1,720,965 research outputs found
Computer Aided Distance Reconstruction in Single Molecule FRET Experiments through Combination with Dye Dynamics from Molecular Dynamics Simulations
No full textIn silico FRET from simulated dye dynamics
Full text linkAbstractSingle molecule fluorescence resonance energy transfer (smFRET) experiments probe molecular distances on the nanometer scale. In such experiments, distances are recorded from FRET transfer efficiencies via the Förster formula, E=1/(1+(R/R0)6).The energy transfer however also depends on the mutual orientation of the two dyes used as distance reporter. Since this information is typically inaccessible in FRET experiments, one has to rely on approximations, which reduce the accuracy of these distance measurements. A common approximation is an isotropic and uncorrelated dye orientation distribution.To assess the impact of such approximations, we present the algorithms and implementation of a computational toolkit for the simulation of smFRET on the basis of molecular dynamics (MD) trajectory ensembles. In this study, the dye orientation dynamics, which are used to determine dynamic FRET efficiencies, are extracted from MD simulations. In a subsequent step, photons and bursts are generated using a Monte Carlo algorithm.The application of the developed toolkit on a poly-proline system demonstrated good agreement between smFRET simulations and experimental results and therefore confirms our computational method. Furthermore, it enabled the identification of the structural basis of measured heterogeneity.The presented computational toolkit is written in Python, available as open-source, applicable to arbitrary systems and can easily be extended and adapted to further problems.Program summaryProgram title: md2fretCatalogue identifier: AENV_v1_0Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AENV_v1_0.htmlProgram obtainable from: CPC Program Library, Queen’s University, Belfast, N. IrelandLicensing provisions: GPLv3, the bundled SIMD friendly Mersenne twister implementation [1] is provided under the SFMT-License.No. of lines in distributed program, including test data, etc.: 317880No. of bytes in distributed program, including test data, etc.: 54774217Distribution format: tar.gzProgramming language: Python, Cython, C (ANSI C99).Computer: Any (see memory requirements).Operating system: Any OS with CPython distribution (e.g. Linux, MacOSX, Windows).Has the code been vectorised or parallelized?: Yes, in Ref. [2], 4 CPU cores were used.RAM: About 700MB per process for the simulation setup in Ref. [2].Classification: 16.1, 16.7, 23.External routines: Calculation of Rκ2-trajectories from GROMACS [3] MD trajectories requires the GromPy Python module described in Ref. [4] or a GROMACS 4.6 installation. The md2fret program uses a standard Python interpreter (CPython) v2.6+ and < v3.0 as well as the NumPy module. The analysis examples require the Matplotlib Python module.Nature of problem:Simulation and interpretation of single molecule FRET experiments.Solution method:Combination of force-field based molecular dynamics (MD) simulating the dye dynamics and Monte Carlo sampling to obtain photon statistics of FRET kinetics.Additional comments:!!!!! The distribution file for this program is over 50 Mbytes and therefore is not delivered directly when download or Email is requested. Instead a html file giving details of how the program can be obtained is sent. !!!!!Running time:A single run in Ref. [2] takes about 10 min on a Quad Core Intel Xeon CPU W3520 2.67GHz with 6GB physical RAMReferences:[1] M. Saito, M. Matsumoto, SIMD-oriented fast Mersenne twister: a 128-bit pseudorandom number generator, in: A. Keller, S. Heinrich, H. Niederreiter (Eds.), Monte Carlo and Quasi-Monte Carlo Methods 2006, Springer; Berlin, Heidelberg, 2008, pp. 607-622.[2] M. Hoefling, N. Lima, D. Hänni, B. Schuler, C. A. M. Seidel, H. Grubmüller, Structural heterogeneity and quantitative FRET efficiency distributions of polyprolines through a hybrid atomistic simulation and Monte Carlo approach, PLoS ONE 6 (5) (2011) e19791.[3] D. V. D. Spoel, E. Lindahl, B. Hess, G. Groenhof, A. E. Mark, H. J. C. Berendsen, GROMACS: fast, flexible, and free., J Comput Chem 26 (16) (2005) 1701–1718.[4] R. Pool, A. Feenstra, M. Hoefling, R. Schulz, J. C. Smith, J. Heringa, Enabling grand-canonical Monte Carlo: Extending the flexibility of gromacs through the GromPy Python interface module, Journal of Chemical Theory and Computation 33 (12) (2012) 1207–1214
Interaction of amino acids with the Au(111) surface: Adsorption free energies from molecular dynamics simulations
No full textThe conformations of amino acids on a gold(111) surface
No full textThe interactions of amino acids with inorganic surfaces are of interest for biologists and biotechnologists alike. However, the structural determinants of peptide-surface interactions have remained elusive, but are important for a structural understanding of the interactions of biomolecules with gold surfaces. Molecular dynamics simulations are a tool to analyze structures of amino acids on surfaces. However, such an approach is challenging due to lacking parameterization for many surfaces and the polarizability of metal surfaces. Herein, we report DFT calculations of amino acid fragments in vacuo and molecular dynamics simulations of the interaction of all amino acids with a gold(111) surface in explicit solvent, using the recently introduced polarizable gold force field GolP. We describe preferred orientations of the amino acids on the metal surface. We find that all amino acids preferably interact with the gold surface at least partially with their backbone, underlining an unfolding..
AMBER-DYES: Characterization of charge fluctuations and force field parameterization of fluorescent dyes for molecular dynamics simulations.
Full text linkRecent advances in single molecule fluorescence experiments and theory allow a direct comparison and improved interpretation of experiment and simulation. To this end, force fields for a larger number of dyes are required which are compatible with and can be integrated into existing biomolecular force fields. Here, we developed, characterized, and implemented AMBER-DYES, a modular fluorescent label force field, for a set of 22 fluorescent dyes and their linkers from the Alexa, Atto, and Cy families, which are in common use for single molecule spectroscopy experiments. The force field is compatible with the AMBER protein force fields and the GROMACS molecular dynamics simulation program. The high electronic polarizability of the delocalized π-electron orbitals, as found in many fluorescent dyes, poses a particular challenge to point charge based force fields such as AMBER. To quantify the charge fluctuations due to the electronic polarizability, we simulated the 22 dyes in explicit solvent and sampled the charge fluctuations using QM/MM simulations at the B3LYP/6-31G*//TIP3P level of theory. The analysis of the simulations enabled us to derive ensemble fitted RESP charges from the solvated charge distributions of multiple trajectories. We observed broad, single peaked charge distributions for the conjugated ring atoms with well-defined mean values. The charge fitting procedure was validated against published charges of the dyelike amino acid tryptophan, which showed good agreement with existing tryptophan parameters from the AMBER, CHARMM, and OPLS force field families. A principal component analysis of the charge fluctuations revealed that a small number of collective coordinates suffices to describe most of the in-plane dye polarizability. The AMBER-DYES force field allows the rapid preparation of all atom molecular dynamics simulations of fluorescent systems for state of the art multi microsecond trajectories
Interaction of β-sheet folds with a gold surface.
Full text linkThe adsorption of proteins on inorganic surfaces is of fundamental biological importance. Further, biomedical and nanotechnological applications increasingly use interfaces between inorganic material and polypeptides. Yet, the underlying adsorption mechanism of polypeptides on surfaces is not well understood and experimentally difficult to analyze. Therefore, we investigate here the interactions of polypeptides with a gold(111) surface using computational molecular dynamics (MD) simulations with a polarizable gold model in explicit water. Our focus in this paper is the investigation of the interaction of polypeptides with β-sheet folds. First, we concentrate on a β-sheet forming model peptide. Second, we investigate the interactions of two domains with high β-sheet content of the biologically important extracellular matrix protein fibronectin (FN). We find that adsorption occurs in a stepwise mechanism both for the model peptide and the protein. The positively charged amino acid Arg facilitates the initial contact formation between protein and gold surface. Our results suggest that an effective gold-binding surface patch is overall uncharged, but contains Arg for contact initiation. The polypeptides do not unfold on the gold surface within the simulation time. However, for the two FN domains, the relative domain-domain orientation changes. The observation of a very fast and strong adsorption indicates that in a biological matrix, no bare gold surfaces will be present. Hence, the bioactivity of gold surfaces (like bare gold nanoparticles) will critically depend on the history of particle administration and the proteins present during initial contact between gold and biological material. Further, gold particles may act as seeds for protein aggregation. Structural re-organization and protein aggregation are potentially of immunological importance
g_membed: Efficient insertion of a membrane protein into an equilibrated lipid bilayer with minimal perturbation
No full textTo efficiently insert a protein into an equilibrated and fully hydrated membrane with minimal membrane perturbation we present a computational tool, called g_membed, which is part of the Gromacs suite of programs. The input consists of an equilibrated membrane system, either flat or curved, and a protein structure in the right position and orientation with respect to the lipid bilayer. g_membed first decreases the width of the protein in the xy-plane and removes all molecules (generally lipids and waters) that overlap with the narrowed protein. Then the protein is grown back to its full size in a short molecular dynamics simulation (typically 1000 steps), thereby pushing the lipids away to optimally accommodate the protein in the membrane. After embedding the protein in the membrane, both the lipid properties and the hydration layer are still close to equilibrium. Thus, only a short equilibration run (less then 1 ns in the cases tested) is required to re-equilibrate the membrane. Its simplicity makes g_membed very practical for use in scripting and high-throughput molecular dynamics simulations
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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