Protein structure prediction using basin-hopping.
14 Jun 2008-Journal of Chemical Physics (American Institute of Physics)-Vol. 128, Iss: 22, pp 225106-225106
TL;DR: In this article, basin-hopping global optimization can identify low-lying minima for the corresponding mildly frustrated energy landscapes and improve the energy surface by employing bioinformatic techniques.
Abstract: Associative memory Hamiltonian structure prediction potentials are not overly rugged, thereby suggesting their landscapes are like those of actual proteins. In the present contribution we show how basin-hopping global optimization can identify low-lying minima for the corresponding mildly frustrated energy landscapes. For small systems the basin-hopping algorithm succeeds in locating both lower minima and conformations closer to the experimental structure than does molecular dynamics with simulated annealing. For large systems the efficiency of basin-hopping decreases for our initial implementation, where the steps consist of random perturbations to the Cartesian coordinates. We implemented umbrella sampling using basin-hopping to further confirm when the global minima are reached. We have also improved the energy surface by employing bioinformatic techniques for reducing the roughness or variance of the energy surface. Finally, the basin-hopping calculations have guided improvements in the excluded volume of the Hamiltonian, producing better structures. These results suggest a novel and transferable optimization scheme for future energy function development.
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TL;DR: The phases used to drive an ultrasonic phased array are optimized and it is shown that acoustic levitation can be employed to translate, rotate and manipulate particles using even a single-sided emitter.
Abstract: Sound can levitate objects of different sizes and materials through air, water and tissue. This allows us to manipulate cells, liquids, compounds or living things without touching or contaminating them. However, acoustic levitation has required the targets to be enclosed with acoustic elements or had limited manoeuvrability. Here we optimize the phases used to drive an ultrasonic phased array and show that acoustic levitation can be employed to translate, rotate and manipulate particles using even a single-sided emitter. Furthermore, we introduce the holographic acoustic elements framework that permits the rapid generation of traps and provides a bridge between optical and acoustical trapping. Acoustic structures shaped as tweezers, twisters or bottles emerge as the optimum mechanisms for tractor beams or containerless transportation. Single-beam levitation could manipulate particles inside our body for applications in targeted drug delivery or acoustically controlled micro-machines that do not interfere with magnetic resonance imaging.
602 citations
Paris Diderot University1, European Space Agency2, Spanish National Research Council3, Max Planck Society4, University of Padua5, Aix-Marseille University6, International Space Science Institute7, Uppsala University8, Braunschweig University of Technology9, University of Maryland, College Park10, Centre national de la recherche scientifique11, INAF12, University of Trento13, National Central University14, University of Bern15, Open University16
TL;DR: In this paper, the photometric and spectrophotometric properties of the nucleus of the comet 67P/Churyumov-Gerasimenko (67P) were derived from the OSIRIS imaging system, which consists of a WAC and a Narrow Angle Camera (NAC).
Abstract: The Rosetta mission of the European Space Agency has been orbiting the comet 67P/Churyumov-Gerasimenko (67P) since August 2014 and is now in its escort phase. A large complement of scientific experiments designed to complete the most detailed study of a comet ever attempted are onboard Rosetta.
Aims. We present results for the photometric and spectrophotometric properties of the nucleus of 67P derived from the OSIRIS imaging system, which consists of a Wide Angle Camera (WAC) and a Narrow Angle Camera (NAC). The observations presented here were performed during July and the beginning of August 2014, during the approach phase, when OSIRIS was mapping the surface of the comet with several filters at different phase angles (1.3°–54°). The resolution reached up to 2.1 m/px.
Methods. The OSIRIS images were processed with the OSIRIS standard pipeline, then converted into I/F radiance factors and corrected for the illumination conditions at each pixel using the Lommel-Seeliger disk law. Color cubes of the surface were produced by stacking registered and illumination-corrected images. Furthermore, photometric analysis was performed both on disk-averaged photometry in several filters and on disk-resolved images acquired with the NAC orange filter, centered at 649 nm, using Hapke modeling.
Results. The disk-averaged phase function of the nucleus of 67P shows a strong opposition surge with a G parameter value of - 0.13±0.01 in the HG system formalism and an absolute magnitude Hv (1, 1, 0) = 15.74±0.02 mag. The integrated spectrophotometry in 20 filters covering the 250-1000 nm wavelength range shows a red spectral behavior, without clear absorption bands except for a potential absorption centered at ∼ 290 nm that is possibly due to SO2 ice. The nucleus shows strong phase reddening, with disk- averaged spectral slopes increasing from 11%/(100 nm) to 16%/(100 nm) in the 1.3°–54° phase angle range. The geometric albedo of the comet is 6.5±0.2% at 649 nm, with local variations of up to ∼ 16% in the Hapi region. From the disk-resolved images we computed the spectral slope together with local spectrophotometry and identified three distinct groups of regions (blue, moderately red, and red). The Hapi region is the brightest, the bluest in term of spectral slope, and the most active surface on the comet. Local spectrophotometry shows an enhancement of the flux in the 700-750 nm that is associated with coma emissions.
199 citations
TL;DR: This review highlights state-of-the-art algorithmic techniques proposed to overcome challenges posed in silico by the disparate spatial and time scales accessed by dynamic macromolecules.
Abstract: Investigation of macromolecular structure and dynamics is fundamental to understanding how macromolecules carry out their functions in the cell. Significant advances have been made toward this end in silico, with a growing number of computational methods proposed yearly to study and simulate various aspects of macromolecular structure and dynamics. This review aims to provide an overview of recent advances, focusing primarily on methods proposed for exploring the structure space of macromolecules in isolation and in assemblies for the purpose of characterizing equilibrium structure and dynamics. In addition to surveying recent applications that showcase current capabilities of computational methods, this review highlights state-of-the-art algorithmic techniques proposed to overcome challenges posed in silico by the disparate spatial and time scales accessed by dynamic macromolecules. This review is not meant to be exhaustive, as such an endeavor is impossible, but rather aims to balance breadth and depth of strategies for modeling macromolecular structure and dynamics for a broad audience of novices and experts.
188 citations
Paris Diderot University1, European Space Agency2, Spanish National Research Council3, Max Planck Society4, University of Padua5, Aix-Marseille University6, International Space Science Institute7, Uppsala University8, Braunschweig University of Technology9, University of Maryland, College Park10, Centre national de la recherche scientifique11, INAF12, University of Trento13, National Central University14, University of Bern15, Open University16
TL;DR: In this paper, the photometric and spectrophotometric properties of the nucleus of the comet 67P/Churyumov-Gerasimenko (67P) derived from the OSIRIS imaging system, which consists of a Wide Angle Camera (WAC) and a narrow angle camera (NAC).
Abstract: The Rosetta mission of the European Space Agency has been orbiting the comet 67P/Churyumov-Gerasimenko (67P) since August 2014 and is now in its escort phase. A large complement of scientific experiments designed to complete the most detailed study of a comet ever attempted are onboard Rosetta. We present results for the photometric and spectrophotometric properties of the nucleus of 67P derived from the OSIRIS imaging system, which consists of a Wide Angle Camera (WAC) and a Narrow Angle Camera (NAC). The disk-averaged phase function of the nucleus of 67P shows a strong opposition surge with a G parameter value of -0.13$\pm$0.01 in the HG system formalism and an absolute magnitude $H_v(1,1,0)$ = 15.74$\pm$0.02 mag. The integrated spectrophotometry in 20 filters covering the 250-1000 nm wavelength range shows a red spectral behavior, without clear absorption bands except for a potential absorption centered at $\sim$ 290 nm that is possibly due to SO$_2$ ice. The nucleus shows strong phase reddening, with disk-averaged spectral slopes increasing from 11\%/(100 nm) to 16\%/(100 nm) in the 1.3$^{\circ}$--54$^{\circ}$ phase angle range. The geometric albedo of the comet is 6.5$\pm$0.2\% at 649 nm, with local variations of up to $\sim$ 16\% in the Hapi region. From the disk-resolved images we computed the spectral slope together with local spectrophotometry and identified three distinct groups of regions (blue, moderately red, and red). The Hapi region is the brightest, the bluest in term of spectral slope, and the most active surface on the comet. Local spectrophotometry shows an enhancement of the flux in the 700-750 nm that is associated with coma emissions.
173 citations
TL;DR: It is argued that MC simulations, while underutilized biomacromolecular simulation community, hold promise for simulations of complex systems and phenomena that span multiple length scales, especially when used in conjunction with implicit solvation models or other coarse graining strategies.
Abstract: The state-of-the-art for Monte Carlo (MC) simulations of biomacromolecules is reviewed Available methodologies for sampling conformational equilibria and associations of biomacromolecules in the canonical ensemble, given a continuum description of the solvent environment, are reviewed Detailed sections are provided dealing with the choice of degrees of freedom, the efficiencies of MC algorithms and algorithmic peculiarities, as well as the optimization of simple movesets The issue of introducing correlations into elementary MC moves and the applicability of such methods to simulations of biomacromolecules are discussed A brief discussion of multicanonical methods and an overview of recent simulation work highlighting the potential of MC methods are also provided It is argued that MC simulations, although underutilized in the biomacromolecular simulation community, hold promise for simulations of complex systems and phenomena that span multiple length scales, especially when used in conjunction with implicit solvation models or other coarse-graining strategies
126 citations
References
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TL;DR: A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original.
Abstract: The BLAST programs are widely used tools for searching protein and DNA databases for sequence similarities. For protein comparisons, a variety of definitional, algorithmic and statistical refinements described here permits the execution time of the BLAST programs to be decreased substantially while enhancing their sensitivity to weak similarities. A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original. In addition, a method is introduced for automatically combining statistically significant alignments produced by BLAST into a position-specific score matrix, and searching the database using this matrix. The resulting Position-Specific Iterated BLAST (PSIBLAST) program runs at approximately the same speed per iteration as gapped BLAST, but in many cases is much more sensitive to weak but biologically relevant sequence similarities. PSI-BLAST is used to uncover several new and interesting members of the BRCT superfamily.
70,111 citations
TL;DR: The sensitivity of the commonly used progressive multiple sequence alignment method has been greatly improved and modifications are incorporated into a new program, CLUSTAL W, which is freely available.
Abstract: The sensitivity of the commonly used progressive multiple sequence alignment method has been greatly improved for the alignment of divergent protein sequences. Firstly, individual weights are assigned to each sequence in a partial alignment in order to down-weight near-duplicate sequences and up-weight the most divergent ones. Secondly, amino acid substitution matrices are varied at different alignment stages according to the divergence of the sequences to be aligned. Thirdly, residue-specific gap penalties and locally reduced gap penalties in hydrophilic regions encourage new gaps in potential loop regions rather than regular secondary structure. Fourthly, positions in early alignments where gaps have been opened receive locally reduced gap penalties to encourage the opening up of new gaps at these positions. These modifications are incorporated into a new program, CLUSTAL W which is freely available.
63,427 citations
TL;DR: The goals of the PDB are described, the systems in place for data deposition and access, how to obtain further information and plans for the future development of the resource are described.
Abstract: The Protein Data Bank (PDB; http://www.rcsb.org/pdb/ ) is the single worldwide archive of structural data of biological macromolecules. This paper describes the goals of the PDB, the systems in place for data deposition and access, how to obtain further information, and near-term plans for the future development of the resource.
34,239 citations
TL;DR: In this paper, a numerical algorithm integrating the 3N Cartesian equations of motion of a system of N points subject to holonomic constraints is formulated, and the relations of constraint remain perfectly fulfilled at each step of the trajectory despite the approximate character of numerical integration.
18,394 citations
TL;DR: NAMD as discussed by the authors is a parallel molecular dynamics code designed for high-performance simulation of large biomolecular systems that scales to hundreds of processors on high-end parallel platforms, as well as tens of processors in low-cost commodity clusters, and also runs on individual desktop and laptop computers.
Abstract: NAMD is a parallel molecular dynamics code designed for high-performance simulation of large biomolecular systems. NAMD scales to hundreds of processors on high-end parallel platforms, as well as tens of processors on low-cost commodity clusters, and also runs on individual desktop and laptop computers. NAMD works with AMBER and CHARMM potential functions, parameters, and file formats. This article, directed to novices as well as experts, first introduces concepts and methods used in the NAMD program, describing the classical molecular dynamics force field, equations of motion, and integration methods along with the efficient electrostatics evaluation algorithms employed and temperature and pressure controls used. Features for steering the simulation across barriers and for calculating both alchemical and conformational free energy differences are presented. The motivations for and a roadmap to the internal design of NAMD, implemented in C++ and based on Charm++ parallel objects, are outlined. The factors affecting the serial and parallel performance of a simulation are discussed. Finally, typical NAMD use is illustrated with representative applications to a small, a medium, and a large biomolecular system, highlighting particular features of NAMD, for example, the Tcl scripting language. The article also provides a list of the key features of NAMD and discusses the benefits of combining NAMD with the molecular graphics/sequence analysis software VMD and the grid computing/collaboratory software BioCoRE. NAMD is distributed free of charge with source code at www.ks.uiuc.edu.
14,558 citations