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Sample records for computers molecular

  1. Molecular computing origins and promises

    CERN Document Server

    Rambidi, Nicholas G

    2014-01-01

    Molecular Computing explores whether molecular primitives can prove to be real alternatives to contemporary semiconductor means. The text discusses molecular primitives and circuitry for information processing devices.

  2. Exercises in molecular computing.

    Science.gov (United States)

    Stojanovic, Milan N; Stefanovic, Darko; Rudchenko, Sergei

    2014-06-17

    CONSPECTUS: The successes of electronic digital logic have transformed every aspect of human life over the last half-century. The word "computer" now signifies a ubiquitous electronic device, rather than a human occupation. Yet evidently humans, large assemblies of molecules, can compute, and it has been a thrilling challenge to develop smaller, simpler, synthetic assemblies of molecules that can do useful computation. When we say that molecules compute, what we usually mean is that such molecules respond to certain inputs, for example, the presence or absence of other molecules, in a precisely defined but potentially complex fashion. The simplest way for a chemist to think about computing molecules is as sensors that can integrate the presence or absence of multiple analytes into a change in a single reporting property. Here we review several forms of molecular computing developed in our laboratories. When we began our work, combinatorial approaches to using DNA for computing were used to search for solutions to constraint satisfaction problems. We chose to work instead on logic circuits, building bottom-up from units based on catalytic nucleic acids, focusing on DNA secondary structures in the design of individual circuit elements, and reserving the combinatorial opportunities of DNA for the representation of multiple signals propagating in a large circuit. Such circuit design directly corresponds to the intuition about sensors transforming the detection of analytes into reporting properties. While this approach was unusual at the time, it has been adopted since by other groups working on biomolecular computing with different nucleic acid chemistries. We created logic gates by modularly combining deoxyribozymes (DNA-based enzymes cleaving or combining other oligonucleotides), in the role of reporting elements, with stem-loops as input detection elements. For instance, a deoxyribozyme that normally exhibits an oligonucleotide substrate recognition region is

  3. Computational methods for molecular imaging

    CERN Document Server

    Shi, Kuangyu; Li, Shuo

    2015-01-01

    This volume contains original submissions on the development and application of molecular imaging computing. The editors invited authors to submit high-quality contributions on a wide range of topics including, but not limited to: • Image Synthesis & Reconstruction of Emission Tomography (PET, SPECT) and other Molecular Imaging Modalities • Molecular Imaging Enhancement • Data Analysis of Clinical & Pre-clinical Molecular Imaging • Multi-Modal Image Processing (PET/CT, PET/MR, SPECT/CT, etc.) • Machine Learning and Data Mining in Molecular Imaging. Molecular imaging is an evolving clinical and research discipline enabling the visualization, characterization and quantification of biological processes taking place at the cellular and subcellular levels within intact living subjects. Computational methods play an important role in the development of molecular imaging, from image synthesis to data analysis and from clinical diagnosis to therapy individualization. This work will bring readers fro...

  4. Computer representation of molecular surfaces

    International Nuclear Information System (INIS)

    Max, N.L.

    1981-01-01

    This review article surveys recent work on computer representation of molecular surfaces. Several different algorithms are discussed for producing vector or raster drawings of space-filling models formed as the union of spheres. Other smoother surfaces are also considered

  5. Molecular Magnets for Quantum Computation

    Science.gov (United States)

    Kuroda, Takayoshi

    2009-06-01

    We review recent progress in molecular magnets especially in the viewpoint of the application for quantum computing. After a brief introduction to single-molecule magnets (SMMs), a method for qubit manipulation by using non-equidistant spin sublevels of a SMM will be introduced. A weakly-coupled dimer of two SMMs is also a candidate for quantum computing, which shows no quantum tunneling of magnetization (QTM) at zero field. In the AF ring Cr7Ni system, the large tunnel splitting is a great advantage to reduce decoherence during manipulation, which can be a possible candidate to realize quantum computer devices in future.

  6. Molecular Science Computing: 2010 Greenbook

    Energy Technology Data Exchange (ETDEWEB)

    De Jong, Wibe A.; Cowley, David E.; Dunning, Thom H.; Vorpagel, Erich R.

    2010-04-02

    This 2010 Greenbook outlines the science drivers for performing integrated computational environmental molecular research at EMSL and defines the next-generation HPC capabilities that must be developed at the MSC to address this critical research. The EMSL MSC Science Panel used EMSL’s vision and science focus and white papers from current and potential future EMSL scientific user communities to define the scientific direction and resulting HPC resource requirements presented in this 2010 Greenbook.

  7. Synthetic biology: engineering molecular computers

    CERN Multimedia

    CERN. Geneva

    2018-01-01

    Complicated systems cannot survive the rigors of a chaotic environment, without balancing mechanisms that sense, decide upon and counteract the exerted disturbances. Especially so with living organisms, forced by competition to incredible complexities, escalating also their self-controlling plight. Therefore, they compute. Can we harness biological mechanisms to create artificial computing systems? Biology offers several levels of design abstraction: molecular machines, cells, organisms... ranging from the more easily-defined to the more inherently complex. At the bottom of this stack we find the nucleic acids, RNA and DNA, with their digital structure and relatively precise interactions. They are central enablers of designing artificial biological systems, in the confluence of engineering and biology, that we call Synthetic biology. In the first part, let us follow their trail towards an overview of building computing machines with molecules -- and in the second part, take the case study of iGEM Greece 201...

  8. Computational Design of Molecularly Imprinted Polymers

    Science.gov (United States)

    Subrahmanyam, Sreenath; Piletsky, Sergey A.

    Artificial receptors have been in use for several decades as sensor elements, in affinity separation, and as models for investigation of molecular recognition. Although there have been numerous publications on the use of molecular modeling in characterization of their affinity and selectivity, very few attempts have been made on the application of molecular modeling in computational design of synthetic receptors. This chapter discusses recent successes in the use of computational design for the development of one particular branch of synthetic receptors - molecularly imprinted polymers.

  9. Computational Nanotechnology Molecular Electronics, Materials and Machines

    Science.gov (United States)

    Srivastava, Deepak; Biegel, Bryan A. (Technical Monitor)

    2002-01-01

    This presentation covers research being performed on computational nanotechnology, carbon nanotubes and fullerenes at the NASA Ames Research Center. Topics cover include: nanomechanics of nanomaterials, nanotubes and composite materials, molecular electronics with nanotube junctions, kinky chemistry, and nanotechnology for solid-state quantum computers using fullerenes.

  10. Molecular computing: paths to chemical Turing machines.

    Science.gov (United States)

    Varghese, Shaji; Elemans, Johannes A A W; Rowan, Alan E; Nolte, Roeland J M

    2015-11-13

    To comply with the rapidly increasing demand of information storage and processing, new strategies for computing are needed. The idea of molecular computing, where basic computations occur through molecular, supramolecular, or biomolecular approaches, rather than electronically, has long captivated researchers. The prospects of using molecules and (bio)macromolecules for computing is not without precedent. Nature is replete with examples where the handling and storing of data occurs with high efficiencies, low energy costs, and high-density information encoding. The design and assembly of computers that function according to the universal approaches of computing, such as those in a Turing machine, might be realized in a chemical way in the future; this is both fascinating and extremely challenging. In this perspective, we highlight molecular and (bio)macromolecular systems that have been designed and synthesized so far with the objective of using them for computing purposes. We also present a blueprint of a molecular Turing machine, which is based on a catalytic device that glides along a polymer tape and, while moving, prints binary information on this tape in the form of oxygen atoms.

  11. Computational methods for molecular docking

    Energy Technology Data Exchange (ETDEWEB)

    Klebe, G. [BASF AG, Ludwigshafen (Germany); Lengauer, T.

    1995-12-31

    This tutorial was one of eight tutorials selected to be presented at the Third International Conference on Intelligent Systems for Molecular Biology which was held in the United Kingdom from July 16 to 19, 1995. Recently, it has been demonstrated that the knowledge of the three-dimensional structure of the protein can be used to derive new protein ligands with improved binding properties. This tutorial focuses on the following questions: What is its binding affinity toward a particular receptor? What are putative conformations of a ligand at the binding site? What are the similarities of different ligands in terms of their recognition capabilities? Where and in which orientation will a ligand bind to the active site? How is a new putative protein ligand selected? An overview is presented of the algorithms which are presently used to handle and predict protein-ligand interactions and to dock small molecule ligands into proteins.

  12. Grid computing in large pharmaceutical molecular modeling.

    Science.gov (United States)

    Claus, Brian L; Johnson, Stephen R

    2008-07-01

    Most major pharmaceutical companies have employed grid computing to expand their compute resources with the intention of minimizing additional financial expenditure. Historically, one of the issues restricting widespread utilization of the grid resources in molecular modeling is the limited set of suitable applications amenable to coarse-grained parallelization. Recent advances in grid infrastructure technology coupled with advances in application research and redesign will enable fine-grained parallel problems, such as quantum mechanics and molecular dynamics, which were previously inaccessible to the grid environment. This will enable new science as well as increase resource flexibility to load balance and schedule existing workloads.

  13. A molecular computer to classify cells

    CERN Multimedia

    CERN. Geneva

    2018-01-01

    If only we had a small molecular computer to leverage this disparity, programmable to optimally recognize different classes of cells and, once inside a target cell, to execute an action. Like what a student team researched for this year's synthetic biology iGEM competition.

  14. Integrated multiscale modeling of molecular computing devices

    International Nuclear Information System (INIS)

    Cummings, Peter T; Leng Yongsheng

    2005-01-01

    Molecular electronics, in which single organic molecules are designed to perform the functions of transistors, diodes, switches and other circuit elements used in current siliconbased microelecronics, is drawing wide interest as a potential replacement technology for conventional silicon-based lithographically etched microelectronic devices. In addition to their nanoscopic scale, the additional advantage of molecular electronics devices compared to silicon-based lithographically etched devices is the promise of being able to produce them cheaply on an industrial scale using wet chemistry methods (i.e., self-assembly from solution). The design of molecular electronics devices, and the processes to make them on an industrial scale, will require a thorough theoretical understanding of the molecular and higher level processes involved. Hence, the development of modeling techniques for molecular electronics devices is a high priority from both a basic science point of view (to understand the experimental studies in this field) and from an applied nanotechnology (manufacturing) point of view. Modeling molecular electronics devices requires computational methods at all length scales - electronic structure methods for calculating electron transport through organic molecules bonded to inorganic surfaces, molecular simulation methods for determining the structure of self-assembled films of organic molecules on inorganic surfaces, mesoscale methods to understand and predict the formation of mesoscale patterns on surfaces (including interconnect architecture), and macroscopic scale methods (including finite element methods) for simulating the behavior of molecular electronic circuit elements in a larger integrated device. Here we describe a large Department of Energy project involving six universities and one national laboratory aimed at developing integrated multiscale methods for modeling molecular electronics devices. The project is funded equally by the Office of Basic

  15. Computer simulation of molecular sorption in zeolites

    International Nuclear Information System (INIS)

    Calmiano, Mark Daniel

    2001-01-01

    The work presented in this thesis encompasses the computer simulation of molecular sorption. In Chapter 1 we outline the aims and objectives of this work. Chapter 2 follows in which an introduction to sorption in zeolites is presented, with discussion of structure and properties of the main zeolites studied. Chapter 2 concludes with a description of the principles and theories of adsorption. In Chapter 3 we describe the methodology behind the work carried out in this thesis. In Chapter 4 we present our first computational study, that of the sorption of krypton in silicalite. We describe work carried out to investigate low energy sorption sites of krypton in silicalite where we observe krypton to preferentially sorb into straight and sinusoidal channels over channel intersections. We simulate single step type I adsorption isotherms and use molecular dynamics to study the diffusion of krypton and obtain division coefficients and the activation energy. We compare our results to previous experimental and computational studies where we show our work to be in good agreement. In Chapter 5 we present a systematic study of the sorption of oxygen and nitrogen in five lithium substituted zeolites using a transferable interatomic potential that we have developed from ab initio calculations. We show increased loading of nitrogen compared to oxygen in all five zeolites studied as expected and simulate adsorption isotherms, which we compare to experimental and simulated data in the literature. In Chapter 6 we present work on the sorption of ferrocene in the zeolite NaY. We show that a simulated, low energy sorption site for ferrocene is correctly located by comparing to X-ray powder diffraction results for this same system. The thesis concludes with some overall conclusions and discussion of opportunities for future work. (author)

  16. Molecular computation: RNA solutions to chess problems.

    Science.gov (United States)

    Faulhammer, D; Cukras, A R; Lipton, R J; Landweber, L F

    2000-02-15

    We have expanded the field of "DNA computers" to RNA and present a general approach for the solution of satisfiability problems. As an example, we consider a variant of the "Knight problem," which asks generally what configurations of knights can one place on an n x n chess board such that no knight is attacking any other knight on the board. Using specific ribonuclease digestion to manipulate strands of a 10-bit binary RNA library, we developed a molecular algorithm and applied it to a 3 x 3 chessboard as a 9-bit instance of this problem. Here, the nine spaces on the board correspond to nine "bits" or placeholders in a combinatorial RNA library. We recovered a set of "winning" molecules that describe solutions to this problem.

  17. Molecular computing towards a novel computing architecture for complex problem solving

    CERN Document Server

    Chang, Weng-Long

    2014-01-01

    This textbook introduces a concise approach to the design of molecular algorithms for students or researchers who are interested in dealing with complex problems. Through numerous examples and exercises, you will understand the main difference of molecular circuits and traditional digital circuits to manipulate the same problem and you will also learn how to design a molecular algorithm of solving any a problem from start to finish. The book starts with an introduction to computational aspects of digital computers and molecular computing, data representation of molecular computing, molecular operations of molecular computing and number representation of molecular computing, and provides many molecular algorithm to construct the parity generator and the parity checker of error-detection codes on digital communication, to encode integers of different formats, single precision and double precision of floating-point numbers, to implement addition and subtraction of unsigned integers, to construct logic operations...

  18. Using a Computer Animation to Teach High School Molecular Biology

    Science.gov (United States)

    Rotbain, Yosi; Marbach-Ad, Gili; Stavy, Ruth

    2008-01-01

    We present an active way to use a computer animation in secondary molecular genetics class. For this purpose we developed an activity booklet that helps students to work interactively with a computer animation which deals with abstract concepts and processes in molecular biology. The achievements of the experimental group were compared with those…

  19. Magnetic polyoxometalates: from molecular magnetism to molecular spintronics and quantum computing.

    Science.gov (United States)

    Clemente-Juan, Juan M; Coronado, Eugenio; Gaita-Ariño, Alejandro

    2012-11-21

    In this review we discuss the relevance of polyoxometalate (POM) chemistry to provide model objects in molecular magnetism. We present several potential applications in nanomagnetism, in particular, in molecular spintronics and quantum computing.

  20. The emerging role of cloud computing in molecular modelling.

    Science.gov (United States)

    Ebejer, Jean-Paul; Fulle, Simone; Morris, Garrett M; Finn, Paul W

    2013-07-01

    There is a growing recognition of the importance of cloud computing for large-scale and data-intensive applications. The distinguishing features of cloud computing and their relationship to other distributed computing paradigms are described, as are the strengths and weaknesses of the approach. We review the use made to date of cloud computing for molecular modelling projects and the availability of front ends for molecular modelling applications. Although the use of cloud computing technologies for molecular modelling is still in its infancy, we demonstrate its potential by presenting several case studies. Rapid growth can be expected as more applications become available and costs continue to fall; cloud computing can make a major contribution not just in terms of the availability of on-demand computing power, but could also spur innovation in the development of novel approaches that utilize that capacity in more effective ways. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Computer modeling of properties of complex molecular systems

    Energy Technology Data Exchange (ETDEWEB)

    Kulkova, E.Yu. [Moscow State University of Technology “STANKIN”, Vadkovsky per., 1, Moscow 101472 (Russian Federation); Khrenova, M.G.; Polyakov, I.V. [Lomonosov Moscow State University, Chemistry Department, Leninskie Gory 1/3, Moscow 119991 (Russian Federation); Nemukhin, A.V. [Lomonosov Moscow State University, Chemistry Department, Leninskie Gory 1/3, Moscow 119991 (Russian Federation); N.M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Kosygina 4, Moscow 119334 (Russian Federation)

    2015-03-10

    Large molecular aggregates present important examples of strongly nonhomogeneous systems. We apply combined quantum mechanics / molecular mechanics approaches that assume treatment of a part of the system by quantum-based methods and the rest of the system with conventional force fields. Herein we illustrate these computational approaches by two different examples: (1) large-scale molecular systems mimicking natural photosynthetic centers, and (2) components of prospective solar cells containing titan dioxide and organic dye molecules. We demonstrate that modern computational tools are capable to predict structures and spectra of such complex molecular aggregates.

  2. Numerical computation of molecular integrals via optimized (vectorized) FORTRAN code

    International Nuclear Information System (INIS)

    Scott, T.C.; Grant, I.P.; Saunders, V.R.

    1997-01-01

    The calculation of molecular properties based on quantum mechanics is an area of fundamental research whose horizons have always been determined by the power of state-of-the-art computers. A computational bottleneck is the numerical calculation of the required molecular integrals to sufficient precision. Herein, we present a method for the rapid numerical evaluation of molecular integrals using optimized FORTRAN code generated by Maple. The method is based on the exploitation of common intermediates and the optimization can be adjusted to both serial and vectorized computations. (orig.)

  3. DNA-Enabled Integrated Molecular Systems for Computation and Sensing

    Science.gov (United States)

    2014-05-21

    Computational devices can be chemically conjugated to different strands of DNA that are then self-assembled according to strict Watson − Crick binding rules... DNA -Enabled Integrated Molecular Systems for Computation and Sensing Craig LaBoda,† Heather Duschl,† and Chris L. Dwyer*,†,‡ †Department of...guided folding of DNA , inspired by nature, allows designs to manipulate molecular-scale processes unlike any other material system. Thus, DNA can be

  4. Computational methods in molecular imaging technologies

    CERN Document Server

    Gunjan, Vinit Kumar; Venkatesh, C; Amarnath, M

    2017-01-01

    This book highlights the experimental investigations that have been carried out on magnetic resonance imaging and computed tomography (MRI & CT) images using state-of-the-art Computational Image processing techniques, and tabulates the statistical values wherever necessary. In a very simple and straightforward way, it explains how image processing methods are used to improve the quality of medical images and facilitate analysis. It offers a valuable resource for researchers, engineers, medical doctors and bioinformatics experts alike.

  5. Demystifying computer science for molecular ecologists.

    Science.gov (United States)

    Belcaid, Mahdi; Toonen, Robert J

    2015-06-01

    In this age of data-driven science and high-throughput biology, computational thinking is becoming an increasingly important skill for tackling both new and long-standing biological questions. However, despite its obvious importance and conspicuous integration into many areas of biology, computer science is still viewed as an obscure field that has, thus far, permeated into only a few of the biology curricula across the nation. A national survey has shown that lack of computational literacy in environmental sciences is the norm rather than the exception [Valle & Berdanier (2012) Bulletin of the Ecological Society of America, 93, 373-389]. In this article, we seek to introduce a few important concepts in computer science with the aim of providing a context-specific introduction aimed at research biologists. Our goal was to help biologists understand some of the most important mainstream computational concepts to better appreciate bioinformatics methods and trade-offs that are not obvious to the uninitiated. © 2015 John Wiley & Sons Ltd.

  6. Computer aided molecular design with combined molecular modeling and group contribution

    DEFF Research Database (Denmark)

    Harper, Peter Mathias; Gani, Rafiqul; Kolar, Petr

    1999-01-01

    Computer-aided molecular design (CAMD) provides a means for determining molecules or mixtures of molecules (CAMMD) having a desirable set of physicochemical properties. The application range of CAMD is restricted due to limitations on the complexity of the generated molecular structures and on th......Computer-aided molecular design (CAMD) provides a means for determining molecules or mixtures of molecules (CAMMD) having a desirable set of physicochemical properties. The application range of CAMD is restricted due to limitations on the complexity of the generated molecular structures...

  7. Molecular computational elements encode large populations of small objects

    Science.gov (United States)

    Prasanna de Silva, A.; James, Mark R.; McKinney, Bernadine O. F.; Pears, David A.; Weir, Sheenagh M.

    2006-10-01

    Since the introduction of molecular computation, experimental molecular computational elements have grown to encompass small-scale integration, arithmetic and games, among others. However, the need for a practical application has been pressing. Here we present molecular computational identification (MCID), a demonstration that molecular logic and computation can be applied to a widely relevant issue. Examples of populations that need encoding in the microscopic world are cells in diagnostics or beads in combinatorial chemistry (tags). Taking advantage of the small size (about 1nm) and large `on/off' output ratios of molecular logic gates and using the great variety of logic types, input chemical combinations, switching thresholds and even gate arrays in addition to colours, we produce unique identifiers for members of populations of small polymer beads (about 100μm) used for synthesis of combinatorial libraries. Many millions of distinguishable tags become available. This method should be extensible to far smaller objects, with the only requirement being a `wash and watch' protocol. Our focus on converting molecular science into technology concerning analog sensors, turns to digital logic devices in the present work.

  8. Molecular Science Computing Facility Scientific Challenges: Linking Across Scales

    Energy Technology Data Exchange (ETDEWEB)

    De Jong, Wibe A.; Windus, Theresa L.

    2005-07-01

    The purpose of this document is to define the evolving science drivers for performing environmental molecular research at the William R. Wiley Environmental Molecular Sciences Laboratory (EMSL) and to provide guidance associated with the next-generation high-performance computing center that must be developed at EMSL's Molecular Science Computing Facility (MSCF) in order to address this critical research. The MSCF is the pre-eminent computing facility?supported by the U.S. Department of Energy's (DOE's) Office of Biological and Environmental Research (BER)?tailored to provide the fastest time-to-solution for current computational challenges in chemistry and biology, as well as providing the means for broad research in the molecular and environmental sciences. The MSCF provides integral resources and expertise to emerging EMSL Scientific Grand Challenges and Collaborative Access Teams that are designed to leverage the multiple integrated research capabilities of EMSL, thereby creating a synergy between computation and experiment to address environmental molecular science challenges critical to DOE and the nation.

  9. NATO Advanced Study Institute on Methods in Computational Molecular Physics

    CERN Document Server

    Diercksen, Geerd

    1992-01-01

    This volume records the lectures given at a NATO Advanced Study Institute on Methods in Computational Molecular Physics held in Bad Windsheim, Germany, from 22nd July until 2nd. August, 1991. This NATO Advanced Study Institute sought to bridge the quite considerable gap which exist between the presentation of molecular electronic structure theory found in contemporary monographs such as, for example, McWeeny's Methods 0/ Molecular Quantum Mechanics (Academic Press, London, 1989) or Wilson's Electron correlation in moleeules (Clarendon Press, Oxford, 1984) and the realization of the sophisticated computational algorithms required for their practical application. It sought to underline the relation between the electronic structure problem and the study of nuc1ear motion. Software for performing molecular electronic structure calculations is now being applied in an increasingly wide range of fields in both the academic and the commercial sectors. Numerous applications are reported in areas as diverse as catalysi...

  10. Quantum computing applied to calculations of molecular energies

    Czech Academy of Sciences Publication Activity Database

    Pittner, Jiří; Veis, L.

    2011-01-01

    Roč. 241, - (2011), 151-phys ISSN 0065-7727. [National Meeting and Exposition of the American-Chemical-Society (ACS) /241./. 27.03.2011-31.03.2011, Anaheim] Institutional research plan: CEZ:AV0Z40400503 Keywords : molecular energie * quantum computers Subject RIV: CF - Physical ; Theoretical Chemistry

  11. Harwell's atomic, molecular and solid state computer programs

    International Nuclear Information System (INIS)

    Harker, A.H.

    1976-02-01

    This document is intended to introduce the computational facilities available in the fields of atomic, molecular the solid state theory on the IBM370/165 at Harwell. The programs have all been implemented and thoroughly tested by the Theory of Solid State Materials Group. (author)

  12. MOLECULAR DYNAMICS COMPUTER SIMULATIONS OF MULTIDRUG RND EFFLUX PUMPS

    Directory of Open Access Journals (Sweden)

    Paolo Ruggerone

    2013-02-01

    Full Text Available Over-expression of multidrug efflux pumps of the Resistance Nodulation Division (RND protein super family counts among the main causes for microbial resistance against pharmaceuticals. Understanding the molecular basis of this process is one of the major challenges of modern biomedical research, involving a broad range of experimental and computational techniques. Here we review the current state of RND transporter investigation employing molecular dynamics simulations providing conformational samples of transporter components to obtain insights into the functional mechanism underlying efflux pump-mediated antibiotics resistance in Escherichia coli and Pseudomonas aeruginosa.

  13. Molecular Dynamics Computer Simulations of Multidrug RND Efflux Pumps

    Directory of Open Access Journals (Sweden)

    Paolo Ruggerone

    2013-02-01

    Full Text Available Over-expression of multidrug efflux pumps of the Resistance Nodulation Division (RND protein super family counts among the main causes for microbial resistance against pharmaceuticals. Understanding the molecular basis of this process is one of the major challenges of modern biomedical research, involving a broad range of experimental and computational techniques. Here we review the current state of RND transporter investigation employing molecular dynamics simulations providing conformational samples of transporter components to obtain insights into the functional mechanism underlying efflux pump-mediated antibiotics resistance in Escherichia coli and Pseudomonas aeruginosa.

  14. Design of Carborane Molecular Architectures via Electronic Structure Computations

    International Nuclear Information System (INIS)

    Oliva, J.M.; Serrano-Andres, L.; Klein, D.J.; Schleyer, P.V.R.; Mich, J.

    2009-01-01

    Quantum-mechanical electronic structure computations were employed to explore initial steps towards a comprehensive design of poly carborane architectures through assembly of molecular units. Aspects considered were (i) the striking modification of geometrical parameters through substitution, (ii) endohedral carboranes and proposed ejection mechanisms for energy/ion/atom/energy storage/transport, (iii) the excited state character in single and dimeric molecular units, and (iv) higher architectural constructs. A goal of this work is to find optimal architectures where atom/ion/energy/spin transport within carborane superclusters is feasible in order to modernize and improve future photo energy processes.

  15. MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms.

    Science.gov (United States)

    Kumar, Sudhir; Stecher, Glen; Li, Michael; Knyaz, Christina; Tamura, Koichiro

    2018-06-01

    The Molecular Evolutionary Genetics Analysis (Mega) software implements many analytical methods and tools for phylogenomics and phylomedicine. Here, we report a transformation of Mega to enable cross-platform use on Microsoft Windows and Linux operating systems. Mega X does not require virtualization or emulation software and provides a uniform user experience across platforms. Mega X has additionally been upgraded to use multiple computing cores for many molecular evolutionary analyses. Mega X is available in two interfaces (graphical and command line) and can be downloaded from www.megasoftware.net free of charge.

  16. Large-scale theoretical calculations in molecular science - design of a large computer system for molecular science and necessary conditions for future computers

    Energy Technology Data Exchange (ETDEWEB)

    Kashiwagi, H [Institute for Molecular Science, Okazaki, Aichi (Japan)

    1982-06-01

    A large computer system was designed and established for molecular science under the leadership of molecular scientists. Features of the computer system are an automated operation system and an open self-service system. Large-scale theoretical calculations have been performed to solve many problems in molecular science, using the computer system. Necessary conditions for future computers are discussed on the basis of this experience.

  17. Large-scale theoretical calculations in molecular science - design of a large computer system for molecular science and necessary conditions for future computers

    International Nuclear Information System (INIS)

    Kashiwagi, H.

    1982-01-01

    A large computer system was designed and established for molecular science under the leadership of molecular scientists. Features of the computer system are an automated operation system and an open self-service system. Large-scale theoretical calculations have been performed to solve many problems in molecular science, using the computer system. Necessary conditions for future computers are discussed on the basis of this experience. (orig.)

  18. Computational Exploration of Molecular Scaffolds in Medicinal Chemistry.

    Science.gov (United States)

    Hu, Ye; Stumpfe, Dagmar; Bajorath, Jürgen

    2016-05-12

    The scaffold concept is widely applied in medicinal chemistry. Scaffolds are mostly used to represent core structures of bioactive compounds. Although the scaffold concept has limitations and is often viewed differently from a chemical and computational perspective, it has provided a basis for systematic investigations of molecular cores and building blocks, going far beyond the consideration of individual compound series. Over the past 2 decades, alternative scaffold definitions and organization schemes have been introduced and scaffolds have been studied in a variety of ways and increasingly on a large scale. Major applications of the scaffold concept include the generation of molecular hierarchies, structural classification, association of scaffolds with biological activities, and activity prediction. This contribution discusses computational approaches for scaffold generation and analysis, with emphasis on recent developments impacting medicinal chemistry. A variety of scaffold-based studies are discussed, and a perspective on scaffold methods is provided.

  19. Parallel computing and molecular dynamics of biological membranes

    International Nuclear Information System (INIS)

    La Penna, G.; Letardi, S.; Minicozzi, V.; Morante, S.; Rossi, G.C.; Salina, G.

    1998-01-01

    In this talk I discuss the general question of the portability of molecular dynamics codes for diffusive systems on parallel computers of the APE family. The intrinsic single precision of the today available platforms does not seem to affect the numerical accuracy of the simulations, while the absence of integer addressing from CPU to individual nodes puts strong constraints on possible programming strategies. Liquids can be satisfactorily simulated using the ''systolic'' method. For more complex systems, like the biological ones at which we are ultimately interested in, the ''domain decomposition'' approach is best suited to beat the quadratic growth of the inter-molecular computational time with the number of atoms of the system. The promising perspectives of using this strategy for extensive simulations of lipid bilayers are briefly reviewed. (orig.)

  20. Molecular dynamics simulations and applications in computational toxicology and nanotoxicology.

    Science.gov (United States)

    Selvaraj, Chandrabose; Sakkiah, Sugunadevi; Tong, Weida; Hong, Huixiao

    2018-02-01

    Nanotoxicology studies toxicity of nanomaterials and has been widely applied in biomedical researches to explore toxicity of various biological systems. Investigating biological systems through in vivo and in vitro methods is expensive and time taking. Therefore, computational toxicology, a multi-discipline field that utilizes computational power and algorithms to examine toxicology of biological systems, has gained attractions to scientists. Molecular dynamics (MD) simulations of biomolecules such as proteins and DNA are popular for understanding of interactions between biological systems and chemicals in computational toxicology. In this paper, we review MD simulation methods, protocol for running MD simulations and their applications in studies of toxicity and nanotechnology. We also briefly summarize some popular software tools for execution of MD simulations. Published by Elsevier Ltd.

  1. Computational Dehydration of Crystalline Hydrates Using Molecular Dynamics Simulations

    DEFF Research Database (Denmark)

    Larsen, Anders Støttrup; Rantanen, Jukka; Johansson, Kristoffer E

    2017-01-01

    Molecular dynamics (MD) simulations have evolved to an increasingly reliable and accessible technique and are today implemented in many areas of biomedical sciences. We present a generally applicable method to study dehydration of hydrates based on MD simulations and apply this approach...... to the dehydration of ampicillin trihydrate. The crystallographic unit cell of the trihydrate is used to construct the simulation cell containing 216 ampicillin and 648 water molecules. This system is dehydrated by removing water molecules during a 2200 ps simulation, and depending on the computational dehydration....... The structural changes could be followed in real time, and in addition, an intermediate amorphous phase was identified. The computationally identified dehydrated structure (anhydrate) was slightly different from the experimentally known anhydrate structure suggesting that the simulated computational structure...

  2. Modeling molecular boiling points using computed interaction energies.

    Science.gov (United States)

    Peterangelo, Stephen C; Seybold, Paul G

    2017-12-20

    The noncovalent van der Waals interactions between molecules in liquids are typically described in textbooks as occurring between the total molecular dipoles (permanent, induced, or transient) of the molecules. This notion was tested by examining the boiling points of 67 halogenated hydrocarbon liquids using quantum chemically calculated molecular dipole moments, ionization potentials, and polarizabilities obtained from semi-empirical (AM1 and PM3) and ab initio Hartree-Fock [HF 6-31G(d), HF 6-311G(d,p)], and density functional theory [B3LYP/6-311G(d,p)] methods. The calculated interaction energies and an empirical measure of hydrogen bonding were employed to model the boiling points of the halocarbons. It was found that only terms related to London dispersion energies and hydrogen bonding proved significant in the regression analyses, and the performances of the models generally improved at higher levels of quantum chemical computation. An empirical estimate for the molecular polarizabilities was also tested, and the best models for the boiling points were obtained using either this empirical polarizability itself or the polarizabilities calculated at the B3LYP/6-311G(d,p) level, along with the hydrogen-bonding parameter. The results suggest that the cohesive forces are more appropriately described as resulting from highly localized interactions rather than interactions between the global molecular dipoles.

  3. Molecular models of zinc phthalocyanines: semi-empirical molecular orbital computations and physicochemical properties studied by molecular mechanics simulations

    International Nuclear Information System (INIS)

    Gantchev, Tsvetan G.; van Lier, Johan E.; Hunting, Darel J.

    2005-01-01

    To build 3D-molecular models of Zinc-phthalocyanines (ZnPc) and to study their diverse chemical and photosensitization properties, we performed quantum mechanical molecular orbital (MO) semi-empirical (AM1) computations of the ground, excited singlet and triplet states as well as free radical (ionic) species. RHF and UHF (open shell) geometry optimizations led to near-perfect symmetrical ZnPc. Predicted ionization potentials (IP), electron affinities (EA) and lowest electronic transitions of ZnPc are in good agreement with the published experimental and theoretical data. The computation-derived D 4h /D 2h -symmetry 3D-structures of ground and excited states and free radicals of ZnPc, together with the frontier orbital energies and Mulliken electron population analysis enabled us to build robust molecular models. These models were used to predict important chemical-reactivity entities such as global electronegativity (χ), hardness (η) and local softness based on Fukui-functions analysis. Examples of molecular mechanics (MM) applications of the 3D-molecular models are presented as approaches to evaluate solvation free energy (ΔG 0 ) solv and to estimate ground- and excited- state oxidation/reduction potentials as well as intermolecular interactions and stability of ground and excited state dimers (exciplexes) and radical ion-pairs

  4. Computational Nanotechnology of Molecular Materials, Electronics, and Actuators with Carbon Nanotubes and Fullerenes

    Science.gov (United States)

    Srivastava, Deepak; Menon, Madhu; Cho, Kyeongjae; Biegel, Bryan (Technical Monitor)

    2001-01-01

    The role of computational nanotechnology in developing next generation of multifunctional materials, molecular scale electronic and computing devices, sensors, actuators, and machines is described through a brief review of enabling computational techniques and few recent examples derived from computer simulations of carbon nanotube based molecular nanotechnology.

  5. High performance computer code for molecular dynamics simulations

    International Nuclear Information System (INIS)

    Levay, I.; Toekesi, K.

    2007-01-01

    Complete text of publication follows. Molecular Dynamics (MD) simulation is a widely used technique for modeling complicated physical phenomena. Since 2005 we are developing a MD simulations code for PC computers. The computer code is written in C++ object oriented programming language. The aim of our work is twofold: a) to develop a fast computer code for the study of random walk of guest atoms in Be crystal, b) 3 dimensional (3D) visualization of the particles motion. In this case we mimic the motion of the guest atoms in the crystal (diffusion-type motion), and the motion of atoms in the crystallattice (crystal deformation). Nowadays, it is common to use Graphics Devices in intensive computational problems. There are several ways to use this extreme processing performance, but never before was so easy to programming these devices as now. The CUDA (Compute Unified Device) Architecture introduced by nVidia Corporation in 2007 is a very useful for every processor hungry application. A Unified-architecture GPU include 96-128, or more stream processors, so the raw calculation performance is 576(!) GFLOPS. It is ten times faster, than the fastest dual Core CPU [Fig.1]. Our improved MD simulation software uses this new technology, which speed up our software and the code run 10 times faster in the critical calculation code segment. Although the GPU is a very powerful tool, it has a strongly paralleled structure. It means, that we have to create an algorithm, which works on several processors without deadlock. Our code currently uses 256 threads, shared and constant on-chip memory, instead of global memory, which is 100 times slower than others. It is possible to implement the total algorithm on GPU, therefore we do not need to download and upload the data in every iteration. On behalf of maximal throughput, every thread run with the same instructions

  6. Lightweight computational steering of very large scale molecular dynamics simulations

    International Nuclear Information System (INIS)

    Beazley, D.M.

    1996-01-01

    We present a computational steering approach for controlling, analyzing, and visualizing very large scale molecular dynamics simulations involving tens to hundreds of millions of atoms. Our approach relies on extensible scripting languages and an easy to use tool for building extensions and modules. The system is extremely easy to modify, works with existing C code, is memory efficient, and can be used from inexpensive workstations and networks. We demonstrate how we have used this system to manipulate data from production MD simulations involving as many as 104 million atoms running on the CM-5 and Cray T3D. We also show how this approach can be used to build systems that integrate common scripting languages (including Tcl/Tk, Perl, and Python), simulation code, user extensions, and commercial data analysis packages

  7. Computational challenges in atomic, molecular and optical physics.

    Science.gov (United States)

    Taylor, Kenneth T

    2002-06-15

    Six challenges are discussed. These are the laser-driven helium atom; the laser-driven hydrogen molecule and hydrogen molecular ion; electron scattering (with ionization) from one-electron atoms; the vibrational and rotational structure of molecules such as H(3)(+) and water at their dissociation limits; laser-heated clusters; and quantum degeneracy and Bose-Einstein condensation. The first four concern fundamental few-body systems where use of high-performance computing (HPC) is currently making possible accurate modelling from first principles. This leads to reliable predictions and support for laboratory experiment as well as true understanding of the dynamics. Important aspects of these challenges addressable only via a terascale facility are set out. Such a facility makes the last two challenges in the above list meaningfully accessible for the first time, and the scientific interest together with the prospective role for HPC in these is emphasized.

  8. MAGERI: Computational pipeline for molecular-barcoded targeted resequencing.

    Directory of Open Access Journals (Sweden)

    Mikhail Shugay

    2017-05-01

    Full Text Available Unique molecular identifiers (UMIs show outstanding performance in targeted high-throughput resequencing, being the most promising approach for the accurate identification of rare variants in complex DNA samples. This approach has application in multiple areas, including cancer diagnostics, thus demanding dedicated software and algorithms. Here we introduce MAGERI, a computational pipeline that efficiently handles all caveats of UMI-based analysis to obtain high-fidelity mutation profiles and call ultra-rare variants. Using an extensive set of benchmark datasets including gold-standard biological samples with known variant frequencies, cell-free DNA from tumor patient blood samples and publicly available UMI-encoded datasets we demonstrate that our method is both robust and efficient in calling rare variants. The versatility of our software is supported by accurate results obtained for both tumor DNA and viral RNA samples in datasets prepared using three different UMI-based protocols.

  9. "Simulated molecular evolution" or computer-generated artifacts?

    Science.gov (United States)

    Darius, F; Rojas, R

    1994-11-01

    1. The authors define a function with value 1 for the positive examples and 0 for the negative ones. They fit a continuous function but do not deal at all with the error margin of the fit, which is almost as large as the function values they compute. 2. The term "quality" for the value of the fitted function gives the impression that some biological significance is associated with values of the fitted function strictly between 0 and 1, but there is no justification for this kind of interpretation and finding the point where the fit achieves its maximum does not make sense. 3. By neglecting the error margin the authors try to optimize the fitted function using differences in the second, third, fourth, and even fifth decimal place which have no statistical significance. 4. Even if such a fit could profit from more data points, the authors should first prove that the region of interest has some kind of smoothness, that is, that a continuous fit makes any sense at all. 5. "Simulated molecular evolution" is a misnomer. We are dealing here with random search. Since the margin of error is so large, the fitted function does not provide statistically significant information about the points in search space where strings with cleavage sites could be found. This implies that the method is a highly unreliable stochastic search in the space of strings, even if the neural network is capable of learning some simple correlations. 6. Classical statistical methods are for these kind of problems with so few data points clearly superior to the neural networks used as a "black box" by the authors, which in the way they are structured provide a model with an error margin as large as the numbers being computed.7. And finally, even if someone would provide us with a function which separates strings with cleavage sites from strings without them perfectly, so-called simulated molecular evolution would not be better than random selection.Since a perfect fit would only produce exactly ones or

  10. Computational study on the molecular inclusion of andrographolide by cyclodextrin

    Science.gov (United States)

    Zhou, Hongwei; Lai, Wai-Ping; Zhang, Zhiqiang; Li, Wai-Kee; Cheung, Hon-Yeung

    2009-03-01

    Due to the poor water solubility of andrographolide (andro), an inclusion technique has been developed to modify its physical and chemical properties so as to improve its bioavailability. In contrast with the immense experimental studies on the inclusion complexes of andro:cyclodextrin, no computational study has so far been carried out on this system. In this work, preliminary docking experiments with AutoDock were performed. Density Functional Theory (DFT) and Austin Model 1 (AM1) calculations upon the docking instances were applied to investigate the two possible modes of molecular inclusions between andro and x-cyclodextrin ( xCD, where x is α, β or γ). Atoms-in-Molecules (AIM) analysis based on the B3LYP/cc-pVDZ wavefunction was applied to verify the existence of the intermolecular hydrogen bonds. It was found that the most stable complex among the six possible inclusion complexes was the one formed between andro and βCD with andro's decalin ring moiety wrapped by CD at a ratio of 1:1. The hydrogen bonds between andro and CD were responsible for the stability of the inclusion complexes. The calculated data were found to be consistent with the experimental results. Thus, the results of this study can aid new drug design processes.

  11. Computer-Based Molecular Modelling: Finnish School Teachers' Experiences and Views

    Science.gov (United States)

    Aksela, Maija; Lundell, Jan

    2008-01-01

    Modern computer-based molecular modelling opens up new possibilities for chemistry teaching at different levels. This article presents a case study seeking insight into Finnish school teachers' use of computer-based molecular modelling in teaching chemistry, into the different working and teaching methods used, and their opinions about necessary…

  12. Transforming bases to bytes: Molecular computing with DNA

    Indian Academy of Sciences (India)

    Despite the popular image of silicon-based computers for computation, an embryonic field of mole- cular computation is emerging, where molecules in solution perform computational ..... [4] Mao C, Sun W, Shen Z and Seeman N C 1999. A nanomechanical device based on the B-Z transition of DNA; Nature 397 144–146.

  13. Next Generation Risk Assessment: Incorporation of Recent Advances in Molecular, Computational, and Systems Biology (Final Report)

    Science.gov (United States)

    EPA announced the release of the final report, Next Generation Risk Assessment: Incorporation of Recent Advances in Molecular, Computational, and Systems Biology. This report describes new approaches that are faster, less resource intensive, and more robust that can help ...

  14. Biotechnology Computing: Information Science for the Era of Molecular Medicine.

    Science.gov (United States)

    Masys, Daniel R.

    1989-01-01

    The evolution from classical genetics to biotechnology, an area of research involving key macromolecules in living cells, is chronicled and the current state of biotechnology is described, noting related advances in computing and clinical medicine. (MSE)

  15. Computational Nanotechnology of Molecular Materials, Electronics and Machines

    Science.gov (United States)

    Srivastava, D.; Biegel, Bryan A. (Technical Monitor)

    2002-01-01

    This viewgraph presentation covers carbon nanotubes, their characteristics, and their potential future applications. The presentation include predictions on the development of nanostructures and their applications, the thermal characteristics of carbon nanotubes, mechano-chemical effects upon carbon nanotubes, molecular electronics, and models for possible future nanostructure devices. The presentation also proposes a neural model for signal processing.

  16. A Multi-step and Multi-level approach for Computer Aided Molecular Design

    DEFF Research Database (Denmark)

    . The problem formulation step incorporates a knowledge base for the identification and setup of the design criteria. Candidate compounds are identified using a multi-level generate and test CAMD solution algorithm capable of designing molecules having a high level of molecular detail. A post solution step...... using an Integrated Computer Aided System (ICAS) for result analysis and verification is included in the methodology. Keywords: CAMD, separation processes, knowledge base, molecular design, solvent selection, substitution, group contribution, property prediction, ICAS Introduction The use of Computer...... Aided Molecular Design (CAMD) for the identification of compounds having specific physic...

  17. MC SCF molecular gradients and hessians: computational aspects

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, A; Jensen, J O; Simons, J; Shepard, R

    1984-01-01

    Molecular gradients and hessians for multiconfigurational self-consistent-field wavefunctions are derived in terms of the generators of the unitary group using exponential unitary operators to describe the response of the energy to a geometrical deformation. Final expressions are cast in forms which contain reference only to the primitive non-orthogonal atomic basis set and to the final orthonormal molecular orbitals; all reference to intermediate orthogonalized orbitals is removed. All of the deformation-dependent terms in the working equations reside in the one- and two-electron integral derivatives involving the atomic basis orbitals. The deformation-independent terms, whose contributions can be partially summed, involve symmetrized density matrix elements which have the same eight-fold index permutational symmetry as the one- and two-electron integral derivatives they multiply. This separation of deformation-dependent and -independent factors allows for single-pass integral-derivative-driven implementation of the gradient and hessian expressions. 19 references.

  18. Molecular dynamics computer simulations based on NMR data

    International Nuclear Information System (INIS)

    Vlieg, J. de.

    1989-01-01

    In the work described in this thesis atom-atom distance information obtained from two-dimensional cuclear magnetic resonance is combined with molecular dynamics simulaitons. The simulation is used to improve the accuracy of a structure model constructed on the basis of NMR data. During the MD refinement the crude NMR structure is simultaneously optimized with respect to the atomic interaction function and to the set of atom-atom distances or other NMR information. This means that insufficient experimental data is completed with theoretical knowledge and the combination will lead to more reliable structures than would be obtained from one technique alone. (author). 191 refs.; 17 figs.; 12 schemes; 22 tabs

  19. Molecular Dynamic Simulations of Nanostructured Ceramic Materials on Parallel Computers

    International Nuclear Information System (INIS)

    Vashishta, Priya; Kalia, Rajiv

    2005-01-01

    Large-scale molecular-dynamics (MD) simulations have been performed to gain insight into: (1) sintering, structure, and mechanical behavior of nanophase SiC and SiO2; (2) effects of dynamic charge transfers on the sintering of nanophase TiO2; (3) high-pressure structural transformation in bulk SiC and GaAs nanocrystals; (4) nanoindentation in Si3N4; and (5) lattice mismatched InAs/GaAs nanomesas. In addition, we have designed a multiscale simulation approach that seamlessly embeds MD and quantum-mechanical (QM) simulations in a continuum simulation. The above research activities have involved strong interactions with researchers at various universities, government laboratories, and industries. 33 papers have been published and 22 talks have been given based on the work described in this report

  20. Computational analyses of synergism in small molecular network motifs.

    Directory of Open Access Journals (Sweden)

    Yili Zhang

    2014-03-01

    Full Text Available Cellular functions and responses to stimuli are controlled by complex regulatory networks that comprise a large diversity of molecular components and their interactions. However, achieving an intuitive understanding of the dynamical properties and responses to stimuli of these networks is hampered by their large scale and complexity. To address this issue, analyses of regulatory networks often focus on reduced models that depict distinct, reoccurring connectivity patterns referred to as motifs. Previous modeling studies have begun to characterize the dynamics of small motifs, and to describe ways in which variations in parameters affect their responses to stimuli. The present study investigates how variations in pairs of parameters affect responses in a series of ten common network motifs, identifying concurrent variations that act synergistically (or antagonistically to alter the responses of the motifs to stimuli. Synergism (or antagonism was quantified using degrees of nonlinear blending and additive synergism. Simulations identified concurrent variations that maximized synergism, and examined the ways in which it was affected by stimulus protocols and the architecture of a motif. Only a subset of architectures exhibited synergism following paired changes in parameters. The approach was then applied to a model describing interlocked feedback loops governing the synthesis of the CREB1 and CREB2 transcription factors. The effects of motifs on synergism for this biologically realistic model were consistent with those for the abstract models of single motifs. These results have implications for the rational design of combination drug therapies with the potential for synergistic interactions.

  1. Molecular hydrogen solvated in water – A computational study

    International Nuclear Information System (INIS)

    Śmiechowski, Maciej

    2015-01-01

    The aqueous hydrogen molecule is studied with molecular dynamics simulations at ambient temperature and pressure conditions, using a newly developed flexible and polarizable H 2 molecule model. The design and implementation of this model, compatible with an existing flexible and polarizable force field for water, is presented in detail. The structure of the hydration layer suggests that first-shell water molecules accommodate the H 2 molecule without major structural distortions and two-dimensional, radial-angular distribution functions indicate that as opposed to strictly tangential, the orientation of these water molecules is such that the solute is solvated with one of the free electron pairs of H 2 O. The calculated self-diffusion coefficient of H 2 (aq) agrees very well with experimental results and the time dependence of mean square displacement suggests the presence of caging on a time scale corresponding to hydrogen bond network vibrations in liquid water. Orientational correlation function of H 2 experiences an extremely short-scale decay, making the H 2 –H 2 O interaction potential essentially isotropic by virtue of rotational averaging. The inclusion of explicit polarizability in the model allows for the calculation of Raman spectra that agree very well with available experimental data on H 2 (aq) under differing pressure conditions, including accurate reproduction of the experimentally noted trends with solute pressure or concentration

  2. DNA-programmed dynamic assembly of quantum dots for molecular computation.

    Science.gov (United States)

    He, Xuewen; Li, Zhi; Chen, Muzi; Ma, Nan

    2014-12-22

    Despite the widespread use of quantum dots (QDs) for biosensing and bioimaging, QD-based bio-interfaceable and reconfigurable molecular computing systems have not yet been realized. DNA-programmed dynamic assembly of multi-color QDs is presented for the construction of a new class of fluorescence resonance energy transfer (FRET)-based QD computing systems. A complete set of seven elementary logic gates (OR, AND, NOR, NAND, INH, XOR, XNOR) are realized using a series of binary and ternary QD complexes operated by strand displacement reactions. The integration of different logic gates into a half-adder circuit for molecular computation is also demonstrated. This strategy is quite versatile and straightforward for logical operations and would pave the way for QD-biocomputing-based intelligent molecular diagnostics. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. A resource letter CSSMD-1: computer simulation studies by the method of molecular dynamics

    International Nuclear Information System (INIS)

    Goel, S.P.; Hockney, R.W.

    1974-01-01

    A comprehensive bibliography on computer simulation studies by the method of Molecular Dynamics is presented. The bibliography includes references to relevant literature published up to mid 1973, starting from the first paper of Alder and Wainwright, published in 1957. The procedure of the method of Molecular Dynamics, the main fields of study in which it has been used, its limitations and how these have been overcome in some cases are also discussed [pt

  4. The impact of computer science in molecular medicine: enabling high-throughput research.

    Science.gov (United States)

    de la Iglesia, Diana; García-Remesal, Miguel; de la Calle, Guillermo; Kulikowski, Casimir; Sanz, Ferran; Maojo, Víctor

    2013-01-01

    The Human Genome Project and the explosion of high-throughput data have transformed the areas of molecular and personalized medicine, which are producing a wide range of studies and experimental results and providing new insights for developing medical applications. Research in many interdisciplinary fields is resulting in data repositories and computational tools that support a wide diversity of tasks: genome sequencing, genome-wide association studies, analysis of genotype-phenotype interactions, drug toxicity and side effects assessment, prediction of protein interactions and diseases, development of computational models, biomarker discovery, and many others. The authors of the present paper have developed several inventories covering tools, initiatives and studies in different computational fields related to molecular medicine: medical informatics, bioinformatics, clinical informatics and nanoinformatics. With these inventories, created by mining the scientific literature, we have carried out several reviews of these fields, providing researchers with a useful framework to locate, discover, search and integrate resources. In this paper we present an analysis of the state-of-the-art as it relates to computational resources for molecular medicine, based on results compiled in our inventories, as well as results extracted from a systematic review of the literature and other scientific media. The present review is based on the impact of their related publications and the available data and software resources for molecular medicine. It aims to provide information that can be useful to support ongoing research and work to improve diagnostics and therapeutics based on molecular-level insights.

  5. Molecular Imaging : Computer Reconstruction and Practice - Proceedings of the NATO Advanced Study Institute on Molecular Imaging from Physical Principles to Computer Reconstruction and Practice

    CERN Document Server

    Lemoigne, Yves

    2008-01-01

    This volume collects the lectures presented at the ninth ESI School held at Archamps (FR) in November 2006 and is dedicated to nuclear physics applications in molecular imaging. The lectures focus on the multiple facets of image reconstruction processing and management and illustrate the role of digital imaging in clinical practice. Medical computing and image reconstruction are introduced by analysing the underlying physics principles and their implementation, relevant quality aspects, clinical performance and recent advancements in the field. Several stages of the imaging process are specifically addressed, e.g. optimisation of data acquisition and storage, distributed computing, physiology and detector modelling, computer algorithms for image reconstruction and measurement in tomography applications, for both clinical and biomedical research applications. All topics are presented with didactical language and style, making this book an appropriate reference for students and professionals seeking a comprehen...

  6. Generic Mathematical Programming Formulation and Solution for Computer-Aided Molecular Design

    DEFF Research Database (Denmark)

    Zhang, Lei; Cignitti, Stefano; Gani, Rafiqul

    2015-01-01

    This short communication presents a generic mathematical programming formulation for Computer-Aided Molecular Design (CAMD). A given CAMD problem, based on target properties, is formulated as a Mixed Integer Linear/Non-Linear Program (MILP/MINLP). The mathematical programming model presented here......, which is formulated as an MILP/MINLP problem, considers first-order and second-order molecular groups for molecular structure representation and property estimation. It is shown that various CAMD problems can be formulated and solved through this model....

  7. Computer simulation of molecular absorption spectra for asymmetric top molecules

    International Nuclear Information System (INIS)

    Bende, A.; Tosa, V.; Cosma, V.

    2001-01-01

    particular, for CF 2 HCl (with the asymmetric constant τ = -0.58) we present the basic algorithm used for selecting the vibration-rotation states involved in the excitation process. A computer program has been written and used for the calculation of the number of photons absorbed by the CF 2 HCl as a function of the temperature, exciting laser frequency and laser fluences. (authors)

  8. Petascale molecular dynamics simulation using the fast multipole method on K computer

    KAUST Repository

    Ohno, Yousuke; Yokota, Rio; Koyama, Hiroshi; Morimoto, Gentaro; Hasegawa, Aki; Masumoto, Gen; Okimoto, Noriaki; Hirano, Yoshinori; Ibeid, Huda; Narumi, Tetsu; Taiji, Makoto

    2014-01-01

    In this paper, we report all-atom simulations of molecular crowding - a result from the full node simulation on the "K computer", which is a 10-PFLOPS supercomputer in Japan. The capability of this machine enables us to perform simulation of crowded cellular environments, which are more realistic compared to conventional MD simulations where proteins are simulated in isolation. Living cells are "crowded" because macromolecules comprise ∼30% of their molecular weight. Recently, the effects of crowded cellular environments on protein stability have been revealed through in-cell NMR spectroscopy. To measure the performance of the "K computer", we performed all-atom classical molecular dynamics simulations of two systems: target proteins in a solvent, and target proteins in an environment of molecular crowders that mimic the conditions of a living cell. Using the full system, we achieved 4.4 PFLOPS during a 520 million-atom simulation with cutoff of 28 Å. Furthermore, we discuss the performance and scaling of fast multipole methods for molecular dynamics simulations on the "K computer", as well as comparisons with Ewald summation methods. © 2014 Elsevier B.V. All rights reserved.

  9. On the computation of molecular surface correlations for protein docking using fourier techniques.

    Science.gov (United States)

    Sakk, Eric

    2007-08-01

    The computation of surface correlations using a variety of molecular models has been applied to the unbound protein docking problem. Because of the computational complexity involved in examining all possible molecular orientations, the fast Fourier transform (FFT) (a fast numerical implementation of the discrete Fourier transform (DFT)) is generally applied to minimize the number of calculations. This approach is rooted in the convolution theorem which allows one to inverse transform the product of two DFTs in order to perform the correlation calculation. However, such a DFT calculation results in a cyclic or "circular" correlation which, in general, does not lead to the same result as the linear correlation desired for the docking problem. In this work, we provide computational bounds for constructing molecular models used in the molecular surface correlation problem. The derived bounds are then shown to be consistent with various intuitive guidelines previously reported in the protein docking literature. Finally, these bounds are applied to different molecular models in order to investigate their effect on the correlation calculation.

  10. Petascale molecular dynamics simulation using the fast multipole method on K computer

    KAUST Repository

    Ohno, Yousuke

    2014-10-01

    In this paper, we report all-atom simulations of molecular crowding - a result from the full node simulation on the "K computer", which is a 10-PFLOPS supercomputer in Japan. The capability of this machine enables us to perform simulation of crowded cellular environments, which are more realistic compared to conventional MD simulations where proteins are simulated in isolation. Living cells are "crowded" because macromolecules comprise ∼30% of their molecular weight. Recently, the effects of crowded cellular environments on protein stability have been revealed through in-cell NMR spectroscopy. To measure the performance of the "K computer", we performed all-atom classical molecular dynamics simulations of two systems: target proteins in a solvent, and target proteins in an environment of molecular crowders that mimic the conditions of a living cell. Using the full system, we achieved 4.4 PFLOPS during a 520 million-atom simulation with cutoff of 28 Å. Furthermore, we discuss the performance and scaling of fast multipole methods for molecular dynamics simulations on the "K computer", as well as comparisons with Ewald summation methods. © 2014 Elsevier B.V. All rights reserved.

  11. Proceedings of the international symposium on atomic, molecular, and condensed matter theory and computational methods

    International Nuclear Information System (INIS)

    Loewdin, Per-Olov; Oehrn, N.Y.; Sabin, J.R.; Zerner, M.C.

    1993-01-01

    After an introduction and a personal (World War II and postwar) retrospective by C.C.J. Roothaan, 69 papers are presented in fields of quantum biology, quantum chemistry, and condensed matter physics; topics covered include advanced scientific computing, interaction of photons and matter, quantum molecular dynamics, electronic structure methods, polymeric systems, and quantum chemical methods for extended systems. An author index is included

  12. Fast parallel molecular algorithms for DNA-based computation: factoring integers.

    Science.gov (United States)

    Chang, Weng-Long; Guo, Minyi; Ho, Michael Shan-Hui

    2005-06-01

    The RSA public-key cryptosystem is an algorithm that converts input data to an unrecognizable encryption and converts the unrecognizable data back into its original decryption form. The security of the RSA public-key cryptosystem is based on the difficulty of factoring the product of two large prime numbers. This paper demonstrates to factor the product of two large prime numbers, and is a breakthrough in basic biological operations using a molecular computer. In order to achieve this, we propose three DNA-based algorithms for parallel subtractor, parallel comparator, and parallel modular arithmetic that formally verify our designed molecular solutions for factoring the product of two large prime numbers. Furthermore, this work indicates that the cryptosystems using public-key are perhaps insecure and also presents clear evidence of the ability of molecular computing to perform complicated mathematical operations.

  13. Use of Nonequilibrium Work Methods to Compute Free Energy Differences Between Molecular Mechanical and Quantum Mechanical Representations of Molecular Systems.

    Science.gov (United States)

    Hudson, Phillip S; Woodcock, H Lee; Boresch, Stefan

    2015-12-03

    Carrying out free energy simulations (FES) using quantum mechanical (QM) Hamiltonians remains an attractive, albeit elusive goal. Renewed efforts in this area have focused on using "indirect" thermodynamic cycles to connect "low level" simulation results to "high level" free energies. The main obstacle to computing converged free energy results between molecular mechanical (MM) and QM (ΔA(MM→QM)), as recently demonstrated by us and others, is differences in the so-called "stiff" degrees of freedom (e.g., bond stretching) between the respective energy surfaces. Herein, we demonstrate that this problem can be efficiently circumvented using nonequilibrium work (NEW) techniques, i.e., Jarzynski's and Crooks' equations. Initial applications of computing ΔA(NEW)(MM→QM), for blocked amino acids alanine and serine as well as to generate butane's potentials of mean force via the indirect QM/MM FES method, showed marked improvement over traditional FES approaches.

  14. Molecular structure descriptors in the computer-aided design of biologically active compounds

    International Nuclear Information System (INIS)

    Raevsky, Oleg A

    1999-01-01

    The current state of description of molecular structure in computer-aided molecular design of biologically active compounds by means of descriptors is analysed. The information contents of descriptors increases in the following sequence: element-level descriptors-structural formulae descriptors-electronic structure descriptors-molecular shape descriptors-intermolecular interaction descriptors. Each subsequent class of descriptors normally covers information contained in the previous-level ones. It is emphasised that it is practically impossible to describe all the features of a molecular structure in terms of any single class of descriptors. It is recommended to optimise the number of descriptors used by means of appropriate statistical procedures and characteristics of structure-property models based on these descriptors. The bibliography includes 371 references.

  15. A Parallel Biological Optimization Algorithm to Solve the Unbalanced Assignment Problem Based on DNA Molecular Computing.

    Science.gov (United States)

    Wang, Zhaocai; Pu, Jun; Cao, Liling; Tan, Jian

    2015-10-23

    The unbalanced assignment problem (UAP) is to optimally resolve the problem of assigning n jobs to m individuals (m applied mathematics, having numerous real life applications. In this paper, we present a new parallel DNA algorithm for solving the unbalanced assignment problem using DNA molecular operations. We reasonably design flexible-length DNA strands representing different jobs and individuals, take appropriate steps, and get the solutions of the UAP in the proper length range and O(mn) time. We extend the application of DNA molecular operations and simultaneity to simplify the complexity of the computation.

  16. Discovering Unique, Low-Energy Transition States Using Evolutionary Molecular Memetic Computing

    DEFF Research Database (Denmark)

    Ellabaan, Mostafa M Hashim; Ong, Y.S.; Handoko, S.D.

    2013-01-01

    In the last few decades, identification of transition states has experienced significant growth in research interests from various scientific communities. As per the transition states theory, reaction paths and landscape analysis as well as many thermodynamic properties of biochemical systems can...... be accurately identified through the transition states. Transition states describe the paths of molecular systems in transiting across stable states. In this article, we present the discovery of unique, low-energy transition states and showcase the efficacy of their identification using the memetic computing...... paradigm under a Molecular Memetic Computing (MMC) framework. In essence, the MMC is equipped with the tree-based representation of non-cyclic molecules and the covalent-bond-driven evolutionary operators, in addition to the typical backbone of memetic algorithms. Herein, we employ genetic algorithm...

  17. From Computational Photobiology to the Design of Vibrationally Coherent Molecular Devices and Motors

    Science.gov (United States)

    Olivucci, Massimo

    2014-03-01

    In the past multi-configurational quantum chemical computations coupled with molecular mechanics force fields have been employed to investigate spectroscopic, thermal and photochemical properties of visual pigments. Here we show how the same computational technology can nowadays be used to design, characterize and ultimately, prepare light-driven molecular switches which mimics the photophysics of the visual pigment bovine rhodopsin (Rh). When embedded in the protein cavity the chromophore of Rh undergoes an ultrafast and coherent photoisomerization. In order to design a synthetic chromophore displaying similar properties in common solvents, we recently focused on indanylidene-pyrroline (NAIP) systems. We found that these systems display light-induced ground state coherent vibrational motion similar to the one detected in Rh. Semi-classical trajectories provide a mechanistic description of the structural changes associated to the observed coherent motion which is shown to be ultimately due to periodic changes in the π-conjugation.

  18. Chapter 6 – Computer-Aided Molecular Design and Property Prediction

    DEFF Research Database (Denmark)

    Gani, Rafiqul; Zhang, L.; Kalakul, Sawitree

    2017-01-01

    for the initial stages of the design/development process. Therefore, computer-aided molecular design and property prediction techniques are two topics that play important roles in chemical product design, analysis, and application. In this chapter, an overview of the concepts, methods, and tools related......Today's society needs many chemical-based products for its survival, nutrition, health, transportation, agriculture, and the functioning of processes. Chemical-based products have to be designed/developed in order to meet these needs, while at the same time, they must be innovative and sustainable...... to these two topics are given. In addition, a generic computer-aided framework for the design of molecules, mixtures, and blends is presented. The application of the framework is highlighted for molecular products through two case studies involving the design of refrigerants and surfactants....

  19. A computer-aided molecular design framework for crystallization solvent design

    DEFF Research Database (Denmark)

    Karunanithi, Arunprakash T.; Achenie, Luke E.K.; Gani, Rafiqul

    2006-01-01

    One of the key decisions in designing solution crystallization processes is the selection of solvents. In this paper, we present a computer-aided molecular design (CAMD) framework for the design and selection of solvents and/or anti-solvents for solution crystallization. The CAMD problem is formu......One of the key decisions in designing solution crystallization processes is the selection of solvents. In this paper, we present a computer-aided molecular design (CAMD) framework for the design and selection of solvents and/or anti-solvents for solution crystallization. The CAMD problem...... solvent molecules. Solvent design and selection for two types of solution crystallization processes namely cooling crystallization and drowning out crystallization are presented. In the first case study, the design of single compound solvent for crystallization of ibuprofen, which is an important...

  20. Recent Advances in Cardiac Computed Tomography: Dual Energy, Spectral and Molecular CT Imaging

    Science.gov (United States)

    Danad, Ibrahim; Fayad, Zahi A.; Willemink, Martin J.; Min, James K.

    2015-01-01

    Computed tomography (CT) evolved into a powerful diagnostic tool and it is impossible to imagine current clinical practice without CT imaging. Due to its widespread availability, ease of clinical application, superb sensitivity for detection of CAD, and non-invasive nature, CT has become a valuable tool within the armamentarium of the cardiologist. In the last few years, numerous technological advances in CT have occurred—including dual energy CT (DECT), spectral CT and CT-based molecular imaging. By harnessing the advances in technology, cardiac CT has advanced beyond the mere evaluation of coronary stenosis to an imaging modality tool that permits accurate plaque characterization, assessment of myocardial perfusion and even probing of molecular processes that are involved in coronary atherosclerosis. Novel innovations in CT contrast agents and pre-clinical spectral CT devices have paved the way for CT-based molecular imaging. PMID:26068288

  1. A computer program for external modes in complex ionic crystals (the rigid molecular-ion model)

    International Nuclear Information System (INIS)

    Chaplot, S.L.

    1978-01-01

    A computer program DISPR has been developed to calculate the external mode phonon dispersion relation in the harmonic approximation for complex ionic crystals using the rigid molecular ion model. A description of the program, the flow diagram and the required input information are given. A sample calculation for α-KNO 3 is presented. The program can handle any type of crystal lattice with any number of atoms and molecules per unit cell with suitable changes in dimension statements. (M.G.B.)

  2. A Computational and Theoretical Study of Conductance in Hydrogen-bonded Molecular Junctions

    Science.gov (United States)

    Wimmer, Michael

    This thesis is devoted to the theoretical and computational study of electron transport in molecular junctions where one or more hydrogen bonds are involved in the process. While electron transport through covalent bonds has been extensively studied, in recent work the focus has been shifted towards hydrogen-bonded systems due to their ubiquitous presence in biological systems and their potential in forming nano-junctions between molecular electronic devices and biological systems. This analysis allows us to significantly expand our comprehension of the experimentally observed result that the inclusion of hydrogen bonding in a molecular junction significantly impacts its transport properties, a fact that has important implications for our understanding of transport through DNA, and nano-biological interfaces in general. In part of this work I have explored the implications of quasiresonant transport in short chains of weakly-bonded molecular junctions involving hydrogen bonds. I used theoretical and computational analysis to interpret recent experiments and explain the role of Fano resonances in the transmission properties of the junction. In a different direction, I have undertaken the study of the transversal conduction through nucleotide chains that involve a variable number of different hydrogen bonds, e.g. NH˙˙˙O, OH˙˙˙O, and NH˙˙˙N, which are the three most prevalent hydrogen bonds in biological systems and organic electronics. My effort here has focused on the analysis of electronic descriptors that allow a simplified conceptual and computational understanding of transport properties. Specifically, I have expanded our previous work where the molecular polarizability was used as a conductance descriptor to include the possibility of atomic and bond partitions of the molecular polarizability. This is important because it affords an alternative molecular description of conductance that is not based on the conventional view of molecular orbitals as

  3. Parallel computation with molecular-motor-propelled agents in nanofabricated networks.

    Science.gov (United States)

    Nicolau, Dan V; Lard, Mercy; Korten, Till; van Delft, Falco C M J M; Persson, Malin; Bengtsson, Elina; Månsson, Alf; Diez, Stefan; Linke, Heiner; Nicolau, Dan V

    2016-03-08

    The combinatorial nature of many important mathematical problems, including nondeterministic-polynomial-time (NP)-complete problems, places a severe limitation on the problem size that can be solved with conventional, sequentially operating electronic computers. There have been significant efforts in conceiving parallel-computation approaches in the past, for example: DNA computation, quantum computation, and microfluidics-based computation. However, these approaches have not proven, so far, to be scalable and practical from a fabrication and operational perspective. Here, we report the foundations of an alternative parallel-computation system in which a given combinatorial problem is encoded into a graphical, modular network that is embedded in a nanofabricated planar device. Exploring the network in a parallel fashion using a large number of independent, molecular-motor-propelled agents then solves the mathematical problem. This approach uses orders of magnitude less energy than conventional computers, thus addressing issues related to power consumption and heat dissipation. We provide a proof-of-concept demonstration of such a device by solving, in a parallel fashion, the small instance {2, 5, 9} of the subset sum problem, which is a benchmark NP-complete problem. Finally, we discuss the technical advances necessary to make our system scalable with presently available technology.

  4. Quantum and semiclassical spin networks: from atomic and molecular physics to quantum computing and gravity

    Science.gov (United States)

    Aquilanti, Vincenzo; Bitencourt, Ana Carla P.; Ferreira, Cristiane da S.; Marzuoli, Annalisa; Ragni, Mirco

    2008-11-01

    The mathematical apparatus of quantum-mechanical angular momentum (re)coupling, developed originally to describe spectroscopic phenomena in atomic, molecular, optical and nuclear physics, is embedded in modern algebraic settings which emphasize the underlying combinatorial aspects. SU(2) recoupling theory, involving Wigner's 3nj symbols, as well as the related problems of their calculations, general properties, asymptotic limits for large entries, nowadays plays a prominent role also in quantum gravity and quantum computing applications. We refer to the ingredients of this theory—and of its extension to other Lie and quantum groups—by using the collective term of 'spin networks'. Recent progress is recorded about the already established connections with the mathematical theory of discrete orthogonal polynomials (the so-called Askey scheme), providing powerful tools based on asymptotic expansions, which correspond on the physical side to various levels of semi-classical limits. These results are useful not only in theoretical molecular physics but also in motivating algorithms for the computationally demanding problems of molecular dynamics and chemical reaction theory, where large angular momenta are typically involved. As for quantum chemistry, applications of these techniques include selection and classification of complete orthogonal basis sets in atomic and molecular problems, either in configuration space (Sturmian orbitals) or in momentum space. In this paper, we list and discuss some aspects of these developments—such as for instance the hyperquantization algorithm—as well as a few applications to quantum gravity and topology, thus providing evidence of a unifying background structure.

  5. Computation of Dielectric Response in Molecular Solids for High Capacitance Organic Dielectrics.

    Science.gov (United States)

    Heitzer, Henry M; Marks, Tobin J; Ratner, Mark A

    2016-09-20

    The dielectric response of a material is central to numerous processes spanning the fields of chemistry, materials science, biology, and physics. Despite this broad importance across these disciplines, describing the dielectric environment of a molecular system at the level of first-principles theory and computation remains a great challenge and is of importance to understand the behavior of existing systems as well as to guide the design and synthetic realization of new ones. Furthermore, with recent advances in molecular electronics, nanotechnology, and molecular biology, it has become necessary to predict the dielectric properties of molecular systems that are often difficult or impossible to measure experimentally. In these scenarios, it is would be highly desirable to be able to determine dielectric response through efficient, accurate, and chemically informative calculations. A good example of where theoretical modeling of dielectric response would be valuable is in the development of high-capacitance organic gate dielectrics for unconventional electronics such as those that could be fabricated by high-throughput printing techniques. Gate dielectrics are fundamental components of all transistor-based logic circuitry, and the combination high dielectric constant and nanoscopic thickness (i.e., high capacitance) is essential to achieving high switching speeds and low power consumption. Molecule-based dielectrics offer the promise of cheap, flexible, and mass producible electronics when used in conjunction with unconventional organic or inorganic semiconducting materials to fabricate organic field effect transistors (OFETs). The molecular dielectrics developed to date typically have limited dielectric response, which results in low capacitances, translating into poor performance of the resulting OFETs. Furthermore, the development of better performing dielectric materials has been hindered by the current highly empirical and labor-intensive pace of synthetic

  6. Molecular architectures based on π-conjugated block copolymers for global quantum computation

    International Nuclear Information System (INIS)

    Mujica Martinez, C A; Arce, J C; Reina, J H; Thorwart, M

    2009-01-01

    We propose a molecular setup for the physical implementation of a barrier global quantum computation scheme based on the electron-doped π-conjugated copolymer architecture of nine blocks PPP-PDA-PPP-PA-(CCH-acene)-PA-PPP-PDA-PPP (where each block is an oligomer). The physical carriers of information are electrons coupled through the Coulomb interaction, and the building block of the computing architecture is composed by three adjacent qubit systems in a quasi-linear arrangement, each of them allowing qubit storage, but with the central qubit exhibiting a third accessible state of electronic energy far away from that of the qubits' transition energy. The third state is reached from one of the computational states by means of an on-resonance coherent laser field, and acts as a barrier mechanism for the direct control of qubit entanglement. Initial estimations of the spontaneous emission decay rates associated to the energy level structure allow us to compute a damping rate of order 10 -7 s, which suggest a not so strong coupling to the environment. Our results offer an all-optical, scalable, proposal for global quantum computing based on semiconducting π-conjugated polymers.

  7. Molecular architectures based on pi-conjugated block copolymers for global quantum computation

    Energy Technology Data Exchange (ETDEWEB)

    Mujica Martinez, C A; Arce, J C [Universidad del Valle, Departamento de QuImica, A. A. 25360, Cali (Colombia); Reina, J H [Universidad del Valle, Departamento de Fisica, A. A. 25360, Cali (Colombia); Thorwart, M, E-mail: camujica@univalle.edu.c, E-mail: j.reina-estupinan@physics.ox.ac.u, E-mail: jularce@univalle.edu.c [Institut fuer Theoretische Physik IV, Heinrich-Heine-Universitaet Duesseldorf, 40225 Duesseldorf (Germany)

    2009-05-01

    We propose a molecular setup for the physical implementation of a barrier global quantum computation scheme based on the electron-doped pi-conjugated copolymer architecture of nine blocks PPP-PDA-PPP-PA-(CCH-acene)-PA-PPP-PDA-PPP (where each block is an oligomer). The physical carriers of information are electrons coupled through the Coulomb interaction, and the building block of the computing architecture is composed by three adjacent qubit systems in a quasi-linear arrangement, each of them allowing qubit storage, but with the central qubit exhibiting a third accessible state of electronic energy far away from that of the qubits' transition energy. The third state is reached from one of the computational states by means of an on-resonance coherent laser field, and acts as a barrier mechanism for the direct control of qubit entanglement. Initial estimations of the spontaneous emission decay rates associated to the energy level structure allow us to compute a damping rate of order 10{sup -7} s, which suggest a not so strong coupling to the environment. Our results offer an all-optical, scalable, proposal for global quantum computing based on semiconducting pi-conjugated polymers.

  8. Use of Computational Modeling to Evaluate Hypotheses About the Molecular and Cellular Mechanisms of Bystander Effects

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Yuchao; Conolly, Rory B; Andersen, Melvin E.

    2006-11-21

    This report describes the development of a computational systems biology approach to evaluate the hypotheses of molecular and cellular mechanisms of adaptive response to low dose ionizing radiation. Our concept is that computational models of signaling pathways can be developed and linked to biologically based dose response models to evaluate the underlying molecular mechanisms which lead to adaptive response. For development of quantitatively accurate, predictive models, it will be necessary to describe tissues consisting of multiple cell types where the different types each contribute in their own way to the overall function of the tissue. Such a model will probably need to incorporate not only cell type-specific data but also spatial information on the architecture of the tissue and on intercellular signaling. The scope of the current model was more limited. Data obtained in a number of different biological systems were synthesized to describe a chimeric, “average” population cell. Biochemical signaling pathways involved in sensing of DNA damage and in the activation of cell cycle checkpoint controls and the apoptotic path were also included. As with any computational modeling effort, it was necessary to develop these simplified initial descriptions (models) that can be iteratively refined. This preliminary model is a starting point which, with time, can evolve to a level of refinement where large amounts of detailed biological information are synthesized and a capability for robust predictions of dose- and time-response behaviors is obtained.

  9. Molecular interactions in the betaine monohydrate-polyol deep eutectic solvents: Experimental and computational studies

    Science.gov (United States)

    Zahrina, Ida; Mulia, Kamarza; Yanuar, Arry; Nasikin, Mohammad

    2018-04-01

    DES (deep eutectic solvents) are a new class of ionic liquids that have excellent properties. The strength of interaction between molecules in the DES affects their properties and applications. In this work, the strength of molecular interactions between components in the betaine monohydrate salt and polyol (glycerol or/and propylene glycol) eutectic mixtures was studied by experimental and computational studies. The melting point and fusion enthalpy of the mixtures were measured using STA (Simultaneous Thermal Analyzer). The nature and strength of intermolecular interactions were observed by FT-IR and NMR spectroscopy. The molecular dynamics simulation was used to determine the number of H-bonds, percent occupancy, and radial distribution functions in the eutectic mixtures. The interaction between betaine monohydrate and polyol is following order: betaine monohydrate-glycerol-propylene glycol > betaine monohydrate-glycerol > betaine monohydrate-propylene glycol, where the latter is the eutectic mixture with the lowest stability, strength and extent of the hydrogen bonding interactions between component molecules. The presence of intra-molecular hydrogen bonding interactions, the inter-molecular hydrogen bonding interactions between betaine molecule and polyol, and also interactions between polyol and H2O of betaine monohydrate in the eutectic mixtures.

  10. A Parallel Biological Optimization Algorithm to Solve the Unbalanced Assignment Problem Based on DNA Molecular Computing

    Directory of Open Access Journals (Sweden)

    Zhaocai Wang

    2015-10-01

    Full Text Available The unbalanced assignment problem (UAP is to optimally resolve the problem of assigning n jobs to m individuals (m < n, such that minimum cost or maximum profit obtained. It is a vitally important Non-deterministic Polynomial (NP complete problem in operation management and applied mathematics, having numerous real life applications. In this paper, we present a new parallel DNA algorithm for solving the unbalanced assignment problem using DNA molecular operations. We reasonably design flexible-length DNA strands representing different jobs and individuals, take appropriate steps, and get the solutions of the UAP in the proper length range and O(mn time. We extend the application of DNA molecular operations and simultaneity to simplify the complexity of the computation.

  11. Introductory Molecular Orbital Theory: An Honors General Chemistry Computational Lab as Implemented Using Three-Dimensional Modeling Software

    Science.gov (United States)

    Ruddick, Kristie R.; Parrill, Abby L.; Petersen, Richard L.

    2012-01-01

    In this study, a computational molecular orbital theory experiment was implemented in a first-semester honors general chemistry course. Students used the GAMESS (General Atomic and Molecular Electronic Structure System) quantum mechanical software (as implemented in ChemBio3D) to optimize the geometry for various small molecules. Extended Huckel…

  12. Molecular Rearrangement of an Aza-Scorpiand Macrocycle Induced by pH: A Computational Study

    Directory of Open Access Journals (Sweden)

    Jesus Vicente De Julián-Ortiz

    2016-07-01

    Full Text Available Rearrangements and their control are a hot topic in supramolecular chemistry due to the possibilities that these phenomena open in the design of synthetic receptors and molecular machines. Macrocycle aza-scorpiands constitute an interesting system that can reorganize their spatial structure depending on pH variations or the presence of metal cations. In this study, the relative stabilities of these conformations were predicted computationally by semi-empirical and density functional theory approximations, and the reorganization from closed to open conformations was simulated by using the Monte Carlo multiple minimum method.

  13. High resolution color raster computer animation of space filling molecular models

    Energy Technology Data Exchange (ETDEWEB)

    Max, N.L.

    1981-01-01

    The ATOMLLL system efficiently produces realistic photographs of ball-and-stick or space-filling molecular models, with color shading, highlights, shadows, and transparency. The hidden surface problem for a scene composed of intersecting spheres and cylinders is solved on a CDC-7600, which outputs onto magnetic tape the outlines of the visible parts of each object. The outlines are then rendered, at up to 4096 x 4096 resolution, by a Dicomed D-48 color film recorder, controlled by a Varian V-75 minicomputer. The Varian computes the shading and highlights for each pixel in a fast microcoded loop. Recent modifications to give shadows and transparency are described.

  14. Parallel computations of molecular dynamics trajectories using the stochastic path approach

    Science.gov (United States)

    Zaloj, Veaceslav; Elber, Ron

    2000-06-01

    A novel protocol to parallelize molecular dynamics trajectories is discussed and tested on a cluster of PCs running the NT operating system. The new technique does not propagate the solution in small time steps, but uses instead a global optimization of a functional of the whole trajectory. The new approach is especially attractive for parallel and distributed computing and its advantages (and disadvantages) are presented. Two numerical examples are discussed: (a) A conformational transition in a solvated dipeptide, and (b) The R→T conformational transition in solvated hemoglobin.

  15. Metalloporphyrin catalysts for oxygen reduction developed using computer-aided molecular design

    Energy Technology Data Exchange (ETDEWEB)

    Ryba, G.N.; Hobbs, J.D.; Shelnutt, J.A. [and others

    1996-04-01

    The objective of this project is the development of a new class of metalloporphyrin materials used as catalsyts for use in fuel cell applications. The metalloporphyrins are excellent candidates for use as catalysts at both the anode and cathode. The catalysts reduce oxygen in 1 M potassium hydroxide, as well as in 2 M sulfuric acid. Covalent attachment to carbon supports is being investigated. The computer-aided molecular design is an iterative process, in which experimental results feed back into the design of future catalysts.

  16. High resolution color raster computer animation of space filling molecular models

    International Nuclear Information System (INIS)

    Max, N.L.

    1981-01-01

    The ATOMLLL system efficiently produces realistic photographs of ball-and-stick or space-filling molecular models, with color shading, highlights, shadows, and transparency. The hidden surface problem for a scene composed of intersecting spheres and cylinders is solved on a CDC-7600, which outputs onto magnetic tape the outlines of the visible parts of each object. The outlines are then rendered, at up to 4096 x 4096 resolution, by a Dicomed D-48 color film recorder, controlled by a Varian V-75 minicomputer. The Varian computes the shading and highlights for each pixel in a fast microcoded loop. Recent modifications to give shadows and transparency are described

  17. CheckDen, a program to compute quantum molecular properties on spatial grids.

    Science.gov (United States)

    Pacios, Luis F; Fernandez, Alberto

    2009-09-01

    CheckDen, a program to compute quantum molecular properties on a variety of spatial grids is presented. The program reads as unique input wavefunction files written by standard quantum packages and calculates the electron density rho(r), promolecule and density difference function, gradient of rho(r), Laplacian of rho(r), information entropy, electrostatic potential, kinetic energy densities G(r) and K(r), electron localization function (ELF), and localized orbital locator (LOL) function. These properties can be calculated on a wide range of one-, two-, and three-dimensional grids that can be processed by widely used graphics programs to render high-resolution images. CheckDen offers also other options as extracting separate atom contributions to the property computed, converting grid output data into CUBE and OpenDX volumetric data formats, and perform arithmetic combinations with grid files in all the recognized formats.

  18. Computer Simulation and Data Analysis in Molecular Biology and Biophysics An Introduction Using R

    CERN Document Server

    Bloomfield, Victor

    2009-01-01

    This book provides an introduction, suitable for advanced undergraduates and beginning graduate students, to two important aspects of molecular biology and biophysics: computer simulation and data analysis. It introduces tools to enable readers to learn and use fundamental methods for constructing quantitative models of biological mechanisms, both deterministic and with some elements of randomness, including complex reaction equilibria and kinetics, population models, and regulation of metabolism and development; to understand how concepts of probability can help in explaining important features of DNA sequences; and to apply a useful set of statistical methods to analysis of experimental data from spectroscopic, genomic, and proteomic sources. These quantitative tools are implemented using the free, open source software program R. R provides an excellent environment for general numerical and statistical computing and graphics, with capabilities similar to Matlab®. Since R is increasingly used in bioinformat...

  19. The Early Years of Molecular Dynamics and Computers at UCRL, LRL, LLL, and LLNL

    Science.gov (United States)

    Mansigh Karlsen, Mary Ann

    I'm the young woman in the picture shown in Fig. 12.1 that appeared with the invitation to the Symposium to celebrate Berni Alder's ninetieth birthday. I worked with Berni for over 25 years on the computer programs that provided the data he needed to write the fifteen papers published in scientific journals on Studies in Molecular Dynamics. My name appears at the end of each one thanking me for computer support. It has been interesting to look on the Internet to find my name in the middle of many foreign languages, including Japanese characters and Russian Cyrillic script. It shows how Berni's work has been of interest to many scientists all over the world from the earliest years. Figure 12.1 was also included with articles written when he received the National Medal of Science from President Obama in 2009…

  20. Algorithms and computer codes for atomic and molecular quantum scattering theory. Volume I

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, L. (ed.)

    1979-01-01

    The goals of this workshop are to identify which of the existing computer codes for solving the coupled equations of quantum molecular scattering theory perform most efficiently on a variety of test problems, and to make tested versions of those codes available to the chemistry community through the NRCC software library. To this end, many of the most active developers and users of these codes have been invited to discuss the methods and to solve a set of test problems using the LBL computers. The first volume of this workshop report is a collection of the manuscripts of the talks that were presented at the first meeting held at the Argonne National Laboratory, Argonne, Illinois June 25-27, 1979. It is hoped that this will serve as an up-to-date reference to the most popular methods with their latest refinements and implementations.

  1. Algorithms and computer codes for atomic and molecular quantum scattering theory. Volume I

    International Nuclear Information System (INIS)

    Thomas, L.

    1979-01-01

    The goals of this workshop are to identify which of the existing computer codes for solving the coupled equations of quantum molecular scattering theory perform most efficiently on a variety of test problems, and to make tested versions of those codes available to the chemistry community through the NRCC software library. To this end, many of the most active developers and users of these codes have been invited to discuss the methods and to solve a set of test problems using the LBL computers. The first volume of this workshop report is a collection of the manuscripts of the talks that were presented at the first meeting held at the Argonne National Laboratory, Argonne, Illinois June 25-27, 1979. It is hoped that this will serve as an up-to-date reference to the most popular methods with their latest refinements and implementations

  2. Computer-aided Molecular Design of Compounds Targeting Histone Modifying Enzymes

    Science.gov (United States)

    Andreoli, Federico; Del Rio, Alberto

    2015-01-01

    Growing evidences show that epigenetic mechanisms play crucial roles in the genesis and progression of many physiopathological processes. As a result, research in epigenetic grew at a fast pace in the last decade. In particular, the study of histone post-translational modifications encountered an extraordinary progression and many modifications have been characterized and associated to fundamental biological processes and pathological conditions. Histone modifications are the catalytic result of a large set of enzyme families that operate covalent modifications on specific residues at the histone tails. Taken together, these modifications elicit a complex and concerted processing that greatly contribute to the chromatin remodeling and may drive different pathological conditions, especially cancer. For this reason, several epigenetic targets are currently under validation for drug discovery purposes and different academic and industrial programs have been already launched to produce the first pre-clinical and clinical outcomes. In this scenario, computer-aided molecular design techniques are offering important tools, mainly as a consequence of the increasing structural information available for these targets. In this mini-review we will briefly discuss the most common types of known histone modifications and the corresponding operating enzymes by emphasizing the computer-aided molecular design approaches that can be of use to speed-up the efforts to generate new pharmaceutically relevant compounds. PMID:26082827

  3. Engineering integrated digital circuits with allosteric ribozymes for scaling up molecular computation and diagnostics.

    Science.gov (United States)

    Penchovsky, Robert

    2012-10-19

    Here we describe molecular implementations of integrated digital circuits, including a three-input AND logic gate, a two-input multiplexer, and 1-to-2 decoder using allosteric ribozymes. Furthermore, we demonstrate a multiplexer-decoder circuit. The ribozymes are designed to seek-and-destroy specific RNAs with a certain length by a fully computerized procedure. The algorithm can accurately predict one base substitution that alters the ribozyme's logic function. The ability to sense the length of RNA molecules enables single ribozymes to be used as platforms for multiple interactions. These ribozymes can work as integrated circuits with the functionality of up to five logic gates. The ribozyme design is universal since the allosteric and substrate domains can be altered to sense different RNAs. In addition, the ribozymes can specifically cleave RNA molecules with triplet-repeat expansions observed in genetic disorders such as oculopharyngeal muscular dystrophy. Therefore, the designer ribozymes can be employed for scaling up computing and diagnostic networks in the fields of molecular computing and diagnostics and RNA synthetic biology.

  4. Implementing Molecular Dynamics for Hybrid High Performance Computers - 1. Short Range Forces

    International Nuclear Information System (INIS)

    Brown, W. Michael; Wang, Peng; Plimpton, Steven J.; Tharrington, Arnold N.

    2011-01-01

    The use of accelerators such as general-purpose graphics processing units (GPGPUs) have become popular in scientific computing applications due to their low cost, impressive floating-point capabilities, high memory bandwidth, and low electrical power requirements. Hybrid high performance computers, machines with more than one type of floating-point processor, are now becoming more prevalent due to these advantages. In this work, we discuss several important issues in porting a large molecular dynamics code for use on parallel hybrid machines - (1) choosing a hybrid parallel decomposition that works on central processing units (CPUs) with distributed memory and accelerator cores with shared memory, (2) minimizing the amount of code that must be ported for efficient acceleration, (3) utilizing the available processing power from both many-core CPUs and accelerators, and (4) choosing a programming model for acceleration. We present our solution to each of these issues for short-range force calculation in the molecular dynamics package LAMMPS. We describe algorithms for efficient short range force calculation on hybrid high performance machines. We describe a new approach for dynamic load balancing of work between CPU and accelerator cores. We describe the Geryon library that allows a single code to compile with both CUDA and OpenCL for use on a variety of accelerators. Finally, we present results on a parallel test cluster containing 32 Fermi GPGPUs and 180 CPU cores.

  5. Computing the blood brain barrier (BBB) diffusion coefficient: A molecular dynamics approach

    Energy Technology Data Exchange (ETDEWEB)

    Shamloo, Amir, E-mail: shamloo@sharif.edu; Pedram, Maysam Z.; Heidari, Hossein; Alasty, Aria, E-mail: aalasti@sharif.edu

    2016-07-15

    Various physical and biological aspects of the Blood Brain Barrier (BBB) structure still remain unfolded. Therefore, among the several mechanisms of drug delivery, only a few have succeeded in breaching this barrier, one of which is the use of Magnetic Nanoparticles (MNPs). However, a quantitative characterization of the BBB permeability is desirable to find an optimal magnetic force-field. In the present study, a molecular model of the BBB is introduced that precisely represents the interactions between MNPs and the membranes of Endothelial Cells (ECs) that form the BBB. Steered Molecular Dynamics (SMD) simulations of the BBB crossing phenomenon have been carried out. Mathematical modeling of the BBB as an input-output system has been considered from a system dynamics modeling viewpoint, enabling us to analyze the BBB behavior based on a robust model. From this model, the force profile required to overcome the barrier has been extracted for a single NP from the SMD simulations at a range of velocities. Using this data a transfer function model has been obtained and the diffusion coefficient is evaluated. This study is a novel approach to bridge the gap between nanoscale models and microscale models of the BBB. The characteristic diffusion coefficient has the nano-scale molecular effects inherent, furthermore reducing the computational costs of a nano-scale simulation model and enabling much more complex studies to be conducted. - Highlights: • Molecular dynamics simulation of crossing nano-particles through the BBB membrane at different velocities. • Recording the position of nano-particle and the membrane-NP interaction force profile. • Identification of a frequency domain model for the membrane. • Calculating the diffusion coefficient based on MD simulation and identified model. • Obtaining a relation between continuum medium and discrete medium.

  6. Oxytetracycline recovery from aqueous media using computationally designed molecularly imprinted polymers.

    Science.gov (United States)

    Rodríguez-Dorado, Rosalía; Carro, Antonia M; Chianella, Iva; Karim, Kal; Concheiro, Angel; Lorenzo, Rosa A; Piletsky, Sergey; Alvarez-Lorenzo, Carmen

    2016-09-01

    Polymers for recovery/removal of the antimicrobial agent oxytetracycline (OTC) from aqueous media were developed with use of computational design and molecular imprinting. 2-Hydroxyethyl methacrylate, 2-acrylamide-2-methylpropane sulfonic acid (AMPS), and mixtures of the two were chosen according to their predicted affinity for OTC and evaluated as functional monomers in molecularly imprinted polymers and nonimprinted polymers. Two levels of AMPS were tested. After bulk polymerization, the polymers were crushed into particles (200-1000 μm). Pressurized liquid extraction was implemented for template removal with a low amount of methanol (less than 20 mL in each extraction) and a few extractions (12-18 for each polymer) in a short period (20 min per extraction). Particle size distribution, microporous structure, and capacity to rebind OTC from aqueous media were evaluated. Adsorption isotherms obtained from OTC solutions (30-110 mg L(-1)) revealed that the polymers prepared with AMPS had the highest affinity for OTC. The uptake capacity depended on the ionic strength as follows: purified water > saline solution (0.9 % NaCl) > seawater (3.5 % NaCl). Polymer particles containing AMPS as a functional monomer showed a remarkable ability to clean water contaminated with OTC. The usefulness of the stationary phase developed for molecularly imprinted solid-phase extraction was also demonstrated. Graphical Abstract Selection of functional monomers by molecular modeling renders polymer networks suitable for removal of pollutants from contaminated aqueous environments, under either dynamic or static conditions.

  7. Computational modeling on the recognition of the HRE motif by HIF-1: molecular docking and molecular dynamics studies.

    Science.gov (United States)

    Sokkar, Pandian; Sathis, Vani; Ramachandran, Murugesan

    2012-05-01

    Hypoxia inducible factor-1 (HIF-1) is a bHLH-family transcription factor that controls genes involved in glycolysis, angiogenesis, migration, as well as invasion factors that are important for tumor progression and metastasis. HIF-1, a heterodimer of HIF-1α and HIF-1β, binds to the hypoxia responsive element (HRE) present in the promoter regions of hypoxia responsive genes, such as vascular endothelial growth factor (VEGF). Neither the structure of free HIF-1 nor that of its complex with HRE is available. Computational modeling of the transcription factor-DNA complex has always been challenging due to their inherent flexibility and large conformational space. The present study aims to model the interaction between the DNA-binding domain of HIF-1 and HRE. Experiments showed that rigid macromolecular docking programs (HEX and GRAMM-X) failed to predict the optimal dimerization of individually modeled HIF-1 subunits. Hence, the HIF-1 heterodimer was modeled based on the phosphate system positive regulatory protein (PHO4) homodimer. The duplex VEGF-DNA segment containing HRE with flanking nucleotides was modeled in the B form and equilibrated via molecular dynamics (MD) simulation. A rigid docking approach was used to predict the crude binding mode of HIF-1 dimer with HRE, in which the putative contacts were found to be present. An MD simulation (5 ns) of the HIF-1-HRE complex in explicit water was performed to account for its flexibility and to optimize its interactions. All of the conserved amino acid residues were found to play roles in the recognition of HRE. The present work, which sheds light on the recognition of HRE by HIF-1, could be beneficial in the design of peptide or small molecule therapeutics that can mimic HIF-1 and bind with the HRE sequence.

  8. Concept of a Cloud Service for Data Preparation and Computational Control on Custom HPC Systems in Application to Molecular Dynamics

    Science.gov (United States)

    Puzyrkov, Dmitry; Polyakov, Sergey; Podryga, Viktoriia; Markizov, Sergey

    2018-02-01

    At the present stage of computer technology development it is possible to study the properties and processes in complex systems at molecular and even atomic levels, for example, by means of molecular dynamics methods. The most interesting are problems related with the study of complex processes under real physical conditions. Solving such problems requires the use of high performance computing systems of various types, for example, GRID systems and HPC clusters. Considering the time consuming computational tasks, the need arises of software for automatic and unified monitoring of such computations. A complex computational task can be performed over different HPC systems. It requires output data synchronization between the storage chosen by a scientist and the HPC system used for computations. The design of the computational domain is also quite a problem. It requires complex software tools and algorithms for proper atomistic data generation on HPC systems. The paper describes the prototype of a cloud service, intended for design of atomistic systems of large volume for further detailed molecular dynamic calculations and computational management for this calculations, and presents the part of its concept aimed at initial data generation on the HPC systems.

  9. Concept of a Cloud Service for Data Preparation and Computational Control on Custom HPC Systems in Application to Molecular Dynamics

    Directory of Open Access Journals (Sweden)

    Puzyrkov Dmitry

    2018-01-01

    Full Text Available At the present stage of computer technology development it is possible to study the properties and processes in complex systems at molecular and even atomic levels, for example, by means of molecular dynamics methods. The most interesting are problems related with the study of complex processes under real physical conditions. Solving such problems requires the use of high performance computing systems of various types, for example, GRID systems and HPC clusters. Considering the time consuming computational tasks, the need arises of software for automatic and unified monitoring of such computations. A complex computational task can be performed over different HPC systems. It requires output data synchronization between the storage chosen by a scientist and the HPC system used for computations. The design of the computational domain is also quite a problem. It requires complex software tools and algorithms for proper atomistic data generation on HPC systems. The paper describes the prototype of a cloud service, intended for design of atomistic systems of large volume for further detailed molecular dynamic calculations and computational management for this calculations, and presents the part of its concept aimed at initial data generation on the HPC systems.

  10. A New Optimization Model for Computer-Aided Molecular Design Problems

    DEFF Research Database (Denmark)

    Zhang, Lei; Cignitti, Stefano; Gani, Rafiqul

    Computer-Aided Molecular Design (CAMD) is a method to design molecules with desired properties. That is, through CAMD, it is possible to generate molecules that match a specified set of target properties. CAMD has attracted much attention in recent years due to its ability to design novel as well...... with structure information considered due to the increased size of the mathematical problem and number of alternatives. Thus, decomposition-based approach is proposed to solve the problem. In this approach, only first-order groups are considered in the first step to obtain the building block of the designed...... molecule, then the property model is refined with second-order groups based on the results of the first step. However, this may result in the possibility of an optimal solution being excluded. Samudra and Sahinidis [4] used property relaxation method in the first step to avoid this situation...

  11. Molecular dynamics computer simulation study of Pdn (n=13, 19, 38 and 55) clusters

    International Nuclear Information System (INIS)

    Karabacak, M.; Oezcelik, S.; Guevenc, Z.B.

    2002-01-01

    Using constant-energy molecular dynamics and thermal quenching simulations, we have studied minimum-energy structures and energetics, Pd n (n=13, 19, 38, and 55) clusters employing the Voter and Chen's version of parameterisation of the embedded-atom potential surface. Isomer statistics for Pdn ( n = 13 and 19 ) is obtained from 10000 initial independent configurations, which have been generated along high-energy trajectories (chosen energy values are high enough to melt the clusters). The thermal quenching technique is employed to remove the internal kinetic energy of the clusters. The locally stable isomers are separated from metastable ones. Probabilities belonging to sampling the basins of attractions of each isomers are computed, and then, isomers' energy spectra are analyzed

  12. Ab Initio Molecular-Dynamics Simulation of Neuromorphic Computing in Phase-Change Memory Materials.

    Science.gov (United States)

    Skelton, Jonathan M; Loke, Desmond; Lee, Taehoon; Elliott, Stephen R

    2015-07-08

    We present an in silico study of the neuromorphic-computing behavior of the prototypical phase-change material, Ge2Sb2Te5, using ab initio molecular-dynamics simulations. Stepwise changes in structural order in response to temperature pulses of varying length and duration are observed, and a good reproduction of the spike-timing-dependent plasticity observed in nanoelectronic synapses is demonstrated. Short above-melting pulses lead to instantaneous loss of structural and chemical order, followed by delayed partial recovery upon structural relaxation. We also investigate the link between structural order and electrical and optical properties. These results pave the way toward a first-principles understanding of phase-change physics beyond binary switching.

  13. Screening of photosynthetic pigments for herbicidal activity with a new computational molecular approach.

    Science.gov (United States)

    Krishnaraj, R Navanietha; Chandran, Saravanan; Pal, Parimal; Berchmans, Sheela

    2013-12-01

    There is an immense interest among the researchers to identify new herbicides which are effective against the herbs without affecting the environment. In this work, photosynthetic pigments are used as the ligands to predict their herbicidal activity. The enzyme 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase is a good target for the herbicides. Homology modeling of the target enzyme is done using Modeler 9.11 and the model is validated. Docking studies were performed with AutoDock Vina algorithm to predict the binding of the natural pigments such as β-carotene, chlorophyll a, chlorophyll b, phycoerythrin and phycocyanin to the target. β-carotene, phycoerythrin and phycocyanin have higher binding energies indicating the herbicidal activity of the pigments. This work reports a procedure to screen herbicides with computational molecular approach. These pigments will serve as potential bioherbicides in the future.

  14. Elucidating Mechanisms of Molecular Recognition Between Human Argonaute and miRNA Using Computational Approaches

    KAUST Repository

    Jiang, Hanlun

    2016-12-06

    MicroRNA (miRNA) and Argonaute (AGO) protein together form the RNA-induced silencing complex (RISC) that plays an essential role in the regulation of gene expression. Elucidating the underlying mechanism of AGO-miRNA recognition is thus of great importance not only for the in-depth understanding of miRNA function but also for inspiring new drugs targeting miRNAs. In this chapter we introduce a combined computational approach of molecular dynamics (MD) simulations, Markov state models (MSMs), and protein-RNA docking to investigate AGO-miRNA recognition. Constructed from MD simulations, MSMs can elucidate the conformational dynamics of AGO at biologically relevant timescales. Protein-RNA docking can then efficiently identify the AGO conformations that are geometrically accessible to miRNA. Using our recent work on human AGO2 as an example, we explain the rationale and the workflow of our method in details. This combined approach holds great promise to complement experiments in unraveling the mechanisms of molecular recognition between large, flexible, and complex biomolecules.

  15. COBRA: A Computational Brewing Application for Predicting the Molecular Composition of Organic Aerosols

    Energy Technology Data Exchange (ETDEWEB)

    Fooshee, David R.; Nguyen, Tran B.; Nizkorodov, Sergey A.; Laskin, Julia; Laskin, Alexander; Baldi, Pierre

    2012-05-08

    Atmospheric organic aerosols (OA) represent a significant fraction of airborne particulate matter and can impact climate, visibility, and human health. These mixtures are difficult to characterize experimentally due to the enormous complexity and dynamic nature of their chemical composition. We introduce a novel Computational Brewing Application (COBRA) and apply it to modeling oligomerization chemistry stemming from condensation and addition reactions of monomers pertinent to secondary organic aerosol (SOA) formed by photooxidation of isoprene. COBRA uses two lists as input: a list of chemical structures comprising the molecular starting pool, and a list of rules defining potential reactions between molecules. Reactions are performed iteratively, with products of all previous iterations serving as reactants for the next one. The simulation generated thousands of molecular structures in the mass range of 120-500 Da, and correctly predicted ~70% of the individual SOA constituents observed by high-resolution mass spectrometry (HR-MS). Selected predicted structures were confirmed with tandem mass spectrometry. Esterification and hemiacetal formation reactions were shown to play the most significant role in oligomer formation, whereas aldol condensation was shown to be insignificant. COBRA is not limited to atmospheric aerosol chemistry, but is broadly applicable to the prediction of reaction products in other complex mixtures for which reasonable reaction mechanisms and seed molecules can be supplied by experimental or theoretical methods.

  16. Hidden Markov models and other machine learning approaches in computational molecular biology

    Energy Technology Data Exchange (ETDEWEB)

    Baldi, P. [California Inst. of Tech., Pasadena, CA (United States)

    1995-12-31

    This tutorial was one of eight tutorials selected to be presented at the Third International Conference on Intelligent Systems for Molecular Biology which was held in the United Kingdom from July 16 to 19, 1995. Computational tools are increasingly needed to process the massive amounts of data, to organize and classify sequences, to detect weak similarities, to separate coding from non-coding regions, and reconstruct the underlying evolutionary history. The fundamental problem in machine learning is the same as in scientific reasoning in general, as well as statistical modeling: to come up with a good model for the data. In this tutorial four classes of models are reviewed. They are: Hidden Markov models; artificial Neural Networks; Belief Networks; and Stochastic Grammars. When dealing with DNA and protein primary sequences, Hidden Markov models are one of the most flexible and powerful alignments and data base searches. In this tutorial, attention is focused on the theory of Hidden Markov Models, and how to apply them to problems in molecular biology.

  17. Elucidating Mechanisms of Molecular Recognition Between Human Argonaute and miRNA Using Computational Approaches.

    Science.gov (United States)

    Jiang, Hanlun; Zhu, Lizhe; Héliou, Amélie; Gao, Xin; Bernauer, Julie; Huang, Xuhui

    2017-01-01

    MicroRNA (miRNA) and Argonaute (AGO) protein together form the RNA-induced silencing complex (RISC) that plays an essential role in the regulation of gene expression. Elucidating the underlying mechanism of AGO-miRNA recognition is thus of great importance not only for the in-depth understanding of miRNA function but also for inspiring new drugs targeting miRNAs. In this chapter we introduce a combined computational approach of molecular dynamics (MD) simulations, Markov state models (MSMs), and protein-RNA docking to investigate AGO-miRNA recognition. Constructed from MD simulations, MSMs can elucidate the conformational dynamics of AGO at biologically relevant timescales. Protein-RNA docking can then efficiently identify the AGO conformations that are geometrically accessible to miRNA. Using our recent work on human AGO2 as an example, we explain the rationale and the workflow of our method in details. This combined approach holds great promise to complement experiments in unraveling the mechanisms of molecular recognition between large, flexible, and complex biomolecules.

  18. MDGRAPE-4: a special-purpose computer system for molecular dynamics simulations.

    Science.gov (United States)

    Ohmura, Itta; Morimoto, Gentaro; Ohno, Yousuke; Hasegawa, Aki; Taiji, Makoto

    2014-08-06

    We are developing the MDGRAPE-4, a special-purpose computer system for molecular dynamics (MD) simulations. MDGRAPE-4 is designed to achieve strong scalability for protein MD simulations through the integration of general-purpose cores, dedicated pipelines, memory banks and network interfaces (NIFs) to create a system on chip (SoC). Each SoC has 64 dedicated pipelines that are used for non-bonded force calculations and run at 0.8 GHz. Additionally, it has 65 Tensilica Xtensa LX cores with single-precision floating-point units that are used for other calculations and run at 0.6 GHz. At peak performance levels, each SoC can evaluate 51.2 G interactions per second. It also has 1.8 MB of embedded shared memory banks and six network units with a peak bandwidth of 7.2 GB s(-1) for the three-dimensional torus network. The system consists of 512 (8×8×8) SoCs in total, which are mounted on 64 node modules with eight SoCs. The optical transmitters/receivers are used for internode communication. The expected maximum power consumption is 50 kW. While MDGRAPE-4 software has still been improved, we plan to run MD simulations on MDGRAPE-4 in 2014. The MDGRAPE-4 system will enable long-time molecular dynamics simulations of small systems. It is also useful for multiscale molecular simulations where the particle simulation parts often become bottlenecks.

  19. Molecular Computational Investigation of Electron Transfer Kinetics across Cytochrome-Iron Oxide Interfaces

    International Nuclear Information System (INIS)

    Kerisit, Sebastien N.; Rosso, Kevin M.; Dupuis, Michel; Valiev, Marat

    2007-01-01

    The interface between electron transfer proteins such as cytochromes and solid phase mineral oxides is central to the activity of dissimilatory-metal reducing bacteria. A combination of potential-based molecular dynamics simulations and ab initio electronic structure calculations are used in the framework of Marcus' electron transfer theory to compute elementary electron transfer rates from a well-defined cytochrome model, namely the small tetraheme cytochrome (STC) from Shewanella oneidensis, to surfaces of the iron oxide mineral hematite (a-Fe2O3). Room temperature molecular dynamics simulations show that an isolated STC molecule favors surface attachment via direct contact of hemes I and IV at the poles of the elongated axis, with electron transfer distances as small as 9 Angstroms. The cytochrome remains attached to the mineral surface in the presence of water and shows limited surface diffusion at the interface. Ab initio electronic coupling matrix element (VAB) calculations of configurations excised from the molecular dynamics simulations reveal VAB values ranging from 1 to 20 cm-1, consistent with nonadiabaticity. Using these results, together with experimental data on the redox potential of hematite and hemes in relevant cytochromes and calculations of the reorganization energy from cluster models, we estimate the rate of electron transfer across this model interface to range from 1 to 1000 s-1 for the most exothermic driving force considered in this work, and from 0.01 to 20 s-1 for the most endothermic. This fairly large range of electron transfer rates highlights the sensitivity of the rate upon the electronic coupling matrix element, which is in turn dependent on the fluctuations of the heme configuration at the interface. We characterize this dependence using an idealized bis-imidazole heme to compute from first principles the VAB variation due to porphyrin ring orientation, electron transfer distance, and mineral surface termination. The electronic

  20. Computational screening and molecular dynamics simulation of disease associated nsSNPs in CENP-E

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Ambuj [Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology University, Vellore 632014, Tamil Nadu (India); Purohit, Rituraj, E-mail: riturajpurohit@gmail.com [Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology University, Vellore 632014, Tamil Nadu (India)

    2012-10-15

    Aneuploidy and chromosomal instability (CIN) are hallmarks of most solid tumors. Mutations in centroemere proteins have been observed in promoting aneuploidy and tumorigenesis. Recent studies reported that Centromere-associated protein-E (CENP-E) is involved in inducing cancers. In this study we investigated the pathogenic effect of 132 nsSNPs reported in CENP-E using computational platform. Y63H point mutation found to be associated with cancer using SIFT, Polyphen, PhD-SNP, MutPred, CanPredict and Dr. Cancer tools. Further we investigated the binding affinity of ATP molecule to the CENP-E motor domain. Complementarity scores obtained from docking studies showed significant loss in ATP binding affinity of mutant structure. Molecular dynamics simulation was carried to examine the structural consequences of Y63H mutation. Root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (R{sub g}), solvent accessibility surface area (SASA), energy value, hydrogen bond (NH Bond), eigenvector projection, trace of covariance matrix and atom density analysis results showed notable loss in stability for mutant structure. Y63H mutation was also shown to disrupt the native conformation of ATP binding region in CENP-E motor domain. Docking studies for remaining 18 mutations at 63rd residue position as well as other two computationally predicted disease associated mutations S22L and P69S were also carried to investigate their affect on ATP binding affinity of CENP-E motor domain. Our study provided a promising computational methodology to study the tumorigenic consequences of nsSNPs that have not been characterized and clear clue to the wet lab scientist.

  1. Computational screening and molecular dynamics simulation of disease associated nsSNPs in CENP-E

    International Nuclear Information System (INIS)

    Kumar, Ambuj; Purohit, Rituraj

    2012-01-01

    Aneuploidy and chromosomal instability (CIN) are hallmarks of most solid tumors. Mutations in centroemere proteins have been observed in promoting aneuploidy and tumorigenesis. Recent studies reported that Centromere-associated protein-E (CENP-E) is involved in inducing cancers. In this study we investigated the pathogenic effect of 132 nsSNPs reported in CENP-E using computational platform. Y63H point mutation found to be associated with cancer using SIFT, Polyphen, PhD-SNP, MutPred, CanPredict and Dr. Cancer tools. Further we investigated the binding affinity of ATP molecule to the CENP-E motor domain. Complementarity scores obtained from docking studies showed significant loss in ATP binding affinity of mutant structure. Molecular dynamics simulation was carried to examine the structural consequences of Y63H mutation. Root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (R g ), solvent accessibility surface area (SASA), energy value, hydrogen bond (NH Bond), eigenvector projection, trace of covariance matrix and atom density analysis results showed notable loss in stability for mutant structure. Y63H mutation was also shown to disrupt the native conformation of ATP binding region in CENP-E motor domain. Docking studies for remaining 18 mutations at 63rd residue position as well as other two computationally predicted disease associated mutations S22L and P69S were also carried to investigate their affect on ATP binding affinity of CENP-E motor domain. Our study provided a promising computational methodology to study the tumorigenic consequences of nsSNPs that have not been characterized and clear clue to the wet lab scientist.

  2. Reactivity of etoricoxib based on computational study of molecular orbitals, molecular electrostatic potential surface and Mulliken charge analysis

    Science.gov (United States)

    Sachdeva, Ritika; Soni, Abhinav; Singh, V. P.; Saini, G. S. S.

    2018-05-01

    Etoricoxib is one of the selective cyclooxygenase inhibitor drug which plays a significant role in the pharmacological management of arthritis and pain. The theoretical investigation of its reactivity is done using Density Functional Theory calculations. Molecular Electrostatic Potential Surface of etoricoxib and its Mulliken atomic charge distribution are used for the prediction of its electrophilic and nucleophilic sites. The detailed analysis of its frontier molecular orbitals is also done.

  3. Computational methods to study the structure and dynamics of biomolecules and biomolecular processes from bioinformatics to molecular quantum mechanics

    CERN Document Server

    2014-01-01

    Since the second half of the 20th century machine computations have played a critical role in science and engineering. Computer-based techniques have become especially important in molecular biology, since they often represent the only viable way to gain insights into the behavior of a biological system as a whole. The complexity of biological systems, which usually needs to be analyzed on different time- and size-scales and with different levels of accuracy, requires the application of different approaches, ranging from comparative analysis of sequences and structural databases, to the analysis of networks of interdependence between cell components and processes, through coarse-grained modeling to atomically detailed simulations, and finally to molecular quantum mechanics. This book provides a comprehensive overview of modern computer-based techniques for computing the structure, properties and dynamics of biomolecules and biomolecular processes. The twenty-two chapters, written by scientists from all over t...

  4. Computational study of the human dystrophin repeats: interaction properties and molecular dynamics.

    Directory of Open Access Journals (Sweden)

    Baptiste Legrand

    Full Text Available Dystrophin is a large protein involved in the rare genetic disease Duchenne muscular dystrophy (DMD. It functions as a mechanical linker between the cytoskeleton and the sarcolemma, and is able to resist shear stresses during muscle activity. In all, 75% of the dystrophin molecule consists of a large central rod domain made up of 24 repeat units that share high structural homology with spectrin-like repeats. However, in the absence of any high-resolution structure of these repeats, the molecular basis of dystrophin central domain's functions has not yet been deciphered. In this context, we have performed a computational study of the whole dystrophin central rod domain based on the rational homology modeling of successive and overlapping tandem repeats and the analysis of their surface properties. Each tandem repeat has very specific surface properties that make it unique. However, the repeats share enough electrostatic-surface similarities to be grouped into four separate clusters. Molecular dynamics simulations of four representative tandem repeats reveal specific flexibility or bending properties depending on the repeat sequence. We thus suggest that the dystrophin central rod domain is constituted of seven biologically relevant sub-domains. Our results provide evidence for the role of the dystrophin central rod domain as a scaffold platform with a wide range of surface features and biophysical properties allowing it to interact with its various known partners such as proteins and membrane lipids. This new integrative view is strongly supported by the previous experimental works that investigated the isolated domains and the observed heterogeneity of the severity of dystrophin related pathologies, especially Becker muscular dystrophy.

  5. Identification of control targets in Boolean molecular network models via computational algebra.

    Science.gov (United States)

    Murrugarra, David; Veliz-Cuba, Alan; Aguilar, Boris; Laubenbacher, Reinhard

    2016-09-23

    Many problems in biomedicine and other areas of the life sciences can be characterized as control problems, with the goal of finding strategies to change a disease or otherwise undesirable state of a biological system into another, more desirable, state through an intervention, such as a drug or other therapeutic treatment. The identification of such strategies is typically based on a mathematical model of the process to be altered through targeted control inputs. This paper focuses on processes at the molecular level that determine the state of an individual cell, involving signaling or gene regulation. The mathematical model type considered is that of Boolean networks. The potential control targets can be represented by a set of nodes and edges that can be manipulated to produce a desired effect on the system. This paper presents a method for the identification of potential intervention targets in Boolean molecular network models using algebraic techniques. The approach exploits an algebraic representation of Boolean networks to encode the control candidates in the network wiring diagram as the solutions of a system of polynomials equations, and then uses computational algebra techniques to find such controllers. The control methods in this paper are validated through the identification of combinatorial interventions in the signaling pathways of previously reported control targets in two well studied systems, a p53-mdm2 network and a blood T cell lymphocyte granular leukemia survival signaling network. Supplementary data is available online and our code in Macaulay2 and Matlab are available via http://www.ms.uky.edu/~dmu228/ControlAlg . This paper presents a novel method for the identification of intervention targets in Boolean network models. The results in this paper show that the proposed methods are useful and efficient for moderately large networks.

  6. Computation of Collision-Induced Absorption by Simple Molecular Complexes, for Astrophysical Applications

    Science.gov (United States)

    Abel, Martin; Frommhold, Lothar; Li, Xiaoping; Hunt, Katharine L. C.

    2012-06-01

    The interaction-induced absorption by collisional pairs of H{_2} molecules is an important opacity source in the atmospheres of various types of planets and cool stars, such as late stars, low-mass stars, brown dwarfs, cool white dwarf stars, the ambers of the smaller, burnt out main sequence stars, exoplanets, etc., and therefore of special astronomical interest The emission spectra of cool white dwarf stars differ significantly in the infrared from the expected blackbody spectra of their cores, which is largely due to absorption by collisional H{_2}-H{_2}, H{_2}-He, and H{_2}-H complexes in the stellar atmospheres. Using quantum-chemical methods we compute the atmospheric absorption from hundreds to thousands of kelvin. Laboratory measurements of interaction-induced absorption spectra by H{_2} pairs exist only at room temperature and below. We show that our results reproduce these measurements closely, so that our computational data permit reliable modeling of stellar atmosphere opacities even for the higher temperatures. First results for H_2-He complexes have already been applied to astrophysical models have shown great improvements in these models. L. Frommhold, Collision-Induced Absorption in Gases, Cambridge University Press, Cambridge, New York, 1993 and 2006 X. Li, K. L. C. Hunt, F. Wang, M. Abel, and L. Frommhold, Collision-Induced Infrared Absorption by Molecular Hydrogen Pairs at Thousands of Kelvin, Int. J. of Spect., vol. 2010, Article ID 371201, 11 pages, 2010. doi: 10.1155/2010/371201 M. Abel, L. Frommhold, X. Li, and K. L. C. Hunt, Collision-induced absorption by H{_2} pairs: From hundreds to thousands of Kelvin, J. Phys. Chem. A, 115, 6805-6812, 2011} L. Frommhold, M. Abel, F. Wang, M. Gustafsson, X. Li, and K. L. C. Hunt, "Infrared atmospheric emission and absorption by simple molecular complexes, from first principles", Mol. Phys. 108, 2265, 2010 M. Abel, L. Frommhold, X. Li, and K. L. C. Hunt, Infrared absorption by collisional H_2-He complexes

  7. Introduction to Computational Chemistry: Teaching Hu¨ckel Molecular Orbital Theory Using an Excel Workbook for Matrix Diagonalization

    Science.gov (United States)

    Litofsky, Joshua; Viswanathan, Rama

    2015-01-01

    Matrix diagonalization, the key technique at the heart of modern computational chemistry for the numerical solution of the Schrödinger equation, can be easily introduced in the physical chemistry curriculum in a pedagogical context using simple Hückel molecular orbital theory for p bonding in molecules. We present details and results of…

  8. Analog series-based scaffolds: computational design and exploration of a new type of molecular scaffolds for medicinal chemistry

    Science.gov (United States)

    Dimova, Dilyana; Stumpfe, Dagmar; Hu, Ye; Bajorath, Jürgen

    2016-01-01

    Aim: Computational design of and systematic search for a new type of molecular scaffolds termed analog series-based scaffolds. Materials & methods: From currently available bioactive compounds, analog series were systematically extracted, key compounds identified and new scaffolds isolated from them. Results: Using our computational approach, more than 12,000 scaffolds were extracted from bioactive compounds. Conclusion: A new scaffold definition is introduced and a computational methodology developed to systematically identify such scaffolds, yielding a large freely available scaffold knowledge base. PMID:28116132

  9. Computational prediction and molecular confirmation of Helitron transposons in the maize genome

    Directory of Open Access Journals (Sweden)

    He Limei

    2008-01-01

    Full Text Available Abstract Background Helitrons represent a new class of transposable elements recently uncovered in plants and animals. One remarkable feature of Helitrons is their ability to capture gene sequences, which makes them of considerable potential evolutionary importance. However, because Helitrons lack the typical structural features of other DNA transposable elements, identifying them is a challenge. Currently, most researchers identify Helitrons manually by comparing sequences. With the maize whole genome sequencing project underway, an automated computational Helitron searching tool is needed. The characterization of Helitron activities in maize needs to be addressed in order to better understand the impact of Helitrons on the organization of the genome. Results We developed and implemented a heuristic searching algorithm in PERL for identifying Helitrons. Our HelitronFinder program will (i take FASTA-formatted DNA sequences as input and identify the hairpin looping patterns, and (ii exploit the consensus 5' and 3' end sequences of known Helitrons to identify putative ends. We randomly selected five predicted Helitrons from the program's high quality output for molecular verification. Four out of the five predicted Helitrons were confirmed by PCR assays and DNA sequencing in different maize inbred lines. The HelitronFinder program identified two head-to-head dissimilar Helitrons in a maize BAC sequence. Conclusion We have identified 140 new Helitron candidates in maize with our computational tool HelitronFinder by searching maize DNA sequences currently available in GenBank. Four out of five candidates were confirmed to be real by empirical methods, thus validating the predictions of HelitronFinder. Additional points to emerge from our study are that Helitrons do not always insert at an AT dinucleotide in the host sequences, that they can insert immediately adjacent to an existing Helitron, and that their movement may cause changes in the flanking

  10. Fast Computation of Solvation Free Energies with Molecular Density Functional Theory: Thermodynamic-Ensemble Partial Molar Volume Corrections.

    Science.gov (United States)

    Sergiievskyi, Volodymyr P; Jeanmairet, Guillaume; Levesque, Maximilien; Borgis, Daniel

    2014-06-05

    Molecular density functional theory (MDFT) offers an efficient implicit-solvent method to estimate molecule solvation free-energies, whereas conserving a fully molecular representation of the solvent. Even within a second-order approximation for the free-energy functional, the so-called homogeneous reference fluid approximation, we show that the hydration free-energies computed for a data set of 500 organic compounds are of similar quality as those obtained from molecular dynamics free-energy perturbation simulations, with a computer cost reduced by 2-3 orders of magnitude. This requires to introduce the proper partial volume correction to transform the results from the grand canonical to the isobaric-isotherm ensemble that is pertinent to experiments. We show that this correction can be extended to 3D-RISM calculations, giving a sound theoretical justification to empirical partial molar volume corrections that have been proposed recently.

  11. Computational and Experimental Investigations of the Molecular Scale Structure and Dynamics of Gologically Important Fluids and Mineral-Fluid Interfaces

    Energy Technology Data Exchange (ETDEWEB)

    Bowers, Geoffrey [Alfred Univ., NY (United States)

    2017-04-05

    United States Department of Energy grant DE-FG02-10ER16128, “Computational and Spectroscopic Investigations of the Molecular Scale Structure and Dynamics of Geologically Important Fluids and Mineral-Fluid Interfaces” (Geoffrey M. Bowers, P.I.) focused on developing a molecular-scale understanding of processes that occur in fluids and at solid-fluid interfaces using the combination of spectroscopic, microscopic, and diffraction studies with molecular dynamics computer modeling. The work is intimately tied to the twin proposal at Michigan State University (DOE DE-FG02-08ER15929; same title: R. James Kirkpatrick, P.I. and A. Ozgur Yazaydin, co-P.I.).

  12. Computation of Ground-State Properties in Molecular Systems: Back-Propagation with Auxiliary-Field Quantum Monte Carlo.

    Science.gov (United States)

    Motta, Mario; Zhang, Shiwei

    2017-11-14

    We address the computation of ground-state properties of chemical systems and realistic materials within the auxiliary-field quantum Monte Carlo method. The phase constraint to control the Fermion phase problem requires the random walks in Slater determinant space to be open-ended with branching. This in turn makes it necessary to use back-propagation (BP) to compute averages and correlation functions of operators that do not commute with the Hamiltonian. Several BP schemes are investigated, and their optimization with respect to the phaseless constraint is considered. We propose a modified BP method for the computation of observables in electronic systems, discuss its numerical stability and computational complexity, and assess its performance by computing ground-state properties in several molecular systems, including small organic molecules.

  13. Computing pKa Values with a Mixing Hamiltonian Quantum Mechanical/Molecular Mechanical Approach.

    Science.gov (United States)

    Liu, Yang; Fan, Xiaoli; Jin, Yingdi; Hu, Xiangqian; Hu, Hao

    2013-09-10

    Accurate computation of the pKa value of a compound in solution is important but challenging. Here, a new mixing quantum mechanical/molecular mechanical (QM/MM) Hamiltonian method is developed to simulate the free-energy change associated with the protonation/deprotonation processes in solution. The mixing Hamiltonian method is designed for efficient quantum mechanical free-energy simulations by alchemically varying the nuclear potential, i.e., the nuclear charge of the transforming nucleus. In pKa calculation, the charge on the proton is varied in fraction between 0 and 1, corresponding to the fully deprotonated and protonated states, respectively. Inspired by the mixing potential QM/MM free energy simulation method developed previously [H. Hu and W. T. Yang, J. Chem. Phys. 2005, 123, 041102], this method succeeds many advantages of a large class of λ-coupled free-energy simulation methods and the linear combination of atomic potential approach. Theory and technique details of this method, along with the calculation results of the pKa of methanol and methanethiol molecules in aqueous solution, are reported. The results show satisfactory agreement with the experimental data.

  14. Rational design of DNA sequences for nanotechnology, microarrays and molecular computers using Eulerian graphs.

    Science.gov (United States)

    Pancoska, Petr; Moravek, Zdenek; Moll, Ute M

    2004-01-01

    Nucleic acids are molecules of choice for both established and emerging nanoscale technologies. These technologies benefit from large functional densities of 'DNA processing elements' that can be readily manufactured. To achieve the desired functionality, polynucleotide sequences are currently designed by a process that involves tedious and laborious filtering of potential candidates against a series of requirements and parameters. Here, we present a complete novel methodology for the rapid rational design of large sets of DNA sequences. This method allows for the direct implementation of very complex and detailed requirements for the generated sequences, thus avoiding 'brute force' filtering. At the same time, these sequences have narrow distributions of melting temperatures. The molecular part of the design process can be done without computer assistance, using an efficient 'human engineering' approach by drawing a single blueprint graph that represents all generated sequences. Moreover, the method eliminates the necessity for extensive thermodynamic calculations. Melting temperature can be calculated only once (or not at all). In addition, the isostability of the sequences is independent of the selection of a particular set of thermodynamic parameters. Applications are presented for DNA sequence designs for microarrays, universal microarray zip sequences and electron transfer experiments.

  15. Exploiting Genomic Knowledge in Optimising Molecular Breeding Programmes: Algorithms from Evolutionary Computing

    Science.gov (United States)

    O'Hagan, Steve; Knowles, Joshua; Kell, Douglas B.

    2012-01-01

    Comparatively few studies have addressed directly the question of quantifying the benefits to be had from using molecular genetic markers in experimental breeding programmes (e.g. for improved crops and livestock), nor the question of which organisms should be mated with each other to best effect. We argue that this requires in silico modelling, an approach for which there is a large literature in the field of evolutionary computation (EC), but which has not really been applied in this way to experimental breeding programmes. EC seeks to optimise measurable outcomes (phenotypic fitnesses) by optimising in silico the mutation, recombination and selection regimes that are used. We review some of the approaches from EC, and compare experimentally, using a biologically relevant in silico landscape, some algorithms that have knowledge of where they are in the (genotypic) search space (G-algorithms) with some (albeit well-tuned ones) that do not (F-algorithms). For the present kinds of landscapes, F- and G-algorithms were broadly comparable in quality and effectiveness, although we recognise that the G-algorithms were not equipped with any ‘prior knowledge’ of epistatic pathway interactions. This use of algorithms based on machine learning has important implications for the optimisation of experimental breeding programmes in the post-genomic era when we shall potentially have access to the full genome sequence of every organism in a breeding population. The non-proprietary code that we have used is made freely available (via Supplementary information). PMID:23185279

  16. The accuracy of molecular bond lengths computed by multireference electronic structure methods

    International Nuclear Information System (INIS)

    Shepard, Ron; Kedziora, Gary S.; Lischka, Hans; Shavitt, Isaiah; Mueller, Thomas; Szalay, Peter G.; Kallay, Mihaly; Seth, Michael

    2008-01-01

    We compare experimental R e values with computed R e values for 20 molecules using three multireference electronic structure methods, MCSCF, MR-SDCI, and MR-AQCC. Three correlation-consistent orbital basis sets are used, along with complete basis set extrapolations, for all of the molecules. These data complement those computed previously with single-reference methods. Several trends are observed. The SCF R e values tend to be shorter than the experimental values, and the MCSCF values tend to be longer than the experimental values. We attribute these trends to the ionic contamination of the SCF wave function and to the corresponding systematic distortion of the potential energy curve. For the individual bonds, the MR-SDCI R e values tend to be shorter than the MR-AQCC values, which in turn tend to be shorter than the MCSCF values. Compared to the previous single-reference results, the MCSCF values are roughly comparable to the MP4 and CCSD methods, which are more accurate than might be expected due to the fact that these MCSCF wave functions include no extra-valence electron correlation effects. This suggests that static valence correlation effects, such as near-degeneracies and the ability to dissociate correctly to neutral fragments, play an important role in determining the shape of the potential energy surface, even near equilibrium structures. The MR-SDCI and MR-AQCC methods predict R e values with an accuracy comparable to, or better than, the best single-reference methods (MP4, CCSD, and CCSD(T)), despite the fact that triple and higher excitations into the extra-valence orbital space are included in the single-reference methods but are absent in the multireference wave functions. The computed R e values using the multireference methods tend to be smooth and monotonic with basis set improvement. The molecular structures are optimized using analytic energy gradients, and the timings for these calculations show the practical advantage of using variational wave

  17. The accuracy of molecular bond lengths computed by multireference electronic structure methods

    Energy Technology Data Exchange (ETDEWEB)

    Shepard, Ron [Chemical Sciences and Engineering Division, Argonne National Laboratory, Argonne, IL 60439 (United States)], E-mail: shepard@tcg.anl.gov; Kedziora, Gary S. [High Performance Technologies Inc., 2435 5th Street, WPAFB, OH 45433 (United States); Lischka, Hans [Institute for Theoretical Chemistry, University of Vienna, Waehringerstrasse 17, A-1090 Vienna (Austria); Shavitt, Isaiah [Department of Chemistry, University of Illinois, 600 S. Mathews Avenue, Urbana, IL 61801 (United States); Mueller, Thomas [Juelich Supercomputer Centre, Research Centre Juelich, D-52425 Juelich (Germany); Szalay, Peter G. [Laboratory for Theoretical Chemistry, Institute of Chemistry, Eoetvoes Lorand University, P.O. Box 32, H-1518 Budapest (Hungary); Kallay, Mihaly [Department of Physical Chemistry and Materials Science, Budapest University of Technology and Economics, P.O. Box 91, H-1521 Budapest (Hungary); Seth, Michael [Department of Chemistry, University of Calgary, 2500 University Drive, N.W., Calgary, Alberta, T2N 1N4 (Canada)

    2008-06-16

    We compare experimental R{sub e} values with computed R{sub e} values for 20 molecules using three multireference electronic structure methods, MCSCF, MR-SDCI, and MR-AQCC. Three correlation-consistent orbital basis sets are used, along with complete basis set extrapolations, for all of the molecules. These data complement those computed previously with single-reference methods. Several trends are observed. The SCF R{sub e} values tend to be shorter than the experimental values, and the MCSCF values tend to be longer than the experimental values. We attribute these trends to the ionic contamination of the SCF wave function and to the corresponding systematic distortion of the potential energy curve. For the individual bonds, the MR-SDCI R{sub e} values tend to be shorter than the MR-AQCC values, which in turn tend to be shorter than the MCSCF values. Compared to the previous single-reference results, the MCSCF values are roughly comparable to the MP4 and CCSD methods, which are more accurate than might be expected due to the fact that these MCSCF wave functions include no extra-valence electron correlation effects. This suggests that static valence correlation effects, such as near-degeneracies and the ability to dissociate correctly to neutral fragments, play an important role in determining the shape of the potential energy surface, even near equilibrium structures. The MR-SDCI and MR-AQCC methods predict R{sub e} values with an accuracy comparable to, or better than, the best single-reference methods (MP4, CCSD, and CCSD(T)), despite the fact that triple and higher excitations into the extra-valence orbital space are included in the single-reference methods but are absent in the multireference wave functions. The computed R{sub e} values using the multireference methods tend to be smooth and monotonic with basis set improvement. The molecular structures are optimized using analytic energy gradients, and the timings for these calculations show the practical

  18. EDF: Computing electron number probability distribution functions in real space from molecular wave functions

    Science.gov (United States)

    Francisco, E.; Pendás, A. Martín; Blanco, M. A.

    2008-04-01

    Given an N-electron molecule and an exhaustive partition of the real space ( R) into m arbitrary regions Ω,Ω,…,Ω ( ⋃i=1mΩ=R), the edf program computes all the probabilities P(n,n,…,n) of having exactly n electrons in Ω, n electrons in Ω,…, and n electrons ( n+n+⋯+n=N) in Ω. Each Ω may correspond to a single basin (atomic domain) or several such basins (functional group). In the later case, each atomic domain must belong to a single Ω. The program can manage both single- and multi-determinant wave functions which are read in from an aimpac-like wave function description ( .wfn) file (T.A. Keith et al., The AIMPAC95 programs, http://www.chemistry.mcmaster.ca/aimpac, 1995). For multi-determinantal wave functions a generalization of the original .wfn file has been introduced. The new format is completely backwards compatible, adding to the previous structure a description of the configuration interaction (CI) coefficients and the determinants of correlated wave functions. Besides the .wfn file, edf only needs the overlap integrals over all the atomic domains between the molecular orbitals (MO). After the P(n,n,…,n) probabilities are computed, edf obtains from them several magnitudes relevant to chemical bonding theory, such as average electronic populations and localization/delocalization indices. Regarding spin, edf may be used in two ways: with or without a splitting of the P(n,n,…,n) probabilities into α and β spin components. Program summaryProgram title: edf Catalogue identifier: AEAJ_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEAJ_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 5387 No. of bytes in distributed program, including test data, etc.: 52 381 Distribution format: tar.gz Programming language: Fortran 77 Computer

  19. THE APPLICATION OF PASS-COMPUTER PROGRAMME AND MOLECULAR DOCKING FOR THE SEARCH OF NEW ANTICONVULSANTS

    Directory of Open Access Journals (Sweden)

    Perekhoda L.O.

    2014-12-01

    Full Text Available Introduction. Currently the priority goal of designing drugs is the integration of the methods of organic chemistry and pharmacology. The application of computer programmes which can predict interaction of Annals of potential drugs with molecules of biological targets makes possible to decrease the number of experiments on laboratory animals. Thereby the economic efficiency of production of new medicines increases. Models of the research the anticonvulsant activity (in particular, korazol, thiosemikarbazid, strychnine, etc. are the most rigid experimental models of pharmacological screening, which basically entails the pains of laboratory animals or their death. The application of computer programmes in the research of potential anticonvulsants has economic and social desirability and high level of importance for the pharmaceutical science and health care. The most perspective methods of research are the virtual screening, molecular docking. These methods allow to evaluate the affinity of a substance to a specific biological target, i.e. to identify an inhibitor of a particular enzyme or protein. Material and methods. We have carried out the construction of 50 groups substances (507 hypothetical structures. We have chosen the five-membered di(threeazaheterocycle as basic pharmacophores to form virtual structures because firstly their structure is similar to cyclic conformation of neurotransmitter and secondly according to the literature perspective anticonvulsants had already found among these derivatives. Computer prediction of pharmacological activity for all compounds of virtual database was performed using the PASS (Prediction of Activity Spectra for Substances computer programme. Results obtained by PASS-computer programme showed prospects of search the anticonvulsants among 10 groups of derivatives di(threeazaheterocycles (probable activity (Pa of substances of these groups are from 0.5 to 0.84. In order to determine the potential

  20. IN SILICO EVALUATION OF ANGIOTENSIN II RECEPTOR ANTAGONIST’S PLASMA PROTEIN BINDING USING COMPUTED MOLECULAR DESCRIPTORS

    Directory of Open Access Journals (Sweden)

    Jadranka Odović

    2014-03-01

    Full Text Available The discovery of new pharmacologically active substances and drugs modeling led to necessity of predicting drugs properties and its ADME data. Angiotensin II receptor antagonists are a group of pharmaceuticals which modulate the renin-angiotensin-aldosterone system and today represent the most commonly prescribed anti-hypertensive drugs. The aim of this study was to compare different molecular properties of seven angiotensin II receptor antagonists / blockers (ARBs, (eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan and their plasma protein binding (PPB data. Several ARBs molecular descriptors were calculated using software package Molinspiration Depiction Software as well as Virtual Computational Chemistry Laboratory (electronic descriptor – PSA, constitutional parameter – Mw, geometric descriptor – Vol, lipophilicity descriptors - logP values, aqueous solubility data – logS. The correlations between all collected descriptors and plasma protein binding data obtained from relevant literature were established. In the simple linear regression poor correlations were obtained in relationships between PPB data and all calculated molecular descriptors. In the next stage of the study multiple linear regression (MLR was used for correlation of PPB data with two different descriptors as independent variables. The best correlation (R2=0.70 with P<0.05 was established between PPB data and molecular weight with addition of volume values as independent variables. The possible application of computed molecular descriptors in drugs protein binding evaluation can be of great importance in drug research.

  1. Quantum wavepacket ab initio molecular dynamics: an approach for computing dynamically averaged vibrational spectra including critical nuclear quantum effects.

    Science.gov (United States)

    Sumner, Isaiah; Iyengar, Srinivasan S

    2007-10-18

    We have introduced a computational methodology to study vibrational spectroscopy in clusters inclusive of critical nuclear quantum effects. This approach is based on the recently developed quantum wavepacket ab initio molecular dynamics method that combines quantum wavepacket dynamics with ab initio molecular dynamics. The computational efficiency of the dynamical procedure is drastically improved (by several orders of magnitude) through the utilization of wavelet-based techniques combined with the previously introduced time-dependent deterministic sampling procedure measure to achieve stable, picosecond length, quantum-classical dynamics of electrons and nuclei in clusters. The dynamical information is employed to construct a novel cumulative flux/velocity correlation function, where the wavepacket flux from the quantized particle is combined with classical nuclear velocities to obtain the vibrational density of states. The approach is demonstrated by computing the vibrational density of states of [Cl-H-Cl]-, inclusive of critical quantum nuclear effects, and our results are in good agreement with experiment. A general hierarchical procedure is also provided, based on electronic structure harmonic frequencies, classical ab initio molecular dynamics, computation of nuclear quantum-mechanical eigenstates, and employing quantum wavepacket ab initio dynamics to understand vibrational spectroscopy in hydrogen-bonded clusters that display large degrees of anharmonicities.

  2. Computation of diatomic molecular spectra for selected transitions of aluminum monoxide, cyanide, diatomic carbon, and titanium monoxide

    Energy Technology Data Exchange (ETDEWEB)

    Parigger, Christian G., E-mail: cparigge@tennessee.edu [The University of Tennessee/University of Tennessee Space Institute, Center for Laser Applications, 411 B.H. Goethert Parkway, Tullahoma, TN 37388-9700 (United States); Woods, Alexander C.; Surmick, David M.; Gautam, Ghaneshwar; Witte, Michael J. [The University of Tennessee/University of Tennessee Space Institute, Center for Laser Applications, 411 B.H. Goethert Parkway, Tullahoma, TN 37388-9700 (United States); Hornkohl, James O. [Hornkohl Consulting, Tullahoma, TN 37388 (United States)

    2015-05-01

    Laser ablation studies with laser-induced breakdown spectroscopy (LIBS) typically emphasize atomic species yet fingerprints from molecular species can occur subsequently or concurrently. In this work, selected molecular transitions of aluminum monixide (AlO), diatomic carbon (C{sub 2}), cyanide (CN), and titanium monoxide (TiO) are accurately computed. Line strength tables are used to describe the radiative transitions of diatomic molecules primarily in the visible, optical region. Details are elaborated of the computational procedure that allows one to utilize diatomic spectra as a predictive and as a diagnostic tool. In order to create a computed spectrum, the procedure requires information regarding the temperature of the diatomic transitions along with other input such as the spectral resolution. When combined with a fitting algorithm to optimize such parameters, this procedure is used to infer information from an experimentally obtained spectrum. Furthermore, the programs and data files are provided for LIBS investigations that also reveal AlO, C{sub 2}, CN, and TiO diatomic spectra. - Highlights: • We present a program for fitting of molecular spectra. • This includes data base for AlO, C{sub 2}, CN, and TiO. • We discuss the details of the program including fitting. • We show computed examples and reference current work.

  3. Nonlinear Hamiltonian mechanics applied to molecular dynamics theory and computational methods for understanding molecular spectroscopy and chemical reactions

    CERN Document Server

    Farantos, Stavros C

    2014-01-01

    This brief presents numerical methods for describing and calculating invariant phase space structures, as well as solving the classical and quantum equations of motion for polyatomic molecules. Examples covered include simple model systems to realistic cases of molecules spectroscopically studied. Vibrationally excited and reacting molecules are nonlinear dynamical systems, and thus, nonlinear mechanics is the proper theory to elucidate molecular dynamics by investigating invariant structures in phase space. Intramolecular energy transfer, and the breaking and forming of a chemical bond have now found a rigorous explanation by studying phase space structures.

  4. Steady state analysis of Boolean molecular network models via model reduction and computational algebra.

    Science.gov (United States)

    Veliz-Cuba, Alan; Aguilar, Boris; Hinkelmann, Franziska; Laubenbacher, Reinhard

    2014-06-26

    A key problem in the analysis of mathematical models of molecular networks is the determination of their steady states. The present paper addresses this problem for Boolean network models, an increasingly popular modeling paradigm for networks lacking detailed kinetic information. For small models, the problem can be solved by exhaustive enumeration of all state transitions. But for larger models this is not feasible, since the size of the phase space grows exponentially with the dimension of the network. The dimension of published models is growing to over 100, so that efficient methods for steady state determination are essential. Several methods have been proposed for large networks, some of them heuristic. While these methods represent a substantial improvement in scalability over exhaustive enumeration, the problem for large networks is still unsolved in general. This paper presents an algorithm that consists of two main parts. The first is a graph theoretic reduction of the wiring diagram of the network, while preserving all information about steady states. The second part formulates the determination of all steady states of a Boolean network as a problem of finding all solutions to a system of polynomial equations over the finite number system with two elements. This problem can be solved with existing computer algebra software. This algorithm compares favorably with several existing algorithms for steady state determination. One advantage is that it is not heuristic or reliant on sampling, but rather determines algorithmically and exactly all steady states of a Boolean network. The code for the algorithm, as well as the test suite of benchmark networks, is available upon request from the corresponding author. The algorithm presented in this paper reliably determines all steady states of sparse Boolean networks with up to 1000 nodes. The algorithm is effective at analyzing virtually all published models even those of moderate connectivity. The problem for

  5. Development of a model for the rational design of molecular imprinted polymer: Computational approach for combined molecular dynamics/quantum mechanics calculations

    International Nuclear Information System (INIS)

    Dong Cunku; Li Xin; Guo Zechong; Qi Jingyao

    2009-01-01

    A new rational approach for the preparation of molecularly imprinted polymer (MIP) based on the combination of molecular dynamics (MD) simulations and quantum mechanics (QM) calculations is described in this work. Before performing molecular modeling, a virtual library of functional monomers was created containing forty frequently used monomers. The MD simulations were first conducted to screen the top three monomers from virtual library in each porogen-acetonitrile, chloroform and carbon tetrachloride. QM simulations were then performed with an aim to select the optimum monomer and progen solvent in which the QM simulations were carried out; the monomers giving the highest binding energies were chosen as the candidate to prepare MIP in its corresponding solvent. The acetochlor, a widely used herbicide, was chosen as the target analyte. According to the theoretical calculation results, the MIP with acetochlor as template was prepared by emulsion polymerization method using N,N-methylene bisacrylamide (MBAAM) as functional monomer and divinylbenzene (DVB) as cross-linker in chloroform. The synthesized MIP was then tested by equilibrium-adsorption method, and the MIP demonstrated high removal efficiency to the acetochlor. Mulliken charge distribution and 1 H NMR spectroscopy of the synthesized MIP provided insight on the nature of recognition during the imprinting process probing the governing interactions for selective binding site formation at a molecular level. We think the computer simulation method first proposed in this paper is a novel and reliable method for the design and synthesis of MIP.

  6. Estimation and Uncertainty Analysis of Flammability Properties for Computer-aided molecular design of working fluids for thermodynamic cycles

    DEFF Research Database (Denmark)

    Frutiger, Jerome; Abildskov, Jens; Sin, Gürkan

    Computer Aided Molecular Design (CAMD) is an important tool to generate, test and evaluate promising chemical products. CAMD can be used in thermodynamic cycle for the design of pure component or mixture working fluids in order to improve the heat transfer capacity of the system. The safety......, there is no information about the reliability of the data. Furthermore, the global optimality of the GC parameters estimation is often not ensured....

  7. Numerical methodologies for investigation of moderate-velocity flow using a hybrid computational fluid dynamics - molecular dynamics simulation approach

    International Nuclear Information System (INIS)

    Ko, Soon Heum; Kim, Na Yong; Nikitopoulos, Dimitris E.; Moldovan, Dorel; Jha, Shantenu

    2014-01-01

    Numerical approaches are presented to minimize the statistical errors inherently present due to finite sampling and the presence of thermal fluctuations in the molecular region of a hybrid computational fluid dynamics (CFD) - molecular dynamics (MD) flow solution. Near the fluid-solid interface the hybrid CFD-MD simulation approach provides a more accurate solution, especially in the presence of significant molecular-level phenomena, than the traditional continuum-based simulation techniques. It also involves less computational cost than the pure particle-based MD. Despite these advantages the hybrid CFD-MD methodology has been applied mostly in flow studies at high velocities, mainly because of the higher statistical errors associated with low velocities. As an alternative to the costly increase of the size of the MD region to decrease statistical errors, we investigate a few numerical approaches that reduce sampling noise of the solution at moderate-velocities. These methods are based on sampling of multiple simulation replicas and linear regression of multiple spatial/temporal samples. We discuss the advantages and disadvantages of each technique in the perspective of solution accuracy and computational cost.

  8. Communication: A method to compute the transport coefficient of pure fluids diffusing through planar interfaces from equilibrium molecular dynamics simulations.

    Science.gov (United States)

    Vermorel, Romain; Oulebsir, Fouad; Galliero, Guillaume

    2017-09-14

    The computation of diffusion coefficients in molecular systems ranks among the most useful applications of equilibrium molecular dynamics simulations. However, when dealing with the problem of fluid diffusion through vanishingly thin interfaces, classical techniques are not applicable. This is because the volume of space in which molecules diffuse is ill-defined. In such conditions, non-equilibrium techniques allow for the computation of transport coefficients per unit interface width, but their weak point lies in their inability to isolate the contribution of the different physical mechanisms prone to impact the flux of permeating molecules. In this work, we propose a simple and accurate method to compute the diffusional transport coefficient of a pure fluid through a planar interface from equilibrium molecular dynamics simulations, in the form of a diffusion coefficient per unit interface width. In order to demonstrate its validity and accuracy, we apply our method to the case study of a dilute gas diffusing through a smoothly repulsive single-layer porous solid. We believe this complementary technique can benefit to the interpretation of the results obtained on single-layer membranes by means of complex non-equilibrium methods.

  9. Fast parallel molecular algorithms for DNA-based computation: solving the elliptic curve discrete logarithm problem over GF2.

    Science.gov (United States)

    Li, Kenli; Zou, Shuting; Xv, Jin

    2008-01-01

    Elliptic curve cryptographic algorithms convert input data to unrecognizable encryption and the unrecognizable data back again into its original decrypted form. The security of this form of encryption hinges on the enormous difficulty that is required to solve the elliptic curve discrete logarithm problem (ECDLP), especially over GF(2(n)), n in Z+. This paper describes an effective method to find solutions to the ECDLP by means of a molecular computer. We propose that this research accomplishment would represent a breakthrough for applied biological computation and this paper demonstrates that in principle this is possible. Three DNA-based algorithms: a parallel adder, a parallel multiplier, and a parallel inverse over GF(2(n)) are described. The biological operation time of all of these algorithms is polynomial with respect to n. Considering this analysis, cryptography using a public key might be less secure. In this respect, a principal contribution of this paper is to provide enhanced evidence of the potential of molecular computing to tackle such ambitious computations.

  10. Structure and Interface Properties of Nanophase Ceramics: Multimillion Particle Molecular-Dynamics Simulations on Parallel Computer

    National Research Council Canada - National Science Library

    Kalia, Rajiv

    1997-01-01

    Large-scale molecular-dynamics (MD) simulations were performed to investigate: (1) sintering process, structural correlations, and mechanical behavior including dynamic fracture in microporous and nanophase Si3N4...

  11. Integrating Molecular Computation and Material Production in an Artificial Subcellular Matrix

    DEFF Research Database (Denmark)

    Fellermann, Harold; Hadorn, Maik; Bönzli, Eva

    Living systems are unique in that they integrate molecular recognition and information processing with material production on the molecular scale. Pre- dominant locus of this integration is the cellular matrix, where a multitude of biochemical reactions proceed simultaneously in highly compartmen......Living systems are unique in that they integrate molecular recognition and information processing with material production on the molecular scale. Pre- dominant locus of this integration is the cellular matrix, where a multitude of biochemical reactions proceed simultaneously in highly...... compartmentalized re- action compartments that interact and get delivered through vesicle trafficking. The European Commission funded project MatchIT (Matrix for Chemical IT) aims at creating an artificial cellular matrix that seamlessly integrates infor- mation processing and material production in much the same...

  12. Molecular device computer: point of departure for large scale cellular automata

    Energy Technology Data Exchange (ETDEWEB)

    Carter, F L

    1984-01-01

    Switching is possible at the molecular size level because of the conformational changes that occur. Three of the most promising switching mechanisms include electron tunnelling in short periodic arrays, soliton switching and soliton valving. Assuming a 3-d architecture and molecular dimensions, memory and switching elements with densities of 10/sup 15/ to 10 /sup 18/ elements per cc are possible. The active elements are connected together conceptionally with molecular wires like polysulfur nitride (sn)/sub x/ and polyacetylene (ch)/sub x/. Simple cellular automata involving soliton propagation in conjugated systems would include soliton valves and cyclic configurations of valves. In the latter, soliton propagation becomes isomorphous with group operations giving rise to possible non-binary finite-state machines. The development of a molecular electron device (MED) synthetic capability in combination with the above devices would suggest that large 3-d arrays of parallel processors will be possible with automata, biological, and crystallographic implications. 41 references.

  13. Random sampling technique for ultra-fast computations of molecular opacities for exoplanet atmospheres

    Science.gov (United States)

    Min, M.

    2017-10-01

    Context. Opacities of molecules in exoplanet atmospheres rely on increasingly detailed line-lists for these molecules. The line lists available today contain for many species up to several billions of lines. Computation of the spectral line profile created by pressure and temperature broadening, the Voigt profile, of all of these lines is becoming a computational challenge. Aims: We aim to create a method to compute the Voigt profile in a way that automatically focusses the computation time into the strongest lines, while still maintaining the continuum contribution of the high number of weaker lines. Methods: Here, we outline a statistical line sampling technique that samples the Voigt profile quickly and with high accuracy. The number of samples is adjusted to the strength of the line and the local spectral line density. This automatically provides high accuracy line shapes for strong lines or lines that are spectrally isolated. The line sampling technique automatically preserves the integrated line opacity for all lines, thereby also providing the continuum opacity created by the large number of weak lines at very low computational cost. Results: The line sampling technique is tested for accuracy when computing line spectra and correlated-k tables. Extremely fast computations ( 3.5 × 105 lines per second per core on a standard current day desktop computer) with high accuracy (≤1% almost everywhere) are obtained. A detailed recipe on how to perform the computations is given.

  14. Computation of Hydration Free Energies Using the Multiple Environment Single System Quantum Mechanical/Molecular Mechanical Method.

    Science.gov (United States)

    König, Gerhard; Mei, Ye; Pickard, Frank C; Simmonett, Andrew C; Miller, Benjamin T; Herbert, John M; Woodcock, H Lee; Brooks, Bernard R; Shao, Yihan

    2016-01-12

    A recently developed MESS-E-QM/MM method (multiple-environment single-system quantum mechanical molecular/mechanical calculations with a Roothaan-step extrapolation) is applied to the computation of hydration free energies for the blind SAMPL4 test set and for 12 small molecules. First, free energy simulations are performed with a classical molecular mechanics force field using fixed-geometry solute molecules and explicit TIP3P solvent, and then the non-Boltzmann-Bennett method is employed to compute the QM/MM correction (QM/MM-NBB) to the molecular mechanical hydration free energies. For the SAMPL4 set, MESS-E-QM/MM-NBB corrections to the hydration free energy can be obtained 2 or 3 orders of magnitude faster than fully converged QM/MM-NBB corrections, and, on average, the hydration free energies predicted with MESS-E-QM/MM-NBB fall within 0.10-0.20 kcal/mol of full-converged QM/MM-NBB results. Out of five density functionals (BLYP, B3LYP, PBE0, M06-2X, and ωB97X-D), the BLYP functional is found to be most compatible with the TIP3P solvent model and yields the most accurate hydration free energies against experimental values for solute molecules included in this study.

  15. Computational methods for molecular structure determination: theory and technique. NRCC Proceedings No. 8

    International Nuclear Information System (INIS)

    1979-01-01

    Goal of this workshop was to provide an introduction to the use of state-of-the-art computer codes for the semi-empirical and ab initio computation of the electronic structure and geometry of small and large molecules. The workshop consisted of 15 lectures on the theoretical foundations of the codes, followed by laboratory sessions which utilized these codes

  16. Computing molecular fluctuations in biochemical reaction systems based on a mechanistic, statistical theory of irreversible processes.

    Science.gov (United States)

    Kulasiri, Don

    2011-01-01

    We discuss the quantification of molecular fluctuations in the biochemical reaction systems within the context of intracellular processes associated with gene expression. We take the molecular reactions pertaining to circadian rhythms to develop models of molecular fluctuations in this chapter. There are a significant number of studies on stochastic fluctuations in intracellular genetic regulatory networks based on single cell-level experiments. In order to understand the fluctuations associated with the gene expression in circadian rhythm networks, it is important to model the interactions of transcriptional factors with the E-boxes in the promoter regions of some of the genes. The pertinent aspects of a near-equilibrium theory that would integrate the thermodynamical and particle dynamic characteristics of intracellular molecular fluctuations would be discussed, and the theory is extended by using the theory of stochastic differential equations. We then model the fluctuations associated with the promoter regions using general mathematical settings. We implemented ubiquitous Gillespie's algorithms, which are used to simulate stochasticity in biochemical networks, for each of the motifs. Both the theory and the Gillespie's algorithms gave the same results in terms of the time evolution of means and variances of molecular numbers. As biochemical reactions occur far away from equilibrium-hence the use of the Gillespie algorithm-these results suggest that the near-equilibrium theory should be a good approximation for some of the biochemical reactions. © 2011 Elsevier Inc. All rights reserved.

  17. Application of computational methods to the design and characterisation of porous molecular materials.

    Science.gov (United States)

    Evans, Jack D; Jelfs, Kim E; Day, Graeme M; Doonan, Christian J

    2017-06-06

    Composed from discrete units, porous molecular materials (PMMs) possess unique properties not observed for conventional, extended, solids, such as solution processibility and permanent porosity in the liquid phase. However, identifying the origin of porosity is not a trivial process, especially for amorphous or liquid phases. Furthermore, the assembly of molecular components is typically governed by a subtle balance of weak intermolecular forces that makes structure prediction challenging. Accordingly, in this review we canvass the crucial role of molecular simulations in the characterisation and design of PMMs. We will outline strategies for modelling porosity in crystalline, amorphous and liquid phases and also describe the state-of-the-art methods used for high-throughput screening of large datasets to identify materials that exhibit novel performance characteristics.

  18. Molecular design of highly efficient extractants for separation of lanthanides and actinides by computational chemistry

    International Nuclear Information System (INIS)

    Uezu, Kazuya; Yamagawa, Jun-ichiro; Goto, Masahiro

    2006-01-01

    Novel organophosphorus extractants, which have two functional moieties in the molecular structure, were developed for the recycle system of transuranium elements using liquid-liquid extraction. The synthesized extractants showed extremely high extractability to lanthanides elements compared to those of commercially available extractants. The results of extraction equilibrium suggested that the structural effect of extractants is one of the key factors to enhance the selectivity and extractability in lanthanides extractions. Furthermore, molecular modeling was carried out to evaluate the extraction properties for extraction of lanthanides by the synthesized extractants. Molecular modeling was shown to be very useful for designing new extractants. The new concept to connect some functional moieties with a spacer is very useful and is a promising method to develop novel extractants for treatment of nuclear fuel. (author)

  19. Computational Molecular Nanoscience Study of the Properties of Copper Complexes for Dye-Sensitized Solar Cells

    Science.gov (United States)

    Baldenebro-López, Jesús; Castorena-González, José; Flores-Holguín, Norma; Almaral-Sánchez, Jorge; Glossman-Mitnik, Daniel

    2012-01-01

    In this work, we studied a copper complex-based dye, which is proposed for potential photovoltaic applications and is named Cu (I) biquinoline dye. Results of electron affinities and ionization potentials have been used for the correlation between different levels of calculation used in this study, which are based on The Density Functional Theory (DFT) and time-dependent (TD) DFT. Further, the maximum absorption wavelengths of our theoretical calculations were compared with the experimental data. It was found that the M06/LANL2DZ + DZVP level of calculation provides the best approximation. This level of calculation was used to find the optimized molecular structure and to predict the main molecular vibrations, the molecular orbitals energies, dipole moment, isotropic polarizability and the chemical reactivity parameters that arise from Conceptual DFT. PMID:23443107

  20. Phase behaviour of macromolecular liquid crystalline materials. Computational studies at the molecular level

    International Nuclear Information System (INIS)

    Stimson, Lorna M.

    2003-01-01

    Molecular simulations provide an increasingly useful insight into the static and dynamic characteristics of materials. In this thesis molecular simulations of macro-molecular liquid crystalline materials are reported. The first liquid crystalline material that has been investigated is a side chain liquid crystal polymer (SCLCP). In this study semi-atomistic molecular dynamics simulations have been conducted at a range of temperatures and an aligning potential has been applied to mimic the effect of a magnetic field. In cooling the SCLCP from an isotropic melt, microphase separation was observed yielding a domain structure. The application of a magnetic field to this structure aligns the domains producing a stable smectic mesophase. This is the first study in which mesophases have been observed using an off-lattice model of a SCLCP. The second material that has been investigated is a dendrimer with terminal mesogenic functionalization. Here, a multi-scale approach has been taken with Monte Carlo studies of a single dendrimer molecule in the gas phase at the atomistic level, semi-atomistic molecular dynamics of a single molecule in liquid crystalline solvents and a coarse-grained molecular dynamics study of the dendrimer in the bulk. The coarse-grained model has been developed and parameterized using the results of the atomistic and semi-atomistic work. The single molecule studies showed that the liquid crystalline dendrimer was able to change its structure by conformational changes in the flexible chains that link the mesogenic groups to the core. Structural change was seen under the application of a mean field ordering potential in the gas phase, and in the presence of liquid crystalline solvents. No liquid crystalline phases were observed for the bulk phase studies of the coarse-grained model. However, when the length of the mesogenic units was increased there was some evidence for microphase separation in these systems. (author)

  1. Experimental and computational studies on molecularly imprinted solid-phase extraction for gonyautoxins 2,3 from dinoflagellate Alexandrium minutum.

    Science.gov (United States)

    Lian, Ziru; Li, Hai-Bei; Wang, Jiangtao

    2016-08-01

    An innovative and effective extraction procedure based on molecularly imprinted solid-phase extraction (MISPE) was developed for the isolation of gonyautoxins 2,3 (GTX2,3) from Alexandrium minutum sample. Molecularly imprinted polymer microspheres were prepared by suspension polymerization and and were employed as sorbents for the solid-phase extraction of GTX2,3. An off-line MISPE protocol was optimized. Subsequently, the extract samples from A. minutum were analyzed. The results showed that the interference matrices in the extract were obviously cleaned up by MISPE procedures. This outcome enabled the direct extraction of GTX2,3 in A. minutum samples with extraction efficiency as high as 83 %, rather significantly, without any need for a cleanup step prior to the extraction. Furthermore, computational approach also provided direct evidences of the high selective isolation of GTX2,3 from the microalgal extracts.

  2. Combinatorial computational chemistry approach of tight-binding quantum chemical molecular dynamics method to the design of the automotive catalysts

    International Nuclear Information System (INIS)

    Ito, Yuki; Jung, Changho; Luo, Yi; Koyama, Michihisa; Endou, Akira; Kubo, Momoji; Imamura, Akira; Miyamoto, Akira

    2006-01-01

    Recently, we have developed a new tight-binding quantum chemical molecular dynamics program 'Colors' for combinatorial computational chemistry approach. This methodology is based on our original tight-binding approximation and realized over 5000 times acceleration compared to the conventional first-principles molecular dynamics method. In the present study, we applied our new program to the simulations on various realistic large-scale models of the automotive three-way catalysts, ultrafine Pt particle/CeO 2 (111) support. Significant electron transfer from the Pt particle to the CeO 2 (111) surface was observed and it was found to strongly depend on the size of the Pt particle. Furthermore, our simulation results suggest that the reduction of the Ce atom due to the electron transfer from the Pt particle to the CeO 2 surface is a main reason for the strong interaction of the Pt particle and CeO 2 (111) support

  3. Computational challenges of large-scale, long-time, first-principles molecular dynamics

    International Nuclear Information System (INIS)

    Kent, P R C

    2008-01-01

    Plane wave density functional calculations have traditionally been able to use the largest available supercomputing resources. We analyze the scalability of modern projector-augmented wave implementations to identify the challenges in performing molecular dynamics calculations of large systems containing many thousands of electrons. Benchmark calculations on the Cray XT4 demonstrate that global linear-algebra operations are the primary reason for limited parallel scalability. Plane-wave related operations can be made sufficiently scalable. Improving parallel linear-algebra performance is an essential step to reaching longer timescales in future large-scale molecular dynamics calculations

  4. Effects of Organics on the Adsorption and Mobility of Metal Cations in Clay Systems: Computational Molecular Modeling Approach

    International Nuclear Information System (INIS)

    Kalinichev, Andrey G.; Ngouana Wakou, Brice F.; Loganathan, Narasimhan

    2013-01-01

    Understanding and prediction of many natural and anthropogenic environmental processes ultimately depend on a fundamental understanding of the chemistry occurring at the mineral-fluid inter-faces. Clay-related minerals and natural organic matter (NOM) are ubiquitous in the environment, and metal-NOM complexation induces strong correlations between the NOM concentration in water and the capacity of clay particles to bind metals, thus affecting their speciation, solubility and toxicity in the environment. Despite significant geochemical, environmental and technological interest, the molecular-level mechanisms and dynamics of the physical and chemical processes involving NOM are not yet well understood. In this presentation we compare three different molecular dynamics (MD) computer simulations of metal-NOM complexation in aqueous solutions. The simulation results indicate that despite some obvious quantitative variations in the computed values depending on the size of the simulated system and on the parameters of the force field models used, all three simulations are quite robust and consistent. In particular, approximately 35-50% of Ca 2+ ions in all simulations are associated with the carboxylic groups of NOM at near-neutral pH. The stability of bidentate-coordinated contact ion pair complexes is also always strongly preferred. Easy association of metal cations with negatively charged NOM functional groups and negatively charged clay surfaces allows us to predict that cationic bridging could be the most probable mechanism of NOM association with clays in natural environments. New MD simulations are currently in progress to quantitatively assess these predictions on a molecular scale for nuclear waste disposal applications. New larger-scale clay models incorporate a more realistic representation of the structural and compositional disorder of natural illites and smectites and employ CLAYFF - a fully flexible general force field suitable for the molecular simulations

  5. QuBiLS-MIDAS: a parallel free-software for molecular descriptors computation based on multilinear algebraic maps.

    Science.gov (United States)

    García-Jacas, César R; Marrero-Ponce, Yovani; Acevedo-Martínez, Liesner; Barigye, Stephen J; Valdés-Martiní, José R; Contreras-Torres, Ernesto

    2014-07-05

    The present report introduces the QuBiLS-MIDAS software belonging to the ToMoCoMD-CARDD suite for the calculation of three-dimensional molecular descriptors (MDs) based on the two-linear (bilinear), three-linear, and four-linear (multilinear or N-linear) algebraic forms. Thus, it is unique software that computes these tensor-based indices. These descriptors, establish relations for two, three, and four atoms by using several (dis-)similarity metrics or multimetrics, matrix transformations, cutoffs, local calculations and aggregation operators. The theoretical background of these N-linear indices is also presented. The QuBiLS-MIDAS software was developed in the Java programming language and employs the Chemical Development Kit library for the manipulation of the chemical structures and the calculation of the atomic properties. This software is composed by a desktop user-friendly interface and an Abstract Programming Interface library. The former was created to simplify the configuration of the different options of the MDs, whereas the library was designed to allow its easy integration to other software for chemoinformatics applications. This program provides functionalities for data cleaning tasks and for batch processing of the molecular indices. In addition, it offers parallel calculation of the MDs through the use of all available processors in current computers. The studies of complexity of the main algorithms demonstrate that these were efficiently implemented with respect to their trivial implementation. Lastly, the performance tests reveal that this software has a suitable behavior when the amount of processors is increased. Therefore, the QuBiLS-MIDAS software constitutes a useful application for the computation of the molecular indices based on N-linear algebraic maps and it can be used freely to perform chemoinformatics studies. Copyright © 2014 Wiley Periodicals, Inc.

  6. Thermodynamic and transport properties of nitrogen fluid: Molecular theory and computer simulations

    Science.gov (United States)

    Eskandari Nasrabad, A.; Laghaei, R.

    2018-04-01

    Computer simulations and various theories are applied to compute the thermodynamic and transport properties of nitrogen fluid. To model the nitrogen interaction, an existing potential in the literature is modified to obtain a close agreement between the simulation results and experimental data for the orthobaric densities. We use the Generic van der Waals theory to calculate the mean free volume and apply the results within the modified Cohen-Turnbull relation to obtain the self-diffusion coefficient. Compared to experimental data, excellent results are obtained via computer simulations for the orthobaric densities, the vapor pressure, the equation of state, and the shear viscosity. We analyze the results of the theory and computer simulations for the various thermophysical properties.

  7. Computer aided drug discovery of highly ligand efficient, low molecular weight imidazopyridine analogs as FLT3 inhibitors.

    Science.gov (United States)

    Frett, Brendan; McConnell, Nick; Smith, Catherine C; Wang, Yuanxiang; Shah, Neil P; Li, Hong-yu

    2015-04-13

    The FLT3 kinase represents an attractive target to effectively treat AML. Unfortunately, no FLT3 targeted therapeutic is currently approved. In line with our continued interests in treating kinase related disease for anti-FLT3 mutant activity, we utilized pioneering synthetic methodology in combination with computer aided drug discovery and identified low molecular weight, highly ligand efficient, FLT3 kinase inhibitors. Compounds were analyzed for biochemical inhibition, their ability to selectively inhibit cell proliferation, for FLT3 mutant activity, and preliminary aqueous solubility. Validated hits were discovered that can serve as starting platforms for lead candidates. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  8. Fast automatic segmentation of anatomical structures in x-ray computed tomography images to improve fluorescence molecular tomography reconstruction.

    Science.gov (United States)

    Freyer, Marcus; Ale, Angelique; Schulz, Ralf B; Zientkowska, Marta; Ntziachristos, Vasilis; Englmeier, Karl-Hans

    2010-01-01

    The recent development of hybrid imaging scanners that integrate fluorescence molecular tomography (FMT) and x-ray computed tomography (XCT) allows the utilization of x-ray information as image priors for improving optical tomography reconstruction. To fully capitalize on this capacity, we consider a framework for the automatic and fast detection of different anatomic structures in murine XCT images. To accurately differentiate between different structures such as bone, lung, and heart, a combination of image processing steps including thresholding, seed growing, and signal detection are found to offer optimal segmentation performance. The algorithm and its utilization in an inverse FMT scheme that uses priors is demonstrated on mouse images.

  9. Non-opioid analgesic drug flupirtine: Spectral analysis, DFT computations, in vitro bioactivity and molecular docking study

    Science.gov (United States)

    Leenaraj, D. R.; Hubert Joe, I.

    2017-06-01

    Spectral features of non-opioid analgesic drug flupirtine have been explored by the Fourier transform infrared, Raman and Nuclear magnetic resonance spectroscopic techniques combined with density functional theory computations. The bioactive conformer of flupirtine is stabilized by an intramolecular Csbnd H⋯N hydrogen bonding resulting by the steric strain of hydrogen atoms. Natural bond orbital and natural population analysis support this result. The charge redistribution also has been analyzed. Antimicrobial activities of flupirtine have been screened by agar well disc diffusion and molecular docking methods, which exposes the importance of triaminopyridine in flupirtine.

  10. Spintronics: The molecular way

    Science.gov (United States)

    Cornia, Andrea; Seneor, Pierre

    2017-05-01

    Molecular spintronics is an interdisciplinary field at the interface between organic spintronics, molecular magnetism, molecular electronics and quantum computing, which is advancing fast and promises large technological payoffs.

  11. Computational exploration of single-protein mechanics by steered molecular dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Sotomayor, Marcos [Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio (United States)

    2015-12-31

    Hair cell mechanotransduction happens in tens of microseconds, involves forces of a few picoNewtons, and is mediated by nanometer-scale molecular conformational changes. As proteins involved in this process become identified and their high resolution structures become available, multiple tools are being used to explore their “single-molecule responses” to force. Optical tweezers and atomic force microscopy offer exquisite force and extension resolution, but cannot reach the high loading rates expected for high frequency auditory stimuli. Molecular dynamics (MD) simulations can reach these fast time scales, and also provide a unique view of the molecular events underlying protein mechanics, but its predictions must be experimentally verified. Thus a combination of simulations and experiments might be appropriate to study the molecular mechanics of hearing. Here I review the basics of MD simulations and the different methods used to apply force and study protein mechanics in silico. Simulations of tip link proteins are used to illustrate the advantages and limitations of this method.

  12. Molecular mobility on interstellar ices. Computational nanoscience on the galactic scale

    NARCIS (Netherlands)

    Karssemeijer, L.J.

    2015-01-01

    Understanding nature on the largest scales can sometimes require minute details of its very smallest processes. This is certainly true in the field of astrochemistry, the study of the formation and evolution of molecules in outer space; in particular in molecular clouds. Here, in the birthplace of

  13. Fast parallel DNA-based algorithms for molecular computation: the set-partition problem.

    Science.gov (United States)

    Chang, Weng-Long

    2007-12-01

    This paper demonstrates that basic biological operations can be used to solve the set-partition problem. In order to achieve this, we propose three DNA-based algorithms, a signed parallel adder, a signed parallel subtractor and a signed parallel comparator, that formally verify our designed molecular solutions for solving the set-partition problem.

  14. Molecular structure and vibrational spectra of Bis(melaminium) terephthalate dihydrate: A DFT computational study

    Science.gov (United States)

    Tanak, Hasan; Marchewka, Mariusz K.; Drozd, Marek

    2013-03-01

    The experimental and theoretical vibrational spectra of Bis(melaminium) terephthalate dihydrate were studied. The Fourier transform infrared (FT-IR) spectra of the Bis(melaminium) terephthalate dihydrate and its deuterated analogue were recorded in the solid phase. The molecular geometry and vibrational frequencies of Bis(melaminium) terephthalate dihydrate in the ground state have been calculated by using the density functional method (B3LYP) with 6-31++G(d,p) basis set. The results of the optimized molecular structure are presented and compared with the experimental X-ray diffraction. The molecule contains the weak hydrogen bonds of Nsbnd H⋯O, Nsbnd H⋯N and Osbnd H⋯O types, and those bonds are calculated with DFT method. In addition, molecular electrostatic potential, frontier molecular orbitals and natural bond orbital analysis of the title compound were investigated by theoretical calculations. The lack of the second harmonic generation (SHG) confirms the presence of macroscopic center of inversion.

  15. Sensitivity analysis of Computer-aided molecular design problem for the development of novel working fluids for power cycles

    DEFF Research Database (Denmark)

    Frutiger, Jerome; Abildskov, Jens; Sin, Gürkan

    is vital. Multi-criteria database search and Computer Aided Molecular Design(CAMD) can be applied to generate, test and evaluate promising pure component/mixture candidate as process fluids to help optimize cycle design and performance. The problem formulation for the development of novel working fluids...... is anadvanced CAMD challenge both in terms of data and computational demand, because includes process related as wellas property related equations.In CAMD problems the identification of target properties is often based on expert knowledge. To support identification of relevant target properties, in this study...... allows the ranking ofsignificance of properties and also the identification of a set of properties which are relevant for the design of a workingfluids.In this study the CAMD problem for the development of novel working fluids for organic Rankine cycles (ORC) isformulated as a mathematical optimization...

  16. Computing the binding affinity of a ligand buried deep inside a protein with the hybrid steered molecular dynamics

    International Nuclear Information System (INIS)

    Villarreal, Oscar D.; Yu, Lili; Rodriguez, Roberto A.; Chen, Liao Y.

    2017-01-01

    Computing the ligand-protein binding affinity (or the Gibbs free energy) with chemical accuracy has long been a challenge for which many methods/approaches have been developed and refined with various successful applications. False positives and, even more harmful, false negatives have been and still are a common occurrence in practical applications. Inevitable in all approaches are the errors in the force field parameters we obtain from quantum mechanical computation and/or empirical fittings for the intra- and inter-molecular interactions. These errors propagate to the final results of the computed binding affinities even if we were able to perfectly implement the statistical mechanics of all the processes relevant to a given problem. And they are actually amplified to various degrees even in the mature, sophisticated computational approaches. In particular, the free energy perturbation (alchemical) approaches amplify the errors in the force field parameters because they rely on extracting the small differences between similarly large numbers. In this paper, we develop a hybrid steered molecular dynamics (hSMD) approach to the difficult binding problems of a ligand buried deep inside a protein. Sampling the transition along a physical (not alchemical) dissociation path of opening up the binding cavity- -pulling out the ligand- -closing back the cavity, we can avoid the problem of error amplifications by not relying on small differences between similar numbers. We tested this new form of hSMD on retinol inside cellular retinol-binding protein 1 and three cases of a ligand (a benzylacetate, a 2-nitrothiophene, and a benzene) inside a T4 lysozyme L99A/M102Q(H) double mutant. In all cases, we obtained binding free energies in close agreement with the experimentally measured values. This indicates that the force field parameters we employed are accurate and that hSMD (a brute force, unsophisticated approach) is free from the problem of error amplification suffered by

  17. Numerical Nuclear Second Derivatives on a Computing Grid: Enabling and Accelerating Frequency Calculations on Complex Molecular Systems.

    Science.gov (United States)

    Yang, Tzuhsiung; Berry, John F

    2018-06-04

    The computation of nuclear second derivatives of energy, or the nuclear Hessian, is an essential routine in quantum chemical investigations of ground and transition states, thermodynamic calculations, and molecular vibrations. Analytic nuclear Hessian computations require the resolution of costly coupled-perturbed self-consistent field (CP-SCF) equations, while numerical differentiation of analytic first derivatives has an unfavorable 6 N ( N = number of atoms) prefactor. Herein, we present a new method in which grid computing is used to accelerate and/or enable the evaluation of the nuclear Hessian via numerical differentiation: NUMFREQ@Grid. Nuclear Hessians were successfully evaluated by NUMFREQ@Grid at the DFT level as well as using RIJCOSX-ZORA-MP2 or RIJCOSX-ZORA-B2PLYP for a set of linear polyacenes with systematically increasing size. For the larger members of this group, NUMFREQ@Grid was found to outperform the wall clock time of analytic Hessian evaluation; at the MP2 or B2LYP levels, these Hessians cannot even be evaluated analytically. We also evaluated a 156-atom catalytically relevant open-shell transition metal complex and found that NUMFREQ@Grid is faster (7.7 times shorter wall clock time) and less demanding (4.4 times less memory requirement) than an analytic Hessian. Capitalizing on the capabilities of parallel grid computing, NUMFREQ@Grid can outperform analytic methods in terms of wall time, memory requirements, and treatable system size. The NUMFREQ@Grid method presented herein demonstrates how grid computing can be used to facilitate embarrassingly parallel computational procedures and is a pioneer for future implementations.

  18. SCELib2: the new revision of SCELib, the parallel computational library of molecular properties in the single center approach

    Science.gov (United States)

    Sanna, N.; Morelli, G.

    2004-09-01

    In this paper we present the new version of the SCELib program (CPC Catalogue identifier ADMG) a full numerical implementation of the Single Center Expansion (SCE) method. The physics involved is that of producing the SCE description of molecular electronic densities, of molecular electrostatic potentials and of molecular perturbed potentials due to a point negative or positive charge. This new revision of the program has been optimized to run in serial as well as in parallel execution mode, to support a larger set of molecular symmetries and to permit the restart of long-lasting calculations. To measure the performance of this new release, a comparative study has been carried out on the most powerful computing architectures in serial and parallel runs. The results of the calculations reported in this paper refer to real cases medium to large molecular systems and they are reported in full details to benchmark at best the parallel architectures the new SCELib code will run on. Program summaryTitle of program: SCELib2 Catalogue identifier: ADGU Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADGU Program obtainable from: CPC Program Library, Queen's University of Belfast, N. Ireland Reference to previous versions: Comput. Phys. Commun. 128 (2) (2000) 139 (CPC catalogue identifier: ADMG) Does the new version supersede the original program?: Yes Computer for which the program is designed and others on which it has been tested: HP ES45 and rx2600, SUN ES4500, IBM SP and any single CPU workstation based on Alpha, SPARC, POWER, Itanium2 and X86 processors Installations: CASPUR, local Operating systems under which the program has been tested: HP Tru64 V5.X, SUNOS V5.8, IBM AIX V5.X, Linux RedHat V8.0 Programming language used: C Memory required to execute with typical data: 10 Mwords. Up to 2000 Mwords depending on the molecular system and runtime parameters No. of bits in a word: 64 No. of processors used: 1 to 32 Has the code been vectorized or parallelized?: Yes

  19. Experimental and computational study on molecular structure and vibrational analysis of an antihyperglycemic biomolecule: Gliclazide

    Science.gov (United States)

    Karakaya, Mustafa; Kürekçi, Mehmet; Eskiyurt, Buse; Sert, Yusuf; Çırak, Çağrı

    2015-01-01

    In present study, the experimental and theoretical harmonic vibrational frequencies of gliclazide molecule have been investigated. The experimental FT-IR (400-4000 cm-1) and Laser-Raman spectra (100-4000 cm-1) of the molecule in the solid phase were recorded. Theoretical vibrational frequencies and geometric parameters (bond lengths and bond angles) have been calculated using ab initio Hartree Fock (HF), density functional theory (B3LYP hybrid function) methods with 6-311++G(d,p) and 6-31G(d,p) basis sets by Gaussian 09W program. The assignments of the vibrational frequencies were performed by potential energy distribution (PED) analysis by using VEDA 4 program. Theoretical optimized geometric parameters and vibrational frequencies have been compared with the corresponding experimental data, and they have been shown to be in a good agreement with each other. Also, the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies have been found.

  20. Biopython: freely available Python tools for computational molecular biology and bioinformatics

    DEFF Research Database (Denmark)

    Cock, Peter J A; Antao, Tiago; Chang, Jeffrey T

    2009-01-01

    SUMMARY: The Biopython project is a mature open source international collaboration of volunteer developers, providing Python libraries for a wide range of bioinformatics problems. Biopython includes modules for reading and writing different sequence file formats and multiple sequence alignments......, dealing with 3D macro molecular structures, interacting with common tools such as BLAST, ClustalW and EMBOSS, accessing key online databases, as well as providing numerical methods for statistical learning. AVAILABILITY: Biopython is freely available, with documentation and source code at (www...

  1. Computational and molecular dissection of an X-box cis-Regulatory module

    OpenAIRE

    Warrington, Timothy Burton

    2015-01-01

    Ciliopathies are a class of human diseases marked by dysfunction of the cellular organelle, cilia. While many of the molecular components that make up cilia have been identified and studied, comparatively little is understood about the transcriptional regulation of genes encoding these components. The conserved transcription factor Regulatory Factor X (RFX)/DAF-19, which acts through binding to the cis-regulatory motif known as X-box, has been shown to regulate ciliary genes in many animals f...

  2. Computational Study of Geometry, Solvation Free Energy, Dipole Moment, Polarizability, Hyperpolarizability and Molecular Properties of 2-Methylimidazole

    Directory of Open Access Journals (Sweden)

    Mohammad Firoz Khan

    2016-12-01

    Full Text Available Ab initio calculations were carried out to study the geometry, solvation free energy, dipole moment, molecular electrostatic potential (MESP, Mulliken and Natural charge distribution, polarizability, hyperpolarizability, Natural Bond Orbital (NBO energetic and different molecular properties like global reactivity descriptors (chemical hardness, softness, chemical potential, electronegativity, electrophilicity index of 2-methylimidazole. B3LYP/6-31G(d,p level of theory was used to optimize the structure both in the gas phase and in solution. The solvation free energy, dipole moment and molecular properties were calculated by applying the Solvation Model on Density (SMD in four solvent systems, namely water, dimethylsulfoxide (DMSO, n-octanol and chloroform. The computed bond distances, bond angles and dihedral angles of 2-methylimidazole agreed reasonably well with the experimental data except for C(2-N(1, C(4-C(5 and N(1-H(7 bond lengths and N(1-C(5-C(4 bond angle. The solvation free energy, dipole moment, polarizability, first order hyperpolarizability, chemical potential, electronegativity and electrophilicity index of 2-methylimidazole increased on going from non-polar to polar solvents. Chemical hardness also increased with increasing polarity of the solvent and the opposite relation was found in the case of softness. These results provide better understanding of the stability and reactivity of 2-methylimidazole in different solvent systems.

  3. Computational Analysis of Molecular Interaction Networks Underlying Change of HIV-1 Resistance to Selected Reverse Transcriptase Inhibitors.

    Science.gov (United States)

    Kierczak, Marcin; Dramiński, Michał; Koronacki, Jacek; Komorowski, Jan

    2010-12-12

    Despite more than two decades of research, HIV resistance to drugs remains a serious obstacle in developing efficient AIDS treatments. Several computational methods have been developed to predict resistance level from the sequence of viral proteins such as reverse transcriptase (RT) or protease. These methods, while powerful and accurate, give very little insight into the molecular interactions that underly acquisition of drug resistance/hypersusceptibility. Here, we attempt at filling this gap by using our Monte Carlo feature selection and interdependency discovery method (MCFS-ID) to elucidate molecular interaction networks that characterize viral strains with altered drug resistance levels. We analyzed a number of HIV-1 RT sequences annotated with drug resistance level using the MCFS-ID method. This let us expound interdependency networks that characterize change of drug resistance to six selected RT inhibitors: Abacavir, Lamivudine, Stavudine, Zidovudine, Tenofovir and Nevirapine. The networks consider interdependencies at the level of physicochemical properties of mutating amino acids, eg,: polarity. We mapped each network on the 3D structure of RT in attempt to understand the molecular meaning of interacting pairs. The discovered interactions describe several known drug resistance mechanisms and, importantly, some previously unidentified ones. Our approach can be easily applied to a whole range of problems from the domain of protein engineering. A portable Java implementation of our MCFS-ID method is freely available for academic users and can be obtained at: http://www.ipipan.eu/staff/m.draminski/software.htm.

  4. Quantum computing applied to calculations of molecular energies: CH2 benchmark

    Czech Academy of Sciences Publication Activity Database

    Veis, L.; Pittner, Jiří

    2010-01-01

    Roč. 133, č. 19 (2010), s. 194106 ISSN 0021-9606 R&D Projects: GA ČR GA203/08/0626 Institutional research plan: CEZ:AV0Z40400503 Keywords : computation * algorithm * systems Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.920, year: 2010

  5. Algorithms and computer codes for atomic and molecular quantum scattering theory

    International Nuclear Information System (INIS)

    Thomas, L.

    1979-01-01

    This workshop has succeeded in bringing up 11 different coupled equation codes on the NRCC computer, testing them against a set of 24 different test problems and making them available to the user community. These codes span a wide variety of methodologies, and factors of up to 300 were observed in the spread of computer times on specific problems. A very effective method was devised for examining the performance of the individual codes in the different regions of the integration range. Many of the strengths and weaknesses of the codes have been identified. Based on these observations, a hybrid code has been developed which is significantly superior to any single code tested. Thus, not only have the original goals been fully met, the workshop has resulted directly in an advancement of the field. All of the computer programs except VIVS are available upon request from the NRCC. Since an improved version of VIVS is contained in the hybrid program, VIVAS, it was not made available for distribution. The individual program LOGD is, however, available. In addition, programs which compute the potential energy matrices of the test problems are also available. The software library names for Tests 1, 2 and 4 are HEH2, LICO, and EN2, respectively

  6. Exploring the Genomic Roadmap and Molecular Phylogenetics Associated with MODY Cascades Using Computational Biology.

    Science.gov (United States)

    Chakraborty, Chiranjib; Bandyopadhyay, Sanghamitra; Doss, C George Priya; Agoramoorthy, Govindasamy

    2015-04-01

    Maturity onset diabetes of the young (MODY) is a metabolic and genetic disorder. It is different from type 1 and type 2 diabetes with low occurrence level (1-2%) among all diabetes. This disorder is a consequence of β-cell dysfunction. Till date, 11 subtypes of MODY have been identified, and all of them can cause gene mutations. However, very little is known about the gene mapping, molecular phylogenetics, and co-expression among MODY genes and networking between cascades. This study has used latest servers and software such as VarioWatch, ClustalW, MUSCLE, G Blocks, Phylogeny.fr, iTOL, WebLogo, STRING, and KEGG PATHWAY to perform comprehensive analyses of gene mapping, multiple sequences alignment, molecular phylogenetics, protein-protein network design, co-expression analysis of MODY genes, and pathway development. The MODY genes are located in chromosomes-2, 7, 8, 9, 11, 12, 13, 17, and 20. Highly aligned block shows Pro, Gly, Leu, Arg, and Pro residues are highly aligned in the positions of 296, 386, 437, 455, 456 and 598, respectively. Alignment scores inform us that HNF1A and HNF1B proteins have shown high sequence similarity among MODY proteins. Protein-protein network design shows that HNF1A, HNF1B, HNF4A, NEUROD1, PDX1, PAX4, INS, and GCK are strongly connected, and the co-expression analyses between MODY genes also show distinct association between HNF1A and HNF4A genes. This study has used latest tools of bioinformatics to develop a rapid method to assess the evolutionary relationship, the network development, and the associations among eleven MODY genes and cascades. The prediction of sequence conservation, molecular phylogenetics, protein-protein network and the association between the MODY cascades enhances opportunities to get more insights into the less-known MODY disease.

  7. Dynamics of Oxidation of Aluminum Nanoclusters using Variable Charge Molecular-Dynamics Simulations on Parallel Computers

    Science.gov (United States)

    Campbell, Timothy; Kalia, Rajiv K.; Nakano, Aiichiro; Vashishta, Priya; Ogata, Shuji; Rodgers, Stephen

    1999-06-01

    Oxidation of aluminum nanoclusters is investigated with a parallel molecular-dynamics approach based on dynamic charge transfer among atoms. Structural and dynamic correlations reveal that significant charge transfer gives rise to large negative pressure in the oxide which dominates the positive pressure due to steric forces. As a result, aluminum moves outward and oxygen moves towards the interior of the cluster with the aluminum diffusivity 60% higher than that of oxygen. A stable 40 Å thick amorphous oxide is formed; this is in excellent agreement with experiments.

  8. Quantum computing applied to calculations of molecular energies: CH2 benchmark.

    Science.gov (United States)

    Veis, Libor; Pittner, Jiří

    2010-11-21

    Quantum computers are appealing for their ability to solve some tasks much faster than their classical counterparts. It was shown in [Aspuru-Guzik et al., Science 309, 1704 (2005)] that they, if available, would be able to perform the full configuration interaction (FCI) energy calculations with a polynomial scaling. This is in contrast to conventional computers where FCI scales exponentially. We have developed a code for simulation of quantum computers and implemented our version of the quantum FCI algorithm. We provide a detailed description of this algorithm and the results of the assessment of its performance on the four lowest lying electronic states of CH(2) molecule. This molecule was chosen as a benchmark, since its two lowest lying (1)A(1) states exhibit a multireference character at the equilibrium geometry. It has been shown that with a suitably chosen initial state of the quantum register, one is able to achieve the probability amplification regime of the iterative phase estimation algorithm even in this case.

  9. Rational computational design for the development of andrographolide molecularly imprinted polymer

    Science.gov (United States)

    Krishnan, Hemavathi; Islam, K. M. Shafiqul; Hamzah, Zainab; Ahmad, Mohd Noor

    2017-10-01

    Andrographolide is a popular medicinal compound derived from Andrographis Paniculata (AP). Molecularly Imprint Polymer (MIP) is a "Lock and Key" approach, where MIP is the lock and Andrographolide is the key which fits to the MIP lock by both physically and chemically. MIP will be used as selective extraction tool to enrich Andrographolide bioactive compound. Pre-polymerization step is crucial to design MIP. This work investigates molecular interactions and the Gibbs free binding energies on the development of MIP. The structure of Andrographolide (template) and functional monomers were drawn in HyperChem 8.0.10. A hybrid quantum chemical model was used with a few functional monomers. Possible conformations of template and functional monomer as 1:n (n < 4) were designed and simulated to geometrically optimize the complex to the lowest energy in gas phase. The Gibbs free binding energies of each conformation were calculated using semi-empirical PM3 simulation method. Results proved that functional monomers that contain carboxylic group shows higher binding energy compared to those with amine functional group. Itaconic acid (IA) chosen as the best functional monomer at optimum ratio (1:3) of template: monomer to prepare andrographolide MIP. This study demonstrates the importance of studying intermolecular interaction among template, functional monomer and template-monomer ratio in developing MIP.

  10. Quantitative computational models of molecular self-assembly in systems biology.

    Science.gov (United States)

    Thomas, Marcus; Schwartz, Russell

    2017-05-23

    Molecular self-assembly is the dominant form of chemical reaction in living systems, yet efforts at systems biology modeling are only beginning to appreciate the need for and challenges to accurate quantitative modeling of self-assembly. Self-assembly reactions are essential to nearly every important process in cell and molecular biology and handling them is thus a necessary step in building comprehensive models of complex cellular systems. They present exceptional challenges, however, to standard methods for simulating complex systems. While the general systems biology world is just beginning to deal with these challenges, there is an extensive literature dealing with them for more specialized self-assembly modeling. This review will examine the challenges of self-assembly modeling, nascent efforts to deal with these challenges in the systems modeling community, and some of the solutions offered in prior work on self-assembly specifically. The review concludes with some consideration of the likely role of self-assembly in the future of complex biological system models more generally.

  11. Molecular structure, vibrational spectra and DFT computational studies of melaminium N-acetylglycinate dihydrate

    Science.gov (United States)

    Tanak, H.; Pawlus, K.; Marchewka, M. K.

    2016-10-01

    Melaminium N-acetylglycinate dihydrate, an organic material has been synthesized and characterized by X-ray diffraction, FT-IR, and FT-Raman spectroscopies for the protiated and deuteriated crystals. The title complex crystallizes in the triclinic system, and the space group is P-1 with a = 5.642(1) Å, b = 7.773(2) Å, c = 15.775(3) Å, α = 77.28(1)°, β = 84.00(1)°, γ = 73.43(1)° and Z = 2. The molecular geometry, vibrational frequencies and intensity of the vibrational bands have been interpreted with the aid of structure optimization based on density functional method (B3LYP) with the 6-311++G(d,p) basis set. The obtained vibrational wavenumbers and optimized geometric parameters were seen to be in good agreement with the experimental data. The intermolecular hydrogen bonding interactions of the title compound have been investigated using the natural bonding orbital analysis. It reveals that the O-H···O, N-H···N and N-H···O intermolecular interactions significantly influence crystal packing of this molecule. The non-linear optical properties are also addressed theoretically. The predicted NLO properties of the title compound are much greater than ones of urea. In addition, DFT calculations of the title compound, molecular electrostatic potential, thermodynamic properties, frontier orbitals and chemical reactivity descriptors were also performed at 6-311++G(d,p) level of theory.

  12. Experimental and Computational Approaches to the Molecular Structure of 3-(2-Mercaptopyridine)phthalonitrile

    International Nuclear Information System (INIS)

    Tanak, Hasan; Koysal, Yavuz; Isik, Samil; Yaman, Hanifi; Ahsen, Vefa

    2011-01-01

    The compound 3-(2-Mercaptopyridine)phthalonitrile has been synthesized and characterized by IR, UV-vis, and X-ray single-crystal determination. The molecular geometry from X-ray determination of the title compound in the ground state has been compared using the Hartree-Fock (HF) and density functional theory (DFT) with the 6-31G(d) basis set. The calculated results show that the DFT and HF can well reproduce the structure of the title compound. The energetic behavior of the title compound in solvent media was examined using the B3LYP method with the 6-31G(d) basis set by applying the Onsager and polarizable continuum model. Using the TD-DFT and TD-HF methods, electronic absorption spectra of the title compound have been predicted and good agreement with the TD-DFT method and the experimental determination was found. The predicted nonlinear optical properties of the title compound are much greater than those of urea. Besides, molecular electrostatic potential of the title compound were investigated by theoretical calculations. The thermodynamic properties of the compound at different temperatures have been calculated and corresponding relations between the properties and temperature have also been obtained

  13. Experimental and Computational Approaches to the Molecular Structure of 3-(2-Mercaptopyridine)phthalonitrile

    Energy Technology Data Exchange (ETDEWEB)

    Tanak, Hasan [Amasya University, Amasys (Turkmenistan); Koysal, Yavuz; Isik, Samil [Ondokuz Mayis University, Samsun (Turkmenistan); Yaman, Hanifi; Ahsen, Vefa [Gebze Institute of Technology Department of Chemistry, Gebze-Kocaeli (Turkmenistan)

    2011-02-15

    The compound 3-(2-Mercaptopyridine)phthalonitrile has been synthesized and characterized by IR, UV-vis, and X-ray single-crystal determination. The molecular geometry from X-ray determination of the title compound in the ground state has been compared using the Hartree-Fock (HF) and density functional theory (DFT) with the 6-31G(d) basis set. The calculated results show that the DFT and HF can well reproduce the structure of the title compound. The energetic behavior of the title compound in solvent media was examined using the B3LYP method with the 6-31G(d) basis set by applying the Onsager and polarizable continuum model. Using the TD-DFT and TD-HF methods, electronic absorption spectra of the title compound have been predicted and good agreement with the TD-DFT method and the experimental determination was found. The predicted nonlinear optical properties of the title compound are much greater than those of urea. Besides, molecular electrostatic potential of the title compound were investigated by theoretical calculations. The thermodynamic properties of the compound at different temperatures have been calculated and corresponding relations between the properties and temperature have also been obtained.

  14. Molecular simulation workflows as parallel algorithms: the execution engine of Copernicus, a distributed high-performance computing platform.

    Science.gov (United States)

    Pronk, Sander; Pouya, Iman; Lundborg, Magnus; Rotskoff, Grant; Wesén, Björn; Kasson, Peter M; Lindahl, Erik

    2015-06-09

    Computational chemistry and other simulation fields are critically dependent on computing resources, but few problems scale efficiently to the hundreds of thousands of processors available in current supercomputers-particularly for molecular dynamics. This has turned into a bottleneck as new hardware generations primarily provide more processing units rather than making individual units much faster, which simulation applications are addressing by increasingly focusing on sampling with algorithms such as free-energy perturbation, Markov state modeling, metadynamics, or milestoning. All these rely on combining results from multiple simulations into a single observation. They are potentially powerful approaches that aim to predict experimental observables directly, but this comes at the expense of added complexity in selecting sampling strategies and keeping track of dozens to thousands of simulations and their dependencies. Here, we describe how the distributed execution framework Copernicus allows the expression of such algorithms in generic workflows: dataflow programs. Because dataflow algorithms explicitly state dependencies of each constituent part, algorithms only need to be described on conceptual level, after which the execution is maximally parallel. The fully automated execution facilitates the optimization of these algorithms with adaptive sampling, where undersampled regions are automatically detected and targeted without user intervention. We show how several such algorithms can be formulated for computational chemistry problems, and how they are executed efficiently with many loosely coupled simulations using either distributed or parallel resources with Copernicus.

  15. Computational Modeling and Theoretical Calculations on the Interactions between Spermidine and Functional Monomer (Methacrylic Acid in a Molecularly Imprinted Polymer

    Directory of Open Access Journals (Sweden)

    Yujie Huang

    2015-01-01

    Full Text Available This paper theoretically investigates interactions between a template and functional monomer required for synthesizing an efficient molecularly imprinted polymer (MIP. We employed density functional theory (DFT to compute geometry, single-point energy, and binding energy (ΔE of an MIP system, where spermidine (SPD and methacrylic acid (MAA were selected as template and functional monomer, respectively. The geometry was calculated by using B3LYP method with 6-31+(d basis set. Furthermore, 6-311++(d, p basis set was used to compute the single-point energy of the above geometry. The optimized geometries at different template to functional monomer molar ratios, mode of bonding between template and functional monomer, changes in charge on natural bond orbital (NBO, and binding energy were analyzed. The simulation results show that SPD and MAA form a stable complex via hydrogen bonding. At 1 : 5 SPD to MAA ratio, the binding energy is minimum, while the amount of transferred charge between the molecules is maximum; SPD and MAA form a stable complex at 1 : 5 molar ratio through six hydrogen bonds. Optimizing structure of template-functional monomer complex, through computational modeling prior synthesis, significantly contributes towards choosing a suitable pair of template-functional monomer that yields an efficient MIP with high specificity and selectivity.

  16. Matched molecular pair-based data sets for computer-aided medicinal chemistry

    Science.gov (United States)

    Bajorath, Jürgen

    2014-01-01

    Matched molecular pairs (MMPs) are widely used in medicinal chemistry to study changes in compound properties including biological activity, which are associated with well-defined structural modifications. Herein we describe up-to-date versions of three MMP-based data sets that have originated from in-house research projects. These data sets include activity cliffs, structure-activity relationship (SAR) transfer series, and second generation MMPs based upon retrosynthetic rules. The data sets have in common that they have been derived from compounds included in the ChEMBL database (release 17) for which high-confidence activity data are available. Thus, the activity data associated with MMP-based activity cliffs, SAR transfer series, and retrosynthetic MMPs cover the entire spectrum of current pharmaceutical targets. Our data sets are made freely available to the scientific community. PMID:24627802

  17. Molecular Imaging and Precision Medicine: PET/Computed Tomography and Therapy Response Assessment in Oncology.

    Science.gov (United States)

    Sheikhbahaei, Sara; Mena, Esther; Pattanayak, Puskar; Taghipour, Mehdi; Solnes, Lilja B; Subramaniam, Rathan M

    2017-01-01

    A variety of methods have been developed to assess tumor response to therapy. Standardized qualitative criteria based on 18F-fluoro-deoxyglucose PET/computed tomography have been proposed to evaluate the treatment effectiveness in specific cancers and these allow more accurate therapy response assessment and survival prognostication. Multiple studies have addressed the utility of the volumetric PET biomarkers as prognostic indicators but there is no consensus about the preferred segmentation methodology for these metrics. Heterogeneous intratumoral uptake was proposed as a novel PET metric for therapy response assessment. PET imaging techniques will be used to study the biological behavior of cancers during therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Thermodynamic Molecular Switch in Sequence-Specific Hydrophobic Interaction: Two Computational Models Compared

    Directory of Open Access Journals (Sweden)

    Paul Chun

    2003-01-01

    Full Text Available We have shown in our published work the existence of a thermodynamic switch in biological systems wherein a change of sign in ΔCp°(Treaction leads to a true negative minimum in the Gibbs free energy change of reaction, and hence, a maximum in the related Keq. We have examined 35 pair-wise, sequence-specific hydrophobic interactions over the temperature range of 273–333 K, based on data reported by Nemethy and Scheraga in 1962. A closer look at a single example, the pair-wise hydrophobic interaction of leucine-isoleucine, will demonstrate the significant differences when the data are analyzed using the Nemethy-Scheraga model or treated by the Planck-Benzinger methodology which we have developed. The change in inherent chemical bond energy at 0 K, ΔH°(T0 is 7.53 kcal mol-1 compared with 2.4 kcal mol-1, while ‹ts› is 365 K as compared with 355 K, for the Nemethy-Scheraga and Planck-Benzinger model, respectively. At ‹tm›, the thermal agitation energy is about five times greater than ΔH°(T0 in the Planck-Benzinger model, that is 465 K compared to 497 K in the Nemethy-Scheraga model. The results imply that the negative Gibbs free energy minimum at a well-defined ‹ts›, where TΔS° = 0 at about 355 K, has its origin in the sequence-specific hydrophobic interactions, which are highly dependent on details of molecular structure. The Nemethy-Scheraga model shows no evidence of the thermodynamic molecular switch that we have found to be a universal feature of biological interactions. The Planck-Benzinger method is the best known for evaluating the innate temperature-invariant enthalpy, ΔH°(T0, and provides for better understanding of the heat of reaction for biological molecules.

  19. COMPUTING

    CERN Multimedia

    M. Kasemann

    Overview In autumn the main focus was to process and handle CRAFT data and to perform the Summer08 MC production. The operational aspects were well covered by regular Computing Shifts, experts on duty and Computing Run Coordination. At the Computing Resource Board (CRB) in October a model to account for service work at Tier 2s was approved. The computing resources for 2009 were reviewed for presentation at the C-RRB. The quarterly resource monitoring is continuing. Facilities/Infrastructure operations Operations during CRAFT data taking ran fine. This proved to be a very valuable experience for T0 workflows and operations. The transfers of custodial data to most T1s went smoothly. A first round of reprocessing started at the Tier-1 centers end of November; it will take about two weeks. The Computing Shifts procedure was tested full scale during this period and proved to be very efficient: 30 Computing Shifts Persons (CSP) and 10 Computing Resources Coordinators (CRC). The shift program for the shut down w...

  20. Computational and Spectroscopic Investigations of the Molecular Scale Structure and Dynamics of Geologically Important Fluids and Mineral-Fluid Interfaces

    International Nuclear Information System (INIS)

    Kirkpatrick, R. James; Kalinichev, Andrey G.

    2008-01-01

    Research supported by this grant focuses on molecular scale understanding of central issues related to the structure and dynamics of geochemically important fluids, fluid-mineral interfaces, and confined fluids using computational modeling and experimental methods. Molecular scale knowledge about fluid structure and dynamics, how these are affected by mineral surfaces and molecular-scale (nano-) confinement, and how water molecules and dissolved species interact with surfaces is essential to understanding the fundamental chemistry of a wide range of low-temperature geochemical processes, including sorption and geochemical transport. Our principal efforts are devoted to continued development of relevant computational approaches, application of these approaches to important geochemical questions, relevant NMR and other experimental studies, and application of computational modeling methods to understanding the experimental results. The combination of computational modeling and experimental approaches is proving highly effective in addressing otherwise intractable problems. In 2006-2007 we have significantly advanced in new, highly promising research directions along with completion of on-going projects and final publication of work completed in previous years. New computational directions are focusing on modeling proton exchange reactions in aqueous solutions using ab initio molecular dynamics (AIMD), metadynamics (MTD), and empirical valence bond (EVB) approaches. Proton exchange is critical to understanding the structure, dynamics, and reactivity at mineral-water interfaces and for oxy-ions in solution, but has traditionally been difficult to model with molecular dynamics (MD). Our ultimate objective is to develop this capability, because MD is much less computationally demanding than quantum-chemical approaches. We have also extended our previous MD simulations of metal binding to natural organic matter (NOM) to a much longer time scale (up to 10 ns) for

  1. Current-voltage curves for molecular junctions computed using all-electron basis sets

    International Nuclear Information System (INIS)

    Bauschlicher, Charles W.; Lawson, John W.

    2006-01-01

    We present current-voltage (I-V) curves computed using all-electron basis sets on the conducting molecule. The all-electron results are very similar to previous results obtained using effective core potentials (ECP). A hybrid integration scheme is used that keeps the all-electron calculations cost competitive with respect to the ECP calculations. By neglecting the coupling of states to the contacts below a fixed energy cutoff, the density matrix for the core electrons can be evaluated analytically. The full density matrix is formed by adding this core contribution to the valence part that is evaluated numerically. Expanding the definition of the core in the all-electron calculations significantly reduces the computational effort and, up to biases of about 2 V, the results are very similar to those obtained using more rigorous approaches. The convergence of the I-V curves and transmission coefficients with respect to basis set is discussed. The addition of diffuse functions is critical in approaching basis set completeness

  2. Transport coefficients of liquid CF4 and SF6 computed by molecular dynamics using polycenter Lennard-Jones potentials

    Science.gov (United States)

    Hoheisel, C.

    1989-01-01

    For several liquid states of CF4 and SF4, the shear and the bulk viscosity as well as the thermal conductivity were determined by equilibrium molecular dynamics (MD) calculations. Lennard-Jones four- and six-center pair potentials were applied, and the method of constraints was chosen for the MD. The computed Green-Kubo integrands show a steep time decay, and no particular longtime behavior occurs. The molecule number dependence of the results is found to be small, and 3×105 integration steps allow an accuracy of about 10% for the shear viscosity and the thermal conductivity coefficient. Comparison with experimental data shows a fair agreement for CF4, while for SF6 the transport coefficients fall below the experimental ones by about 30%.

  3. Transport coefficients of liquid CF4 and SF6 computed by molecular dynamics using polycenter Lennard-Jones potentials

    International Nuclear Information System (INIS)

    Hoheisel, C.

    1989-01-01

    For several liquid states of CF 4 and SF 6 , the shear and the bulk viscosity as well as the thermal conductivity were determined by equilibrium molecular dynamics (MD) calculations. Lennard-Jones four- and six-center pair potentials were applied, and the method of constraints were chosen for the MD. The computed Green-Kubo integrands show a steep time decay, and no particular longtime behavior occurs. The molecule number dependence of the results is found to be small, and 3 x 10 5 integration steps allow an accuracy of about 10% for the shear viscosity and the thermal conductivity coefficient. Comparison with experimental data shows a fair agreement for CF 4 , while for SF 6 the transport coefficients fall below the experimental ones by about 30%

  4. Molecular dynamics computer simulation study of Pd{sub n} (n=13, 19, 38 and 55) clusters

    Energy Technology Data Exchange (ETDEWEB)

    Karabacak, M [Afyon Kocatepe University, Department of Physics, Afyon (Turkey); Oezcelik, S [Gazi University, Department of Physics, Ankara (Turkey); Guevenc, Z B [Cankaya University, Department of Electronics and Communication Engineering, Ankara (Turkey)

    2002-07-01

    Using constant-energy molecular dynamics and thermal quenching simulations, we have studied minimum-energy structures and energetics, Pd{sub n} (n=13, 19, 38, and 55) clusters employing the Voter and Chen's version of parameterisation of the embedded-atom potential surface. Isomer statistics for Pdn ( n = 13 and 19 ) is obtained from 10000 initial independent configurations, which have been generated along high-energy trajectories (chosen energy values are high enough to melt the clusters). The thermal quenching technique is employed to remove the internal kinetic energy of the clusters. The locally stable isomers are separated from metastable ones. Probabilities belonging to sampling the basins of attractions of each isomers are computed, and then, isomers' energy spectra are analyzed.

  5. Improving limited-projection-angle fluorescence molecular tomography using a co-registered x-ray computed tomography scan.

    Science.gov (United States)

    Radrich, Karin; Ale, Angelique; Ermolayev, Vladimir; Ntziachristos, Vasilis

    2012-12-01

    We examine the improvement in imaging performance, such as axial resolution and signal localization, when employing limited-projection-angle fluorescence molecular tomography (FMT) together with x-ray computed tomography (XCT) measurements versus stand-alone FMT. For this purpose, we employed living mice, bearing a spontaneous lung tumor model, and imaged them with FMT and XCT under identical geometrical conditions using fluorescent probes for cancer targeting. The XCT data was employed, herein, as structural prior information to guide the FMT reconstruction. Gold standard images were provided by fluorescence images of mouse cryoslices, providing the ground truth in fluorescence bio-distribution. Upon comparison of FMT images versus images reconstructed using hybrid FMT and XCT data, we demonstrate marked improvements in image accuracy. This work relates to currently disseminated FMT systems, using limited projection scans, and can be employed to enhance their performance.

  6. Compression of Born ratio for fluorescence molecular tomography/x-ray computed tomography hybrid imaging: methodology and in vivo validation.

    Science.gov (United States)

    Mohajerani, Pouyan; Ntziachristos, Vasilis

    2013-07-01

    The 360° rotation geometry of the hybrid fluorescence molecular tomography/x-ray computed tomography modality allows for acquisition of very large datasets, which pose numerical limitations on the reconstruction. We propose a compression method that takes advantage of the correlation of the Born-normalized signal among sources in spatially formed clusters to reduce the size of system model. The proposed method has been validated using an ex vivo study and an in vivo study of a nude mouse with a subcutaneous 4T1 tumor, with and without inclusion of a priori anatomical information. Compression rates of up to two orders of magnitude with minimum distortion of reconstruction have been demonstrated, resulting in large reduction in weight matrix size and reconstruction time.

  7. A molecular dynamics computer simulation of the time dependence of surface damage production in ion irradiated metal targets

    International Nuclear Information System (INIS)

    Webb, R.P.; Harrison, D.E.

    1984-01-01

    Molecular dynamics computer simulations have been used to study the development of ion-induced cascades in the surface region of an initially perfect single crystal metal target. A 16 mm movie has been produced to show the temporal progress of individual cascades. The cascades can then be seen to be formed from a few high energy primary knock-on initiated replacement collision sequences which overlap to form the more usual interpretation of a mature collision cascade. However, it is before the collision cascade has matured, and while the replacement sequences are spreading, that the majority of atoms (> 80%) are ejected. These qualitative observations are also upheld more quantatively in a global average, over many cascades, of the ejection time of each atom. This gives rise to the appearance of a statistical ejection front which propagates radially outwards, from the impact point on the crystal surface, with a well defined velocity. (author)

  8. Propagator formalism and computer simulation of restricted diffusion behaviors of inter-molecular multiple-quantum coherences

    International Nuclear Information System (INIS)

    Cai Congbo; Chen Zhong; Cai Shuhui; Zhong Jianhui

    2005-01-01

    In this paper, behaviors of single-quantum coherences and inter-molecular multiple-quantum coherences under restricted diffusion in nuclear magnetic resonance experiments were investigated. The propagator formalism based on the loss of spin phase memory during random motion was applied to describe the diffusion-induced signal attenuation. The exact expression of the signal attenuation under the short gradient pulse approximation for restricted diffusion between two parallel plates was obtained using this propagator method. For long gradient pulses, a modified formalism was proposed. The simulated signal attenuation under the effects of gradient pulses of different width based on the Monte Carlo method agrees with the theoretical predictions. The propagator formalism and computer simulation can provide convenient, intuitive and precise methods for the study of the diffusion behaviors

  9. COMPUTING

    CERN Multimedia

    I. Fisk

    2011-01-01

    Introduction CMS distributed computing system performed well during the 2011 start-up. The events in 2011 have more pile-up and are more complex than last year; this results in longer reconstruction times and harder events to simulate. Significant increases in computing capacity were delivered in April for all computing tiers, and the utilisation and load is close to the planning predictions. All computing centre tiers performed their expected functionalities. Heavy-Ion Programme The CMS Heavy-Ion Programme had a very strong showing at the Quark Matter conference. A large number of analyses were shown. The dedicated heavy-ion reconstruction facility at the Vanderbilt Tier-2 is still involved in some commissioning activities, but is available for processing and analysis. Facilities and Infrastructure Operations Facility and Infrastructure operations have been active with operations and several important deployment tasks. Facilities participated in the testing and deployment of WMAgent and WorkQueue+Request...

  10. COMPUTING

    CERN Multimedia

    P. McBride

    The Computing Project is preparing for a busy year where the primary emphasis of the project moves towards steady operations. Following the very successful completion of Computing Software and Analysis challenge, CSA06, last fall, we have reorganized and established four groups in computing area: Commissioning, User Support, Facility/Infrastructure Operations and Data Operations. These groups work closely together with groups from the Offline Project in planning for data processing and operations. Monte Carlo production has continued since CSA06, with about 30M events produced each month to be used for HLT studies and physics validation. Monte Carlo production will continue throughout the year in the preparation of large samples for physics and detector studies ramping to 50 M events/month for CSA07. Commissioning of the full CMS computing system is a major goal for 2007. Site monitoring is an important commissioning component and work is ongoing to devise CMS specific tests to be included in Service Availa...

  11. COMPUTING

    CERN Multimedia

    M. Kasemann

    Overview During the past three months activities were focused on data operations, testing and re-enforcing shift and operational procedures for data production and transfer, MC production and on user support. Planning of the computing resources in view of the new LHC calendar in ongoing. Two new task forces were created for supporting the integration work: Site Commissioning, which develops tools helping distributed sites to monitor job and data workflows, and Analysis Support, collecting the user experience and feedback during analysis activities and developing tools to increase efficiency. The development plan for DMWM for 2009/2011 was developed at the beginning of the year, based on the requirements from the Physics, Computing and Offline groups (see Offline section). The Computing management meeting at FermiLab on February 19th and 20th was an excellent opportunity discussing the impact and for addressing issues and solutions to the main challenges facing CMS computing. The lack of manpower is particul...

  12. Digitized molecular diagnostics: reading disk-based bioassays with standard computer drives.

    Science.gov (United States)

    Li, Yunchao; Ou, Lily M L; Yu, Hua-Zhong

    2008-11-01

    We report herein a digital signal readout protocol for screening disk-based bioassays with standard optical drives of ordinary desktop/notebook computers. Three different types of biochemical recognition reactions (biotin-streptavidin binding, DNA hybridization, and protein-protein interaction) were performed directly on a compact disk in a line array format with the help of microfluidic channel plates. Being well-correlated with the optical darkness of the binding sites (after signal enhancement by gold nanoparticle-promoted autometallography), the reading error levels of prerecorded audio files can serve as a quantitative measure of biochemical interaction. This novel readout protocol is about 1 order of magnitude more sensitive than fluorescence labeling/scanning and has the capability of examining multiplex microassays on the same disk. Because no modification to either hardware or software is needed, it promises a platform technology for rapid, low-cost, and high-throughput point-of-care biomedical diagnostics.

  13. On computing stress in polymer systems involving multi-body potentials from molecular dynamics simulation

    Science.gov (United States)

    Fu, Yao; Song, Jeong-Hoon

    2014-08-01

    Hardy stress definition has been restricted to pair potentials and embedded-atom method potentials due to the basic assumptions in the derivation of a symmetric microscopic stress tensor. Force decomposition required in the Hardy stress expression becomes obscure for multi-body potentials. In this work, we demonstrate the invariance of the Hardy stress expression for a polymer system modeled with multi-body interatomic potentials including up to four atoms interaction, by applying central force decomposition of the atomic force. The balance of momentum has been demonstrated to be valid theoretically and tested under various numerical simulation conditions. The validity of momentum conservation justifies the extension of Hardy stress expression to multi-body potential systems. Computed Hardy stress has been observed to converge to the virial stress of the system with increasing spatial averaging volume. This work provides a feasible and reliable linkage between the atomistic and continuum scales for multi-body potential systems.

  14. Experimental and computational study on the molecular energetics of benzyloxyphenol isomers

    International Nuclear Information System (INIS)

    Ribeiro da Silva, Manuel A.V.; Lobo Ferreira, Ana I.M.C.; Cimas, Alvaro

    2011-01-01

    Highlights: → Combustion calorimetry was used to determine Δ f H m 0 (cr) of 4-benzyloxyphenol. → Vapor pressures were determined by the Knudsen mass-loss effusion technique. → Gas-phase Δ f H m 0 of benzyloxyphenol isomers have been derived. - Abstract: This paper reports a combined experimental and computational thermochemical study of 4-benzyloxyphenol. Static bomb combustion calorimetry and Knudsen mass-loss effusion technique were used to determine the standard (p o = 0.1 MPa) molar enthalpy of combustion, Δ c H m 0 =-(6580.1±1.8)kJ.mol -1 , and of sublimation, Δ cr g H m 0 =(131.0±0.9)kJ.mol -1 , respectively, from which the standard (p o = 0.1 MPa) molar enthalpy of formation, in the gaseous phase, at T = 298.15 K, Δ f H m 0 =-(119.5±2.7)kJ.mol -1 were derived. For comparison purposes, the gas-phase enthalpy of formation of this compound was estimated by G3(MP2)//B3LYP calculations, using a set of gas-phase working reactions; the results are in excellent agreement with experimental data. G3(MP2)//B3LYP computations were also extended to the calculation of the gas-phase enthalpies of formation of the 2- and 3-benzyloxyphenol isomers. Furthermore, this composite approach was also used to obtain information about the gas-phase acidities, gas-phase basicities, proton and electron affinities, adiabatic ionization enthalpies and, finally, O-H bond dissociation enthalpies.

  15. Molecular determinants of enzyme cold adaptation: comparative structural and computational studies of cold- and warm-adapted enzymes.

    Science.gov (United States)

    Papaleo, Elena; Tiberti, Matteo; Invernizzi, Gaetano; Pasi, Marco; Ranzani, Valeria

    2011-11-01

    The identification of molecular mechanisms underlying enzyme cold adaptation is a hot-topic both for fundamental research and industrial applications. In the present contribution, we review the last decades of structural computational investigations on cold-adapted enzymes in comparison to their warm-adapted counterparts. Comparative sequence and structural studies allow the definition of a multitude of adaptation strategies. Different enzymes carried out diverse mechanisms to adapt to low temperatures, so that a general theory for enzyme cold adaptation cannot be formulated. However, some common features can be traced in dynamic and flexibility properties of these enzymes, as well as in their intra- and inter-molecular interaction networks. Interestingly, the current data suggest that a family-centered point of view is necessary in the comparative analyses of cold- and warm-adapted enzymes. In fact, enzymes belonging to the same family or superfamily, thus sharing at least the three-dimensional fold and common features of the functional sites, have evolved similar structural and dynamic patterns to overcome the detrimental effects of low temperatures.

  16. Computational and experimental investigation of molecular imprinted polymers for selective extraction of dimethoate and its metabolite omethoate from olive oil.

    Science.gov (United States)

    Bakas, Idriss; Oujji, Najwa Ben; Moczko, Ewa; Istamboulie, Georges; Piletsky, Sergey; Piletska, Elena; Ait-Addi, Elhabib; Ait-Ichou, Ihya; Noguer, Thierry; Rouillon, Régis

    2013-01-25

    This work presents the development of molecularly imprinted polymers (MIPs) for the selective extraction of dimethoate from olive oil. Computational simulations allowed selecting itaconic acid as the monomer showing the highest affinity towards dimethoate. Experimental validation confirmed modelling predictions and showed that the polymer based on IA as functional monomer and omethoate as template molecule displays the highest selectivity for the structurally similar pesticides dimethoate, omethoate and monocrotophos. Molecularly imprinted solid phase extraction (MISPE) method was developed and applied to the clean-up of olive oil extracts. It was found that the most suitable solvents for loading, washing and elution step were respectively hexane, hexane-dichloromethane (85:15%) and methanol. The developed MIPSE was successfully applied to extraction of dimethoate from olive oil, with recovery rates up to 94%. The limits of detection and quantification of the described method were respectively 0.012 and 0.05 μg g(-1). Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Molecular Imaging of Cancer Using X-ray Computed Tomography with Protease Targeted Iodinated Activity-Based Probes.

    Science.gov (United States)

    Gaikwad, Hanmant K; Tsvirkun, Darya; Ben-Nun, Yael; Merquiol, Emmanuelle; Popovtzer, Rachela; Blum, Galia

    2018-03-14

    X-ray computed tomography (CT) is a robust, precise, fast, and reliable imaging method that enables excellent spatial resolution and quantification of contrast agents throughout the body. However, CT is largely inadequate for molecular imaging applications due mainly to its low contrast sensitivity that forces the use of large concentrations of contrast agents for detection. To overcome this limitation, we generated a new class of iodinated nanoscale activity-based probes (IN-ABPs) that sufficiently accumulates at the target site by covalently binding cysteine cathepsins that are exceptionally highly expressed in cancer. The IN-ABPs are comprised of a short targeting peptide selective to specific cathepsins, an electrophilic moiety that allows activity-dependent covalent binding, and tags containing dendrimers with up to 48 iodine atoms. IN-ABPs selectively bind and inhibit activity of recombinant and intracellular cathepsin B, L, and S. We compared the in vivo kinetics, biodistribution, and tumor accumulation of IN-ABPs bearing 18 and 48 iodine atoms each, and their control counterparts lacking the targeting moiety. Here we show that although both IN-ABPs bind specifically to cathepsins within the tumor and produce detectable CT contrast, the 48-iodine bearing IN-ABP was found to be optimal with signals over 2.1-fold higher than its nontargeted counterpart. In conclusion, this study shows the synthetic feasibility and potential utility of IN-ABPs as potent contrast agents that enable molecular imaging of tumors using CT.

  18. Hybrid Quantum Mechanics/Molecular Mechanics Solvation Scheme for Computing Free Energies of Reactions at Metal-Water Interfaces.

    Science.gov (United States)

    Faheem, Muhammad; Heyden, Andreas

    2014-08-12

    We report the development of a quantum mechanics/molecular mechanics free energy perturbation (QM/MM-FEP) method for modeling chemical reactions at metal-water interfaces. This novel solvation scheme combines planewave density function theory (DFT), periodic electrostatic embedded cluster method (PEECM) calculations using Gaussian-type orbitals, and classical molecular dynamics (MD) simulations to obtain a free energy description of a complex metal-water system. We derive a potential of mean force (PMF) of the reaction system within the QM/MM framework. A fixed-size, finite ensemble of MM conformations is used to permit precise evaluation of the PMF of QM coordinates and its gradient defined within this ensemble. Local conformations of adsorbed reaction moieties are optimized using sequential MD-sampling and QM-optimization steps. An approximate reaction coordinate is constructed using a number of interpolated states and the free energy difference between adjacent states is calculated using the QM/MM-FEP method. By avoiding on-the-fly QM calculations and by circumventing the challenges associated with statistical averaging during MD sampling, a computational speedup of multiple orders of magnitude is realized. The method is systematically validated against the results of ab initio QM calculations and demonstrated for C-C cleavage in double-dehydrogenated ethylene glycol on a Pt (111) model surface.

  19. Computational Modelling of Dapsone Interaction With Dihydropteroate Synthase in Mycobacterium leprae; Insights Into Molecular Basis of Dapsone Resistance in Leprosy.

    Science.gov (United States)

    Chaitanya V, Sundeep; Das, Madhusmita; Bhat, Pritesh; Ebenezer, Mannam

    2015-10-01

    The molecular basis for determination of resistance to anti-leprosy drugs is the presence of point mutations within the genes of Mycobacterium leprae (M. leprae) that encode active drug targets. The downstream structural and functional implications of these point mutations on drug targets were scarcely studied. In this study, we utilized computational tools to develop native and mutant protein models for 5 point mutations at codon positions 53 and 55 in 6-hydroxymethyl-7, 8-dihydropteroate synthase (DHPS) of M. leprae, an active target for dapsone encoded by folp1 gene, that confer resistance to dapsone. Molecular docking was performed to identify variations in dapsone interaction with mutant DHPS in terms of hydrogen bonding, hydrophobic interactions, and energy changes. Schrodinger Suite 2014-3 was used to build homology models and in performing molecular docking. An increase in volume of the binding cavities of mutant structures was noted when compared to native form indicating a weakening in interaction (60.7 Å(3) in native vs. 233.6 Å(3) in Thr53Ala, 659.9 Å(3) in Thr53Ile, 400 Å(3) for Thr53Val, 385 Å(3) for Pro55Arg, and 210 Å(3) for Pro55Leu). This was also reflected by changes in hydrogen bonds and decrease in hydrophobic interactions in the mutant models. The total binding energy (ΔG) decreased significantly in mutant forms when compared to the native form (-51.92 Kcal/mol for native vs. -35.64, -35.24, -46.47, -47.69, and -41.36 Kcal/mol for mutations Thr53Ala, Thr53Ile, Thr53Val, Pro55Arg, and Pro55Leu, respectively. In brief, this analysis provided structural and mechanistic insights to the degree of dapsone resistance contributed by each of these DHPS mutants in leprosy. © 2015 Wiley Periodicals, Inc.

  20. Hierarchical bounding structures for efficient virial computations: Towards a realistic molecular description of cholesterics

    Science.gov (United States)

    Tortora, Maxime M. C.; Doye, Jonathan P. K.

    2017-12-01

    We detail the application of bounding volume hierarchies to accelerate second-virial evaluations for arbitrary complex particles interacting through hard and soft finite-range potentials. This procedure, based on the construction of neighbour lists through the combined use of recursive atom-decomposition techniques and binary overlap search schemes, is shown to scale sub-logarithmically with particle resolution in the case of molecular systems with high aspect ratios. Its implementation within an efficient numerical and theoretical framework based on classical density functional theory enables us to investigate the cholesteric self-assembly of a wide range of experimentally relevant particle models. We illustrate the method through the determination of the cholesteric behavior of hard, structurally resolved twisted cuboids, and report quantitative evidence of the long-predicted phase handedness inversion with increasing particle thread angles near the phenomenological threshold value of 45°. Our results further highlight the complex relationship between microscopic structure and helical twisting power in such model systems, which may be attributed to subtle geometric variations of their chiral excluded-volume manifold.

  1. Charge Transport in 4 nm Molecular Wires with Interrupted Conjugation: Combined Experimental and Computational Evidence for Thermally Assisted Polaron Tunneling.

    Science.gov (United States)

    Taherinia, Davood; Smith, Christopher E; Ghosh, Soumen; Odoh, Samuel O; Balhorn, Luke; Gagliardi, Laura; Cramer, Christopher J; Frisbie, C Daniel

    2016-04-26

    We report the synthesis, transport measurements, and electronic structure of conjugation-broken oligophenyleneimine (CB-OPI 6) molecular wires with lengths of ∼4 nm. The wires were grown from Au surfaces using stepwise aryl imine condensation reactions between 1,4-diaminobenzene and terephthalaldehyde (1,4-benzenedicarbaldehyde). Saturated spacers (conjugation breakers) were introduced into the molecular backbone by replacing the aromatic diamine with trans-1,4-diaminocyclohexane at specific steps during the growth processes. FT-IR and ellipsometry were used to follow the imination reactions on Au surfaces. Surface coverages (∼4 molecules/nm(2)) and electronic structures of the wires were determined by cyclic voltammetry and UV-vis spectroscopy, respectively. The current-voltage (I-V) characteristics of the wires were acquired using conducting probe atomic force microscopy (CP-AFM) in which an Au-coated AFM probe was brought into contact with the wires to form metal-molecule-metal junctions with contact areas of ∼50 nm(2). The low bias resistance increased with the number of saturated spacers, but was not sensitive to the position of the spacer within the wire. Temperature dependent measurements of resistance were consistent with a localized charge (polaron) hopping mechanism in all of the wires. Activation energies were in the range of 0.18-0.26 eV (4.2-6.0 kcal/mol) with the highest belonging to the fully conjugated OPI 6 wire and the lowest to the CB3,5-OPI 6 wire (the wire with two saturated spacers). For the two other wires with a single conjugation breaker, CB3-OPI 6 and CB5-OPI 6, activation energies of 0.20 eV (4.6 kcal/mol) and 0.21 eV (4.8 kcal/mol) were found, respectively. Computational studies using density functional theory confirmed the polaronic nature of charge carriers but predicted that the semiclassical activation energy of hopping should be higher for CB-OPI molecular wires than for the OPI 6 wire. To reconcile the experimental and

  2. Fabrication of an electrochemical sensor based on computationally designed molecularly imprinted polymer for the determination of mesalamine in real samples

    Energy Technology Data Exchange (ETDEWEB)

    Torkashvand, M. [Department of Analytical Chemistry, Razi University, Kermanshah (Iran, Islamic Republic of); Gholivand, M.B., E-mail: mbgholivand@yahoo.com [Department of Analytical Chemistry, Razi University, Kermanshah (Iran, Islamic Republic of); Taherkhani, F. [Department of Physical Chemistry, Razi University, Kermanshah (Iran, Islamic Republic of)

    2015-10-01

    A novel electrochemical sensor based on mesalamine molecularly imprinted polymer (MIP) film on a glassy carbon electrode was fabricated. Density functional theory (DFT) in gas and solution phases was developed to study the intermolecular interactions in the pre-polymerization mixture and to find the suitable functional monomers in MIP preparation. On the basis of computational results, o-phenylenediamine (OP), gallic acid (GA) and p-aminobenzoic acid (ABA) were selected as functional monomers. The MIP film was cast on glassy carbon electrode by electropolymerization of solution containing ternary monomers and then followed by Ag dendrites (AgDs) with nanobranch deposition. The surface feature of the modified electrode (AgDs/MIP/GCE) was characterized by scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS). Under the optimal experimental conditions, the peak current was proportional to the concentration of mesalamine ranging from 0.05 to 100 μM, with the detection limit of 0.015 μM. The proposed sensor was applied successfully for mesalamine determination in real samples. - Highlights: • The determination of MES using AgDs/MIP/GCE is reported for the first time. • The computer assisted design of terpolymer MIPs was used to screen monomers. • Theoretical results of DFT approach were in agreement with experimental results. • The sensor displayed a high selectivity for template in the presence of interferes. • The developed sensor has been applied to determine mesalamine in real samples.

  3. Fabrication of an electrochemical sensor based on computationally designed molecularly imprinted polymer for the determination of mesalamine in real samples

    International Nuclear Information System (INIS)

    Torkashvand, M.; Gholivand, M.B.; Taherkhani, F.

    2015-01-01

    A novel electrochemical sensor based on mesalamine molecularly imprinted polymer (MIP) film on a glassy carbon electrode was fabricated. Density functional theory (DFT) in gas and solution phases was developed to study the intermolecular interactions in the pre-polymerization mixture and to find the suitable functional monomers in MIP preparation. On the basis of computational results, o-phenylenediamine (OP), gallic acid (GA) and p-aminobenzoic acid (ABA) were selected as functional monomers. The MIP film was cast on glassy carbon electrode by electropolymerization of solution containing ternary monomers and then followed by Ag dendrites (AgDs) with nanobranch deposition. The surface feature of the modified electrode (AgDs/MIP/GCE) was characterized by scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS). Under the optimal experimental conditions, the peak current was proportional to the concentration of mesalamine ranging from 0.05 to 100 μM, with the detection limit of 0.015 μM. The proposed sensor was applied successfully for mesalamine determination in real samples. - Highlights: • The determination of MES using AgDs/MIP/GCE is reported for the first time. • The computer assisted design of terpolymer MIPs was used to screen monomers. • Theoretical results of DFT approach were in agreement with experimental results. • The sensor displayed a high selectivity for template in the presence of interferes. • The developed sensor has been applied to determine mesalamine in real samples

  4. MEGA-CC: computing core of molecular evolutionary genetics analysis program for automated and iterative data analysis.

    Science.gov (United States)

    Kumar, Sudhir; Stecher, Glen; Peterson, Daniel; Tamura, Koichiro

    2012-10-15

    There is a growing need in the research community to apply the molecular evolutionary genetics analysis (MEGA) software tool for batch processing a large number of datasets and to integrate it into analysis workflows. Therefore, we now make available the computing core of the MEGA software as a stand-alone executable (MEGA-CC), along with an analysis prototyper (MEGA-Proto). MEGA-CC provides users with access to all the computational analyses available through MEGA's graphical user interface version. This includes methods for multiple sequence alignment, substitution model selection, evolutionary distance estimation, phylogeny inference, substitution rate and pattern estimation, tests of natural selection and ancestral sequence inference. Additionally, we have upgraded the source code for phylogenetic analysis using the maximum likelihood methods for parallel execution on multiple processors and cores. Here, we describe MEGA-CC and outline the steps for using MEGA-CC in tandem with MEGA-Proto for iterative and automated data analysis. http://www.megasoftware.net/.

  5. COMPUTING

    CERN Multimedia

    I. Fisk

    2013-01-01

    Computing activity had ramped down after the completion of the reprocessing of the 2012 data and parked data, but is increasing with new simulation samples for analysis and upgrade studies. Much of the Computing effort is currently involved in activities to improve the computing system in preparation for 2015. Operations Office Since the beginning of 2013, the Computing Operations team successfully re-processed the 2012 data in record time, not only by using opportunistic resources like the San Diego Supercomputer Center which was accessible, to re-process the primary datasets HTMHT and MultiJet in Run2012D much earlier than planned. The Heavy-Ion data-taking period was successfully concluded in February collecting almost 500 T. Figure 3: Number of events per month (data) In LS1, our emphasis is to increase efficiency and flexibility of the infrastructure and operation. Computing Operations is working on separating disk and tape at the Tier-1 sites and the full implementation of the xrootd federation ...

  6. Chiral discrimination in NMR spectroscopy: computation of the relevant molecular pseudoscalars

    Science.gov (United States)

    Buckingham, A. David; Lazzeretti, Paolo; Pelloni, Stefano

    2015-07-01

    Nuclear magnetic resonance (NMR) is normally blind to chirality but it has been predicted that precessing nuclear spins in a strong magnetic field induce a rotating electric polarisation that is of opposite sign for enantiomers. The polarisation is determined by two pseudoscalars, ? and ?. The former arises from the distortion of the electronic structure by the nuclear magnetic moment in the presence of the strong magnetic field and is equivalent to the linear effect of an electric field on the nuclear shielding tensor. ? determines the temperature-dependent partial orientation of the permanent electric dipole moment of the molecule by the antisymmetric part of the nuclear shielding tensor. Computations of these two contributions are reported for the nuclei in the chiral molecules N-methyloxaziridine, 2-methyloxirane, 1,3-dimethylallene, 1-fluoroethanol, 2-fluoroazirine, 1,2-M-dioxin, 1,2-M-dithiin, 1,2-M-diselenin and 1,2-M-ditellurin. For strongly dipolar molecules, ? is typically two to three orders of magnitude greater than ?, raising hopes for the detection of chirality in NMR spectroscopy. This paper is dedicated to the memory of Prof. Nicholas Handy, F.R.S.

  7. RNAdualPF: software to compute the dual partition function with sample applications in molecular evolution theory.

    Science.gov (United States)

    Garcia-Martin, Juan Antonio; Bayegan, Amir H; Dotu, Ivan; Clote, Peter

    2016-10-19

    -content. Using different inverse folding software, another group had earlier shown that pre-miRNA is mutationally robust, even controlling for compositional bias. Our opposite conclusion suggests a cautionary note that computationally based insights into molecular evolution may heavily depend on the software used. C/C++-software for RNAdualPF is available at http://bioinformatics.bc.edu/clotelab/RNAdualPF .

  8. Fast computation of molecular random phase approximation correlation energies using resolution of the identity and imaginary frequency integration

    Science.gov (United States)

    Eshuis, Henk; Yarkony, Julian; Furche, Filipp

    2010-06-01

    The random phase approximation (RPA) is an increasingly popular post-Kohn-Sham correlation method, but its high computational cost has limited molecular applications to systems with few atoms. Here we present an efficient implementation of RPA correlation energies based on a combination of resolution of the identity (RI) and imaginary frequency integration techniques. We show that the RI approximation to four-index electron repulsion integrals leads to a variational upper bound to the exact RPA correlation energy if the Coulomb metric is used. Auxiliary basis sets optimized for second-order Møller-Plesset (MP2) calculations are well suitable for RPA, as is demonstrated for the HEAT [A. Tajti et al., J. Chem. Phys. 121, 11599 (2004)] and MOLEKEL [F. Weigend et al., Chem. Phys. Lett. 294, 143 (1998)] benchmark sets. Using imaginary frequency integration rather than diagonalization to compute the matrix square root necessary for RPA, evaluation of the RPA correlation energy requires O(N4 log N) operations and O(N3) storage only; the price for this dramatic improvement over existing algorithms is a numerical quadrature. We propose a numerical integration scheme that is exact in the two-orbital case and converges exponentially with the number of grid points. For most systems, 30-40 grid points yield μH accuracy in triple zeta basis sets, but much larger grids are necessary for small gap systems. The lowest-order approximation to the present method is a post-Kohn-Sham frequency-domain version of opposite-spin Laplace-transform RI-MP2 [J. Jung et al., Phys. Rev. B 70, 205107 (2004)]. Timings for polyacenes with up to 30 atoms show speed-ups of two orders of magnitude over previous implementations. The present approach makes it possible to routinely compute RPA correlation energies of systems well beyond 100 atoms, as is demonstrated for the octapeptide angiotensin II.

  9. A molecular computational model improves the preoperative diagnosis of thyroid nodules

    International Nuclear Information System (INIS)

    Tomei, Sara; Marchetti, Ivo; Zavaglia, Katia; Lessi, Francesca; Apollo, Alessandro; Aretini, Paolo; Di Coscio, Giancarlo; Bevilacqua, Generoso; Mazzanti, Chiara

    2012-01-01

    Thyroid nodules with indeterminate cytological features on fine needle aspiration (FNA) cytology have a 20% risk of thyroid cancer. The aim of the current study was to determine the diagnostic utility of an 8-gene assay to distinguish benign from malignant thyroid neoplasm. The mRNA expression level of 9 genes (KIT, SYNGR2, C21orf4, Hs.296031, DDI2, CDH1, LSM7, TC1, NATH) was analysed by quantitative PCR (q-PCR) in 93 FNA cytological samples. To evaluate the diagnostic utility of all the genes analysed, we assessed the area under the curve (AUC) for each gene individually and in combination. BRAF exon 15 status was determined by pyrosequencing. An 8-gene computational model (Neural Network Bayesian Classifier) was built and a multiple-variable analysis was then performed to assess the correlation between the markers. The AUC for each significant marker ranged between 0.625 and 0.900, thus all the significant markers, alone and in combination, can be used to distinguish between malignant and benign FNA samples. The classifier made up of KIT, CDH1, LSM7, C21orf4, DDI2, TC1, Hs.296031 and BRAF had a predictive power of 88.8%. It proved to be useful for risk stratification of the most critical cytological group of the indeterminate lesions for which there is the greatest need of accurate diagnostic markers. The genetic classification obtained with this model is highly accurate at differentiating malignant from benign thyroid lesions and might be a useful adjunct in the preoperative management of patients with thyroid nodules

  10. A molecular computational model improves the preoperative diagnosis of thyroid nodules

    Directory of Open Access Journals (Sweden)

    Tomei Sara

    2012-09-01

    Full Text Available Abstract Background Thyroid nodules with indeterminate cytological features on fine needle aspiration (FNA cytology have a 20% risk of thyroid cancer. The aim of the current study was to determine the diagnostic utility of an 8-gene assay to distinguish benign from malignant thyroid neoplasm. Methods The mRNA expression level of 9 genes (KIT, SYNGR2, C21orf4, Hs.296031, DDI2, CDH1, LSM7, TC1, NATH was analysed by quantitative PCR (q-PCR in 93 FNA cytological samples. To evaluate the diagnostic utility of all the genes analysed, we assessed the area under the curve (AUC for each gene individually and in combination. BRAF exon 15 status was determined by pyrosequencing. An 8-gene computational model (Neural Network Bayesian Classifier was built and a multiple-variable analysis was then performed to assess the correlation between the markers. Results The AUC for each significant marker ranged between 0.625 and 0.900, thus all the significant markers, alone and in combination, can be used to distinguish between malignant and benign FNA samples. The classifier made up of KIT, CDH1, LSM7, C21orf4, DDI2, TC1, Hs.296031 and BRAF had a predictive power of 88.8%. It proved to be useful for risk stratification of the most critical cytological group of the indeterminate lesions for which there is the greatest need of accurate diagnostic markers. Conclusion The genetic classification obtained with this model is highly accurate at differentiating malignant from benign thyroid lesions and might be a useful adjunct in the preoperative management of patients with thyroid nodules.

  11. COMPUTING

    CERN Multimedia

    I. Fisk

    2010-01-01

    Introduction It has been a very active quarter in Computing with interesting progress in all areas. The activity level at the computing facilities, driven by both organised processing from data operations and user analysis, has been steadily increasing. The large-scale production of simulated events that has been progressing throughout the fall is wrapping-up and reprocessing with pile-up will continue. A large reprocessing of all the proton-proton data has just been released and another will follow shortly. The number of analysis jobs by users each day, that was already hitting the computing model expectations at the time of ICHEP, is now 33% higher. We are expecting a busy holiday break to ensure samples are ready in time for the winter conferences. Heavy Ion An activity that is still in progress is computing for the heavy-ion program. The heavy-ion events are collected without zero suppression, so the event size is much large at roughly 11 MB per event of RAW. The central collisions are more complex and...

  12. COMPUTING

    CERN Multimedia

    M. Kasemann P. McBride Edited by M-C. Sawley with contributions from: P. Kreuzer D. Bonacorsi S. Belforte F. Wuerthwein L. Bauerdick K. Lassila-Perini M-C. Sawley

    Introduction More than seventy CMS collaborators attended the Computing and Offline Workshop in San Diego, California, April 20-24th to discuss the state of readiness of software and computing for collisions. Focus and priority were given to preparations for data taking and providing room for ample dialog between groups involved in Commissioning, Data Operations, Analysis and MC Production. Throughout the workshop, aspects of software, operating procedures and issues addressing all parts of the computing model were discussed. Plans for the CMS participation in STEP’09, the combined scale testing for all four experiments due in June 2009, were refined. The article in CMS Times by Frank Wuerthwein gave a good recap of the highly collaborative atmosphere of the workshop. Many thanks to UCSD and to the organizers for taking care of this workshop, which resulted in a long list of action items and was definitely a success. A considerable amount of effort and care is invested in the estimate of the comput...

  13. Computer-assisted methods for molecular structure elucidation: realizing a spectroscopist's dream

    Directory of Open Access Journals (Sweden)

    Elyashberg Mikhail

    2009-03-01

    Full Text Available Abstract Background This article coincides with the 40 year anniversary of the first published works devoted to the creation of algorithms for computer-aided structure elucidation (CASE. The general principles on which CASE methods are based will be reviewed and the present state of the art in this field will be described using, as an example, the expert system Structure Elucidator. Results The developers of CASE systems have been forced to overcome many obstacles hindering the development of a software application capable of drastically reducing the time and effort required to determine the structures of newly isolated organic compounds. Large complex molecules of up to 100 or more skeletal atoms with topological peculiarity can be quickly identified using the expert system Structure Elucidator based on spectral data. Logical analysis of 2D NMR data frequently allows for the detection of the presence of COSY and HMBC correlations of "nonstandard" length. Fuzzy structure generation provides a possibility to obtain the correct solution even in those cases when an unknown number of nonstandard correlations of unknown length are present in the spectra. The relative stereochemistry of big rigid molecules containing many stereocenters can be determined using the StrucEluc system and NOESY/ROESY 2D NMR data for this purpose. Conclusion The StrucEluc system continues to be developed in order to expand the general applicability, provide improved workflows, usability of the system and increased reliability of the results. It is expected that expert systems similar to that described in this paper will receive increasing acceptance in the next decade and will ultimately be integrated directly to analytical instruments for the purpose of organic analysis. Work in this direction is in progress. In spite of the fact that many difficulties have already been overcome to deliver on the spectroscopist's dream of "fully automated structure elucidation" there is

  14. COMPUTING

    CERN Multimedia

    P. McBride

    It has been a very active year for the computing project with strong contributions from members of the global community. The project has focused on site preparation and Monte Carlo production. The operations group has begun processing data from P5 as part of the global data commissioning. Improvements in transfer rates and site availability have been seen as computing sites across the globe prepare for large scale production and analysis as part of CSA07. Preparations for the upcoming Computing Software and Analysis Challenge CSA07 are progressing. Ian Fisk and Neil Geddes have been appointed as coordinators for the challenge. CSA07 will include production tests of the Tier-0 production system, reprocessing at the Tier-1 sites and Monte Carlo production at the Tier-2 sites. At the same time there will be a large analysis exercise at the Tier-2 centres. Pre-production simulation of the Monte Carlo events for the challenge is beginning. Scale tests of the Tier-0 will begin in mid-July and the challenge it...

  15. COMPUTING

    CERN Multimedia

    M. Kasemann

    Introduction During the past six months, Computing participated in the STEP09 exercise, had a major involvement in the October exercise and has been working with CMS sites on improving open issues relevant for data taking. At the same time operations for MC production, real data reconstruction and re-reconstructions and data transfers at large scales were performed. STEP09 was successfully conducted in June as a joint exercise with ATLAS and the other experiments. It gave good indication about the readiness of the WLCG infrastructure with the two major LHC experiments stressing the reading, writing and processing of physics data. The October Exercise, in contrast, was conducted as an all-CMS exercise, where Physics, Computing and Offline worked on a common plan to exercise all steps to efficiently access and analyze data. As one of the major results, the CMS Tier-2s demonstrated to be fully capable for performing data analysis. In recent weeks, efforts were devoted to CMS Computing readiness. All th...

  16. COMPUTING

    CERN Multimedia

    I. Fisk

    2011-01-01

    Introduction It has been a very active quarter in Computing with interesting progress in all areas. The activity level at the computing facilities, driven by both organised processing from data operations and user analysis, has been steadily increasing. The large-scale production of simulated events that has been progressing throughout the fall is wrapping-up and reprocessing with pile-up will continue. A large reprocessing of all the proton-proton data has just been released and another will follow shortly. The number of analysis jobs by users each day, that was already hitting the computing model expectations at the time of ICHEP, is now 33% higher. We are expecting a busy holiday break to ensure samples are ready in time for the winter conferences. Heavy Ion The Tier 0 infrastructure was able to repack and promptly reconstruct heavy-ion collision data. Two copies were made of the data at CERN using a large CASTOR disk pool, and the core physics sample was replicated ...

  17. COMPUTING

    CERN Multimedia

    I. Fisk

    2012-01-01

    Introduction Computing continued with a high level of activity over the winter in preparation for conferences and the start of the 2012 run. 2012 brings new challenges with a new energy, more complex events, and the need to make the best use of the available time before the Long Shutdown. We expect to be resource constrained on all tiers of the computing system in 2012 and are working to ensure the high-priority goals of CMS are not impacted. Heavy ions After a successful 2011 heavy-ion run, the programme is moving to analysis. During the run, the CAF resources were well used for prompt analysis. Since then in 2012 on average 200 job slots have been used continuously at Vanderbilt for analysis workflows. Operations Office As of 2012, the Computing Project emphasis has moved from commissioning to operation of the various systems. This is reflected in the new organisation structure where the Facilities and Data Operations tasks have been merged into a common Operations Office, which now covers everything ...

  18. COMPUTING

    CERN Multimedia

    M. Kasemann

    CCRC’08 challenges and CSA08 During the February campaign of the Common Computing readiness challenges (CCRC’08), the CMS computing team had achieved very good results. The link between the detector site and the Tier0 was tested by gradually increasing the number of parallel transfer streams well beyond the target. Tests covered the global robustness at the Tier0, processing a massive number of very large files and with a high writing speed to tapes.  Other tests covered the links between the different Tiers of the distributed infrastructure and the pre-staging and reprocessing capacity of the Tier1’s: response time, data transfer rate and success rate for Tape to Buffer staging of files kept exclusively on Tape were measured. In all cases, coordination with the sites was efficient and no serious problem was found. These successful preparations prepared the ground for the second phase of the CCRC’08 campaign, in May. The Computing Software and Analysis challen...

  19. COMPUTING

    CERN Multimedia

    I. Fisk

    2010-01-01

    Introduction The first data taking period of November produced a first scientific paper, and this is a very satisfactory step for Computing. It also gave the invaluable opportunity to learn and debrief from this first, intense period, and make the necessary adaptations. The alarm procedures between different groups (DAQ, Physics, T0 processing, Alignment/calibration, T1 and T2 communications) have been reinforced. A major effort has also been invested into remodeling and optimizing operator tasks in all activities in Computing, in parallel with the recruitment of new Cat A operators. The teams are being completed and by mid year the new tasks will have been assigned. CRB (Computing Resource Board) The Board met twice since last CMS week. In December it reviewed the experience of the November data-taking period and could measure the positive improvements made for the site readiness. It also reviewed the policy under which Tier-2 are associated with Physics Groups. Such associations are decided twice per ye...

  20. COMPUTING

    CERN Multimedia

    M. Kasemann

    Introduction More than seventy CMS collaborators attended the Computing and Offline Workshop in San Diego, California, April 20-24th to discuss the state of readiness of software and computing for collisions. Focus and priority were given to preparations for data taking and providing room for ample dialog between groups involved in Commissioning, Data Operations, Analysis and MC Production. Throughout the workshop, aspects of software, operating procedures and issues addressing all parts of the computing model were discussed. Plans for the CMS participation in STEP’09, the combined scale testing for all four experiments due in June 2009, were refined. The article in CMS Times by Frank Wuerthwein gave a good recap of the highly collaborative atmosphere of the workshop. Many thanks to UCSD and to the organizers for taking care of this workshop, which resulted in a long list of action items and was definitely a success. A considerable amount of effort and care is invested in the estimate of the co...

  1. Computational modeling and molecular imprinting for the development of acrylic polymers with high affinity for bile salts.

    Science.gov (United States)

    Yañez, Fernando; Chianella, Iva; Piletsky, Sergey A; Concheiro, Angel; Alvarez-Lorenzo, Carmen

    2010-02-05

    This work has focused on the rational development of polymers capable of acting as traps of bile salts. Computational modeling was combined with molecular imprinting technology to obtain networks with high affinity for cholate salts in aqueous medium. The screening of a virtual library of 18 monomers, which are commonly used for imprinted networks, identified N-(3-aminopropyl)-methacrylate hydrochloride (APMA.HCl), N,N-diethylamino ethyl methacrylate (DEAEM) and ethyleneglycol methacrylate phosphate (EGMP) as suitable functional monomers with medium-to-high affinity for cholic acid. The polymers were prepared with a fix cholic acid:functional monomer mole ratio of 1:4, but with various cross-linking densities. Compared to polymers prepared without functional monomer, both imprinted and non-imprinted microparticles showed a high capability to remove sodium cholate from aqueous medium. High affinity APMA-based particles even resembled the performance of commercially available cholesterol-lowering granules. The imprinting effect was evident in most of the networks prepared, showing that computational modeling and molecular imprinting can act synergistically to improve the performance of certain polymers. Nevertheless, both the imprinted and non-imprinted networks prepared with the best monomer (APMA.HCl) identified by the modeling demonstrated such high affinity for the template that the imprinting effect was less important. The fitting of adsorption isotherms to the Freundlich model indicated that, in general, imprinting increases the population of high affinity binding sites, except when the affinity of the functional monomer for the target molecule is already very high. The cross-linking density was confirmed as a key parameter that determines the accessibility of the binding points to sodium cholate. Materials prepared with 9% mol APMA and 91% mol cross-linker showed enough affinity to achieve binding levels of up to 0.4 mmol g(-1) (i.e., 170 mg g(-1)) under flow

  2. FTIR and FT-Raman spectra and density functional computations of the vibrational spectra, molecular geometry and atomic charges of the biomolecule: 5-bromouracil

    Czech Academy of Sciences Publication Activity Database

    Rastogi, V.K.; Palafox, M. A.; Mittal, L.; Peica, N.; Keifer, W.; Lang, Kamil; Ojha, S.P.

    2007-01-01

    Roč. 38, č. 10 (2007), s. 1227-1241 ISSN 0377-0486 Institutional research plan: CEZ:AV0Z40320502 Keywords : FTIR and FT-Raman spectra * density functional computations * molecular geometry Subject RIV: CA - Inorganic Chemistry Impact factor: 3.514, year: 2007

  3. Nano-confined water in the interlayers of hydrocalumite: Reorientational dynamics probed by neutron spectroscopy and molecular dynamics computer simulations

    Science.gov (United States)

    Kalinichev, A. G.; Faraone, A.; Udovic, T.; Kolesnikov, A. I.; de Souza, N. R.; Reinholdt, M. X.; Kirkpatrick, R.

    2008-12-01

    Layered double hydroxides (LDHs, anionic clays) represent excellent model systems for detailed molecular- level studies of the structure, dynamics, and energetics of nano-confined water in mineral interlayers and nano-pores, because LDH interlayers can have a well-defined structures and contain H2O molecules and a wide variety of anions in structurally well-defined positions and coordinations. [Ca2Al(OH)6]Cl·2H2O, also known as hydrocalumite or Friedel's salt, has a well- ordered Ca,Al distribution in the hydroxide layer and a very high degree of H2O,Cl ordering in the interlayer. It is also one of the only LDH phase for which a single crystal structure refinement is available. Thus, it is currently the best model compound for understanding the structure and dynamical behavior of interlayer and surface species in other, less-ordered, LDHs. We investigated the structural and dynamic behavior of water in the interlayers of hydrocalumite using inelastic (INS) and quasielastic (QENS) neutron scattering and molecular dynamics computer simulations. The comperehensive neutron scattering studies were performed for one fully hydrated and one dehydrated sample of hydrocalumite using several complementary instruments (HFBS, DCS and FANS at NCNR; HRMECS and QENS at IPNS) at temperatures above and below the previously discovered order-disorder interlayer phase transition. Together the experimental and molecular modeling results capture the important details of the dynamics of nano-confined water and the effects of the orientational ordering of H2O molecules above and below the phase transition. They provide otherwise unobtainable experimental information about the transformation of H2O librational and diffusional modes across the order-disorder phase transition and significantly add to our current understanding of the structure and dynamics of water in LDH phases based on the earlier NMR, IR, X-ray, and calorimetric measurements. The approach can now be extended to probe the

  4. Three pillars for achieving quantum mechanical molecular dynamics simulations of huge systems: Divide-and-conquer, density-functional tight-binding, and massively parallel computation.

    Science.gov (United States)

    Nishizawa, Hiroaki; Nishimura, Yoshifumi; Kobayashi, Masato; Irle, Stephan; Nakai, Hiromi

    2016-08-05

    The linear-scaling divide-and-conquer (DC) quantum chemical methodology is applied to the density-functional tight-binding (DFTB) theory to develop a massively parallel program that achieves on-the-fly molecular reaction dynamics simulations of huge systems from scratch. The functions to perform large scale geometry optimization and molecular dynamics with DC-DFTB potential energy surface are implemented to the program called DC-DFTB-K. A novel interpolation-based algorithm is developed for parallelizing the determination of the Fermi level in the DC method. The performance of the DC-DFTB-K program is assessed using a laboratory computer and the K computer. Numerical tests show the high efficiency of the DC-DFTB-K program, a single-point energy gradient calculation of a one-million-atom system is completed within 60 s using 7290 nodes of the K computer. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Advanced computational biology methods identify molecular switches for malignancy in an EGF mouse model of liver cancer.

    Directory of Open Access Journals (Sweden)

    Philip Stegmaier

    Full Text Available The molecular causes by which the epidermal growth factor receptor tyrosine kinase induces malignant transformation are largely unknown. To better understand EGFs' transforming capacity whole genome scans were applied to a transgenic mouse model of liver cancer and subjected to advanced methods of computational analysis to construct de novo gene regulatory networks based on a combination of sequence analysis and entrained graph-topological algorithms. Here we identified transcription factors, processes, key nodes and molecules to connect as yet unknown interacting partners at the level of protein-DNA interaction. Many of those could be confirmed by electromobility band shift assay at recognition sites of gene specific promoters and by western blotting of nuclear proteins. A novel cellular regulatory circuitry could therefore be proposed that connects cell cycle regulated genes with components of the EGF signaling pathway. Promoter analysis of differentially expressed genes suggested the majority of regulated transcription factors to display specificity to either the pre-tumor or the tumor state. Subsequent search for signal transduction key nodes upstream of the identified transcription factors and their targets suggested the insulin-like growth factor pathway to render the tumor cells independent of EGF receptor activity. Notably, expression of IGF2 in addition to many components of this pathway was highly upregulated in tumors. Together, we propose a switch in autocrine signaling to foster tumor growth that was initially triggered by EGF and demonstrate the knowledge gain form promoter analysis combined with upstream key node identification.

  6. Insights into the Thiamine Diphosphate Enzyme Activation Mechanism: Computational Model for Transketolase Using a Quantum Mechanical/Molecular Mechanical Method.

    Science.gov (United States)

    Nauton, Lionel; Hélaine, Virgil; Théry, Vincent; Hecquet, Laurence

    2016-04-12

    We propose the first computational model for transketolase (TK), a thiamine diphosphate (ThDP)-dependent enzyme, using a quantum mechanical/molecular mechanical method on the basis of crystallographic TK structures from yeast and Escherichia coli, together with experimental kinetic data reported in the literature with wild-type and mutant TK. This model allowed us to define a new route for ThDP activation in the enzyme environment. We evidenced a strong interaction between ThDP and Glu418B of the TK active site, itself stabilized by Glu162A. The crucial point highlighted here is that deprotonation of ThDP C2 is not performed by ThDP N4' as reported in the literature, but by His481B, involving a HOH688A molecule bridge. Thus, ThDP N4' is converted from an amino form to an iminium form, ensuring the stabilization of the C2 carbanion or carbene. Finally, ThDP activation proceeds via an intermolecular process and not by an intramolecular one as reported in the literature. More generally, this proposed ThDP activation mechanism can be applied to some other ThDP-dependent enzymes and used to define the entire TK mechanism with donor and acceptor substrates more accurately.

  7. The structure and dynamics of energetic displacement cascades in Cu and Ni. A molecular dynamics computer simulation study

    International Nuclear Information System (INIS)

    Diaz de la Rubia, T.

    1989-01-01

    The primary state of damage present in a solid as a result of particle irradiation has been a topic of interest to the physics and materials research community over the last forty years. Energetic displacement cascades resulting from the heavy ion irradiation of a solid play a prominent role in radiation damage and non-equilibrium processing of materials; however, their study has been hampered by the small size (∼10 -20 cm 3 ) and short lifetime (∼10 -11 s) as well as by their highly non-homogeneous nature. In this work, the molecular dynamics computer simulation technique is employed to study the structure and dynamics of energetic displacement cascades in Cu and Ni. The atomic interactions in Cu were described with the use of the Gibson II form of the Born-Mayer pair potential while for Ni the Johnson-Erginsoy pair potential was employed. Calculations were also carried out with the use of the embedded atom method many-body potentials. The results provide the first detailed microscopic description of the evolution of the cascade. The author shows for the first time, that a process akin to melting takes place in the core of the cascade. Atomic mixing, point defect production and point defect agglomeration, all processes directly related to the evolution of the cascade, are then explained in terms of a simple model in which the liquid-like nature of the cascade plays a dominant role in determining the primary state of damage

  8. Imaging performance of a hybrid x-ray computed tomography-fluorescence molecular tomography system using priors.

    Science.gov (United States)

    Ale, Angelique; Schulz, Ralf B; Sarantopoulos, Athanasios; Ntziachristos, Vasilis

    2010-05-01

    The performance is studied of two newly introduced and previously suggested methods that incorporate priors into inversion schemes associated with data from a recently developed hybrid x-ray computed tomography and fluorescence molecular tomography system, the latter based on CCD camera photon detection. The unique data set studied attains accurately registered data of high spatially sampled photon fields propagating through tissue along 360 degrees projections. Approaches that incorporate structural prior information were included in the inverse problem by adding a penalty term to the minimization function utilized for image reconstructions. Results were compared as to their performance with simulated and experimental data from a lung inflammation animal model and against the inversions achieved when not using priors. The importance of using priors over stand-alone inversions is also showcased with high spatial sampling simulated and experimental data. The approach of optimal performance in resolving fluorescent biodistribution in small animals is also discussed. Inclusion of prior information from x-ray CT data in the reconstruction of the fluorescence biodistribution leads to improved agreement between the reconstruction and validation images for both simulated and experimental data.

  9. FMT-XCT: in vivo animal studies with hybrid fluorescence molecular tomography-X-ray computed tomography.

    Science.gov (United States)

    Ale, Angelique; Ermolayev, Vladimir; Herzog, Eva; Cohrs, Christian; de Angelis, Martin Hrabé; Ntziachristos, Vasilis

    2012-06-01

    The development of hybrid optical tomography methods to improve imaging performance has been suggested over a decade ago and has been experimentally demonstrated in animals and humans. Here we examined in vivo performance of a camera-based hybrid fluorescence molecular tomography (FMT) system for 360° imaging combined with X-ray computed tomography (XCT). Offering an accurately co-registered, information-rich hybrid data set, FMT-XCT has new imaging possibilities compared to stand-alone FMT and XCT. We applied FMT-XCT to a subcutaneous 4T1 tumor mouse model, an Aga2 osteogenesis imperfecta model and a Kras lung cancer mouse model, using XCT information during FMT inversion. We validated in vivo imaging results against post-mortem planar fluorescence images of cryoslices and histology data. Besides offering concurrent anatomical and functional information, FMT-XCT resulted in the most accurate FMT performance to date. These findings indicate that addition of FMT optics into the XCT gantry may be a potent upgrade for small-animal XCT systems.

  10. GENESIS 1.1: A hybrid-parallel molecular dynamics simulator with enhanced sampling algorithms on multiple computational platforms.

    Science.gov (United States)

    Kobayashi, Chigusa; Jung, Jaewoon; Matsunaga, Yasuhiro; Mori, Takaharu; Ando, Tadashi; Tamura, Koichi; Kamiya, Motoshi; Sugita, Yuji

    2017-09-30

    GENeralized-Ensemble SImulation System (GENESIS) is a software package for molecular dynamics (MD) simulation of biological systems. It is designed to extend limitations in system size and accessible time scale by adopting highly parallelized schemes and enhanced conformational sampling algorithms. In this new version, GENESIS 1.1, new functions and advanced algorithms have been added. The all-atom and coarse-grained potential energy functions used in AMBER and GROMACS packages now become available in addition to CHARMM energy functions. The performance of MD simulations has been greatly improved by further optimization, multiple time-step integration, and hybrid (CPU + GPU) computing. The string method and replica-exchange umbrella sampling with flexible collective variable choice are used for finding the minimum free-energy pathway and obtaining free-energy profiles for conformational changes of a macromolecule. These new features increase the usefulness and power of GENESIS for modeling and simulation in biological research. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. Computational simulation of electron and ion beams interaction with solid high-molecular dielectrics and inorganic glasses

    International Nuclear Information System (INIS)

    Milyavskiy, V.V.

    1998-01-01

    Numerical investigation of interaction of electron beams (with the energy within the limits 100 keV--20 MeV) and ion beams (with the energy over the range 1 keV--50 MeV) with solid high-molecular dielectrics and inorganic glasses is performed. Note that the problem of interaction of electron beams with glass optical covers is especially interesting in connection with the problem of radiation protection of solar power elements on cosmic satellites and stations. For computational simulation of the above-mentioned processes a mathematical model was developed, describing the propagation of particle beams through the sample thickness, the accumulation and relaxation of volume charge and shock-wave processes, as well as the evolution of electric field in the sample. The calculation of energy deposition by electron beam in a target in the presence of nonuniform electric field was calculated with the assistance of the semiempirical procedure, formerly proposed by author of this work. Propagation of the low energy ions through the sample thickness was simulated using Pearson IV distribution. Damage distribution, ionization distribution and range distribution was taken into account. Propagation of high energy ions was calculated in the approximation of continuous deceleration. For description of hydrodynamic processes the system of equations of continuum mechanics in elastic-plastic approximation and the wide-range equation of state were used

  12. Use of the McQuarrie equation for the computation of shear viscosity via equilibrium molecular dynamics

    International Nuclear Information System (INIS)

    Chialvo, A.A.; Debenedetti, P.G.

    1991-01-01

    To date, the calculation of shear viscosity for soft-core fluids via equilibrium molecular dynamics has been done almost exclusively using the Green-Kubo formalism. The alternative mean-squared displacement approach has not been used, except for hard-sphere fluids, in which case the expression proposed by Helfand [Phys. Rev. 119, 1 (1960)] has invariably been selected. When written in the form given by McQuarrie [Statistical Mechanics (Harper ampersand Row, New York, 1976), Chap. 21], however, the mean-squared displacement approach offers significant computational advantages over both its Green-Kubo and Helfand counterparts. In order to achieve comparable statistical significance, the number of experiments needed when using the Green-Kubo or Helfand formalisms is more than an order of magnitude higher than for the McQuarrie expression. For pairwise-additive systems with zero linear momentum, the McQuarrie method yields frame-independent shear viscosities. The hitherto unexplored McQuarrie implementation of the mean-squared displacement approach to shear-viscosity calculation thus appears superior to alternative methods currently in use

  13. COMPUTING

    CERN Multimedia

    2010-01-01

    Introduction Just two months after the “LHC First Physics” event of 30th March, the analysis of the O(200) million 7 TeV collision events in CMS accumulated during the first 60 days is well under way. The consistency of the CMS computing model has been confirmed during these first weeks of data taking. This model is based on a hierarchy of use-cases deployed between the different tiers and, in particular, the distribution of RECO data to T1s, who then serve data on request to T2s, along a topology known as “fat tree”. Indeed, during this period this model was further extended by almost full “mesh” commissioning, meaning that RECO data were shipped to T2s whenever possible, enabling additional physics analyses compared with the “fat tree” model. Computing activities at the CMS Analysis Facility (CAF) have been marked by a good time response for a load almost evenly shared between ALCA (Alignment and Calibration tasks - highest p...

  14. COMPUTING

    CERN Multimedia

    Contributions from I. Fisk

    2012-01-01

    Introduction The start of the 2012 run has been busy for Computing. We have reconstructed, archived, and served a larger sample of new data than in 2011, and we are in the process of producing an even larger new sample of simulations at 8 TeV. The running conditions and system performance are largely what was anticipated in the plan, thanks to the hard work and preparation of many people. Heavy ions Heavy Ions has been actively analysing data and preparing for conferences.  Operations Office Figure 6: Transfers from all sites in the last 90 days For ICHEP and the Upgrade efforts, we needed to produce and process record amounts of MC samples while supporting the very successful data-taking. This was a large burden, especially on the team members. Nevertheless the last three months were very successful and the total output was phenomenal, thanks to our dedicated site admins who keep the sites operational and the computing project members who spend countless hours nursing the...

  15. COMPUTING

    CERN Multimedia

    M. Kasemann

    Introduction A large fraction of the effort was focused during the last period into the preparation and monitoring of the February tests of Common VO Computing Readiness Challenge 08. CCRC08 is being run by the WLCG collaboration in two phases, between the centres and all experiments. The February test is dedicated to functionality tests, while the May challenge will consist of running at all centres and with full workflows. For this first period, a number of functionality checks of the computing power, data repositories and archives as well as network links are planned. This will help assess the reliability of the systems under a variety of loads, and identifying possible bottlenecks. Many tests are scheduled together with other VOs, allowing the full scale stress test. The data rates (writing, accessing and transfer¬ring) are being checked under a variety of loads and operating conditions, as well as the reliability and transfer rates of the links between Tier-0 and Tier-1s. In addition, the capa...

  16. COMPUTING

    CERN Multimedia

    Matthias Kasemann

    Overview The main focus during the summer was to handle data coming from the detector and to perform Monte Carlo production. The lessons learned during the CCRC and CSA08 challenges in May were addressed by dedicated PADA campaigns lead by the Integration team. Big improvements were achieved in the stability and reliability of the CMS Tier1 and Tier2 centres by regular and systematic follow-up of faults and errors with the help of the Savannah bug tracking system. In preparation for data taking the roles of a Computing Run Coordinator and regular computing shifts monitoring the services and infrastructure as well as interfacing to the data operations tasks are being defined. The shift plan until the end of 2008 is being put together. User support worked on documentation and organized several training sessions. The ECoM task force delivered the report on “Use Cases for Start-up of pp Data-Taking” with recommendations and a set of tests to be performed for trigger rates much higher than the ...

  17. COMPUTING

    CERN Multimedia

    P. MacBride

    The Computing Software and Analysis Challenge CSA07 has been the main focus of the Computing Project for the past few months. Activities began over the summer with the preparation of the Monte Carlo data sets for the challenge and tests of the new production system at the Tier-0 at CERN. The pre-challenge Monte Carlo production was done in several steps: physics generation, detector simulation, digitization, conversion to RAW format and the samples were run through the High Level Trigger (HLT). The data was then merged into three "Soups": Chowder (ALPGEN), Stew (Filtered Pythia) and Gumbo (Pythia). The challenge officially started when the first Chowder events were reconstructed on the Tier-0 on October 3rd. The data operations teams were very busy during the the challenge period. The MC production teams continued with signal production and processing while the Tier-0 and Tier-1 teams worked on splitting the Soups into Primary Data Sets (PDS), reconstruction and skimming. The storage sys...

  18. COMPUTING

    CERN Multimedia

    I. Fisk

    2013-01-01

    Computing operation has been lower as the Run 1 samples are completing and smaller samples for upgrades and preparations are ramping up. Much of the computing activity is focusing on preparations for Run 2 and improvements in data access and flexibility of using resources. Operations Office Data processing was slow in the second half of 2013 with only the legacy re-reconstruction pass of 2011 data being processed at the sites.   Figure 1: MC production and processing was more in demand with a peak of over 750 Million GEN-SIM events in a single month.   Figure 2: The transfer system worked reliably and efficiently and transferred on average close to 520 TB per week with peaks at close to 1.2 PB.   Figure 3: The volume of data moved between CMS sites in the last six months   The tape utilisation was a focus for the operation teams with frequent deletion campaigns from deprecated 7 TeV MC GEN-SIM samples to INVALID datasets, which could be cleaned up...

  19. COMPUTING

    CERN Multimedia

    I. Fisk

    2012-01-01

      Introduction Computing activity has been running at a sustained, high rate as we collect data at high luminosity, process simulation, and begin to process the parked data. The system is functional, though a number of improvements are planned during LS1. Many of the changes will impact users, we hope only in positive ways. We are trying to improve the distributed analysis tools as well as the ability to access more data samples more transparently.  Operations Office Figure 2: Number of events per month, for 2012 Since the June CMS Week, Computing Operations teams successfully completed data re-reconstruction passes and finished the CMSSW_53X MC campaign with over three billion events available in AOD format. Recorded data was successfully processed in parallel, exceeding 1.2 billion raw physics events per month for the first time in October 2012 due to the increase in data-parking rate. In parallel, large efforts were dedicated to WMAgent development and integrati...

  20. COMPUTING

    CERN Multimedia

    I. Fisk

    2011-01-01

    Introduction The Computing Team successfully completed the storage, initial processing, and distribution for analysis of proton-proton data in 2011. There are still a variety of activities ongoing to support winter conference activities and preparations for 2012. Heavy ions The heavy-ion run for 2011 started in early November and has already demonstrated good machine performance and success of some of the more advanced workflows planned for 2011. Data collection will continue until early December. Facilities and Infrastructure Operations Operational and deployment support for WMAgent and WorkQueue+Request Manager components, routinely used in production by Data Operations, are provided. The GlideInWMS and components installation are now deployed at CERN, which is added to the GlideInWMS factory placed in the US. There has been new operational collaboration between the CERN team and the UCSD GlideIn factory operators, covering each others time zones by monitoring/debugging pilot jobs sent from the facto...

  1. A new decomposition-based computer-aided molecular/mixture design methodology for the design of optimal solvents and solvent mixtures

    DEFF Research Database (Denmark)

    Karunanithi, A.T.; Achenie, L.E.K.; Gani, Rafiqul

    2005-01-01

    This paper presents a novel computer-aided molecular/mixture design (CAMD) methodology for the design of optimal solvents and solvent mixtures. The molecular/mixture design problem is formulated as a mixed integer nonlinear programming (MINLP) model in which a performance objective is to be optim......This paper presents a novel computer-aided molecular/mixture design (CAMD) methodology for the design of optimal solvents and solvent mixtures. The molecular/mixture design problem is formulated as a mixed integer nonlinear programming (MINLP) model in which a performance objective...... is to be optimized subject to structural, property, and process constraints. The general molecular/mixture design problem is divided into two parts. For optimal single-compound design, the first part is solved. For mixture design, the single-compound design is first carried out to identify candidates...... and then the second part is solved to determine the optimal mixture. The decomposition of the CAMD MINLP model into relatively easy to solve subproblems is essentially a partitioning of the constraints from the original set. This approach is illustrated through two case studies. The first case study involves...

  2. COMPUTING

    CERN Multimedia

    M. Kasemann

    CMS relies on a well functioning, distributed computing infrastructure. The Site Availability Monitoring (SAM) and the Job Robot submission have been very instrumental for site commissioning in order to increase availability of more sites such that they are available to participate in CSA07 and are ready to be used for analysis. The commissioning process has been further developed, including "lessons learned" documentation via the CMS twiki. Recently the visualization, presentation and summarizing of SAM tests for sites has been redesigned, it is now developed by the central ARDA project of WLCG. Work to test the new gLite Workload Management System was performed; a 4 times increase in throughput with respect to LCG Resource Broker is observed. CMS has designed and launched a new-generation traffic load generator called "LoadTest" to commission and to keep exercised all data transfer routes in the CMS PhE-DEx topology. Since mid-February, a transfer volume of about 12 P...

  3. Insights into the molecular mechanisms of Polygonum multiflorum Thunb-induced liver injury: a computational systems toxicology approach.

    Science.gov (United States)

    Wang, Yin-Yin; Li, Jie; Wu, Zeng-Rui; Zhang, Bo; Yang, Hong-Bin; Wang, Qin; Cai, Ying-Chun; Liu, Gui-Xia; Li, Wei-Hua; Tang, Yun

    2017-05-01

    An increasing number of cases of herb-induced liver injury (HILI) have been reported, presenting new clinical challenges. In this study, taking Polygonum multiflorum Thunb (PmT) as an example, we proposed a computational systems toxicology approach to explore the molecular mechanisms of HILI. First, the chemical components of PmT were extracted from 3 main TCM databases as well as the literature related to natural products. Then, the known targets were collected through data integration, and the potential compound-target interactions (CTIs) were predicted using our substructure-drug-target network-based inference (SDTNBI) method. After screening for hepatotoxicity-related genes by assessing the symptoms of HILI, a compound-target interaction network was constructed. A scoring function, namely, Ascore, was developed to estimate the toxicity of chemicals in the liver. We conducted network analysis to determine the possible mechanisms of the biphasic effects using the analysis tools, including BiNGO, pathway enrichment, organ distribution analysis and predictions of interactions with CYP450 enzymes. Among the chemical components of PmT, 54 components with good intestinal absorption were used for analysis, and 2939 CTIs were obtained. After analyzing the mRNA expression data in the BioGPS database, 1599 CTIs and 125 targets related to liver diseases were identified. In the top 15 compounds, seven with Ascore values >3000 (emodin, quercetin, apigenin, resveratrol, gallic acid, kaempferol and luteolin) were obviously associated with hepatotoxicity. The results from the pathway enrichment analysis suggest that multiple interactions between apoptosis and metabolism may underlie PmT-induced liver injury. Many of the pathways have been verified in specific compounds, such as glutathione metabolism, cytochrome P450 metabolism, and the p53 pathway, among others. Hepatitis symptoms, the perturbation of nine bile acids and yellow or tawny urine also had corresponding pathways

  4. Computational molecular modeling and structural rationalization for the design of a drug-loaded PLLA/PVA biopolymeric membrane

    International Nuclear Information System (INIS)

    Sibeko, B; Pillay, V; Choonara, Y E; Khan, R A; Danckwerts, M P; Modi, G; Iyuke, S E; Naidoo, D

    2009-01-01

    The purpose of this study was to design, characterize and assess the influence of triethanolamine (TEA) on the physicomechanical properties and release of methotrexate (MTX) from a composite biopolymeric membrane. Conjugated poly(L-lactic acid) (PLLA) and poly(vinyl alcohol) (PVA) membranes were prepared by immersion precipitation with and without the addition of TEA. Drug entrapment efficiency (DEE) and release studies were performed in phosphate buffered saline (pH 7.4, 37 deg. C). Scanning electron microscopy elucidated the membrane surface morphology. Computational and structural molecular modeling rationalized the potential mechanisms of membrane formation and MTX release. Bi-axial force-distance (F-D) extensibility profiles were generated to determine the membrane toughness, elasticity and fracturability. Membranes were significantly toughened by the addition of TEA as a discrete rubbery phase within the co-polymer matrix. MTX-TEA-PLLA-PVA membranes were tougher (F = 89 N) and more extensible (D = 8.79 mm) compared to MTX-PLLA-PVA (F = 35 N, D = 3.7 mm) membranes as a greater force of extension and fracture distance were required (N = 10). DEE values were relatively high (>80%, N = 5) for both formulations. Photomicrographs revealed distinct crystalline layered morphologies with macro-pores. MTX was released by tri-phasic kinetics with a lower fractional release of MTX from MTX-TEA-PLLA-PVA membranes compared to MTX-PLLA-PVA. TEA provided a synergistic approach to improving the membrane physicomechanical properties and modulation of MTX release. The composite biopolymeric membrane may therefore be suitable for the novel delivery of MTX in the treatment of chronic primary central nervous system lymphoma.

  5. IBiSA_Tools: A Computational Toolkit for Ion-Binding State Analysis in Molecular Dynamics Trajectories of Ion Channels.

    Directory of Open Access Journals (Sweden)

    Kota Kasahara

    Full Text Available Ion conduction mechanisms of ion channels are a long-standing conundrum. Although the molecular dynamics (MD method has been extensively used to simulate ion conduction dynamics at the atomic level, analysis and interpretation of MD results are not straightforward due to complexity of the dynamics. In our previous reports, we proposed an analytical method called ion-binding state analysis to scrutinize and summarize ion conduction mechanisms by taking advantage of a variety of analytical protocols, e.g., the complex network analysis, sequence alignment, and hierarchical clustering. This approach effectively revealed the ion conduction mechanisms and their dependence on the conditions, i.e., ion concentration and membrane voltage. Here, we present an easy-to-use computational toolkit for ion-binding state analysis, called IBiSA_tools. This toolkit consists of a C++ program and a series of Python and R scripts. From the trajectory file of MD simulations and a structure file, users can generate several images and statistics of ion conduction processes. A complex network named ion-binding state graph is generated in a standard graph format (graph modeling language; GML, which can be visualized by standard network analyzers such as Cytoscape. As a tutorial, a trajectory of a 50 ns MD simulation of the Kv1.2 channel is also distributed with the toolkit. Users can trace the entire process of ion-binding state analysis step by step. The novel method for analysis of ion conduction mechanisms of ion channels can be easily used by means of IBiSA_tools. This software is distributed under an open source license at the following URL: http://www.ritsumei.ac.jp/~ktkshr/ibisa_tools/.

  6. CH(+) Destruction by Reaction with H: Computing Quantum Rates To Model Different Molecular Regions in the Interstellar Medium.

    Science.gov (United States)

    Bovino, S; Grassi, T; Gianturco, F A

    2015-12-17

    A detailed analysis of an ionic reaction that plays a crucial role in the carbon chemistry of the interstellar medium (ISM) is carried out by computing ab initio reactive cross sections with a quantum method and by further obtaining the corresponding CH(+) destruction rates over a range of temperatures that shows good overall agreement with existing experiments. The differences found between all existing calculations and the very-low-T experiments are discussed and explored via a simple numerical model that links these cross section reductions to collinear approaches where nonadiabatic crossing is expected to dominate. The new rates are further linked to a complex chemical network that models the evolution of the CH(+) abundance in the photodissociation region (PDR) and molecular cloud (MC) environments of the ISM. The abundances of CH(+) are given by numerical solutions of a large set of coupled, first-order kinetics equations that employs our new chemical package krome. The analysis that we carry out reveals that the important region for CH(+) destruction is that above 100 K, hence showing that, at least for this reaction, the differences with the existing laboratory low-T experiments are of essentially no importance within the astrochemical environments discussed here because, at those temperatures, other chemical processes involving the title molecule are taking over. A detailed analysis of the chemical network involving CH(+) also shows that a slight decrease in the initial oxygen abundance might lead to higher CH(+) abundances because the main chemical carbon ion destruction channel is reduced in efficiency. This might provide an alternative chemical route to understand the reason why general astrochemical models fail when the observed CH(+) abundances are matched with the outcomes of their calculations.

  7. Design of a tablet computer app for facilitation of a molecular blood culture test in clinical microbiology and preliminary usability evaluation

    DEFF Research Database (Denmark)

    Samson, Lasse L.; Pape-Haugaard, Louise; Meltzer, Michelle C.

    2016-01-01

    through specialized applications (apps) while supporting the mobility of the users. The use of apps for mobile phones and tablet computers may support workflow of complex tasks, for example, molecular-based diagnostic tests in clinical microbiology. Multiplex Blood Culture Test (MuxBCT) is a molecular......-based diagnostic test used for rapid identification of pathogens in positive blood cultures. To facilitate the workflow of the MuxBCT, a specialized tablet computer app was developed as an accessory to the diagnostic test. The app aims to reduce the complexity of the test by step-by-step guidance of microscopy...... and to assist users in reaching an exact bacterial or fungal diagnosis based on blood specimen observations and controls. Additionally, the app allows for entry of test results, and communication thereof to the laboratory information system (LIS). OBJECTIVE: The objective of the study was to describe the design...

  8. Potent New Small-Molecule Inhibitor of Botulinum Neurotoxin Serotype A Endopeptidase Developed by Synthesis-Based Computer-Aided Molecular Design

    Science.gov (United States)

    2009-11-01

    simulations; (4) synthesis and evaluation of the molecules from Step 2 or 3 (e.g., synthesizing and testing AHP). From synthetic chemistry point of view...2000) Synthesis of 6H-indolo [2,3-b][1,6]naphthyridines and related compounds as the 5-Aza analogues of ellipticine alkaloids . J Org Chem 65: 7977–7983...Potent New Small-Molecule Inhibitor of Botulinum Neurotoxin Serotype A Endopeptidase Developed by Synthesis -Based Computer-Aided Molecular Design

  9. An ab initio molecular

    Indian Academy of Sciences (India)

    mechanisms of two molecular crystals: An ab initio molecular dynamics ... for Computation in Molecular and Materials Science and Department of Chemistry, School of ..... NSAF Foundation of National Natural Science Foun- ... Matter 14 2717.

  10. MesoBioNano Explorer-A Universal Program for Multiscale Computer Simulations of Complex Molecular Structure and Dynamics

    DEFF Research Database (Denmark)

    Solov'yov, Ilia; Yakubovich, Alexander V.; Nikolaev, Pavel V.

    2012-01-01

    it significantly different from the existing codes, is its universality and applicability to the description of a broad range of problems involving different molecular systems. Most of the existing codes are developed for particular classes of molecular systems and do not permit multiscale approach while MBN...

  11. Intramembranous bone healing process subsequent to tooth extraction in mice: micro-computed tomography, histomorphometric and molecular characterization.

    Science.gov (United States)

    Vieira, Andreia Espindola; Repeke, Carlos Eduardo; Ferreira Junior, Samuel de Barros; Colavite, Priscila Maria; Biguetti, Claudia Cristina; Oliveira, Rodrigo Cardoso; Assis, Gerson Francisco; Taga, Rumio; Trombone, Ana Paula Favaro; Garlet, Gustavo Pompermaier

    2015-01-01

    Bone tissue has a significant potential for healing, which involves a significant the interplay between bone and immune cells. While fracture healing represents a useful model to investigate endochondral bone healing, intramembranous bone healing models are yet to be developed and characterized. In this study, a micro-computed tomography, histomorphometric and molecular (RealTimePCRarray) characterization of post tooth-extraction alveolar bone healing was performed on C57Bl/6 WT mice. After the initial clot dominance (0 h), the development of a provisional immature granulation tissue is evident (7 d), characterized by marked cell proliferation, angiogenesis and inflammatory cells infiltration; associated with peaks of growth factors (BMP-2-4-7,TGFβ1,VEGFa), cytokines (TNFα, IL-10), chemokines & receptors (CXCL12, CCL25, CCR5, CXCR4), matrix (Col1a1-2, ITGA4, VTN, MMP1a) and MSCs (CD105, CD106, OCT4, NANOG, CD34, CD146) markers expression. Granulation tissue is sequentially replaced by more mature connective tissue (14 d), characterized by inflammatory infiltrate reduction along the increased bone formation, marked expression of matrix remodeling enzymes (MMP-2-9), bone formation/maturation (RUNX2, ALP, DMP1, PHEX, SOST) markers, and chemokines & receptors associated with healing (CCL2, CCL17, CCR2). No evidences of cartilage cells or tissue were observed, strengthening the intramembranous nature of bone healing. Bone microarchitecture analysis supports the evolving healing, with total tissue and bone volumes as trabecular number and thickness showing a progressive increase over time. The extraction socket healing process is considered complete (21 d) when the dental socket is filled by trabeculae bone with well-defined medullary canals; it being the expression of mature bone markers prevalent at this period. Our data confirms the intramembranous bone healing nature of the model used, revealing parallels between the gene expression profile and the

  12. Intramembranous bone healing process subsequent to tooth extraction in mice: micro-computed tomography, histomorphometric and molecular characterization.

    Directory of Open Access Journals (Sweden)

    Andreia Espindola Vieira

    Full Text Available Bone tissue has a significant potential for healing, which involves a significant the interplay between bone and immune cells. While fracture healing represents a useful model to investigate endochondral bone healing, intramembranous bone healing models are yet to be developed and characterized. In this study, a micro-computed tomography, histomorphometric and molecular (RealTimePCRarray characterization of post tooth-extraction alveolar bone healing was performed on C57Bl/6 WT mice. After the initial clot dominance (0 h, the development of a provisional immature granulation tissue is evident (7 d, characterized by marked cell proliferation, angiogenesis and inflammatory cells infiltration; associated with peaks of growth factors (BMP-2-4-7,TGFβ1,VEGFa, cytokines (TNFα, IL-10, chemokines & receptors (CXCL12, CCL25, CCR5, CXCR4, matrix (Col1a1-2, ITGA4, VTN, MMP1a and MSCs (CD105, CD106, OCT4, NANOG, CD34, CD146 markers expression. Granulation tissue is sequentially replaced by more mature connective tissue (14 d, characterized by inflammatory infiltrate reduction along the increased bone formation, marked expression of matrix remodeling enzymes (MMP-2-9, bone formation/maturation (RUNX2, ALP, DMP1, PHEX, SOST markers, and chemokines & receptors associated with healing (CCL2, CCL17, CCR2. No evidences of cartilage cells or tissue were observed, strengthening the intramembranous nature of bone healing. Bone microarchitecture analysis supports the evolving healing, with total tissue and bone volumes as trabecular number and thickness showing a progressive increase over time. The extraction socket healing process is considered complete (21 d when the dental socket is filled by trabeculae bone with well-defined medullary canals; it being the expression of mature bone markers prevalent at this period. Our data confirms the intramembranous bone healing nature of the model used, revealing parallels between the gene expression profile and the

  13. Adsorption of molecular additive onto lead halide perovskite surfaces: A computational study on Lewis base thiophene additive passivation

    Science.gov (United States)

    Zhang, Lei; Yu, Fengxi; Chen, Lihong; Li, Jingfa

    2018-06-01

    Organic additives, such as the Lewis base thiophene, have been successfully applied to passivate halide perovskite surfaces, improving the stability and properties of perovskite devices based on CH3NH3PbI3. Yet, the detailed nanostructure of the perovskite surface passivated by additives and the mechanisms of such passivation are not well understood. This study presents a nanoscopic view on the interfacial structure of an additive/perovskite interface, consisting of a Lewis base thiophene molecular additive and a lead halide perovskite surface substrate, providing insights on the mechanisms that molecular additives can passivate the halide perovskite surfaces and enhance the perovskite-based device performance. Molecular dynamics study on the interactions between water molecules and the perovskite surfaces passivated by the investigated additive reveal the effectiveness of employing the molecular additives to improve the stability of the halide perovskite materials. The additive/perovskite surface system is further probed via molecular engineering the perovskite surfaces. This study reveals the nanoscopic structure-property relationships of the halide perovskite surface passivated by molecular additives, which helps the fundamental understanding of the surface/interface engineering strategies for the development of halide perovskite based devices.

  14. Molecular modeling

    Directory of Open Access Journals (Sweden)

    Aarti Sharma

    2009-01-01

    Full Text Available The use of computational chemistry in the development of novel pharmaceuticals is becoming an increasingly important tool. In the past, drugs were simply screened for effectiveness. The recent advances in computing power and the exponential growth of the knowledge of protein structures have made it possible for organic compounds to be tailored to decrease the harmful side effects and increase the potency. This article provides a detailed description of the techniques employed in molecular modeling. Molecular modeling is a rapidly developing discipline, and has been supported by the dramatic improvements in computer hardware and software in recent years.

  15. The truncated conjugate gradient (TCG), a non-iterative/fixed-cost strategy for computing polarization in molecular dynamics: Fast evaluation of analytical forces

    Science.gov (United States)

    Aviat, Félix; Lagardère, Louis; Piquemal, Jean-Philip

    2017-10-01

    In a recent paper [F. Aviat et al., J. Chem. Theory Comput. 13, 180-190 (2017)], we proposed the Truncated Conjugate Gradient (TCG) approach to compute the polarization energy and forces in polarizable molecular simulations. The method consists in truncating the conjugate gradient algorithm at a fixed predetermined order leading to a fixed computational cost and can thus be considered "non-iterative." This gives the possibility to derive analytical forces avoiding the usual energy conservation (i.e., drifts) issues occurring with iterative approaches. A key point concerns the evaluation of the analytical gradients, which is more complex than that with a usual solver. In this paper, after reviewing the present state of the art of polarization solvers, we detail a viable strategy for the efficient implementation of the TCG calculation. The complete cost of the approach is then measured as it is tested using a multi-time step scheme and compared to timings using usual iterative approaches. We show that the TCG methods are more efficient than traditional techniques, making it a method of choice for future long molecular dynamics simulations using polarizable force fields where energy conservation matters. We detail the various steps required for the implementation of the complete method by software developers.

  16. Applications of the NRGsuite and the Molecular Docking Software FlexAID in Computational Drug Discovery and Design.

    Science.gov (United States)

    Morency, Louis-Philippe; Gaudreault, Francis; Najmanovich, Rafael

    2018-01-01

    Docking simulations help us understand molecular interactions. Here we present a hands-on tutorial to utilize FlexAID (Flexible Artificial Intelligence Docking), an open source molecular docking software between ligands such as small molecules or peptides and macromolecules such as proteins and nucleic acids. The tutorial uses the NRGsuite PyMOL plugin graphical user interface to set up and visualize docking simulations in real time as well as detect and refine target cavities. The ease of use of FlexAID and the NRGsuite combined with its superior performance relative to widely used docking software provides nonexperts with an important tool to understand molecular interactions with direct applications in structure-based drug design and virtual high-throughput screening.

  17. Computational modeling of the behavior of nuclear materials (2). Molecular simulations for nuclear materials. Current situation and future perspective

    International Nuclear Information System (INIS)

    Okita, Taira; Itakura, Mitsuhiro

    2017-01-01

    Molecular simulations for nuclear materials aim to reproduce atomistic-scale phenomena induced by irradiation and infer the change in material properties. In the present work, recent progress in this field is presented. In particular, the following three topics are explained: (1) Quantification of lattice defects formation process induced by fast neutron collision. (2) Identification of dislocation-channeling mechanism induced by interactions between defect clusters and dislocations. (3) Modeling of the three dimensional movement of defect clusters using molecular dynamics and kinetic Monte Carlo simulations. (author)

  18. DIGGING DEEPER INTO DEEP DATA: MOLECULAR DOCKING AS A HYPOTHESIS-DRIVEN BIOPHYSICAL INTERROGATION SYSTEM IN COMPUTATIONAL TOXICOLOGY.

    Science.gov (United States)

    Developing and evaluating prediactive strategies to elucidate the mode of biological activity of environmental chemicals is a major objective of the concerted efforts of the US-EPA's computational toxicology program.

  19. Global sensitivity analysis of computer-aided molecular design problem for the development of novel working fluids for power cycles

    DEFF Research Database (Denmark)

    Frutiger, Jerome; Abildskov, Jens; Sin, Gürkan

    2016-01-01

    This study compares two methods for global sensitivity analysis as a new approach for the identification and ranking of target properties in molecular design problems: A modified Morris Screening technique and Monte Carlo based standard regression. The two methodologies are highlighted in a case ...

  20. A third order accurate Lagrangian finite element scheme for the computation of generalized molecular stress function fluids

    DEFF Research Database (Denmark)

    Fasano, Andrea; Rasmussen, Henrik K.

    2017-01-01

    A third order accurate, in time and space, finite element scheme for the numerical simulation of three- dimensional time-dependent flow of the molecular stress function type of fluids in a generalized formu- lation is presented. The scheme is an extension of the K-BKZ Lagrangian finite element me...

  1. Sputtering of copper atoms by keV atomic and molecular ions A comparison of experiment with analytical and computer based models

    CERN Document Server

    Gillen, D R; Goelich,

    2002-01-01

    Non-resonant multiphoton ionisation combined with quadrupole and time-of-flight analysis has been used to measure energy distributions of sputtered copper atoms. The sputtering of a polycrystalline copper target by 3.6 keV Ar sup + , N sup + and CF sub 2 sup + and 1.8 keV N sup + and CF sub 2 sup + ion bombardment at 45 deg. has been investigated. The linear collision model in the isotropic limit fails to describe the high energy tail of the energy distributions. However the TRIM.SP computer simulation has been shown to provide a good description. The results indicate that an accurate description of sputtering by low energy, molecular ions requires the use of computer simulation rather than analytical approaches. This is particularly important when considering plasma-surface interactions in plasma etching and deposition systems.

  2. Molecular features of interaction between VEGFA and anti-angiogenic drugs used in retinal diseases: a computational approach

    Directory of Open Access Journals (Sweden)

    Chiara Bianca Maria Platania

    2015-10-01

    Full Text Available Anti-angiogenic agents are biological drugs used for treatment of retinal neovascular degenerative diseases. In this study, we aimed at in-silico analysis of interaction of vascular endothelial growth factor A (VEGFA, the main mediator of angiogenesis, with binding domains of anti-angiogenic agents used for treatment of retinal diseases, such as ranibizumab, bevacizumab and aflibercept. The analysis of anti-VEGF/VEGFA complexes was carried out by means of protein-protein docking and molecular dynamics (MD coupled to molecular mechanics-Poisson Boltzmann Surface Area (MM-PBSA calculation. Molecular dynamics simulation was further analyzed by protein contact networks. Rough energetic evaluation with protein-protein docking scores revealed that aflibercept/VEGFA complex was characterized by electrostatic stabilization, whereas ranibizumab and bevacizumab complexes were stabilized by Van der Waals (VdW energy term; these results were confirmed by MM-PBSA. Comparison of MM-PBSA predicted energy terms with experimental binding parameters reported in literature indicated that the high association rate (Kon of aflibercept to VEGFA was consistent with high stabilizing electrostatic energy. On the other hand, the relatively low experimental dissociation rate (Koff of ranibizumab may be attributed to lower conformational fluctuations of the ranibizumab/VEGFA complex, higher number of contacts and hydrogen bonds in comparison to bevacizumab and aflibercept. Thus, the anti-angiogenic agents have been found to be considerably different both in terms of molecular interactions and stabilizing energy. Characterization of such features can improve the design of novel biological drugs potentially useful in clinical practice.

  3. Computational study of molecular electrostatic potential, docking and dynamics simulations of gallic acid derivatives as ABL inhibitors.

    Science.gov (United States)

    Raghi, K R; Sherin, D R; Saumya, M J; Arun, P S; Sobha, V N; Manojkumar, T K

    2018-04-05

    Chronic myeloid leukemia (CML), a hematological malignancy arises due to the spontaneous fusion of the BCR and ABL gene, resulting in a constitutively active tyrosine kinase (BCR-ABL). Pharmacological activity of Gallic acid and 1,3,4-Oxadiazole as potential inhibitors of ABL kinase has already been reported. Objective of this study is to evaluate the ABL kinase inhibitory activity of derivatives of Gallic acid fused with 1,3,4-Oxadiazole moieties. Attempts have been made to identify the key structural features responsible for drug likeness of the Gallic acid and the 1,3,4-Oxadiazole ring using molecular electrostatic potential maps (MESP). To investigate the inhibitory activity of Gallic acid derivatives towards the ABL receptor, we have applied molecular docking and molecular dynamics (MD) simulation approaches. A comparative study was performed using Bosutinib as the standard which is an approved CML drug acting on the same receptor. Furthermore, the novel compounds designed and reported here in were evaluated for ADME properties and the results indicate that they show acceptable pharmacokinetic properties. Accordingly these compounds are predicted to be drug like with low toxicity potential. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Catalytic NH3 Synthesis using N2 /H2 at Molecular Transition Metal Complexes: Concepts for Lead Structure Determination using Computational Chemistry.

    Science.gov (United States)

    Hölscher, Markus; Leitner, Walter

    2017-09-07

    While industrial NH 3 synthesis based on the Haber-Bosch-process was invented more than a century ago, there is still no molecular catalyst available which reduces N 2 in the reaction system N 2 /H 2 to NH 3 . As the many efforts of experimentally working research groups to develop a molecular catalyst for NH 3 synthesis from N 2 /H 2 have led to a variety of stoichiometric reductions it seems justified to undertake the attempt of systematizing the various approaches of how the N 2 molecule might be reduced to NH 3 with H 2 at a transition metal complex. In this contribution therefore a variety of intuition-based concepts are presented with the intention to show how the problem can be approached. While no claim for completeness is made, these concepts intend to generate a working plan for future research. Beyond this, it is suggested that these concepts should be evaluated with regard to experimental feasibility by checking barrier heights of single reaction steps and also by computation of whole catalytic cycles employing density functional theory (DFT) calculations. This serves as a tool which extends the empirically driven search process and expands it by computed insights which can be used to rationalize the various challenges which must be met. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. PopSc: Computing Toolkit for Basic Statistics of Molecular Population Genetics Simultaneously Implemented in Web-Based Calculator, Python and R.

    Directory of Open Access Journals (Sweden)

    Shi-Yi Chen

    Full Text Available Although various computer tools have been elaborately developed to calculate a series of statistics in molecular population genetics for both small- and large-scale DNA data, there is no efficient and easy-to-use toolkit available yet for exclusively focusing on the steps of mathematical calculation. Here, we present PopSc, a bioinformatic toolkit for calculating 45 basic statistics in molecular population genetics, which could be categorized into three classes, including (i genetic diversity of DNA sequences, (ii statistical tests for neutral evolution, and (iii measures of genetic differentiation among populations. In contrast to the existing computer tools, PopSc was designed to directly accept the intermediate metadata, such as allele frequencies, rather than the raw DNA sequences or genotyping results. PopSc is first implemented as the web-based calculator with user-friendly interface, which greatly facilitates the teaching of population genetics in class and also promotes the convenient and straightforward calculation of statistics in research. Additionally, we also provide the Python library and R package of PopSc, which can be flexibly integrated into other advanced bioinformatic packages of population genetics analysis.

  6. PopSc: Computing Toolkit for Basic Statistics of Molecular Population Genetics Simultaneously Implemented in Web-Based Calculator, Python and R.

    Science.gov (United States)

    Chen, Shi-Yi; Deng, Feilong; Huang, Ying; Li, Cao; Liu, Linhai; Jia, Xianbo; Lai, Song-Jia

    2016-01-01

    Although various computer tools have been elaborately developed to calculate a series of statistics in molecular population genetics for both small- and large-scale DNA data, there is no efficient and easy-to-use toolkit available yet for exclusively focusing on the steps of mathematical calculation. Here, we present PopSc, a bioinformatic toolkit for calculating 45 basic statistics in molecular population genetics, which could be categorized into three classes, including (i) genetic diversity of DNA sequences, (ii) statistical tests for neutral evolution, and (iii) measures of genetic differentiation among populations. In contrast to the existing computer tools, PopSc was designed to directly accept the intermediate metadata, such as allele frequencies, rather than the raw DNA sequences or genotyping results. PopSc is first implemented as the web-based calculator with user-friendly interface, which greatly facilitates the teaching of population genetics in class and also promotes the convenient and straightforward calculation of statistics in research. Additionally, we also provide the Python library and R package of PopSc, which can be flexibly integrated into other advanced bioinformatic packages of population genetics analysis.

  7. SCELib3.0: The new revision of SCELib, the parallel computational library of molecular properties in the Single Center Approach

    Science.gov (United States)

    Sanna, N.; Baccarelli, I.; Morelli, G.

    2009-12-01

    SCELib is a computer program which implements the Single Center Expansion (SCE) method to describe molecular electronic densities and the interaction potentials between a charged projectile (electron or positron) and a target molecular system. The first version (CPC Catalog identifier ADMG_v1_0) was submitted to the CPC Program Library in 2000, and version 2.0 (ADMG_v2_0) was submitted in 2004. We here announce the new release 3.0 which presents additional features with respect to the previous versions aiming at a significative enhance of its capabilities to deal with larger molecular systems. SCELib 3.0 allows for ab initio effective core potential (ECP) calculations of the molecular wavefunctions to be used in the SCE method in addition to the standard all-electron description of the molecule. The list of supported architectures has been updated and the code has been ported to platforms based on accelerating coprocessors, such as the NVIDIA GPGPU and the new parallel model adopted is able to efficiently run on a mixed many-core computing system. Program summaryProgram title: SCELib3.0 Catalogue identifier: ADMG_v3_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADMG_v3_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 2 018 862 No. of bytes in distributed program, including test data, etc.: 4 955 014 Distribution format: tar.gz Programming language: C Compilers used: xlc V8.x, Intel C V10.x, Portland Group V7.x, nvcc V2.x Computer: All SMP platforms based on AIX, Linux and SUNOS operating systems over SPARC, POWER, Intel Itanium2, X86, em64t and Opteron processors Operating system: SUNOS, IBM AIX, Linux RedHat (Enterprise), Linux SuSE (SLES) Has the code been vectorized or parallelized?: Yes. 1 to 32 (CPU or GPU) used RAM: Up to 32 GB depending on the molecular

  8. Computer-aided design and synthesis of magnetic molecularly imprinted polymers with high selectivity for the removal of phenol from water.

    Science.gov (United States)

    Yang, Wenming; Liu, Lukuan; Ni, Xiaoni; Zhou, Wei; Huang, Weihong; Liu, Hong; Xu, Wanzhen

    2016-02-01

    A molecular simulation method was introduced to compute the phenol-monomer pre-assembled system of a molecularly imprinted polymer. The interaction type and intensity between phenol and monomer were evaluated by combining binding energy and charge transfer with complex conformation. The simulation results indicate that interaction energies are simultaneously affected by the type of monomer and the ratio between phenol and monomers. At the same time, we considered that by increasing the amount of functional monomer is not always better for preparing molecularly imprinter polymers. In this study, three kinds of novel magnetic phenol-imprinted polymers with favorable specific adsorption effects were prepared by the surface imprinting technique combined with atom transfer radical polymerization. Various measures were selected to characterize the structure and morphology to obtain the optimal polymer. The characterization results show that the optimal polymer has suitable features for further adsorption process. A series of static adsorption experiments were conducted to analyze its adsorption performance, which follows the Elovich model from the kinetic analysis and the Sips equation from the isothermal analysis. To further verify the reliability and accuracy of the simulation results, the effects of different monomers on the adsorption selectivity were also determined. They display higher selectivity towards phenol than 4-nitrophenol.The results from the simulation of the pre-assembled complexes are in reasonable agreement with those from the experiment. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Search for β2 adrenergic receptor ligands by virtual screening via grid computing and investigation of binding modes by docking and molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Qifeng Bai

    Full Text Available We designed a program called MolGridCal that can be used to screen small molecule database in grid computing on basis of JPPF grid environment. Based on MolGridCal program, we proposed an integrated strategy for virtual screening and binding mode investigation by combining molecular docking, molecular dynamics (MD simulations and free energy calculations. To test the effectiveness of MolGridCal, we screened potential ligands for β2 adrenergic receptor (β2AR from a database containing 50,000 small molecules. MolGridCal can not only send tasks to the grid server automatically, but also can distribute tasks using the screensaver function. As for the results of virtual screening, the known agonist BI-167107 of β2AR is ranked among the top 2% of the screened candidates, indicating MolGridCal program can give reasonable results. To further study the binding mode and refine the results of MolGridCal, more accurate docking and scoring methods are used to estimate the binding affinity for the top three molecules (agonist BI-167107, neutral antagonist alprenolol and inverse agonist ICI 118,551. The results indicate agonist BI-167107 has the best binding affinity. MD simulation and free energy calculation are employed to investigate the dynamic interaction mechanism between the ligands and β2AR. The results show that the agonist BI-167107 also has the lowest binding free energy. This study can provide a new way to perform virtual screening effectively through integrating molecular docking based on grid computing, MD simulations and free energy calculations. The source codes of MolGridCal are freely available at http://molgridcal.codeplex.com.

  10. Molecular analogs of the hemihelix: A computational study of chain molecules containing left- and right-handed helices

    Science.gov (United States)

    Pichierri, Fabio

    2014-08-01

    Using density functional theory (DFT) we design two novel chain molecules containing a left-handed (thia)helicene unit connected to a right-handed (thia)helicene unit via a phosphoroussbnd phosphorous (Psbnd P) bond. These chains represent the molecular analogs of the novel hemihelix structure recently discovered by a group of Harvard University scientists. The HOMO and LUMO levels of the heterochiral chains, termed hemihelicenes, are localized on the left- and right-handed blocks, respectively. In contrast, the frontier orbitals of the chains containing homochiral (thia)helicenes connected by a Psbnd P bond are delocalized all over the chain.

  11. Effects of cement organic additives on the adsorption of uranyl ions on calcium silicate hydrate phases: experimental determination and computational molecular modelling

    International Nuclear Information System (INIS)

    Androniuk, Iuliia

    2017-01-01

    Cementitious materials are extensively used in the design and construction of radioactive waste repositories. One of the ways to enhance their performance is to introduce organic admixtures into the cement structure. However, the presence of organics in the pore water may affect the radionuclide mobility: organic molecules can form water-soluble complexes and compete for sorption sites. This work was designed to get detailed understanding of the mechanisms of such interactions on the molecular level. The model system has three components. First, pure C-S-H phases with different Ca/Si ratios were chosen as a cement model. Secondly, gluconate (a simple well-described molecule) is selected as a good starting organic additive model to probe the interaction mechanisms on the molecular scale. A more complex system involving poly-carboxylate super-plasticizer (PCE) was also tested. The third, U(VI), is a representative of the actinide radionuclide series. The development of description of the effects of organics for radioactive waste disposal applications was the primary objective of this work. The study of binary systems provides reference data for the investigation of more complex ternary (C-S-H/organic/U(VI)). The interactions are studied by means of both experimental and computational molecular modelling techniques. Data on sorption and desorption kinetics and isotherms for additives and for U(VI) on C-S-H are acquired in this work. In parallel, atomistic models are developed for the interfaces of interest. Structural, energetic, and dynamic aspects of the sorption processes on surface of cement are quantitatively modeled by molecular dynamics technique. (author)

  12. Computer simulation of different designs of pseudo-random time-of-flight velocity analysers for molecular beam scattering experiments

    International Nuclear Information System (INIS)

    Rotzoll, G.

    1982-01-01

    After a brief summary of the pseudo-random time-of-flight (TOF) method, the design criteria for construction of a pseudo-random TOF disc are considered and complemented by computer simulations. The question of resolution and the choice of the sequence length and number of time channels per element are discussed. Moreover, the stability requirements of the chopper motor frequency are investigated. (author)

  13. Computational revelation of binding mechanisms of inhibitors to endocellular protein tyrosine phosphatase 1B using molecular dynamics simulations.

    Science.gov (United States)

    Yan, Fangfang; Liu, Xinguo; Zhang, Shaolong; Su, Jing; Zhang, Qinggang; Chen, Jianzhong

    2017-11-06

    Endocellular protein tyrosine phosphatase 1B (PTP1B) is one of the most promising target for designing and developing drugs to cure type-II diabetes and obesity. Molecular dynamics (MD) simulations combined with molecular mechanics generalized Born surface area (MM-GBSA) and solvated interaction energy methods were applied to study binding differences of three inhibitors (ID: 901, 941, and 968) to PTP1B, the calculated results show that the inhibitor 901 has the strongest binding ability to PTP1B among the current inhibitors. Principal component (PC) analysis was also carried out to investigate the conformational change of PTP1B, and the results indicate that the associations of inhibitors with PTP1B generate a significant effect on the motion of the WPD-loop. Free energy decomposition method was applied to study the contributions of individual residues to inhibitor bindings, it is found that three inhibitors can generate hydrogen bonding interactions and hydrophobic interactions with different residues of PTP1B, which provide important forces for associations of inhibitors with PTP1B. This research is expected to give a meaningfully theoretical guidance to design and develop of effective drugs curing type-II diabetes and obesity.

  14. Experimental and computational study on molecular structure and vibrational analysis of a modified biomolecule: 5-Bromo-2'-deoxyuridine

    Science.gov (United States)

    Çırak, Çağrı; Sert, Yusuf; Ucun, Fatih

    In the present study, the experimental and theoretical vibrational spectra of 5-bromo-2'-deoxyuridine were investigated. The experimental FT-IR (400-4000 cm-1) and μ-Raman spectra (100-4000 cm-1) of the molecule in the solid phase were recorded. Theoretical vibrational frequencies and geometric parameters (bond lengths and bond angles) were calculated using ab initio Hartree Fock (HF) and density functional B3LYP method with 6-31G(d), 6-31G(d,p), 6-311++G(d) and 6-311++G(d,p) basis sets by Gaussian program, for the first time. The assignments of vibrational frequencies were performed by potential energy distribution by using VEDA 4 program. The optimized geometric parameters and theoretical vibrational frequencies are compared with the corresponding experimental data and they were seen to be in a good agreement with the each other. Also, the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies were found.

  15. Molecular and Thermodynamic Properties of Zwitterions versus Ionic Liquids: A Comprehensive Computational Analysis to Develop Advanced Separation Processes.

    Science.gov (United States)

    Moreno, Daniel; Gonzalez-Miquel, Maria; Ferro, Victor R; Palomar, Jose

    2018-04-05

    Zwitterion ionic liquids (ZIs) are compounds in which both counterions are covalently tethered, conferring them with unique characteristics; however, most of their properties are still unknown, representing a bottleneck to exploit their practical applications. Herein, the molecular and fluid properties of ZIs and their mixtures were explored by means of quantum chemical analysis based on the density functional theory (DFT) and COSMO-RS method, and compared against homologous ionic liquids (ILs) to provide a comprehensive overview of the effect of the distinct structures on their physicochemical and thermodynamic behavior. Overall, ZIs were revealed as compounds with higher polarity and stronger hydrogen-bonding capacity, implying higher density, viscosity, melting point, and even lower volatility than structurally similar ILs. The phase equilibrium of binary and ternary systems supports stronger attractive interactions between ZIs and polar compounds, whereas higher liquid-liquid immiscibility with nonpolar compounds may be expected. Ultimately, the performance of ZIs in the wider context of separation processes is illustrated, while providing molecular insights to allow their selection and design for relevant applications. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Flurbiprofen–antioxidant mutual prodrugs as safer nonsteroidal anti-inflammatory drugs: synthesis, pharmacological investigation, and computational molecular modeling

    Directory of Open Access Journals (Sweden)

    Ashraf Z

    2016-07-01

    prodrugs at all times of assessment. The results of ulcerogenic activity showed that all prodrugs produced less GI irritation than flurbiprofen. Molecular docking and simulation studies were carried out with cyclooxygenase (COX-1 and COX-2 proteins, and it was observed that our prodrugs have more potential to selectively bind to COX-2 than to COX-1. It is concluded that the synthesized prodrugs have promising pharmacological activities with reduced GI adverse effects than the parent drug. Keywords: flurbiprofen prodrugs, natural antioxidants, molecular docking, molecular dynamic simulation, pharmacological investigation, NSAIDs

  17. Design of a Tablet Computer App for Facilitation of a Molecular Blood Culture Test in Clinical Microbiology and Preliminary Usability Evaluation.

    Science.gov (United States)

    Samson, Lasse L; Pape-Haugaard, Louise; Meltzer, Michelle C; Fuchs, Martin; Schønheyder, Henrik C; Hejlesen, Ole

    2016-03-18

    User mobility is an important aspect of the development of clinical information systems for health care professionals. Mobile phones and tablet computers have obtained widespread use by health care professionals, offering an opportunity for supporting the access to patient information through specialized applications (apps) while supporting the mobility of the users. The use of apps for mobile phones and tablet computers may support workflow of complex tasks, for example, molecular-based diagnostic tests in clinical microbiology. Multiplex Blood Culture Test (MuxBCT) is a molecular-based diagnostic test used for rapid identification of pathogens in positive blood cultures. To facilitate the workflow of the MuxBCT, a specialized tablet computer app was developed as an accessory to the diagnostic test. The app aims to reduce the complexity of the test by step-by-step guidance of microscopy and to assist users in reaching an exact bacterial or fungal diagnosis based on blood specimen observations and controls. Additionally, the app allows for entry of test results, and communication thereof to the laboratory information system (LIS). The objective of the study was to describe the design considerations of the MuxBCT app and the results of a preliminary usability evaluation. The MuxBCT tablet app was developed and set up for use in a clinical microbiology laboratory. A near-live simulation study was conducted in the clinical microbiology laboratory to evaluate the usability of the MuxBCT app. The study was designed to achieve a high degree of realism as participants carried out a scenario representing the context of use for the MuxBCT app. As the MuxBCT was under development, the scenario involved the use of molecular blood culture tests similar to the MuxBCT for identification of microorganisms from positive blood culture samples. The study participants were observed, and their interactions with the app were recorded. After the study, the participants were debriefed to

  18. Biologically important conformational features of DNA as interpreted by quantum mechanics and molecular mechanics computations of its simple fragments.

    Science.gov (United States)

    Poltev, V; Anisimov, V M; Dominguez, V; Gonzalez, E; Deriabina, A; Garcia, D; Rivas, F; Polteva, N A

    2018-02-01

    Deciphering the mechanism of functioning of DNA as the carrier of genetic information requires identifying inherent factors determining its structure and function. Following this path, our previous DFT studies attributed the origin of unique conformational characteristics of right-handed Watson-Crick duplexes (WCDs) to the conformational profile of deoxydinucleoside monophosphates (dDMPs) serving as the minimal repeating units of DNA strand. According to those findings, the directionality of the sugar-phosphate chain and the characteristic ranges of dihedral angles of energy minima combined with the geometric differences between purines and pyrimidines determine the dependence on base sequence of the three-dimensional (3D) structure of WCDs. This work extends our computational study to complementary deoxydinucleotide-monophosphates (cdDMPs) of non-standard conformation, including those of Z-family, Hoogsteen duplexes, parallel-stranded structures, and duplexes with mispaired bases. For most of these systems, except Z-conformation, computations closely reproduce experimental data within the tolerance of characteristic limits of dihedral parameters for each conformation family. Computation of cdDMPs with Z-conformation reveals that their experimental structures do not correspond to the internal energy minimum. This finding establishes the leading role of external factors in formation of the Z-conformation. Energy minima of cdDMPs of non-Watson-Crick duplexes demonstrate different sequence-dependence features than those known for WCDs. The obtained results provide evidence that the biologically important regularities of 3D structure distinguish WCDs from duplexes having non-Watson-Crick nucleotide pairing.

  19. Inferring Population Size History from Large Samples of Genome-Wide Molecular Data - An Approximate Bayesian Computation Approach.

    Directory of Open Access Journals (Sweden)

    Simon Boitard

    2016-03-01

    Full Text Available Inferring the ancestral dynamics of effective population size is a long-standing question in population genetics, which can now be tackled much more accurately thanks to the massive genomic data available in many species. Several promising methods that take advantage of whole-genome sequences have been recently developed in this context. However, they can only be applied to rather small samples, which limits their ability to estimate recent population size history. Besides, they can be very sensitive to sequencing or phasing errors. Here we introduce a new approximate Bayesian computation approach named PopSizeABC that allows estimating the evolution of the effective population size through time, using a large sample of complete genomes. This sample is summarized using the folded allele frequency spectrum and the average zygotic linkage disequilibrium at different bins of physical distance, two classes of statistics that are widely used in population genetics and can be easily computed from unphased and unpolarized SNP data. Our approach provides accurate estimations of past population sizes, from the very first generations before present back to the expected time to the most recent common ancestor of the sample, as shown by simulations under a wide range of demographic scenarios. When applied to samples of 15 or 25 complete genomes in four cattle breeds (Angus, Fleckvieh, Holstein and Jersey, PopSizeABC revealed a series of population declines, related to historical events such as domestication or modern breed creation. We further highlight that our approach is robust to sequencing errors, provided summary statistics are computed from SNPs with common alleles.

  20. Exploring the potential of fulvalene dimetals as platforms for molecular solar thermal energy storage: computations, syntheses, structures, kinetics, and catalysis.

    Science.gov (United States)

    Börjesson, Karl; Ćoso, Dušan; Gray, Victor; Grossman, Jeffrey C; Guan, Jingqi; Harris, Charles B; Hertkorn, Norbert; Hou, Zongrui; Kanai, Yosuke; Lee, Donghwa; Lomont, Justin P; Majumdar, Arun; Meier, Steven K; Moth-Poulsen, Kasper; Myrabo, Randy L; Nguyen, Son C; Segalman, Rachel A; Srinivasan, Varadharajan; Tolman, Willam B; Vinokurov, Nikolai; Vollhardt, K Peter C; Weidman, Timothy W

    2014-11-17

    A study of the scope and limitations of varying the ligand framework around the dinuclear core of FvRu2 in its function as a molecular solar thermal energy storage framework is presented. It includes DFT calculations probing the effect of substituents, other metals, and CO exchange for other ligands on ΔHstorage . Experimentally, the system is shown to be robust in as much as it tolerates a number of variations, except for the identity of the metal and certain substitution patterns. Failures include 1,1',3,3'-tetra-tert-butyl (4), 1,2,2',3'-tetraphenyl (9), diiron (28), diosmium (24), mixed iron-ruthenium (27), dimolybdenum (29), and ditungsten (30) derivatives. An extensive screen of potential catalysts for the thermal reversal identified AgNO3 -SiO2 as a good candidate, although catalyst decomposition remains a challenge. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. FT-IR, FT-Raman, and DFT computational studies of melaminium nitrate molecular-ionic crystal

    Science.gov (United States)

    Tanak, Hasan; Marchewka, Mariusz K.

    2013-02-01

    The experimental and theoretical vibrational spectra of melaminium nitrate were studied. The Raman and infrared (FT-IR) spectra of the melaminium nitrate and its deuterated analogue were recorded in the solid phase. Molecular geometry and vibrational frequency values of melaminium nitrate in the electronic ground state were calculated using the density functional method (B3LYP) with the 6-31++G(d,p) basis set. The calculated results show that the optimized geometry can well reproduce the crystal structure, and the theoretical vibrational frequency values show good agreement with experimental values. The NBO analysis reveals that the N-H···O and N-H···N intermolecular interactions significantly influence crystal packing in this molecule.

  2. Computational Immunology Meets Bioinformatics: The Use of Prediction Tools for Molecular Binding in the Simulation of the Immune System

    DEFF Research Database (Denmark)

    Rapin, N.; Lund, Ole; Bernaschi, M.

    2010-01-01

    potential measurements, for assessing molecular binding in the context of immune complexes. We benchmark the resulting model by simulating a classical immunization experiment that reproduces the development of immune memory. We also investigate the role of major histocompatibility complex (MHC) haplotype...... proliferate more than any other. These results show that the simulator produces dynamics that are stable and consistent with basic immunological knowledge. We believe that the combination of genomic information and simulation of the dynamics of the immune system, in one single tool, can offer new perspectives......We present a new approach to the study of the immune system that combines techniques of systems biology with information provided by data-driven prediction methods. To this end, we have extended an agent-based simulator of the immune response, C-IMMSIM, such that it represents pathogens, as well...

  3. Computational design of new molecular scaffolds for medicinal chemistry, part II: generalization of analog series-based scaffolds

    Science.gov (United States)

    Dimova, Dilyana; Stumpfe, Dagmar; Bajorath, Jürgen

    2018-01-01

    Aim: Extending and generalizing the computational concept of analog series-based (ASB) scaffolds. Materials & methods: Methodological modifications were introduced to further increase the coverage of analog series (ASs) and compounds by ASB scaffolds. From bioactive compounds, ASs were systematically extracted and second-generation ASB scaffolds isolated. Results: More than 20,000 second-generation ASB scaffolds with single or multiple substitution sites were extracted from active compounds, achieving more than 90% coverage of ASs. Conclusion: Generalization of the ASB scaffold approach has yielded a large knowledge base of scaffold-capturing compound series and target information. PMID:29379641

  4. Molecular interaction of 2,4-diacetylphloroglucinol (DAPG) with human serum albumin (HSA): The spectroscopic, calorimetric and computational investigation

    Science.gov (United States)

    Pragna Lakshmi, T.; Mondal, Moumita; Ramadas, Krishna; Natarajan, Sakthivel

    2017-08-01

    Drug molecule interaction with human serum albumin (HSA) affects the distribution and elimination of the drug. The compound, 2,4-diacetylphloroglucinol (DAPG) has been known for its antimicrobial, antiviral, antihelminthic and anticancer properties. However, its interaction with HSA is not yet reported. In this study, the interaction between HSA and DAPG was investigated through steady-state fluorescence, time-resolved fluorescence (TRF), circular dichroism (CD), Fourier transform infrared (FT-IR) spectroscopy, isothermal titration calorimetry (ITC), molecular docking and molecular dynamics simulation (MDS). Fluorescence spectroscopy results showed the strong quenching of intrinsic fluorescence of HSA due to interaction with DAPG, through dynamic quenching mechanism. The compound bound to HSA with reversible and moderate affinity which explained its easy diffusion from circulatory system to target tissue. The thermodynamic parameters from fluorescence spectroscopic data clearly revealed the contribution of hydrophobic forces but, the role of hydrogen bonds was not negligible according to the ITC studies. The interaction was exothermic and spontaneous in nature. Binding with DAPG reduced the helical content of protein suggesting the unfolding of HSA. Site marker fluorescence experiments revealed the change in binding constant of DAPG in the presence of site I (warfarin) but not site II marker (ibuprofen) which confirmed that the DAPG bound to site I. ITC experiments also supported this as site I marker could not bind to HSA-DAPG complex while site II marker was accommodated in the complex. In silico studies further showed the lowest binding affinity and more stability of DAPG in site I than in site II. Thus the data presented in this study confirms the binding of DAPG to the site I of HSA which may help in further understanding of pharmacokinetic properties of DAPG.

  5. Computing the non-Markovian coarse-grained interactions derived from the Mori-Zwanzig formalism in molecular systems: Application to polymer melts

    Science.gov (United States)

    Li, Zhen; Lee, Hee Sun; Darve, Eric; Karniadakis, George Em

    2017-01-01

    Memory effects are often introduced during coarse-graining of a complex dynamical system. In particular, a generalized Langevin equation (GLE) for the coarse-grained (CG) system arises in the context of Mori-Zwanzig formalism. Upon a pairwise decomposition, GLE can be reformulated into its pairwise version, i.e., non-Markovian dissipative particle dynamics (DPD). GLE models the dynamics of a single coarse particle, while DPD considers the dynamics of many interacting CG particles, with both CG systems governed by non-Markovian interactions. We compare two different methods for the practical implementation of the non-Markovian interactions in GLE and DPD systems. More specifically, a direct evaluation of the non-Markovian (NM) terms is performed in LE-NM and DPD-NM models, which requires the storage of historical information that significantly increases computational complexity. Alternatively, we use a few auxiliary variables in LE-AUX and DPD-AUX models to replace the non-Markovian dynamics with a Markovian dynamics in a higher dimensional space, leading to a much reduced memory footprint and computational cost. In our numerical benchmarks, the GLE and non-Markovian DPD models are constructed from molecular dynamics (MD) simulations of star-polymer melts. Results show that a Markovian dynamics with auxiliary variables successfully generates equivalent non-Markovian dynamics consistent with the reference MD system, while maintaining a tractable computational cost. Also, transient subdiffusion of the star-polymers observed in the MD system can be reproduced by the coarse-grained models. The non-interacting particle models, LE-NM/AUX, are computationally much cheaper than the interacting particle models, DPD-NM/AUX. However, the pairwise models with momentum conservation are more appropriate for correctly reproducing the long-time hydrodynamics characterised by an algebraic decay in the velocity autocorrelation function.

  6. A supermolecular curcumin for enhanced antiproliferative and proapoptotic activities: molecular characteristics, computer modeling and in vivo pharmacokinetics

    International Nuclear Information System (INIS)

    Tan Qunyou; Wu Jianyong; Li Yi; Zhang Jingqing; Mei Hu; Zhao Chunjing

    2013-01-01

    The supermolecular curcumin (SMCCM) exhibiting remarkably improved solubility and release characteristics was fabricated to increase the oral bioavailability in rat as well as the antiproliferative and proapoptotic activities of curcumin (CCM) against human lung adenocarcinoma cell A549. SMCCM was characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, morphology and structure, aqueous solubility, and release behavior in vitro. Computer modeling of the supermolecular structure was performed. The pharmacokinetics, antiproliferative and proapoptotic activities of SMCCM were evaluated. The mechanisms by which SMCCM inhibited proliferation and induced apoptosis were identified. The formation of SMCCM was testified and the supermolecular structure was studied by a computer modeling technique. Compared to free CCM, SMCCM with much higher aqueous solubility exhibited obviously enhanced release and more favorable pharmacokinetic profiles, and, furthermore, SMCCM showed higher anticancer efficacy, enhanced induction of G2/M-phase arrest and apoptosis in A549 cells, which might be involved with the increases in reactive oxygen species production and intracellular Ca 2+ accumulation, and a decrease in mitochondrial membrane potential. SMCCM remarkably enhanced not only the oral bioavailability but also the antiproliferative and proapoptotic activities of CCM along with improved solubility and release characteristics of CCM. (paper)

  7. A supermolecular curcumin for enhanced antiproliferative and proapoptotic activities: molecular characteristics, computer modeling and in vivo pharmacokinetics

    Science.gov (United States)

    Tan, Qunyou; Wu, Jianyong; Li, Yi; Mei, Hu; Zhao, Chunjing; Zhang, Jingqing

    2013-01-01

    The supermolecular curcumin (SMCCM) exhibiting remarkably improved solubility and release characteristics was fabricated to increase the oral bioavailability in rat as well as the antiproliferative and proapoptotic activities of curcumin (CCM) against human lung adenocarcinoma cell A549. SMCCM was characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, morphology and structure, aqueous solubility, and release behavior in vitro. Computer modeling of the supermolecular structure was performed. The pharmacokinetics, antiproliferative and proapoptotic activities of SMCCM were evaluated. The mechanisms by which SMCCM inhibited proliferation and induced apoptosis were identified. The formation of SMCCM was testified and the supermolecular structure was studied by a computer modeling technique. Compared to free CCM, SMCCM with much higher aqueous solubility exhibited obviously enhanced release and more favorable pharmacokinetic profiles, and, furthermore, SMCCM showed higher anticancer efficacy, enhanced induction of G2/M-phase arrest and apoptosis in A549 cells, which might be involved with the increases in reactive oxygen species production and intracellular Ca2+ accumulation, and a decrease in mitochondrial membrane potential. SMCCM remarkably enhanced not only the oral bioavailability but also the antiproliferative and proapoptotic activities of CCM along with improved solubility and release characteristics of CCM.

  8. Multi-scale multi-physics computational chemistry simulation based on ultra-accelerated quantum chemical molecular dynamics method for structural materials in boiling water reactor

    International Nuclear Information System (INIS)

    Miyamoto, Akira; Sato, Etsuko; Sato, Ryo; Inaba, Kenji; Hatakeyama, Nozomu

    2014-01-01

    In collaboration with experimental experts we have reported in the present conference (Hatakeyama, N. et al., “Experiment-integrated multi-scale, multi-physics computational chemistry simulation applied to corrosion behaviour of BWR structural materials”) the results of multi-scale multi-physics computational chemistry simulations applied to the corrosion behaviour of BWR structural materials. In macro-scale, a macroscopic simulator of anode polarization curve was developed to solve the spatially one-dimensional electrochemical equations on the material surface in continuum level in order to understand the corrosion behaviour of typical BWR structural material, SUS304. The experimental anode polarization behaviours of each pure metal were reproduced by fitting all the rates of electrochemical reactions and then the anode polarization curve of SUS304 was calculated by using the same parameters and found to reproduce the experimental behaviour successfully. In meso-scale, a kinetic Monte Carlo (KMC) simulator was applied to an actual-time simulation of the morphological corrosion behaviour under the influence of an applied voltage. In micro-scale, an ultra-accelerated quantum chemical molecular dynamics (UA-QCMD) code was applied to various metallic oxide surfaces of Fe 2 O 3 , Fe 3 O 4 , Cr 2 O 3 modelled as same as water molecules and dissolved metallic ions on the surfaces, then the dissolution and segregation behaviours were successfully simulated dynamically by using UA-QCMD. In this paper we describe details of the multi-scale, multi-physics computational chemistry method especially the UA-QCMD method. This method is approximately 10,000,000 times faster than conventional first-principles molecular dynamics methods based on density-functional theory (DFT), and the accuracy was also validated for various metals and metal oxides compared with DFT results. To assure multi-scale multi-physics computational chemistry simulation based on the UA-QCMD method for

  9. Imaging of pharmacokinetic rates of indocyanine green in mouse liver with a hybrid fluorescence molecular tomography/x-ray computed tomography system.

    Science.gov (United States)

    Zhang, Guanglei; Liu, Fei; Zhang, Bin; He, Yun; Luo, Jianwen; Bai, Jing

    2013-04-01

    Pharmacokinetic rates have the potential to provide quantitative physiological and pathological information for biological studies and drug development. Fluorescence molecular tomography (FMT) is an attractive imaging tool for three-dimensionally resolving fluorophore distribution in small animals. In this letter, pharmacokinetic rates of indocyanine green (ICG) in mouse liver are imaged with a hybrid FMT and x-ray computed tomography (XCT) system. A recently developed FMT method using structural priors from an XCT system is adopted to improve the quality of FMT reconstruction. In the in vivo experiments, images of uptake and excretion rates of ICG in mouse liver are obtained, which can be used to quantitatively evaluate liver function. The accuracy of the results is validated by a fiber-based fluorescence measurement system.

  10. The fundamentals behind solving for unknown molecular structures using computer-assisted structure elucidation: a free software package at the undergraduate and graduate levels.

    Science.gov (United States)

    Moser, Arvin; Pautler, Brent G

    2016-05-15

    The successful elucidation of an unknown compound's molecular structure often requires an analyst with profound knowledge and experience of advanced spectroscopic techniques, such as Nuclear Magnetic Resonance (NMR) spectroscopy and mass spectrometry. The implementation of Computer-Assisted Structure Elucidation (CASE) software in solving for unknown structures, such as isolated natural products and/or reaction impurities, can serve both as elucidation and teaching tools. As such, the introduction of CASE software with 112 exercises to train students in conjunction with the traditional pen and paper approach will strengthen their overall understanding of solving unknowns and explore of various structural end points to determine the validity of the results quickly. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  11. Computational study of the activity, dynamics, energetics and conformations of insulin analogues using molecular dynamics simulations: Application to hyperinsulinemia and the critical residue B26

    Directory of Open Access Journals (Sweden)

    Anastasios Papaioannou

    2017-09-01

    Full Text Available Due to the increasing prevalence of diabetes, finding therapeutic analogues for insulin has become an urgent issue. While many experimental studies have been performed towards this end, they have limited scope to examine all aspects of the effect of a mutation. Computational studies can help to overcome these limitations, however, relatively few studies that focus on insulin analogues have been performed to date. Here, we present a comprehensive computational study of insulin analogues—three mutant insulins that have been identified with hyperinsulinemia and three mutations on the critical B26 residue that exhibit similar binding affinity to the insulin receptor—using molecular dynamics simulations with the aim of predicting how mutations of insulin affect its activity, dynamics, energetics and conformations. The time evolution of the conformers is studied in long simulations. The probability density function and potential of mean force calculations are performed on each insulin analogue to unravel the effect of mutations on the dynamics and energetics of insulin activation. Our conformational study can decrypt the key features and molecular mechanisms that are responsible for an enhanced or reduced activity of an insulin analogue. We find two key results: 1 hyperinsulinemia may be due to the drastically reduced activity (and binding affinity of the mutant insulins. 2 Y26BS and Y26BE are promising therapeutic candidates for insulin as they are more active than WT-insulin. The analysis in this work can be readily applied to any set of mutations on insulin to guide development of more effective therapeutic analogues.

  12. Performance dependence of hybrid x-ray computed tomography/fluorescence molecular tomography on the optical forward problem.

    Science.gov (United States)

    Hyde, Damon; Schulz, Ralf; Brooks, Dana; Miller, Eric; Ntziachristos, Vasilis

    2009-04-01

    Hybrid imaging systems combining x-ray computed tomography (CT) and fluorescence tomography can improve fluorescence imaging performance by incorporating anatomical x-ray CT information into the optical inversion problem. While the use of image priors has been investigated in the past, little is known about the optimal use of forward photon propagation models in hybrid optical systems. In this paper, we explore the impact on reconstruction accuracy of the use of propagation models of varying complexity, specifically in the context of these hybrid imaging systems where significant structural information is known a priori. Our results demonstrate that the use of generically known parameters provides near optimal performance, even when parameter mismatch remains.

  13. Computational analysis of the effect of surface roughness on the deflection of gold coated silicon micro-cantilevers due to molecular adsorption

    Science.gov (United States)

    Hayden, Victor

    In this work numerical simulations were performed in order to study the effects of surface roughness on the deflection of gold coated silicon cantilevers due to molecular adsorption. The cantilever was modeled using a ball and spring system where the spring constants for the Si-Si, Si-Au, and Au-Au bonds were obtained from first principal calculations. The molecular adsorption process was simulated by elongating the natural bond length at available bonding sites chosen randomly on the cantilever. Increasing the bond length created a surface stress on the cantilever causing it to deflect. In all cases the structure refinement was performed by minimizing the energy of the system using a simulated annealing algorithm and a high quality random number generator called Mersenne Twister. The system studied consisted of a 1 micrometer by 1 micrometer portion of a cantilever of various surface roughnesses with variable boundary condition and was processed in parallel on the ACEnet (Atlantic Computational Excellence Network) cluster. The results have indicated that cantilevers with a rougher gold surface deflected more than those with a smoother surface. The increase in deflection is attributed to an increase in stress raisers in the gold film localized around the surface features. The onset of stress raisers increases the differential stress between the top and bottom surfaces and results in an increase in the deflection of the cantilever.

  14. Explicit Hilbert-space representations of atomic and molecular photoabsorption spectra: Computational studies of Stieltjes-Tchebycheff functions

    International Nuclear Information System (INIS)

    Hermann, M.R.; Langhoff, P.W.

    1983-01-01

    Explicit Hilbert-space techniques are reported for construction of the discrete and continuum Schroedinger states required in atomic and molecular photoexcitation and/or photoionization studies. These developments extend and clarify previously described moment-theory methods for determinations of photoabsorption cross sections from discrete basis-set calculations to include explicit construction of underlying wave functions. The appropriate Stieltjes-Tchebycheff excitation and ionization functions of nth order are defined as Radau-type eigenstates of an appropriate operator in an n-term Cauchy-Lanczos basis. The energies of these states are the Radau quadrature points of the photoabsorption cross section, and their (reciprocal) norms provide the corresponding quadrature weights. Although finite-order Stieltjes-Tchebycheff functions are L 2 integrable, and do not have asymptotic spatial tails in the continuous spectrum, the Radau quadrature weights nevertheless provide information for normalization in the conventional Dirac delta-function sense. Since one Radau point can be placed anywhere in the spectrum, appropriately normalized convergent approximations to any of the discrete or continuum Schroedinger states are obtained from the development. Connections with matrix partitioning methods are established, demonstrating that nth-order Stieltjes-Tchebycheff functions are optical-potential solutions of the matrix Schroedinger equation in the full Cauchy-Lanczos basis

  15. Flurbiprofen–antioxidant mutual prodrugs as safer nonsteroidal anti-inflammatory drugs: synthesis, pharmacological investigation, and computational molecular modeling

    Science.gov (United States)

    Ashraf, Zaman; Alamgeer; Kanwal, Munazza; Hassan, Mubashir; Abdullah, Sahar; Waheed, Mamuna; Ahsan, Haseeb; Kim, Song Ja

    2016-01-01

    Flurbiprofen–antioxidant mutual prodrugs were synthesized to reduce the gastrointestinal (GI) effects associated with flurbiprofen. For reducing the GI toxicity, the free carboxylic group (–COOH) was temporarily masked by esterification with phenolic –OH of natural antioxidants vanillin, thymol, umbelliferone, and sesamol. The in vitro hydrolysis of synthesized prodrugs showed that they were stable in buffer solution at pH 1.2, indicating their stability in the stomach. The synthesized prodrugs undergo significant hydrolysis in 80% human plasma and thus release free flurbiprofen. The minimum reversion was observed at pH 1.2, suggesting that prodrugs are less irritating to the stomach than flurbiprofen. The anti-inflammatory, analgesic, antipyretic, and ulcerogenic activities of prodrugs were evaluated. All the synthesized prodrugs significantly (Pflurbiprofen showed 69% inhibition. Antipyretic activity was investigated using brewer’s yeast-induced pyrexia model, and significant (Pflurbiprofen. Molecular docking and simulation studies were carried out with cyclooxygenase (COX-1 and COX-2) proteins, and it was observed that our prodrugs have more potential to selectively bind to COX-2 than to COX-1. It is concluded that the synthesized prodrugs have promising pharmacological activities with reduced GI adverse effects than the parent drug. PMID:27555750

  16. Flurbiprofen-antioxidant mutual prodrugs as safer nonsteroidal anti-inflammatory drugs: synthesis, pharmacological investigation, and computational molecular modeling.

    Science.gov (United States)

    Ashraf, Zaman; Alamgeer; Kanwal, Munazza; Hassan, Mubashir; Abdullah, Sahar; Waheed, Mamuna; Ahsan, Haseeb; Kim, Song Ja

    2016-01-01

    Flurbiprofen-antioxidant mutual prodrugs were synthesized to reduce the gastrointestinal (GI) effects associated with flurbiprofen. For reducing the GI toxicity, the free carboxylic group (-COOH) was temporarily masked by esterification with phenolic -OH of natural antioxidants vanillin, thymol, umbelliferone, and sesamol. The in vitro hydrolysis of synthesized prodrugs showed that they were stable in buffer solution at pH 1.2, indicating their stability in the stomach. The synthesized prodrugs undergo significant hydrolysis in 80% human plasma and thus release free flurbiprofen. The minimum reversion was observed at pH 1.2, suggesting that prodrugs are less irritating to the stomach than flurbiprofen. The anti-inflammatory, analgesic, antipyretic, and ulcerogenic activities of prodrugs were evaluated. All the synthesized prodrugs significantly (Pflurbiprofen showed 69% inhibition. Antipyretic activity was investigated using brewer's yeast-induced pyrexia model, and significant (Pflurbiprofen. Molecular docking and simulation studies were carried out with cyclooxygenase (COX-1 and COX-2) proteins, and it was observed that our prodrugs have more potential to selectively bind to COX-2 than to COX-1. It is concluded that the synthesized prodrugs have promising pharmacological activities with reduced GI adverse effects than the parent drug.

  17. Molecular Origin of Gerstmann-Str ussler-Scheinker Syndrome: Insight from Computer Simulation of an Amyloidogenic Prion Peptide

    Energy Technology Data Exchange (ETDEWEB)

    Diadone, Isabella [University of L' Aquila, L' Aquila, Italy; DiNola, Alfredo [University of Rome; Smith, Jeremy C [ORNL

    2011-01-01

    Prion proteins become pathogenic through misfolding. Here, we characterize the folding of a peptide consisting of residues 109 122 of the Syrian hamster prion protein (the H1 peptide) and of a more amyloidogenic A117V point mutant that leads in humans to an inheritable form of the Gerstmann-Straeussler-Scheinker syndrome. Atomistic molecular dynamics simulations are performed for 2.5 s. Both peptides lose their -helical starting conformations and assume a -hairpin that is structurally similar in both systems. In each simulation several unfolding/refolding events occur, leading to convergence of the thermodynamics of the conformational states to within 1 kJ/mol. The similar stability of the -hairpin relative to the unfolded state is observed in the two peptides. However, substantial differences are found between the two unfolded states. A local minimum is found within the free energy unfolded basin of the A117V mutant populated by misfolded collapsed conformations of comparable stability to the -hairpin state, consistent with increased amyloidogenicity. This population, in which V117 stabilizes a hydrophobic core, is absent in the wild-type peptide. These results are supported by simulations of oligomers showing a slightly higher stability of the associated structures and a lower barrier to association for the mutated peptide. Hence, a single point mutation carrying only two additional methyl groups is here shown to be responsible for rather dramatic differences of structuring within the unfolded (misfolded) state.

  18. [Interactions of DNA bases with individual water molecules. Molecular mechanics and quantum mechanics computation results vs. experimental data].

    Science.gov (United States)

    Gonzalez, E; Lino, J; Deriabina, A; Herrera, J N F; Poltev, V I

    2013-01-01

    To elucidate details of the DNA-water interactions we performed the calculations and systemaitic search for minima of interaction energy of the systems consisting of one of DNA bases and one or two water molecules. The results of calculations using two force fields of molecular mechanics (MM) and correlated ab initio method MP2/6-31G(d, p) of quantum mechanics (QM) have been compared with one another and with experimental data. The calculations demonstrated a qualitative agreement between geometry characteristics of the most of local energy minima obtained via different methods. The deepest minima revealed by MM and QM methods correspond to water molecule position between two neighbor hydrophilic centers of the base and to the formation by water molecule of hydrogen bonds with them. Nevertheless, the relative depth of some minima and peculiarities of mutual water-base positions in' these minima depend on the method used. The analysis revealed insignificance of some differences in the results of calculations performed via different methods and the importance of other ones for the description of DNA hydration. The calculations via MM methods enable us to reproduce quantitatively all the experimental data on the enthalpies of complex formation of single water molecule with the set of mono-, di-, and trimethylated bases, as well as on water molecule locations near base hydrophilic atoms in the crystals of DNA duplex fragments, while some of these data cannot be rationalized by QM calculations.

  19. The origin of the cooperativity in the streptavidin-biotin system: A computational investigation through molecular dynamics simulations

    Science.gov (United States)

    Liu, Fengjiao; Zhang, John Z. H.; Mei, Ye

    2016-06-01

    Previous experimental study measuring the binding affinities of biotin to the wild type streptavidin (WT) and three mutants (S45A, D128A and S45A/D128A double mutant) has shown that the loss of binding affinity from the double mutation is larger than the direct sum of those from two single mutations. The origin of this cooperativity has been investigated in this work through molecular dynamics simulations and the end-state free energy method using the polarized protein-specific charge. The results show that this cooperativity comes from both the enthalpy and entropy contributions. The former contribution mainly comes from the alternations of solvation free energy. Decomposition analysis shows that the mutated residues nearly have no contributions to the cooperativity. Instead, N49 and S88, which are located at the entry of the binding pocket and interact with the carboxyl group of biotin, make the dominant contribution among all the residues in the first binding shell around biotin.

  20. Computing UV/vis spectra using a combined molecular dynamics and quantum chemistry approach: bis-triazin-pyridine (BTP) ligands studied in solution.

    Science.gov (United States)

    Höfener, Sebastian; Trumm, Michael; Koke, Carsten; Heuser, Johannes; Ekström, Ulf; Skerencak-Frech, Andrej; Schimmelpfennig, Bernd; Panak, Petra J

    2016-03-21

    We report a combined computational and experimental study to investigate the UV/vis spectra of 2,6-bis(5,6-dialkyl-1,2,4-triazin-3-yl)pyridine (BTP) ligands in solution. In order to study molecules in solution using theoretical methods, force-field parameters for the ligand-water interaction are adjusted to ab initio quantum chemical calculations. Based on these parameters, molecular dynamics (MD) simulations are carried out from which snapshots are extracted as input to quantum chemical excitation-energy calculations to obtain UV/vis spectra of BTP ligands in solution using time-dependent density functional theory (TDDFT) employing the Tamm-Dancoff approximation (TDA). The range-separated CAM-B3LYP functional is used to avoid large errors for charge-transfer states occurring in the electronic spectra. In order to study environment effects with theoretical methods, the frozen-density embedding scheme is applied. This computational procedure allows to obtain electronic spectra calculated at the (range-separated) DFT level of theory in solution, revealing solvatochromic shifts upon solvation of up to about 0.6 eV. Comparison to experimental data shows a significantly improved agreement compared to vacuum calculations and enables the analysis of relevant excitations for the line shape in solution.

  1. Computational Approaches to the Determination of the Molecular Geometry of Acrolein in its T_1(n,π*) State

    Science.gov (United States)

    McAnally, Michael O.; Hlavacek, Nikolaus C.; Drucker, Stephen

    2012-06-01

    The spectroscopically derived inertial constants for acrolein (propenal) in its T_1(n,π*) state were used to test predictions from a variety of computational methods. One focus was on multiconfigurational methods, such as CASSCF and CASPT2, that are applicable to excited states. We also examined excited-state methods that utilize single reference configurations, including EOM-EE-CCSD and TD-PBE0. Finally, we applied unrestricted ground-state techniques, such as UCCSD(T) and the more economical UPBE0 method, to the T_1(n,π*) excited state under the constraint of C_s symmetry. The unrestricted ground-state methods are applicable because at a planar geometry, the T_1(n,π*) state of acrolein is the lowest-energy state of its spin multiplicity. Each of the above methods was used with a triple zeta quality basis set to optimize the T_1(n,π*) geometry. This procedure resulted in the following sets of inertial constants: Inertial constants (cm-1) of acrolein in its T_1(n,π*) state Method A B C Method A B C CASPT2(6,5) 1.667 0.1491 0.1368 UCCSD(T)^b 1.668 0.1480 0.1360 CASSCF(6,5) 1.667 0.1491 0.1369 UPBE0 1.699 0.1487 0.1367 EOM-EE-CCSD 1.675 0.1507 0.1383 TD-PBE0 1.719 0.1493 0.1374 Experiment^a 1.662 0.1485 0.1363 The two multiconfigurational methods produce the same inertial constants, and those constants agree closely with experiment. However the sets of computed bond lengths differ significantly for the two methods. In the CASSCF calculation, the lengthening of the C=O and C=C bonds and the shortening of the C--C bond are more pronounced than in CASPT2. O. S. Bokareva et al., Int. J. Quant. Chem. {108}, 2719 (2008).

  2. Computational Studies of the Active and Inactive Regulatory Domains of Response Regulator PhoP Using Molecular Dynamics Simulations.

    Science.gov (United States)

    Qing, Xiao-Yu; Steenackers, Hans; Venken, Tom; De Maeyer, Marc; Voet, Arnout

    2017-11-01

    The response regulator PhoP is part of the PhoP/PhoQ two-component system, which is responsible for regulating the expression of multiple genes involved in controlling virulence, biofilm formation, and resistance to antimicrobial peptides. Therefore, modulating the transcriptional function of the PhoP protein is a promising strategy for developing new antimicrobial agents. There is evidence suggesting that phosphorylation-mediated dimerization in the regulatory domain of PhoP is essential for its transcriptional function. Disruption or stabilization of protein-protein interactions at the dimerization interface may inhibit or enhance the expression of PhoP-dependent genes. In this study, we performed molecular dynamics simulations on the active and inactive dimers and monomers of the PhoP regulatory domains, followed by pocket-detecting screenings and a quantitative hot-spot analysis in order to assess the druggability of the protein. Consistent with prior hypothesis, the calculation of the binding free energy shows that phosphorylation enhances dimerization of PhoP. Furthermore, we have identified two different putative binding sites at the dimerization active site (the α4-β5-α5 face) with energetic "hot-spot" areas, which could be used to search for modulators of protein-protein interactions. This study delivers insight into the dynamics and druggability of the dimerization interface of the PhoP regulatory domain, and may serve as a basis for the rational identification of new antimicrobial drugs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Computational molecular spectroscopy of X ˜ 2 Π NCS: Electronic properties and ro-vibrationally averaged structure

    Science.gov (United States)

    Hirano, Tsuneo; Nagashima, Umpei; Jensen, Per

    2018-04-01

    For NCS in the X ˜ 2 Π electronic ground state, three-dimensional potential energy surfaces (3D PESs) have been calculated ab initio at the core-valence, full-valence MR-SDCI+Q/[aug-cc-pCVQZ (N, C, S)] level of theory. The ab initio 3D PESs are employed in second-order-perturbation-theory and DVR3D calculations to obtain various molecular constants and ro-vibrationally averaged structures. The 3D PESs show that the X ˜ 2 Π NCS has its potential minimum at a linear configuration, and hence it is a "linear molecule." The equilibrium structure has re (N-C) = 1.1778 Å, re (C-S) = 1.6335 Å, and ∠e (N-C-S) = 180°. The ro-vibrationally averaged structure, determined as expectation values over DVR3D wavefunctions, has 〈 r (N-C)〉0 = 1.1836 Å, 〈 r (C-S)〉0 = 1.6356 Å, and 〈 ∠ (N-C-S)〉0 = 172.5°. Using these expectation values as the initial guess, a bent r0 structure having an 〈 ∠ (N-C-S)〉0 of 172.2° is deduced from the experimentally reported B0 values for NC32S and NC34S. Our previous prediction that a linear molecule, in any ro-vibrational state including the ro-vibrational ground state, is to be "observed" as being bent on ro-vibrational average, has been confirmed here theoretically through the expectation value for the bond-angle deviation from linearity, 〈 ρ bar 〉 , and experimentally through the interpretation of the experimentally derived rotational-constant values.

  4. Computational immunology meets bioinformatics: the use of prediction tools for molecular binding in the simulation of the immune system.

    Directory of Open Access Journals (Sweden)

    Nicolas Rapin

    Full Text Available We present a new approach to the study of the immune system that combines techniques of systems biology with information provided by data-driven prediction methods. To this end, we have extended an agent-based simulator of the immune response, C-ImmSim, such that it represents pathogens, as well as lymphocytes receptors, by means of their amino acid sequences and makes use of bioinformatics methods for T and B cell epitope prediction. This is a key step for the simulation of the immune response, because it determines immunogenicity. The binding of the epitope, which is the immunogenic part of an invading pathogen, together with activation and cooperation from T helper cells, is required to trigger an immune response in the affected host. To determine a pathogen's epitopes, we use existing prediction methods. In addition, we propose a novel method, which uses Miyazawa and Jernigan protein-protein potential measurements, for assessing molecular binding in the context of immune complexes. We benchmark the resulting model by simulating a classical immunization experiment that reproduces the development of immune memory. We also investigate the role of major histocompatibility complex (MHC haplotype heterozygosity and homozygosity with respect to the influenza virus and show that there is an advantage to heterozygosity. Finally, we investigate the emergence of one or more dominating clones of lymphocytes in the situation of chronic exposure to the same immunogenic molecule and show that high affinity clones proliferate more than any other. These results show that the simulator produces dynamics that are stable and consistent with basic immunological knowledge. We believe that the combination of genomic information and simulation of the dynamics of the immune system, in one single tool, can offer new perspectives for a better understanding of the immune system.

  5. Automated insertion of sequences into a ribosomal RNA alignment: An application of computational linguistics in molecular biology

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, Ronald C. [Case Western Reserve Univ., Cleveland, OH (United States)

    1991-11-01

    This thesis involved the construction of (1) a grammar that incorporates knowledge on base invariancy and secondary structure in a molecule and (2) a parser engine that uses the grammar to position bases into the structural subunits of the molecule. These concepts were combined with a novel pinning technique to form a tool that semi-automates insertion of a new species into the alignment for the 16S rRNA molecule (a component of the ribosome) maintained by Dr. Carl Woese`s group at the University of Illinois at Urbana. The tool was tested on species extracted from the alignment and on a group of entirely new species. The results were very encouraging, and the tool should be substantial aid to the curators of the 16S alignment. The construction of the grammar was itself automated, allowing application of the tool to alignments for other molecules. The logic programming language Prolog was used to construct all programs involved. The computational linguistics approach used here was found to be a useful way to attach the problem of insertion into an alignment.

  6. Automated insertion of sequences into a ribosomal RNA alignment: An application of computational linguistics in molecular biology

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, R.C.

    1991-11-01

    This thesis involved the construction of (1) a grammar that incorporates knowledge on base invariancy and secondary structure in a molecule and (2) a parser engine that uses the grammar to position bases into the structural subunits of the molecule. These concepts were combined with a novel pinning technique to form a tool that semi-automates insertion of a new species into the alignment for the 16S rRNA molecule (a component of the ribosome) maintained by Dr. Carl Woese's group at the University of Illinois at Urbana. The tool was tested on species extracted from the alignment and on a group of entirely new species. The results were very encouraging, and the tool should be substantial aid to the curators of the 16S alignment. The construction of the grammar was itself automated, allowing application of the tool to alignments for other molecules. The logic programming language Prolog was used to construct all programs involved. The computational linguistics approach used here was found to be a useful way to attach the problem of insertion into an alignment.

  7. Mechanical influences on morphogenesis of the knee joint revealed through morphological, molecular and computational analysis of immobilised embryos.

    Directory of Open Access Journals (Sweden)

    Karen A Roddy

    2011-02-01

    Full Text Available Very little is known about the regulation of morphogenesis in synovial joints. Mechanical forces generated from muscle contractions are required for normal development of several aspects of normal skeletogenesis. Here we show that biophysical stimuli generated by muscle contractions impact multiple events during chick knee joint morphogenesis influencing differential growth of the skeletal rudiment epiphyses and patterning of the emerging tissues in the joint interzone. Immobilisation of chick embryos was achieved through treatment with the neuromuscular blocking agent Decamethonium Bromide. The effects on development of the knee joint were examined using a combination of computational modelling to predict alterations in biophysical stimuli, detailed morphometric analysis of 3D digital representations, cell proliferation assays and in situ hybridisation to examine the expression of a selected panel of genes known to regulate joint development. This work revealed the precise changes to shape, particularly in the distal femur, that occur in an altered mechanical environment, corresponding to predicted changes in the spatial and dynamic patterns of mechanical stimuli and region specific changes in cell proliferation rates. In addition, we show altered patterning of the emerging tissues of the joint interzone with the loss of clearly defined and organised cell territories revealed by loss of characteristic interzone gene expression and abnormal expression of cartilage markers. This work shows that local dynamic patterns of biophysical stimuli generated from muscle contractions in the embryo act as a source of positional information guiding patterning and morphogenesis of the developing knee joint.

  8. Mechanical Influences on Morphogenesis of the Knee Joint Revealed through Morphological, Molecular and Computational Analysis of Immobilised Embryos

    Science.gov (United States)

    Roddy, Karen A.; Prendergast, Patrick J.; Murphy, Paula

    2011-01-01

    Very little is known about the regulation of morphogenesis in synovial joints. Mechanical forces generated from muscle contractions are required for normal development of several aspects of normal skeletogenesis. Here we show that biophysical stimuli generated by muscle contractions impact multiple events during chick knee joint morphogenesis influencing differential growth of the skeletal rudiment epiphyses and patterning of the emerging tissues in the joint interzone. Immobilisation of chick embryos was achieved through treatment with the neuromuscular blocking agent Decamethonium Bromide. The effects on development of the knee joint were examined using a combination of computational modelling to predict alterations in biophysical stimuli, detailed morphometric analysis of 3D digital representations, cell proliferation assays and in situ hybridisation to examine the expression of a selected panel of genes known to regulate joint development. This work revealed the precise changes to shape, particularly in the distal femur, that occur in an altered mechanical environment, corresponding to predicted changes in the spatial and dynamic patterns of mechanical stimuli and region specific changes in cell proliferation rates. In addition, we show altered patterning of the emerging tissues of the joint interzone with the loss of clearly defined and organised cell territories revealed by loss of characteristic interzone gene expression and abnormal expression of cartilage markers. This work shows that local dynamic patterns of biophysical stimuli generated from muscle contractions in the embryo act as a source of positional information guiding patterning and morphogenesis of the developing knee joint. PMID:21386908

  9. Molecular Modelling

    Directory of Open Access Journals (Sweden)

    Aarti Sharma

    2009-12-01

    Full Text Available

    The use of computational chemistry in the development of novel pharmaceuticals is becoming an increasingly important
    tool. In the past, drugs were simply screened for effectiveness. The recent advances in computing power and
    the exponential growth of the knowledge of protein structures have made it possible for organic compounds to tailored to
    decrease harmful side effects and increase the potency. This article provides a detailed description of the techniques
    employed in molecular modeling. Molecular modelling is a rapidly developing discipline, and has been supported from
    the dramatic improvements in computer hardware and software in recent years.

  10. Computer-assisted molecular modeling of tumor promoters: rationale for the activity of phorbol esters, teleocidin B, and aplysiatoxin

    International Nuclear Information System (INIS)

    Jeffrey, A.M.; Liskamp, R.M.J.

    1986-01-01

    In the two-stage model of skin carcinogenesis, it is believed that initiators bind to DNA and that tumor promoters such as phorbol 12-tetradecanoate 13-acetate (TPA) bind noncovalently to membrane-associated high-affinity receptors, probably protein kinase C. Two other types of potent tumor-promoting substances, aplysiatoxin and teleocidin, appear to act also by binding to and activating protein kinase C, even though their chemical structures are quite different. Therefore, the authors have undertaken computer modeling of the special relationship of various functional groups in these three chemical classes of tumor promoters in an attempt to explain how these diverse structures bind to the same receptor molecule. They propose a stereochemical model in which the oxygens in TPA at C-3, C-4, C-9, and C-20 (O-3, O-4, O-9, and O-20) correspond to the O-11, N-13, N-1, and O-24 positions in teleocidin and the O-27, O-3, O-11, and O-30 oxygens in aplysiatoxin, respectively. In this model all distances with respect to overlap of the corresponding atoms are <1 A. In addition, all three types of molecules have their hydrophobic moieties oriented in the similar position. This model is further discussed with respect to other compounds showing various degrees of activity as tumor promoters, including mezerein, ingenol, and 4α-TPA. The model explains how chemically diverse structures can have similar biological activity as tumor promoters and provides a basis for designing both agonists and antagonists of tumor promoters

  11. Magnetismo Molecular (Molecular Magentism)

    Energy Technology Data Exchange (ETDEWEB)

    Reis, Mario S [Universidade Federal Fluminense, Brasil; Moreira Dos Santos, Antonio F [ORNL

    2010-07-01

    The new synthesis processes in chemistry open a new world of research, new and surprising materials never before found in nature can now be synthesized and, as a wonderful result, observed a series of physical phenomena never before imagined. Among these are many new materials the molecular magnets, the subject of this book and magnetic properties that are often reflections of the quantum behavior of these materials. Aside from the wonderful experience of exploring something new, the theoretical models that describe the behavior these magnetic materials are, in most cases, soluble analytically, which allows us to know in detail the physical mechanisms governing these materials. Still, the academic interest in parallel this subject, these materials have a number of properties that are promising to be used in technological devices, such as in computers quantum magnetic recording, magnetocaloric effect, spintronics and many other devices. This volume will journey through the world of molecular magnets, from the structural description of these materials to state of the art research.

  12. Potent new small-molecule inhibitor of botulinum neurotoxin serotype A endopeptidase developed by synthesis-based computer-aided molecular design.

    Directory of Open Access Journals (Sweden)

    Yuan-Ping Pang

    2009-11-01

    Full Text Available Botulinum neurotoxin serotype A (BoNTA causes a life-threatening neuroparalytic disease known as botulism. Current treatment for post exposure of BoNTA uses antibodies that are effective in neutralizing the extracellular toxin to prevent further intoxication but generally cannot rescue already intoxicated neurons. Effective small-molecule inhibitors of BoNTA endopeptidase (BoNTAe are desirable because such inhibitors potentially can neutralize the intracellular BoNTA and offer complementary treatment for botulism. Previously we reported a serotype-selective, small-molecule BoNTAe inhibitor with a K(i (app value of 3.8+/-0.8 microM. This inhibitor was developed by lead identification using virtual screening followed by computer-aided optimization of a lead with an IC(50 value of 100 microM. However, it was difficult to further improve the lead from micromolar to even high nanomolar potency due to the unusually large enzyme-substrate interface of BoNTAe. The enzyme-substrate interface area of 4,840 A(2 for BoNTAe is about four times larger than the typical protein-protein interface area of 750-1,500 A(2. Inhibitors must carry several functional groups to block the unusually large interface of BoNTAe, and syntheses of such inhibitors are therefore time-consuming and expensive. Herein we report the development of a serotype-selective, small-molecule, and competitive inhibitor of BoNTAe with a K(i value of 760+/-170 nM using synthesis-based computer-aided molecular design (SBCAMD. This new approach accounts the practicality and efficiency of inhibitor synthesis in addition to binding affinity and selectivity. We also report a three-dimensional model of BoNTAe in complex with the new inhibitor and the dynamics of the complex predicted by multiple molecular dynamics simulations, and discuss further structural optimization to achieve better in vivo efficacy in neutralizing BoNTA than those of our early micromolar leads. This work provides new insight

  13. Molecular modeling of the human eukaryotic translation initiation factor 5A (eIF5A) based on spectroscopic and computational analyses

    International Nuclear Information System (INIS)

    Costa-Neto, Claudio M.; Parreiras-e-Silva, Lucas T.; Ruller, Roberto; Oliveira, Eduardo B.; Miranda, Antonio; Oliveira, Laerte; Ward, Richard J.

    2006-01-01

    The eukaryotic translation initiation factor 5A (eIF5A) is a protein ubiquitously present in archaea and eukarya, which undergoes a unique two-step post-translational modification called hypusination. Several studies have shown that hypusination is essential for a variety of functional roles for eIF5A, including cell proliferation and synthesis of proteins involved in cell cycle control. Up to now neither a totally selective inhibitor of hypusination nor an inhibitor capable of directly binding to eIF5A has been reported in the literature. The discovery of such an inhibitor might be achieved by computer-aided drug design based on the 3D structure of the human eIF5A. In this study, we present a molecular model for the human eIF5A protein based on the crystal structure of the eIF5A from Leishmania brasiliensis, and compare the modeled conformation of the loop bearing the hypusination site with circular dichroism data obtained with a synthetic peptide of this loop. Furthermore, analysis of amino acid variability between different human eIF5A isoforms revealed peculiar structural characteristics that are of functional relevance

  14. Combination of computational methods, adsorption isotherms and selectivity tests for the conception of a mixed non-covalent-semi-covalent molecularly imprinted polymer of vanillin.

    Science.gov (United States)

    Puzio, Kinga; Delépée, Raphaël; Vidal, Richard; Agrofoglio, Luigi A

    2013-08-06

    A novel molecularly imprinted polymer (MIP) for vanillin was prepared by photo initiated polymerization in dichloromethane using a mixed semi-covalent and non-covalent imprinting strategy. Taking polymerisable syringaldehyde as "dummy" template, acrylamide was chosen as functional monomer on B3LYP/6-31+G(d,p) density functional theory computational method basis with counterpoise. The binding parameters for the recognition of vanillin on imprinted polymers were studied with three different isotherm models (Langmuir, bi-Langmuir and Langmuir-Freundlich) and compared. The results indicate an heterogeneity of binding sites. It was found and proved by DFT calculations that the specific binding of vanillin in the cavities is due to non-covalent interactions of the template with the hydroxyphenyl- and the amide-moieties. The binding geometry of vanillin in the MIP cavity was also modelled. The obtained MIP is highly specific for vanillin (with an imprinting factor of 7.4) and was successfully applied to the extraction of vanillin from vanilla pods, red wine spike with vanillin, natural and artificial vanilla sugar with a recovery of 80%. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Integrin-Targeted Hybrid Fluorescence Molecular Tomography/X-ray Computed Tomography for Imaging Tumor Progression and Early Response in Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xiaopeng Ma

    2017-01-01

    Full Text Available Integrins play an important role in tumor progression, invasion and metastasis. Therefore we aimed to evaluate a preclinical imaging approach applying ανβ3 integrin targeted hybrid Fluorescence Molecular Tomography/X-ray Computed Tomography (FMT-XCT for monitoring tumor progression as well as early therapy response in a syngeneic murine Non-Small Cell Lung Cancer (NSCLC model. Lewis Lung Carcinomas were grown orthotopically in C57BL/6 J mice and imaged in-vivo using a ανβ3 targeted near-infrared fluorescence (NIRF probe. ανβ3-targeted FMT-XCT was able to track tumor progression. Cilengitide was able to substantially block the binding of the NIRF probe and suppress the imaging signal. Additionally mice were treated with an established chemotherapy regimen of Cisplatin and Bevacizumab or with a novel MEK inhibitor (Refametinib for 2 weeks. While μCT revealed only a moderate slowdown of tumor growth, ανβ3 dependent signal decreased significantly compared to non-treated mice already at one week post treatment. ανβ3 targeted imaging might therefore become a promising tool for assessment of early therapy response in the future.

  16. Fluorescence background subtraction technique for hybrid fluorescence molecular tomography/x-ray computed tomography imaging of a mouse model of early stage lung cancer.

    Science.gov (United States)

    Ale, Angelique; Ermolayev, Vladimir; Deliolanis, Nikolaos C; Ntziachristos, Vasilis

    2013-05-01

    The ability to visualize early stage lung cancer is important in the study of biomarkers and targeting agents that could lead to earlier diagnosis. The recent development of hybrid free-space 360-deg fluorescence molecular tomography (FMT) and x-ray computed tomography (XCT) imaging yields a superior optical imaging modality for three-dimensional small animal fluorescence imaging over stand-alone optical systems. Imaging accuracy was improved by using XCT information in the fluorescence reconstruction method. Despite this progress, the detection sensitivity of targeted fluorescence agents remains limited by nonspecific background accumulation of the fluorochrome employed, which complicates early detection of murine cancers. Therefore we examine whether x-ray CT information and bulk fluorescence detection can be combined to increase detection sensitivity. Correspondingly, we research the performance of a data-driven fluorescence background estimator employed for subtraction of background fluorescence from acquisition data. Using mice containing known fluorochromes ex vivo, we demonstrate the reduction of background signals from reconstructed images and sensitivity improvements. Finally, by applying the method to in vivo data from K-ras transgenic mice developing lung cancer, we find small tumors at an early stage compared with reconstructions performed using raw data. We conclude with the benefits of employing fluorescence subtraction in hybrid FMT-XCT for early detection studies.

  17. Application of computational fluid dynamics for the simulation of cryogenic molecular sieve bed absorber of hydrogen isotopes recovery system for Indian LLCB-TBM

    Energy Technology Data Exchange (ETDEWEB)

    Gayathri Devi, V.; Sircar, A.; Sarkar, B. [Institute of Plasma Research, Bhat, Gandhinagar, Gujarar (India)

    2015-03-15

    One of the most challenging tasks in the design of the fuel cycle system lies in the effective design of Tritium Extraction System (TES) which involves proper extraction and purification of tritium in the fuel cycle of the fusion reactor. Indian Lead Lithium cooled Ceramic Breeder Test Blanket Module (LLCB-TBM) would extract hydrogen isotopes through Cryogenic Molecular Sieve Bed (CMSB) adsorber system. A prototype Hydrogen Isotopes Recovery System (HIRS) is being developed to validate the concepts for tritium extraction by adsorption mass transfer mechanism. In this study, a design model has been developed and analyzed to simulate the adsorption mass transfer kinetics in a fixed bed adsorption column. The simulation leads primarily to effective design of HIRS, which is a state-of-the-art technology. The paper describes the process simulation approach and the results of Computational Fluid Dynamics (CFD) analysis. The effects of different operating conditions are studied to investigate their influence on the hydrogen isotopes adsorption capacity. The results of the present simulation study would be used to understand the best optimized transport phenomenon before realizing the TES as a system for LLCB-TBM. (authors)

  18. Molecular docking.

    Science.gov (United States)

    Morris, Garrett M; Lim-Wilby, Marguerita

    2008-01-01

    Molecular docking is a key tool in structural molecular biology and computer-assisted drug design. The goal of ligand-protein docking is to predict the predominant binding mode(s) of a ligand with a protein of known three-dimensional structure. Successful docking methods search high-dimensional spaces effectively and use a scoring function that correctly ranks candidate dockings. Docking can be used to perform virtual screening on large libraries of compounds, rank the results, and propose structural hypotheses of how the ligands inhibit the target, which is invaluable in lead optimization. The setting up of the input structures for the docking is just as important as the docking itself, and analyzing the results of stochastic search methods can sometimes be unclear. This chapter discusses the background and theory of molecular docking software, and covers the usage of some of the most-cited docking software.

  19. Organic Computing

    CERN Document Server

    Würtz, Rolf P

    2008-01-01

    Organic Computing is a research field emerging around the conviction that problems of organization in complex systems in computer science, telecommunications, neurobiology, molecular biology, ethology, and possibly even sociology can be tackled scientifically in a unified way. From the computer science point of view, the apparent ease in which living systems solve computationally difficult problems makes it inevitable to adopt strategies observed in nature for creating information processing machinery. In this book, the major ideas behind Organic Computing are delineated, together with a sparse sample of computational projects undertaken in this new field. Biological metaphors include evolution, neural networks, gene-regulatory networks, networks of brain modules, hormone system, insect swarms, and ant colonies. Applications are as diverse as system design, optimization, artificial growth, task allocation, clustering, routing, face recognition, and sign language understanding.

  20. What makes Ras an efficient molecular switch: a computational, biophysical, and structural study of Ras-GDP interactions with mutants of Raf.

    Science.gov (United States)

    Filchtinski, Daniel; Sharabi, Oz; Rüppel, Alma; Vetter, Ingrid R; Herrmann, Christian; Shifman, Julia M

    2010-06-11

    Ras is a small GTP-binding protein that is an essential molecular switch for a wide variety of signaling pathways including the control of cell proliferation, cell cycle progression and apoptosis. In the GTP-bound state, Ras can interact with its effectors, triggering various signaling cascades in the cell. In the GDP-bound state, Ras looses its ability to bind to known effectors. The interaction of the GTP-bound Ras (Ras(GTP)) with its effectors has been studied intensively. However, very little is known about the much weaker interaction between the GDP-bound Ras (Ras(GDP)) and Ras effectors. We investigated the factors underlying the nucleotide-dependent differences in Ras interactions with one of its effectors, Raf kinase. Using computational protein design, we generated mutants of the Ras-binding domain of Raf kinase (Raf) that stabilize the complex with Ras(GDP). Most of our designed mutations narrow the gap between the affinity of Raf for Ras(GTP) and Ras(GDP), producing the desired shift in binding specificity towards Ras(GDP). A combination of our best designed mutation, N71R, with another mutation, A85K, yielded a Raf mutant with a 100-fold improvement in affinity towards Ras(GDP). The Raf A85K and Raf N71R/A85K mutants were used to obtain the first high-resolution structures of Ras(GDP) bound to its effector. Surprisingly, these structures reveal that the loop on Ras previously termed the switch I region in the Ras(GDP).Raf mutant complex is found in a conformation similar to that of Ras(GTP) and not Ras(GDP). Moreover, the structures indicate an increased mobility of the switch I region. This greater flexibility compared to the same loop in Ras(GTP) is likely to explain the natural low affinity of Raf and other Ras effectors to Ras(GDP). Our findings demonstrate that an accurate balance between a rigid, high-affinity conformation and conformational flexibility is required to create an efficient and stringent molecular switch. Copyright 2010 Elsevier Ltd

  1. A transcriptomic computational analysis of mastic oil-treated Lewis lung carcinomas reveals molecular mechanisms targeting tumor cell growth and survival

    Directory of Open Access Journals (Sweden)

    Roussos Charis

    2009-12-01

    Full Text Available Abstract Background Mastic oil from Pistacia lentiscus variation chia, a blend of bioactive terpenes with recognized medicinal properties, has been recently shown to exert anti-tumor growth activity through inhibition of cancer cell proliferation, survival, angiogenesis and inflammatory response. However, no studies have addressed its mechanisms of action at genome-wide gene expression level. Methods To investigate molecular mechanisms triggered by mastic oil, Lewis Lung Carcinoma cells were treated with mastic oil or DMSO and RNA was collected at five distinct time points (3-48 h. Microarray expression profiling was performed using Illumina mouse-6 v1 beadchips, followed by computational analysis. For a number of selected genes, RT-PCR validation was performed in LLC cells as well as in three human cancer cell lines of different origin (A549, HCT116, K562. PTEN specific inhibition by a bisperovanadium compound was applied to validate its contribution to mastic oil-mediated anti-tumor growth effects. Results In this work we demonstrated that exposure of Lewis lung carcinomas to mastic oil caused a time-dependent alteration in the expression of 925 genes. GO analysis associated expression profiles with several biological processes and functions. Among them, modifications on cell cycle/proliferation, survival and NF-κB cascade in conjunction with concomitant regulation of genes encoding for PTEN, E2F7, HMOX1 (up-regulation and NOD1 (down-regulation indicated some important mechanistic links underlying the anti-proliferative, pro-apoptotic and anti-inflammatory effects of mastic oil. The expression profiles of Hmox1, Pten and E2f7 genes were similarly altered by mastic oil in the majority of test cancer cell lines. Inhibition of PTEN partially reversed mastic oil effects on tumor cell growth, indicating a multi-target mechanism of action. Finally, k-means clustering, organized the significant gene list in eight clusters demonstrating a similar

  2. Structural models of zebrafish (Danio rerio NOD1 and NOD2 NACHT domains suggest differential ATP binding orientations: insights from computational modeling, docking and molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Jitendra Maharana

    Full Text Available Nucleotide-binding oligomerization domain-containing protein 1 (NOD1 and NOD2 are cytosolic pattern recognition receptors playing pivotal roles in innate immune signaling. NOD1 and NOD2 recognize bacterial peptidoglycan derivatives iE-DAP and MDP, respectively and undergoes conformational alternation and ATP-dependent self-oligomerization of NACHT domain followed by downstream signaling. Lack of structural adequacy of NACHT domain confines our understanding about the NOD-mediated signaling mechanism. Here, we predicted the structure of NACHT domain of both NOD1 and NOD2 from model organism zebrafish (Danio rerio using computational methods. Our study highlighted the differential ATP binding modes in NOD1 and NOD2. In NOD1, γ-phosphate of ATP faced toward the central nucleotide binding cavity like NLRC4, whereas in NOD2 the cavity was occupied by adenine moiety. The conserved 'Lysine' at Walker A formed hydrogen bonds (H-bonds and Aspartic acid (Walker B formed electrostatic interaction with ATP. At Sensor 1, Arg328 of NOD1 exhibited an H-bond with ATP, whereas corresponding Arg404 of NOD2 did not. 'Proline' of GxP motif (Pro386 of NOD1 and Pro464 of NOD2 interacted with adenine moiety and His511 at Sensor 2 of NOD1 interacted with γ-phosphate group of ATP. In contrast, His579 of NOD2 interacted with the adenine moiety having a relatively inverted orientation. Our findings are well supplemented with the molecular interaction of ATP with NLRC4, and consistent with mutagenesis data reported for human, which indicates evolutionary shared NOD signaling mechanism. Together, this study provides novel insights into ATP binding mechanism, and highlights the differential ATP binding modes in zebrafish NOD1 and NOD2.

  3. Computational neuroscience

    CERN Document Server

    Blackwell, Kim L

    2014-01-01

    Progress in Molecular Biology and Translational Science provides a forum for discussion of new discoveries, approaches, and ideas in molecular biology. It contains contributions from leaders in their fields and abundant references. This volume brings together different aspects of, and approaches to, molecular and multi-scale modeling, with applications to a diverse range of neurological diseases. Mathematical and computational modeling offers a powerful approach for examining the interaction between molecular pathways and ionic channels in producing neuron electrical activity. It is well accepted that non-linear interactions among diverse ionic channels can produce unexpected neuron behavior and hinder a deep understanding of how ion channel mutations bring about abnormal behavior and disease. Interactions with the diverse signaling pathways activated by G protein coupled receptors or calcium influx adds an additional level of complexity. Modeling is an approach to integrate myriad data sources into a cohesiv...

  4. QuBiLS-MAS, open source multi-platform software for atom- and bond-based topological (2D) and chiral (2.5D) algebraic molecular descriptors computations.

    Science.gov (United States)

    Valdés-Martiní, José R; Marrero-Ponce, Yovani; García-Jacas, César R; Martinez-Mayorga, Karina; Barigye, Stephen J; Vaz d'Almeida, Yasser Silveira; Pham-The, Hai; Pérez-Giménez, Facundo; Morell, Carlos A

    2017-06-07

    In previous reports, Marrero-Ponce et al. proposed algebraic formalisms for characterizing topological (2D) and chiral (2.5D) molecular features through atom- and bond-based ToMoCoMD-CARDD (acronym for Topological Molecular Computational Design-Computer Aided Rational Drug Design) molecular descriptors. These MDs codify molecular information based on the bilinear, quadratic and linear algebraic forms and the graph-theoretical electronic-density and edge-adjacency matrices in order to consider atom- and bond-based relations, respectively. These MDs have been successfully applied in the screening of chemical compounds of different therapeutic applications ranging from antimalarials, antibacterials, tyrosinase inhibitors and so on. To compute these MDs, a computational program with the same name was initially developed. However, this in house software barely offered the functionalities required in contemporary molecular modeling tasks, in addition to the inherent limitations that made its usability impractical. Therefore, the present manuscript introduces the QuBiLS-MAS (acronym for Quadratic, Bilinear and N-Linear mapS based on graph-theoretic electronic-density Matrices and Atomic weightingS) software designed to compute topological (0-2.5D) molecular descriptors based on bilinear, quadratic and linear algebraic forms for atom- and bond-based relations. The QuBiLS-MAS module was designed as standalone software, in which extensions and generalizations of the former ToMoCoMD-CARDD 2D-algebraic indices are implemented, considering the following aspects: (a) two new matrix normalization approaches based on double-stochastic and mutual probability formalisms; (b) topological constraints (cut-offs) to take into account particular inter-atomic relations; (c) six additional atomic properties to be used as weighting schemes in the calculation of the molecular vectors; (d) four new local-fragments to consider molecular regions of interest; (e) number of lone-pair electrons in

  5. Improving Students' Understanding of Molecular Structure through Broad-Based Use of Computer Models in the Undergraduate Organic Chemistry Lecture

    Science.gov (United States)

    Springer, Michael T.

    2014-01-01

    Several articles suggest how to incorporate computer models into the organic chemistry laboratory, but relatively few papers discuss how to incorporate these models broadly into the organic chemistry lecture. Previous research has suggested that "manipulating" physical or computer models enhances student understanding; this study…

  6. Teaching Molecular Biology with Microcomputers.

    Science.gov (United States)

    Reiss, Rebecca; Jameson, David

    1984-01-01

    Describes a series of computer programs that use simulation and gaming techniques to present the basic principles of the central dogma of molecular genetics, mutation, and the genetic code. A history of discoveries in molecular biology is presented and the evolution of these computer assisted instructional programs is described. (MBR)

  7. Possible Radiation-Induced Damage to the Molecular Structure of Wooden Artifacts Due to Micro-Computed Tomography, Handheld X-Ray Fluorescence, and X-Ray Photoelectron Spectroscopic Techniques

    Directory of Open Access Journals (Sweden)

    Madalena Kozachuk

    2016-05-01

    Full Text Available This study was undertaken to ascertain whether radiation produced by X-ray photoelectron spectroscopy (XPS, micro-computed tomography (μCT and/or portable handheld X-ray fluorescence (XRF equipment might damage wood artifacts during analysis. Changes at the molecular level were monitored by Fourier transform infrared (FTIR analysis. No significant changes in FTIR spectra were observed as a result of μCT or handheld XRF analysis. No substantial changes in the collected FTIR spectra were observed when XPS analytical times on the order of minutes were used. However, XPS analysis collected over tens of hours did produce significant changes in the FTIR spectra.

  8. Homogeneous nucleation of water in argon : nucleation rate computation from molecular simulations of TIP4P and TIP4P/2005 water model

    NARCIS (Netherlands)

    Dumitrescu, Lucia R.; Smeulders, David M.J.; Dam, Jacques A.M.; Gaastra-Nedea, Silvia V.

    2017-01-01

    Molecular dynamics (MD) simulations were conducted to study nucleation of water at 350 K in argon using TIP4P and TIP4P/2005 water models. We found that the stability of any cluster, even if large, strongly depends on the energetic interactions with its vicinity, while the stable clusters change

  9. Discovery of molecular mechanism of a clinical herbal formula upregulating serum HDL-c levels in treatment of metabolic syndrome by in vivo and computational studies.

    Science.gov (United States)

    Chen, Meimei; Yang, Fafu; Kang, Jie; Gan, Huijuan; Lai, Xinmei; Gao, Yuxing

    2018-01-15

    Decreased HDL cholesterol (HDL-c) is considered as an independent risk factor of cardiovascular disease in metabolic syndrome (Mets). Wendan decoction (WDD), a famous clinical traditional Chinese medicine formula in Mets in China, which can obviously up-regulate serum HDL-c levels in Mets. However, till now, the molecular mechanism of up-regulation still remained unclear. In this study, an integrated approach that combined serum ABCA1 in vivo assay, QSAR modeling and molecular docking was developed to explore the molecular mechanism and chemical substance basis of WDD upregulating HDL-c levels. Compared with Mets model group, serum ABCA1 and HDL-c levels intervened by two different doses of WDD for two weeks were significantly up-regulated. Then, kohonen and LDA were applied to develop QSAR models for ABCA1 up-regulators based flavonoids. The derived QSAR model produced the overall accuracy of 100%, a very powerful tool for screening ABCA1 up-regulators. The QSAR model prediction revealed 67 flavonoids in WDD were ABCA1 up-regulators. Finally, they were subjected to the molecular docking to understand their roles in up-regulating ABCA1 expression, which led to discovery of 23 ABCA1 up-regulators targeting LXR beta. Overall, QSAR modeling and docking studies well accounted for the observed in vivo activities of ABCA1 affected by WDD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Conformation analysis of trehalose. Molecular dynamics simulation and molecular mechanics

    International Nuclear Information System (INIS)

    Donnamaira, M.C.; Howard, E.I.; Grigera, J.R.

    1992-09-01

    Conformational analysis of the disaccharide trehalose is done by molecular dynamics and molecular mechanics. In spite of the different force fields used in each case, comparison between the molecular dynamics trajectories of the torsional angles of glycosidic linkage and energy conformational map shows a good agreement between both methods. By molecular dynamics it is observed a moderate mobility of the glycosidic linkage. The demands of computer time is comparable in both cases. (author). 6 refs, 4 figs

  11. FPS scientific and supercomputers computers in chemistry

    International Nuclear Information System (INIS)

    Curington, I.J.

    1987-01-01

    FPS Array Processors, scientific computers, and highly parallel supercomputers are used in nearly all aspects of compute-intensive computational chemistry. A survey is made of work utilizing this equipment, both published and current research. The relationship of the computer architecture to computational chemistry is discussed, with specific reference to Molecular Dynamics, Quantum Monte Carlo simulations, and Molecular Graphics applications. Recent installations of the FPS T-Series are highlighted, and examples of Molecular Graphics programs running on the FPS-5000 are shown

  12. Molecular level computational studies of polyethylene and polyacrylonitrile composites containing single walled carbon nanotubes: effect of carboxylic acid functionalization on nanotube-polymer interfacial properties

    Directory of Open Access Journals (Sweden)

    Shayesteh eHaghighatpanah

    2014-09-01

    Full Text Available Molecular dynamics and molecular mechanics methods have been used to investigate additive-polymer interfacial properties in single walled carbon nanotube – polyethylene and single walled carbon nanotube – polyacrylonitrile composites. Properties such as the interfacial shear stress and bonding energy are similar for the two composites. In contrast, functionalizing the single walled carbon nanotubes with carboxylic acid groups leads to an increase in these properties, with a larger increase for the polar polyacrylonitrile composite. Increasing the percentage of carbon atoms that were functionalized from 1% to 5% also leads to an increase in the interfacial properties. In addition, the interfacial properties depend on the location of the functional groups on the single walled carbon nanotube wall.

  13. Atomic-level computer simulation

    International Nuclear Information System (INIS)

    Adams, J.B.; Rockett, Angus; Kieffer, John; Xu Wei; Nomura, Miki; Kilian, K.A.; Richards, D.F.; Ramprasad, R.

    1994-01-01

    This paper provides a broad overview of the methods of atomic-level computer simulation. It discusses methods of modelling atomic bonding, and computer simulation methods such as energy minimization, molecular dynamics, Monte Carlo, and lattice Monte Carlo. ((orig.))

  14. US-Latin American Workshop on Molecular and Materials Sciences: Theoretical and Computational Aspects Held at the University of Florida, Gainesville, on February 8-10, 1994

    Science.gov (United States)

    1994-08-09

    Observables During a Collision Inst. de Fisica , Cuernavaca, Mexico Ruben D. Santiago Acosta An Algebraic Model for 3-dimensional Atom-Diatom Inst C...STRUCTURES. MOLECULAR DYNAMICS SIMULATION M. C .Donnamaria and J. R. Grigera Instituto de Fisica de Liquidos y Sistemas Biologicos (IFLYSIB),CONICET...Crybiology, 1981, 18, 631. ACKNOWLEDGMENTS This work has been partially funded by the Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET) of

  15. Computational analysis of phosphopeptide binding to the polo-box domain of the mitotic kinase PLK1 using molecular dynamics simulation.

    Directory of Open Access Journals (Sweden)

    David J Huggins

    2010-08-01

    Full Text Available The Polo-Like Kinase 1 (PLK1 acts as a central regulator of mitosis and is over-expressed in a wide range of human tumours where high levels of expression correlate with a poor prognosis. PLK1 comprises two structural elements, a kinase domain and a polo-box domain (PBD. The PBD binds phosphorylated substrates to control substrate phosphorylation by the kinase domain. Although the PBD preferentially binds to phosphopeptides, it has a relatively broad sequence specificity in comparison with other phosphopeptide binding domains. We analysed the molecular determinants of recognition by performing molecular dynamics simulations of the PBD with one of its natural substrates, CDC25c. Predicted binding free energies were calculated using a molecular mechanics, Poisson-Boltzmann surface area approach. We calculated the per-residue contributions to the binding free energy change, showing that the phosphothreonine residue and the mainchain account for the vast majority of the interaction energy. This explains the very broad sequence specificity with respect to other sidechain residues. Finally, we considered the key role of bridging water molecules at the binding interface. We employed inhomogeneous fluid solvation theory to consider the free energy of water molecules on the protein surface with respect to bulk water molecules. Such an analysis highlights binding hotspots created by elimination of water molecules from hydrophobic surfaces. It also predicts that a number of water molecules are stabilized by the presence of the charged phosphate group, and that this will have a significant effect on the binding affinity. Our findings suggest a molecular rationale for the promiscuous binding of the PBD and highlight a role for bridging water molecules at the interface. We expect that this method of analysis will be very useful for probing other protein surfaces to identify binding hotspots for natural binding partners and small molecule inhibitors.

  16. Computational modeling in biomechanics

    CERN Document Server

    Mofrad, Mohammad

    2010-01-01

    This book provides a glimpse of the diverse and important roles that modern computational technology is playing in various areas of biomechanics. It includes unique chapters on ab initio quantum mechanical, molecular dynamic and scale coupling methods..

  17. Computed Heats of Formation

    National Research Council Canada - National Science Library

    Politzer, Peter

    1998-01-01

    ..., the heats of vaporization and sublimation. The latter are determined by means of relationships that we have developed involving the computed electrostatic potential on the molecular surface 2,3...

  18. FT-IR, FT-Raman, NMR spectra, density functional computations of the vibrational assignments (for monomer and dimer) and molecular geometry of anticancer drug 7-amino-2-methylchromone

    Science.gov (United States)

    Mariappan, G.; Sundaraganesan, N.

    2014-04-01

    Vibrational assignments for the 7-amino-2-methylchromone (abbreviated as 7A2MC) molecule using a combination of experimental vibrational spectroscopic measurements and ab initio computational methods are reported. The optimized geometry, intermolecular hydrogen bonding, first order hyperpolarizability and harmonic vibrational wavenumbers of 7A2MC have been investigated with the help of B3LYP density functional theory method. The calculated molecular geometry parameters, the theoretically computed vibrational frequencies for monomer and dimer and relative peak intensities were compared with experimental data. DFT calculations using the B3LYP method and 6-31 + G(d,p) basis set were found to yield results that are very comparable to experimental IR and Raman spectra. Detailed vibrational assignments were performed with DFT calculations and the potential energy distribution (PED) obtained from the Vibrational Energy Distribution Analysis (VEDA) program. Natural Bond Orbital (NBO) study revealed the characteristics of the electronic delocalization of the molecular structure. 13C and 1H NMR spectra have been recorded and 13C and 1H nuclear magnetic resonance chemical shifts of the molecule have been calculated using the gauge independent atomic orbital (GIAO) method. Furthermore, All the possible calculated values are analyzed using correlation coefficients linear fitting equation and are shown strong correlation with the experimental data.

  19. Distributed chemical computing using ChemStar: an open source java remote method invocation architecture applied to large scale molecular data from PubChem.

    Science.gov (United States)

    Karthikeyan, M; Krishnan, S; Pandey, Anil Kumar; Bender, Andreas; Tropsha, Alexander

    2008-04-01

    We present the application of a Java remote method invocation (RMI) based open source architecture to distributed chemical computing. This architecture was previously employed for distributed data harvesting of chemical information from the Internet via the Google application programming interface (API; ChemXtreme). Due to its open source character and its flexibility, the underlying server/client framework can be quickly adopted to virtually every computational task that can be parallelized. Here, we present the server/client communication framework as well as an application to distributed computing of chemical properties on a large scale (currently the size of PubChem; about 18 million compounds), using both the Marvin toolkit as well as the open source JOELib package. As an application, for this set of compounds, the agreement of log P and TPSA between the packages was compared. Outliers were found to be mostly non-druglike compounds and differences could usually be explained by differences in the underlying algorithms. ChemStar is the first open source distributed chemical computing environment built on Java RMI, which is also easily adaptable to user demands due to its "plug-in architecture". The complete source codes as well as calculated properties along with links to PubChem resources are available on the Internet via a graphical user interface at http://moltable.ncl.res.in/chemstar/.

  20. Assessment of Molecular Modeling & Simulation

    Energy Technology Data Exchange (ETDEWEB)

    None

    2002-01-03

    This report reviews the development and applications of molecular and materials modeling in Europe and Japan in comparison to those in the United States. Topics covered include computational quantum chemistry, molecular simulations by molecular dynamics and Monte Carlo methods, mesoscale modeling of material domains, molecular-structure/macroscale property correlations like QSARs and QSPRs, and related information technologies like informatics and special-purpose molecular-modeling computers. The panel's findings include the following: The United States leads this field in many scientific areas. However, Canada has particular strengths in DFT methods and homogeneous catalysis; Europe in heterogeneous catalysis, mesoscale, and materials modeling; and Japan in materials modeling and special-purpose computing. Major government-industry initiatives are underway in Europe and Japan, notably in multi-scale materials modeling and in development of chemistry-capable ab-initio molecular dynamics codes.

  1. Molecular robots with sensors and intelligence.

    Science.gov (United States)

    Hagiya, Masami; Konagaya, Akihiko; Kobayashi, Satoshi; Saito, Hirohide; Murata, Satoshi

    2014-06-17

    CONSPECTUS: What we can call a molecular robot is a set of molecular devices such as sensors, logic gates, and actuators integrated into a consistent system. The molecular robot is supposed to react autonomously to its environment by receiving molecular signals and making decisions by molecular computation. Building such a system has long been a dream of scientists; however, despite extensive efforts, systems having all three functions (sensing, computation, and actuation) have not been realized yet. This Account introduces an ongoing research project that focuses on the development of molecular robotics funded by MEXT (Ministry of Education, Culture, Sports, Science and Technology, Japan). This 5 year project started in July 2012 and is titled "Development of Molecular Robots Equipped with Sensors and Intelligence". The major issues in the field of molecular robotics all correspond to a feedback (i.e., plan-do-see) cycle of a robotic system. More specifically, these issues are (1) developing molecular sensors capable of handling a wide array of signals, (2) developing amplification methods of signals to drive molecular computing devices, (3) accelerating molecular computing, (4) developing actuators that are controllable by molecular computers, and (5) providing bodies of molecular robots encapsulating the above molecular devices, which implement the conformational changes and locomotion of the robots. In this Account, the latest contributions to the project are reported. There are four research teams in the project that specialize on sensing, intelligence, amoeba-like actuation, and slime-like actuation, respectively. The molecular sensor team is focusing on the development of molecular sensors that can handle a variety of signals. This team is also investigating methods to amplify signals from the molecular sensors. The molecular intelligence team is developing molecular computers and is currently focusing on a new photochemical technology for accelerating DNA

  2. Computational Studies of Difference in Binding Modes of Peptide and Non-Peptide Inhibitors to MDM2/MDMX Based on Molecular Dynamics Simulations

    Directory of Open Access Journals (Sweden)

    Yuxin Zhang

    2012-02-01

    Full Text Available Inhibition of p53-MDM2/MDMX interaction is considered to be a promising strategy for anticancer drug design to activate wild-type p53 in tumors. We carry out molecular dynamics (MD simulations to study the binding mechanisms of peptide and non-peptide inhibitors to MDM2/MDMX. The rank of binding free energies calculated by molecular mechanics generalized Born surface area (MM-GBSA method agrees with one of the experimental values. The results suggest that van der Waals energy drives two kinds of inhibitors to MDM2/MDMX. We also find that the peptide inhibitors can produce more interaction contacts with MDM2/MDMX than the non-peptide inhibitors. Binding mode predictions based on the inhibitor-residue interactions show that the π–π, CH–π and CH–CH interactions dominated by shape complimentarity, govern the binding of the inhibitors in the hydrophobic cleft of MDM2/MDMX. Our studies confirm the residue Tyr99 in MDMX can generate a steric clash with the inhibitors due to energy and structure. This finding may theoretically provide help to develop potent dual-specific or MDMX inhibitors.

  3. Quantum computational studies, spectroscopic (FT-IR, FT-Raman and UV-Vis) profiling, natural hybrid orbital and molecular docking analysis on 2,4 Dibromoaniline

    Science.gov (United States)

    Abraham, Christina Susan; Prasana, Johanan Christian; Muthu, S.; Rizwana B, Fathima; Raja, M.

    2018-05-01

    The research exploration will comprise of investigating the molecular structure, vibrational assignments, bonding and anti-bonding nature, nonlinear optical, electronic and thermodynamic nature of the molecule. The research is conducted at two levels: First level employs the spectroscopic techniques - FT-IR, FT-Raman and UV-Vis characterizing techniques; at second level the data attained experimentally is analyzed through theoretical methods using and Density Function Theories which involves the basic principle of solving the Schrodinger equation for many body systems. A comparison is drawn between the two levels and discussed. The probability of the title molecule being bio-active theoretically proved by the electrophilicity index leads to further property analyzes of the molecule. The target molecule is found to fit well with Centromere associated protein inhibitor using molecular docking techniques. Higher basis set 6-311++G(d,p) is used to attain results more concurrent to the experimental data. The results of the organic amine 2, 4 Dibromoaniline is analyzed and discussed.

  4. Open source molecular modeling.

    Science.gov (United States)

    Pirhadi, Somayeh; Sunseri, Jocelyn; Koes, David Ryan

    2016-09-01

    The success of molecular modeling and computational chemistry efforts are, by definition, dependent on quality software applications. Open source software development provides many advantages to users of modeling applications, not the least of which is that the software is free and completely extendable. In this review we categorize, enumerate, and describe available open source software packages for molecular modeling and computational chemistry. An updated online version of this catalog can be found at https://opensourcemolecularmodeling.github.io. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  5. Molecular interactions of agonist and inverse agonist ligands at serotonin 5-HT2C G protein-coupled receptors: computational ligand docking and molecular dynamics studies validated by experimental mutagenesis results

    Science.gov (United States)

    Córdova-Sintjago, Tania C.; Liu, Yue; Booth, Raymond G.

    2015-02-01

    To understand molecular determinants for ligand activation of the serotonin 5-HT2C G protein-coupled receptor (GPCR), a drug target for obesity and neuropsychiatric disorders, a 5-HT2C homology model was built according to an adrenergic β2 GPCR (β2AR) structure and validated using a 5-HT2B GPCR crystal structure. The models were equilibrated in a simulated phosphatidyl choline membrane for ligand docking and molecular dynamics studies. Ligands included (2S, 4R)-(-)-trans-4-(3'-bromo- and trifluoro-phenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalene-2-amine (3'-Br-PAT and 3'-CF3-PAT), a 5-HT2C agonist and inverse agonist, respectively. Distinct interactions of 3'-Br-PAT and 3'-CF3-PAT at the wild-type (WT) 5-HT2C receptor model were observed and experimental 5-HT2C receptor mutagenesis studies were undertaken to validate the modelling results. For example, the inverse agonist 3'-CF3-PAT docked deeper in the WT 5-HT2C binding pocket and altered the orientation of transmembrane helices (TM) 6 in comparison to the agonist 3'-Br-PAT, suggesting that changes in TM orientation that result from ligand binding impact function. For both PATs, mutation of 5-HT2C residues S3.36, T3.37, and F5.47 to alanine resulted in significantly decreased affinity, as predicted from modelling results. It was concluded that upon PAT binding, 5-HT2C residues T3.37 and F5.47 in TMs 3 and 5, respectively, engage in inter-helical interactions with TMs 4 and 6, respectively. The movement of TMs 5 and 6 upon agonist and inverse agonist ligand binding observed in the 5-HT2C receptor modelling studies was similar to movements reported for the activation and deactivation of the β2AR, suggesting common mechanisms among aminergic neurotransmitter GPCRs.

  6. Computer aided drug design

    Science.gov (United States)

    Jain, A.

    2017-08-01

    Computer based method can help in discovery of leads and can potentially eliminate chemical synthesis and screening of many irrelevant compounds, and in this way, it save time as well as cost. Molecular modeling systems are powerful tools for building, visualizing, analyzing and storing models of complex molecular structure that can help to interpretate structure activity relationship. The use of various techniques of molecular mechanics and dynamics and software in Computer aided drug design along with statistics analysis is powerful tool for the medicinal chemistry to synthesis therapeutic and effective drugs with minimum side effect.

  7. Molecular Structure, Spectroscopic and DFT Computational Studies of Arylidene-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H-trione

    Directory of Open Access Journals (Sweden)

    Assem Barakat

    2016-09-01

    Full Text Available Reaction of barbituric acid derivatives and di-substituted benzaldehyde in water afforded arylidene-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H-trione derivatives (1 and 2. The one step reaction proceeded efficiently, smoothly, and in excellent yield. The arylidene compounds were characterized by spectrophotometric tools plus X-ray single crystal diffraction technique. Quantum chemical calculations were performed using the DFT/B3LYP method to optimize the structure of the two isomers (1 and 2 in the gas phase. The optimized structures were found to agree well with the experimental X-ray structure data. The highest occupied (HOMO and lowest unoccupied (LUMO frontier molecular orbitals analyses were performed and the atomic charges were calculated using natural populationanalysis.

  8. Computation and analysis of the transverse current autocorrelation function, Ct(k,t), for small wave vectors: A molecular-dynamics study for a Lennard-Jones fluid

    Science.gov (United States)

    Vogelsang, R.; Hoheisel, C.

    1987-02-01

    Molecular-dynamics (MD) calculations are reported for three thermodynamic states of a Lennard-Jones fluid. Systems of 2048 particles and 105 integration steps were used. The transverse current autocorrelation function, Ct(k,t), has been determined for wave vectors of the range 0.5viscosities which showed a systematic behavior as a function of k. Extrapolation to the hydrodynamic region at k=0 gave shear viscosity coefficients in good agreement with direct Green-Kubo results obtained in previous work. The two-exponential model fit for the memory function proposed by other authors does not provide a reasonable description of the MD results, as the fit parameters show no systematic wave-vector dependence, although the Ct(k,t) functions are somewhat better fitted. Similarly, the semiempirical interpolation formula for the decay time based on the viscoelastic concept proposed by Akcasu and Daniels fails to reproduce the correct k dependence for the wavelength range investigated herein.

  9. Matched molecular pair-based data sets for computer-aided medicinal chemistry [v1; ref status: indexed, http://f1000r.es/2w9

    Directory of Open Access Journals (Sweden)

    Ye Hu

    2014-02-01

    Full Text Available Matched molecular pairs (MMPs are widely used in medicinal chemistry to study changes in compound properties including biological activity, which are associated with well-defined structural modifications. Herein we describe up-to-date versions of three MMP-based data sets that have originated from in-house research projects. These data sets include activity cliffs, structure-activity relationship (SAR transfer series, and second generation MMPs based upon retrosynthetic rules. The data sets have in common that they have been derived from compounds included in the latest release of the ChEMBL database for which high-confidence activity data are available. Thus, the activity data associated with MMP-based activity cliffs, SAR transfer series, and retrosynthetic MMPs cover the entire spectrum of current pharmaceutical targets. Our data sets are made freely available to the scientific community.

  10. Computational genomics of hyperthermophiles

    NARCIS (Netherlands)

    Werken, van de H.J.G.

    2008-01-01

    With the ever increasing number of completely sequenced prokaryotic genomes and the subsequent use of functional genomics tools, e.g. DNA microarray and proteomics, computational data analysis and the integration of microbial and molecular data is inevitable. This thesis describes the computational

  11. Computational docking, molecular dynamics simulation and subsite structure analysis of a maltogenic amylase from Bacillus lehensis G1 provide insights into substrate and product specificity.

    Science.gov (United States)

    Manas, Nor Hasmaliana Abdul; Bakar, Farah Diba Abu; Illias, Rosli Md

    2016-06-01

    Maltogenic amylase (MAG1) from Bacillus lehensis G1 displayed the highest hydrolysis activity on β-cyclodextrin (β-CD) to produce maltose as a main product and exhibited high transglycosylation activity on malto-oligosaccharides with polymerization degree of three and above. These substrate and product specificities of MAG1 were elucidated from structural point of view in this study. A three-dimensional structure of MAG1 was constructed using homology modeling. Docking of β-CD and malto-oligosaccharides was then performed in the MAG1 active site. An aromatic platform in the active site was identified which is responsible in substrate recognition especially in determining the enzyme's preference toward β-CD. Molecular dynamics (MD) simulation showed MAG1 structure is most stable when docked with β-CD and least stable when docked with maltose. The docking analysis and MD simulation showed that the main subsites for substrate stabilization in the active site are -2, -1, +1 and +2. A bulky residue, Trp359 at the +2 subsite was identified to cause steric interference to the bound linear malto-oligosaccharides thus prevented it to occupy subsite +3, which can only be reached by a highly bent glucose molecule such as β-CD. The resulted modes of binding from docking simulation show a good correlation with the experimentally determined hydrolysis pattern. The subsite structure generated from this study led to a possible mode of action that revealed how maltose was mainly produced during hydrolysis. Furthermore, maltose only occupies subsite +1 and +2, therefore could not be hydrolyzed or transglycosylated by the enzyme. This important knowledge has paved the way for a novel structure-based molecular design for modulation of its catalytic activities. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Understanding molecular simulation: from algorithms to applications

    NARCIS (Netherlands)

    Frenkel, D.; Smit, B.

    2002-01-01

    Second and revised edition Understanding Molecular Simulation: From Algorithms to Applications explains the physics behind the "recipes" of molecular simulation for materials science. Computer simulators are continuously confronted with questions concerning the choice of a particular technique

  13. FT-IR, FT-Raman spectra, density functional computations of the vibrational spectra and molecular conformational analysis of 2,5-di-tert-butyl-hydroquinone

    Science.gov (United States)

    Subramanian, N.; Sundaraganesan, N.; Dereli, Ö.; Türkkan, E.

    2011-12-01

    The purpose of finding conformer among six different possible conformers of 2,5-di-tert-butyl-hydroquinone (DTBHQ), its equilibrium geometry and harmonic wavenumbers were calculated by the B3LYP/6-31G(d,p) method. The infrared and Raman spectra of DTBHQ were recorded in the region 400-4000 cm -1 and 50-3500 cm -1, respectively. In addition, the IR spectra in CCl 4 at various concentrations of DTBHQ are also recorded. The computed vibrational wavenumbers were compared with the IR and Raman experimental data. Computational calculations at B3LYP level with two different basis sets 6-31G(d,p) and 6-311++G(d,p) are also employed in the study of the possible conformer of DTBHQ. The complete assignments were performed on the basis of the potential energy distribution (PED) of the vibrational modes, calculated using VEDA 4 program. The general agreement between the observed and calculated frequencies was established.

  14. Synthesis, characterization and biological application of four novel metal-Schiff base complexes derived from allylamine and their interactions with human serum albumin: Experimental, molecular docking and ONIOM computational study.

    Science.gov (United States)

    Kazemi, Zahra; Rudbari, Hadi Amiri; Sahihi, Mehdi; Mirkhani, Valiollah; Moghadam, Majid; Tangestaninejad, Shahram; Mohammadpoor-Baltork, Iraj; Gharaghani, Sajjad

    2016-09-01

    Novel metal-based drug candidate including VOL2, NiL2, CuL2 and PdL2 have been synthesized from 2-hydroxy-1-allyliminomethyl-naphthalen ligand and have been characterized by means of elemental analysis (CHN), FT-IR and UV-vis spectroscopies. In addition, (1)H and (13)C NMR techniques were employed for characterization of the PdL2 complex. Single-crystal X-ray diffraction technique was utilized to characterise the structure of the complexes. The Cu(II), Ni(II) and Pd(II) complexes show a square planar trans-coordination geometry, while in the VOL2, the vanadium center has a distorted tetragonal pyramidal N2O3 coordination sphere. The HSA-binding was also determined, using fluorescence quenching, UV-vis spectroscopy, and circular dichroism (CD) titration method. The obtained results revealed that the HSA affinity for binding the synthesized compounds follows as PdL2>CuL2>VOL2>NiL2, indicating the effect of metal ion on binding constant. The distance between these compounds and HSA was obtained based on the Förster's theory of non-radiative energy transfer. Furthermore, computational methods including molecular docking and our Own N-layered Integrated molecular Orbital and molecular Mechanics (ONIOM) were carried out to investigate the HSA-binding of the compounds. Molecular docking calculation indicated the existence of hydrogen bond between amino acid residues of HSA and all synthesized compounds. The formation of the hydrogen bond in the HSA-compound systems leads to their stabilization. The ONIOM method was utilized in order to investigate HSA binding of compounds more precisely in which molecular mechanics method (UFF) and semi empirical method (PM6) were selected for the low layer and the high layer, respectively. The results show that the structural parameters of the compounds changed along with binding to HSA, indicating the strong interaction between the compounds and HSA. The value of binding constant depends on the extent of the resultant changes. This

  15. Computational neurogenetic modeling

    CERN Document Server

    Benuskova, Lubica

    2010-01-01

    Computational Neurogenetic Modeling is a student text, introducing the scope and problems of a new scientific discipline - Computational Neurogenetic Modeling (CNGM). CNGM is concerned with the study and development of dynamic neuronal models for modeling brain functions with respect to genes and dynamic interactions between genes. These include neural network models and their integration with gene network models. This new area brings together knowledge from various scientific disciplines, such as computer and information science, neuroscience and cognitive science, genetics and molecular biol

  16. Predicting the Metabolic Sites by Flavin-Containing Monooxygenase on Drug Molecules Using SVM Classification on Computed Quantum Mechanics and Circular Fingerprints Molecular Descriptors.

    Directory of Open Access Journals (Sweden)

    Chien-Wei Fu

    Full Text Available As an important enzyme in Phase I drug metabolism, the flavin-containing monooxygenase (FMO also metabolizes some xenobiotics with soft nucleophiles. The site of metabolism (SOM on a molecule is the site where the metabolic reaction is exerted by an enzyme. Accurate prediction of SOMs on drug molecules will assist the search for drug leads during the optimization process. Here, some quantum mechanics features such as the condensed Fukui function and attributes from circular fingerprints (called Molprint2D are computed and classified using the support vector machine (SVM for predicting some potential SOMs on a series of drugs that can be metabolized by FMO enzymes. The condensed Fukui function fA- representing the nucleophilicity of central atom A and the attributes from circular fingerprints accounting the influence of neighbors on the central atom. The total number of FMO substrates and non-substrates collected in the study is 85 and they are equally divided into the training and test sets with each carrying roughly the same number of potential SOMs. However, only N-oxidation and S-oxidation features were considered in the prediction since the available C-oxidation data was scarce. In the training process, the LibSVM package of WEKA package and the option of 10-fold cross validation are employed. The prediction performance on the test set evaluated by accuracy, Matthews correlation coefficient and area under ROC curve computed are 0.829, 0.659, and 0.877 respectively. This work reveals that the SVM model built can accurately predict the potential SOMs for drug molecules that are metabolizable by the FMO enzymes.

  17. Computation-Assisted Molecularly Imprinted Polymer Synthesis for Extraction of Naltrexone from Urine Using Experimental Design and Determination by UPLC-DAD.

    Science.gov (United States)

    Rahmani, Mahdiyeh Ebrahimi; Ansari, Mehdi; Nateghi, Mohammadreza; Kazemipour, Maryam

    2017-05-01

    To design a molecularly imprinted polymer (MIP) for naltrexone, calculations were performed using Gaussian 03 software, and the interaction energy (ΔE) of template-monomer complexes was estimated using the density functional theory method with the B3LYP function and 6-311G (d) basis set. The effect of different solvents in the polymerization process was studied using the polarizable continuum model. It was shown that five molecules of methacrylic acid gave the largest ΔE with tetrahydrofuran as the polymerization solvent. Effective factors of the removal efficiency of naltrexone by the MIP were selected using a central composite design, and thereafter, the optimization of significant factors was performed by response surface methodology. The results predicted through these models showed good agreement with experimental values. The adsorption amount, selectivity distribution coefficient, and selectivity coefficient were found to be 11.60 mg/g, 35.31, and 2.27, respectively. Experiments of naltrexone adsorption onto the MIP were in accordance with the first-order and Langmuir-Freundlich adsorption models. By applying the data to the Scatchard equation, the KD and Qmax were determined as 526.31 mg/L and 19.47 mg/g, respectively.

  18. Understanding the adsorptive interactions of arsenate-iron nanoparticles with curved fullerene-like sheets in activated carbon using a quantum mechanics/molecular mechanics computational approach.

    Science.gov (United States)

    Ha, Nguyen Ngoc; Cam, Le Minh; Ha, Nguyen Thi Thu; Goh, Bee-Min; Saunders, Martin; Jiang, Zhong-Tao; Altarawneh, Mohammednoor; Dlugogorski, Bogdan Z; El-Harbawi, Mohanad; Yin, Chun-Yang

    2017-06-07

    The prevalence of global arsenic groundwater contamination has driven widespread research on developing effective treatment systems including adsorption using various sorbents. The uptake of arsenic-based contaminants onto established sorbents such as activated carbon (AC) can be effectively enhanced via immobilization/impregnation of iron-based elements on the porous AC surface. Recent suggestions that AC pores structurally consist of an eclectic mix of curved fullerene-like sheets may affect the arsenic adsorption dynamics within the AC pores and is further complicated by the presence of nano-sized iron-based elements. We have therefore, attempted to shed light on the adsorptive interactions of arsenate-iron nanoparticles with curved fullerene-like sheets by using hybridized quantum mechanics/molecular mechanics (QMMM) calculations and microscopy characterization. It is found that, subsequent to optimization, chemisorption between HAsO 4 2- and the AC carbon sheet (endothermic process) is virtually non-existent - this observation is supported by experimental results. Conversely, the incorporation of iron nanoparticles (FeNPs) into the AC carbon sheet greatly facilitates chemisorption of HAsO 4 2- . Our calculation implies that iron carbide is formed at the junction between the iron and the AC interface and this tightly chemosorbed layer prevents detachment of the FeNPs on the AC surface. Other aspects including electronic structure/properties, carbon arrangement defects and rate of adsorptive interaction, which are determined using the Climbing-Image NEB method, are also discussed.

  19. Homogeneous nucleation of water in argon. Nucleation rate computation from molecular simulations of TIP4P and TIP4P/2005 water model.

    Science.gov (United States)

    Dumitrescu, Lucia R; Smeulders, David M J; Dam, Jacques A M; Gaastra-Nedea, Silvia V

    2017-02-28

    Molecular dynamics (MD) simulations were conducted to study nucleation of water at 350 K in argon using TIP4P and TIP4P/2005 water models. We found that the stability of any cluster, even if large, strongly depends on the energetic interactions with its vicinity, while the stable clusters change their composition almost entirely during nucleation. Using the threshold method, direct nucleation rates are obtained. Our nucleation rates are found to be 1.08×10 27 cm -3 s -1 for TIP4P and 2.30×10 27 cm -3 s -1 for TIP4P/2005. The latter model prescribes a faster dynamics than the former, with a nucleation rate two times larger due to its higher electrostatic charges. The non-equilibrium water densities derived from simulations and state-of-art equilibrium parameters from Vega and de Miguel [J. Chem. Phys. 126, 154707 (2007)] are used for the classical nucleation theory (CNT) prediction. The CNT overestimates our results for both water models, where TIP4P/2005 shows largest discrepancy. Our results complement earlier data at high nucleation rates and supersaturations in the Hale plot [Phys. Rev. A 33, 4156 (1986)], and are consistent with MD data on the SPC/E and the TIP4P/2005 model.

  20. Combined computational-experimental approach to predict blood-brain barrier (BBB) permeation based on "green" salting-out thin layer chromatography supported by simple molecular descriptors.

    Science.gov (United States)

    Ciura, Krzesimir; Belka, Mariusz; Kawczak, Piotr; Bączek, Tomasz; Markuszewski, Michał J; Nowakowska, Joanna

    2017-09-05

    The objective of this paper is to build QSRR/QSAR model for predicting the blood-brain barrier (BBB) permeability. The obtained models are based on salting-out thin layer chromatography (SOTLC) constants and calculated molecular descriptors. Among chromatographic methods SOTLC was chosen, since the mobile phases are free of organic solvent. As consequences, there are less toxic, and have lower environmental impact compared to classical reserved phases liquid chromatography (RPLC). During the study three stationary phase silica gel, cellulose plates and neutral aluminum oxide were examined. The model set of solutes presents a wide range of log BB values, containing compounds which cross the BBB readily and molecules poorly distributed to the brain including drugs acting on the nervous system as well as peripheral acting drugs. Additionally, the comparison of three regression models: multiple linear regression (MLR), partial least-squares (PLS) and orthogonal partial least squares (OPLS) were performed. The designed QSRR/QSAR models could be useful to predict BBB of systematically synthesized newly compounds in the drug development pipeline and are attractive alternatives of time-consuming and demanding directed methods for log BB measurement. The study also shown that among several regression techniques, significant differences can be obtained in models performance, measured by R 2 and Q 2 , hence it is strongly suggested to evaluate all available options as MLR, PLS and OPLS. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Discovery of Highly Potent Tyrosinase Inhibitor, T1, with Significant Anti-Melanogenesis Ability by zebrafish in vivo Assay and Computational Molecular Modeling

    Science.gov (United States)

    Chen, Wang-Chuan; Tseng, Tien-Sheng; Hsiao, Nai-Wan; Lin, Yun-Lian; Wen, Zhi-Hong; Tsai, Chin-Chuan; Lee, Yu-Ching; Lin, Hui-Hsiung; Tsai, Keng-Chang

    2015-01-01

    Tyrosinase is involved in melanin biosynthesis and the abnormal accumulation of melanin pigments leading to hyperpigmentation disorders that can be treated with depigmenting agents. A natural product T1, bis(4-hydroxybenzyl)sulfide, isolated from the Chinese herbal plant, Gastrodia elata, is a strong competitive inhibitor against mushroom tyrosinase (IC50 = 0.53 μM, Ki = 58 +/- 6 nM), outperforms than kojic acid. The cell viability and melanin quantification assay demonstrate that 50 μM of T1 apparently attenuates 20% melanin content of human normal melanocytes without significant cell toxicity. Moreover, the zebrafish in vivo assay reveals that T1 effectively reduces melanogenesis with no adverse side effects. The acute oral toxicity study evidently confirms that T1 molecule is free of discernable cytotoxicity in mice. Furthermore, the molecular modeling demonstrates that the sulfur atom of T1 coordinating with the copper ions in the active site of tyrosinase is essential for mushroom tyrosinase inhibition and the ability of diminishing the human melanin synthesis. These results evident that T1 isolated from Gastrodia elata is a promising candidate in developing pharmacological and cosmetic agents of great potency in skin-whitening.

  2. A computational systems biology software platform for multiscale modeling and simulation: Integrating whole-body physiology, disease biology, and molecular reaction networks

    Directory of Open Access Journals (Sweden)

    Thomas eEissing

    2011-02-01

    Full Text Available Today, in silico studies and trial simulations already complement experimental approaches in pharmaceutical R&D and have become indispensable tools for decision making and communication with regulatory agencies. While biology is multi-scale by nature, project work and software tools usually focus on isolated aspects of drug action, such as pharmacokinetics at the organism scale or pharmacodynamic interaction on the molecular level. We present a modeling and simulation software platform consisting of PK-Sim® and MoBi® capable of building and simulating models that integrate across biological scales. A prototypical multiscale model for the progression of a pancreatic tumor and its response to pharmacotherapy is constructed and virtual patients are treated with a prodrug activated by hepatic metabolization. Tumor growth is driven by signal transduction leading to cell cycle transition and proliferation. Free tumor concentrations of the active metabolite inhibit Raf kinase in the signaling cascade and thereby cell cycle progression. In a virtual clinical study, the individual therapeutic outcome of the chemotherapeutic intervention is simulated for a large population with heterogeneous genomic background. Thereby, the platform allows efficient model building and integration of biological knowledge and prior data from all biological scales. Experimental in vitro model systems can be linked with observations in animal experiments and clinical trials. The interplay between patients, diseases, and drugs and topics with high clinical relevance such as the role of pharmacogenomics, drug-drug or drug-metabolite interactions can be addressed using this mechanistic, insight driven multiscale modeling approach.

  3. Stepwise dissection and visualization of the catalytic mechanism of haloalkane dehalogenase LinB using molecular dynamics simulations and computer graphics.

    Science.gov (United States)

    Negri, Ana; Marco, Esther; Damborsky, Jiri; Gago, Federico

    2007-10-01

    The different steps of the dehalogenation reaction carried out by LinB on three different substrates have been characterized using a combination of quantum mechanical calculations and molecular dynamics simulations. This has allowed us to obtain information in atomic detail about each step of the reaction mechanism, that is, substrate entrance and achievement of the near-attack conformation, transition state stabilization within the active site, halide stabilization, water molecule activation and subsequent hydrolytic attack on the ester intermediate with formation of alcohol, and finally product release. Importantly, no bias or external forces were applied during the whole procedure so that both intermediates and products were completely free to sample configuration space in order to adapt to the plasticity of the active site and/or search for an exit. Differences in substrate reactivity were found to be correlated with the ease of adopting the near-attack conformation and two different exit pathways were found for product release that do not interfere with substrate entrance. Additional support for the different entry and exit pathways was independently obtained from an examination of the enzyme's normal modes.

  4. Clustering, microalloying and mechanical properties in Cu/Zr-based glassy models by molecular dynamics simulations and ab-initio computations

    Energy Technology Data Exchange (ETDEWEB)

    Lekka, Ch.E.; Bokas, G.B. [University of Ioannina, Department of Materials Science and Engineering, Ioannina 45100 (Greece); Almyras, G.A. [University of Ioannina, Department of Physics, Ioannina 45110 (Greece); Papageorgiou, D.G. [University of Ioannina, Department of Materials Science and Engineering, Ioannina 45100 (Greece); Evangelakis, G.A., E-mail: gevagel@cc.uoi.gr [University of Ioannina, Department of Physics, Ioannina 45110 (Greece)

    2012-09-25

    Highlights: Black-Right-Pointing-Pointer Cu-Zr MGs consist of interpenetrating ICO-like clusters (superclusters (SCs)). Black-Right-Pointing-Pointer The SCs participate in the accommodation of the tensile deformation. Black-Right-Pointing-Pointer The SCs may exhibit a free of bonds (FoB) plane. Black-Right-Pointing-Pointer Al microalloying changes the SCs' electronic structure inducing FoB planes. Black-Right-Pointing-Pointer Control of SCs' electronic structure may lead to control of MGs' properties. - Abstract: We present results on the microstructure of Cu-Zr metallic glasses (MGs) at equilibrium and under tensile deformation by means of large scale molecular dynamics (MD) simulations and density functional theory (DFT) calculations. We found that the MGs are composed by interpenetrating icosahedral-like (ICO) clusters forming superclusters (SCs). The deformation accommodation is associated with the destruction and recreation of these ICO clusters and SCs. DFT calculations on the Cu{sub 13}Zr{sub 10} SCs with Cu-Cu core atoms revealed the presence of a free of bonds (FoB) plane that could be viewed as analog of a slip plane of the crystalline materials. The microalloying (MA) effect in a similar SC (one of the core atoms substituted by Al) yielded that Al is associated with the formation of a FoB plane. These results provide possible explanations of the experimental findings referring to the short range order, the MA effect and could potentially be used for the design of new MGs.

  5. An examination of intrinsic errors in electronic structure methods using the Environmental Molecular Sciences Laboratory computational results database and the Gaussian-2 set

    International Nuclear Information System (INIS)

    Feller, D.; Peterson, K.A.

    1998-01-01

    The Gaussian-2 (G2) collection of atoms and molecules has been studied with Hartree endash Fock and correlated levels of theory, ranging from second-order perturbation theory to coupled cluster theory with noniterative inclusion of triple excitations. By exploiting the systematic convergence properties of the correlation consistent family of basis sets, complete basis set limits were estimated for a large number of the G2 energetic properties. Deviations with respect to experimentally derived energy differences corresponding to rigid molecules were obtained for 15 basis set/method combinations, as well as the estimated complete basis set limit. The latter values are necessary for establishing the intrinsic error for each method. In order to perform this analysis, the information generated in the present study was combined with the results of many previous benchmark studies in an electronic database, where it is available for use by other software tools. Such tools can assist users of electronic structure codes in making appropriate basis set and method choices that will increase the likelihood of achieving their accuracy goals without wasteful expenditures of computer resources. copyright 1998 American Institute of Physics

  6. Handbook of computational quantum chemistry

    CERN Document Server

    Cook, David B

    2005-01-01

    Quantum chemistry forms the basis of molecular modeling, a tool widely used to obtain important chemical information and visual images of molecular systems. Recent advances in computing have resulted in considerable developments in molecular modeling, and these developments have led to significant achievements in the design and synthesis of drugs and catalysts. This comprehensive text provides upper-level undergraduates and graduate students with an introduction to the implementation of quantum ideas in molecular modeling, exploring practical applications alongside theoretical explanations.Wri

  7. Molecular hematology

    National Research Council Canada - National Science Library

    Provan, Drew; Gribben, John

    2010-01-01

    ... The molecular basis of hemophilia, 219 Paul LF Giangrande 4 The genetics of acute myeloid leukemias, 42 Carolyn J Owen & Jude Fitzgibbon 19 The molecular basis of von Willebrand disease, 233 Luciano Baronc...

  8. A survey of computational physics introductory computational science

    CERN Document Server

    Landau, Rubin H; Bordeianu, Cristian C

    2008-01-01

    Computational physics is a rapidly growing subfield of computational science, in large part because computers can solve previously intractable problems or simulate natural processes that do not have analytic solutions. The next step beyond Landau's First Course in Scientific Computing and a follow-up to Landau and Páez's Computational Physics, this text presents a broad survey of key topics in computational physics for advanced undergraduates and beginning graduate students, including new discussions of visualization tools, wavelet analysis, molecular dynamics, and computational fluid dynamics

  9. Another cat and mouse game: Deciphering the evolution of the SCGB superfamily and exploring the molecular similarity of major cat allergen Fel d 1 and mouse ABP using computational approaches

    Science.gov (United States)

    Pageat, Patrick; Bienboire-Frosini, Cécile

    2018-01-01

    The mammalian secretoglobin (SCGB) superfamily contains functionally diverse members, among which the major cat allergen Fel d 1 and mouse salivary androgen-binding protein (ABP) display similar subunits. We searched for molecular similarities between Fel d 1 and ABP to examine the possibility that they play similar roles. We aimed to i) cluster the evolutionary relationships of the SCGB superfamily; ii) identify divergence patterns, structural overlap, and protein-protein docking between Fel d 1 and ABP dimers; and iii) explore the residual interaction between ABP dimers and steroid binding in chemical communication using computational approaches. We also report that the evolutionary tree of the SCGB superfamily comprises seven unique palm-like clusters, showing the evolutionary pattern and divergence time tree of Fel d 1 with 28 ABP paralogs. Three ABP subunits (A27, BG27, and BG26) share phylogenetic relationships with Fel d 1 chains. The Fel d 1 and ABP subunits show similarities in terms of sequence conservation, identical motifs and binding site clefts. Topologically equivalent positions were visualized through superimposition of ABP A27:BG27 (AB) and ABP A27:BG26 (AG) dimers on a heterodimeric Fel d 1 model. In docking, Fel d 1-ABP dimers exhibit the maximum surface binding ability of AG compared with that of AB dimers and the several polar interactions between ABP dimers with steroids. Hence, cat Fel d 1 is an ABP-like molecule in which monomeric chains 1 and 2 are the equivalent of the ABPA and ABPBG monomers, respectively. These findings suggest that the biological and molecular function of Fel d 1 is similar to that of ABP in chemical communication, possibly via pheromone and/or steroid binding. PMID:29771985

  10. Another cat and mouse game: Deciphering the evolution of the SCGB superfamily and exploring the molecular similarity of major cat allergen Fel d 1 and mouse ABP using computational approaches.

    Science.gov (United States)

    Durairaj, Rajesh; Pageat, Patrick; Bienboire-Frosini, Cécile

    2018-01-01

    The mammalian secretoglobin (SCGB) superfamily contains functionally diverse members, among which the major cat allergen Fel d 1 and mouse salivary androgen-binding protein (ABP) display similar subunits. We searched for molecular similarities between Fel d 1 and ABP to examine the possibility that they play similar roles. We aimed to i) cluster the evolutionary relationships of the SCGB superfamily; ii) identify divergence patterns, structural overlap, and protein-protein docking between Fel d 1 and ABP dimers; and iii) explore the residual interaction between ABP dimers and steroid binding in chemical communication using computational approaches. We also report that the evolutionary tree of the SCGB superfamily comprises seven unique palm-like clusters, showing the evolutionary pattern and divergence time tree of Fel d 1 with 28 ABP paralogs. Three ABP subunits (A27, BG27, and BG26) share phylogenetic relationships with Fel d 1 chains. The Fel d 1 and ABP subunits show similarities in terms of sequence conservation, identical motifs and binding site clefts. Topologically equivalent positions were visualized through superimposition of ABP A27:BG27 (AB) and ABP A27:BG26 (AG) dimers on a heterodimeric Fel d 1 model. In docking, Fel d 1-ABP dimers exhibit the maximum surface binding ability of AG compared with that of AB dimers and the several polar interactions between ABP dimers with steroids. Hence, cat Fel d 1 is an ABP-like molecule in which monomeric chains 1 and 2 are the equivalent of the ABPA and ABPBG monomers, respectively. These findings suggest that the biological and molecular function of Fel d 1 is similar to that of ABP in chemical communication, possibly via pheromone and/or steroid binding.

  11. From the X-rays to a reliable “low cost” computational structure of caffeic acid: DFT, MP2, HF and integrated molecular dynamics-X-ray diffraction approach to condensed phases

    Science.gov (United States)

    Lombardo, Giuseppe M.; Portalone, Gustavo; Colapietro, Marcello; Rescifina, Antonio; Punzo, Francesco

    2011-05-01

    The ability of caffeic acid to act as antioxidant against hyperoxo-radicals as well as its recently found therapeutic properties in the treatment of hepatocarcinoma, still make this compound, more than 20 years later the refinement of its crystal structure, object of study. It belongs to the vast family of humic substances, which play a key role in the biodegradation processes and easily form complexes with ions widely diffused in the environment. This class of compounds is therefore interesting for potential environmental chemistry applications concerning the possible complexation of heavy metals. Our study focused on the characterization of caffeic acid as a starting necessary step, which will be followed in the future by the application of our findings on the study of the properties of caffeate anion interaction with heavy metal ions. To reach this goal, we applied a low cost approach - in terms of computational time and resources - aimed at the achievement of a high resolution, robust and trustable structure using the X-ray single crystal data, recollected with a higher resolution, as touchstone for a detailed check. A comparison between the calculations carried out with density functional theory (DFT), Hartree-Fock (HF) method and post SCF second order Møller-Plesset perturbation method (MP2), at the 6-31G ** level of the theory, molecular mechanics (MM) and molecular dynamics (MD) was performed. As a consequence we explained on one hand the possible reasons for the pitfalls of the DFT approach and on the other the benefits of using a good and robust force field developed for condensed phases, as AMBER, with MM and MD. The reliability of the latter, highlighted by the overall agreement extended up to the anisotropic displacement parameters calculated by means of MD and the ones gathered by X-ray measurements, makes it very promising for the above-mentioned goals.

  12. Phylogenetic molecular function annotation

    International Nuclear Information System (INIS)

    Engelhardt, Barbara E; Jordan, Michael I; Repo, Susanna T; Brenner, Steven E

    2009-01-01

    It is now easier to discover thousands of protein sequences in a new microbial genome than it is to biochemically characterize the specific activity of a single protein of unknown function. The molecular functions of protein sequences have typically been predicted using homology-based computational methods, which rely on the principle that homologous proteins share a similar function. However, some protein families include groups of proteins with different molecular functions. A phylogenetic approach for predicting molecular function (sometimes called 'phylogenomics') is an effective means to predict protein molecular function. These methods incorporate functional evidence from all members of a family that have functional characterizations using the evolutionary history of the protein family to make robust predictions for the uncharacterized proteins. However, they are often difficult to apply on a genome-wide scale because of the time-consuming step of reconstructing the phylogenies of each protein to be annotated. Our automated approach for function annotation using phylogeny, the SIFTER (Statistical Inference of Function Through Evolutionary Relationships) methodology, uses a statistical graphical model to compute the probabilities of molecular functions for unannotated proteins. Our benchmark tests showed that SIFTER provides accurate functional predictions on various protein families, outperforming other available methods.

  13. Computation of the free energy change associated with one-electron reduction of coenzyme immersed in water: a novel approach within the framework of the quantum mechanical/molecular mechanical method combined with the theory of energy representation.

    Science.gov (United States)

    Takahashi, Hideaki; Ohno, Hajime; Kishi, Ryohei; Nakano, Masayoshi; Matubayasi, Nobuyuki

    2008-11-28

    The isoalloxazine ring (flavin ring) is a part of the coenzyme flavin adenine dinucleotide and acts as an active site in the oxidation of a substrate. We have computed the free energy change Deltamicro(red) associated with one-electron reduction of the flavin ring immersed in water by utilizing the quantum mechanical/molecular mechanical method combined with the theory of energy representation (QM/MM-ER method) recently developed. As a novel treatment in implementing the QM/MM-ER method, we have identified the excess charge to be attached on the flavin ring as a solute while the remaining molecules, i.e., flavin ring and surrounding water molecules, are treated as solvent species. Then, the reduction free energy can be decomposed into the contribution Deltamicro(red)(QM) due to the oxidant described quantum chemically and the free energy Deltamicro(red)(MM) due to the water molecules represented by a classical model. By the sum of these contributions, the total reduction free energy Deltamicro(red) has been given as -80.1 kcal/mol. To examine the accuracy and efficiency of this approach, we have also conducted the Deltamicro(red) calculation using the conventional scheme that Deltamicro(red) is constructed from the solvation free energies of the flavin rings at the oxidized and reduced states. The conventional scheme has been implemented with the QM/MM-ER method and the calculated Deltamicro(red) has been estimated as -81.0 kcal/mol, showing excellent agreement with the value given by the new approach. The present approach is efficient, in particular, to compute free energy change for the reaction occurring in a protein since it enables ones to circumvent the numerical problem brought about by subtracting the huge solvation free energies of the proteins in two states before and after the reduction.

  14. Substructured multibody molecular dynamics.

    Energy Technology Data Exchange (ETDEWEB)

    Grest, Gary Stephen; Stevens, Mark Jackson; Plimpton, Steven James; Woolf, Thomas B. (Johns Hopkins University, Baltimore, MD); Lehoucq, Richard B.; Crozier, Paul Stewart; Ismail, Ahmed E.; Mukherjee, Rudranarayan M. (Rensselaer Polytechnic Institute, Troy, NY); Draganescu, Andrei I.

    2006-11-01

    We have enhanced our parallel molecular dynamics (MD) simulation software LAMMPS (Large-scale Atomic/Molecular Massively Parallel Simulator, lammps.sandia.gov) to include many new features for accelerated simulation including articulated rigid body dynamics via coupling to the Rensselaer Polytechnic Institute code POEMS (Parallelizable Open-source Efficient Multibody Software). We use new features of the LAMMPS software package to investigate rhodopsin photoisomerization, and water model surface tension and capillary waves at the vapor-liquid interface. Finally, we motivate the recipes of MD for practitioners and researchers in numerical analysis and computational mechanics.

  15. Bringing molecules back into molecular evolution.

    Directory of Open Access Journals (Sweden)

    Claus O Wilke

    Full Text Available Much molecular-evolution research is concerned with sequence analysis. Yet these sequences represent real, three-dimensional molecules with complex structure and function. Here I highlight a growing trend in the field to incorporate molecular structure and function into computational molecular-evolution work. I consider three focus areas: reconstruction and analysis of past evolutionary events, such as phylogenetic inference or methods to infer selection pressures; development of toy models and simulations to identify fundamental principles of molecular evolution; and atom-level, highly realistic computational modeling of molecular structure and function aimed at making predictions about possible future evolutionary events.

  16. Homology modeling, docking studies and molecular dynamic simulations using graphical processing unit architecture to probe the type-11 phosphodiesterase catalytic site: a computational approach for the rational design of selective inhibitors.

    Science.gov (United States)

    Cichero, Elena; D'Ursi, Pasqualina; Moscatelli, Marco; Bruno, Olga; Orro, Alessandro; Rotolo, Chiara; Milanesi, Luciano; Fossa, Paola

    2013-12-01

    Phosphodiesterase 11 (PDE11) is the latest isoform of the PDEs family to be identified, acting on both cyclic adenosine monophosphate and cyclic guanosine monophosphate. The initial reports of PDE11 found evidence for PDE11 expression in skeletal muscle, prostate, testis, and salivary glands; however, the tissue distribution of PDE11 still remains a topic of active study and some controversy. Given the sequence similarity between PDE11 and PDE5, several PDE5 inhibitors have been shown to cross-react with PDE11. Accordingly, many non-selective inhibitors, such as IBMX, zaprinast, sildenafil, and dipyridamole, have been documented to inhibit PDE11. Only recently, a series of dihydrothieno[3,2-d]pyrimidin-4(3H)-one derivatives proved to be selective toward the PDE11 isoform. In the absence of experimental data about PDE11 X-ray structures, we found interesting to gain a better understanding of the enzyme-inhibitor interactions using in silico simulations. In this work, we describe a computational approach based on homology modeling, docking, and molecular dynamics simulation to derive a predictive 3D model of PDE11. Using a Graphical Processing Unit architecture, it is possible to perform long simulations, find stable interactions involved in the complex, and finally to suggest guideline for the identification and synthesis of potent and selective inhibitors. © 2013 John Wiley & Sons A/S.

  17. Connecting Molecular Dynamics and Computational Fluid Dynamics

    NARCIS (Netherlands)

    Markesteijn, A.P.

    2011-01-01

    One of the most important developments in the last centuries is the process of miniaturisation and understanding everything that it entails. For the physical sciences this meant the continuing discovery what matter is and how it behaves, while from a practical point of view it meant that more

  18. Molecular Diagnostics

    OpenAIRE

    Choe, Hyonmin; Deirmengian, Carl A.; Hickok, Noreen J.; Morrison, Tiffany N.; Tuan, Rocky S.

    2015-01-01

    Orthopaedic infections are complex conditions that require immediate diagnosis and accurate identification of the causative organisms to facilitate appropriate management. Conventional methodologies for diagnosis of these infections sometimes lack accuracy or sufficient rapidity. Current molecular diagnostics are an emerging area of bench-to-bedside research in orthopaedic infections. Examples of promising molecular diagnostics include measurement of a specific biomarker in the synovial fluid...

  19. Molecular genetics

    International Nuclear Information System (INIS)

    Parkinson, D.R.; Krontiris, T.G.

    1986-01-01

    In this chapter the authors review new findings concerning the molecular genetics of malignant melanoma in the context of other information obtained from clinical, epidemiologic, and cytogenetic studies in this malignancy. These new molecular approaches promise to provide a more complete understanding of the mechanisms involved in the development of melanoma, thereby suggesting new methods for its treatment and prevention

  20. Molecular Modeling

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 9; Issue 5. Molecular Modeling: A Powerful Tool for Drug Design and Molecular Docking. Rama Rao Nadendla. General Article Volume 9 Issue 5 May 2004 pp 51-60. Fulltext. Click here to view fulltext PDF. Permanent link:

  1. Designing the molecular future

    OpenAIRE

    Schneider Gisbert

    2011-01-01

    Approximately 25 years ago the first computer applications were conceived for the purpose of automated 'de novo' drug design prominent pioneering tools being ALADDIN CAVEAT GENOA and DYLOMMS. Many of these early concepts were enabled by innovative techniques for ligand receptor interaction modeling like GRID MCSS DOCK and CoMFA which still provide the theoretical framework for several more recently developed molecular design algorithms. After a first wave of software tools and groundbreaking ...

  2. Nanotechnology Review: Molecular Electronics to Molecular Motors

    Science.gov (United States)

    Srivastava, Deepak; Saini, Subhash (Technical Monitor)

    1998-01-01

    Reviewing the status of current approaches and future projections, as already published in scientific journals and books, the talk will summarize the direction in which computational and experimental nanotechnologies are progressing. Examples of nanotechnological approaches to the concepts of design and simulation of carbon nanotube based molecular electronic and mechanical devices will be presented. The concepts of nanotube based gears and motors will be discussed. The above is a non-technical review talk which covers long term precompetitive basic research in already published material that has been presented before many US scientific meeting audiences.

  3. Quantifying and Visualizing Uncertainties in Molecular Models

    OpenAIRE

    Rasheed, Muhibur; Clement, Nathan; Bhowmick, Abhishek; Bajaj, Chandrajit

    2015-01-01

    Computational molecular modeling and visualization has seen significant progress in recent years with sev- eral molecular modeling and visualization software systems in use today. Nevertheless the molecular biology community lacks techniques and tools for the rigorous analysis, quantification and visualization of the associated errors in molecular structure and its associated properties. This paper attempts at filling this vacuum with the introduction of a systematic statistical framework whe...

  4. Molecular geometry

    CERN Document Server

    Rodger, Alison

    1995-01-01

    Molecular Geometry discusses topics relevant to the arrangement of atoms. The book is comprised of seven chapters that tackle several areas of molecular geometry. Chapter 1 reviews the definition and determination of molecular geometry, while Chapter 2 discusses the unified view of stereochemistry and stereochemical changes. Chapter 3 covers the geometry of molecules of second row atoms, and Chapter 4 deals with the main group elements beyond the second row. The book also talks about the complexes of transition metals and f-block elements, and then covers the organometallic compounds and trans

  5. Optical Computing

    OpenAIRE

    Woods, Damien; Naughton, Thomas J.

    2008-01-01

    We consider optical computers that encode data using images and compute by transforming such images. We give an overview of a number of such optical computing architectures, including descriptions of the type of hardware commonly used in optical computing, as well as some of the computational efficiencies of optical devices. We go on to discuss optical computing from the point of view of computational complexity theory, with the aim of putting some old, and some very recent, re...

  6. Molecular Electronics

    DEFF Research Database (Denmark)

    Jennum, Karsten Stein

    This thesis includes the synthesis and characterisation of organic compounds designed for molecular electronics. The synthesised organic molecules are mainly based on two motifs, the obigo(phenyleneethynylenes) (OPE)s and tetrathiafulvalene (TTF) as shown below. These two scaffolds (OPE and TTF......) are chemically merged together to form cruciform-like structures that are an essential part of the thesis. The cruciform molecules were subjected to molecular conductance measurements to explore their capability towards single-crystal field-effect transistors (Part 1), molecular wires, and single electron......, however, was obtained by a study of a single molecular transistor. The investigated OPE5-TTF compound was captured in a three-terminal experiment, whereby manipulation of the molecule’s electronic spin was possible in different charge states. Thus, we demonstrated how the cruciform molecules could...

  7. Molecular sciences

    International Nuclear Information System (INIS)

    Anon.

    1975-01-01

    The research in molecular sciences summarized includes photochemistry, radiation chemistry, geophysics, electromechanics, heavy-element oxidizers , heavy element chemistry collisions, atoms, organic solids. A list of publications is included

  8. Molecular digital pathology: progress and potential of exchanging molecular data.

    Science.gov (United States)

    Roy, Somak; Pfeifer, John D; LaFramboise, William A; Pantanowitz, Liron

    2016-09-01

    Many of the demands to perform next generation sequencing (NGS) in the clinical laboratory can be resolved using the principles of telepathology. Molecular telepathology can allow facilities to outsource all or a portion of their NGS operation such as cloud computing, bioinformatics pipelines, variant data management, and knowledge curation. Clinical pathology laboratories can electronically share diverse types of molecular data with reference laboratories, technology service providers, and/or regulatory agencies. Exchange of electronic molecular data allows laboratories to perform validation of rare diseases using foreign data, check the accuracy of their test results against benchmarks, and leverage in silico proficiency testing. This review covers the emerging subject of molecular telepathology, describes clinical use cases for the appropriate exchange of molecular data, and highlights key issues such as data integrity, interoperable formats for massive genomic datasets, security, malpractice and emerging regulations involved with this novel practice.

  9. Light and redox switchable molecular components for molecular electronics.

    Science.gov (United States)

    Browne, Wesley R; Feringa, Ben L

    2010-01-01

    The field of molecular and organic electronics has seen rapid progress in recent years, developing from concept and design to actual demonstration devices in which both single molecules and self-assembled monolayers are employed as light-responsive components. Research in this field has seen numerous unexpected challenges that have slowed progress and the initial promise of complex molecular-based computers has not yet been realised. Primarily this has been due to the realisation at an early stage that molecular-based nano-electronics brings with it the interface between the hard (semiconductor) and soft (molecular) worlds and the challenges which accompany working in such an environment. Issues such as addressability, cross-talk, molecular stability and perturbation of molecular properties (e.g., inhibition of photochemistry) have nevertheless driven development in molecular design and synthesis as well as our ability to interface molecular components with bulk metal contacts to a very high level of sophistication. Numerous groups have played key roles in progressing this field not least teams such as those led by Whitesides, Aviram, Ratner, Stoddart and Heath. In this short review we will however focus on the contributions from our own group and those of our collaborators, in employing diarylethene based molecular components.

  10. Molecular dynamics for irradiation driven chemistry

    DEFF Research Database (Denmark)

    Sushko, Gennady B.; Solov'yov, Ilia A.; Solov'yov, Andrey V.

    2016-01-01

    A new molecular dynamics (MD) approach for computer simulations of irradiation driven chemical transformations of complex molecular systems is suggested. The approach is based on the fact that irradiation induced quantum transformations can often be treated as random, fast and local processes...... that describe the classical MD of complex molecular systems under irradiation. The proposed irradiation driven molecular dynamics (IDMD) methodology is designed for the molecular level description of the irradiation driven chemistry. The IDMD approach is implemented into the MBN Explorer software package...... involving small molecules or molecular fragments. We advocate that the quantum transformations, such as molecular bond breaks, creation and annihilation of dangling bonds, electronic charge redistributions, changes in molecular topologies, etc., could be incorporated locally into the molecular force fields...

  11. Molecular calculations with B functions

    International Nuclear Information System (INIS)

    Steinborn, E.O.; Homeier, H.H.H.; Ema, I.; Lopez, R.; Ramirez, G.

    2000-01-01

    A program for molecular calculations with B functions is reported and its performance is analyzed. All the one- and two-center integrals and the three-center nuclear attraction integrals are computed by direct procedures, using previously developed algorithms. The three- and four-center electron repulsion integrals are computed by means of Gaussian expansions of the B functions. A new procedure for obtaining these expansions is also reported. Some results on full molecular calculations are included to show the capabilities of the program and the quality of the B functions to represent the electronic functions in molecules

  12. Computer group

    International Nuclear Information System (INIS)

    Bauer, H.; Black, I.; Heusler, A.; Hoeptner, G.; Krafft, F.; Lang, R.; Moellenkamp, R.; Mueller, W.; Mueller, W.F.; Schati, C.; Schmidt, A.; Schwind, D.; Weber, G.

    1983-01-01

    The computer groups has been reorganized to take charge for the general purpose computers DEC10 and VAX and the computer network (Dataswitch, DECnet, IBM - connections to GSI and IPP, preparation for Datex-P). (orig.)

  13. Computer Engineers.

    Science.gov (United States)

    Moncarz, Roger

    2000-01-01

    Looks at computer engineers and describes their job, employment outlook, earnings, and training and qualifications. Provides a list of resources related to computer engineering careers and the computer industry. (JOW)

  14. Molecular fountain.

    Energy Technology Data Exchange (ETDEWEB)

    Strecker, Kevin E.; Chandler, David W.

    2009-09-01

    A molecular fountain directs slowly moving molecules against gravity to further slow them to translational energies that they can be trapped and studied. If the molecules are initially slow enough they will return some time later to the position from which they were launched. Because this round trip time can be on the order of a second a single molecule can be observed for times sufficient to perform Hz level spectroscopy. The goal of this LDRD proposal was to construct a novel Molecular Fountain apparatus capable of producing dilute samples of molecules at near zero temperatures in well-defined user-selectable, quantum states. The slowly moving molecules used in this research are produced by the previously developed Kinematic Cooling technique, which uses a crossed atomic and molecular beam apparatus to generate single rotational level molecular samples moving slowly in the laboratory reference frame. The Kinematic Cooling technique produces cold molecules from a supersonic molecular beam via single collisions with a supersonic atomic beam. A single collision of an atom with a molecule occurring at the correct energy and relative velocity can cause a small fraction of the molecules to move very slowly vertically against gravity in the laboratory. These slowly moving molecules are captured by an electrostatic hexapole guiding field that both orients and focuses the molecules. The molecules are focused into the ionization region of a time-of-flight mass spectrometer and are ionized by laser radiation. The new molecular fountain apparatus was built utilizing a new design for molecular beam apparatus that has allowed us to miniaturize the apparatus. This new design minimizes the volumes and surface area of the machine allowing smaller pumps to maintain the necessary background pressures needed for these experiments.

  15. NASA Applications of Molecular Nanotechnology

    Science.gov (United States)

    Globus, Al; Bailey, David; Han, Jie; Jaffe, Richard; Levit, Creon; Merkle, Ralph; Srivastava, Deepak

    1998-01-01

    Laboratories throughout the world are rapidly gaining atomically precise control over matter. As this control extends to an ever wider variety of materials, processes and devices, opportunities for applications relevant to NASA's missions will be created. This document surveys a number of future molecular nanotechnology capabilities of aerospace interest. Computer applications, launch vehicle improvements, and active materials appear to be of particular interest. We also list a number of applications for each of NASA's enterprises. If advanced molecular nanotechnology can be developed, almost all of NASA's endeavors will be radically improved. In particular, a sufficiently advanced molecular nanotechnology can arguably bring large scale space colonization within our grasp.

  16. Computer Music

    Science.gov (United States)

    Cook, Perry R.

    This chapter covers algorithms, technologies, computer languages, and systems for computer music. Computer music involves the application of computers and other digital/electronic technologies to music composition, performance, theory, history, and the study of perception. The field combines digital signal processing, computational algorithms, computer languages, hardware and software systems, acoustics, psychoacoustics (low-level perception of sounds from the raw acoustic signal), and music cognition (higher-level perception of musical style, form, emotion, etc.).

  17. Introduction Of Computational Materials Science

    International Nuclear Information System (INIS)

    Lee, Jun Geun

    2006-08-01

    This book gives, descriptions of computer simulation, computational materials science, typical three ways of computational materials science, empirical methods ; molecular dynamics such as potential energy, Newton's equation of motion, data production and analysis of results, quantum mechanical methods like wave equation, approximation, Hartree method, and density functional theory, dealing of solid such as pseudopotential method, tight-binding methods embedded atom method, Car-Parrinello method and combination simulation.

  18. Exploring the boundaries of molecular modeling : a study of nanochannels and transmembrane proteins

    NARCIS (Netherlands)

    Spijker, P.

    2009-01-01

    Many interesting physical and biological phenomena can be investigated using molecular modeling techniques, either theoretically or by using computer simulation methods, such as molecular dynamics and Monte Carlo simulations. Due to the increasing power of computer processing units, these simulation

  19. Estimation of the binding modes with important human cytochrome P450 enzymes, drug interaction potential, pharmacokinetics, and hepatotoxicity of ginger components using molecular docking, computational, and pharmacokinetic modeling studies.

    Science.gov (United States)

    Qiu, Jia-Xuan; Zhou, Zhi-Wei; He, Zhi-Xu; Zhang, Xueji; Zhou, Shu-Feng; Zhu, Shengrong

    2015-01-01

    Ginger is one of the most commonly used herbal medicines for the treatment of numerous ailments and improvement of body functions. It may be used in combination with prescribed drugs. The coadministration of ginger with therapeutic drugs raises a concern of potential deleterious drug interactions via the modulation of the expression and/or activity of drug-metabolizing enzymes and drug transporters, resulting in unfavorable therapeutic outcomes. This study aimed to determine the molecular interactions between 12 main active ginger components (6-gingerol, 8-gingerol, 10-gingerol, 6-shogaol, 8-shogaol, 10-shogaol, ar-curcumene, β-bisabolene, β-sesquiphelandrene, 6-gingerdione, (-)-zingiberene, and methyl-6-isogingerol) and human cytochrome P450 (CYP) 1A2, 2C9, 2C19, 2D6, and 3A4 and to predict the absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the 12 ginger components using computational approaches and comprehensive literature search. Docking studies showed that ginger components interacted with a panel of amino acids in the active sites of CYP1A2, 2C9, 2C19, 2D6, and 3A4 mainly through hydrogen bond formation, to a lesser extent, via π-π stacking. The pharmacokinetic simulation studies showed that the [I]/[Ki ] value for CYP2C9, 2C19, and 3A4 ranged from 0.0002 to 19.6 and the R value ranged from 1.0002 to 20.6 and that ginger might exhibit a high risk of drug interaction via inhibition of the activity of human CYP2C9 and CYP3A4, but a low risk of drug interaction toward CYP2C19-mediated drug metabolism. Furthermore, it has been evaluated that the 12 ginger components possessed a favorable ADMET profiles with regard to the solubility, absorption, permeability across the blood-brain barrier, interactions with CYP2D6, hepatotoxicity, and plasma protein binding. The validation results showed that there was no remarkable effect of ginger on the metabolism of warfarin in humans, whereas concurrent use of ginger and nifedipine exhibited a

  20. Analog computing

    CERN Document Server

    Ulmann, Bernd

    2013-01-01

    This book is a comprehensive introduction to analog computing. As most textbooks about this powerful computing paradigm date back to the 1960s and 1970s, it fills a void and forges a bridge from the early days of analog computing to future applications. The idea of analog computing is not new. In fact, this computing paradigm is nearly forgotten, although it offers a path to both high-speed and low-power computing, which are in even more demand now than they were back in the heyday of electronic analog computers.

  1. Dynamical processes in atomic and molecular physics

    CERN Document Server

    Ogurtsov, Gennadi

    2012-01-01

    Atomic and molecular physics underlie a basis for our knowledge of fundamental processes in nature and technology and in such applications as solid state physics, chemistry and biology. In recent years, atomic and molecular physics has undergone a revolutionary change due to great achievements in computing and experimental techniques. As a result, it has become possible to obtain information both on atomic and molecular characteristics and on dynamics of atomic and molecular processes. This e-book highlights the present state of investigations in the field of atomic and molecular physics. Rece

  2. Topology in Molecular Biology

    CERN Document Server

    Monastyrsky, Michail Ilych

    2007-01-01

    The book presents a class of new results in molecular biology for which topological methods and ideas are important. These include: the large-scale conformation properties of DNA; computational methods (Monte Carlo) allowing the simulation of large-scale properties of DNA; the tangle model of DNA recombination and other applications of Knot theory; dynamics of supercoiled DNA and biocatalitic properties of DNA; the structure of proteins; and other very recent problems in molecular biology. The text also provides a short course of modern topology intended for the broad audience of biologists and physicists. The authors are renowned specialists in their fields and some of the new results presented here are documented for the first time in monographic form.

  3. COMPUTATIONAL SCIENCE CENTER

    International Nuclear Information System (INIS)

    DAVENPORT, J.

    2006-01-01

    Computational Science is an integral component of Brookhaven's multi science mission, and is a reflection of the increased role of computation across all of science. Brookhaven currently has major efforts in data storage and analysis for the Relativistic Heavy Ion Collider (RHIC) and the ATLAS detector at CERN, and in quantum chromodynamics. The Laboratory is host for the QCDOC machines (quantum chromodynamics on a chip), 10 teraflop/s computers which boast 12,288 processors each. There are two here, one for the Riken/BNL Research Center and the other supported by DOE for the US Lattice Gauge Community and other scientific users. A 100 teraflop/s supercomputer will be installed at Brookhaven in the coming year, managed jointly by Brookhaven and Stony Brook, and funded by a grant from New York State. This machine will be used for computational science across Brookhaven's entire research program, and also by researchers at Stony Brook and across New York State. With Stony Brook, Brookhaven has formed the New York Center for Computational Science (NYCCS) as a focal point for interdisciplinary computational science, which is closely linked to Brookhaven's Computational Science Center (CSC). The CSC has established a strong program in computational science, with an emphasis on nanoscale electronic structure and molecular dynamics, accelerator design, computational fluid dynamics, medical imaging, parallel computing and numerical algorithms. We have been an active participant in DOES SciDAC program (Scientific Discovery through Advanced Computing). We are also planning a major expansion in computational biology in keeping with Laboratory initiatives. Additional laboratory initiatives with a dependence on a high level of computation include the development of hydrodynamics models for the interpretation of RHIC data, computational models for the atmospheric transport of aerosols, and models for combustion and for energy utilization. The CSC was formed to bring together

  4. COMPUTATIONAL SCIENCE CENTER

    Energy Technology Data Exchange (ETDEWEB)

    DAVENPORT, J.

    2006-11-01

    Computational Science is an integral component of Brookhaven's multi science mission, and is a reflection of the increased role of computation across all of science. Brookhaven currently has major efforts in data storage and analysis for the Relativistic Heavy Ion Collider (RHIC) and the ATLAS detector at CERN, and in quantum chromodynamics. The Laboratory is host for the QCDOC machines (quantum chromodynamics on a chip), 10 teraflop/s computers which boast 12,288 processors each. There are two here, one for the Riken/BNL Research Center and the other supported by DOE for the US Lattice Gauge Community and other scientific users. A 100 teraflop/s supercomputer will be installed at Brookhaven in the coming year, managed jointly by Brookhaven and Stony Brook, and funded by a grant from New York State. This machine will be used for computational science across Brookhaven's entire research program, and also by researchers at Stony Brook and across New York State. With Stony Brook, Brookhaven has formed the New York Center for Computational Science (NYCCS) as a focal point for interdisciplinary computational science, which is closely linked to Brookhaven's Computational Science Center (CSC). The CSC has established a strong program in computational science, with an emphasis on nanoscale electronic structure and molecular dynamics, accelerator design, computational fluid dynamics, medical imaging, parallel computing and numerical algorithms. We have been an active participant in DOES SciDAC program (Scientific Discovery through Advanced Computing). We are also planning a major expansion in computational biology in keeping with Laboratory initiatives. Additional laboratory initiatives with a dependence on a high level of computation include the development of hydrodynamics models for the interpretation of RHIC data, computational models for the atmospheric transport of aerosols, and models for combustion and for energy utilization. The CSC was formed to

  5. Computational composites

    DEFF Research Database (Denmark)

    Vallgårda, Anna K. A.; Redström, Johan

    2007-01-01

    Computational composite is introduced as a new type of composite material. Arguing that this is not just a metaphorical maneuver, we provide an analysis of computational technology as material in design, which shows how computers share important characteristics with other materials used in design...... and architecture. We argue that the notion of computational composites provides a precise understanding of the computer as material, and of how computations need to be combined with other materials to come to expression as material. Besides working as an analysis of computers from a designer’s point of view......, the notion of computational composites may also provide a link for computer science and human-computer interaction to an increasingly rapid development and use of new materials in design and architecture....

  6. Molecular spectroscopy

    International Nuclear Information System (INIS)

    Kokh, Eh.; Zonntag, B.

    1981-01-01

    The latest investigation results on molecular spectroscopy with application of synchrotron radiation in the region of vacuum ultraviolet are generalized. Some results on investigation of excited, superexcited and ionized molecule states with the use of adsorption spectroscopy, photoelectron spectroscopy, by fluorescent and mass-spectrometric methods are considered [ru

  7. Molecular Foundry

    Science.gov (United States)

    . New Study Indicates Greater Capacity for Carbon Storage in the Earth's Subsurface A team of Foundry minerals which make up the dominant clays in the Earth's deep subsurface. Doubling Down on Energy Storage identify molecular components within small volumes of biological samples, such as blood or urine. Industry

  8. Molecular farming

    NARCIS (Netherlands)

    Merck, K.B.; Vereijken, J.M.

    2006-01-01

    Molecular Farming is a new and emerging technology that promises relatively cheap and flexible production of large quantities of pharmaceuticals in genetically modified plants. Many stakeholders are involved in the production of pharmaceuticals in plants, which complicates the discussion on the

  9. Molecular gastronomy

    Science.gov (United States)

    This, Hervé

    2005-01-01

    For centuries, cooks have been applying recipes without looking for the mechanisms of the culinary transformations. A scientific discipline that explores these changes from raw ingredients to eating the final dish, is developing into its own field, termed molecular gastronomy. Here, one of the founders of the discipline discusses its aims and importance.

  10. Molecular Star

    Indian Academy of Sciences (India)

    In molecular self-assembly, molecules put themselves together in a predefined way ... work has been already published in Chemistry- A European Jour- nal in the September ... prevalent in matter ranging from atoms to molecules to biomolecules; it is also ... erate chemical forces are reversible and dynamic in nature mean-.

  11. Molecular ferromagnetism

    International Nuclear Information System (INIS)

    Epstein, A.J.

    1990-01-01

    This past year has been one of substantial advancement in both the physics and chemistry of molecular and polymeric ferromagnets. The specific heat studies of (DMeFc)(TCNE) have revealed a cusp at the three-dimensional ferromagnetic transition temperature with a crossover to primarily 1-D behavior at higher temperatures. This paper discusses these studies

  12. Quantum Computing

    OpenAIRE

    Scarani, Valerio

    1998-01-01

    The aim of this thesis was to explain what quantum computing is. The information for the thesis was gathered from books, scientific publications, and news articles. The analysis of the information revealed that quantum computing can be broken down to three areas: theories behind quantum computing explaining the structure of a quantum computer, known quantum algorithms, and the actual physical realizations of a quantum computer. The thesis reveals that moving from classical memor...

  13. Molecular bioinformatics: algorithms and applications

    National Research Council Canada - National Science Library

    Schulze-Kremer, S

    1996-01-01

    ... on molecular biology, especially D N A sequence analysis and protein structure prediction. These two issues are also central to this book. Other application areas covered here are: interpretation of spectroscopic data and discovery of structure-function relationships in D N A and proteins. Figure 1 depicts the interdependence of computer science,...

  14. Computational quantum chemistry website

    International Nuclear Information System (INIS)

    1997-01-01

    This report contains the contents of a web page related to research on the development of quantum chemistry methods for computational thermochemistry and the application of quantum chemistry methods to problems in material chemistry and chemical sciences. Research programs highlighted include: Gaussian-2 theory; Density functional theory; Molecular sieve materials; Diamond thin-film growth from buckyball precursors; Electronic structure calculations on lithium polymer electrolytes; Long-distance electronic coupling in donor/acceptor molecules; and Computational studies of NOx reactions in radioactive waste storage

  15. Computational Biology and High Performance Computing 2000

    Energy Technology Data Exchange (ETDEWEB)

    Simon, Horst D.; Zorn, Manfred D.; Spengler, Sylvia J.; Shoichet, Brian K.; Stewart, Craig; Dubchak, Inna L.; Arkin, Adam P.

    2000-10-19

    The pace of extraordinary advances in molecular biology has accelerated in the past decade due in large part to discoveries coming from genome projects on human and model organisms. The advances in the genome project so far, happening well ahead of schedule and under budget, have exceeded any dreams by its protagonists, let alone formal expectations. Biologists expect the next phase of the genome project to be even more startling in terms of dramatic breakthroughs in our understanding of human biology, the biology of health and of disease. Only today can biologists begin to envision the necessary experimental, computational and theoretical steps necessary to exploit genome sequence information for its medical impact, its contribution to biotechnology and economic competitiveness, and its ultimate contribution to environmental quality. High performance computing has become one of the critical enabling technologies, which will help to translate this vision of future advances in biology into reality. Biologists are increasingly becoming aware of the potential of high performance computing. The goal of this tutorial is to introduce the exciting new developments in computational biology and genomics to the high performance computing community.

  16. The nonequilibrium molecular dynamics

    International Nuclear Information System (INIS)

    Hoover, W.G.

    1992-03-01

    MOLECULAR DYNAMICS has been generalized in order to simulate a variety of NONEQUILIBRIUM systems. This generalization has been achieved by adopting microscopic mechanical definitions of macroscopic thermodynamic and hydrodynamic variables, such as temperature and stress. Some of the problems already treated include rapid plastic deformation, intense heat conduction, strong shockwaves simulation, and far-from-equilibrium phase transformations. Continuing advances in technique and in the modeling of interatomic forces, coupled with qualitative improvements in computer hardware, are enabling such simulations to approximate real-world microscale and nanoscale experiments

  17. Pattern recognition in molecular dynamics. [FORTRAN

    Energy Technology Data Exchange (ETDEWEB)

    Zurek, W H; Schieve, W C [Texas Univ., Austin (USA)

    1977-07-01

    An algorithm for the recognition of the formation of bound molecular states in the computer simulation of a dilute gas is presented. Applications to various related problems in physics and chemistry are pointed out. Data structure and decision processes are described. Performance of the FORTRAN program based on the algorithm in cooperation with the molecular dynamics program is described and the results are presented.

  18. Molecular simulations and visualization: introduction and overview.

    Science.gov (United States)

    Hirst, Jonathan D; Glowacki, David R; Baaden, Marc

    2014-01-01

    Here we provide an introduction and overview of current progress in the field of molecular simulation and visualization, touching on the following topics: (1) virtual and augmented reality for immersive molecular simulations; (2) advanced visualization and visual analytic techniques; (3) new developments in high performance computing; and (4) applications and model building.

  19. Molecular scale

    Directory of Open Access Journals (Sweden)

    Christopher H. Childers

    2016-03-01

    Full Text Available This manuscript demonstrates the molecular scale cure rate dependence of di-functional epoxide based thermoset polymers cured with amines. A series of cure heating ramp rates were used to determine the influence of ramp rate on the glass transition temperature (Tg and sub-Tg transitions and the average free volume hole size in these systems. The networks were comprised of 3,3′-diaminodiphenyl sulfone (33DDS and diglycidyl ether of bisphenol F (DGEBF and were cured at ramp rates ranging from 0.5 to 20 °C/min. Differential scanning calorimetry (DSC and NIR spectroscopy were used to explore the cure ramp rate dependence of the polymer network growth, whereas broadband dielectric spectroscopy (BDS and free volume hole size measurements were used to interrogate networks’ molecular level structural variations upon curing at variable heating ramp rates. It was found that although the Tg of the polymer matrices was similar, the NIR and DSC measurements revealed a strong correlation for how these networks grow in relation to the cure heating ramp rate. The free volume analysis and BDS results for the cured samples suggest differences in the molecular architecture of the matrix polymers due to cure heating rate dependence.

  20. Computational Medicine

    DEFF Research Database (Denmark)

    Nygaard, Jens Vinge

    2017-01-01

    The Health Technology Program at Aarhus University applies computational biology to investigate the heterogeneity of tumours......The Health Technology Program at Aarhus University applies computational biology to investigate the heterogeneity of tumours...

  1. Grid Computing

    Indian Academy of Sciences (India)

    A computing grid interconnects resources such as high performancecomputers, scientific databases, and computercontrolledscientific instruments of cooperating organizationseach of which is autonomous. It precedes and is quitedifferent from cloud computing, which provides computingresources by vendors to customers ...

  2. Green Computing

    Directory of Open Access Journals (Sweden)

    K. Shalini

    2013-01-01

    Full Text Available Green computing is all about using computers in a smarter and eco-friendly way. It is the environmentally responsible use of computers and related resources which includes the implementation of energy-efficient central processing units, servers and peripherals as well as reduced resource consumption and proper disposal of electronic waste .Computers certainly make up a large part of many people lives and traditionally are extremely damaging to the environment. Manufacturers of computer and its parts have been espousing the green cause to help protect environment from computers and electronic waste in any way.Research continues into key areas such as making the use of computers as energy-efficient as Possible, and designing algorithms and systems for efficiency-related computer technologies.

  3. Estimation of the binding modes with important human cytochrome P450 enzymes, drug interaction potential, pharmacokinetics, and hepatotoxicity of ginger components using molecular docking, computational, and pharmacokinetic modeling studies

    Directory of Open Access Journals (Sweden)

    Qiu JX

    2015-02-01

    Full Text Available Jia-Xuan Qiu,1,2 Zhi-Wei Zhou,3 Zhi-Xu He,4 Xueji Zhang,5 Shu-Feng Zhou,3 Shengrong Zhu11Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; 4Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Center and Sino-US Joint Laboratory for Medical Sciences, Guiyang Medical University, Guiyang, Guizhou, People’s Republic of China; 5Research Center for Bioengineering and Sensing Technology, University of Science and Technology Beijing, Beijing, People’s Republic of ChinaAbstract: Ginger is one of the most commonly used herbal medicines for the treatment of numerous ailments and improvement of body functions. It may be used in combination with prescribed drugs. The coadministration of ginger with therapeutic drugs raises a concern of potential deleterious drug interactions via the modulation of the expression and/or activity of drug-metabolizing enzymes and drug transporters, resulting in unfavorable therapeutic outcomes. This study aimed to determine the molecular interactions between 12 main active ginger components (6-gingerol, 8-gingerol, 10-gingerol, 6-shogaol, 8-shogaol, 10-shogaol, ar-curcumene, ß-bisabolene, ß-sesquiphelandrene, 6-gingerdione, (--zingiberene, and methyl-6-isogingerol and human cytochrome P450 (CYP 1A2, 2C9, 2C19, 2D6, and 3A4 and to predict the absorption, distribution, metabolism, excretion, and toxicity (ADMET of the 12 ginger components using computational approaches and comprehensive literature search. Docking studies showed that ginger components interacted with a panel of amino acids in the active sites of CYP1A

  4. Quantum computers and quantum computations

    International Nuclear Information System (INIS)

    Valiev, Kamil' A

    2005-01-01

    This review outlines the principles of operation of quantum computers and their elements. The theory of ideal computers that do not interact with the environment and are immune to quantum decohering processes is presented. Decohering processes in quantum computers are investigated. The review considers methods for correcting quantum computing errors arising from the decoherence of the state of the quantum computer, as well as possible methods for the suppression of the decohering processes. A brief enumeration of proposed quantum computer realizations concludes the review. (reviews of topical problems)

  5. Quantum Computing for Computer Architects

    CERN Document Server

    Metodi, Tzvetan

    2011-01-01

    Quantum computers can (in theory) solve certain problems far faster than a classical computer running any known classical algorithm. While existing technologies for building quantum computers are in their infancy, it is not too early to consider their scalability and reliability in the context of the design of large-scale quantum computers. To architect such systems, one must understand what it takes to design and model a balanced, fault-tolerant quantum computer architecture. The goal of this lecture is to provide architectural abstractions for the design of a quantum computer and to explore

  6. Pervasive Computing

    NARCIS (Netherlands)

    Silvis-Cividjian, N.

    This book provides a concise introduction to Pervasive Computing, otherwise known as Internet of Things (IoT) and Ubiquitous Computing (Ubicomp) which addresses the seamless integration of computing systems within everyday objects. By introducing the core topics and exploring assistive pervasive

  7. Computational vision

    CERN Document Server

    Wechsler, Harry

    1990-01-01

    The book is suitable for advanced courses in computer vision and image processing. In addition to providing an overall view of computational vision, it contains extensive material on topics that are not usually covered in computer vision texts (including parallel distributed processing and neural networks) and considers many real applications.

  8. Spatial Computation

    Science.gov (United States)

    2003-12-01

    Computation and today’s microprocessors with the approach to operating system architecture, and the controversy between microkernels and monolithic kernels...Both Spatial Computation and microkernels break away a relatively monolithic architecture into in- dividual lightweight pieces, well specialized...for their particular functionality. Spatial Computation removes global signals and control, in the same way microkernels remove the global address

  9. Parallel computations

    CERN Document Server

    1982-01-01

    Parallel Computations focuses on parallel computation, with emphasis on algorithms used in a variety of numerical and physical applications and for many different types of parallel computers. Topics covered range from vectorization of fast Fourier transforms (FFTs) and of the incomplete Cholesky conjugate gradient (ICCG) algorithm on the Cray-1 to calculation of table lookups and piecewise functions. Single tridiagonal linear systems and vectorized computation of reactive flow are also discussed.Comprised of 13 chapters, this volume begins by classifying parallel computers and describing techn

  10. Human Computation

    CERN Multimedia

    CERN. Geneva

    2008-01-01

    What if people could play computer games and accomplish work without even realizing it? What if billions of people collaborated to solve important problems for humanity or generate training data for computers? My work aims at a general paradigm for doing exactly that: utilizing human processing power to solve computational problems in a distributed manner. In particular, I focus on harnessing human time and energy for addressing problems that computers cannot yet solve. Although computers have advanced dramatically in many respects over the last 50 years, they still do not possess the basic conceptual intelligence or perceptual capabilities...

  11. Quantum computation

    International Nuclear Information System (INIS)

    Deutsch, D.

    1992-01-01

    As computers become ever more complex, they inevitably become smaller. This leads to a need for components which are fabricated and operate on increasingly smaller size scales. Quantum theory is already taken into account in microelectronics design. This article explores how quantum theory will need to be incorporated into computers in future in order to give them their components functionality. Computation tasks which depend on quantum effects will become possible. Physicists may have to reconsider their perspective on computation in the light of understanding developed in connection with universal quantum computers. (UK)

  12. Molecular Simulation of Adsorption in Microporous Materials

    OpenAIRE

    Yiannourakou M.; Ungerer P.; Leblanc B.; Rozanska X.; Saxe P.; Vidal-Gilbert S.; Gouth F.; Montel F.

    2013-01-01

    The development of industrial software, the decreasing cost of computing time, and the availability of well-tested forcefields make molecular simulation increasingly attractive for chemical engineers. We present here several applications of Monte-Carlo simulation techniques, applied to the adsorption of fluids in microporous solids such as zeolites and model carbons (pores < 2 nm). Adsorption was computed in the Grand Canonical ensemble ...

  13. Molecular nanomagnets

    CERN Document Server

    Gatteschi, Dante; Villain, Jacques

    2006-01-01

    Nanomagnetism is a rapidly expanding area of research which appears to be able to provide novel applications. Magnetic molecules are at the very bottom of the possible size of nanomagnets and they provide a unique opportunity to observe the coexistence of classical and quantum properties. The discovery in the early 90's that a cluster comprising twelve manganese ions shows hysteresis of molecular origin, and later proved evidence of quantum effects, opened a new research area whichis still flourishing through the collaboration of chemists and physicists. This book is the first attempt to cover

  14. Molecular plasmonics

    CERN Document Server

    Fritzsche, Wolfgang

    2014-01-01

    Adopting a novel approach, this book provides a unique ""molecular perspective"" on plasmonics, concisely presenting the fundamentals and applications in a way suitable for beginners entering this hot field as well as for experienced researchers and practitioners. It begins by introducing readers to the optical effects that occur at the nanoscale and particularly their modification in the presence of biomolecules, followed by a concise yet thorough overview of the different methods for the actual fabrication of nanooptical materials. Further chapters address the relevant nanooptics, as well as

  15. Transuranic Computational Chemistry.

    Science.gov (United States)

    Kaltsoyannis, Nikolas

    2018-02-26

    Recent developments in the chemistry of the transuranic elements are surveyed, with particular emphasis on computational contributions. Examples are drawn from molecular coordination and organometallic chemistry, and from the study of extended solid systems. The role of the metal valence orbitals in covalent bonding is a particular focus, especially the consequences of the stabilization of the 5f orbitals as the actinide series is traversed. The fledgling chemistry of transuranic elements in the +II oxidation state is highlighted. Throughout, the symbiotic interplay of experimental and computational studies is emphasized; the extraordinary challenges of experimental transuranic chemistry afford computational chemistry a particularly valuable role at the frontier of the periodic table. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Computer software.

    Science.gov (United States)

    Rosenthal, L E

    1986-10-01

    Software is the component in a computer system that permits the hardware to perform the various functions that a computer system is capable of doing. The history of software and its development can be traced to the early nineteenth century. All computer systems are designed to utilize the "stored program concept" as first developed by Charles Babbage in the 1850s. The concept was lost until the mid-1940s, when modern computers made their appearance. Today, because of the complex and myriad tasks that a computer system can perform, there has been a differentiation of types of software. There is software designed to perform specific business applications. There is software that controls the overall operation of a computer system. And there is software that is designed to carry out specialized tasks. Regardless of types, software is the most critical component of any computer system. Without it, all one has is a collection of circuits, transistors, and silicone chips.

  17. Computer sciences

    Science.gov (United States)

    Smith, Paul H.

    1988-01-01

    The Computer Science Program provides advanced concepts, techniques, system architectures, algorithms, and software for both space and aeronautics information sciences and computer systems. The overall goal is to provide the technical foundation within NASA for the advancement of computing technology in aerospace applications. The research program is improving the state of knowledge of fundamental aerospace computing principles and advancing computing technology in space applications such as software engineering and information extraction from data collected by scientific instruments in space. The program includes the development of special algorithms and techniques to exploit the computing power provided by high performance parallel processors and special purpose architectures. Research is being conducted in the fundamentals of data base logic and improvement techniques for producing reliable computing systems.

  18. Deep Generative Models for Molecular Science

    DEFF Research Database (Denmark)

    Jørgensen, Peter Bjørn; Schmidt, Mikkel Nørgaard; Winther, Ole

    2018-01-01

    Generative deep machine learning models now rival traditional quantum-mechanical computations in predicting properties of new structures, and they come with a significantly lower computational cost, opening new avenues in computational molecular science. In the last few years, a variety of deep...... generative models have been proposed for modeling molecules, which differ in both their model structure and choice of input features. We review these recent advances within deep generative models for predicting molecular properties, with particular focus on models based on the probabilistic autoencoder (or...

  19. Molecular-beam scattering

    International Nuclear Information System (INIS)

    Vernon, M.F.

    1983-07-01

    The molecular-beam technique has been used in three different experimental arrangements to study a wide range of inter-atomic and molecular forces. Chapter 1 reports results of a low-energy (0.2 kcal/mole) elastic-scattering study of the He-Ar pair potential. The purpose of the study was to accurately characterize the shape of the potential in the well region, by scattering slow He atoms produced by expanding a mixture of He in N 2 from a cooled nozzle. Chapter 2 contains measurements of the vibrational predissociation spectra and product translational energy for clusters of water, benzene, and ammonia. The experiments show that most of the product energy remains in the internal molecular motions. Chapter 3 presents measurements of the reaction Na + HCl → NaCl + H at collision energies of 5.38 and 19.4 kcal/mole. This is the first study to resolve both scattering angle and velocity for the reaction of a short lived (16 nsec) electronic excited state. Descriptions are given of computer programs written to analyze molecular-beam expansions to extract information characterizing their velocity distributions, and to calculate accurate laboratory elastic-scattering differential cross sections accounting for the finite apparatus resolution. Experimental results which attempted to determine the efficiency of optically pumping the Li(2 2 P/sub 3/2/) and Na(3 2 P/sub 3/2/) excited states are given. A simple three-level model for predicting the steady-state fraction of atoms in the excited state is included

  20. Computer programming and computer systems

    CERN Document Server

    Hassitt, Anthony

    1966-01-01

    Computer Programming and Computer Systems imparts a "reading knowledge? of computer systems.This book describes the aspects of machine-language programming, monitor systems, computer hardware, and advanced programming that every thorough programmer should be acquainted with. This text discusses the automatic electronic digital computers, symbolic language, Reverse Polish Notation, and Fortran into assembly language. The routine for reading blocked tapes, dimension statements in subroutines, general-purpose input routine, and efficient use of memory are also elaborated.This publication is inten

  1. Numerical computer methods part D

    CERN Document Server

    Johnson, Michael L

    2004-01-01

    The aim of this volume is to brief researchers of the importance of data analysis in enzymology, and of the modern methods that have developed concomitantly with computer hardware. It is also to validate researchers' computer programs with real and synthetic data to ascertain that the results produced are what they expected. Selected Contents: Prediction of protein structure; modeling and studying proteins with molecular dynamics; statistical error in isothermal titration calorimetry; analysis of circular dichroism data; model comparison methods.

  2. Logic circuits based on molecular spider systems.

    Science.gov (United States)

    Mo, Dandan; Lakin, Matthew R; Stefanovic, Darko

    2016-08-01

    Spatial locality brings the advantages of computation speed-up and sequence reuse to molecular computing. In particular, molecular walkers that undergo localized reactions are of interest for implementing logic computations at the nanoscale. We use molecular spider walkers to implement logic circuits. We develop an extended multi-spider model with a dynamic environment wherein signal transmission is triggered via localized reactions, and use this model to implement three basic gates (AND, OR, NOT) and a cascading mechanism. We develop an algorithm to automatically generate the layout of the circuit. We use a kinetic Monte Carlo algorithm to simulate circuit computations, and we analyze circuit complexity: our design scales linearly with formula size and has a logarithmic time complexity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Computational biomechanics

    International Nuclear Information System (INIS)

    Ethier, C.R.

    2004-01-01

    Computational biomechanics is a fast-growing field that integrates modern biological techniques and computer modelling to solve problems of medical and biological interest. Modelling of blood flow in the large arteries is the best-known application of computational biomechanics, but there are many others. Described here is work being carried out in the laboratory on the modelling of blood flow in the coronary arteries and on the transport of viral particles in the eye. (author)

  4. Approximation of quantum observables by molecular dynamics simulations

    KAUST Repository

    Sandberg, Mattias

    2016-01-01

    In this talk I will discuss how to estimate the uncertainty in molecular dynamics simulations. Molecular dynamics is a computational method to study molecular systems in materials science, chemistry, and molecular biology. The wide popularity of molecular dynamics simulations relies on the fact that in many cases it agrees very well with experiments. If we however want the simulation to predict something that has no comparing experiment, we need a mathematical estimate of the accuracy of the computation. In the case of molecular systems with few particles, such studies are made by directly solving the Schrodinger equation. In this talk I will discuss theoretical results on the accuracy between quantum mechanics and molecular dynamics, to be used for systems that are too large to be handled computationally by the Schrodinger equation.

  5. Approximation of quantum observables by molecular dynamics simulations

    KAUST Repository

    Sandberg, Mattias

    2016-01-06

    In this talk I will discuss how to estimate the uncertainty in molecular dynamics simulations. Molecular dynamics is a computational method to study molecular systems in materials science, chemistry, and molecular biology. The wide popularity of molecular dynamics simulations relies on the fact that in many cases it agrees very well with experiments. If we however want the simulation to predict something that has no comparing experiment, we need a mathematical estimate of the accuracy of the computation. In the case of molecular systems with few particles, such studies are made by directly solving the Schrodinger equation. In this talk I will discuss theoretical results on the accuracy between quantum mechanics and molecular dynamics, to be used for systems that are too large to be handled computationally by the Schrodinger equation.

  6. Computational Composites

    DEFF Research Database (Denmark)

    Vallgårda, Anna K. A.

    to understand the computer as a material like any other material we would use for design, like wood, aluminum, or plastic. That as soon as the computer forms a composition with other materials it becomes just as approachable and inspiring as other smart materials. I present a series of investigations of what...... Computational Composite, and Telltale). Through the investigations, I show how the computer can be understood as a material and how it partakes in a new strand of materials whose expressions come to be in context. I uncover some of their essential material properties and potential expressions. I develop a way...

  7. Charge Transport Processes in Molecular Junctions

    Science.gov (United States)

    Smith, Christopher Eugene

    Molecular electronics (ME) has evolved into a rich area of exploration that combines the fields of chemistry, materials, electronic engineering and computational modeling to explore the physics behind electronic conduction at the molecular level. Through studying charge transport properties of single molecules and nanoscale molecular materials the field has gained the potential to bring about new avenues for the miniaturization of electrical components where quantum phenomena are utilized to achieve solid state molecular device functionality. Molecular junctions are platforms that enable these studies and consist of a single molecule or a small group of molecules directly connected to electrodes. The work presented in this thesis has built upon the current understanding of the mechanisms of charge transport in ordered junctions using self-assembled monolayer (SAM) molecular thin films. Donor and acceptor compounds were synthesized and incorporated into SAMs grown on metal substrates then the transport properties were measured with conducting probe atomic force microscopy (CP-AFM). In addition to experimentally measured current-voltage (I-V) curves, the transport properties were addressed computationally and modeled theoretically. The key objectives of this project were to 1) investigate the impact of molecular structure on hole and electron charge transport, 2) understand the nature of the charge carriers and their structure-transport properties through long (chemically gated to modulate the transport. These results help advance our understanding of transport behavior in semiconducting molecular thin films, and open opportunities to engineer improved electronic functionality into molecular devices.

  8. Progress on molecular imaging

    International Nuclear Information System (INIS)

    Chen Quan; Zhang Yongxue

    2011-01-01

    Molecular imaging is a new era of medical imaging,which can non-invasively monitor biological processes at the cellular and molecular level in vivo, including molecular imaging of nuclear medicine, magnetic resonance molecular imaging, ultrasound molecular imaging,optical molecular imaging and molecular imaging with X-ray. Recently, with the development of multi-subjects amalgamation, multimodal molecular imaging technology has been applied in clinical imaging, such as PET-CT and PET-MRI. We believe that with development of molecular probe and multi-modal imaging, more and more molecular imaging techniques will be applied in clinical diagnosis and treatment. (authors)

  9. Computer Code for Interpreting 13C NMR Relaxation Measurements with Specific Models of Molecular Motion: The Rigid Isotropic and Symmetric Top Rotor Models and the Flexible Symmetric Top Rotor Model

    Science.gov (United States)

    2017-01-01

    top rotor superimposes an effective correlation time, τe, onto a symmetric top rotor to account for internal motion. 2. THEORY The purpose...specifically describe how simple 13C relaxation theory is used to describe quantitatively simple molecular 3 motions. More-detailed accounts ...of nuclear magnetic relaxation can be found in a number of basic textbooks (i.e., Farrar and Becker, 1971; Fukushima and Roeder, 1981; Harris, 1986

  10. Computational Physics' Greatest Hits

    Science.gov (United States)

    Bug, Amy

    2011-03-01

    The digital computer, has worked its way so effectively into our profession that now, roughly 65 years after its invention, it is virtually impossible to find a field of experimental or theoretical physics unaided by computational innovation. It is tough to think of another device about which one can make that claim. In the session ``What is computational physics?'' speakers will distinguish computation within the field of computational physics from this ubiquitous importance across all subfields of physics. This talk will recap the invited session ``Great Advances...Past, Present and Future'' in which five dramatic areas of discovery (five of our ``greatest hits'') are chronicled: The physics of many-boson systems via Path Integral Monte Carlo, the thermodynamic behavior of a huge number of diverse systems via Monte Carlo Methods, the discovery of new pharmaceutical agents via molecular dynamics, predictive simulations of global climate change via detailed, cross-disciplinary earth system models, and an understanding of the formation of the first structures in our universe via galaxy formation simulations. The talk will also identify ``greatest hits'' in our field from the teaching and research perspectives of other members of DCOMP, including its Executive Committee.

  11. GPGPU COMPUTING

    Directory of Open Access Journals (Sweden)

    BOGDAN OANCEA

    2012-05-01

    Full Text Available Since the first idea of using GPU to general purpose computing, things have evolved over the years and now there are several approaches to GPU programming. GPU computing practically began with the introduction of CUDA (Compute Unified Device Architecture by NVIDIA and Stream by AMD. These are APIs designed by the GPU vendors to be used together with the hardware that they provide. A new emerging standard, OpenCL (Open Computing Language tries to unify different GPU general computing API implementations and provides a framework for writing programs executed across heterogeneous platforms consisting of both CPUs and GPUs. OpenCL provides parallel computing using task-based and data-based parallelism. In this paper we will focus on the CUDA parallel computing architecture and programming model introduced by NVIDIA. We will present the benefits of the CUDA programming model. We will also compare the two main approaches, CUDA and AMD APP (STREAM and the new framwork, OpenCL that tries to unify the GPGPU computing models.

  12. Quantum Computing

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 5; Issue 9. Quantum Computing - Building Blocks of a Quantum Computer. C S Vijay Vishal Gupta. General Article Volume 5 Issue 9 September 2000 pp 69-81. Fulltext. Click here to view fulltext PDF. Permanent link:

  13. Platform computing

    CERN Multimedia

    2002-01-01

    "Platform Computing releases first grid-enabled workload management solution for IBM eServer Intel and UNIX high performance computing clusters. This Out-of-the-box solution maximizes the performance and capability of applications on IBM HPC clusters" (1/2 page) .

  14. Quantum Computing

    Indian Academy of Sciences (India)

    In the first part of this article, we had looked at how quantum physics can be harnessed to make the building blocks of a quantum computer. In this concluding part, we look at algorithms which can exploit the power of this computational device, and some practical difficulties in building such a device. Quantum Algorithms.

  15. Quantum computing

    OpenAIRE

    Burba, M.; Lapitskaya, T.

    2017-01-01

    This article gives an elementary introduction to quantum computing. It is a draft for a book chapter of the "Handbook of Nature-Inspired and Innovative Computing", Eds. A. Zomaya, G.J. Milburn, J. Dongarra, D. Bader, R. Brent, M. Eshaghian-Wilner, F. Seredynski (Springer, Berlin Heidelberg New York, 2006).

  16. Computational Pathology

    Science.gov (United States)

    Louis, David N.; Feldman, Michael; Carter, Alexis B.; Dighe, Anand S.; Pfeifer, John D.; Bry, Lynn; Almeida, Jonas S.; Saltz, Joel; Braun, Jonathan; Tomaszewski, John E.; Gilbertson, John R.; Sinard, John H.; Gerber, Georg K.; Galli, Stephen J.; Golden, Jeffrey A.; Becich, Michael J.

    2016-01-01

    Context We define the scope and needs within the new discipline of computational pathology, a discipline critical to the future of both the practice of pathology and, more broadly, medical practice in general. Objective To define the scope and needs of computational pathology. Data Sources A meeting was convened in Boston, Massachusetts, in July 2014 prior to the annual Association of Pathology Chairs meeting, and it was attended by a variety of pathologists, including individuals highly invested in pathology informatics as well as chairs of pathology departments. Conclusions The meeting made recommendations to promote computational pathology, including clearly defining the field and articulating its value propositions; asserting that the value propositions for health care systems must include means to incorporate robust computational approaches to implement data-driven methods that aid in guiding individual and population health care; leveraging computational pathology as a center for data interpretation in modern health care systems; stating that realizing the value proposition will require working with institutional administrations, other departments, and pathology colleagues; declaring that a robust pipeline should be fostered that trains and develops future computational pathologists, for those with both pathology and non-pathology backgrounds; and deciding that computational pathology should serve as a hub for data-related research in health care systems. The dissemination of these recommendations to pathology and bioinformatics departments should help facilitate the development of computational pathology. PMID:26098131

  17. Molecular imaging: current status and emerging strategies

    International Nuclear Information System (INIS)

    Pysz, M.A.; Gambhir, S.S.; Willmann, J.K.

    2010-01-01

    In vivo molecular imaging has a great potential to impact medicine by detecting diseases in early stages (screening), identifying extent of disease, selecting disease- and patient-specific treatment (personalized medicine), applying a directed or targeted therapy, and measuring molecular-specific effects of treatment. Current clinical molecular imaging approaches primarily use positron-emission tomography (PET) or single photon-emission computed tomography (SPECT)-based techniques. In ongoing preclinical research, novel molecular targets of different diseases are identified and, sophisticated and multifunctional contrast agents for imaging these molecular targets are developed along with new technologies and instrumentation for multi-modality molecular imaging. Contrast-enhanced molecular ultrasound (US) with molecularly-targeted contrast microbubbles is explored as a clinically translatable molecular imaging strategy for screening, diagnosing, and monitoring diseases at the molecular level. Optical imaging with fluorescent molecular probes and US imaging with molecularly-targeted microbubbles are attractive strategies as they provide real-time imaging, are relatively inexpensive, produce images with high spatial resolution, and do not involve exposure to ionizing irradiation. Raman spectroscopy/microscopy has emerged as a molecular optical imaging strategy for ultrasensitive detection of multiple biomolecules/biochemicals with both in vivo and ex vivo versatility. Photoacoustic imaging is a hybrid of optical and US techniques involving optically-excitable molecularly-targeted contrast agents and quantitative detection of resulting oscillatory contrast agent movement with US. Current preclinical findings and advances in instrumentation, such as endoscopes and microcatheters, suggest that these molecular imaging methods have numerous potential clinical applications and will be translated into clinical use in the near future.

  18. Cloud Computing

    DEFF Research Database (Denmark)

    Krogh, Simon

    2013-01-01

    with technological changes, the paradigmatic pendulum has swung between increased centralization on one side and a focus on distributed computing that pushes IT power out to end users on the other. With the introduction of outsourcing and cloud computing, centralization in large data centers is again dominating...... the IT scene. In line with the views presented by Nicolas Carr in 2003 (Carr, 2003), it is a popular assumption that cloud computing will be the next utility (like water, electricity and gas) (Buyya, Yeo, Venugopal, Broberg, & Brandic, 2009). However, this assumption disregards the fact that most IT production......), for instance, in establishing and maintaining trust between the involved parties (Sabherwal, 1999). So far, research in cloud computing has neglected this perspective and focused entirely on aspects relating to technology, economy, security and legal questions. While the core technologies of cloud computing (e...

  19. Computability theory

    CERN Document Server

    Weber, Rebecca

    2012-01-01

    What can we compute--even with unlimited resources? Is everything within reach? Or are computations necessarily drastically limited, not just in practice, but theoretically? These questions are at the heart of computability theory. The goal of this book is to give the reader a firm grounding in the fundamentals of computability theory and an overview of currently active areas of research, such as reverse mathematics and algorithmic randomness. Turing machines and partial recursive functions are explored in detail, and vital tools and concepts including coding, uniformity, and diagonalization are described explicitly. From there the material continues with universal machines, the halting problem, parametrization and the recursion theorem, and thence to computability for sets, enumerability, and Turing reduction and degrees. A few more advanced topics round out the book before the chapter on areas of research. The text is designed to be self-contained, with an entire chapter of preliminary material including re...

  20. Computational Streetscapes

    Directory of Open Access Journals (Sweden)

    Paul M. Torrens

    2016-09-01

    Full Text Available Streetscapes have presented a long-standing interest in many fields. Recently, there has been a resurgence of attention on streetscape issues, catalyzed in large part by computing. Because of computing, there is more understanding, vistas, data, and analysis of and on streetscape phenomena than ever before. This diversity of lenses trained on streetscapes permits us to address long-standing questions, such as how people use information while mobile, how interactions with people and things occur on streets, how we might safeguard crowds, how we can design services to assist pedestrians, and how we could better support special populations as they traverse cities. Amid each of these avenues of inquiry, computing is facilitating new ways of posing these questions, particularly by expanding the scope of what-if exploration that is possible. With assistance from computing, consideration of streetscapes now reaches across scales, from the neurological interactions that form among place cells in the brain up to informatics that afford real-time views of activity over whole urban spaces. For some streetscape phenomena, computing allows us to build realistic but synthetic facsimiles in computation, which can function as artificial laboratories for testing ideas. In this paper, I review the domain science for studying streetscapes from vantages in physics, urban studies, animation and the visual arts, psychology, biology, and behavioral geography. I also review the computational developments shaping streetscape science, with particular emphasis on modeling and simulation as informed by data acquisition and generation, data models, path-planning heuristics, artificial intelligence for navigation and way-finding, timing, synthetic vision, steering routines, kinematics, and geometrical treatment of collision detection and avoidance. I also discuss the implications that the advances in computing streetscapes might have on emerging developments in cyber

  1. Gas Phase Molecular Dynamics

    International Nuclear Information System (INIS)

    Hall, G.E.; Prrese, J.M.; Sears, T.J.; Weston, R.E.

    1999-01-01

    The goal of this research is the understanding of elementary chemical and physical processes important in the combustion of fossil fuels. Interest centers on reactions involving short-lived chemical intermediates and their properties. High-resolution high-sensitivity laser absorption methods are augmented by high temperature flow-tube reaction kinetics studies with mass spectrometric sampling. These experiments provide information on the energy levels, structures and reactivity of molecular flee radical species and, in turn, provide new tools for the study of energy flow and chemical bond cleavage in the radicals in chemical systems. The experimental work is supported by theoretical and computational work using time-dependent quantum wave packet calculations that provide insights into energy flow between the vibrational modes of the molecule

  2. Molecular dynamics simulations

    International Nuclear Information System (INIS)

    Alder, B.J.

    1985-07-01

    The molecular dynamics computer simulation discovery of the slow decay of the velocity autocorrelation function in fluids is briefly reviewed in order to contrast that long time tail with those observed for the stress autocorrelation function in fluids and the velocity autocorrelation function in the Lorentz gas. For a non-localized particle in the Lorentz gas it is made plausible that even if it behaved quantum mechanically its long time tail would be the same as the classical one. The generalization of Fick's law for diffusion for the Lorentz gas, necessary to avoid divergences due to the slow decay of correlations, is presented. For fluids, that generalization has not yet been established, but the region of validity of generalized hydrodynamics is discussed. 20 refs., 5 figs

  3. Visualizing functional motions of membrane transporters with molecular dynamics simulations.

    Science.gov (United States)

    Shaikh, Saher A; Li, Jing; Enkavi, Giray; Wen, Po-Chao; Huang, Zhijian; Tajkhorshid, Emad

    2013-01-29

    Computational modeling and molecular simulation techniques have become an integral part of modern molecular research. Various areas of molecular sciences continue to benefit from, indeed rely on, the unparalleled spatial and temporal resolutions offered by these technologies, to provide a more complete picture of the molecular problems at hand. Because of the continuous development of more efficient algorithms harvesting ever-expanding computational resources, and the emergence of more advanced and novel theories and methodologies, the scope of computational studies has expanded significantly over the past decade, now including much larger molecular systems and far more complex molecular phenomena. Among the various computer modeling techniques, the application of molecular dynamics (MD) simulation and related techniques has particularly drawn attention in biomolecular research, because of the ability of the method to describe the dynamical nature of the molecular systems and thereby to provide a more realistic representation, which is often needed for understanding fundamental molecular properties. The method has proven to be remarkably successful in capturing molecular events and structural transitions highly relevant to the function and/or physicochemical properties of biomolecular systems. Herein, after a brief introduction to the method of MD, we use a number of membrane transport proteins studied in our laboratory as examples to showcase the scope and applicability of the method and its power in characterizing molecular motions of various magnitudes and time scales that are involved in the function of this important class of membrane proteins.

  4. COMPUTATIONAL THINKING

    Directory of Open Access Journals (Sweden)

    Evgeniy K. Khenner

    2016-01-01

    Full Text Available Abstract. The aim of the research is to draw attention of the educational community to the phenomenon of computational thinking which actively discussed in the last decade in the foreign scientific and educational literature, to substantiate of its importance, practical utility and the right on affirmation in Russian education.Methods. The research is based on the analysis of foreign studies of the phenomenon of computational thinking and the ways of its formation in the process of education; on comparing the notion of «computational thinking» with related concepts used in the Russian scientific and pedagogical literature.Results. The concept «computational thinking» is analyzed from the point of view of intuitive understanding and scientific and applied aspects. It is shown as computational thinking has evolved in the process of development of computers hardware and software. The practice-oriented interpretation of computational thinking which dominant among educators is described along with some ways of its formation. It is shown that computational thinking is a metasubject result of general education as well as its tool. From the point of view of the author, purposeful development of computational thinking should be one of the tasks of the Russian education.Scientific novelty. The author gives a theoretical justification of the role of computational thinking schemes as metasubject results of learning. The dynamics of the development of this concept is described. This process is connected with the evolution of computer and information technologies as well as increase of number of the tasks for effective solutions of which computational thinking is required. Author substantiated the affirmation that including «computational thinking » in the set of pedagogical concepts which are used in the national education system fills an existing gap.Practical significance. New metasubject result of education associated with

  5. Computer interfacing

    CERN Document Server

    Dixey, Graham

    1994-01-01

    This book explains how computers interact with the world around them and therefore how to make them a useful tool. Topics covered include descriptions of all the components that make up a computer, principles of data exchange, interaction with peripherals, serial communication, input devices, recording methods, computer-controlled motors, and printers.In an informative and straightforward manner, Graham Dixey describes how to turn what might seem an incomprehensible 'black box' PC into a powerful and enjoyable tool that can help you in all areas of your work and leisure. With plenty of handy

  6. Computational physics

    CERN Document Server

    Newman, Mark

    2013-01-01

    A complete introduction to the field of computational physics, with examples and exercises in the Python programming language. Computers play a central role in virtually every major physics discovery today, from astrophysics and particle physics to biophysics and condensed matter. This book explains the fundamentals of computational physics and describes in simple terms the techniques that every physicist should know, such as finite difference methods, numerical quadrature, and the fast Fourier transform. The book offers a complete introduction to the topic at the undergraduate level, and is also suitable for the advanced student or researcher who wants to learn the foundational elements of this important field.

  7. Computational physics

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1987-01-15

    Computers have for many years played a vital role in the acquisition and treatment of experimental data, but they have more recently taken up a much more extended role in physics research. The numerical and algebraic calculations now performed on modern computers make it possible to explore consequences of basic theories in a way which goes beyond the limits of both analytic insight and experimental investigation. This was brought out clearly at the Conference on Perspectives in Computational Physics, held at the International Centre for Theoretical Physics, Trieste, Italy, from 29-31 October.

  8. Cloud Computing

    CERN Document Server

    Baun, Christian; Nimis, Jens; Tai, Stefan

    2011-01-01

    Cloud computing is a buzz-word in today's information technology (IT) that nobody can escape. But what is really behind it? There are many interpretations of this term, but no standardized or even uniform definition. Instead, as a result of the multi-faceted viewpoints and the diverse interests expressed by the various stakeholders, cloud computing is perceived as a rather fuzzy concept. With this book, the authors deliver an overview of cloud computing architecture, services, and applications. Their aim is to bring readers up to date on this technology and thus to provide a common basis for d

  9. Computational Viscoelasticity

    CERN Document Server

    Marques, Severino P C

    2012-01-01

    This text is a guide how to solve problems in which viscoelasticity is present using existing commercial computational codes. The book gives information on codes’ structure and use, data preparation  and output interpretation and verification. The first part of the book introduces the reader to the subject, and to provide the models, equations and notation to be used in the computational applications. The second part shows the most important Computational techniques: Finite elements formulation, Boundary elements formulation, and presents the solutions of Viscoelastic problems with Abaqus.

  10. Optical computing.

    Science.gov (United States)

    Stroke, G. W.

    1972-01-01

    Applications of the optical computer include an approach for increasing the sharpness of images obtained from the most powerful electron microscopes and fingerprint/credit card identification. The information-handling capability of the various optical computing processes is very great. Modern synthetic-aperture radars scan upward of 100,000 resolvable elements per second. Fields which have assumed major importance on the basis of optical computing principles are optical image deblurring, coherent side-looking synthetic-aperture radar, and correlative pattern recognition. Some examples of the most dramatic image deblurring results are shown.

  11. Computational physics

    International Nuclear Information System (INIS)

    Anon.

    1987-01-01

    Computers have for many years played a vital role in the acquisition and treatment of experimental data, but they have more recently taken up a much more extended role in physics research. The numerical and algebraic calculations now performed on modern computers make it possible to explore consequences of basic theories in a way which goes beyond the limits of both analytic insight and experimental investigation. This was brought out clearly at the Conference on Perspectives in Computational Physics, held at the International Centre for Theoretical Physics, Trieste, Italy, from 29-31 October

  12. Phenomenological Computation?

    DEFF Research Database (Denmark)

    Brier, Søren

    2014-01-01

    Open peer commentary on the article “Info-computational Constructivism and Cognition” by Gordana Dodig-Crnkovic. Upshot: The main problems with info-computationalism are: (1) Its basic concept of natural computing has neither been defined theoretically or implemented practically. (2. It cannot...... encompass human concepts of subjective experience and intersubjective meaningful communication, which prevents it from being genuinely transdisciplinary. (3) Philosophically, it does not sufficiently accept the deep ontological differences between various paradigms such as von Foerster’s second- order...

  13. A computer model for one-dimensional mass and energy transport in and around chemically reacting particles, including complex gas-phase chemistry, multicomponent molecular diffusion, surface evaporation, and heterogeneous reaction

    Science.gov (United States)

    Cho, S. Y.; Yetter, R. A.; Dryer, F. L.

    1992-01-01

    Various chemically reacting flow problems highlighting chemical and physical fundamentals rather than flow geometry are presently investigated by means of a comprehensive mathematical model that incorporates multicomponent molecular diffusion, complex chemistry, and heterogeneous processes, in the interest of obtaining sensitivity-related information. The sensitivity equations were decoupled from those of the model, and then integrated one time-step behind the integration of the model equations, and analytical Jacobian matrices were applied to improve the accuracy of sensitivity coefficients that are calculated together with model solutions.

  14. Molecular Electronic Terms and Molecular Orbital Configurations.

    Science.gov (United States)

    Mazo, R. M.

    1990-01-01

    Discussed are the molecular electronic terms which can arise from a given electronic configuration. Considered are simple cases, molecular states, direct products, closed shells, and open shells. Two examples are provided. (CW)

  15. Essentials of cloud computing

    CERN Document Server

    Chandrasekaran, K

    2014-01-01

    ForewordPrefaceComputing ParadigmsLearning ObjectivesPreambleHigh-Performance ComputingParallel ComputingDistributed ComputingCluster ComputingGrid ComputingCloud ComputingBiocomputingMobile ComputingQuantum ComputingOptical ComputingNanocomputingNetwork ComputingSummaryReview PointsReview QuestionsFurther ReadingCloud Computing FundamentalsLearning ObjectivesPreambleMotivation for Cloud ComputingThe Need for Cloud ComputingDefining Cloud ComputingNIST Definition of Cloud ComputingCloud Computing Is a ServiceCloud Computing Is a Platform5-4-3 Principles of Cloud computingFive Essential Charact

  16. Personal Computers.

    Science.gov (United States)

    Toong, Hoo-min D.; Gupta, Amar

    1982-01-01

    Describes the hardware, software, applications, and current proliferation of personal computers (microcomputers). Includes discussions of microprocessors, memory, output (including printers), application programs, the microcomputer industry, and major microcomputer manufacturers (Apple, Radio Shack, Commodore, and IBM). (JN)

  17. Computational Literacy

    DEFF Research Database (Denmark)

    Chongtay, Rocio; Robering, Klaus

    2016-01-01

    In recent years, there has been a growing interest in and recognition of the importance of Computational Literacy, a skill generally considered to be necessary for success in the 21st century. While much research has concentrated on requirements, tools, and teaching methodologies for the acquisit......In recent years, there has been a growing interest in and recognition of the importance of Computational Literacy, a skill generally considered to be necessary for success in the 21st century. While much research has concentrated on requirements, tools, and teaching methodologies...... for the acquisition of Computational Literacy at basic educational levels, focus on higher levels of education has been much less prominent. The present paper considers the case of courses for higher education programs within the Humanities. A model is proposed which conceives of Computational Literacy as a layered...

  18. Computing Religion

    DEFF Research Database (Denmark)

    Nielbo, Kristoffer Laigaard; Braxton, Donald M.; Upal, Afzal

    2012-01-01

    The computational approach has become an invaluable tool in many fields that are directly relevant to research in religious phenomena. Yet the use of computational tools is almost absent in the study of religion. Given that religion is a cluster of interrelated phenomena and that research...... concerning these phenomena should strive for multilevel analysis, this article argues that the computational approach offers new methodological and theoretical opportunities to the study of religion. We argue that the computational approach offers 1.) an intermediary step between any theoretical construct...... and its targeted empirical space and 2.) a new kind of data which allows the researcher to observe abstract constructs, estimate likely outcomes, and optimize empirical designs. Because sophisticated mulitilevel research is a collaborative project we also seek to introduce to scholars of religion some...

  19. Computational Controversy

    NARCIS (Netherlands)

    Timmermans, Benjamin; Kuhn, Tobias; Beelen, Kaspar; Aroyo, Lora

    2017-01-01

    Climate change, vaccination, abortion, Trump: Many topics are surrounded by fierce controversies. The nature of such heated debates and their elements have been studied extensively in the social science literature. More recently, various computational approaches to controversy analysis have

  20. Grid Computing

    Indian Academy of Sciences (India)

    IAS Admin

    emergence of supercomputers led to the use of computer simula- tion as an .... Scientific and engineering applications (e.g., Tera grid secure gate way). Collaborative ... Encryption, privacy, protection from malicious software. Physical Layer.