geophysical Fluid Dynamics Laboratory (GFDL) Flexible Modeling System (FMS), the atmospheric radiative transfer component has been configured to run in parallel with a composite component consisting of every other atmospheric component, including the atmospheric dynamics and all other atmospheric physics components. We will explore the algorithmic challenges involved in such an approach, and present results from such simulations. Plans to achieve even greater levels of

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

    PubMed

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

    2016-05-25

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

  6. Reorientation Dynamics of Chromophores in Photosensitive Polymers by Means of Coarse-Grained Modeling.

    PubMed

    Ilnytskyi, Jaroslav M; Saphiannikova, Marina

    2015-10-26

    We study the photoisomerization of azobenzene chromophores embedded into a polymer matrix by using coarse-grained simulations. Two types of beads are considered: t- and c-beads, which are rich in trans and cis isomers, respectively. Simulations combine deterministic (molecular dynamics) and stochastic (random-type switching) parts. The ratio between the characteristic times for photoinduced reorientation and for orientation relaxation is tuned to be of the order found in experiments. The essential features of the phenomenon: 1) the existence of a stationary state, and 2) anisotropic distribution of the orientations of t-beads (orientation hole-burning effect), are reproduced. We study population dynamics of c-beads and the strength of the orientation hole burning, depending on the illumination wavelength and its intensity. The form of the reorientation potential of the mean force acting on the t-beads is analyzed and its use is validated. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Approach to the unfolding and folding dynamics of add A-riboswitch upon adenine dissociation using a coarse-grained elastic network model

    PubMed Central

    Li, Chunhua; Lv, Dashuai; Zhang, Lei; Yang, Feng; Wang, Cunxin; Su, Jiguo; Zhang, Yang

    2016-01-01

    Riboswitches are noncoding mRNA segments that can regulate the gene expression via altering their structures in response to specific metabolite binding. We proposed a coarse-grained Gaussian network model (GNM) to examine the unfolding and folding dynamics of adenosine deaminase (add) A-riboswitch upon the adenine dissociation, in which the RNA is modeled by a nucleotide chain with interaction networks formed by connecting adjoining atomic contacts. It was shown that the adenine binding is critical to the folding of the add A-riboswitch while the removal of the ligand can result in drastic increase of the thermodynamic fluctuations especially in the junction regions between helix domains. Under the assumption that the native contacts with the highest thermodynamic fluctuations break first, the iterative GNM simulations showed that the unfolding process of the adenine-free add A-riboswitch starts with the denature of the terminal helix stem, followed by the loops and junctions involving ligand binding pocket, and then the central helix domains. Despite the simplified coarse-grained modeling, the unfolding dynamics and pathways are shown in close agreement with the results from atomic-level MD simulations and the NMR and single-molecule force spectroscopy experiments. Overall, the study demonstrates a new avenue to investigate the binding and folding dynamics of add A-riboswitch molecule which can be readily extended for other RNA molecules. PMID:27394096

  8. Approach to the unfolding and folding dynamics of add A-riboswitch upon adenine dissociation using a coarse-grained elastic network model.

    PubMed

    Li, Chunhua; Lv, Dashuai; Zhang, Lei; Yang, Feng; Wang, Cunxin; Su, Jiguo; Zhang, Yang

    2016-07-07

    Riboswitches are noncoding mRNA segments that can regulate the gene expression via altering their structures in response to specific metabolite binding. We proposed a coarse-grained Gaussian network model (GNM) to examine the unfolding and folding dynamics of adenosine deaminase (add) A-riboswitch upon the adenine dissociation, in which the RNA is modeled by a nucleotide chain with interaction networks formed by connecting adjoining atomic contacts. It was shown that the adenine binding is critical to the folding of the add A-riboswitch while the removal of the ligand can result in drastic increase of the thermodynamic fluctuations especially in the junction regions between helix domains. Under the assumption that the native contacts with the highest thermodynamic fluctuations break first, the iterative GNM simulations showed that the unfolding process of the adenine-free add A-riboswitch starts with the denature of the terminal helix stem, followed by the loops and junctions involving ligand binding pocket, and then the central helix domains. Despite the simplified coarse-grained modeling, the unfolding dynamics and pathways are shown in close agreement with the results from atomic-level MD simulations and the NMR and single-molecule force spectroscopy experiments. Overall, the study demonstrates a new avenue to investigate the binding and folding dynamics of add A-riboswitch molecule which can be readily extended for other RNA molecules.

  9. Approach to the unfolding and folding dynamics of add A-riboswitch upon adenine dissociation using a coarse-grained elastic network model

    NASA Astrophysics Data System (ADS)

    Li, Chunhua; Lv, Dashuai; Zhang, Lei; Yang, Feng; Wang, Cunxin; Su, Jiguo; Zhang, Yang

    2016-07-01

    Riboswitches are noncoding mRNA segments that can regulate the gene expression via altering their structures in response to specific metabolite binding. We proposed a coarse-grained Gaussian network model (GNM) to examine the unfolding and folding dynamics of adenosine deaminase (add) A-riboswitch upon the adenine dissociation, in which the RNA is modeled by a nucleotide chain with interaction networks formed by connecting adjoining atomic contacts. It was shown that the adenine binding is critical to the folding of the add A-riboswitch while the removal of the ligand can result in drastic increase of the thermodynamic fluctuations especially in the junction regions between helix domains. Under the assumption that the native contacts with the highest thermodynamic fluctuations break first, the iterative GNM simulations showed that the unfolding process of the adenine-free add A-riboswitch starts with the denature of the terminal helix stem, followed by the loops and junctions involving ligand binding pocket, and then the central helix domains. Despite the simplified coarse-grained modeling, the unfolding dynamics and pathways are shown in close agreement with the results from atomic-level MD simulations and the NMR and single-molecule force spectroscopy experiments. Overall, the study demonstrates a new avenue to investigate the binding and folding dynamics of add A-riboswitch molecule which can be readily extended for other RNA molecules.

  10. One-particle-thick, solvent-free, coarse-grained model for biological and biomimetic fluid membranes.

    PubMed

    Yuan, Hongyan; Huang, Changjin; Li, Ju; Lykotrafitis, George; Zhang, Sulin

    2010-07-01

    Biological membranes are involved in numerous intriguing biophysical and biological cellular phenomena of different length scales, ranging from nanoscale raft formation, vesiculation, to microscale shape transformations. With extended length and time scales as compared to atomistic simulations, solvent-free coarse-grained membrane models have been exploited in mesoscopic membrane simulations. In this study, we present a one-particle-thick fluid membrane model, where each particle represents a cluster of lipid molecules. The model features an anisotropic interparticle pair potential with the interaction strength weighed by the relative particle orientations. With the anisotropic pair potential, particles can robustly self-assemble into fluid membranes with experimentally relevant bending rigidity. Despite its simple mathematical form, the model is highly tunable. Three potential parameters separately and effectively control diffusivity, bending rigidity, and spontaneous curvature of the model membrane. As demonstrated by selected examples, our model can naturally simulate dynamics of phase separation in multicomponent membranes and the topological change of fluid vesicles.

  11. Surfactant chain length and concentration influence on the interfacial tension of two immiscible model liquids: a coarse-grained approach.

    PubMed

    Catarino Centeno, R; Bustamante-Rendón, R A; Hernández-Fragoso, J S; Arroyo-Ordoñez, I; Pérez, E; Alas, S J; Gama Goicochea, A

    2017-10-06

    The interfacial tension between immiscible liquids is studied as a function of a model linear surfactant length and concentration using coarse-grained, dissipative particle dynamics numerical simulations. The adsorption isotherms obtained from the simulations are found to be in agreement with Langmuir's model. The reduction of the interfacial tension with increasing surfactant concentration is found to display some common characteristics for all the values of chain length modeled, with our predictions being in agreement with Szyszkowski's equation. Lastly, the critical micelle concentration is predicted for all surfactant lengths, finding exponentially decaying behavior, in agreement with Kleven's model. It is argued that these findings can be helpful guiding tools in the interpretation of available experiments and in the design of new ones with new surfactants and polymers.

  12. Molecular Renormalization Group Coarse-Graining of Polymer Chains: Application to Double-Stranded DNA

    PubMed Central

    Savelyev, Alexey; Papoian, Garegin A.

    2009-01-01

    Coarse-graining of atomistic force fields allows us to investigate complex biological problems, occurring at long timescales and large length scales. In this work, we have developed an accurate coarse-grained model for double-stranded DNA chain, derived systematically from atomistic simulations. Our approach is based on matching correlators obtained from atomistic and coarse-grained simulations, for observables that explicitly enter the coarse-grained Hamiltonian. We show that this requirement leads to equivalency of the corresponding partition functions, resulting in a one-step renormalization. Compared to prior works exploiting similar ideas, the main novelty of this work is the introduction of a highly compact set of Hamiltonian basis functions, based on molecular interaction potentials. We demonstrate that such compactification allows us to reproduce many-body effects, generated by one-step renormalization, at low computational cost. In addition, compact Hamiltonians greatly increase the likelihood of finding unique solutions for the coarse-grained force-field parameter values. By successfully applying our molecular renormalization group coarse-graining technique to double-stranded DNA, we solved, for the first time, a long-standing problem in coarse-graining polymer systems, namely, how to accurately capture the correlations among various polymeric degrees of freedom. Excellent agreement is found among atomistic and coarse-grained distribution functions for various structural observables, including those not included in the Hamiltonian. We also suggest higher-order generalization of this method, which may allow capturing more subtle correlations in biopolymer dynamics. PMID:19450476

  13. Estimation of Liposome Penetration Barriers of Drug Molecules with All-Atom and Coarse-Grained Models.

    PubMed

    Genheden, Samuel; Eriksson, Leif A

    2016-09-13

    Liposomes are common carriers of drug molecules, providing enhanced delivery and accumulation of hydrophilic agents or larger biomolecules. Molecular simulations can be used to estimate key features of the drug molecules upon interaction with the liposomes, such as penetration barriers and localization. Herein, we investigate several aspects of the computational estimation of penetration barriers, viz. the potential of mean force (PMFs) along a vector spanning the membrane. First, we provide an evaluation of the all-atom (AA) and coarse-grained (CG) parametrization of 5-aminolevulinic acid (5-ALA) and two of its alkyl esters by computing n-octanol/water partition coefficients. We find that the CG parametrization of the esters performs significantly better than the CG model of 5-ALA, highlighting the difficulty to coarse-grain small, polar molecules. However, the expected trend in partition coefficients is reproduced also with the CG models. Second, we compare PMFs in a small membrane slab described with either the AA or CG models. Here, we are able to reproduce the all-atom PMF of 5-ALA with CG. However, for the alkyl esters it is unfortunately not possible to correctly reproduce both the depth and the penetration barrier of the PMF seen in the AA simulations with any of the tested CG models. We argue that it is more important to choose a CG parametrization that reproduces the depth of the PMF. Third, we compare, using the CG model, PMFs in the membrane slab with PMFs in a large, realistic liposome. We find similar depths but slightly different penetration barriers most likely due to differences in the lipid density along the membrane axis. Finally, we compute PMFs in liposomes with three different lipid compositions. Unfortunately, differences in the PMFs could not be quantified, and it remains to be investigated to what extent liposome simulations can fully reproduce experimental findings.

  14. A stochastic thermostat algorithm for coarse-grained thermomechanical modeling of large-scale soft matters: Theory and application to microfilaments

    SciTech Connect

    Li, Tong; Gu, YuanTong

    2014-04-15

    As all-atom molecular dynamics method is limited by its enormous computational cost, various coarse-grained strategies have been developed to extend the length scale of soft matters in the modeling of mechanical behaviors. However, the classical thermostat algorithm in highly coarse-grained molecular dynamics method would underestimate the thermodynamic behaviors of soft matters (e.g. microfilaments in cells), which can weaken the ability of materials to overcome local energy traps in granular modeling. Based on all-atom molecular dynamics modeling of microfilament fragments (G-actin clusters), a new stochastic thermostat algorithm is developed to retain the representation of thermodynamic properties of microfilaments at extra coarse-grained level. The accuracy of this stochastic thermostat algorithm is validated by all-atom MD simulation. This new stochastic thermostat algorithm provides an efficient way to investigate the thermomechanical properties of large-scale soft matters.

  15. Coarse-Grained Conformational Sampling of Protein Structure Improves the Fit to Experimental Hydrogen-Exchange Data.

    PubMed

    Devaurs, Didier; Antunes, Dinler A; Papanastasiou, Malvina; Moll, Mark; Ricklin, Daniel; Lambris, John D; Kavraki, Lydia E

    2017-01-01

    Monitoring hydrogen/deuterium exchange (HDX) undergone by a protein in solution produces experimental data that translates into valuable information about the protein's structure. Data produced by HDX experiments is often interpreted using a crystal structure of the protein, when available. However, it has been shown that the correspondence between experimental HDX data and crystal structures is often not satisfactory. This creates difficulties when trying to perform a structural analysis of the HDX data. In this paper, we evaluate several strategies to obtain a conformation providing a good fit to the experimental HDX data, which is a premise of an accurate structural analysis. We show that performing molecular dynamics simulations can be inadequate to obtain such conformations, and we propose a novel methodology involving a coarse-grained conformational sampling approach instead. By extensively exploring the intrinsic flexibility of a protein with this approach, we produce a conformational ensemble from which we extract a single conformation providing a good fit to the experimental HDX data. We successfully demonstrate the applicability of our method to four small and medium-sized proteins.

  16. Coarse-Grained Conformational Sampling of Protein Structure Improves the Fit to Experimental Hydrogen-Exchange Data

    PubMed Central

    Devaurs, Didier; Antunes, Dinler A.; Papanastasiou, Malvina; Moll, Mark; Ricklin, Daniel; Lambris, John D.; Kavraki, Lydia E.

    2017-01-01

    Monitoring hydrogen/deuterium exchange (HDX) undergone by a protein in solution produces experimental data that translates into valuable information about the protein's structure. Data produced by HDX experiments is often interpreted using a crystal structure of the protein, when available. However, it has been shown that the correspondence between experimental HDX data and crystal structures is often not satisfactory. This creates difficulties when trying to perform a structural analysis of the HDX data. In this paper, we evaluate several strategies to obtain a conformation providing a good fit to the experimental HDX data, which is a premise of an accurate structural analysis. We show that performing molecular dynamics simulations can be inadequate to obtain such conformations, and we propose a novel methodology involving a coarse-grained conformational sampling approach instead. By extensively exploring the intrinsic flexibility of a protein with this approach, we produce a conformational ensemble from which we extract a single conformation providing a good fit to the experimental HDX data. We successfully demonstrate the applicability of our method to four small and medium-sized proteins. PMID:28344973

  17. Fast relaxation of coarse-grained models of polymer interphases by hybrid particle-field molecular dynamics: Polystyrene-silica nanocomposites as an example

    NASA Astrophysics Data System (ADS)

    De Nicola, Antonio; Kawakatsu, Toshihiro; Müller-Plathe, Florian; Milano, Giuseppe

    2016-10-01

    Polymer composites attract large attention for their industrial use because of their unique features. The preparation of equilibrated melts of long entangled chains in the presence of a solid nanoparticle in molecular dynamics simulations is a very difficult task due to the slow relaxation time. We present a coarse-grained (CG) model suitable for polymer nanocomposites which combines Iterative-Boltzmann-Inversion derived polymer models, the hybrid particle-field representation of non-bonded interactions, and a convenient description of a solid nanoparticle suitable for hybrid particle-field models. The proposed approach is applied to test simulations of well characterized polystyrene-silica nanocomposites models. Finally, procedures for an efficient relaxation of pure polymer melts and interphase structures of large molecular weight nanocomposites are proposed.

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

    PubMed

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

    2016-09-08

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

  19. RNA pseudo-knots simulated with a one-bead coarse-grained model

    NASA Astrophysics Data System (ADS)

    Taxilaga-Zetina, Oscar; Pliego-Pastrana, Patricia; Carbajal-Tinoco, Mauricio D.

    2014-03-01

    We present a revised version of a Monte Carlo simulation model for RNA molecules that was introduced in a previous communication [O. Taxilaga-Zetina, P. Pliego-Pastrana, and M. D. Carbajal-Tinoco, Phys. Rev. E 81, 041914 (2010)]. The basic model consists of a series of knowledge-based pair potentials that were obtained from the statistical analysis of large RNAs belonging to the Protein Data Bank. These effective interactions are then used to dress a polymeric chain that reproduces relatively simple secondary structures (e.g., small hairpins). In order to describe more complicated three-dimensional structures such as pseudo-knots, here we include orientational information for the interaction between nucleotides forming hydrogen bonds, as in the case of the Watson-Crick base pairs. As a result, the simulated molecules obtained through the modified model are now consistent with their corresponding experimental configurations.

  20. Translocation thermodynamics of linear and cyclic nonaarginine into model DPPC bilayer via coarse-grained molecular dynamics simulation: implications of pore formation and nonadditivity.

    PubMed

    Hu, Yuan; Liu, Xiaorong; Sinha, Sudipta Kumar; Patel, Sandeep

    2014-03-13

    Structural mechanisms and underlying thermodynamic determinants of efficient internalization of charged cationic peptides (cell-penetrating peptides, CPPs) such as TAT, polyarginine, and their variants, into cells, cellular constructs, and model membrane/lipid bilayers (large and giant unilamellar or multilamelar vesicles) continue to garner significant attention. Two widely held views on the translocation mechanism center on endocytotic and nonendocytotic (diffusive) processes. Espousing the view of a purely diffusive internalization process (supported by recent experimental evidence, [Säälik, P.; et al. J. Controlled Release 2011, 153, 117-125]), we consider the underlying free energetics of the translocation of a nonaarginine peptide (Arg9) into a model DPPC bilayer. In the case of the Arg9 cationic peptide, recent experiments indicate a higher internalization efficiency of the cyclic structure (cyclic Arg9) relative to the linear conformer. Furthermore, recent all-atom resolution molecular dynamics simulations of cyclic Arg9 [Huang, K.; et al. Biophys. J., 2013, 104, 412-420] suggested a critical stabilizing role of water- and lipid-constituted pores that form within the bilayer as the charged Arg9 translocates deep into the bilayer center. Herein, we use umbrella sampling molecular dynamics simulations with coarse-grained Martini lipids, polarizable coarse-grained water, and peptide to explore the dependence of translocation free energetics on peptide structure and conformation via calculation of potentials of mean force along preselected reaction paths allowing and preventing membrane deformations that lead to pore formation. Within the context of the coarse-grained force fields we employ, we observe significant barriers for Arg9 translocation from bulk aqueous solution to bilayer center. Moreover, we do not find free-energy minima in the headgroup-water interfacial region, as observed in simulations using all-atom force fields. The pore-forming paths

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

    PubMed Central

    2015-01-01

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

  2. Comparing and contrasting size-based particle segregation models - Applying coarse-graining to perfectly bidisperse systems

    NASA Astrophysics Data System (ADS)

    Tunuguntla, Deepak R.; Weinhart, Thomas; Thornton, Anthony R.

    2016-10-01

    Over the last 12 years, numerous new theoretical continuum models have been formulated to predict particle segregation in the size-based bidisperse granular flows over inclined channels. Despite their presence, to our knowledge, no attempts have been made to compare and contrast the fundamental basis upon which these continuum models have been formulated. In this paper, firstly, we aim to illustrate the difference in these models including the incompatible nomenclature which impedes direct comparison. Secondly, we utilise (i) our robust and efficient in-house particle solver MercuryDPM, and (ii) our accurate micro-macro (discrete to continuum) mapping tool called coarse-graining, to compare several proposed models. Through our investigation involving size-bidisperse mixtures, we find that (i) the proposed total partial stress fraction expressions do not match the results obtained from our simulation, and (ii) the kinetic partial stress fraction dominates over the total partial stress fraction and the contact partial stress fraction. However, the proposed theoretical total stress fraction expressions do capture the kinetic partial stress fraction profile, obtained from simulations, very well, thus possibly highlighting the reason why mixture theory segregation models work for inclined channel flows. However, further investigation is required to strengthen the basis upon which the existing mixture theory segregation models are built upon.

  3. Coarse-grained modeling of the titration and conductance behavior of aqueous fullerene hexa malonic acid (FHMA) solutions.

    PubMed

    Allison, Stuart A; Wu, Hengfu; Moyher, Avery; Soegiarto, Linda; Truong, Bi; Nguyen, Duy; Nguyen, Tam; Park, Donghyun

    2014-03-20

    The coarse-grained continuum primitive model is developed and used to characterize the titration and electrical conductance behavior of aqueous solutions of fullerene hexa malonic acid (FHMA). The spherical FHMA molecule, a highly charged electrolyte with an absolute valence charge as large as 12, is modeled as a dielectric sphere in Newtonian fluid, and electrostatics are treated numerically at the level of the non-linear Poisson-Boltzmann equation. Transport properties (electrophoretic mobilities and conductances) of the various charge states of FHMA are numerically computed using established numerical algorithms. For reasonable choices of the model parameters, good agreement between experiment (published literature) and modeling is achieved. In order to accomplish this, however, a moderate degree of specific binding of principal counterion and FHMA must be included in the modeling. It should be emphasized, however, that alternative explanations are possible. This comparison is made at 25 °C for both Na(+) and Ca(2+) principal counterions. The model is also used to characterize the different charge states and degree of counterion binding to those charge states as a function of pH.

  4. Free vibration of super-graphene carbon nanotube networks via a beam element based coarse-grained method

    NASA Astrophysics Data System (ADS)

    Gu, Ruifeng; Wang, Lifeng; He, Xiaoqiao

    2017-08-01

    A new beam element based coarse-grained model is developed to investigate efficiently the mechanical behavior of a large system of super-graphene carbon nanotube (SGCNT) networks with all boundaries clamped supported. The natural frequencies and mode shapes of the SGCNT networks made of single-walled carbon nanotubes (SWCNTs) with different diameters and lengths are obtained via the proposed coarse-grained model. The applicability of the coarse-grained model for the SGCNT networks is verified by comparison with the molecular structural mechanics model. The natural frequencies and associated mode shapes obtained via the coarse-grained model agree well with the results obtained from the molecular structural mechanics method, indicating that the coarse-grained model developed in this study can be applied for the dynamic prediction of the SGCNT networks.

  5. Mechanisms and Kinetics of Amyloid Aggregation Investigated by a Phenomenological Coarse-Grained Model

    NASA Astrophysics Data System (ADS)

    Magno, Andrea; Pellarin, Riccardo; Caflisch, Amedeo

    Amyloid fibrils are ordered polypeptide aggregates that have been implicated in several neurodegenerative pathologies, such as Alzheimer's, Parkinson's, Huntington's, and prion diseases, [1, 2] and, more recently, also in biological functionalities. [3, 4, 5] These findings have paved the way for a wide range of experimental and computational studies aimed at understanding the details of the fibril-formation mechanism. Computer simulations using low-resolution models, which employ a simplified representation of protein geometry and energetics, have provided insights into the basic physical principles underlying protein aggregation in general [6, 7, 8] and ordered amyloid aggregation. [9, 10, 11, 12, 13, 14, 15] For example, Dokholyan and coworkers have used the Discrete Molecular Dynamics method [16, 17] to shed light on the mechanisms of protein oligomerization [18] and the conformational changes that take place in proteins before the aggregation onset. [19, 20] One challenging observation, which is difficult to observe by computer simulations, is the wide range of aggregation scenarios emerging from a variety of biophysical measurements. [21, 22] Atomistic models have been employed to study the conformational space of amyloidogenic polypeptides in the monomeric state, [23, 24, 25] the very initial steps of amyloid formation, [26, 27, 28, 29, 30, 31, 32] and the structural stability of fibril models. [33, 34, 35) However, all-atom simulations of the kinetics of fibril formation are beyond what can be done with modern computers.

  6. Discrete breathers in a realistic coarse-grained model of proteins.

    PubMed

    Luccioli, Stefano; Imparato, Alberto; Lepri, Stefano; Piazza, Francesco; Torcini, Alessandro

    2011-08-01

    We report the results of molecular dynamics simulations of an off-lattice protein model featuring a physical force-field and amino-acid sequence. We show that localized modes of nonlinear origin, discrete breathers (DBs), emerge naturally as continuations of a subset of high-frequency normal modes residing at specific sites dictated by the native fold. DBs are time-periodic, space-localized vibrational modes that exist generically in nonlinear discrete systems and are known for their resilience and ability to concentrate energy for long times. In the case of the small β-barrel structure that we consider, DB-mediated localization occurs on the turns connecting the strands. At high energies, DBs stabilize the structure by concentrating energy on a few sites, while their collapse marks the onset of large-amplitude fluctuations of the protein. Furthermore, we show how breathers develop as energy-accumulating centres following perturbations even at distant locations, thus mediating efficient and irreversible energy transfers. Remarkably, due to the presence of angular potentials, the breather induces a local static distortion of the native fold. Altogether, the combination of these two nonlinear effects may provide a ready means for remotely controlling local conformational changes in proteins.

  7. Coarse-grained free energy functions for studying protein conformational changes: a double-well network model.

    PubMed

    Chu, Jhih-Wei; Voth, Gregory A

    2007-12-01

    In this work, a double-well network model (DWNM) is presented for generating a coarse-grained free energy function that can be used to study the transition between reference conformational states of a protein molecule. Compared to earlier work that uses a single, multidimensional double-well potential to connect two conformational states, the DWNM uses a set of interconnected double-well potentials for this purpose. The DWNM free energy function has multiple intermediate states and saddle points, and is hence a "rough" free energy landscape. In this implementation of the DWNM, the free energy function is reduced to an elastic-network model representation near the two reference states. The effects of free energy function roughness on the reaction pathways of protein conformational change is demonstrated by applying the DWNM to the conformational changes of two protein systems: the coil-to-helix transition of the DB-loop in G-actin and the open-to-closed transition of adenylate kinase. In both systems, the rough free energy function of the DWNM leads to the identification of distinct minimum free energy paths connecting two conformational states. These results indicate that while the elastic-network model captures the low-frequency vibrational motions of a protein, the roughness in the free energy function introduced by the DWNM can be used to characterize the transition mechanism between protein conformations.

  8. Coarse-grained Monte Carlo simulations of the phase transition of the Potts model on weighted networks.

    PubMed

    Shen, Chuansheng; Chen, Hanshuang; Hou, Zhonghuai; Xin, Houwen

    2011-06-01

    Developing an effective coarse-grained (CG) approach is a promising way for studying dynamics on large size networks. In the present work, we have proposed a strength-based CG (s-CG) method to study critical phenomena of the Potts model on weighted complex networks. By merging nodes with close strengths together, the original network is reduced to a CG network with much smaller size, on which the CG Hamiltonian can be well defined. In particular, we make an error analysis and show that our s-CG approach satisfies the condition of statistical consistency, which demands that the equilibrium probability distribution of the CG model matches that of the microscopic counterpart. Extensive numerical simulations are performed on scale-free networks and random networks, without or with strength correlation, showing that this s-CG approach works very well in reproducing the phase diagrams, fluctuations, and finite-size effects of the microscopic model, while the d-CG approach proposed in our recent work [Phys. Rev. E 82, 011107 (2010)] does not.

  9. Suppression of sub-surface freezing in free-standing thin films of a coarse-grained model of water.

    PubMed

    Haji-Akbari, Amir; DeFever, Ryan S; Sarupria, Sapna; Debenedetti, Pablo G

    2014-12-21

    Freezing in the vicinity of water-vapor interfaces is of considerable interest to a wide range of disciplines, most notably the atmospheric sciences. In this work, we use molecular dynamics and two advanced sampling techniques, forward flux sampling and umbrella sampling, to study homogeneous nucleation of ice in free-standing thin films of supercooled water. We use a coarse-grained monoatomic model of water, known as mW, and we find that in this model a vapor-liquid interface suppresses crystallization in its vicinity. This suppression occurs in the vicinity of flat interfaces where no net Laplace pressure in induced. Our free energy calculations reveal that the pre-critical crystalline nuclei that emerge near the interface are thermodynamically less stable than those that emerge in the bulk. We investigate the origin of this instability by computing the average asphericity of nuclei that form in different regions of the film, and observe that average asphericity increases closer to the interface, which is consistent with an increase in the free energy due to increased surface-to-volume ratios.

  10. Understanding diffusion and density anomaly in a coarse-grained model for water confined between hydrophobic walls.

    PubMed

    de los Santos, Francisco; Franzese, Giancarlo

    2011-12-08

    We study, by Monte Carlo simulations, a coarse-grained model of a water monolayer between hydrophobic walls at partial hydration, with a wall-to-wall distance of about 0.5 nm. We analyze how the diffusion constant parallel to the walls, D(∥), changes and correlates to the phase diagram of the system. We find a locus of D(∥) maxima and a locus of D(∥) minima along isotherms, with lines of constant D(∥) resembling the melting line of bulk water. The two loci of D(∥) extrema envelope the line of temperatures of density maxima at constant P. We show how these loci are related to the anomalous volume behavior due to the hydrogen bonds. At much lower T, confined water becomes subdiffusive, and we discuss how this behavior is a consequence of the increased correlations among water molecules when the hydrogen bond network develops. Within the subdiffusive region, although translations are largely hampered, we observe that the hydrogen bond network can equilibrate, and its rearrangement is responsible for the appearance of density minima along isobars. We clarify that the minima are not necessarily related to the saturation of the hydrogen bond network.

  11. Are coarse-grained models apt to detect protein thermal stability? The case of OPEP force field

    PubMed Central

    Kalimeri, Maria; Derreumaux, Philippe; Sterpone, Fabio

    2017-01-01

    We present the first investigation of the kinetic and thermodynamic stability of two homologous thermophilic and mesophilic proteins based on the coarse-grained model OPEP. The object of our investigation is a pair of G-domains of relatively large size, 200 amino acids each, with an experimental stability gap of about 40 K. The OPEP force field is able to maintain stable the fold of these relatively large proteins within the hundrend-nanosecond time scale without including external constraints. This makes possible to characterize the conformational landscape of the folded protein as well as to explore the unfolding. In agreement with all-atom simulations used as a reference, we show that the conformational landscape of the thermophilic protein is characterized by a larger number of substates with slower dynamics on the network of states and more resilient to temperature increase. Moreover, we verify the stability gap between the two proteins using replica-exchange simulations and estimate a difference between the melting temperatures of about 23 K, in fair agreement with experiment. The detailed investigation of the unfolding thermodynamics, allows to gain insight into the mechanism underlying the enhanced stability of the thermophile relating it to a smaller heat capacity of unfolding. PMID:28100926

  12. Are coarse-grained models apt to detect protein thermal stability? The case of OPEP force field.

    PubMed

    Kalimeri, Maria; Derreumaux, Philippe; Sterpone, Fabio

    2015-01-01

    We present the first investigation of the kinetic and thermodynamic stability of two homologous thermophilic and mesophilic proteins based on the coarse-grained model OPEP. The object of our investigation is a pair of G-domains of relatively large size, 200 amino acids each, with an experimental stability gap of about 40 K. The OPEP force field is able to maintain stable the fold of these relatively large proteins within the hundrend-nanosecond time scale without including external constraints. This makes possible to characterize the conformational landscape of the folded protein as well as to explore the unfolding. In agreement with all-atom simulations used as a reference, we show that the conformational landscape of the thermophilic protein is characterized by a larger number of substates with slower dynamics on the network of states and more resilient to temperature increase. Moreover, we verify the stability gap between the two proteins using replica-exchange simulations and estimate a difference between the melting temperatures of about 23 K, in fair agreement with experiment. The detailed investigation of the unfolding thermodynamics, allows to gain insight into the mechanism underlying the enhanced stability of the thermophile relating it to a smaller heat capacity of unfolding.

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

    NASA Astrophysics Data System (ADS)

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

    2012-06-01

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

  14. Preparation of Entangled Polymer Melts of Various Architecture for Coarse-Grained Models

    DTIC Science & Technology

    2011-09-01

    thermostat, see the original papers by Hoogerbrugge and Koelman (7) and Español and Warren (8). 3. Generation of Initial Structure Using gel 3.1...1–19. 7. Koelman, J. M. V. A.; Hoogerbrugge, P. J. Europhys. Lett. 1993, 21, 363–368. 8. Español , P.; Warren, P. B. Europhys. Lett. 1995, 30, 191

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

    PubMed Central

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

    2016-01-01

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

  16. Electro-acoustic behavior of the mitotic spindle: a semi-classical coarse-grained model.

    PubMed

    Havelka, Daniel; Kučera, Ondřej; Deriu, Marco A; Cifra, Michal

    2014-01-01

    The regulation of chromosome separation during mitosis is not fully understood yet. Microtubules forming mitotic spindles are targets of treatment strategies which are aimed at (i) the triggering of the apoptosis or (ii) the interruption of uncontrolled cell division. Despite these facts, only few physical models relating to the dynamics of mitotic spindles exist up to now. In this paper, we present the first electromechanical model which enables calculation of the electromagnetic field coupled to acoustic vibrations of the mitotic spindle. This electromagnetic field originates from the electrical polarity of microtubules which form the mitotic spindle. The model is based on the approximation of resonantly vibrating microtubules by a network of oscillating electric dipoles. Our computational results predict the existence of a rapidly changing electric field which is generated by either driven or endogenous vibrations of the mitotic spindle. For certain values of parameters, the intensity of the electric field and its gradient reach values which may exert a not-inconsiderable force on chromosomes which are aligned in the spindle midzone. Our model may describe possible mechanisms of the effects of ultra-short electrical and mechanical pulses on dividing cells--a strategy used in novel methods for cancer treatment.

  17. Electro-Acoustic Behavior of the Mitotic Spindle: A Semi-Classical Coarse-Grained Model

    PubMed Central

    Havelka, Daniel; Kučera, Ondřej; Deriu, Marco A.; Cifra, Michal

    2014-01-01

    The regulation of chromosome separation during mitosis is not fully understood yet. Microtubules forming mitotic spindles are targets of treatment strategies which are aimed at (i) the triggering of the apoptosis or (ii) the interruption of uncontrolled cell division. Despite these facts, only few physical models relating to the dynamics of mitotic spindles exist up to now. In this paper, we present the first electromechanical model which enables calculation of the electromagnetic field coupled to acoustic vibrations of the mitotic spindle. This electromagnetic field originates from the electrical polarity of microtubules which form the mitotic spindle. The model is based on the approximation of resonantly vibrating microtubules by a network of oscillating electric dipoles. Our computational results predict the existence of a rapidly changing electric field which is generated by either driven or endogenous vibrations of the mitotic spindle. For certain values of parameters, the intensity of the electric field and its gradient reach values which may exert a not-inconsiderable force on chromosomes which are aligned in the spindle midzone. Our model may describe possible mechanisms of the effects of ultra-short electrical and mechanical pulses on dividing cells—a strategy used in novel methods for cancer treatment. PMID:24497952

  18. Definition of the persistence length in the coarse-grained models of DNA elasticity.

    PubMed

    Fathizadeh, A; Eslami-Mossallam, B; Ejtehadi, M R

    2012-11-01

    By considering the detailed structure of DNA in the base pair level, two possible definitions of the persistence length are compared. One definition is related to the orientation of the terminal base pairs, and the other is based on the vectors which connect two adjacent base pairs at each end of the molecule. It is shown that although these definitions approach each other for long DNA molecules, they are dramatically different on short length scales. We show analytically that the difference mostly comes from the shear flexibility of the molecule and can be used to measure the shear modulus of DNA.

  19. Definition of the persistence length in the coarse-grained models of DNA elasticity

    NASA Astrophysics Data System (ADS)

    Fathizadeh, A.; Eslami-Mossallam, B.; Ejtehadi, M. R.

    2012-11-01

    By considering the detailed structure of DNA in the base pair level, two possible definitions of the persistence length are compared. One definition is related to the orientation of the terminal base pairs, and the other is based on the vectors which connect two adjacent base pairs at each end of the molecule. It is shown that although these definitions approach each other for long DNA molecules, they are dramatically different on short length scales. We show analytically that the difference mostly comes from the shear flexibility of the molecule and can be used to measure the shear modulus of DNA.

  20. Linear models of activation cascades: analytical solutions and coarse-graining of delayed signal transduction.

    PubMed

    Beguerisse-Díaz, Mariano; Desikan, Radhika; Barahona, Mauricio

    2016-08-01

    Cellular signal transduction usually involves activation cascades, the sequential activation of a series of proteins following the reception of an input signal. Here, we study the classic model of weakly activated cascades and obtain analytical solutions for a variety of inputs. We show that in the special but important case of optimal gain cascades (i.e. when the deactivation rates are identical) the downstream output of the cascade can be represented exactly as a lumped nonlinear module containing an incomplete gamma function with real parameters that depend on the rates and length of the cascade, as well as parameters of the input signal. The expressions obtained can be applied to the non-identical case when the deactivation rates are random to capture the variability in the cascade outputs. We also show that cascades can be rearranged so that blocks with similar rates can be lumped and represented through our nonlinear modules. Our results can be used both to represent cascades in computational models of differential equations and to fit data efficiently, by reducing the number of equations and parameters involved. In particular, the length of the cascade appears as a real-valued parameter and can thus be fitted in the same manner as Hill coefficients. Finally, we show how the obtained nonlinear modules can be used instead of delay differential equations to model delays in signal transduction.

  1. Linear models of activation cascades: analytical solutions and coarse-graining of delayed signal transduction

    PubMed Central

    Desikan, Radhika

    2016-01-01

    Cellular signal transduction usually involves activation cascades, the sequential activation of a series of proteins following the reception of an input signal. Here, we study the classic model of weakly activated cascades and obtain analytical solutions for a variety of inputs. We show that in the special but important case of optimal gain cascades (i.e. when the deactivation rates are identical) the downstream output of the cascade can be represented exactly as a lumped nonlinear module containing an incomplete gamma function with real parameters that depend on the rates and length of the cascade, as well as parameters of the input signal. The expressions obtained can be applied to the non-identical case when the deactivation rates are random to capture the variability in the cascade outputs. We also show that cascades can be rearranged so that blocks with similar rates can be lumped and represented through our nonlinear modules. Our results can be used both to represent cascades in computational models of differential equations and to fit data efficiently, by reducing the number of equations and parameters involved. In particular, the length of the cascade appears as a real-valued parameter and can thus be fitted in the same manner as Hill coefficients. Finally, we show how the obtained nonlinear modules can be used instead of delay differential equations to model delays in signal transduction. PMID:27581482

  2. Sequence determines degree of knottedness in a coarse-grained protein model.

    PubMed

    Wüst, Thomas; Reith, Daniel; Virnau, Peter

    2015-01-16

    Knots are abundant in globular homopolymers but rare in globular proteins. To shed new light on this long-standing conundrum, we study the influence of sequence on the formation of knots in proteins under native conditions within the framework of the hydrophobic-polar lattice protein model. By employing large-scale Wang-Landau simulations combined with suitable Monte Carlo trial moves we show that even though knots are still abundant on average, sequence introduces large variability in the degree of self-entanglements. Moreover, we are able to design sequences which are either almost always or almost never knotted. Our findings serve as proof of concept that the introduction of just one additional degree of freedom per monomer (in our case sequence) facilitates evolution towards a protein universe in which knots are rare.

  3. Hybrid Quantum Mechanics/Molecular Mechanics/Coarse Grained Modeling: A Triple-Resolution Approach for Biomolecular Systems.

    PubMed

    Sokkar, Pandian; Boulanger, Eliot; Thiel, Walter; Sanchez-Garcia, Elsa

    2015-04-14

    We present a hybrid quantum mechanics/molecular mechanics/coarse-grained (QM/MM/CG) multiresolution approach for solvated biomolecular systems. The chemically important active-site region is treated at the QM level. The biomolecular environment is described by an atomistic MM force field, and the solvent is modeled with the CG Martini force field using standard or polarizable (pol-CG) water. Interactions within the QM, MM, and CG regions, and between the QM and MM regions, are treated in the usual manner, whereas the CG-MM and CG-QM interactions are evaluated using the virtual sites approach. The accuracy and efficiency of our implementation is tested for two enzymes, chorismate mutase (CM) and p-hydroxybenzoate hydroxylase (PHBH). In CM, the QM/MM/CG potential energy scans along the reaction coordinate yield reaction energies that are too large, both for the standard and polarizable Martini CG water models, which can be attributed to adverse effects of using large CG water beads. The inclusion of an atomistic MM water layer (10 Å for uncharged CG water and 5 Å for polarizable CG water) around the QM region improves the energy profiles compared to the reference QM/MM calculations. In analogous QM/MM/CG calculations on PHBH, the use of the pol-CG description for the outer water does not affect the stabilization of the highly charged FADHOOH-pOHB transition state compared to the fully atomistic QM/MM calculations. Detailed performance analysis in a glycine-water model system indicates that computation times for QM energy and gradient evaluations at the density functional level are typically reduced by 40-70% for QM/MM/CG relative to fully atomistic QM/MM calculations.

  4. Coarse-grained short-range correlations

    NASA Astrophysics Data System (ADS)

    Simo, I. Ruiz; Pérez, R. Navarro; Amaro, J. E.; Ruiz Arriola, E.

    2017-05-01

    We develop a scheme to take into account the effects of short-range nucleon-nucleon correlations in the nucleon-pair wave function by solving the Bethe-Goldstone equation for a coarse-grained delta shell potential in S -wave configuration. The S -wave delta shell potential has been adjusted to reproduce the 1S0 phase shifts of the AV18 potential for this partial wave up to 2 GeV in the laboratory kinetic energy. We show that a coarse-grained potential can describe the high momentum tail of the back-to-back correlated pairs and the G matrix in momentum space. We discuss the easiness and robustness of the calculation in coordinate space and the future improvements and utilities of this model. This work suggests the possibility of using perturbation theory for describing the short-range correlations and, related to this, to substitute the G matrix by an appropriate coarse-grained potential.

  5. Two-bead polarizable water models combined with a two-bead multipole force field (TMFF) for coarse-grained simulation of proteins.

    PubMed

    Li, Min; Zhang, John Z H

    2017-03-08

    The development of polarizable water models at coarse-grained (CG) levels is of much importance to CG molecular dynamics simulations of large biomolecular systems. In this work, we combined the newly developed two-bead multipole force field (TMFF) for proteins with the two-bead polarizable water models to carry out CG molecular dynamics simulations for benchmark proteins. In our simulations, two different two-bead polarizable water models are employed, the RTPW model representing five water molecules by Riniker et al. and the LTPW model representing four water molecules. The LTPW model is developed in this study based on the Martini three-bead polarizable water model. Our simulation results showed that the combination of TMFF with the LTPW model significantly stabilizes the protein's native structure in CG simulations, while the use of the RTPW model gives better agreement with all-atom simulations in predicting the residue-level fluctuation dynamics. Overall, the TMFF coupled with the two-bead polarizable water models enables one to perform an efficient and reliable CG dynamics study of the structural and functional properties of large biomolecules.

  6. Coarse-grained kinetic Monte Carlo models: Complex lattices, multicomponent systems, and homogenization at the stochastic level

    NASA Astrophysics Data System (ADS)

    Collins, Stuart D.; Chatterjee, Abhijit; Vlachos, Dionisios G.

    2008-11-01

    On-lattice kinetic Monte Carlo (KMC) simulations have extensively been applied to numerous systems. However, their applicability is severely limited to relatively short time and length scales. Recently, the coarse-grained MC (CGMC) method was introduced to greatly expand the reach of the lattice KMC technique. Herein, we extend the previous spatial CGMC methods to multicomponent species and/or site types. The underlying theory is derived and numerical examples are presented to demonstrate the method. Furthermore, we introduce the concept of homogenization at the stochastic level over all site types of a spatially coarse-grained cell. Homogenization provides a novel coarsening of the number of processes, an important aspect for complex problems plagued by the existence of numerous microscopic processes (combinatorial complexity). As expected, the homogenized CGMC method outperforms the traditional KMC method on computational cost while retaining good accuracy.

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

    SciTech Connect

    Markutsya, Sergiy; Lamm, Monica H.

    2014-11-07

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

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

    NASA Astrophysics Data System (ADS)

    Markutsya, Sergiy; Lamm, Monica H.

    2014-11-01

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

  9. Ergodicity and model quality in template-restrained canonical and temperature/Hamiltonian replica exchange coarse-grained molecular dynamics simulations of proteins.

    PubMed

    Karczyńska, Agnieszka S; Czaplewski, Cezary; Krupa, Paweł; Mozolewska, Magdalena A; Joo, Keehyoung; Lee, Jooyoung; Liwo, Adam

    2017-09-22

    Molecular simulations restrained to single or multiple templates are commonly used in protein-structure modeling. However, the restraints introduce additional barriers, thus impairing the ergodicity of simulations, which can affect the quality of the resulting models. In this work, the effect of restraint types and simulation schemes on ergodicity and model quality was investigated by performing template-restrained canonical molecular dynamics (MD), multiplexed replica-exchange molecular dynamics, and Hamiltonian replica exchange molecular dynamics (HREMD) simulations with the coarse-grained UNRES force field on nine selected proteins, with pseudo-harmonic log-Gaussian (unbounded) or Lorentzian (bounded) restraint functions. The best ergodicity was exhibited by HREMD. It has been found that non-ergodicity does not affect model quality if good templates are used to generate restraints. However, when poor-quality restraints not covering the entire protein are used, the improved ergodicity of HREMD can lead to significantly improved protein models. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  10. Solid-liquid work of adhesion of coarse-grained models of n-hexane on graphene layers derived from the conditional reversible work method

    SciTech Connect

    Ardham, Vikram Reddy; Leroy, Frédéric E-mail: f.leroy@theo.chemie.tu-darmstadt.de; Deichmann, Gregor; Vegt, Nico F. A. van der E-mail: f.leroy@theo.chemie.tu-darmstadt.de

    2015-12-28

    We address the question of how reducing the number of degrees of freedom modifies the interfacial thermodynamic properties of heterogeneous solid-liquid systems. We consider the example of n-hexane interacting with multi-layer graphene which we model both with fully atomistic and coarse-grained (CG) models. The CG models are obtained by means of the conditional reversible work (CRW) method. The interfacial thermodynamics of these models is characterized by the solid-liquid work of adhesion W{sub SL} calculated by means of the dry-surface methodology through molecular dynamics simulations. We find that the CRW potentials lead to values of W{sub SL} that are larger than the atomistic ones. Clear understanding of the relationship between the structure of n-hexane in the vicinity of the surface and W{sub SL} is elucidated through a detailed study of the energy and entropy components of W{sub SL}. We highlight the crucial role played by the solid-liquid energy fluctuations. Our approach suggests that CG potentials should be designed in such a way that they preserve the range of solid-liquid interaction energies, but also their fluctuations in order to preserve the reference atomistic value of W{sub SL}. Our study thus opens perspectives into deriving CG interaction potentials that preserve the thermodynamics of solid-liquid contacts and will find application in studies that intend to address materials driven by interfaces.

  11. Coarse-Graining in Simulations of Multicomponent Polymer Systems

    NASA Astrophysics Data System (ADS)

    Sethuraman, Vaidyanathan; Ganesan, Venkat

    2015-03-01

    We investigate the mapping required between the interaction parameters of two different coarse-grained simulation models to ensure a match of the long-range structural characteristics of multicomponent polymeric system. We investigate the extensibility of mapping functions deduced in the context of symmetric block copolymers by Morse and coworkers to other polymeric systems by studying a variety of systems, including, asymmetric diblock copolymers, symmetric triblock copolymers and diblock copolymer-solvent mixtures. We observe excellent agreement for peak in the inverse structure between two popular coarse grained models for all sets of polymeric melt systems investigated, thus showing that the mapping function proposed for diblock copolymer melts is transferable to other polymer melts irrespective of the blockiness or overall composition. We use our findings to propose a methodology to create ordered morphologies in simulations involving hard repulsive potentials in a computationally efficient manner.

  12. Prediction of solution properties and dynamics of RNAs by means of Brownian dynamics simulation of coarse-grained models: Ribosomal 5S RNA and phenylalanine transfer RNA.

    PubMed

    Benítez, Aarón Ayllón; Hernández Cifre, José Ginés; Díaz Baños, Francisco Guillermo; de la Torre, José García

    2015-01-01

    The possibility of validating biological macromolecules with locally disordered domains like RNA against solution properties is helpful to understand their function. In this work, we present a computational scheme for predicting global properties and mimicking the internal dynamics of RNA molecules in solution. A simple coarse-grained model with one bead per nucleotide and two types of intra-molecular interactions (elastic interactions and excluded volume interactions) is used to represent the RNA chain. The elastic interactions are modeled by a set of Hooke springs that form a minimalist elastic network. The Brownian dynamics technique is employed to simulate the time evolution of the RNA conformations. That scheme is applied to the 5S ribosomal RNA of E. Coli and the yeast phenylalanine transfer RNA. From the Brownian trajectory, several solution properties (radius of gyration, translational diffusion coefficient, and a rotational relaxation time) are calculated. For the case of yeast phenylalanine transfer RNA, the time evolution and the probability distribution of the inter-arm angle is also computed. The general good agreement between our results and some experimental data indicates that the model is able to capture the tertiary structure of RNA in solution. Our simulation results also compare quite well with other numerical data. An advantage of the scheme described here is the possibility of visualizing the real time macromolecular dynamics.

  13. Coarse-graining in simulations of multicomponent polymer systems

    NASA Astrophysics Data System (ADS)

    Sethuraman, Vaidyanathan; Nguyen, Bryan H.; Ganesan, Venkat

    2014-12-01

    We investigate the mapping required between the interaction parameters of two different coarse-grained simulation models to ensure a match of the long-range structural characteristics of multicomponent polymeric system. The basis for our studies is the recent work of Morse and workers, which demonstrated the existence of a mapping between the interaction parameters of different coarse-grained simulation models which allow for a matching of the peak of the disordered state structure factor in symmetric diblock copolymers. We investigate the extensibility of their results to other polymeric systems by studying a variety of systems, including, asymmetric diblock copolymers, symmetric triblock copolymers, and diblock copolymer-solvent mixtures. By using the mapping deduced in the context of symmetric diblock copolymers, we observe excellent agreement for peak in the inverse structure between both two popular coarse grained models for all sets of polymeric melt systems investigated, thus showing that the mapping function proposed for diblock copolymer melts is transferable to other polymer melts irrespective of the blockiness or overall composition. Interestingly, for the limited parameter range of polymer-solvent systems investigated in this article, the mapping functions developed for polymer melts are shown to be equally effective in mapping the structure factor of the coarse-grained simulation models. We use our findings to propose a methodology to create ordered morphologies in simulations involving hard repulsive potentials in a computationally efficient manner. We demonstrate the outcomes of methodology by creating lamellar and cylindrical phases of diblock copolymers of long chains in the popularly used Kremer-Grest simulation model.

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

    NASA Astrophysics Data System (ADS)

    Cao, Zhen; Voth, Gregory A.

    2015-12-01

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

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

    SciTech Connect

    Cao, Zhen; Voth, Gregory A.

    2015-12-28

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

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

    PubMed

    Saielli, Giacomo; Wang, Yanting

    2016-09-01

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

  17. Atomistic and Coarse-grained Simulations of Hexabenzocoronene Crystals

    NASA Astrophysics Data System (ADS)

    Ziogos, G.; Megariotis, G.; Theodorou, D. N.

    2016-08-01

    This study concerns atomistic and coarse-grained Molecular Dynamics simulations of pristine hexabenzocoronene (HBC) molecular crystals. HBC is a symmetric graphene flake of nanometric size that falls in the category of polyaromatic hydrocarbons, finding numerous applications in the field of organic electronics. The HBC molecule is simulated in its crystalline phase initially by means of an all-atom representation, where the molecules self- organize into well aligned molecular stacks, which in turn create a perfect monoclinic molecular crystal. The atomistic model reproduces fairly well the structural experimental properties and thus can be used as a reliable starting point for the development of a coarsegrained model following a bottom-up approach. The coarse-grained model is developed by applying Iterative Boltzmann Inversion, a systematic coarse-graining method which reproduces a set of target atomistic radial distribution functions and intramolecular distributions at the coarser level of description. This model allows the simulation of HBC crystals over longer time and length scales. The crystalline phase is analyzed in terms of the Saupe tensor and thermomechanical properties are probed at the atomistic level.

  18. Coarse graining flow of spin foam intertwiners

    NASA Astrophysics Data System (ADS)

    Dittrich, Bianca; Schnetter, Erik; Seth, Cameron J.; Steinhaus, Sebastian

    2016-12-01

    Simplicity constraints play a crucial role in the construction of spin foam models, yet their effective behavior on larger scales is scarcely explored. In this article we introduce intertwiner and spin net models for the quantum group SU (2 )k×SU (2 )k, which implement the simplicity constraints analogous to four-dimensional Euclidean spin foam models, namely the Barrett-Crane (BC) and the Engle-Pereira-Rovelli-Livine/Freidel-Krasnov (EPRL/FK) model. These models are numerically coarse grained via tensor network renormalization, allowing us to trace the flow of simplicity constraints to larger scales. In order to perform these simulations we have substantially adapted tensor network algorithms, which we discuss in detail as they can be of use in other contexts. The BC and the EPRL/FK model behave very differently under coarse graining: While the unique BC intertwiner model is a fixed point and therefore constitutes a two-dimensional topological phase, BC spin net models flow away from the initial simplicity constraints and converge to several different topological phases. Most of these phases correspond to decoupling spin foam vertices; however we find also a new phase in which this is not the case, and in which a nontrivial version of the simplicity constraints holds. The coarse graining flow of the BC spin net models indicates furthermore that the transitions between these phases are not of second order. The EPRL/FK model by contrast reveals a far more intricate and complex dynamics. We observe an immediate flow away from the original simplicity constraints; however, with the truncation employed here, the models generically do not converge to a fixed point. The results show that the imposition of simplicity constraints can indeed lead to interesting and also very complex dynamics. Thus we need to further develop coarse graining tools to efficiently study the large scale behavior of spin foam models, in particular for the EPRL/FK model.

  19. An Advanced Coarse-Grained Nucleosome Core Particle Model for Computer Simulations of Nucleosome-Nucleosome Interactions under Varying Ionic Conditions

    PubMed Central

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

    2013-01-01

    In the eukaryotic cell nucleus, DNA exists as chromatin, a compact but dynamic complex with histone proteins. The first level of DNA organization is the linear array of nucleosome core particles (NCPs). The NCP is a well-defined complex of 147 bp DNA with an octamer of histones. Interactions between NCPs are of paramount importance for higher levels of chromatin compaction. The polyelectrolyte nature of the NCP implies that nucleosome-nucleosome interactions must exhibit a great influence from both the ionic environment as well as the positively charged and highly flexible N-terminal histone tails, protruding out from the NCP. The large size of the system precludes a modelling analysis of chromatin at an all-atom level and calls for coarse-grained approximations. Here, a model of the NCP that include the globular histone core and the flexible histone tails described by one particle per each amino acid and taking into account their net charge is proposed. DNA wrapped around the histone core was approximated at the level of two base pairs represented by one bead (bases and sugar) plus four beads of charged phosphate groups. Computer simulations, using a Langevin thermostat, in a dielectric continuum with explicit monovalent (K+), divalent (Mg2+) or trivalent (Co(NH3)63+) cations were performed for systems with one or ten NCPs. Increase of the counterion charge results in a switch from repulsive NCP-NCP interaction in the presence of K+, to partial aggregation with Mg2+ and to strong mutual attraction of all 10 NCPs in the presence of CoHex3+. The new model reproduced experimental results and the structure of the NCP-NCP contacts is in agreement with available data. Cation screening, ion-ion correlations and tail bridging contribute to the NCP-NCP attraction and the new NCP model accounts for these interactions. PMID:23418426

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

    PubMed

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

    2013-01-01

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

  1. A coarse-grained elastic network atom contact model and its use in the simulation of protein dynamics and the prediction of the effect of mutations.

    PubMed

    Frappier, Vincent; Najmanovich, Rafael J

    2014-04-01

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

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

    PubMed Central

    Frappier, Vincent; Najmanovich, Rafael J.

    2014-01-01

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

  3. Measuring Crack Length in Coarse Grain Ceramics

    NASA Technical Reports Server (NTRS)

    Salem, Jonathan A.; Ghosn, Louis J.

    2010-01-01

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

  4. Efficient prediction of thermodynamic properties of quadrupolar fluids from simulation of a coarse-grained model: the case of carbon dioxide.

    PubMed

    Mognetti, B M; Yelash, L; Virnau, P; Paul, W; Binder, K; Müller, M; MacDowell, L G

    2008-03-14

    Monte Carlo simulations are presented for a coarse-grained model of real quadrupolar fluids. Molecules are represented by particles interacting with Lennard-Jones forces plus the thermally averaged quadrupole-quadrupole interaction. The properties discussed include the vapor-liquid coexistence curve, the vapor pressure along coexistence, and the surface tension. The full isotherms are also accessible over a wide range of temperatures and densities. It is shown that the critical parameters (critical temperature, density, and pressure) depend almost linearly on a quadrupolar parameter q=Q(*4)T*, where Q* is the reduced quadrupole moment of the molecule and T* the reduced temperature. The model can be applied to a variety of small quadrupolar molecules. We focus on carbon dioxide as a test case, but consider nitrogen and benzene, too. Experimental critical temperature, density, and quadrupolar moment are sufficient to fix the parameters of the model. The resulting agreement with experiments is excellent and marks a significant improvement over approaches which neglect quadrupolar effects. The same coarse-grained model was also applied in the framework of perturbation theory in the mean spherical approximation. As expected, the latter deviates from the Monte Carlo results in the critical region, but is reasonably accurate at lower temperatures.

  5. Isotropic pressure model in the presence of coarse-graining scale Alfvén waves and its consequence for modulational instability

    NASA Astrophysics Data System (ADS)

    Nariyuki, Y.

    2017-09-01

    A scalar pressure model of solar wind plasma in the presence of Alfvén waves at the coarse-graining scale is discussed. Using a simple sub-grid-scale model, it is shown that the scalar pressure model can be applied to describe the background pressure, because the off-diagonal components of the sub-grid-scale stress tensor disappear in the presence of one-dimensional, sub-grid scale Alfvén waves. Local equilibrium velocity distribution functions corresponding to the scalar pressure including wave dynamics (apparent temperature) are also presented. The specific heat ratio of the apparent temperature is given by the Wentzel-Kramers-Brillouin approximation of the Alfvén waves. The consequence of the local equilibrium velocity distribution functions in the coarse-graining scale model is discussed by using a nonlinear equation set describing envelope-modulated nonlinear Alfvén waves. It is recognized that without sufficient separation between the scale of waves and the scale of integration, artificial changes of the growth rates appear in the solutions of linear growth rates owing to the finite length of the filter function.

  6. The Theory of Ultra Coarse-graining

    NASA Astrophysics Data System (ADS)

    Voth, Gregory

    2013-03-01

    Coarse-grained (CG) models provide a computationally efficient means to study biomolecular and other soft matter processes involving large numbers of atoms correlated over distance scales of many covalent bond lengths and long time scales. Variational methods based on information from simulations of finer-grained (e.g., all-atom) models, for example the multiscale coarse-graining (MS-CG) and relative entropy minimization methods, provide attractive tools for the systematic development of CG models. However, these methods have important drawbacks when used in the ``ultra coarse-grained'' (UCG) regime, e.g., at a resolution level coarser or much coarser than one amino acid residue per effective CG particle in proteins. This is due to the possible existece of multiple metastable states ``within'' the CG sites for a given UCG model configuration. In this talk I will describe systematic variational UCG methods specifically designed to CG entire protein domains and subdomains into single effective CG particles. This is accomplished by augmenting existing effective particle CG schemes to allow for discrete state transitions and configuration-dependent resolution. Additionally, certain conclusions of this work connect back to single-state force matching and open up new avenues for method development in that area. These results provide a formal statistical mechanical basis for UCG methods related to force matching and relative entropy CG methods and suggest practical algorithms for constructing optimal approximate UCG models from fine-grained simulation data.

  7. Transport and dielectric properties of water and the influence of coarse-graining: comparing BMW, SPC/E, and TIP3P models.

    PubMed

    Braun, Daniel; Boresch, Stefan; Steinhauser, Othmar

    2014-02-14

    Long-term molecular dynamics simulations are used to compare the single particle dipole reorientation time, the diffusion constant, the viscosity, and the frequency-dependent dielectric constant of the coarse-grained big multipole water (BMW) model to two common atomistic three-point water models, SPC/E and TIP3P. In particular, the agreement between the calculated viscosity of BMW and the experimental viscosity of water is satisfactory. We also discuss contradictory values for the static dielectric properties reported in the literature. Employing molecular hydrodynamics, we show that the viscosity can be computed from single particle dynamics, circumventing the slow convergence of the standard approaches. Furthermore, our data indicate that the Kivelson relation connecting single particle and collective reorientation time holds true for all systems investigated. Since simulations with coarse-grained force fields often employ extremely large time steps, we also investigate the influence of time step on dynamical properties. We observe a systematic acceleration of system dynamics when increasing the time step. Carefully monitoring energy/temperature conservation is found to be a sufficient criterion for the reliable calculation of dynamical properties. By contrast, recommended criteria based on the ratio of fluctuations of total vs. kinetic energy are not sensitive enough.

  8. Transport and dielectric properties of water and the influence of coarse-graining: Comparing BMW, SPC/E, and TIP3P models

    SciTech Connect

    Braun, Daniel; Boresch, Stefan; Steinhauser, Othmar

    2014-02-14

    Long-term molecular dynamics simulations are used to compare the single particle dipole reorientation time, the diffusion constant, the viscosity, and the frequency-dependent dielectric constant of the coarse-grained big multipole water (BMW) model to two common atomistic three-point water models, SPC/E and TIP3P. In particular, the agreement between the calculated viscosity of BMW and the experimental viscosity of water is satisfactory. We also discuss contradictory values for the static dielectric properties reported in the literature. Employing molecular hydrodynamics, we show that the viscosity can be computed from single particle dynamics, circumventing the slow convergence of the standard approaches. Furthermore, our data indicate that the Kivelson relation connecting single particle and collective reorientation time holds true for all systems investigated. Since simulations with coarse-grained force fields often employ extremely large time steps, we also investigate the influence of time step on dynamical properties. We observe a systematic acceleration of system dynamics when increasing the time step. Carefully monitoring energy/temperature conservation is found to be a sufficient criterion for the reliable calculation of dynamical properties. By contrast, recommended criteria based on the ratio of fluctuations of total vs. kinetic energy are not sensitive enough.

  9. Transport and dielectric properties of water and the influence of coarse-graining: Comparing BMW, SPC/E, and TIP3P models

    NASA Astrophysics Data System (ADS)

    Braun, Daniel; Boresch, Stefan; Steinhauser, Othmar

    2014-02-01

    Long-term molecular dynamics simulations are used to compare the single particle dipole reorientation time, the diffusion constant, the viscosity, and the frequency-dependent dielectric constant of the coarse-grained big multipole water (BMW) model to two common atomistic three-point water models, SPC/E and TIP3P. In particular, the agreement between the calculated viscosity of BMW and the experimental viscosity of water is satisfactory. We also discuss contradictory values for the static dielectric properties reported in the literature. Employing molecular hydrodynamics, we show that the viscosity can be computed from single particle dynamics, circumventing the slow convergence of the standard approaches. Furthermore, our data indicate that the Kivelson relation connecting single particle and collective reorientation time holds true for all systems investigated. Since simulations with coarse-grained force fields often employ extremely large time steps, we also investigate the influence of time step on dynamical properties. We observe a systematic acceleration of system dynamics when increasing the time step. Carefully monitoring energy/temperature conservation is found to be a sufficient criterion for the reliable calculation of dynamical properties. By contrast, recommended criteria based on the ratio of fluctuations of total vs. kinetic energy are not sensitive enough.

  10. Spatial image compounding applied to a phase coherence corrected UT-PA technique for inspecting nuclear components of coarse-grained structure

    NASA Astrophysics Data System (ADS)

    Brizuela, Jose; Katchadjian, Pablo; Garcia, Alejandro; Desimone, Carlos

    2016-02-01

    The aim of this work is to obtain a C-Scan view of an austenitic stainless steel weld from a nuclear use pipe. In order to obtain this result Sectorial Scans (S-Scan) from both sides of the weld are obtained by Ultrasonic Phase Array (UT-PA). Then, spatial image compounding is performed to generate a single image from the S-Scans acquired at the same circumferential position of the transducer. These joints have a coarse grain structure which significantly reduce the transmission of the ultrasonic wave due to attenuation characteristics and backscattered noise from microstructures inside the material. For this reason, phase coherence imaging technique has been also applied to reduce the structural noise and improve the image quality. To verify detected defects, and given the impossibility of cutting the component, gammagraphy were performed with Co60.

  11. High-Resolution Coarse-Grained Model of Hydrated Anion-Exchange Membranes that Accounts for Hydrophobic and Ionic Interactions through Short-Ranged Potentials.

    PubMed

    Lu, Jibao; Jacobson, Liam C; Perez Sirkin, Yamila A; Molinero, Valeria

    2017-01-10

    Molecular simulations provide a versatile tool to study the structure, anion conductivity, and stability of anion-exchange membrane (AEM) materials and can provide a fundamental understanding of the relation between structure and property of membranes that is key for their use in fuel cells and other applications. The quest for large spatial and temporal scales required to model the multiscale structure and transport processes in the polymer electrolyte membranes, however, cannot be met with fully atomistic models, and the available coarse-grained (CG) models suffer from several challenges associated with their low-resolution. Here, we develop a high-resolution CG force field for hydrated polyphenylene oxide/trimethylamine chloride (PPO/TMACl) membranes compatible with the mW water model using a hierarchical parametrization approach based on Uncertainty Quantification and reference atomistic simulations modeled with the Generalized Amber Force Field (GAFF) and TIP4P/2005 water. The parametrization weighs multiple properties, including coordination numbers, radial distribution functions (RDFs), self-diffusion coefficients of water and ions, relative vapor pressure of water in the solution, hydration enthalpy of the tetramethylammonium chloride (TMACl) salt, and cohesive energy of its aqueous solutions. We analyze the interdependence between properties and address how to compromise between the accuracies of the properties to achieve an overall best representability. Our optimized CG model FFcomp quantitatively reproduces the diffusivities and RDFs of the reference atomistic model and qualitatively reproduces the experimental relative vapor pressure of water in solutions of tetramethylammonium chloride. These properties are of utmost relevance for the design and operation of fuel cell membranes. To our knowledge, this is the first CG model that includes explicitly each water and ion and accounts for hydrophobic, ionic, and intramolecular interactions explicitly

  12. Coarse-Grained Force field for the Nucleosome from Self-Consistent Multiscaling

    SciTech Connect

    Voltz, Karine; Trylska, Joanna; Tozzini, Valentina; Kurkal-Siebert, V; Smith, Jeremy C; Langowski, Jorg

    2008-02-01

    A coarse-grained simulation model for the nucleosome is developed, using a methodology modified from previous work on the ribosome. Protein residues and DNA nucleotides are represented as beads, interacting through harmonic (for neighboring) or Morse (for nonbonded) potentials. Force-field parameters were estimated by Boltzmann inversion of the corresponding radial distribution functions obtained from a 5-ns all-atom molecular dynamics (MD) simulation, and were refined to produce agreement with the all-atom MD simulation. This self-consistent multiscale approach yields a coarse-grained model that is capable of reproducing equilibrium structural properties calculated from a 50-ns all-atom MD simulation. This coarse-grained model speeds up nucleosome simulations by a factor of 10{sup 3} and is expected to be useful in examining biologically relevant dynamical nucleosome phenomena on the microsecond timescale and beyond.

  13. Performance Comparison of Systematic Methods for Rigorous Definition of Coarse-Grained Sites of Large Biomolecules.

    PubMed

    Zhang, Yuwei; Cao, Zexing; Zhang, John Zenghui; Xia, Fei

    2017-02-27

    Construction of coarse-grained (CG) models for large biomolecules used for multiscale simulations demands a rigorous definition of CG sites for them. Several coarse-graining methods such as the simulated annealing and steepest descent (SASD) based on the essential dynamics coarse-graining (ED-CG) or the stepwise local iterative optimization (SLIO) based on the fluctuation maximization coarse-graining (FM-CG), were developed to do it. However, the practical applications of these methods such as SASD based on ED-CG are subject to limitations because they are too expensive. In this work, we extend the applicability of ED-CG by combining it with the SLIO algorithm. A comprehensive comparison of optimized results and accuracy of various algorithms based on ED-CG show that SLIO is the fastest as well as the most accurate algorithm among them. ED-CG combined with SLIO could give converged results as the number of CG sites increases, which demonstrates that it is another efficient method for coarse-graining large biomolecules. The construction of CG sites for Ras protein by using MD fluctuations demonstrates that the CG sites derived from FM-CG can reflect the fluctuation properties of secondary structures in Ras accurately.

  14. Assessing the Quality of the OPEP Coarse-Grained Force Field.

    PubMed

    Barducci, Alessandro; Bonomi, Massimiliano; Derreumaux, Philippe

    2011-06-14

    A coarse-grained potential that could accurately describe the overall conformational landscape of proteins would be extremely valuable not only for structure prediction but also for studying protein dynamics, large conformational motions, and intrinsically disordered systems. Here, we assessed the quality of the OPEP coarse-grained potential by comparing the reconstructed free-energy surfaces (FESs) of two prototypical β-hairpin and α-helix peptides to all-atom calculations in explicit solvent. We found remarkable agreement between the OPEP FES and those obtained using atomistic models, despite a general overstabilization of α- and β-structures by the coarse-grained potential. The use of advanced sampling techniques based on metadynamics and parallel tempering guaranteed a thorough exploration of the conformational space accessible to the two peptides studied.

  15. Coarse-graining with information theory and the relative entropy

    NASA Astrophysics Data System (ADS)

    Shell, M. Scott

    2013-03-01

    There remain many both fundamental and practical/methodological questions regarding how coarse-grained models should be developed. Are there theoretically intuitive and numerically robust strategies for turning small-scale all-atom simulations into coarse models suitable for large-scale modeling? How can we identify what atomic details are unnecessary and can be discarded? Are there systematic ways to detect emergent physics? Here we discuss a fundamentally new approach to this problem. We propose that a natural way of viewing the coarse-graining problem is in terms of information theory. A quantity called the relative entropy measures the information lost upon coarse graining and hence the (inverse) fitness of a particular coarse-grained model. Minimization of the relative entropy thus provides a sort-of universal variational principle for coarse-graining, and a way to ``automatically'' discover and generate coarse models of many systems. We show that this new approach enables us to develop very simple but surprisingly accurate models of water, hydrophobic interactions, self-assembling peptides, and proteins that enable new physical insights as well as simulations of large-scale interactions. We discuss both theoretical and numerical aspects of this approach, in particular highlighting a new coarse-graining algorithm that efficiently optimizes coarse-grained models with even thousands of free parameters. We also discuss how the relative entropy approach suggests novel strategies for predicting the errors of coarse models, for identifying relevant degrees of freedom to retain, and for understanding the relationships among other coarse-graining methodologies.

  16. Spectral coarse graining for random walks in bipartite networks.

    PubMed

    Wang, Yang; Zeng, An; Di, Zengru; Fan, Ying

    2013-03-01

    Many real-world networks display a natural bipartite structure, yet analyzing and visualizing large bipartite networks is one of the open challenges in complex network research. A practical approach to this problem would be to reduce the complexity of the bipartite system while at the same time preserve its functionality. However, we find that existing coarse graining methods for monopartite networks usually fail for bipartite networks. In this paper, we use spectral analysis to design a coarse graining scheme specific for bipartite networks, which keeps their random walk properties unchanged. Numerical analysis on both artificial and real-world networks indicates that our coarse graining can better preserve most of the relevant spectral properties of the network. We validate our coarse graining method by directly comparing the mean first passage time of the walker in the original network and the reduced one.

  17. A New Coarse-Grained Model for E. coli Cytoplasm: Accurate Calculation of the Diffusion Coefficient of Proteins and Observation of Anomalous Diffusion

    PubMed Central

    Hasnain, Sabeeha; McClendon, Christopher L.; Hsu, Monica T.; Jacobson, Matthew P.; Bandyopadhyay, Pradipta

    2014-01-01

    A new coarse-grained model of the E. coli cytoplasm is developed by describing the proteins of the cytoplasm as flexible units consisting of one or more spheres that follow Brownian dynamics (BD), with hydrodynamic interactions (HI) accounted for by a mean-field approach. Extensive BD simulations were performed to calculate the diffusion coefficients of three different proteins in the cellular environment. The results are in close agreement with experimental or previously simulated values, where available. Control simulations without HI showed that use of HI is essential to obtain accurate diffusion coefficients. Anomalous diffusion inside the crowded cellular medium was investigated with Fractional Brownian motion analysis, and found to be present in this model. By running a series of control simulations in which various forces were removed systematically, it was found that repulsive interactions (volume exclusion) are the main cause for anomalous diffusion, with a secondary contribution from HI. PMID:25180859

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

    NASA Astrophysics Data System (ADS)

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

    2016-01-01

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

  19. Parameterization of a coarse-grained model with short-ranged interactions for modeling fuel cell membranes with controlled water uptake.

    PubMed

    Lu, Jibao; Miller, Chance; Molinero, Valeria

    2017-07-21

    The design of polymer electrolyte membranes with controlled water uptake is of high importance for high-performance fuel cells, because the water content of the membranes modulates their conductivity, chemical stability and mechanical strength. The water activity aw controls the equilibrium water uptake of a system. Predicting aw of materials is currently a daunting challenge for molecular simulations, because calculations of water activity require grand canonical simulations that are extremely expensive even with classical non-polarizable force fields. Moreover, force fields do not generally reproduce aw of solutions. Here, we first present a general strategy to parameterize force fields that reproduce the experimental aw of solutions, and then implement that strategy to re-parameterize the interactions in FFcomp, a coarse-grained model for hydrated polyphenylene oxide/trimethylamine chloride (PPO/TMACl) membranes in which the TMA cation is attached to the PPO backbone and the Cl anion is in the mobile water nanophase. Coarse-grained models based on short-ranged potentials successfully model fuel cell membranes and other concentrated aqueous electrolyte solutions because electrostatic interactions are highly screened in these systems. The new force field, FFpvap, differs from the original FFcomp only in the parameters of the ion-ion interactions, yet it reproduces aw in TMACl solutions with accuracy within 0.5 and 3% of the experimental value in all the concentration range relevant to the operation of fuel cell membranes. We find that the heat needed to vaporize water in solutions with as little as five water molecules per ion pair is essentially the same as in pure water, despite the strong water-ion interactions and their impact on the water activity. We review the literature to demonstrate that this is independent of the model and a general feature of water solutions. FFpvap reproduces the radial distribution functions and captures well the relative

  20. Coarse-grained modeling study of nonpeptide RGD ligand density and PEG molecular weight on the conformation of poly(γ-glutamyl-glutamate) paclitaxel conjugates.

    PubMed

    Peng, Lili X; Das, Sanjib K; Yu, Lei; Howell, Stephen B; Gough, David A

    2011-11-01

    Molecular shape, flexibility, and surface hydrophilicity are thought to influence the ability of nanoparticles to cross biological barriers during drug delivery. In this study, coarse-grained (CG) molecular dynamics (MD) simulations were used to study these properties of a polymer-drug construct in potential clinical development: poly(γ-glutamyl-glutamate)-paclitaxel-poly(ethylene glycol) nonpeptide RGD (PGG-PTX-PEG-npRGD), a linear glutamyl-glutamate polymer with paclitaxel and poly(ethylene glycol)-nonpeptide RGD side groups. It was hypothesized that the PEG molecular weight (MW) (500 Da; 1,000 Da; and 2,000 Da) and nonpeptide RGD ligand density (4, 8, 12, and 16 per molecule), respectively, may have advantageous effects on the shape, flexibility, and surface hydrophilicity of PGG-PTX-PEG-npRGD. Circular dichroism spectroscopy was used to suggest initial structures for the all-atom (AA) models of PGG-PTX-PEG-npRGD, which were further converted to CG models using a commercially available mapping algorithm. Due to its semi-flexibility, PGG-PTX-PEG-npRGD is not limited to one specific conformation. Thus, CG MD simulations were run until statistical equilibrium, at which PGG-PTX-PEG-npRGD is represented as an ensemble of statistically similar conformations. The size of a PGG-PTX-PEG-npRGD molecule is not affected by the PEG MW or the nonpeptide RGD density, but higher PEG MW results in increased surface density of a PGG-PTX-PEG-npRGD molecule. Most PGG-PTX-PEG-npRGD shapes are globular, although filamentous shapes were also observed in the PEG500 and PEG1000 molecules. PEG500 and PEG1000 molecules are more flexible than PEG2000 systems. A higher presence of npRGD ligands results in decrease surface hydrophilicity of PGG-PTX-PEG-npRGD. These results indicate that the PGG-PTX-PEG1000-npRGD(4) and PGG-PTX-PEG1000-npRGD(8) molecules are the most efficacious candidates and are further recommended for experimental preclinical studies.

  1. Interlaced coarse-graining for the dynamical cluster approximation

    NASA Astrophysics Data System (ADS)

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

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

  2. Molecular Dynamics Simulation of a Coarse Grained Model of Tetra-PEG Gel with Monomers of 5 and 9 particles

    NASA Astrophysics Data System (ADS)

    Ogawa, Shizuka; Waide, Sayaka; Takasu, Masako; Miyakawa, Takeshi; Morikawa, Ryota; Sakai, Takamasa; Chung, Ung-il

    We study the early process of gelation using our model of 5 particles and 9 particles in a monomer. We compare our models and obtain slower reaction for model of 9 particles. We also study the effect of random force and obtain slower reaction with random force but more extended structure.

  3. Macroscopic coherent structures in a stochastic neural network: from interface dynamics to coarse-grained bifurcation analysis.

    PubMed

    Avitable, Daniele; Wedgwood, Kyle C A

    2017-02-01

    We study coarse pattern formation in a cellular automaton modelling a spatially-extended stochastic neural network. The model, originally proposed by Gong and Robinson (Phys Rev E 85(5):055,101(R), 2012), is known to support stationary and travelling bumps of localised activity. We pose the model on a ring and study the existence and stability of these patterns in various limits using a combination of analytical and numerical techniques. In a purely deterministic version of the model, posed on a continuum, we construct bumps and travelling waves analytically using standard interface methods from neural field theory. In a stochastic version with Heaviside firing rate, we construct approximate analytical probability mass functions associated with bumps and travelling waves. In the full stochastic model posed on a discrete lattice, where a coarse analytic description is unavailable, we compute patterns and their linear stability using equation-free methods. The lifting procedure used in the coarse time-stepper is informed by the analysis in the deterministic and stochastic limits. In all settings, we identify the synaptic profile as a mesoscopic variable, and the width of the corresponding activity set as a macroscopic variable. Stationary and travelling bumps have similar meso- and macroscopic profiles, but different microscopic structure, hence we propose lifting operators which use microscopic motifs to disambiguate them. We provide numerical evidence that waves are supported by a combination of high synaptic gain and long refractory times, while meandering bumps are elicited by short refractory times.

  4. Exploring the dynamics and interaction of a full ErbB2 receptor and Trastuzumab-Fab antibody in a lipid bilayer model using Martini coarse-grained force field

    NASA Astrophysics Data System (ADS)

    Franco-Gonzalez, Juan Felipe; Ramos, Javier; Cruz, Victor L.; Martinez-Salazar, Javier

    2014-11-01

    Coarse grained (CG) modeling has been applied to study the influence of the Trastuzumab monoclonal antibody on the structure and dynamics of the full ErbB2 receptor dimer, including the lipid bilayer. The usage of CG models to study such complexes is almost mandatory, at present, due to the large size of the whole system. We will show that the Martini model performs satisfactorily well, giving results well-matched with those obtained by atomistic models as well as with the experimental information existing on homolog receptors. For example, the extra and intracellular domains approach the bilayer surface in both the monomer and dimer cases. The Trastuzumab-Fab hinders the interaction of the receptors with the lipid bilayer. Another interesting effect of the antibody is the disruption of the antiparallel arrangement of the juxtamembrane segments in the dimer case. These findings might help to understand the effect of the antibody on the receptor bioactivity.

  5. Preface: Special Topic on Coarse Graining of Macromolecules, Biopolymers, and Membranes.

    PubMed

    Holm, Christian; Gompper, Gerhard; Dill, Ken A

    2015-12-28

    This special issue highlights new developments in theory and coarse-graining in biological and synthetic macromolecules and membranes. Such approaches give unique insights into the principles and design of the structures, dynamics, and assembly processes of these complex fluids and soft materials, where the length and time scales are often prohibitively long for fully atomistic modeling.

  6. Preface: Special Topic on Coarse Graining of Macromolecules, Biopolymers, and Membranes

    SciTech Connect

    Holm, Christian; Gompper, Gerhard; Dill, Ken A.

    2015-12-28

    This special issue highlights new developments in theory and coarse-graining in biological and synthetic macromolecules and membranes. Such approaches give unique insights into the principles and design of the structures, dynamics, and assembly processes of these complex fluids and soft materials, where the length and time scales are often prohibitively long for fully atomistic modeling.

  7. Inferring coarse-grain histone-DNA interaction potentials from high-resolution structures of the nucleosome

    NASA Astrophysics Data System (ADS)

    Meyer, Sam; Everaers, Ralf

    2015-02-01

    The histone-DNA interaction in the nucleosome is a fundamental mechanism of genomic compaction and regulation, which remains largely unknown despite increasing structural knowledge of the complex. In this paper, we propose a framework for the extraction of a nanoscale histone-DNA force-field from a collection of high-resolution structures, which may be adapted to a larger class of protein-DNA complexes. We applied the procedure to a large crystallographic database extended by snapshots from molecular dynamics simulations. The comparison of the structural models first shows that, at histone-DNA contact sites, the DNA base-pairs are shifted outwards locally, consistent with locally repulsive forces exerted by the histones. The second step shows that the various force profiles of the structures under analysis derive locally from a unique, sequence-independent, quadratic repulsive force-field, while the sequence preferences are entirely due to internal DNA mechanics. We have thus obtained the first knowledge-derived nanoscale interaction potential for histone-DNA in the nucleosome. The conformations obtained by relaxation of nucleosomal DNA with high-affinity sequences in this potential accurately reproduce the experimental values of binding preferences. Finally we address the more generic binding mechanisms relevant to the 80% genomic sequences incorporated in nucleosomes, by computing the conformation of nucleosomal DNA with sequence-averaged properties. This conformation differs from those found in crystals, and the analysis suggests that repulsive histone forces are related to local stretch tension in nucleosomal DNA, mostly between adjacent contact points. This tension could play a role in the stability of the complex.

  8. Coarse grain modeling of the high-rate stress-strain behavior for select model Poly[urethane urea] (PUU) elastomers

    NASA Astrophysics Data System (ADS)

    Chantawansri, T. L.; Sliozberg, Y. R.; Hsieh, A.; Andzelm, J. W.

    2012-02-01

    Microphase-separated PUU, which consists of 4,4'-dicyclohexylmethane diisocyanate, diethyltoluenediamine and poly[tetramethylene oxide](PTMO), exhibits versatile mechanical properties making them an excellent choice for potential applications in the form of films, adhesives, coatings and matrix materials for composites. To elucidate the effects of composition, including the hard segment content & molecular weight of PTMO, on rate-dependent mechanical deformation in the high strain-rate regime (>> 10^5/s) the stress-strain behavior for PUU at various rates are calculated for four model systems using a coarse-grain model. Pair interactions between topologically non-connected particles are described by the standard truncated Lennard-Jones (LJ) pair potential, where bonded particles interact according to the standard FENE/LJ potential. An angle harmonic potential is also used to enforce the rigidity of the hard segments, and the system is evolved using molecular dynamics. Stress-strain curves are calculated at various strain-rates and qualitatively agree with experimental results when extrapolated to higher rate. Further analysis of the morphology is also performed to characterize the morphology and discern its connection to the calculated mechanical properties.

  9. Simulating the Entropic Collapse of Coarse-Grained Chromosomes

    PubMed Central

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

    2015-01-01

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

  10. Systematic Coarse-graining of Molecular Dynamics Simulations

    NASA Astrophysics Data System (ADS)

    Voth, Gregory

    2015-03-01

    Coarse-grained (CG) models can provide a computationally efficient means to study biomolecular and other soft matter processes involving large numbers of atoms that are correlated over distance scales of many covalent bond lengths and at long time scales. Systematic variational coarse-graining methods based on information from molecular dynamics simulations of finer-grained (e.g., all-atom) models provide attractive tools for the systematic development of CG models. Examples include the multiscale coarse-graining (MS-CG) and relative entropy minimization methods, and results from the former theory will be presented in this talk. In addition, a new approach will be presented that is appropriate for the ``ultra coarse-grained'' (UCG) regime, e.g., at a coarse-grained resolution that is much coarser than one amino acid residue per CG particle in a protein. At this level of coarse-graining, one is faced with the possible existence of multiple metastable states ``within'' the CG sites for a given UCG model configuration. I will therefore describe newer systematic variational UCG methods specifically designed to CG entire protein domains and subdomains into single effective CG particles. This is accomplished by augmenting existing effective particle CG schemes to allow for discrete state transitions and configuration-dependent resolution. Additionally, certain aspects of this work connect back to single-state force matching and open up new avenues for method development. This general body of theory and algorithm provides a formal statistical mechanical basis for the coarse-graining of fine-grained molecular dynamics simulation data at various levels of CG resolution. Representative applications will be described as time allows.

  11. Structure and phase transformations of DPPC lipid bilayers in the presence of nanoparticles: insights from coarse-grained molecular dynamics simulations.

    PubMed

    Prates Ramalho, J P; Gkeka, P; Sarkisov, L

    2011-04-05

    In this article, we investigate fluid-gel transformations of a DPPC lipid bilayer in the presence of nanoparticles, using coarse-grained molecular dynamics. Two types of nanoparticles are considered, specifically a 3 nm hydrophobic nanoparticle located in the core of the bilayer and a 6 nm charged nanoparticle located at the interface between the bilayer and water phase. Both negatively and positively charged nanoparticles at the bilayer interface are investigated. We demonstrate that the presence of all types of nanoparticles induces disorder effects in the structure of the lipid bilayer. These effects are characterized using computer visualization of the gel phase in the presence of nanoparticles, radial distribution functions, and order parameters. The 3 nm hydrophobic nanoparticle immersed in the bilayer core and the positively charged nanoparticle at the bilayer surface have no effect on the temperature of the fluid-gel transformation, compared to the bulk case. Interestingly, a negatively charged hydrophobic nanoparticle located at the surface of the bilayer causes slight shift of the fluid-gel transformation to a lower temperature, compared to the bulk bilayer case.

  12. Coarse-grained/molecular mechanics of the TAS2R38 bitter taste receptor: experimentally-validated detailed structural prediction of agonist binding.

    PubMed

    Marchiori, Alessandro; Capece, Luciana; Giorgetti, Alejandro; Gasparini, Paolo; Behrens, Maik; Carloni, Paolo; Meyerhof, Wolfgang

    2013-01-01

    Bitter molecules in humans are detected by ∼25 G protein-coupled receptors (GPCRs). The lack of atomic resolution structure for any of them is complicating an in depth understanding of the molecular mechanisms underlying bitter taste perception. Here, we investigate the molecular determinants of the interaction of the TAS2R38 bitter taste receptor with its agonists phenylthiocarbamide (PTC) and propylthiouracil (PROP). We use the recently developed hybrid Molecular Mechanics/Coarse Grained (MM/CG) method tailored specifically for GPCRs. The method, through an extensive exploration of the conformational space in the binding pocket, allows the identification of several residues important for agonist binding that would have been very difficult to capture from the standard bioinformatics/docking approach. Our calculations suggest that both agonists bind to Asn103, Phe197, Phe264 and Trp201, whilst they do not interact with the so-called extra cellular loop 2, involved in cis-retinal binding in the GPCR rhodopsin. These predictions are consistent with data sets based on more than 20 site-directed mutagenesis and functional calcium imaging experiments of TAS2R38. The method could be readily used for other GPCRs for which experimental information is currently lacking.

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

    PubMed

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

    2016-04-14

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

  14. Interrogating Nucleosome Positioning Through Coarse-Grain Molecular Simulation

    NASA Astrophysics Data System (ADS)

    Freeman, Gordon S.; Hinckley, Daniel M.; Ortiz, Vanessa; de Pablo, Juan J.

    2012-02-01

    Nucleosome positioning plays a crucial role in biology. As the fundamental unit in chromosome structure, the nucleosome core particle (NCP) binds to approximately 147 DNA base pairs. The location of bound NCPs in the genome, therefore, affects gene expression. The specific positioning of NCPs has been experimentally probed and competing viewpoints have been presented in the literature. Models for nucleosome positioning based on sequence-dependent flexibility (a genomic ``code" for nucleosome positioning) have been demonstrated to explain available experimental data. However, so do statistical models with no built-in sequence preference; the driving force for NCP positioning therefore remains an open question. We use a coarse-grain model for the NCP in combination with advanced sampling techniques to probe the sequence preference of NCPs. We present a method for determining the relative affinity of two DNA sequences for the NCP and use this method to compare high- and low-affinity sequences. We discuss several coarse-grain protein models with varying level of detail to examine the impact of model resolution on the agreement of our results with experimental evidence. We also investigate the dynamics of the NCP-DNA complex and their dependence on system characteristics.

  15. Development of Multiscale Materials Modeling Techniques and Coarse- Graining Strategies for Predicting Materials Degradation in Extreme Irradiation Environments

    SciTech Connect

    Wirth, Brian

    2016-01-12

    Exposure of metallic structural materials to irradiation environments results in significant microstructural evolution, property changes and performance degradation, which limits the extended operation of current generation light water reactors and restricts the design of advanced fission and fusion reactors [1-8]. This effect of irradiation on materials microstructure and properties is a classic example of an inherently multiscale phenomenon, as schematically illustrated in Figure 1a. Pertinent processes range from the atomic nucleus to structural component length scales, spanning more than 15 orders of magnitude. Time scales bridge more than 22 orders of magnitude, with the shortest being less than a femtosecond [1,8]. Further, the mix of radiation-induced features formed and the corresponding property degradation depend on a wide range of material and irradiation variables. This emphasizes the importance of closely integrating models with high-resolution experimental characterization of the evolving radiation- damaged microstructure, including measurements performed in-situ during irradiation. In this article, we review some recent successes through the use of closely coordinated modeling and experimental studies of the defect cluster evolution in irradiated body-centered cubic materials, followed by a discussion of outstanding challenges still to be addressed, which are necessary for the development of comprehensive models of radiation effects in structural materials.

  16. Electronically coarse-grained molecular dynamics using quantum Drude oscillators

    NASA Astrophysics Data System (ADS)

    Jones, A. P.; Crain, J.; Cipcigan, F. S.; Sokhan, V. P.; Modani, M.; Martyna, G. J.

    2013-12-01

    Standard molecular dynamics (MD) simulations generally make use of a basic description of intermolecular forces which consists of fixed, pairwise, atom-centred Coulomb, van der Waals and short-range repulsive terms. Important interactions such as many-body polarisation and many-body dispersion which are sensitive to changes in the environment are usually neglected, and their effects treated effectively within mean-field approximations to reproduce a single thermodynamic state point or physical environment. This leads to difficulties in modelling the complex interfaces of interest today where the behaviour may be quite different from the regime of parameterisation. Here, we describe the construction and properties of a Gaussian coarse-grained electronic structure, which naturally generates many-body polarisation and dispersion interactions. The electronic structure arises from a fully quantum mechanical treatment of a set of distributed quantum Drude oscillators (QDOs), harmonic atoms which interact with each other and other moieties via electrostatic (Coulomb) interactions; this coarse-grained approach is capable of describing many-body polarisation and dispersion but not short-range interactions which must be parametrised. We describe how on-the-fly forces due to this exchange-free Gaussian model may be generated with linear scale in the number of atoms in the system using an adiabatic path integral molecular dynamics for quantum Drude oscillators technique (APIMD-QDO). We demonstrate the applicability of the QDO approach to realistic systems via a study of the liquid-vapour interface of water.

  17. Structural Changes in Lipid Vesicles Generated by the Shock Blast Waves: Coarse-Grained Molecular Dynamics Simulation

    DTIC Science & Technology

    2013-11-01

    mechanism of shock-wave-induced damage to phospholipid vesicles (liposomes) as the simplified generic model for the cell membranes . Vesicles or liposomes...are composed of phospholipids that encapsulate a core region of water inside a hydrophobic membrane . Simulation studies of vesicles have some clear...molecular dynamics (MD). However, the complexity of the atomistic force fields limits them to membrane patches and vesicles some tens of nanometers in

  18. A coarse grained perturbation theory for the Large Scale Structure, with cosmology and time independence in the UV

    SciTech Connect

    Manzotti, Alessandro; Peloso, Marco; Pietroni, Massimo; Viel, Matteo; Villaescusa-Navarro, Francisco E-mail: peloso@physics.umn.edu E-mail: viel@oats.inaf.it

    2014-09-01

    Standard cosmological perturbation theory (SPT) for the Large Scale Structure (LSS) of the Universe fails at small scales (UV) due to strong nonlinearities and to multistreaming effects. In ref. [1] a new framework was proposed in which the large scales (IR) are treated perturbatively while the information on the UV, mainly small scale velocity dispersion, is obtained by nonlinear methods like N-body simulations. Here we develop this approach, showing that it is possible to reproduce the fully nonlinear power spectrum (PS) by combining a simple (and fast) 1-loop computation for the IR scales and the measurement of a single, dominant, correlator from N-body simulations for the UV ones. We measure this correlator for a suite of seven different cosmologies, and we show that its inclusion in our perturbation scheme reproduces the fully non-linear PS with percent level accuracy, for wave numbers up to k∼ 0.4 h Mpc{sup -1} down to 0z=. We then show that, once this correlator has been measured in a given cosmology, there is no need to run a new simulation for a different cosmology in the suite. Indeed, by rescaling this correlator by a proper function computable in SPT, the reconstruction procedure works also for the other cosmologies and for all redshifts, with comparable accuracy. Finally, we clarify the relation of this approach to the Effective Field Theory methods recently proposed in the LSS context.

  19. Self-assembly of the beta2-microglobulin NHVTLSQ peptide using a coarse-grained protein model reveals a beta-barrel species.

    PubMed

    Song, Wei; Wei, Guanghong; Mousseau, Normand; Derreumaux, Philippe

    2008-04-10

    Although a wide variety of proteins can assemble into amyloid fibrils, the structure of the early oligomeric species on the aggregation pathways remains unknown at an atomic level of detail. In this paper we report, using molecular dynamics simulations with the OPEP coarse-grained force field, the free energy landscape of a tetramer and a heptamer of the beta2-microglobulin NHVTLSQ peptide. On the basis of a total of more than 17 ns trajectories started from various states, we find that both species are in equilibrium between amorphous and well-ordered aggregates with cross-beta-structure, a perpendicular bilayer beta-sheet, and, for the heptamer, six- or seven-stranded closed and open beta-barrels. Moreover, analysis of the heptamer trajectories shows that the perpendicular bilayer beta-sheet is one possible precursor of the beta-barrel, but that this barrel can also be formed from a twisted monolayer beta-sheet with successive addition of chains. Comparison with previous aggregation simulations and the fact that nature constructs transmembrane beta-sheet proteins with pores open the possibility that beta-barrels with small inner diameters may represent a common intermediate during the early steps of aggregation.

  20. Coarse-grained Simulations of Conformational Changes in Multidrug Resistance Transporters

    NASA Astrophysics Data System (ADS)

    Jewel, S. M. Yead; Dutta, Prashanta; Liu, Jin

    2016-11-01

    The overexpression of multidrug resistance (MDR) systems on the gram negative bacteria causes serious problems for treatment of bacterial infectious diseases. The system effectively pumps the antibiotic drugs out of the bacterial cells. During the pumping process one of the MDR components, AcrB undergoes a series of large-scale conformational changes which are responsible for drug recognition, binding and expelling. All-atom simulations are unable to capture those conformational changes because of computational cost. Here, we implement a hybrid coarse-grained force field that couples the united-atom protein models with the coarse-grained MARTINI water/lipid, to investigate the proton-dependent conformational changes of AcrB. The simulation results in early stage ( 100 ns) of proton-dependent conformational changes agree with all-atom simulations, validating the coarse-grained model. The coarse-grained force field allows us to explore the process in microsecond simulations. Starting from the crystal structures of Access(A)/Binding(B)/Extrusion(E) monomers in AcrB, we find that deprotonation of Asp407 and Asp408 in monomer E causes a series of large-scale conformational changes from ABE to AAA in absence of drug molecules, which is consistent with experimental findings. This work is supported by NIH Grant: 1R01GM122081-01.

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

    SciTech Connect

    Harmandaris, Vagelis; Katsoulakis, Markos; Plecháč, Petr

    2016-06-01

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

  2. Mean-field coarse-grained model for poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer systems.

    PubMed

    García Daza, Fabián A; Colville, Alexander J; Mackie, Allan D

    2015-03-31

    The microscopic modeling of surfactant systems is of the utmost importance in understanding the mechanisms related to the micellization process because it allows for prediction and comparison with experimental data of diverse equilibrium system properties. In this work, we present a coarse-grained model for Pluronics, a trademarked type of triblock copolymer, from simulations based on a single-chain mean-field theory (SCMF). This microscopic model is used to quantify the micellization process of these nonionic surfactants at 37 °C and has been shown to be able to quantitatively reproduce experimental data of the critical micelle concentration (CMC) along with other equilibrium properties. In particular, these results correctly capture the experimental behavior with respect to the lengths of the hydrophobic and hydrophilic moieties of the surfactants for low and medium hydrophobicities. However, for the more highly hydrophobic systems with low CMCs, a deviation is found which has been previously attributed to nonequilibrium effects in the experimental data (Garcı́a Daza, F. A.; Mackie, A. D. Low Critical Micelle Concentration Discrepancy between Theory and Experiment. J. Phys. Chem. Lett. 2014, 5, 2027-2032).

  3. Fractal network dimension and viscoelastic powerlaw behavior: I. A modeling approach based on a coarse-graining procedure combined with shear oscillatory rheometry

    NASA Astrophysics Data System (ADS)

    Posnansky, Oleg; Guo, Jing; Hirsch, Sebastian; Papazoglou, Sebastian; Braun, Jürgen; Sack, Ingolf

    2012-06-01

    Recent advances in dynamic elastography and biorheology have revealed that the complex shear modulus, G*, of various biological soft tissues obeys a frequency-dependent powerlaw. This viscoelastic powerlaw behavior implies that mechanical properties are communicated in tissue across the continuum of scales from microscopic to macroscopic. For deriving constitutive constants from the dispersion of G* in a biological tissue, a hierarchical fractal model is introduced that accounts for multiscale networks. Effective-media powerlaw constants are derived by a constitutive law based on cross-linked viscoelastic clusters embedded in a rigid environment. The spatial variation of G* is considered at each level of hierarchy by an iterative coarse-graining procedure. The establishment of cross-links in this model network is associated with an increasing fractal dimension and an increasing viscoelastic powerlaw exponent. This fundamental relationship between shear modulus dynamics and fractal dimension of the mechanical network in tissue is experimentally reproduced in phantoms by applying shear oscillatory rheometry to layers of tangled paper strips embedded in agarose gel. Both model and experiments demonstrate the sensitivity of G* to the density of the mechanical network in tissue, corroborating disease-related alterations of the viscoelastic powerlaw exponent in human parenchyma demonstrated by in vivo elastography.

  4. Aggregation in complex triacylglycerol oils: coarse-grained models, nanophase separation, and predicted x-ray intensities

    NASA Astrophysics Data System (ADS)

    Quinn, Bonnie; Peyronel, Fernanda; Gordon, Tyler; Marangoni, Alejandro; Hanna, Charles B.; Pink, David A.

    2014-11-01

    Triacylglycerols (TAGs) are biologically important molecules which form crystalline nanoplatelets (CNPs) and, ultimately, fat crystal networks in edible oils. Characterizing the self-assembled hierarchies of these networks is important to understanding their functionality and oil binding capacity. We have modelled CNPs in multicomponent oils and studied their aggregation. The oil comprises (a) a liquid componentt, and (b) components which phase separately on a nano-scale (nano-phase separation) to coat the surfaces of the CNPs impenetrably, either isotropically or anisotropically, with either liquid-like coatings or crystallites, forming a coating of thickness Δ. We modelled three cases: (i) liquid-liquid nano-phase separation, (ii) solid-liquid nano-phase separation, with CNPs coated isotropically, and (iii) CNPs coated anisotropically. The models were applied to mixes of tristearin and triolein with fully hydrogenated canola oil, shea butter with high oleic sunflower oil, and cotton seed oil. We performed Monte Carlo simulations, computed structure functions and concluded: (1) three regimes arose: (a) thin coating regime, Δ \\lt 0.0701 u (b) transition regime, 0.0701 u≤slant Δ ≤slant 0.0916 u and (c) thick coating regime, Δ \\gt 0.0916 u . (arbitrary units, u) (2) The thin coating regime exhibits 1D TAGwoods, which aggregate, via DLCA/RLCA, into fractal structures which are uniformly distributed in space. (3) In the thick coating regime, for an isotropic coating, TAGwoods are not formed and coated CNPs will not aggregate but will be uniformly distributed in space. For anisotropic coating, TAGwoods can be formed and might form 1D strings but will not form DLCA/RLCA clusters. (4) The regimes are, approximately: thin coating, 0\\lt Δ \\lt 7.0 \\text{nm} transition regime, 7.0\\ltΔ \\lt 9.2 \\text{nm} and thick coating, Δ \\gt 9.2 \\text{nm} (5) The minimum minority TAG concentration required to undergo nano-phase separation is, approximately, 0.29% (thin

  5. Aggregation in complex triacylglycerol oils: coarse-grained models, nanophase separation, and predicted x-ray intensities.

    PubMed

    Quinn, Bonnie; Peyronel, Fernanda; Gordon, Tyler; Marangoni, Alejandro; Hanna, Charles B; Pink, David A

    2014-11-19

    Triacylglycerols (TAGs) are biologically important molecules which form crystalline nanoplatelets (CNPs) and, ultimately, fat crystal networks in edible oils. Characterizing the self-assembled hierarchies of these networks is important to understanding their functionality and oil binding capacity. We have modelled CNPs in multicomponent oils and studied their aggregation. The oil comprises (a) a liquid component, and (b) components which phase separately on a nano-scale (nano-phase separation) to coat the surfaces of the CNPs impenetrably, either isotropically or anisotropically, with either liquid-like coatings or crystallites, forming a coating of thickness ?. We modelled three cases: (i) liquid?liquid nano-phase separation, (ii) solid?liquid nano-phase separation, with CNPs coated isotropically, and (iii) CNPs coated anisotropically. The models were applied to mixes of tristearin and triolein with fully hydrogenated canola oil, shea butter with high oleic sunflower oil, and cotton seed oil. We performed Monte Carlo simulations, computed structure functions and concluded: (1) three regimes arose: (a) thin coating regime, Δ < 0.0701 u (b) transition regime, 0.0701 u ≤ Δ ≤ 0.0916 u and (c) thick coating regime, Δ > 0.0916 u. (arbitrary units, u) (2) The thin coating regime exhibits 1D TAGwoods, which aggregate, via DLCA/RLCA, into fractal structures which are uniformly distributed in space. (3) In the thick coating regime, for an isotropic coating, TAGwoods are not formed and coated CNPs will not aggregate but will be uniformly distributed in space. For anisotropic coating, TAGwoods can be formed and might form 1D strings but will not form DLCA/RLCA clusters. (4) The regimes are, approximately: thin coating, 0 < Δ < 7.0 nm transition regime, 7.0 < Δ < 9.2 nm and thick coating, Δ > 9.2 nm (5) The minimum minority TAG concentration required to undergo nano-phase separation is, approximately, 0.29% (thin coatings) and 0.94% (thick coatings). Minority

  6. Understanding the Functional Roles of Multiple Extracellular Domains in Cell Adhesion Molecules with a Coarse-Grained Model.

    PubMed

    Chen, Jiawen; Wu, Yinghao

    2017-04-07

    Intercellular contacts in multicellular organisms are maintained by membrane receptors called cell adhesion molecules (CAMs), which are expressed on cell surfaces. One interesting feature of CAMs is that almost all of their extracellular regions contain repeating copies of structural domains. It is not clear why so many extracellular domains need to be evolved through natural selection. We tackled this problem by computational modeling. A generic model of CAMs was constructed based on the domain organization of neuronal CAM, which is engaged in maintaining neuron-neuron adhesion in central nervous system. By placing these models on a cell-cell interface, we developed a Monte-Carlo simulation algorithm that incorporates both molecular factors including conformational changes of CAMs and cellular factor including fluctuations of plasma membranes to approach the physical process of CAM-mediated adhesion. We found that the presence of multiple domains at the extracellular region of a CAM plays a positive role in regulating its trans-interaction with other CAMs from the opposite side of cell surfaces. The trans-interaction can further be facilitated by the intramolecular contacts between different extracellular domains of a CAM. Finally, if more than one CAM is introduced on each side of cell surfaces, the lateral binding (cis-interactions) between these CAMs will positively correlate with their trans-interactions only within a small energetic range, suggesting that cell adhesion is an elaborately designed process in which both trans- and cis-interactions are fine-tuned collectively by natural selection. In short, this study deepens our general understanding of the molecular mechanisms of cell adhesion. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Coarse-graining RNA nanostructures for molecular dynamics simulations

    PubMed Central

    Paliy, Maxim; Melnik, Roderick; Shapiro, Bruce A

    2013-01-01

    A series of coarse-grained models have been developed for study of the molecular dynamics of RNA nanostructures. The models in the series have one to three beads per nucleotide and include different amounts of detailed structural information. Such a treatment allows us to reach, for systems of thousands of nucleotides, a time scale of microseconds (i.e. by three orders of magnitude longer than in full atomistic modeling) and thus to enable simulations of large RNA polymers in the context of bionanotechnology. We find that the three-beads-per-nucleotide models, described by a set of just a few universal parameters, are able to describe different RNA conformations and are comparable in structural precision to the models where detailed values of the backbone P-C4′ dihedrals taken from a reference structure are included. These findings are discussed in the context of RNA conformation classes. PMID:20577037

  8. Coarse graining atomistic simulations of plastically deforming amorphous solids

    NASA Astrophysics Data System (ADS)

    Hinkle, Adam R.; Rycroft, Chris H.; Shields, Michael D.; Falk, Michael L.

    2017-05-01

    The primary mode of failure in disordered solids results from the formation and persistence of highly localized regions of large plastic strains known as shear bands. Continuum-level field theories capable of predicting this mechanical response rely upon an accurate representation of the initial and evolving states of the amorphous structure. We perform molecular dynamics simulations of a metallic glass and propose a methodology for coarse graining discrete, atomistic quantities, such as the potential energies of the elemental constituents. A strain criterion is established and used to distinguish the coarse-grained degrees-of-freedom inside the emerging shear band from those of the surrounding material. A signal-to-noise ratio provides a means of evaluating the strength of the signal of the shear band as a function of the coarse graining. Finally, we investigate the effect of different coarse graining length scales by comparing a two-dimensional, numerical implementation of the effective-temperature description in the shear transformation zone (STZ) theory with direct molecular dynamics simulations. These comparisons indicate the coarse graining length scale has a lower bound, above which there is a high level of agreement between the atomistics and the STZ theory, and below which the concept of effective temperature breaks down.

  9. Conformation of a coarse-grained protein chain (an aspartic acid protease) model in effective solvent by a bond-fluctuating Monte Carlo simulation

    NASA Astrophysics Data System (ADS)

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

    2008-03-01

    In a coarse-grained description of a protein chain, all of the 20 amino acid residues can be broadly divided into three groups: Hydrophobic (H) , polar (P) , and electrostatic (E) . A protein can be described by nodes tethered in a chain with a node representing an amino acid group. Aspartic acid protease consists of 99 residues in a well-defined sequence of H , P , and E nodes tethered together by fluctuating bonds. The protein chain is placed on a cubic lattice where empty lattice sites constitute an effective solvent medium. The amino groups (nodes) interact with the solvent (S) sites with appropriate attractive (PS) and repulsive (HS) interactions with the solvent and execute their stochastic movement with the Metropolis algorithm. Variations of the root mean square displacements of the center of mass and that of its center node of the protease chain and its gyration radius with the time steps are examined for different solvent strength. The structure of the protease swells on increasing the solvent interaction strength which tends to enhance the relaxation time to reach the diffusive behavior of the chain. Equilibrium radius of gyration increases linearly on increasing the solvent strength: A slow rate of increase in weak solvent regime is followed by a faster swelling in stronger solvent. Variation of the gyration radius with the time steps suggests that the protein chain moves via contraction and expansion in a somewhat quasiperiodic pattern particularly in strong solvent.

  10. Coarse-grained molecular dynamics simulation of self-assembly and surface adsorption of ionic surfactants using an implicit water model.

    PubMed

    Wang, Shihu; Larson, Ronald G

    2015-02-03

    We perform coarse-grained molecular dynamics simulations for sodium dodecyl sulfate (SDS) surfactant using a modification of the Dry Martini force field (Arnarez et al. 2014) with implicit water. After inclusion of particle mesh Ewald (PME) electrostatics, an artificially high dielectric constant for water (ε(r) = 150), and reparameterization, we obtain structural and thermodynamic properties of SDS micelles that are close to those obtained from the standard Martini force field with explicit water, which in turn match those of atomistic simulations. The gains in computational efficiency obtained by removing explicit water allow direct simulations of the self-assembly of SDS in solution. We observe surfactant exchange among micelles and micelle fission and fusion and obtain realistic, equilibrated micelle size distributions at modest computational cost, as well as a transition to cylindrical micelles at high surfactant concentration or with added salt. We further apply this parametrized force field to study the adsorption of SDS onto hydrophobic surfaces and calculate the adsorption kinetics and equilibrium adsorption isotherm. The greatly increased speed of computation of surfactant self-assembly made possible by this Dry Martini method should allow future simulation of competitive adsorption of multiple surfactant species to surfaces, as well as simulation of micellar shape transitions.

  11. Coarse grain forces in star polymer melts.

    PubMed

    Liu, L; den Otter, W K; Briels, W J

    2014-10-21

    An analysis is presented of forces acting on the centers of mass of three-armed star polymers in the molten state. The arms consist of 35 Kremer-Grest beads, which is slightly larger than needed for one entanglement mass. For a given configuration of the centers of mass, instantaneous forces fluctuate wildly around averages which are two orders of magnitude smaller than their root mean square deviations. Average forces are well described by an implicit many-body potential, while pair models fail completely. The fluctuating forces are modelled by means of dynamical variables quantifying the degree of mixing of the various polymer pairs. All functions and parameters in a coarse grain model based on these concepts are obtained from the underlying small scale simulation. The coarse model reproduces both the diffusion coefficient and the shear relaxation modulus. Ways to improve the model suggest themselves on the basis of our findings.

  12. A refined polarizable water model for the coarse-grained MARTINI force field with long-range electrostatic interactions

    NASA Astrophysics Data System (ADS)

    Michalowsky, Julian; Schäfer, Lars V.; Holm, Christian; Smiatek, Jens

    2017-02-01

    We present a refined version of the polarizable Martini water model - coined refPOL - designed specifically for the use with long-range electrostatics. The refPOL model improves the agreement with the experimentally measured dielectric constant and the mass density of water at room temperature compared to the original polarizable Martini water force field when particle mesh Ewald electrostatics are employed. Our study reveals that the model remains applicable with various commonly used settings for the non-bonded interactions, including reaction field electrostatics. The oil/water partitioning behavior of uncharged Martini bead types is thoroughly investigated: Lennard-Jones interactions between the refPOL model and the remaining Martini beads are adjusted to reproduce the hydration free energies obtained with the original polarizable water model, while free energies of solvation in apolar media remain unchanged. The cross-interactions with charged bead types are parameterized to agree with the experimentally observed area per lipid of a fully solvated dipalmitoylphosphatidylcholine bilayer. We additionally verify the model by analyzing the potentials of mean force between different sample pairs in refPOL water and comparing the results to reference data obtained using the original polarizable Martini water model as well as fully atomistic simulations. Based on the results, we suggest to replace the original polarizable Martini water model with the new refPOL model for future applications.

  13. A Coarse-Grained Biophysical Model of E. coli and Its Application to Perturbation of the rRNA Operon Copy Number

    PubMed Central

    Tadmor, Arbel D.; Tlusty, Tsvi

    2008-01-01

    We propose a biophysical model of Escherichia coli that predicts growth rate and an effective cellular composition from an effective, coarse-grained representation of its genome. We assume that E. coli is in a state of balanced exponential steady-state growth, growing in a temporally and spatially constant environment, rich in resources. We apply this model to a series of past measurements, where the growth rate and rRNA-to-protein ratio have been measured for seven E. coli strains with an rRNA operon copy number ranging from one to seven (the wild-type copy number). These experiments show that growth rate markedly decreases for strains with fewer than six copies. Using the model, we were able to reproduce these measurements. We show that the model that best fits these data suggests that the volume fraction of macromolecules inside E. coli is not fixed when the rRNA operon copy number is varied. Moreover, the model predicts that increasing the copy number beyond seven results in a cytoplasm densely packed with ribosomes and proteins. Assuming that under such overcrowded conditions prolonged diffusion times tend to weaken binding affinities, the model predicts that growth rate will not increase substantially beyond the wild-type growth rate, as indicated by other experiments. Our model therefore suggests that changing the rRNA operon copy number of wild-type E. coli cells growing in a constant rich environment does not substantially increase their growth rate. Other observations regarding strains with an altered rRNA operon copy number, such as nucleoid compaction and the rRNA operon feedback response, appear to be qualitatively consistent with this model. In addition, we discuss possible design principles suggested by the model and propose further experiments to test its validity. PMID:18437222

  14. A Coarse-Grained Biophysical Model of E. coli and Its Application to Perturbation of the rRNA Operon Copy Number

    NASA Astrophysics Data System (ADS)

    Tadmor, Arbel

    2009-03-01

    In this work a biophysical model of Escherichia coli is presented that predicts growth rate and an effective cellular composition from an effective, coarse-grained representation of its genome. We assume that E. coli is in a state of balanced exponential steady-state growth, growing in a temporally and spatially constant environment, rich in resources. We apply this model to a series of past measurements, where the growth rate and rRNA-to-protein ratio have been measured for seven E. coli strains with an rRNA operon copy number ranging from one to seven (the wild-type copy number). These experiments show that growth rate markedly decreases for strains with fewer than six copies. Using the model, we were able to reproduce these measurements. We show that the model that best fits these data suggests that the volume fraction of macromolecules inside E. coli is not fixed when the rRNA operon copy number is varied. Moreover, the model predicts that increasing the copy number beyond seven results in a cytoplasm densely packed with ribosomes and proteins. Assuming that under such overcrowded conditions prolonged diffusion times tend to weaken binding affinities, the model predicts that growth rate will not increase substantially beyond the wild-type growth rate, as indicated by other experiments. Our model therefore suggests that changing the rRNA operon copy number of wild-type E. coli cells growing in a constant rich environment does not substantially increase their growth rate. Other observations regarding strains with an altered rRNA operon copy number, such as nucleoid compaction and the rRNA operon feedback response, appear to be qualitatively consistent with this model. In addition, we discuss possible design principles suggested by the model and propose further experiments to test its validity.

  15. Rapid Simulation of Blast Wave Propagation in Built Environments Using Coarse-Grain Based Intelligent Modeling Methods

    DTIC Science & Technology

    2011-04-01

    experiments was performed using an artificial neural network to try to capture the nonlinearities. The radial Gaussian artificial neural network system...Modeling Blast-Wave Propagation using Artificial Neural Network Methods‖, in International Journal of Advanced Engineering Informatics, Elsevier

  16. Coarse-grained model for N2-N relaxation in hypersonic shock conditions using two-dimensional bins

    NASA Astrophysics Data System (ADS)

    Zhu, Tong; Li, Zheng; Levin, Deborah A.

    2016-11-01

    A high fidelity internal energy relaxation model for N2-N suitable for use in direct simulation Monte Carlo (DSMC) modeling of chemically reacting flows is proposed. A novel two-dimensional binning approach with variable bin energy resolutions in the rotational and vibrational modes is developed for treating the internal mode of N2. Both bin-to-bin and state-specific relaxation cross sections are obtained using the molecular dynamics/quasi-classical trajectory (MD/QCT) method with two potential energy surfaces as well as the state-specific database of Jaffe et al. The 99 bin model is used in homogeneous DSMC relaxation simulations and is found to be able to recover the state-specific master equation results of Panesi et al. when the Jaffe state-specific cross sections are used. Rotational relaxation energy profiles and relaxation times obtained using the ReaxFF and Jaffe potential energy surfaces (PESs) are in general agreement but there are larger differences between the vibrational relaxation times. These differences become smaller as the translational temperature increases because the difference in the PES energy barrier becomes less important.

  17. Acceleration of coarse grain molecular dynamics on GPU architectures.

    PubMed

    Shkurti, Ardita; Orsi, Mario; Macii, Enrico; Ficarra, Elisa; Acquaviva, Andrea

    2013-04-05

    Coarse grain (CG) molecular models have been proposed to simulate complex systems with lower computational overheads and longer timescales with respect to atomistic level models. However, their acceleration on parallel architectures such as graphic processing units (GPUs) presents original challenges that must be carefully evaluated. The objective of this work is to characterize the impact of CG model features on parallel simulation performance. To achieve this, we implemented a GPU-accelerated version of a CG molecular dynamics simulator, to which we applied specific optimizations for CG models, such as dedicated data structures to handle different bead type interactions, obtaining a maximum speed-up of 14 on the NVIDIA GTX480 GPU with Fermi architecture. We provide a complete characterization and evaluation of algorithmic and simulated system features of CG models impacting the achievable speed-up and accuracy of results, using three different GPU architectures as case studies. Copyright © 2012 Wiley Periodicals, Inc.

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

    PubMed Central

    Schneider, Anna R.; Geissler, Phillip L.

    2013-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

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

  20. Collapse transition of a hydrophobic self-avoiding random walk in a coarse-grained model solvent.

    PubMed

    Gaudreault, Mathieu; Viñals, Jorge

    2009-08-01

    In order to study solvation effects on protein folding, we analyze the collapse transition of a self-avoiding random walk composed of hydrophobic segments that is embedded in a lattice model of a solvent. As expected, hydrophobic interactions lead to an attractive potential of mean force among chain segments. As a consequence, the random walk in solvent undergoes a collapse transition at a higher temperature than in its absence. Chain collapse is accompanied by the formation of a region depleted of solvent around the chain. In our simulation, the depleted region at collapse is as large as our computational domain.

  1. A coarse-grained model of the myofibril: Overall dynamics and the evolution of sarcomere non-uniformities

    NASA Astrophysics Data System (ADS)

    Givli, Sefi; Bhattacharya, Kaushik

    2009-02-01

    A theoretical framework for predicting the macroscopic behavior of a muscle myofibril based on the collective behavior of sarcomeres is presented. The analysis is accomplished by rigorously transforming the nonlinear dynamics of an assemblage of sarcomeres into a partial differential equation for the probability distribution function of sarcomere lengths in the presence of stochastic temporal fluctuations and biological variability. This enables the study of biologically relevant specimens with reasonable computational effort. The model is validated by a comparison to quantitative experimental results. Further, it reproduces experimental observations that cannot be explained by standard single sarcomere models, and provides new insights into muscle function and muscle damage during cyclic loading. We show that the accumulation of overstretched sarcomeres, which is related to muscle damage, depends on a delicate interplay between the dynamics of a large number of sarcomeres and the load characteristics, such as its magnitude and frequency. Further, we show that biological variability rather than stochastic fluctuations are the main source for sarcomere non-uniformities.

  2. Chain architecture and micellization: A mean-field coarse-grained model for poly(ethylene oxide) alkyl ether surfactants

    SciTech Connect

    García Daza, Fabián A.; Mackie, Allan D.; Colville, Alexander J.

    2015-03-21

    Microscopic modeling of surfactant systems is expected to be an important tool to describe, understand, and take full advantage of the micellization process for different molecular architectures. Here, we implement a single chain mean field theory to study the relevant equilibrium properties such as the critical micelle concentration (CMC) and aggregation number for three sets of surfactants with different geometries maintaining constant the number of hydrophobic and hydrophilic monomers. The results demonstrate the direct effect of the block organization for the surfactants under study by means of an analysis of the excess energy and entropy which can be accurately determined from the mean-field scheme. Our analysis reveals that the CMC values are sensitive to branching in the hydrophilic head part of the surfactant and can be observed in the entropy-enthalpy balance, while aggregation numbers are also affected by splitting the hydrophobic tail of the surfactant and are manifested by slight changes in the packing entropy.

  3. Chain architecture and micellization: A mean-field coarse-grained model for poly(ethylene oxide) alkyl ether surfactants

    NASA Astrophysics Data System (ADS)

    García Daza, Fabián A.; Colville, Alexander J.; Mackie, Allan D.

    2015-03-01

    Microscopic modeling of surfactant systems is expected to be an important tool to describe, understand, and take full advantage of the micellization process for different molecular architectures. Here, we implement a single chain mean field theory to study the relevant equilibrium properties such as the critical micelle concentration (CMC) and aggregation number for three sets of surfactants with different geometries maintaining constant the number of hydrophobic and hydrophilic monomers. The results demonstrate the direct effect of the block organization for the surfactants under study by means of an analysis of the excess energy and entropy which can be accurately determined from the mean-field scheme. Our analysis reveals that the CMC values are sensitive to branching in the hydrophilic head part of the surfactant and can be observed in the entropy-enthalpy balance, while aggregation numbers are also affected by splitting the hydrophobic tail of the surfactant and are manifested by slight changes in the packing entropy.

  4. Coarse-graining approach to quantum cosmology

    NASA Astrophysics Data System (ADS)

    Calzetta, Esteban; Castagnino, Mario; Scoccimarro, Román

    1992-04-01

    We consider a Friedmann-Robertson-Walker model with both classical radiation and a massive (conformally coupled) quantum scalar field in the framework of quantum cosmology. We define a density matrix and introduce a notion of ``relevance'' which splits this density matrix into a ``relevant'' and an ``irrelevant'' part. A ``generalized coarse-graining method'' is used to obtain the evolution (in Robertson-Walker a ``time'') of the relevant density matrix, taking into account the back reaction of the irrelevant variables. We discuss the physical basis for the choice of a concept of relevance, and the features of cosmic evolution brought forward by the effective dynamics. In the limit of ``small universes,'' the relevant subdynamics is dissipative.

  5. Coarse-grained Simulations of Viral Assembly

    NASA Astrophysics Data System (ADS)

    Elrad, Oren M.

    2011-12-01

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

  6. Enhanced Sampling of an Atomic Model with Hybrid Nonequilibrium Molecular Dynamics-Monte Carlo Simulations Guided by a Coarse-Grained Model.

    PubMed

    Chen, Yunjie; Roux, Benoît

    2015-08-11

    Molecular dynamics (MD) trajectories based on a classical equation of motion provide a straightforward, albeit somewhat inefficient approach, to explore and sample the configurational space of a complex molecular system. While a broad range of techniques can be used to accelerate and enhance the sampling efficiency of classical simulations, only algorithms that are consistent with the Boltzmann equilibrium distribution yield a proper statistical mechanical computational framework. Here, a multiscale hybrid algorithm relying simultaneously on all-atom fine-grained (FG) and coarse-grained (CG) representations of a system is designed to improve sampling efficiency by combining the strength of nonequilibrium molecular dynamics (neMD) and Metropolis Monte Carlo (MC). This CG-guided hybrid neMD-MC algorithm comprises six steps: (1) a FG configuration of an atomic system is dynamically propagated for some period of time using equilibrium MD; (2) the resulting FG configuration is mapped onto a simplified CG model; (3) the CG model is propagated for a brief time interval to yield a new CG configuration; (4) the resulting CG configuration is used as a target to guide the evolution of the FG system; (5) the FG configuration (from step 1) is driven via a nonequilibrium MD (neMD) simulation toward the CG target; (6) the resulting FG configuration at the end of the neMD trajectory is then accepted or rejected according to a Metropolis criterion before returning to step 1. A symmetric two-ends momentum reversal prescription is used for the neMD trajectories of the FG system to guarantee that the CG-guided hybrid neMD-MC algorithm obeys microscopic detailed balance and rigorously yields the equilibrium Boltzmann distribution. The enhanced sampling achieved with the method is illustrated with a model system with hindered diffusion and explicit-solvent peptide simulations. Illustrative tests indicate that the method can yield a speedup of about 80 times for the model system and up

  7. Polymer translocation through a nanopore induced by adsorption: Monte Carlo simulation of a coarse-grained model

    NASA Astrophysics Data System (ADS)

    Milchev, Andrey; Binder, Kurt; Bhattacharya, Aniket

    2004-09-01

    Dynamic Monte Carlo simulation of a bead-spring model of flexible macromolecules threading through a very narrow pore in a very thin rigid membrane are presented, assuming at the cis side of the membrane a purely repulsive monomer-wall interaction, while the trans side is attractive. Two choices of monomer-wall attraction ɛ are considered, one choice is slightly below and the other slightly above the "mushroom to pancake" adsorption threshold ɛc for an infinitely long chain. Studying chain lengths N=32, 64, 128, and 256 and varying the number of monomers Ntrans (time t=0) that have already passed the pore when the simulation started, over a wide range, we find for ɛ<ɛc (nonadsorbing case) that the translocation probability varies proportional to ctrans=Ntrans(t=0)/N for small ctrans, while for ɛ>ɛc a finite number Ntrans(t=0) suffices that the translocation probability is close to unity. In the case ɛ<ɛc, however, the time it takes for those chains to get through the pore to complete the translocation process scales as τ∝N2.23±0.04. This result agrees with the suggestion of Chuang, Kantor, and Kardar [Phys. Rev. E 65, 011802 (2001)] that the translocation time is proportional to the Rouse time, that scales under good solvent condition as τRouse∝N2ν+1, with the excluded-volume exponent ν≈0.59 in d=3 dimensions. Our results hence disagree with the suggestions that the translocation time should scale as either N2 or N3. For ɛ>ɛc, we find that the translocation time scales as τ∝N1.65±0.08. We suggest a tentative scaling explanation for this result. Also the distribution of translocation times is obtained and discussed.

  8. Inferring a weighted elastic network from partial unfolding with coarse-grained simulations.

    PubMed

    de Mendonça, Matheus R; Rizzi, Leandro G; Contessoto, Vinicius; Leite, Vitor B P; Alves, Nelson A

    2014-01-01

    A number of studies have demonstrated that simple elastic network models can reproduce experimental B-factors, providing insights into the structure-function properties of proteins. Here, we report a study on how to improve an elastic network model and explore its performance by predicting the experimental B-factors. Elastic network models are built on the experimental Cα coordinates, and they only take the pairs of Cα atoms within a given cutoff distance rc into account. These models describe the interactions by elastic springs with the same force constant. We have developed a method based on numerical simulations with a simple coarse-grained force field, to attribute weights to these spring constants. This method considers the time that two Cα atoms remain connected in the network during partial unfolding, establishing a means of measuring the strength of each link. We examined two different coarse-grained force fields and explored the computation of these weights by unfolding the native structures.

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

    NASA Astrophysics Data System (ADS)

    Stanzione, Francesca; Jayaraman, Arthi

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

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

    PubMed

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

    2013-03-07

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

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