Lessons learned from comparing molecular dynamics engines on the SAMPL5 dataset

NASA Astrophysics Data System (ADS)

Shirts, Michael R.; Klein, Christoph; Swails, Jason M.; Yin, Jian; Gilson, Michael K.; Mobley, David L.; Case, David A.; Zhong, Ellen D.

2017-01-01

We describe our efforts to prepare common starting structures and models for the SAMPL5 blind prediction challenge. We generated the starting input files and single configuration potential energies for the host-guest in the SAMPL5 blind prediction challenge for the GROMACS, AMBER, LAMMPS, DESMOND and CHARMM molecular simulation programs. All conversions were fully automated from the originally prepared AMBER input files using a combination of the ParmEd and InterMol conversion programs. We find that the energy calculations for all molecular dynamics engines for this molecular set agree to better than 0.1 % relative absolute energy for all energy components, and in most cases an order of magnitude better, when reasonable choices are made for different cutoff parameters. However, there are some surprising sources of statistically significant differences. Most importantly, different choices of Coulomb's constant between programs are one of the largest sources of discrepancies in energies. We discuss the measures required to get good agreement in the energies for equivalent starting configurations between the simulation programs, and the energy differences that occur when simulations are run with program-specific default simulation parameter values. Finally, we discuss what was required to automate this conversion and comparison.

A software platform for continuum modeling of ion channels based on unstructured mesh

NASA Astrophysics Data System (ADS)

Tu, B.; Bai, S. Y.; Chen, M. X.; Xie, Y.; Zhang, L. B.; Lu, B. Z.

2014-01-01

Most traditional continuum molecular modeling adopted finite difference or finite volume methods which were based on a structured mesh (grid). Unstructured meshes were only occasionally used, but an increased number of applications emerge in molecular simulations. To facilitate the continuum modeling of biomolecular systems based on unstructured meshes, we are developing a software platform with tools which are particularly beneficial to those approaches. This work describes the software system specifically for the simulation of a typical, complex molecular procedure: ion transport through a three-dimensional channel system that consists of a protein and a membrane. The platform contains three parts: a meshing tool chain for ion channel systems, a parallel finite element solver for the Poisson-Nernst-Planck equations describing the electrodiffusion process of ion transport, and a visualization program for continuum molecular modeling. The meshing tool chain in the platform, which consists of a set of mesh generation tools, is able to generate high-quality surface and volume meshes for ion channel systems. The parallel finite element solver in our platform is based on the parallel adaptive finite element package PHG which wass developed by one of the authors [1]. As a featured component of the platform, a new visualization program, VCMM, has specifically been developed for continuum molecular modeling with an emphasis on providing useful facilities for unstructured mesh-based methods and for their output analysis and visualization. VCMM provides a graphic user interface and consists of three modules: a molecular module, a meshing module and a numerical module. A demonstration of the platform is provided with a study of two real proteins, the connexin 26 and hemolysin ion channels.

Protocorms and Protocorm-Like Bodies Are Molecularly Distinct from Zygotic Embryonic Tissues in Phalaenopsis aphrodite1[OPEN

PubMed Central

Chen, Jhun-Chen; Wei, Miao-Ju

2016-01-01

The distinct reproductive program of orchids provides a unique evolutionary model with pollination-triggered ovule development and megasporogenesis, a modified embryogenesis program resulting in seeds with immature embryos, and mycorrhiza-induced seed germination. However, the molecular mechanisms that have evolved to establish these unparalleled developmental programs are largely unclear. Here, we conducted comparative studies of genome-wide gene expression of various reproductive tissues and captured the molecular events associated with distinct reproductive programs in Phalaenopsis aphrodite. Importantly, our data provide evidence to demonstrate that protocorm-like body (PLB) regeneration (the clonal regeneration practice used in the orchid industry) does not follow the embryogenesis program. Instead, we propose that SHOOT MERISTEMLESS, a class I KNOTTED-LIKE HOMEOBOX gene, is likely to play a role in PLB regeneration. Our studies challenge the current understanding of the embryonic identity of PLBs. Taken together, the data obtained establish a fundamental framework for orchid reproductive development and provide a valuable new resource to enable the prediction of gene regulatory networks that is required for specialized developmental programs of orchid species. PMID:27338813

In vitro molecular machine learning algorithm via symmetric internal loops of DNA.

PubMed

Lee, Ji-Hoon; Lee, Seung Hwan; Baek, Christina; Chun, Hyosun; Ryu, Je-Hwan; Kim, Jin-Woo; Deaton, Russell; Zhang, Byoung-Tak

2017-08-01

Programmable biomolecules, such as DNA strands, deoxyribozymes, and restriction enzymes, have been used to solve computational problems, construct large-scale logic circuits, and program simple molecular games. Although studies have shown the potential of molecular computing, the capability of computational learning with DNA molecules, i.e., molecular machine learning, has yet to be experimentally verified. Here, we present a novel molecular learning in vitro model in which symmetric internal loops of double-stranded DNA are exploited to measure the differences between training instances, thus enabling the molecules to learn from small errors. The model was evaluated on a data set of twenty dialogue sentences obtained from the television shows Friends and Prison Break. The wet DNA-computing experiments confirmed that the molecular learning machine was able to generalize the dialogue patterns of each show and successfully identify the show from which the sentences originated. The molecular machine learning model described here opens the way for solving machine learning problems in computer science and biology using in vitro molecular computing with the data encoded in DNA molecules. Copyright © 2017. Published by Elsevier B.V.

Institute for Molecular Medicine Research Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phelps, Michael E

2012-12-14

The objectives of the project are the development of new Positron Emission Tomography (PET) imaging instrumentation, chemistry technology platforms and new molecular imaging probes to examine the transformations from normal cellular and biological processes to those of disease in pre-clinical animal models. These technology platforms and imaging probes provide the means to: 1. Study the biology of disease using pre-clinical mouse models and cells. 2. Develop molecular imaging probes for imaging assays of proteins in pre-clinical models. 3. Develop imaging assays in pre-clinical models to provide to other scientists the means to guide and improve the processes for discovering newmore » drugs. 4. Develop imaging assays in pre-clinical models for others to use in judging the impact of drugs on the biology of disease.« less

Molecular analysis of the replication program in unicellular model organisms.

PubMed

Raghuraman, M K; Brewer, Bonita J

2010-01-01

Eukaryotes have long been reported to show temporal programs of replication, different portions of the genome being replicated at different times in S phase, with the added possibility of developmentally regulated changes in this pattern depending on species and cell type. Unicellular model organisms, primarily the budding yeast Saccharomyces cerevisiae, have been central to our current understanding of the mechanisms underlying the regulation of replication origins and the temporal program of replication in particular. But what exactly is a temporal program of replication, and how might it arise? In this article, we explore this question, drawing again on the wealth of experimental information in unicellular model organisms.

Simulating the Physical World

NASA Astrophysics Data System (ADS)

Berendsen, Herman J. C.

2004-06-01

The simulation of physical systems requires a simplified, hierarchical approach which models each level from the atomistic to the macroscopic scale. From quantum mechanics to fluid dynamics, this book systematically treats the broad scope of computer modeling and simulations, describing the fundamental theory behind each level of approximation. Berendsen evaluates each stage in relation to its applications giving the reader insight into the possibilities and limitations of the models. Practical guidance for applications and sample programs in Python are provided. With a strong emphasis on molecular models in chemistry and biochemistry, this book will be suitable for advanced undergraduate and graduate courses on molecular modeling and simulation within physics, biophysics, physical chemistry and materials science. It will also be a useful reference to all those working in the field. Additional resources for this title including solutions for instructors and programs are available online at www.cambridge.org/9780521835275. The first book to cover the wide range of modeling and simulations, from atomistic to the macroscopic scale, in a systematic fashion Providing a wealth of background material, it does not assume advanced knowledge and is eminently suitable for course use Contains practical examples and sample programs in Python

A Gas-Surface Interaction Model based on Accelerated Reactive Molecular Dynamics for Hypersonic Conditions including Thermal Conduction

DTIC Science & Technology

2012-02-28

Interaction Model based on Accelerated Reactive Molecular Dynamics for Hypersonic conditions including Thermal Conduction FA9550-09-1-0157 Schwartzentruber...Dynamics for Hypersonic Conditions including Thermal Conduction Grant/Contract Number: FA9550-09-1-0157 Program Manager: Dr. John Schmisseur PI...through the boundary layer and may chemically react with the vehicle’s thermal protection system (TPS). Many TPS materials act as a catalyst for the

Free Molecular Heat Transfer Programs for Setup and Dynamic Updating the Conductors in Thermal Desktop

NASA Technical Reports Server (NTRS)

Malroy, Eric T.

2007-01-01

The programs, arrays and logic structure were developed to enable the dynamic update of conductors in thermal desktop. The MatLab program FMHTPRE.m processes the Thermal Desktop conductors and sets up the arrays. The user needs to manually copy portions of the output to different input regions in Thermal Desktop. Also, Fortran subroutines are provided that perform the actual updates to the conductors. The subroutines are setup for helium gas, but the equations can be modified for other gases. The maximum number of free molecular conductors allowed is 10,000 for a given radiation task. Additional radiation tasks for FMHT can be generated to account for more conductors. Modifications to the Fortran subroutines may be warranted, when the mode of heat transfer is in the mixed or continuum mode. The FMHT Thermal Desktop model should be activated by using the "Case Set Manager" once the model is setup. Careful setup of the model is needed to avoid excessive solve times.

Application of the AMPLE cluster-and-truncate approach to NMR structures for molecular replacement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bibby, Jaclyn; Keegan, Ronan M.; Mayans, Olga

2013-11-01

Processing of NMR structures for molecular replacement by AMPLE works well. AMPLE is a program developed for clustering and truncating ab initio protein structure predictions into search models for molecular replacement. Here, it is shown that its core cluster-and-truncate methods also work well for processing NMR ensembles into search models. Rosetta remodelling helps to extend success to NMR structures bearing low sequence identity or high structural divergence from the target protein. Potential future routes to improved performance are considered and practical, general guidelines on using AMPLE are provided.

Pteros: fast and easy to use open-source C++ library for molecular analysis.

PubMed

Yesylevskyy, Semen O

2012-07-15

An open-source Pteros library for molecular modeling and analysis of molecular dynamics trajectories for C++ programming language is introduced. Pteros provides a number of routine analysis operations ranging from reading and writing trajectory files and geometry transformations to structural alignment and computation of nonbonded interaction energies. The library features asynchronous trajectory reading and parallel execution of several analysis routines, which greatly simplifies development of computationally intensive trajectory analysis algorithms. Pteros programming interface is very simple and intuitive while the source code is well documented and easily extendible. Pteros is available for free under open-source Artistic License from http://sourceforge.net/projects/pteros/. Copyright © 2012 Wiley Periodicals, Inc.

A molecular dynamics implementation of the 3D Mercedes-Benz water model

NASA Astrophysics Data System (ADS)

Hynninen, T.; Dias, C. L.; Mkrtchyan, A.; Heinonen, V.; Karttunen, M.; Foster, A. S.; Ala-Nissila, T.

2012-02-01

The three-dimensional Mercedes-Benz model was recently introduced to account for the structural and thermodynamic properties of water. It treats water molecules as point-like particles with four dangling bonds in tetrahedral coordination, representing H-bonds of water. Its conceptual simplicity renders the model attractive in studies where complex behaviors emerge from H-bond interactions in water, e.g., the hydrophobic effect. A molecular dynamics (MD) implementation of the model is non-trivial and we outline here the mathematical framework of its force-field. Useful routines written in modern Fortran are also provided. This open source code is free and can easily be modified to account for different physical context. The provided code allows both serial and MPI-parallelized execution. Program summaryProgram title: CASHEW (Coarse Approach Simulator for Hydrogen-bonding Effects in Water) Catalogue identifier: AEKM_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEKM_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.: 20 501 No. of bytes in distributed program, including test data, etc.: 551 044 Distribution format: tar.gz Programming language: Fortran 90 Computer: Program has been tested on desktop workstations and a Cray XT4/XT5 supercomputer. Operating system: Linux, Unix, OS X Has the code been vectorized or parallelized?: The code has been parallelized using MPI. RAM: Depends on size of system, about 5 MB for 1500 molecules. Classification: 7.7 External routines: A random number generator, Mersenne Twister ( http://www.math.sci.hiroshima-u.ac.jp/m-mat/MT/VERSIONS/FORTRAN/mt95.f90), is used. A copy of the code is included in the distribution. Nature of problem: Molecular dynamics simulation of a new geometric water model. Solution method: New force-field for water molecules, velocity-Verlet integration, representation of molecules as rigid particles with rotations described using quaternion algebra. Restrictions: Memory and cpu time limit the size of simulations. Additional comments: Software web site: https://gitorious.org/cashew/. Running time: Depends on the size of system. The sample tests provided only take a few seconds.

Modeling Molecules

NASA Technical Reports Server (NTRS)

2000-01-01

The molecule modeling method known as Multibody Order (N) Dynamics, or MBO(N)D, was developed by Moldyn, Inc. at Goddard Space Flight Center through funding provided by the SBIR program. The software can model the dynamics of molecules through technology which stimulates low-frequency molecular motions and properties, such as movements among a molecule's constituent parts. With MBO(N)D, a molecule is substructured into a set of interconnected rigid and flexible bodies. These bodies replace the computation burden of mapping individual atoms. Moldyn's technology cuts computation time while increasing accuracy. The MBO(N)D technology is available as Insight II 97.0 from Molecular Simulations, Inc. Currently the technology is used to account for forces on spacecraft parts and to perform molecular analyses for pharmaceutical purposes. It permits the solution of molecular dynamics problems on a moderate workstation, as opposed to on a supercomputer.

High-Resolution Spectroscopic Database for the NASA Earth Observing System Program

NASA Technical Reports Server (NTRS)

Rothman, Laurence

2003-01-01

The purpose of this project is to develop and enhance the HITRAN molecular spectroscopic database and associated software to support the observational programs of the Earth Observing System (EOS). In particular, the focus is on the EOS projects: the Atmospheric Infrared Sounder (AIRS), the High-Resolution Dynamics Limb Sounder (HIRDLS), Measurements of Pollution in the Troposphere (MOPITT), the Tropospheric Emission Spectrometer (TES), and the Stratospheric Aerosol and Gas Experiment (SAGE III). The HITRAN program is also involved in the Ozone Monitoring Experiment (OMI). The data requirements of these programs in terms of spectroscopy are varied with respect to constituents being observed, required remote-sensing parameters, and spectral coverage. A general requisite is for additional spectral parameters and improvements to existing molecular bands sufficient for the simulation of the observations leading to retrieval of the atmospheric state. In addition, cross-section data for heavier molecular species must be expanded and made amenable to modeling in remote sensing. The effort in the project also includes developing software and distribution to make access, manipulation, and use of HITRAN functional to the EOS program.

High Resolution Spectroscopic Database for the NASA Earth Observing System Program

NASA Technical Reports Server (NTRS)

Rothman, Laurence

2004-01-01

The purpose of this project has been to develop and enhance the HITRAN molecular spectroscopic database and associated software to support the observational programs of the Earth Observing System (EOS). Emphasis has been on the EOS projects: the Atmospheric Infrared Sounder (AIRS), the High-Resolution Dynamics Limb Sounder (HIRDLS), Measurements of Pollution in the Troposphere (MOPITT), the Tropospheric Emission Spectrometer (TES), and the Stratospheric Aerosol and Gas Experiment (SAGE III). The HITRAN program is also involved in the Ozone Monitoring Experiment (OMI). The data requirements of these programs in terms of spectroscopy are varied with respect to constituents being observed, required remote-sensing parameters, and spectral coverage. A general requisite is for additional spectral parameters and improvements to existing molecular bands sufficient for the simulation of the observations leading to retrieval of the atmospheric state. In addition, cross-section data for heavier molecular species must be expanded and made amenable to modeling in remote sensing. The effort in the project also includes developing software and distribution to make access, manipulation, and use of HITRAN functional to the EOS program.

High-Resolution Spectroscopic Database for the NASA Earth Observing System Program

NASA Technical Reports Server (NTRS)

Rothman, Laurence S.

2004-01-01

The purpose of this project is to develop and enhance the HITRAN molecular spectroscopic database and associated - software to support the observational programs of the Earth observing System (EOS). In particular, the focus is on the EOS projects: the Atmospheric Infrared Sounder (AIRS), the High-Resolution Dynamics Limb Sounder (HIRDLS), Measurements of Pollution in the Troposphere (MOPITT), the Tropospheric Emission Spectrometer (TES), and the Stratospheric Aerosol and Gas Experiment (SAGE III). The HITRAN program is also involved in the Ozone Monitoring Experiment (OMI). The data requirements of these programs in terms of spectroscopy are varied with respect to constituents being observed, required remote-sensing parameters, and spectral coverage. A general requisite is for additional spectral parameters and improvements to existing molecular bands sufficient for the simulation of the observations leading to retrieval of the atmospheric state. In addition cross-section data for heavier molecular species must be expanded and made amenable to modeling in remote sensing. The effort in the project also includes developing software and distribution to make access, manipulation, and use HITRAN functional to the EOS program.

Atomic and Molecular Data and their Applications★

NASA Astrophysics Data System (ADS)

Drake, Gordon W. F.; Yoon, Jung-Sik; Kato, Daiji; Karwasz, Grzegorz

2018-03-01

This topical issue on Atomic and molecular data and their applications was motivated by the 10th International Conference on Atomic and Molecular Data (ICAMDATA 2016), which was held from September 26 to 29, 2016 in Gunsan, Republic of Korea. The topics of this issue reflect those of the conference program. The scientific papers in the topical issue cover the fields of atomic and molecular structure, radiative transitions, scattering processes, data base development, and the applications of atomic and molecular data to plasma modeling. Contribution to the Topical Issue "Atomic and Molecular Data and their Applications", edited by Gordon W.F. Drake, Jung-Sik Yoon, Daiji Kato, and Grzegorz Karwasz.

Improved Adherence Rates and Clinical Outcomes of an Integrated, Closed-Loop, Pharmacist-Led Oral Chemotherapy Management Program.

PubMed

Muluneh, Benyam; Schneider, Molly; Faso, Aimee; Amerine, Lindsey; Daniels, Rowell; Crisp, Brett; Valgus, John; Savage, Scott

2018-06-01

To address the growing use of oral anticancer therapy, an integrated, closed-loop, pharmacist-led oral chemotherapy management program was created within an academic medical center. An integrated, closed-loop, pharmacy-led oral chemotherapy management program was established. From September 2014 until June 2015, demographic information, rates of adherence, patient understanding of treatment, pharmacist interventions, patient and provider satisfaction, and molecular response rates in patients with chronic myeloid leukemia (CML) were collected. After full implementation, 107 patients were enrolled in our oral chemotherapy management program from September 2014 until June 2015. All patients were educated before starting oral chemotherapy, and using pre- and postassessment tests, comprehension of oral chemotherapy treatment increased from 43% to 95%. Patient-reported adherence was 86% and 94.7% for the GI/breast and malignant hematology patient populations, respectively, and these were validated with medication possession ratio, revealing adherence rates of 85% and 93.9% for the GI/breast and malignant hematology patient populations, respectively. A total of 350 encounters with a clinical pharmacist and 318 adverse effects were reported, which led to 235 interventions. This program led to a higher major molecular response rate (83%) in our CML population compared with published clinical trials (average major molecular response rates, 40% and 60% with 1- and 2-year follow-up, respectively). An innovative model was developed and resulted in improved patient knowledge regarding oral chemotherapy, improved adherence rates that exceeded nationally established thresholds, and superior major molecular response outcomes for patients with CML compared with published literature. As a result, this model has produced the gold standard in managing patients receiving oral chemotherapy.

The Amber Biomolecular Simulation Programs

PubMed Central

CASE, DAVID A.; CHEATHAM, THOMAS E.; DARDEN, TOM; GOHLKE, HOLGER; LUO, RAY; MERZ, KENNETH M.; ONUFRIEV, ALEXEY; SIMMERLING, CARLOS; WANG, BING; WOODS, ROBERT J.

2006-01-01

We describe the development, current features, and some directions for future development of the Amber package of computer programs. This package evolved from a program that was constructed in the late 1970s to do Assisted Model Building with Energy Refinement, and now contains a group of programs embodying a number of powerful tools of modern computational chemistry, focused on molecular dynamics and free energy calculations of proteins, nucleic acids, and carbohydrates. PMID:16200636

CoMD Implementation Suite in Emerging Programming Models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haque, Riyaz; Reeve, Sam; Juallmes, Luc

CoMD-Em is a software implementation suite of the CoMD [4] proxy app using different emerging programming models. It is intended to analyze the features and capabilities of novel programming models that could help ensure code and performance portability and scalability across heterogeneous platforms while improving programmer productivity. Another goal is to provide the authors and venders with some meaningful feedback regarding the capabilities and limitations of their models. The actual application is a classical molecular dynamics (MD) simulation using either the Lennard-Jones method (LJ) or the embedded atom method (EAM) for primary particle interaction. The code can be extended tomore » support alternate interaction models. The code is expected ro run on a wide class of heterogeneous hardware configurations like shard/distributed/hybrid memory, GPU's and any other platform supported by the underlying programming model.« less

Applications of Molecular and Materials Modeling

DTIC Science & Technology

2002-01-01

MSI, GdR 12090). In principle, the NSF GOALI program facilitates exchanges of people, although the paperwork and difficulty of moving people with...industrial, and national-laboratory collaborations. The NSF GOALI program was seen as a step in the right direction, limited mostly by the difficulty...cyclododecane); methyl aluminoxane models (Simeral GOALI project at LSU with Randall Hall and NIST ATP project) Drs. Gary Zhao and Larry S. Simeral http

Construction of a 3D model of nattokinase, a novel fibrinolytic enzyme from Bacillus natto. A novel nucleophilic catalytic mechanism for nattokinase.

PubMed

Zheng, Zhong-liang; Zuo, Zhen-yu; Liu, Zhi-gang; Tsai, Keng-chang; Liu, Ai-fu; Zou, Guo-lin

2005-01-01

A three-dimensional structural model of nattokinase (NK) from Bacillus natto was constructed by homology modeling. High-resolution X-ray structures of Subtilisin BPN' (SB), Subtilisin Carlsberg (SC), Subtilisin E (SE) and Subtilisin Savinase (SS), four proteins with sequential, structural and functional homology were used as templates. Initial models of NK were built by MODELLER and analyzed by the PROCHECK programs. The best quality model was chosen for further refinement by constrained molecular dynamics simulations. The overall quality of the refined model was evaluated. The refined model NKC1 was analyzed by different protein analysis programs including PROCHECK for the evaluation of Ramachandran plot quality, PROSA for testing interaction energies and WHATIF for the calculation of packing quality. This structure was found to be satisfactory and also stable at room temperature as demonstrated by a 300ps long unconstrained molecular dynamics (MD) simulation. Further docking analysis promoted the coming of a new nucleophilic catalytic mechanism for NK, which is induced by attacking of hydroxyl rich in catalytic environment and locating of S221.

Teaching Undergraduate Research: The One-Room Schoolhouse Model

ERIC Educational Resources Information Center

Henderson, LaRhee; Buising, Charisse; Wall, Piper

2008-01-01

Undergraduate research in the biochemistry, cell, and molecular biology program at Drake University uses apprenticeship, cooperative-style learning, and peer mentoring in a cross-disciplinary and cross-community educational program. We call it the one-room schoolhouse approach to teaching undergraduate research. This approach is cost effective,…

The R.E.D. tools: advances in RESP and ESP charge derivation and force field library building.

PubMed

Dupradeau, François-Yves; Pigache, Adrien; Zaffran, Thomas; Savineau, Corentin; Lelong, Rodolphe; Grivel, Nicolas; Lelong, Dimitri; Rosanski, Wilfried; Cieplak, Piotr

2010-07-28

Deriving atomic charges and building a force field library for a new molecule are key steps when developing a force field required for conducting structural and energy-based analysis using molecular mechanics. Derivation of popular RESP charges for a set of residues is a complex and error prone procedure because it depends on numerous input parameters. To overcome these problems, the R.E.D. Tools (RESP and ESP charge Derive, ) have been developed to perform charge derivation in an automatic and straightforward way. The R.E.D. program handles chemical elements up to bromine in the periodic table. It interfaces different quantum mechanical programs employed for geometry optimization and computing molecular electrostatic potential(s), and performs charge fitting using the RESP program. By defining tight optimization criteria and by controlling the molecular orientation of each optimized geometry, charge values are reproduced at any computer platform with an accuracy of 0.0001 e. The charges can be fitted using multiple conformations, making them suitable for molecular dynamics simulations. R.E.D. allows also for defining charge constraints during multiple molecule charge fitting, which are used to derive charges for molecular fragments. Finally, R.E.D. incorporates charges into a force field library, readily usable in molecular dynamics computer packages. For complex cases, such as a set of homologous molecules belonging to a common family, an entire force field topology database is generated. Currently, the atomic charges and force field libraries have been developed for more than fifty model systems and stored in the RESP ESP charge DDataBase. Selected results related to non-polarizable charge models are presented and discussed.

Receptor Surface Models in the Classroom: Introducing Molecular Modeling to Students in a 3-D World

ERIC Educational Resources Information Center

Geldenhuys, Werner J.; Hayes, Michael; Van der Schyf, Cornelis J.; Allen, David D.; Malan, Sarel F.

2007-01-01

A simple, novel and generally applicable method to demonstrate structure-activity associations of a group of biologically interesting compounds in relation to receptor binding is described. This method is useful for undergraduates and graduate students in medicinal chemistry and computer modeling programs.

A 1-D Model of the 4 Bed Molecular Sieve of the Carbon Dioxide Removal Assembly

NASA Technical Reports Server (NTRS)

Coker, Robert; Knox, Jim

2015-01-01

Developments to improve system efficiency and reliability for water and carbon dioxide separation systems on crewed vehicles combine sub-scale systems testing and multi-physics simulations. This paper describes the development of COMSOL simulations in support of the Life Support Systems (LSS) project within NASA's Advanced Exploration Systems (AES) program. Specifically, we model the 4 Bed Molecular Sieve (4BMS) of the Carbon Dioxide Removal Assembly (CDRA) operating on the International Space Station (ISS).

Interactive display of molecular models using a microcomputer system

NASA Technical Reports Server (NTRS)

Egan, J. T.; Macelroy, R. D.

1980-01-01

A simple, microcomputer-based, interactive graphics display system has been developed for the presentation of perspective views of wire frame molecular models. The display system is based on a TERAK 8510a graphics computer system with a display unit consisting of microprocessor, television display and keyboard subsystems. The operating system includes a screen editor, file manager, PASCAL and BASIC compilers and command options for linking and executing programs. The graphics program, written in USCD PASCAL, involves the centering of the coordinate system, the transformation of centered model coordinates into homogeneous coordinates, the construction of a viewing transformation matrix to operate on the coordinates, clipping invisible points, perspective transformation and scaling to screen coordinates; commands available include ZOOM, ROTATE, RESET, and CHANGEVIEW. Data file structure was chosen to minimize the amount of disk storage space. Despite the inherent slowness of the system, its low cost and flexibility suggests general applicability.

Interactive Visualization of Infrared Spectral Data: Synergy of Computation, Visualization, and Experiment for Learning Spectroscopy

NASA Astrophysics Data System (ADS)

Lahti, Paul M.; Motyka, Eric J.; Lancashire, Robert J.

2000-05-01

A straightforward procedure is described to combine computation of molecular vibrational modes using commonly available molecular modeling programs with visualization of the modes using advanced features of the MDL Information Systems Inc. Chime World Wide Web browser plug-in. Minor editing of experimental spectra that are stored in the JCAMP-DX format allows linkage of IR spectral frequency ranges to Chime molecular display windows. The spectra and animation files can be combined by Hypertext Markup Language programming to allow interactive linkage between experimental spectra and computationally generated vibrational displays. Both the spectra and the molecular displays can be interactively manipulated to allow the user maximum control of the objects being viewed. This procedure should be very valuable not only for aiding students through visual linkage of spectra and various vibrational animations, but also by assisting them in learning the advantages and limitations of computational chemistry by comparison to experiment.

Logic integer programming models for signaling networks.

PubMed

Haus, Utz-Uwe; Niermann, Kathrin; Truemper, Klaus; Weismantel, Robert

2009-05-01

We propose a static and a dynamic approach to model biological signaling networks, and show how each can be used to answer relevant biological questions. For this, we use the two different mathematical tools of Propositional Logic and Integer Programming. The power of discrete mathematics for handling qualitative as well as quantitative data has so far not been exploited in molecular biology, which is mostly driven by experimental research, relying on first-order or statistical models. The arising logic statements and integer programs are analyzed and can be solved with standard software. For a restricted class of problems the logic models reduce to a polynomial-time solvable satisfiability algorithm. Additionally, a more dynamic model enables enumeration of possible time resolutions in poly-logarithmic time. Computational experiments are included.

Energy Minimization of Molecular Features Observed on the (110) Face of Lysozyme Crystals

NASA Technical Reports Server (NTRS)

Perozzo, Mary A.; Konnert, John H.; Li, Huayu; Nadarajah, Arunan; Pusey, Marc

1999-01-01

Molecular dynamics and energy minimization have been carried out using the program XPLOR to check the plausibility of a model lysozyme crystal surface. The molecular features of the (110) face of lysozyme were observed using atomic force microscopy (AFM). A model of the crystal surface was constructed using the PDB file 193L, and was used to simulate an AFM image. Molecule translations, van der Waals radii, and assumed AFM tip shape were adjusted to maximize the correlation coefficient between the experimental and simulated images. The highest degree of 0 correlation (0.92) was obtained with the molecules displaced over 6 A from their positions within the bulk of the crystal. The quality of this starting model, the extent of energy minimization, and the correlation coefficient between the final model and the experimental data will be discussed.

DockoMatic 2.0: high throughput inverse virtual screening and homology modeling.

PubMed

Bullock, Casey; Cornia, Nic; Jacob, Reed; Remm, Andrew; Peavey, Thomas; Weekes, Ken; Mallory, Chris; Oxford, Julia T; McDougal, Owen M; Andersen, Timothy L

2013-08-26

DockoMatic is a free and open source application that unifies a suite of software programs within a user-friendly graphical user interface (GUI) to facilitate molecular docking experiments. Here we describe the release of DockoMatic 2.0; significant software advances include the ability to (1) conduct high throughput inverse virtual screening (IVS); (2) construct 3D homology models; and (3) customize the user interface. Users can now efficiently setup, start, and manage IVS experiments through the DockoMatic GUI by specifying receptor(s), ligand(s), grid parameter file(s), and docking engine (either AutoDock or AutoDock Vina). DockoMatic automatically generates the needed experiment input files and output directories and allows the user to manage and monitor job progress. Upon job completion, a summary of results is generated by Dockomatic to facilitate interpretation by the user. DockoMatic functionality has also been expanded to facilitate the construction of 3D protein homology models using the Timely Integrated Modeler (TIM) wizard. The wizard TIM provides an interface that accesses the basic local alignment search tool (BLAST) and MODELER programs and guides the user through the necessary steps to easily and efficiently create 3D homology models for biomacromolecular structures. The DockoMatic GUI can be customized by the user, and the software design makes it relatively easy to integrate additional docking engines, scoring functions, or third party programs. DockoMatic is a free comprehensive molecular docking software program for all levels of scientists in both research and education.

Molecular ping-pong Game of Life on a two-dimensional DNA origami array.

PubMed

Jonoska, N; Seeman, N C

2015-07-28

We propose a design for programmed molecular interactions that continuously change molecular arrangements in a predesigned manner. We introduce a model where environmental control through laser illumination allows platform attachment/detachment oscillations between two floating molecular species. The platform is a two-dimensional DNA origami array of tiles decorated with strands that provide both, the floating molecular tiles to attach and to pass communicating signals to neighbouring array tiles. In particular, we show how algorithmic molecular interactions can control cyclic molecular arrangements by exhibiting a system that can simulate the dynamics similar to two-dimensional cellular automata on a DNA origami array platform. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Dipole-Oriented Molecular Solids Can Undergo a Phase Change and Still Maintain Electrical Polarization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cassidy, Andrew; Jørgensen, Mads R. V.; Rosu-Finsen, Alexander

2016-10-02

It has recently been demonstrated that nanoscale molecular films can spontaneously assemble to self-generate intrinsic electric fields that can exceed 10 8 V/m. These electric fields originate from polarization charges in the material that arise because the films self-assemble to orient molecular dipole moments. This has been called the spontelectric effect. Such growth of spontaneously polarized layers of molecular solids has implications for our understanding of how intermolecular interactions dictate the structure of molecular materials used in a range of applications, for example, molecular semiconductors, sensors, and catalysts. In this paper, we present the first in situ structural characterization ofmore » a representative spontelectric solid, nitrous oxide. Infrared spectroscopy, temperature-programmed desorption, and neutron reflectivity measurements demonstrate that polarized films of nitrous oxide undergo a structural phase transformation upon heating above 48 K. A mean-field model can be used to describe quantitatively the magnitude of the spontaneously generated field as a function of film-growth temperature, and this model also recreates the phase change. Finally, this reinforces the spontelectric model as a means of describing long-range dipole–dipole interactions and points to a new type of ordering in molecular thin films.« less

Computational modeling of epidermal cell fate determination systems.

PubMed

Ryu, Kook Hui; Zheng, Xiaohua; Huang, Ling; Schiefelbein, John

2013-02-01

Cell fate decisions are of primary importance for plant development. Their simple 'either-or' outcome and dynamic nature has attracted the attention of computational modelers. Recent efforts have focused on modeling the determination of several epidermal cell types in the root and shoot of Arabidopsis where many molecular components have been defined. Results of integrated modeling and molecular biology experimentation in these systems have highlighted the importance of competitive positive and negative factors and interconnected feedback loops in generating flexible yet robust mechanisms for establishing distinct gene expression programs in neighboring cells. These models have proven useful in judging hypotheses and guiding future research. Copyright © 2012 Elsevier Ltd. All rights reserved.

Early Experiences Porting the NAMD and VMD Molecular Simulation and Analysis Software to GPU-Accelerated OpenPOWER Platforms

PubMed Central

Stone, John E.; Hynninen, Antti-Pekka; Phillips, James C.; Schulten, Klaus

2017-01-01

All-atom molecular dynamics simulations of biomolecules provide a powerful tool for exploring the structure and dynamics of large protein complexes within realistic cellular environments. Unfortunately, such simulations are extremely demanding in terms of their computational requirements, and they present many challenges in terms of preparation, simulation methodology, and analysis and visualization of results. We describe our early experiences porting the popular molecular dynamics simulation program NAMD and the simulation preparation, analysis, and visualization tool VMD to GPU-accelerated OpenPOWER hardware platforms. We report our experiences with compiler-provided autovectorization and compare with hand-coded vector intrinsics for the POWER8 CPU. We explore the performance benefits obtained from unique POWER8 architectural features such as 8-way SMT and its value for particular molecular modeling tasks. Finally, we evaluate the performance of several GPU-accelerated molecular modeling kernels and relate them to other hardware platforms. PMID:29202130

PAL: an object-oriented programming library for molecular evolution and phylogenetics.

PubMed

Drummond, A; Strimmer, K

2001-07-01

Phylogenetic Analysis Library (PAL) is a collection of Java classes for use in molecular evolution and phylogenetics. PAL provides a modular environment for the rapid construction of both special-purpose and general analysis programs. PAL version 1.1 consists of 145 public classes or interfaces in 13 packages, including classes for models of character evolution, maximum-likelihood estimation, and the coalescent, with a total of more than 27000 lines of code. The PAL project is set up as a collaborative project to facilitate contributions from other researchers. AVAILIABILTY: The program is free and is available at http://www.pal-project.org. It requires Java 1.1 or later. PAL is licensed under the GNU General Public License.

Open discovery: An integrated live Linux platform of Bioinformatics tools.

PubMed

Vetrivel, Umashankar; Pilla, Kalabharath

2008-01-01

Historically, live linux distributions for Bioinformatics have paved way for portability of Bioinformatics workbench in a platform independent manner. Moreover, most of the existing live Linux distributions limit their usage to sequence analysis and basic molecular visualization programs and are devoid of data persistence. Hence, open discovery - a live linux distribution has been developed with the capability to perform complex tasks like molecular modeling, docking and molecular dynamics in a swift manner. Furthermore, it is also equipped with complete sequence analysis environment and is capable of running windows executable programs in Linux environment. Open discovery portrays the advanced customizable configuration of fedora, with data persistency accessible via USB drive or DVD. The Open Discovery is distributed free under Academic Free License (AFL) and can be downloaded from http://www.OpenDiscovery.org.in.

Molecular emission in chemically active protostellar outflows

NASA Astrophysics Data System (ADS)

Lefloch, B.

2011-12-01

Protostellar outflows play an important role in the dynamical and chemical evolution of cloud through shocks. The Herschel Space Observatory (HSO) brings new insight both on the molecular content and the physical conditions in protostellar shocks through high spectral and angular resolution studies of the emission of major gas cooling agents and hydrides. The Herschel/CHESS key-program is carrying out an in depth study of the prototypical shock region L1157-B1. Analysis of the line profiles detected allows to constrain the formation/destruction route of various molecular species, in relation with the predictions of MHD shock models. The Herschel/WISH key-program investigates the properties and origin of water emission in a broad sample of protostellar outflows and envelopes. Implications of the first results for future studies on mass-loss phenomena are discussed.

Pteros 2.0: Evolution of the fast parallel molecular analysis library for C++ and python.

PubMed

Yesylevskyy, Semen O

2015-07-15

Pteros is the high-performance open-source library for molecular modeling and analysis of molecular dynamics trajectories. Starting from version 2.0 Pteros is available for C++ and Python programming languages with very similar interfaces. This makes it suitable for writing complex reusable programs in C++ and simple interactive scripts in Python alike. New version improves the facilities for asynchronous trajectory reading and parallel execution of analysis tasks by introducing analysis plugins which could be written in either C++ or Python in completely uniform way. The high level of abstraction provided by analysis plugins greatly simplifies prototyping and implementation of complex analysis algorithms. Pteros is available for free under Artistic License from http://sourceforge.net/projects/pteros/. © 2015 Wiley Periodicals, Inc.

Discovery of an Unexplored Protein Structural Scaffold of Serine Protease from Big Blue Octopus (Octopus cyanea): A New Prospective Lead Molecule.

PubMed

Panda, Subhamay; Kumari, Leena

2017-01-01

Serine proteases are a group of enzymes that hydrolyses the peptide bonds in proteins. In mammals, these enzymes help in the regulation of several major physiological functions such as digestion, blood clotting, responses of immune system, reproductive functions and the complement system. Serine proteases obtained from the venom of Octopodidae family is a relatively unexplored area of research. In the present work, we tried to effectively utilize comparative composite molecular modeling technique. Our key aim was to propose the first molecular model structure of unexplored serine protease 5 derived from big blue octopus. The other objective of this study was to analyze the distribution of negatively and positively charged amino acid over molecular modeled structure, distribution of secondary structural elements, hydrophobicity molecular surface analysis and electrostatic potential analysis with the aid of different bioinformatic tools. In the present study, molecular model has been generated with the help of I-TASSER suite. Afterwards the refined structural model was validated with standard methods. For functional annotation of protein molecule we used Protein Information Resource (PIR) database. Serine protease 5 of big blue octopus was analyzed with different bioinformatical algorithms for the distribution of negatively and positively charged amino acid over molecular modeled structure, distribution of secondary structural elements, hydrophobicity molecular surface analysis and electrostatic potential analysis. The functionally critical amino acids and ligand- binding site (LBS) of the proteins (modeled) were determined using the COACH program. The molecular model data in cooperation to other pertinent post model analysis data put forward molecular insight to proteolytic activity of serine protease 5, which helps in the clear understanding of procoagulant and anticoagulant characteristics of this natural lead molecule. Our approach was to investigate the octopus venom protein as a whole or a part of their structure that may result in the development of new lead molecule. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Integrating Computational Chemistry into the Physical Chemistry Curriculum

ERIC Educational Resources Information Center

Johnson, Lewis E.; Engel, Thomas

2011-01-01

Relatively few undergraduate physical chemistry programs integrate molecular modeling into their quantum mechanics curriculum owing to concerns about limited access to computational facilities, the cost of software, and concerns about increasing the course material. However, modeling exercises can be integrated into an undergraduate course at a…

Modelface: an Application Programming Interface (API) for Homology Modeling Studies Using Modeller Software

PubMed Central

Sakhteman, Amirhossein; Zare, Bijan

2016-01-01

An interactive application, Modelface, was presented for Modeller software based on windows platform. The application is able to run all steps of homology modeling including pdb to fasta generation, running clustal, model building and loop refinement. Other modules of modeler including energy calculation, energy minimization and the ability to make single point mutations in the PDB structures are also implemented inside Modelface. The API is a simple batch based application with no memory occupation and is free of charge for academic use. The application is also able to repair missing atom types in the PDB structures making it suitable for many molecular modeling studies such as docking and molecular dynamic simulation. Some successful instances of modeling studies using Modelface are also reported. PMID:28243276

A Combination of Hand-Held Models and Computer Imaging Programs Helps Students Answer Oral Questions about Molecular Structure and Function: A Controlled Investigation of Student Learning

ERIC Educational Resources Information Center

Harris, Michelle A.; Peck, Ronald F.; Colton, Shannon; Morris, Jennifer; Neto, Elias Chaibub; Kallio, Julie

2009-01-01

We conducted a controlled investigation to examine whether a combination of computer imagery and tactile tools helps introductory cell biology laboratory undergraduate students better learn about protein structure/function relationships as compared with computer imagery alone. In all five laboratory sections, students used the molecular imaging…

Research experiences and mentoring practices in selected east Asian graduate programs: predictors of research productivity among doctoral students in molecular biology.

PubMed

Ynalvez, Ruby; Garza-Gongora, Claudia; Ynalvez, Marcus Antonius; Hara, Noriko

2014-01-01

Although doctoral mentors recognize the benefits of providing quality advisement and close guidance, those of sharing project management responsibilities with mentees are still not well recognized. We observed that mentees, who have the opportunity to co-manage projects, generate more written output. Here we examine the link between research productivity, doctoral mentoring practices (DMP), and doctoral research experiences (DRE) of mentees in programs in the non-West. Inspired by previous findings that early career productivity is a strong predictor of later productivity, we examine the research productivity of 210 molecular biology doctoral students in selected programs in Japan, Singapore, and Taiwan. Using principal component (PC) analysis, we derive two sets of PCs: one set from 15 DMP and another set from 16 DRE items. We model research productivity using Poisson and negative-binomial regression models with these sets as predictors. Our findings suggest a need to re-think extant practices and to allocate resources toward professional career development in training future scientists. We contend that doctoral science training must not only be an occasion for future scientists to learn scientific and technical skills, but it must also be the opportunity to experience, to acquire, and to hone research management skills. © 2014 The International Union of Biochemistry and Molecular Biology.

3D Printing of Protein Models in an Undergraduate Laboratory: Leucine Zippers

ERIC Educational Resources Information Center

Meyer, Scott C.

2015-01-01

An upper-division undergraduate laboratory experiment is described that explores the structure/function relationship of protein domains, namely leucine zippers, through a molecular graphics computer program and physical models fabricated by 3D printing. By generating solvent accessible surfaces and color-coding hydrophobic, basic, and acidic amino…

Discrimination between native and intentionally misfolded conformations of proteins: ES/IS, a new method for calculating conformational free energy that uses both dynamics simulations with an explicit solvent and an implicit solvent continuum model.

PubMed

Vorobjev, Y N; Almagro, J C; Hermans, J

1998-09-01

A new method for calculating the total conformational free energy of proteins in water solvent is presented. The method consists of a relatively brief simulation by molecular dynamics with explicit solvent (ES) molecules to produce a set of microstates of the macroscopic conformation. Conformational energy and entropy are obtained from the simulation, the latter in the quasi-harmonic approximation by analysis of the covariance matrix. The implicit solvent (IS) dielectric continuum model is used to calculate the average solvation free energy as the sum of the free energies of creating the solute-size hydrophobic cavity, of the van der Waals solute-solvent interactions, and of the polarization of water solvent by the solute's charges. The reliability of the solvation free energy depends on a number of factors: the details of arrangement of the protein's charges, especially those near the surface; the definition of the molecular surface; and the method chosen for solving the Poisson equation. Molecular dynamics simulation in explicit solvent relaxes the protein's conformation and allows polar surface groups to assume conformations compatible with interaction with solvent, while averaging of internal energy and solvation free energy tend to enhance the precision. Two recently developed methods--SIMS, for calculation of a smooth invariant molecular surface, and FAMBE, for solution of the Poisson equation via a fast adaptive multigrid boundary element--have been employed. The SIMS and FAMBE programs scale linearly with the number of atoms. SIMS is superior to Connolly's MS (molecular surface) program: it is faster, more accurate, and more stable, and it smooths singularities of the molecular surface. Solvation free energies calculated with these two programs do not depend on molecular position or orientation and are stable along a molecular dynamics trajectory. We have applied this method to calculate the conformational free energy of native and intentionally misfolded globular conformations of proteins (the EMBL set of deliberately misfolded proteins) and have obtained good discrimination in favor of the native conformations in all instances.

DockoMatic 2.0: High Throughput Inverse Virtual Screening and Homology Modeling

PubMed Central

Bullock, Casey; Cornia, Nic; Jacob, Reed; Remm, Andrew; Peavey, Thomas; Weekes, Ken; Mallory, Chris; Oxford, Julia T.; McDougal, Owen M.; Andersen, Timothy L.

2013-01-01

DockoMatic is a free and open source application that unifies a suite of software programs within a user-friendly Graphical User Interface (GUI) to facilitate molecular docking experiments. Here we describe the release of DockoMatic 2.0; significant software advances include the ability to: (1) conduct high throughput Inverse Virtual Screening (IVS); (2) construct 3D homology models; and (3) customize the user interface. Users can now efficiently setup, start, and manage IVS experiments through the DockoMatic GUI by specifying a receptor(s), ligand(s), grid parameter file(s), and docking engine (either AutoDock or AutoDock Vina). DockoMatic automatically generates the needed experiment input files and output directories, and allows the user to manage and monitor job progress. Upon job completion, a summary of results is generated by Dockomatic to facilitate interpretation by the user. DockoMatic functionality has also been expanded to facilitate the construction of 3D protein homology models using the Timely Integrated Modeler (TIM) wizard. The wizard TIM provides an interface that accesses the basic local alignment search tool (BLAST) and MODELLER programs, and guides the user through the necessary steps to easily and efficiently create 3D homology models for biomacromolecular structures. The DockoMatic GUI can be customized by the user, and the software design makes it relatively easy to integrate additional docking engines, scoring functions, or third party programs. DockoMatic is a free comprehensive molecular docking software program for all levels of scientists in both research and education. PMID:23808933

Space Research Program on Planarian Schmidtea Mediterranea's Establishment of the Anterior-Posterior Axis in Altered Gravity Conditions

NASA Astrophysics Data System (ADS)

Auletta, G.; Adell, T.; Colagè, I.; D'Ambrosio, P.; Salò, E.

2012-12-01

Planarians of the species Schmidtea mediterranea are a well-established model for regeneration studies. In this paper, we first recall the morphological characters and the molecular mechanisms involved in the regeneration process, especially focussing on the Wnt pathway and the establishment of the antero-posterior axial polarity. Then, after an assessment of a space-experiment (run in 2006 on the Russian Segment of the International Space Station) on planarians of the species Girardia tigrina, we present our experimental program to ascertain the effects that altered-gravity conditions may have on regeneration processes in S. mediterrnea at the molecular and genetic level.

i-PI: A Python interface for ab initio path integral molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Ceriotti, Michele; More, Joshua; Manolopoulos, David E.

2014-03-01

Recent developments in path integral methodology have significantly reduced the computational expense of including quantum mechanical effects in the nuclear motion in ab initio molecular dynamics simulations. However, the implementation of these developments requires a considerable programming effort, which has hindered their adoption. Here we describe i-PI, an interface written in Python that has been designed to minimise the effort required to bring state-of-the-art path integral techniques to an electronic structure program. While it is best suited to first principles calculations and path integral molecular dynamics, i-PI can also be used to perform classical molecular dynamics simulations, and can just as easily be interfaced with an empirical forcefield code. To give just one example of the many potential applications of the interface, we use it in conjunction with the CP2K electronic structure package to showcase the importance of nuclear quantum effects in high-pressure water. Catalogue identifier: AERN_v1_0 Program summary URL: http://cpc.cs.qub.ac.uk/summaries/AERN_v1_0.html Program obtainable from: CPC Program Library, Queen’s University, Belfast, N. Ireland Licensing provisions: GNU General Public License, version 3 No. of lines in distributed program, including test data, etc.: 138626 No. of bytes in distributed program, including test data, etc.: 3128618 Distribution format: tar.gz Programming language: Python. Computer: Multiple architectures. Operating system: Linux, Mac OSX, Windows. RAM: Less than 256 Mb Classification: 7.7. External routines: NumPy Nature of problem: Bringing the latest developments in the modelling of nuclear quantum effects with path integral molecular dynamics to ab initio electronic structure programs with minimal implementational effort. Solution method: State-of-the-art path integral molecular dynamics techniques are implemented in a Python interface. Any electronic structure code can be patched to receive the atomic coordinates from the Python interface, and to return the forces and energy that are used to integrate the equations of motion. Restrictions: This code only deals with distinguishable particles. It does not include fermonic or bosonic exchanges between equivalent nuclei, which can become important at very low temperatures. Running time: Depends dramatically on the nature of the simulation being performed. A few minutes for short tests with empirical force fields, up to several weeks for production calculations with ab initio forces. The examples provided with the code run in less than an hour.

METAGUI. A VMD interface for analyzing metadynamics and molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Biarnés, Xevi; Pietrucci, Fabio; Marinelli, Fabrizio; Laio, Alessandro

2012-01-01

We present a new computational tool, METAGUI, which extends the VMD program with a graphical user interface that allows constructing a thermodynamic and kinetic model of a given process simulated by large-scale molecular dynamics. The tool is specially designed for analyzing metadynamics based simulations. The huge amount of diverse structures generated during such a simulation is partitioned into a set of microstates (i.e. structures with similar values of the collective variables). Their relative free energies are then computed by a weighted-histogram procedure and the most relevant free energy wells are identified by diagonalization of the rate matrix followed by a commitor analysis. All this procedure leads to a convenient representation of the metastable states and long-time kinetics of the system which can be compared with experimental data. The tool allows to seamlessly switch between a collective variables space representation of microstates and their atomic structure representation, which greatly facilitates the set-up and analysis of molecular dynamics simulations. METAGUI is based on the output format of the PLUMED plugin, making it compatible with a number of different molecular dynamics packages like AMBER, NAMD, GROMACS and several others. The METAGUI source files can be downloaded from the PLUMED web site ( http://www.plumed-code.org). Program summaryProgram title: METAGUI Catalogue identifier: AEKH_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEKH_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: GNU General Public License version 3 No. of lines in distributed program, including test data, etc.: 117 545 No. of bytes in distributed program, including test data, etc.: 8 516 203 Distribution format: tar.gz Programming language: TK/TCL, Fortran Computer: Any computer with a VMD installation and capable of running an executable produced by a gfortran compiler Operating system: Linux, Unix OS-es RAM: 1 073 741 824 bytes Classification: 23 External routines: A VMD installation ( http://www.ks.uiuc.edu/Research/vmd/) Nature of problem: Extract thermodynamic data and build a kinetic model of a given process simulated by metadynamics or molecular dynamics simulations, and provide this information on a dual representation that allows navigating and exploring the molecular structures corresponding to each point along the multi-dimensional free energy hypersurface. Solution method: Graphical-user interface linked to VMD that clusterizes the simulation trajectories in the space of a set of collective variables and assigns each frame to a given microstate, determines the free energy of each microstate by a weighted histogram analysis method, and identifies the most relevant free energy wells (kinetic basins) by diagonalization of the rate matrix followed by a commitor analysis. Restrictions: Input format files compatible with PLUMED and all the MD engines supported by PLUMED and VMD. Running time: A few minutes.

A Combination of Hand-held Models and Computer Imaging Programs Helps Students Answer Oral Questions about Molecular Structure and Function: A Controlled Investigation of Student Learning

PubMed Central

Peck, Ronald F.; Colton, Shannon; Morris, Jennifer; Chaibub Neto, Elias; Kallio, Julie

2009-01-01

We conducted a controlled investigation to examine whether a combination of computer imagery and tactile tools helps introductory cell biology laboratory undergraduate students better learn about protein structure/function relationships as compared with computer imagery alone. In all five laboratory sections, students used the molecular imaging program, Protein Explorer (PE). In the three experimental sections, three-dimensional physical models were made available to the students, in addition to PE. Student learning was assessed via oral and written research summaries and videotaped interviews. Differences between the experimental and control group students were not found in our typical course assessments such as research papers, but rather were revealed during one-on-one interviews with students at the end of the semester. A subset of students in the experimental group produced superior answers to some higher-order interview questions as compared with students in the control group. During the interview, students in both groups preferred to use either the hand-held models alone or in combination with the PE imaging program. Students typically did not use any tools when answering knowledge (lower-level thinking) questions, but when challenged with higher-level thinking questions, students in both the control and experimental groups elected to use the models. PMID:19255134

Open discovery: An integrated live Linux platform of Bioinformatics tools

PubMed Central

Vetrivel, Umashankar; Pilla, Kalabharath

2008-01-01

Historically, live linux distributions for Bioinformatics have paved way for portability of Bioinformatics workbench in a platform independent manner. Moreover, most of the existing live Linux distributions limit their usage to sequence analysis and basic molecular visualization programs and are devoid of data persistence. Hence, open discovery ‐ a live linux distribution has been developed with the capability to perform complex tasks like molecular modeling, docking and molecular dynamics in a swift manner. Furthermore, it is also equipped with complete sequence analysis environment and is capable of running windows executable programs in Linux environment. Open discovery portrays the advanced customizable configuration of fedora, with data persistency accessible via USB drive or DVD. Availability The Open Discovery is distributed free under Academic Free License (AFL) and can be downloaded from http://www.OpenDiscovery.org.in PMID:19238235

Training a molecular automaton to play a game

NASA Astrophysics Data System (ADS)

Pei, Renjun; Matamoros, Elizabeth; Liu, Manhong; Stefanovic, Darko; Stojanovic, Milan N.

2010-11-01

Research at the interface between chemistry and cybernetics has led to reports of `programmable molecules', but what does it mean to say `we programmed a set of solution-phase molecules to do X'? A survey of recently implemented solution-phase circuitry indicates that this statement could be replaced with `we pre-mixed a set of molecules to do X and functional subsets of X'. These hard-wired mixtures are then exposed to a set of molecular inputs, which can be interpreted as being keyed to human moves in a game, or as assertions of logical propositions. In nucleic acids-based systems, stemming from DNA computation, these inputs can be seen as generic oligonucleotides. Here, we report using reconfigurable nucleic acid catalyst-based units to build a multipurpose reprogrammable molecular automaton that goes beyond single-purpose `hard-wired' molecular automata. The automaton covers all possible responses to two consecutive sets of four inputs (such as four first and four second moves for a generic set of trivial two-player two-move games). This is a model system for more general molecular field programmable gate array (FPGA)-like devices that can be programmed by example, which means that the operator need not have any knowledge of molecular computing methods.

Training a molecular automaton to play a game.

PubMed

Pei, Renjun; Matamoros, Elizabeth; Liu, Manhong; Stefanovic, Darko; Stojanovic, Milan N

2010-11-01

Research at the interface between chemistry and cybernetics has led to reports of 'programmable molecules', but what does it mean to say 'we programmed a set of solution-phase molecules to do X'? A survey of recently implemented solution-phase circuitry indicates that this statement could be replaced with 'we pre-mixed a set of molecules to do X and functional subsets of X'. These hard-wired mixtures are then exposed to a set of molecular inputs, which can be interpreted as being keyed to human moves in a game, or as assertions of logical propositions. In nucleic acids-based systems, stemming from DNA computation, these inputs can be seen as generic oligonucleotides. Here, we report using reconfigurable nucleic acid catalyst-based units to build a multipurpose reprogrammable molecular automaton that goes beyond single-purpose 'hard-wired' molecular automata. The automaton covers all possible responses to two consecutive sets of four inputs (such as four first and four second moves for a generic set of trivial two-player two-move games). This is a model system for more general molecular field programmable gate array (FPGA)-like devices that can be programmed by example, which means that the operator need not have any knowledge of molecular computing methods.

Structure and conformational dynamics of scaffolded DNA origami nanoparticles

DTIC Science & Technology

2017-05-08

all-atom molecular dynamics and coarse-grained finite element modeling to DX-based nanoparticles to elucidate their fine-scale and global conforma... finite element (FE) modeling approach CanDo is also routinely used to predict the 3D equilibrium conformation of programmed DNA assemblies based on a...model with both experimental cryo-electron microscopy (cryo-EM) data and all-atom modeling. MATERIALS AND METHODS Lattice-free finite element model

Collision-induced Absorption in the Infrared: A Data Base for Modelling Planetary and Stellar Atmospheres

NASA Technical Reports Server (NTRS)

Borysow, Aleksandra

1998-01-01

Accurate knowledge of certain collision-induced absorption continua of molecular pairs such as H2-H2, H2-He, H2-CH4, CO2-CO2, etc., is a prerequisite for most spectral analyses and modelling attempts of atmospheres of planets and cold stars. We collect and regularly update simple, state of the art computer programs for the calculation of the absorption coefficient of such molecular pairs over a broad range of temperatures and frequencies, for the various rotovibrational bands. The computational results are in agreement with the existing laboratory measurements of such absorption continua, recorded with a spectral resolution of a few wavenumbers, but reliable computational results may be expected even in the far wings, and at temperatures for which laboratory measurements do not exist. Detailed information is given concerning the systems thus studied, the temperature and frequency ranges considered, the rotovibrational bands thus modelled, and how one may obtain copies of the FORTRAN77 computer programs by e-mail.

Experimental and theoretical studies on the gas/solid/gas transformation cycle in extraterrestrial environments

NASA Astrophysics Data System (ADS)

Cottin, Hervé; Gazeau, Marie-Claire; Chaquin, Patrick; Raulin, François; Bénilan, Yves

2001-12-01

The ubiquity of molecular material in the universe, from hydrogen to complex organic matter, is the result of intermixed physicochemical processes that have occurred throughout history. In particular, the gas/solid/gas phase transformation cycle plays a key role in chemical evolution of organic matter from the interstellar medium to planetary systems. This paper focuses on two examples that are representative of the diversity of environments where such transformations occur in the Solar System: (1) the photolytic evolution from gaseous to solid material in methane containing planetary atmospheres and (2) the degradation of high molecular weight compounds into gas phase molecules in comets. We are currently developing two programs which couple experimental and theoretical studies. The aim of this research is to provide data necessary to build models in order to better understand (1) the photochemical evolution of Titan's atmosphere, through a laboratory program to determine quantitative spectroscopic data on long carbon chain molecules (polyynes) obtained in the SCOOP program (French acronym for Spectroscopy of Organic Compounds Oriented for Planetology), and (2) the extended sources in comets, through a laboratory program of quantitative studies of photochemical and thermal degradation processes on relevant polymers (e.g., Polyoxymethylene) by the SEMAPhOrE Cometaire program (French acronym for Experimental Simulation and Modeling Applied to Organic Chemistry in Cometary Environment).

Cross-scale efficient tensor contractions for coupled cluster computations through multiple programming model backends

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ibrahim, Khaled Z.; Epifanovsky, Evgeny; Williams, Samuel

Coupled-cluster methods provide highly accurate models of molecular structure through explicit numerical calculation of tensors representing the correlation between electrons. These calculations are dominated by a sequence of tensor contractions, motivating the development of numerical libraries for such operations. While based on matrix–matrix multiplication, these libraries are specialized to exploit symmetries in the molecular structure and in electronic interactions, and thus reduce the size of the tensor representation and the complexity of contractions. The resulting algorithms are irregular and their parallelization has been previously achieved via the use of dynamic scheduling or specialized data decompositions. We introduce our efforts tomore » extend the Libtensor framework to work in the distributed memory environment in a scalable and energy-efficient manner. We achieve up to 240× speedup compared with the optimized shared memory implementation of Libtensor. We attain scalability to hundreds of thousands of compute cores on three distributed-memory architectures (Cray XC30 and XC40, and IBM Blue Gene/Q), and on a heterogeneous GPU-CPU system (Cray XK7). As the bottlenecks shift from being compute-bound DGEMM's to communication-bound collectives as the size of the molecular system scales, we adopt two radically different parallelization approaches for handling load-imbalance, tasking and bulk synchronous models. Nevertheless, we preserve a unified interface to both programming models to maintain the productivity of computational quantum chemists.« less

Cross-scale efficient tensor contractions for coupled cluster computations through multiple programming model backends

DOE PAGES

Ibrahim, Khaled Z.; Epifanovsky, Evgeny; Williams, Samuel; ...

2017-03-08

Coupled-cluster methods provide highly accurate models of molecular structure through explicit numerical calculation of tensors representing the correlation between electrons. These calculations are dominated by a sequence of tensor contractions, motivating the development of numerical libraries for such operations. While based on matrix–matrix multiplication, these libraries are specialized to exploit symmetries in the molecular structure and in electronic interactions, and thus reduce the size of the tensor representation and the complexity of contractions. The resulting algorithms are irregular and their parallelization has been previously achieved via the use of dynamic scheduling or specialized data decompositions. We introduce our efforts tomore » extend the Libtensor framework to work in the distributed memory environment in a scalable and energy-efficient manner. We achieve up to 240× speedup compared with the optimized shared memory implementation of Libtensor. We attain scalability to hundreds of thousands of compute cores on three distributed-memory architectures (Cray XC30 and XC40, and IBM Blue Gene/Q), and on a heterogeneous GPU-CPU system (Cray XK7). As the bottlenecks shift from being compute-bound DGEMM's to communication-bound collectives as the size of the molecular system scales, we adopt two radically different parallelization approaches for handling load-imbalance, tasking and bulk synchronous models. Nevertheless, we preserve a unified interface to both programming models to maintain the productivity of computational quantum chemists.« less

A molecular model for the active site of S-adenosyl- l-homocysteine hydrolase

NASA Astrophysics Data System (ADS)

Yeh, Jerry C.; Borchardt, Ronald T.; Vedani, Angelo

1991-06-01

S-adenosyl- l-homocysteine hydrolase (AdoHcy hydrolase, EC 3.3.1.1.), a specific target for antiviral drug design, catalyzes the hydrolysis of AdoHcy to adenosine (Ado) and homocysteine (Hcy) as well as the synthesis of AdoHcy from Ado and Hcy. The enzyme isolated from different sources has been shown to contain tightly bound NAD+. Based on the 2.0 Å-resolution X-ray crystal structure of dogfish lactate dehydrogenase (LDH), which is functionally homologous to AdoHcy hydrolase, and the primary sequence of rat liver AdoHcy hydrolase, we have derived a molecular model of an extended active site for AdoHcy hydrolase. The computational mutation was performed using the software MUTAR (Yeh et al., University of Kansas, Lawrence), followed by molecular mechanics optimizations using the programs AMBER (Singh et al., University of California, San Francisco) and YETI (Vedani, University of Kansas). Solvation of the model structure was achieved by use of the program SOLVGEN (Jacober, University of Kansas); 56 water molecules were explicitly included in all refinements. Some of these may be involved in the catalytic reaction. We also studied a model of the complex of AdoHcy hydrolase with NAD+, as well as the ternary complexes of the redox reaction catalyzed by AdoHcy hydrolase and has been used to differentiate the relative binding strength of inhibitors.

Computational challenges in modeling gene regulatory events.

PubMed

Pataskar, Abhijeet; Tiwari, Vijay K

2016-10-19

Cellular transcriptional programs driven by genetic and epigenetic mechanisms could be better understood by integrating "omics" data and subsequently modeling the gene-regulatory events. Toward this end, computational biology should keep pace with evolving experimental procedures and data availability. This article gives an exemplified account of the current computational challenges in molecular biology.

Guidance for the application of a population modeling framework in coordination with field based monitoring studies for multiple species and sites

EPA Science Inventory

A modeling framework was developed that can be applied in conjunction with field based monitoring efforts (e.g., through effects-based monitoring programs) to link chemically-induced alterations in molecular and biochemical endpoints to adverse outcomes in whole organisms and pop...

An Infrared Spectral Radiance Code for the Auroral Thermosphere (AARC)

DTIC Science & Technology

1987-11-24

Program Description and Usage 136 3,1 Main Modules 136 3.2 Input, Output, and Program Communication 138 3.2.1 Input of User-Defined Program Control ...a test date set with which to compare the model predic- tions. Secondly, a number of theoretical papers are available describing some of the basic...necessary since secondary electrons aro a very important source of molecular nitrogen in vibrationally excited states [N2(v)), and the N2 (v) controls

Developments in the CCP4 molecular-graphics project.

PubMed

Potterton, Liz; McNicholas, Stuart; Krissinel, Eugene; Gruber, Jan; Cowtan, Kevin; Emsley, Paul; Murshudov, Garib N; Cohen, Serge; Perrakis, Anastassis; Noble, Martin

2004-12-01

Progress towards structure determination that is both high-throughput and high-value is dependent on the development of integrated and automatic tools for electron-density map interpretation and for the analysis of the resulting atomic models. Advances in map-interpretation algorithms are extending the resolution regime in which fully automatic tools can work reliably, but at present human intervention is required to interpret poor regions of macromolecular electron density, particularly where crystallographic data is only available to modest resolution [for example, I/sigma(I) < 2.0 for minimum resolution 2.5 A]. In such cases, a set of manual and semi-manual model-building molecular-graphics tools is needed. At the same time, converting the knowledge encapsulated in a molecular structure into understanding is dependent upon visualization tools, which must be able to communicate that understanding to others by means of both static and dynamic representations. CCP4 mg is a program designed to meet these needs in a way that is closely integrated with the ongoing development of CCP4 as a program suite suitable for both low- and high-intervention computational structural biology. As well as providing a carefully designed user interface to advanced algorithms of model building and analysis, CCP4 mg is intended to present a graphical toolkit to developers of novel algorithms in these fields.

The Development of a Post-Baccalaureate Certificate Program in Molecular Diagnostics

PubMed Central

Williams, Gail S.; Brown, Judith D.; Keagle, Martha B.

2000-01-01

A post-baccalaureate certificate program in diagnostic molecular sciences was created in 1995 by the Diagnostic Genetic Sciences Program in the School of Allied Health at the University of Connecticut. The required on-campus lecture and laboratory courses include basic laboratory techniques, health care issues, cell biology, immunology, human genetics, research, management, and molecular diagnostic techniques and laboratory in molecular diagnostics. These courses precede a 6-month, full-time practicum at an affiliated full-service molecular laboratory. The practicum includes amplification and blotting methods, a research project, and a choice of specialized electives including DNA sequencing, mutagenesis, in situ hybridization methods, or molecular diagnostic applications in microbiology. Graduates of the program are immediately eligible to sit for the National Credentialing Agency examination in molecular biology to obtain the credential Clinical Laboratory Specialist in Molecular Biology (CLSp(MB). This description of the University of Connecticut program may assist other laboratory science programs in creating similar curricula. PMID:11232107

Reagent-Free Programming of Shape-Memory Behavior in Gelatin by Electron Beams: Experiments and Modeling

NASA Astrophysics Data System (ADS)

Riedel, Stefanie; Mayr, Stefan G.

2018-02-01

Recent years have seen a paradigm shift in biomaterials toward stimuli-responsive switchable systems that actively interact with their environment. This work demonstrates how to turn the ubiquitous off-the-shelf material gelatin into such a smart biomaterial. This is achieved by realizing the shape-memory effect, viz., a temperature-induced transition from a secondary into a primary shape that has been programmed in the first place merely by exposure to energetic electrons without addition of potentially hazardous cross-linkers. While this scenario is experimentally quantified for exemplary actuators, a theoretical framework capable of unraveling the molecular foundations and predicting experiments is also presented. It particularly employs molecular dynamics modeling based on force fields that are also derived within this work. Implementing this functionality into a highly accepted material, these findings open an avenue for large-scale application in a broad range of areas.

Systems Biology-Driven Hypotheses Tested In Vivo: The Need to Advancing Molecular Imaging Tools.

PubMed

Verma, Garima; Palombo, Alessandro; Grigioni, Mauro; La Monaca, Morena; D'Avenio, Giuseppe

2018-01-01

Processing and interpretation of biological images may provide invaluable insights on complex, living systems because images capture the overall dynamics as a "whole." Therefore, "extraction" of key, quantitative morphological parameters could be, at least in principle, helpful in building a reliable systems biology approach in understanding living objects. Molecular imaging tools for system biology models have attained widespread usage in modern experimental laboratories. Here, we provide an overview on advances in the computational technology and different instrumentations focused on molecular image processing and analysis. Quantitative data analysis through various open source software and algorithmic protocols will provide a novel approach for modeling the experimental research program. Besides this, we also highlight the predictable future trends regarding methods for automatically analyzing biological data. Such tools will be very useful to understand the detailed biological and mathematical expressions under in-silico system biology processes with modeling properties.

Effects of Maternal Obesity on Fetal Programming: Molecular Approaches

PubMed Central

Neri, Caterina; Edlow, Andrea G.

2016-01-01

Maternal obesity has become a worldwide epidemic. Obesity and a high-fat diet have been shown to have deleterious effects on fetal programming, predisposing offspring to adverse cardiometabolic and neurodevelopmental outcomes. Although large epidemiological studies have shown an association between maternal obesity and adverse outcomes for offspring, the underlying mechanisms remain unclear. Molecular approaches have played a key role in elucidating the mechanistic underpinnings of fetal malprogramming in the setting of maternal obesity. These approaches include, among others, characterization of epigenetic modifications, microRNA expression, the gut microbiome, the transcriptome, and evaluation of specific mRNA expression via quantitative reverse transcription polmerase chain reaction (RT-qPCR) in fetuses and offspring of obese females. This work will review the data from animal models and human fluids/cells regarding the effects of maternal obesity on fetal and offspring neurodevelopment and cardiometabolic outcomes, with a particular focus on molecular approaches. PMID:26337113

Potential human cholesterol esterase inhibitor design: benefits from the molecular dynamics simulations and pharmacophore modeling studies.

PubMed

John, Shalini; Thangapandian, Sundarapandian; Lee, Keun Woo

2012-01-01

Human pancreatic cholesterol esterase (hCEase) is one of the lipases found to involve in the digestion of large and broad spectrum of substrates including triglycerides, phospholipids, cholesteryl esters, etc. The presence of bile salts is found to be very important for the activation of hCEase. Molecular dynamic simulations were performed for the apoform and bile salt complexed form of hCEase using the co-ordinates of two bile salts from bovine CEase. The stability of the systems throughout the simulation time was checked and two representative structures from the highly populated regions were selected using cluster analysis. These two representative structures were used in pharmacophore model generation. The generated pharmacophore models were validated and used in database screening. The screened hits were refined for their drug-like properties based on Lipinski's rule of five and ADMET properties. The drug-like compounds were further refined by molecular docking simulation using GOLD program based on the GOLD fitness score, mode of binding, and molecular interactions with the active site amino acids. Finally, three hits of novel scaffolds were selected as potential leads to be used in novel and potent hCEase inhibitor design. The stability of binding modes and molecular interactions of these final hits were re-assured by molecular dynamics simulations.

Joint Service Chemical and Biological Defense Program: FY 06-07 Overview

DTIC Science & Technology

2006-01-01

Performers Molecular model of human plasma-derived butyryl Electronmicrograph of bacillus spores adhering to cell membrane processes 38866_BATT_TX 11...agents, and radioactive fallout. CPS is integrated with the ship’s Heating, Ventilation, and Air-Conditioning ( HVAC ) systems and provides filtered air...molecules for intervention against protein NTA. • Identify and evaluate effectiveness of spore germination inhibitors. • Expand drug discovery program

Molecular beam mass spectrometer development

NASA Technical Reports Server (NTRS)

Brock, F. J.; Hueser, J. E.

1976-01-01

An analytical model, based on the kinetics theory of a drifting Maxwellian gas is used to determine the nonequilibrium molecular density distribution within a hemispherical shell open aft with its axis parallel to its velocity. The concept of a molecular shield in terrestrial orbit above 200 km is also analyzed using the kinetic theory of a drifting Maxwellian gas. Data are presented for the components of the gas density within the shield due to the free stream atmosphere, outgassing from the shield and enclosed experiments, and atmospheric gas scattered off a shield orbiter system. A description is given of a FORTRAN program for computating the three dimensional transition flow regime past the space shuttle orbiter that employs the Monte Carlo simulation method to model real flow by some thousands of simulated molecules.

Neural network error correction for solving coupled ordinary differential equations

NASA Technical Reports Server (NTRS)

Shelton, R. O.; Darsey, J. A.; Sumpter, B. G.; Noid, D. W.

1992-01-01

A neural network is presented to learn errors generated by a numerical algorithm for solving coupled nonlinear differential equations. The method is based on using a neural network to correctly learn the error generated by, for example, Runge-Kutta on a model molecular dynamics (MD) problem. The neural network programs used in this study were developed by NASA. Comparisons are made for training the neural network using backpropagation and a new method which was found to converge with fewer iterations. The neural net programs, the MD model and the calculations are discussed.

3D-QSAR and docking studies on 4-anilinoquinazoline and 4-anilinoquinoline epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors

NASA Astrophysics Data System (ADS)

Assefa, Haregewein; Kamath, Shantaram; Buolamwini, John K.

2003-08-01

The overexpression and/or mutation of the epidermal growth factor receptor (EGFR) tyrosine kinase has been observed in many human solid tumors, and is under intense investigation as a novel anticancer molecular target. Comparative 3D-QSAR analyses using different alignments were undertaken employing comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA) for 122 anilinoquinazoline and 50 anilinoquinoline inhibitors of EGFR kinase. The SYBYL multifit alignment rule was applied to three different conformational templates, two obtained from a MacroModel Monte Carlo conformational search, and one from the bound conformation of erlotinib in complex with EGFR in the X-ray crystal structure. In addition, a flexible ligand docking alignment obtained with the GOLD docking program, and a novel flexible receptor-guided consensus dynamics alignment obtained with the DISCOVER program in the INSIGHTII modeling package were also investigated. 3D-QSAR models with q2 values up to 0.70 and r2 values up to 0.97 were obtained. Among the 4-anilinoquinazoline set, the q2 values were similar, but the ability of the different conformational models to predict the activities of an external test set varied considerably. In this regard, the model derived using the X-ray crystallographically determined bioactive conformation of erlotinib afforded the best predictive model. Electrostatic, hydrophobic and H-bond donor descriptors contributed the most to the QSAR models of the 4-anilinoquinazolines, whereas electrostatic, hydrophobic and H-bond acceptor descriptors contributed the most to the 4-anilinoquinoline QSAR, particularly the H-bond acceptor descriptor. A novel receptor-guided consensus dynamics alignment has also been introduced for 3D-QSAR studies. This new alignment method may incorporate to some extent ligand-receptor induced fit effects into 3D-QSAR models.

Molecular contamination math model support

NASA Technical Reports Server (NTRS)

Wells, R.

1983-01-01

The operation and features of a preprocessor for the Shuttle/Payload Contamination Evaluation Program Version 2) are described. A preliminary preprocessor for SPACE 2 is developed. Further refinements and enhancements of the preprocessor to insure complete user friendly operation, are recommended.

COMPUTATIONAL TOXICOLOGY: FRAMEWORK, PARTNERSHIPS, AND PROGRAM DEVELOPMENT

EPA Science Inventory

Computational toxicology is a new research initiative being developed within the Office of Research and Development (ORD) of the US Environmental Protection Agency (EPA). Operationally, it is defined as the application of mathematical and computer models together with molecular c...

Molecular pathophysiology of cerebral edema

PubMed Central

Gerzanich, Volodymyr; Simard, J Marc

2015-01-01

Advancements in molecular biology have led to a greater understanding of the individual proteins responsible for generating cerebral edema. In large part, the study of cerebral edema is the study of maladaptive ion transport. Following acute CNS injury, cells of the neurovascular unit, particularly brain endothelial cells and astrocytes, undergo a program of pre- and post-transcriptional changes in the activity of ion channels and transporters. These changes can result in maladaptive ion transport and the generation of abnormal osmotic forces that, ultimately, manifest as cerebral edema. This review discusses past models and current knowledge regarding the molecular and cellular pathophysiology of cerebral edema. PMID:26661240

Computational challenges in modeling gene regulatory events

PubMed Central

Pataskar, Abhijeet; Tiwari, Vijay K.

2016-01-01

ABSTRACT Cellular transcriptional programs driven by genetic and epigenetic mechanisms could be better understood by integrating “omics” data and subsequently modeling the gene-regulatory events. Toward this end, computational biology should keep pace with evolving experimental procedures and data availability. This article gives an exemplified account of the current computational challenges in molecular biology. PMID:27390891

Altered Placental Tryptophan Metabolism: A Crucial Molecular Pathway for the Fetal Programming of Neurodevelopmental Disorders

DTIC Science & Technology

2014-07-01

Molecular Pathway for the Fetal Programming of Neurodevelopmental Disorders PRINCIPAL INVESTIGATOR: Alexandre Bonnin, PhD CONTRACTING...Fetal Programming of Neurodevelopmental Disorders 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Alexandre Bonnin, PhD; Betty...metabolism by maternal inflammation during early gestation constitutes a new molecular pathway for the fetal programming of neurodevelopmental

Competing dynamic phases of active polymer networks

NASA Astrophysics Data System (ADS)

Freedman, Simon; Banerjee, Shiladitya; Dinner, Aaron R.

Recent experiments on in-vitro reconstituted assemblies of F-actin, myosin-II motors, and cross-linking proteins show that tuning local network properties can changes the fundamental biomechanical behavior of the system. For example, by varying cross-linker density and actin bundle rigidity, one can switch between contractile networks useful for reshaping cells, polarity sorted networks ideal for directed molecular transport, and frustrated networks with robust structural properties. To efficiently investigate the dynamic phases of actomyosin networks, we developed a coarse grained non-equilibrium molecular dynamics simulation of model semiflexible filaments, molecular motors, and cross-linkers with phenomenologically defined interactions. The simulation's accuracy was verified by benchmarking the mechanical properties of its individual components and collective behavior against experimental results at the molecular and network scales. By adjusting the model's parameters, we can reproduce the qualitative phases observed in experiment and predict the protein characteristics where phase crossovers could occur in collective network dynamics. Our model provides a framework for understanding cells' multiple uses of actomyosin networks and their applicability in materials research. Supported by the Department of Defense (DoD) through the National Defense Science & Engineering Graduate Fellowship (NDSEG) Program.

Modelling the effect of structural QSAR parameters on skin penetration using genetic programming

NASA Astrophysics Data System (ADS)

Chung, K. K.; Do, D. Q.

2010-09-01

In order to model relationships between chemical structures and biological effects in quantitative structure-activity relationship (QSAR) data, an alternative technique of artificial intelligence computing—genetic programming (GP)—was investigated and compared to the traditional method—statistical. GP, with the primary advantage of generating mathematical equations, was employed to model QSAR data and to define the most important molecular descriptions in QSAR data. The models predicted by GP agreed with the statistical results, and the most predictive models of GP were significantly improved when compared to the statistical models using ANOVA. Recently, artificial intelligence techniques have been applied widely to analyse QSAR data. With the capability of generating mathematical equations, GP can be considered as an effective and efficient method for modelling QSAR data.

Evidence for transgenerational metabolic programming in Drosophila

PubMed Central

Buescher, Jessica L.; Musselman, Laura P.; Wilson, Christina A.; Lang, Tieming; Keleher, Madeline; Baranski, Thomas J.; Duncan, Jennifer G.

2013-01-01

SUMMARY Worldwide epidemiologic studies have repeatedly demonstrated an association between prenatal nutritional environment, birth weight and susceptibility to adult diseases including obesity, cardiovascular disease and type 2 diabetes. Despite advances in mammalian model systems, the molecular mechanisms underlying this phenomenon are unclear, but might involve programming mechanisms such as epigenetics. Here we describe a new system for evaluating metabolic programming mechanisms using a simple, genetically tractable Drosophila model. We examined the effect of maternal caloric excess on offspring and found that a high-sugar maternal diet alters body composition of larval offspring for at least two generations, augments an obese-like phenotype under suboptimal (high-calorie) feeding conditions in adult offspring, and modifies expression of metabolic genes. Our data indicate that nutritional programming mechanisms could be highly conserved and support the use of Drosophila as a model for evaluating the underlying genetic and epigenetic contributions to this phenomenon. PMID:23649823

In Vitro Models of Human Toxicity Pathways

EPA Science Inventory

For toxicity testing and assessment programs to address the large numbers of substances of potential concern, a paradigm shift in the assessment of chemical hazard and risk is needed that takes advantage of advances in molecular toxicology, computational sciences, and information...

Water Buffalo (Bubalus bubalis) as a spontaneous animal model of Vitiligo.

PubMed

Singh, Vijay Pal; Motiani, Rajender K; Singh, Archana; Malik, Garima; Aggarwal, Rangoli; Pratap, Kunal; Wani, Mohan R; Gokhale, Suresh B; Natarajan, Vivek T; Gokhale, Rajesh S

2016-07-01

Vitiligo is a multifactorial acquired depigmenting disorder. Recent insights into the molecular mechanisms driving the gradual destruction of melanocytes in vitiligo will likely lead to the discovery of novel therapies, which need to be evaluated in animal models that closely recapitulate the pathogenesis of human vitiligo. In humans, vitiligo is characterized by a spontaneous loss of functional melanocytes from the epidermis, but most animal models of vitiligo are either inducible or genetically programmed. Here, we report that acquired depigmentation in water buffalo recapitulates molecular, histological, immunohistochemical, and ultrastructural changes observed in human vitiligo and hence could be used as a model to study vitiligo pathogenesis and facilitate the discovery and evaluation of therapeutic interventions for vitiligo. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

uPy: a ubiquitous computer graphics Python API with Biological Modeling Applications

PubMed Central

Autin, L.; Johnson, G.; Hake, J.; Olson, A.; Sanner, M.

2015-01-01

In this paper we describe uPy, an extension module for the Python programming language that provides a uniform abstraction of the APIs of several 3D computer graphics programs called hosts, including: Blender, Maya, Cinema4D, and DejaVu. A plugin written with uPy is a unique piece of code that will run in all uPy-supported hosts. We demonstrate the creation of complex plug-ins for molecular/cellular modeling and visualization and discuss how uPy can more generally simplify programming for many types of projects (not solely science applications) intended for multi-host distribution. uPy is available at http://upy.scripps.edu PMID:24806987

A numerical solution for the diffusion equation in hydrogeologic systems

USGS Publications Warehouse

Ishii, A.L.; Healy, R.W.; Striegl, Robert G.

1989-01-01

The documentation of a computer code for the numerical solution of the linear diffusion equation in one or two dimensions in Cartesian or cylindrical coordinates is presented. Applications of the program include molecular diffusion, heat conduction, and fluid flow in confined systems. The flow media may be anisotropic and heterogeneous. The model is formulated by replacing the continuous linear diffusion equation by discrete finite-difference approximations at each node in a block-centered grid. The resulting matrix equation is solved by the method of preconditioned conjugate gradients. The conjugate gradient method does not require the estimation of iteration parameters and is guaranteed convergent in the absence of rounding error. The matrixes are preconditioned to decrease the steps to convergence. The model allows the specification of any number of boundary conditions for any number of stress periods, and the output of a summary table for selected nodes showing flux and the concentration of the flux quantity for each time step. The model is written in a modular format for ease of modification. The model was verified by comparison of numerical and analytical solutions for cases of molecular diffusion, two-dimensional heat transfer, and axisymmetric radial saturated fluid flow. Application of the model to a hypothetical two-dimensional field situation of gas diffusion in the unsaturated zone is demonstrated. The input and output files are included as a check on program installation. The definition of variables, input requirements, flow chart, and program listing are included in the attachments. (USGS)

High Performance Parallel Computational Nanotechnology

NASA Technical Reports Server (NTRS)

Saini, Subhash; Craw, James M. (Technical Monitor)

1995-01-01

At a recent press conference, NASA Administrator Dan Goldin encouraged NASA Ames Research Center to take a lead role in promoting research and development of advanced, high-performance computer technology, including nanotechnology. Manufacturers of leading-edge microprocessors currently perform large-scale simulations in the design and verification of semiconductor devices and microprocessors. Recently, the need for this intensive simulation and modeling analysis has greatly increased, due in part to the ever-increasing complexity of these devices, as well as the lessons of experiences such as the Pentium fiasco. Simulation, modeling, testing, and validation will be even more important for designing molecular computers because of the complex specification of millions of atoms, thousands of assembly steps, as well as the simulation and modeling needed to ensure reliable, robust and efficient fabrication of the molecular devices. The software for this capacity does not exist today, but it can be extrapolated from the software currently used in molecular modeling for other applications: semi-empirical methods, ab initio methods, self-consistent field methods, Hartree-Fock methods, molecular mechanics; and simulation methods for diamondoid structures. In as much as it seems clear that the application of such methods in nanotechnology will require powerful, highly powerful systems, this talk will discuss techniques and issues for performing these types of computations on parallel systems. We will describe system design issues (memory, I/O, mass storage, operating system requirements, special user interface issues, interconnects, bandwidths, and programming languages) involved in parallel methods for scalable classical, semiclassical, quantum, molecular mechanics, and continuum models; molecular nanotechnology computer-aided designs (NanoCAD) techniques; visualization using virtual reality techniques of structural models and assembly sequences; software required to control mini robotic manipulators for positional control; scalable numerical algorithms for reliability, verifications and testability. There appears no fundamental obstacle to simulating molecular compilers and molecular computers on high performance parallel computers, just as the Boeing 777 was simulated on a computer before manufacturing it.

Quantum Entanglement Molecular Absorption Spectrum Simulator

NASA Technical Reports Server (NTRS)

Nguyen, Quang-Viet; Kojima, Jun

2006-01-01

Quantum Entanglement Molecular Absorption Spectrum Simulator (QE-MASS) is a computer program for simulating two photon molecular-absorption spectroscopy using quantum-entangled photons. More specifically, QE-MASS simulates the molecular absorption of two quantum-entangled photons generated by the spontaneous parametric down-conversion (SPDC) of a fixed-frequency photon from a laser. The two-photon absorption process is modeled via a combination of rovibrational and electronic single-photon transitions, using a wave-function formalism. A two-photon absorption cross section as a function of the entanglement delay time between the two photons is computed, then subjected to a fast Fourier transform to produce an energy spectrum. The program then detects peaks in the Fourier spectrum and displays the energy levels of very short-lived intermediate quantum states (or virtual states) of the molecule. Such virtual states were only previously accessible using ultra-fast (femtosecond) laser systems. However, with the use of a single-frequency continuous wave laser to produce SPDC photons, and QEMASS program, these short-lived molecular states can now be studied using much simpler laser systems. QE-MASS can also show the dependence of the Fourier spectrum on the tuning range of the entanglement time of any externally introduced optical-path delay time. QE-MASS can be extended to any molecule for which an appropriate spectroscopic database is available. It is a means of performing an a priori parametric analysis of entangled photon spectroscopy for development and implementation of emerging quantum-spectroscopic sensing techniques. QE-MASS is currently implemented using the Mathcad software package.

Programming chemical kinetics: engineering dynamic reaction networks with DNA strand displacement

NASA Astrophysics Data System (ADS)

Srinivas, Niranjan

Over the last century, the silicon revolution has enabled us to build faster, smaller and more sophisticated computers. Today, these computers control phones, cars, satellites, assembly lines, and other electromechanical devices. Just as electrical wiring controls electromechanical devices, living organisms employ "chemical wiring" to make decisions about their environment and control physical processes. Currently, the big difference between these two substrates is that while we have the abstractions, design principles, verification and fabrication techniques in place for programming with silicon, we have no comparable understanding or expertise for programming chemistry. In this thesis we take a small step towards the goal of learning how to systematically engineer prescribed non-equilibrium dynamical behaviors in chemical systems. We use the formalism of chemical reaction networks (CRNs), combined with mass-action kinetics, as our programming language for specifying dynamical behaviors. Leveraging the tools of nucleic acid nanotechnology (introduced in Chapter 1), we employ synthetic DNA molecules as our molecular architecture and toehold-mediated DNA strand displacement as our reaction primitive. Abstraction, modular design and systematic fabrication can work only with well-understood and quantitatively characterized tools. Therefore, we embark on a detailed study of the "device physics" of DNA strand displacement (Chapter 2). We present a unified view of strand displacement biophysics and kinetics by studying the process at multiple levels of detail, using an intuitive model of a random walk on a 1-dimensional energy landscape, a secondary structure kinetics model with single base-pair steps, and a coarse-grained molecular model that incorporates three-dimensional geometric and steric effects. Further, we experimentally investigate the thermodynamics of three-way branch migration. Our findings are consistent with previously measured or inferred rates for hybridization, fraying, and branch migration, and provide a biophysical explanation of strand displacement kinetics. Our work paves the way for accurate modeling of strand displacement cascades, which would facilitate the simulation and construction of more complex molecular systems. In Chapters 3 and 4, we identify and overcome the crucial experimental challenges involved in using our general DNA-based technology for engineering dynamical behaviors in the test tube. In this process, we identify important design rules that inform our choice of molecular motifs and our algorithms for designing and verifying DNA sequences for our molecular implementation. We also develop flexible molecular strategies for "tuning" our reaction rates and stoichiometries in order to compensate for unavoidable non-idealities in the molecular implementation, such as imperfectly synthesized molecules and spurious "leak" pathways that compete with desired pathways. We successfully implement three distinct autocatalytic reactions, which we then combine into a de novo chemical oscillator. Unlike biological networks, which use sophisticated evolved molecules (like proteins) to realize such behavior, our test tube realization is the first to demonstrate that Watson-Crick base pairing interactions alone suffice for oscillatory dynamics. Since our design pipeline is general and applicable to any CRN, our experimental demonstration of a de novo chemical oscillator could enable the systematic construction of CRNs with other dynamic behaviors.

MTOR-driven quasi-programmed aging as a disposable soma theory: blind watchmaker vs. intelligent designer.

PubMed

Blagosklonny, Mikhail V

2013-06-15

If life were created by intelligent design, we would indeed age from accumulation of molecular damage. Repair is costly and limited by energetic resources, and we would allocate resources rationally. But, albeit elegant, this design is fictional. Instead, nature blindly selects for short-term benefits of robust developmental growth. "Quasi-programmed" by the blind watchmaker, aging is a wasteful and aimless continuation of developmental growth, driven by nutrient-sensing, growth-promoting signaling pathways such as MTOR (mechanistic target of rapamycin). A continuous post-developmental activity of such gerogenic pathways leads to hyperfunctions (aging), loss of homeostasis, age-related diseases, non-random organ damage and death. This model is consistent with a view that (1) soma is disposable, (2) aging and menopause are not programmed and (3) accumulation of random molecular damage is not a cause of aging as we know it.

The new program OPAL for molecular dynamics simulations and energy refinements of biological macromolecules.

PubMed

Luginbühl, P; Güntert, P; Billeter, M; Wüthrich, K

1996-09-01

A new program for molecular dynamics (MD) simulation and energy refinement of biological macromolecules, OPAL, is introduced. Combined with the supporting program TRAJEC for the analysis of MD trajectories, OPAL affords high efficiency and flexibility for work with different force fields, and offers a user-friendly interface and extensive trajectory analysis capabilities. Salient features are computational speeds of up to 1.5 GFlops on vector supercomputers such as the NEC SX-3, ellipsoidal boundaries to reduce the system size for studies in explicit solvents, and natural treatment of the hydrostatic pressure. Practical applications of OPAL are illustrated with MD simulations of pure water, energy minimization of the NMR structure of the mixed disulfide of a mutant E. coli glutaredoxin with glutathione in different solvent models, and MD simulations of a small protein, pheromone Er-2, using either instantaneous or time-averaged NMR restraints, or no restraints.

Optimizing legacy molecular dynamics software with directive-based offload

NASA Astrophysics Data System (ADS)

Michael Brown, W.; Carrillo, Jan-Michael Y.; Gavhane, Nitin; Thakkar, Foram M.; Plimpton, Steven J.

2015-10-01

Directive-based programming models are one solution for exploiting many-core coprocessors to increase simulation rates in molecular dynamics. They offer the potential to reduce code complexity with offload models that can selectively target computations to run on the CPU, the coprocessor, or both. In this paper, we describe modifications to the LAMMPS molecular dynamics code to enable concurrent calculations on a CPU and coprocessor. We demonstrate that standard molecular dynamics algorithms can run efficiently on both the CPU and an x86-based coprocessor using the same subroutines. As a consequence, we demonstrate that code optimizations for the coprocessor also result in speedups on the CPU; in extreme cases up to 4.7X. We provide results for LAMMPS benchmarks and for production molecular dynamics simulations using the Stampede hybrid supercomputer with both Intel® Xeon Phi™ coprocessors and NVIDIA GPUs. The optimizations presented have increased simulation rates by over 2X for organic molecules and over 7X for liquid crystals on Stampede. The optimizations are available as part of the "Intel package" supplied with LAMMPS.

Toward a reaction rate model of condensed-phase RDX decomposition under high temperatures

NASA Astrophysics Data System (ADS)

Schweigert, Igor

2014-03-01

Shock ignition of energetic molecular solids is driven by microstructural heterogeneities, at which even moderate stresses can result in sufficiently high temperatures to initiate material decomposition and the release of the chemical energy. Mesoscale modeling of these ``hot spots'' requires a chemical reaction rate model that describes the energy release with a sub-microsecond resolution and under a wide range of temperatures. No such model is available even for well-studied energetic materials such as RDX. In this presentation, I will describe an ongoing effort to develop a reaction rate model of condensed-phase RDX decomposition under high temperatures using first-principles molecular dynamics, transition-state theory, and reaction network analysis. This work was supported by the Naval Research Laboratory, by the Office of Naval Research, and by the DOD High Performance Computing Modernization Program Software Application Institute for Multiscale Reactive Modeling of Insensitive Munitions.

Toward a reaction rate model of condensed-phase RDX decomposition under high temperatures

NASA Astrophysics Data System (ADS)

Schweigert, Igor

2015-06-01

Shock ignition of energetic molecular solids is driven by microstructural heterogeneities, at which even moderate stresses can result in sufficiently high temperatures to initiate material decomposition and chemical energy release. Mesoscale modeling of these ``hot spots'' requires a reaction rate model that describes the energy release with a sub-microsecond resolution and under a wide range of temperatures. No such model is available even for well-studied energetic materials such as RDX. In this presentation, I will describe an ongoing effort to develop a reaction rate model of condensed-phase RDX decomposition under high temperatures using first-principles molecular dynamics, transition-state theory, and reaction network analysis. This work was supported by the Naval Research Laboratory, by the Office of Naval Research, and by the DoD High Performance Computing Modernization Program Software Application Institute for Multiscale Reactive Modeling of Insensitive Munitions.

Evaluation of protein-protein docking model structures using all-atom molecular dynamics simulations combined with the solution theory in the energy representation

NASA Astrophysics Data System (ADS)

Takemura, Kazuhiro; Guo, Hao; Sakuraba, Shun; Matubayasi, Nobuyuki; Kitao, Akio

2012-12-01

We propose a method to evaluate binding free energy differences among distinct protein-protein complex model structures through all-atom molecular dynamics simulations in explicit water using the solution theory in the energy representation. Complex model structures are generated from a pair of monomeric structures using the rigid-body docking program ZDOCK. After structure refinement by side chain optimization and all-atom molecular dynamics simulations in explicit water, complex models are evaluated based on the sum of their conformational and solvation free energies, the latter calculated from the energy distribution functions obtained from relatively short molecular dynamics simulations of the complex in water and of pure water based on the solution theory in the energy representation. We examined protein-protein complex model structures of two protein-protein complex systems, bovine trypsin/CMTI-1 squash inhibitor (PDB ID: 1PPE) and RNase SA/barstar (PDB ID: 1AY7), for which both complex and monomer structures were determined experimentally. For each system, we calculated the energies for the crystal complex structure and twelve generated model structures including the model most similar to the crystal structure and very different from it. In both systems, the sum of the conformational and solvation free energies tended to be lower for the structure similar to the crystal. We concluded that our energy calculation method is useful for selecting low energy complex models similar to the crystal structure from among a set of generated models.

Evaluation of protein-protein docking model structures using all-atom molecular dynamics simulations combined with the solution theory in the energy representation.

PubMed

Takemura, Kazuhiro; Guo, Hao; Sakuraba, Shun; Matubayasi, Nobuyuki; Kitao, Akio

2012-12-07

We propose a method to evaluate binding free energy differences among distinct protein-protein complex model structures through all-atom molecular dynamics simulations in explicit water using the solution theory in the energy representation. Complex model structures are generated from a pair of monomeric structures using the rigid-body docking program ZDOCK. After structure refinement by side chain optimization and all-atom molecular dynamics simulations in explicit water, complex models are evaluated based on the sum of their conformational and solvation free energies, the latter calculated from the energy distribution functions obtained from relatively short molecular dynamics simulations of the complex in water and of pure water based on the solution theory in the energy representation. We examined protein-protein complex model structures of two protein-protein complex systems, bovine trypsin/CMTI-1 squash inhibitor (PDB ID: 1PPE) and RNase SA/barstar (PDB ID: 1AY7), for which both complex and monomer structures were determined experimentally. For each system, we calculated the energies for the crystal complex structure and twelve generated model structures including the model most similar to the crystal structure and very different from it. In both systems, the sum of the conformational and solvation free energies tended to be lower for the structure similar to the crystal. We concluded that our energy calculation method is useful for selecting low energy complex models similar to the crystal structure from among a set of generated models.

21st International Conference on DNA Computing and Molecular Programming: 8.1 Biochemistry

DTIC Science & Technology

include information storage and biological applications of DNA systems, biomolecular chemical reaction networks, applications of self -assembled DNA...nanostructures, tile self -assembly and computation, principles and models of self -assembly, and strand displacement and biomolecular circuits. The fund

Monopropellant hydrazine resistoject: Engineering model fabrication and test task

NASA Technical Reports Server (NTRS)

Murch, C. K.

1973-01-01

The monopropellant hydrazine resistojet, termed the electrothermal hydrazine thruster (EHT) by TRW systems, thermally decomposes anhydrous hydrazine propellant to produce a high-temperature, low-molecular-weight gas for expulsion through a propulsive nozzle. The EHT developed for this program required about 3-5 watts of electrical power and produced 0.020 to 0.070 pound of thrust over the inlet pressure range of 100 to 400 psia. The thruster was designed for both pulsed and steady state operation. A summary of the GSFC original requirements and GSFC modified requirements, and the performance of the engineering model EHT is given. The experimental program leading to the engineering model EHT design, modifications necessary to achieve the required thruster life capability, and the results of the life test prgram. Other facets of the program, including analyses, preliminary design, specifications, data correlation, and recommendations for a flight model are discussed.

In silico study of in vitro GPCR assays by QSAR modeling ...

EPA Pesticide Factsheets

The U.S. EPA is screening thousands of chemicals of environmental interest in hundreds of in vitro high-throughput screening (HTS) assays (the ToxCast program). One goal is to prioritize chemicals for more detailed analyses based on activity in molecular initiating events (MIE) of adverse outcome pathways (AOPs). However, the chemical space of interest for environmental exposure is much wider than this set of chemicals. Thus, there is a need to fill data gaps with in silico methods, and quantitative structure-activity relationships (QSARs) are a proven and cost effective approach to predict biological activity. ToxCast in turn provides relatively large datasets that are ideal for training and testing QSAR models. The overall goal of the study described here was to develop QSAR models to fill the data gaps in a larger environmental database of ~32k structures. The specific aim of the current work was to build QSAR models for 18 G-Protein Coupled Receptor (GPCR) assays, part of the aminergic category. Two QSAR modeling strategies were adopted: classification models were developed to separate chemicals into active/non-active classes, and then regression models were built to predict the potency values of the bioassays for the active chemicals. Multiple software programs were used to calculate constitutional, topological and substructural molecular descriptors from two-dimensional (2D) chemical structures. Model-fitting methods included PLSDA (partial least squares d

Descriptions and Implementations of DL_F Notation: A Natural Chemical Expression System of Atom Types for Molecular Simulations.

PubMed

Yong, Chin W

2016-08-22

DL_F Notation is an easy-to-understand, standardized atom typesetting expression for molecular simulations for a range of organic force field (FF) schemes such as OPLSAA, PCFF, and CVFF. It is implemented within DL_FIELD, a software program that facilitates the setting up of molecular FF models for DL_POLY molecular dynamics simulation software. By making use of the Notation, a single core conversion module (the DL_F conversion Engine) implemented within DL_FIELD can be used to analyze a molecular structure and determine the types of atoms for a given FF scheme. Users only need to provide the molecular input structure in a simple xyz format and DL_FIELD can produce the necessary force field file for DL_POLY automatically. In commensurate with the development concept of DL_FIELD, which placed emphasis on robustness and user friendliness, the Engine provides a single-step solution to setup complex FF models. This allows users to switch from one of the above-mentioned FF seamlessly to another while at the same time provides a consistent atom typing that is expressed in a natural chemical sense.

Educational Gaps in Molecular Diagnostics, Genomics, and Personalized Medicine in Dermatopathology Training: A Survey of U.S. Dermatopathology Fellowship Program Directors.

PubMed

Torre, Kristin; Russomanno, Kristen; Ferringer, Tammie; Elston, Dirk; Murphy, Michael J

2018-01-01

Molecular technologies offer clinicians the tools to provide high-quality, cost-effective patient care. We evaluated education focused on molecular diagnostics, genomics, and personalized medicine in dermatopathology fellowship training. A 20-question online survey was emailed to all (n = 53) Accreditation Council for Graduate Medical Education (ACGME)-accredited dermatopathology training programs in the United States. Thirty-one of 53 program directors responded (response rate = 58%). Molecular training is undertaken in 74% of responding dermatopathology fellowships, with levels of instruction varying among dermatology-based and pathology-based programs. Education differed for dermatology- and pathology-trained fellows in approximately one-fifth (19%) of programs. Almost half (48%) of responding program directors believe that fellows are not currently receiving adequate molecular education, although the majority (97%) expect to incorporate additional instruction in the next 2-5 years. Factors influencing the incorporation of relevant education include perceived clinical utility and Accreditation Council for Graduate Medical Education/residency review committee (RRC) requirements. Potential benefits of molecular education include increased medical knowledge, improved patient care, and promotion of effective communication with other healthcare professionals. More than two-thirds (68%) of responding program directors believe that instruction in molecular technologies should be required in dermatopathology fellowship training. Although all responding dermatopathology fellowship program directors agreed that molecular education is important, only a little over half of survey participants believe that their fellows receive adequate instruction. This represents an important educational gap. Discussion among those who oversee fellow education is necessary to best integrate and evaluate teaching of molecular dermatopathology.

Software Applications on the Peregrine System | High-Performance Computing

Science.gov Websites

programming and optimization. Gaussian Chemistry Program for calculating molecular electronic structure and Materials Science Open-source classical molecular dynamics program designed for massively parallel systems framework Q-Chem Chemistry ab initio quantum chemistry package for predictin molecular structures

Research on Spectroscopy, Opacity, and Atmospheres

NASA Technical Reports Server (NTRS)

Kurucz, Robert L.; West, Donald (Technical Monitor)

2001-01-01

With this funding I produced a web site kurucz.harvard.edu that can also be accessed by FTP. it has a 73GB disk that holds all of my atomic and diatomic molecular data, my tables of distribution function opacities, my grids of model atmospheres, colors, fluxes, etc., my programs that are ready for distribution, and most of my recent papers. Atlases and computed spectra will be added as they are completed. New atomic and molecular calculations will be added as they are completed.

Application of computer-assisted molecular modeling for immunoassay of low molecular weight food contaminants: A review.

PubMed

Xu, Zhen-Lin; Shen, Yu-Dong; Beier, Ross C; Yang, Jin-Yi; Lei, Hong-Tao; Wang, Hong; Sun, Yuan-Ming

2009-08-11

Immunoassay for low molecular weight food contaminants, such as pesticides, veterinary drugs, and mycotoxins is now a well-established technique which meets the demand for a rapid, reliable, and cost-effective analytical method. However, due to limited understanding of the molecular structure of antibody binding sites and antigenic epitopes, as well as the intermolecular binding forces that come into play, the traditional 'trial and error' method used to develop antibodies still remains the method of choice. Therefore, development of enhanced immunochemical techniques for specific- and generic-assays, requires new approaches for antibody design that will improve affinity and specificity of the antibody in a more rapid and economic manner. Computer-assisted molecular modeling (CAMM) has been demonstrated to be a useful tool to help the immunochemist develop immunoassays. CAMM methods can be used to help direct improvements to important antibody features, and can provide insights into the effects of molecular structure on biological activity that are difficult or impossible to obtain in any other way. In this review, we briefly summarize applications of CAMM in immunoassay development, including assisting in hapten design, explaining cross-reactivity, modeling antibody-antigen interactions, and providing insights into the effects of the mouse body temperature on the three-dimensional conformation of a hapten during antibody production. The fundamentals and theory, programs and software, limitations, and prospects of CAMM in immunoassay development were also discussed.

Modeling of three dimensional structure of human alpha-fetoprotein complexed with diethylstilbestrol: docking and molecular dynamics simulation study.

PubMed

Terentiev, Alexander A; Moldogazieva, Nurbubu T; Levtsova, Olga V; Maximenko, Dmitry M; Borozdenko, Denis A; Shaitan, Konstantin V

2012-04-01

It has been long experimentally demonstrated that human alpha-fetoprotein (HAFP) has an ability to bind immobilized estrogens with the most efficiency for synthetic estrogen analog - diethylstilbestrol (DES). However, the question remains why the human AFP (HAFP), unlike rodent AFP, cannot bind free estrogens. Moreover, despite the fact that AFP was first discovered more than 50 years ago and is presently recognized as a "golden standard" among onco-biomarkers, its three-dimensional (3D) structure has not been experimentally solved yet. In this work using MODELLER program, we generated 3D model of HAFP on the basis of homology with human serum albumin (HSA) and Vitamin D-binding protein (VTDB) with subsequent molecular docking of DES to the model structure and molecular dynamics (MD) simulation study of the complex obtained. The model constructed has U-shaped structure in which a cavity may be distinguished. In this cavity the putative estrogen-binding site is localized. Validation by RMSD calculation and with the use of PROCHECK program showed good quality of the model and stability of extended region of four alpha-helical structures that contains putative hormone-binding residues. Data extracted from MD simulation trajectory allow proposing two types of interactions between amino acid residues of HAFP and DES molecule: (1) hydrogen bonding with involvement of residues S445, R452, and E551; (2) hydrophobic interactions with participation of L138, M448, and M548 residues. A suggestion is made that immobilization of the hormone using a long spacer provides delivery of the estrogen molecule to the binding site and, thereby, facilitates interaction between HAFP and the hormone.

Modeling of capacitively and inductively coupled plasma for molecular decontamination

NASA Astrophysics Data System (ADS)

Mihailova, Diana; Hagelaar, Gerjan; Belenguer, Philippe; Laurent, Christopher; Lo, Juslan; Caillier, Bruno; Therese, Laurent; Guillot, Philippe

2013-09-01

This project aims to study and to develop new technology bricks for next generation of molecular decontamination systems, including plasma solution, for various applications. The contamination control in the processing stages is a major issue for the industrial performance as well as for the development of new technologies in the surface treatment area. The main task is to create uniform low temperature plasma inside a reactor containing the object to be treated. Different plasma sources are modeled with the aim of finding the most efficient one for surface decontamination: inductively coupled plasma, capacitively coupled plasma and combination of both. The model used for testing the various plasma sources is a time dependent two-dimensional multi-fluid model. The model is applied to a simplified cylindrically symmetric geometry in pure argon gas. The modeling results are validated by comparison with experimental results and observations based on optical and physical diagnostic tools. The influence of various parameters (power, pressure, flow) is studied and the corresponding results are presented, compared and discussed. This work has been performed in the frame of the collaborative program PAUD (Plasma Airborne molecular contamination Ultra Desorption) funded by the French agency OSEO and certified by French global competitive clusters Minalogic and Trimatec.

Molecular pathology curriculum for medical laboratory scientists: A report of the association for molecular pathology training and education committee.

PubMed

Taylor, Sara; Bennett, Katie M; Deignan, Joshua L; Hendrix, Ericka C; Orton, Susan M; Verma, Shalini; Schutzbank, Ted E

2014-05-01

Molecular diagnostics is a rapidly growing specialty in the clinical laboratory assessment of pathology. Educational programs in medical laboratory science and specialized programs in molecular diagnostics must address the training of clinical scientists in molecular diagnostics, but the educational curriculum for this field is not well defined. Moreover, our understanding of underlying genetic contributions to specific diseases and the technologies used in molecular diagnostics laboratories change rapidly, challenging providers of training programs in molecular diagnostics to keep their curriculum current and relevant. In this article, we provide curriculum recommendations to molecular diagnostics training providers at both the baccalaureate and master's level of education. We base our recommendations on several factors. First, we considered National Accrediting Agency for Clinical Laboratory Sciences guidelines for accreditation of molecular diagnostics programs, because educational programs in clinical laboratory science should obtain its accreditation. Second, the guidelines of several of the best known certifying agencies for clinical laboratory scientists were incorporated into our recommendations. Finally, we relied on feedback from current employers of molecular diagnostics scientists, regarding the skills and knowledge that they believe are essential for clinical scientists who will be performing molecular testing in their laboratories. We have compiled these data into recommendations for a molecular diagnostics curriculum at both the baccalaureate and master's level of education. Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

IADE: a system for intelligent automatic design of bioisosteric analogs

NASA Astrophysics Data System (ADS)

Ertl, Peter; Lewis, Richard

2012-11-01

IADE, a software system supporting molecular modellers through the automatic design of non-classical bioisosteric analogs, scaffold hopping and fragment growing, is presented. The program combines sophisticated cheminformatics functionalities for constructing novel analogs and filtering them based on their drug-likeness and synthetic accessibility using automatic structure-based design capabilities: the best candidates are selected according to their similarity to the template ligand and to their interactions with the protein binding site. IADE works in an iterative manner, improving the fitness of designed molecules in every generation until structures with optimal properties are identified. The program frees molecular modellers from routine, repetitive tasks, allowing them to focus on analysis and evaluation of the automatically designed analogs, considerably enhancing their work efficiency as well as the area of chemical space that can be covered. The performance of IADE is illustrated through a case study of the design of a nonclassical bioisosteric analog of a farnesyltransferase inhibitor—an analog that has won a recent "Design a Molecule" competition.

IADE: a system for intelligent automatic design of bioisosteric analogs.

PubMed

Ertl, Peter; Lewis, Richard

2012-11-01

IADE, a software system supporting molecular modellers through the automatic design of non-classical bioisosteric analogs, scaffold hopping and fragment growing, is presented. The program combines sophisticated cheminformatics functionalities for constructing novel analogs and filtering them based on their drug-likeness and synthetic accessibility using automatic structure-based design capabilities: the best candidates are selected according to their similarity to the template ligand and to their interactions with the protein binding site. IADE works in an iterative manner, improving the fitness of designed molecules in every generation until structures with optimal properties are identified. The program frees molecular modellers from routine, repetitive tasks, allowing them to focus on analysis and evaluation of the automatically designed analogs, considerably enhancing their work efficiency as well as the area of chemical space that can be covered. The performance of IADE is illustrated through a case study of the design of a nonclassical bioisosteric analog of a farnesyltransferase inhibitor--an analog that has won a recent "Design a Molecule" competition.

Cometary MHD and chemistry

NASA Technical Reports Server (NTRS)

Wegmann, R.; Schmidt, H. U.; Huebner, W. F.; Boice, D. C.

1987-01-01

An MHD and chemical comet-coma model was developed, applying the computer program of Huebner (1985) for the detailed chemical evolution of a spherically expanding coma and the program of Schmidt and Wegman (1982) and Wegman (1987) for the MHD flow of plasma and magnetic field in a comet to the Giotto-mission data on the ion abundances measured by the HIS ion mass spectrometer. The physics and chemistry of the coma are modeled in great detail, including photoprocesses, gas-phase chemical kinetics, energy balance with a separate electron temperature, multifluid hydrodynamics with a transition to free molecular flow, fast-streaming atomic and molecular hydrogen, counter and cross streaming of the ionized species relative to the neutral species in the coma-solar wind interaction region with momentum exchange by elastic collisions, mass-loading through ion pick-up, and Lorentz forces of the advected magnetic field. The results, both inside and outside of the contact surface, are discussed and compared with the relevant HIS ion mass spectra.

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

NASA Astrophysics Data System (ADS)

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 No. of bytes in distributed program, including test data, etc.: 3 798 507 No. of lines in distributed program, including test data, etc.: 187 226 Distribution format: tar.gz Nature of physical problem: In this set of codes an efficient procedure is implemented to describe the wavefunction and related molecular properties of a polyatomic molecular system within the Single Center of Expansion (SCE) approximation. The resulting SCE wavefunction, electron density, electrostatic and exchange/correlation potentials can then be used via a proper Application Programming Interface (API) to describe the target molecular system which can be employed in electron-molecule scattering calculations. The molecular properties expanded over a single center turn out to also be of more general application and some possible uses in quantum chemistry, biomodelling and drug design are also outlined. Method of solution: The polycentre Hartee-Fock solution for a molecule of arbitrary geometry, based on linear combination of Gaussian-Type Orbital (GTO), is expanded over a single center, typically the Center Of Mass (C.O.M.), by means of a Gauss-Legendre/Chebyschev quadrature over the θ, φ angular coordinates. The resulting SCE numerical wavefunction is then used to calculate the one-particle electron density, the electrostatic potential and two different models for the correlation/polarization potentials induced by the impinging electron, which have the correct asymptotic behaviour for the leading dipole molecular polarizabilities. Restrictions on the complexity of the problem: Depending on the molecular system under study and on the operating conditions the program may or may not fit into available RAM memory. In this case a feature of the program is to memory map a disk file in order to efficiently access the memory data through a disk device. Typical running time: The execution time strongly depends on the molecular target description and on the hardware/OS chosen, it is directly proportional to the ( r, θ, φ) grid size and to the number of angular basis functions used. Thus, from the program printout of the main arrays memory occupancy, the user can approximately derive the expected computer time needed for a given calculation executed in serial mode. For parallel executions the overall efficiency must be further taken into account, and this depends on the no. of processors used as well as on the parallel architecture chosen, so a simple general law is at present not determinable. Unusual features of the program: The code has been engineered to use dynamical, runtime determined, global parameters with the aim to have all the data fitted in the RAM memory. Some unusual circumstances, e.g., when using large values of those parameters, may cause the program to run with unexpected performance reductions due to runtime bottlenecks like those caused by memory swap operations which strongly depend on the hardware used. In such cases, a parallel execution of the code is generally sufficient to fix the problem since the data size is partitioned over the available processors. When a suitable parallel system is not available for execution, a mechanism of memory mapped file can be used; with this option on, all the available memory will be used as a buffer for a disk file which contains the whole data set, thus having a better throughput with respect to the traditional swapping/paging of the Unix OS.

Promoting convergence: The integrated graduate program in physical and engineering biology at Yale University, a new model for graduate education.

PubMed

Noble, Dorottya B; Mochrie, Simon G J; O'Hern, Corey S; Pollard, Thomas D; Regan, Lynne

2016-11-12

In 2008, we established the Integrated Graduate Program in Physical and Engineering Biology (IGPPEB) at Yale University. Our goal was to create a comprehensive graduate program to train a new generation of scientists who possess a sophisticated understanding of biology and who are capable of applying physical and quantitative methodologies to solve biological problems. Here we describe the framework of the training program, report on its effectiveness, and also share the insights we gained during its development and implementation. The program features co-teaching by faculty with complementary specializations, student peer learning, and novel hands-on courses that facilitate the seamless blending of interdisciplinary research and teaching. It also incorporates enrichment activities to improve communication skills, engage students in science outreach, and foster a cohesive program cohort, all of which promote the development of transferable skills applicable in a variety of careers. The curriculum of the graduate program is integrated with the curricular requirements of several Ph.D.-granting home programs in the physical, engineering, and biological sciences. Moreover, the wide-ranging recruiting activities of the IGPPEB serve to enhance the quality and diversity of students entering graduate school at Yale. We also discuss some of the challenges we encountered in establishing and optimizing the program, and describe the institution-level changes that were catalyzed by the introduction of the new graduate program. The goal of this article is to serve as both an inspiration and as a practical "how to" manual for those who seek to establish similar programs at their own institutions. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(6):537-549, 2016. © 2016 The Authors Biochemistry and Molecular Biology Education published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology.

Programming molecular self-assembly of intrinsically disordered proteins containing sequences of low complexity

NASA Astrophysics Data System (ADS)

Simon, Joseph R.; Carroll, Nick J.; Rubinstein, Michael; Chilkoti, Ashutosh; López, Gabriel P.

2017-06-01

Dynamic protein-rich intracellular structures that contain phase-separated intrinsically disordered proteins (IDPs) composed of sequences of low complexity (SLC) have been shown to serve a variety of important cellular functions, which include signalling, compartmentalization and stabilization. However, our understanding of these structures and our ability to synthesize models of them have been limited. We present design rules for IDPs possessing SLCs that phase separate into diverse assemblies within droplet microenvironments. Using theoretical analyses, we interpret the phase behaviour of archetypal IDP sequences and demonstrate the rational design of a vast library of multicomponent protein-rich structures that ranges from uniform nano-, meso- and microscale puncta (distinct protein droplets) to multilayered orthogonally phase-separated granular structures. The ability to predict and program IDP-rich assemblies in this fashion offers new insights into (1) genetic-to-molecular-to-macroscale relationships that encode hierarchical IDP assemblies, (2) design rules of such assemblies in cell biology and (3) molecular-level engineering of self-assembled recombinant IDP-rich materials.

Workshop on High-Field NMR and Biological Applications

NASA Astrophysics Data System (ADS)

Scientists at the Pacific Northwest Laboratory have been working toward the establishment of a new Molecular Science Research Center (MSRC). The primary scientific thrust of this new research center is in the areas of theoretical chemistry, chemical dynamics, surface and interfacial science, and studies on the structure and interactions of biological macromolecules. The MSRC will provide important new capabilities for studies on the structure of biological macromolecules. The MSRC program includes several types of advanced spectroscopic techniques for molecular structure analysis, and a theory and modeling laboratory for molecular mechanics/dynamics calculations and graphics. It is the goal to closely integrate experimental and theoretical studies on macromolecular structure, and to join these research efforts with those of the molecular biological programs to provide new insights into the structure/function relationships of biological macromolecules. One of the areas of structural biology on which initial efforts in the MSRC will be focused is the application of high field, 2-D NMR to the study of biological macromolecules. First, there is interest in obtaining 3-D structural information on large proteins and oligonucleotides. Second, one of the primary objectives is to closely link theoretical approaches to molecular structure analysis with the results obtained in experimental research using NMR and other spectroscopies.

Department of Defense High Performance Computing Modernization Program. 2006 Annual Report

DTIC Science & Technology

2007-03-01

Department. We successfully completed several software development projects that introduced parallel, scalable production software now in use across the...imagined. They are developing and deploying weather and ocean models that allow our soldiers, sailors, marines and airmen to plan missions more effectively...and to navigate adverse environments safely. They are modeling molecular interactions leading to the development of higher energy fuels, munitions

Predicting human skin absorption of chemicals: development of a novel quantitative structure activity relationship.

PubMed

Luo, Wen; Medrek, Sarah; Misra, Jatin; Nohynek, Gerhard J

2007-02-01

The objective of this study was to construct and validate a quantitative structure-activity relationship model for skin absorption. Such models are valuable tools for screening and prioritization in safety and efficacy evaluation, and risk assessment of drugs and chemicals. A database of 340 chemicals with percutaneous absorption was assembled. Two models were derived from the training set consisting 306 chemicals (90/10 random split). In addition to the experimental K(ow) values, over 300 2D and 3D atomic and molecular descriptors were analyzed using MDL's QsarIS computer program. Subsequently, the models were validated using both internal (leave-one-out) and external validation (test set) procedures. Using the stepwise regression analysis, three molecular descriptors were determined to have significant statistical correlation with K(p) (R2 = 0.8225): logK(ow), X0 (quantification of both molecular size and the degree of skeletal branching), and SsssCH (count of aromatic carbon groups). In conclusion, two models to estimate skin absorption were developed. When compared to other skin absorption QSAR models in the literature, our model incorporated more chemicals and explored a large number of descriptors. Additionally, our models are reasonably predictive and have met both internal and external statistical validations.

Easy GROMACS: A Graphical User Interface for GROMACS Molecular Dynamics Simulation Package

NASA Astrophysics Data System (ADS)

Dizkirici, Ayten; Tekpinar, Mustafa

2015-03-01

GROMACS is a widely used molecular dynamics simulation package. Since it is a command driven program, it is difficult to use this program for molecular biologists, biochemists, new graduate students and undergraduate researchers who are interested in molecular dynamics simulations. To alleviate the problem for those researchers, we wrote a graphical user interface that simplifies protein preparation for a classical molecular dynamics simulation. Our program can work with various GROMACS versions and it can perform essential analyses of GROMACS trajectories as well as protein preparation. We named our open source program `Easy GROMACS'. Easy GROMACS can give researchers more time for scientific research instead of dealing with technical intricacies.

Modeling Reproductive Toxicity for Chemical Prioritization into an Integrated Testing Strategy

EPA Science Inventory

The EPA ToxCast research program uses a high-throughput screening (HTS) approach for predicting the toxicity of large numbers of chemicals. Phase-I tested 309 well-characterized chemicals in over 500 assays of different molecular targets, cellular responses and cell-states. Of th...

PREDICTION OF THE VAPOR PRESSURE, BOILING POINT, HEAT OF VAPORIZATION AND DIFFUSION COEFFICIENT OF ORGANIC COMPOUNDS

EPA Science Inventory

The prototype computer program SPARC has been under development for several years to estimate physical properties and chemical reactivity parameters of organic compounds strictly from molecular structure. SPARC solute-solute physical process models have been developed and tested...

Catalysis and biocatalysis program

NASA Technical Reports Server (NTRS)

1991-01-01

The annual report presents the fiscal year (FY) 1990 research activities and accomplishments for the Catalysis and Biocatalysis Program of the Advanced Industrial Concepts Division (AICD), Office of Industrial Technologies of the Department of Energy (DOE). The mission of the AICD is to create a balanced program of high risk, long term, directed interdisciplinary research and development that will improve energy efficiency and enhance fuel flexibility in the industrial sector. The Catalysis and Biocatalysis Program's technical activities were organized into five work elements: the Molecular Modeling and Catalysis by Design element; the Applied Microbiology and Genetics element; the Bioprocess Engineering element; the Separations and Novel Chemical Processes element; and the Process Design and Analysis element.

Highlights of Transient Plume Impingement Model Validation and Applications

NASA Technical Reports Server (NTRS)

Woronowicz, Michael

2011-01-01

This paper describes highlights of an ongoing validation effort conducted to assess the viability of applying a set of analytic point source transient free molecule equations to model behavior ranging from molecular effusion to rocket plumes. The validation effort includes encouraging comparisons to both steady and transient studies involving experimental data and direct simulation Monte Carlo results. Finally, this model is applied to describe features of two exotic transient scenarios involving NASA Goddard Space Flight Center satellite programs.

Genetic algorithms and genetic programming for multiscale modeling: Applications in materials science and chemistry and advances in scalability

NASA Astrophysics Data System (ADS)

Sastry, Kumara Narasimha

2007-03-01

Effective and efficient rnultiscale modeling is essential to advance both the science and synthesis in a, wide array of fields such as physics, chemistry, materials science; biology, biotechnology and pharmacology. This study investigates the efficacy and potential of rising genetic algorithms for rnultiscale materials modeling and addresses some of the challenges involved in designing competent algorithms that solve hard problems quickly, reliably and accurately. In particular, this thesis demonstrates the use of genetic algorithms (GAs) and genetic programming (GP) in multiscale modeling with the help of two non-trivial case studies in materials science and chemistry. The first case study explores the utility of genetic programming (GP) in multi-timescaling alloy kinetics simulations. In essence, GP is used to bridge molecular dynamics and kinetic Monte Carlo methods to span orders-of-magnitude in simulation time. Specifically, GP is used to regress symbolically an inline barrier function from a limited set of molecular dynamics simulations to enable kinetic Monte Carlo that simulate seconds of real time. Results on a non-trivial example of vacancy-assisted migration on a surface of a face-centered cubic (fcc) Copper-Cobalt (CuxCo 1-x) alloy show that GP predicts all barriers with 0.1% error from calculations for less than 3% of active configurations, independent of type of potentials used to obtain the learning set of barriers via molecular dynamics. The resulting method enables 2--9 orders-of-magnitude increase in real-time dynamics simulations taking 4--7 orders-of-magnitude less CPU time. The second case study presents the application of multiobjective genetic algorithms (MOGAs) in multiscaling quantum chemistry simulations. Specifically, MOGAs are used to bridge high-level quantum chemistry and semiempirical methods to provide accurate representation of complex molecular excited-state and ground-state behavior. Results on ethylene and benzene---two common building blocks in organic chemistry---indicate that MOGAs produce High-quality semiempirical methods that (1) are stable to small perturbations, (2) yield accurate configuration energies on untested and critical excited states, and (3) yield ab initio quality excited-state dynamics. The proposed method enables simulations of more complex systems to realistic, multi-picosecond timescales, well beyond previous attempts or expectation of human experts, and 2--3 orders-of-magnitude reduction in computational cost. While the two applications use simple evolutionary operators, in order to tackle more complex systems, their scalability and limitations have to be investigated. The second part of the thesis addresses some of the challenges involved with a successful design of genetic algorithms and genetic programming for multiscale modeling. The first issue addressed is the scalability of genetic programming, where facetwise models are built to assess the population size required by GP to ensure adequate supply of raw building blocks and also to ensure accurate decision-making between competing building blocks. This study also presents a design of competent genetic programming, where traditional fixed recombination operators are replaced by building and sampling probabilistic models of promising candidate programs. The proposed scalable GP, called extended compact GP (eCGP), combines the ideas from extended compact genetic algorithm (eCGA) and probabilistic incremental program evolution (PIPE) and adaptively identifies, propagates and exchanges important subsolutions of a search problem. Results show that eCGP scales cubically with problem size on both GP-easy and GP-hard problems. Finally, facetwise models are developed to explore limitations of scalability of MOGAs, where the scalability of multiobjective algorithms in reliably maintaining Pareto-optimal solutions is addressed. The results show that even when the building blocks are accurately identified, massive multimodality of the search problems can easily overwhelm the nicher (diversity preserving operator) and lead to exponential scale-up. Facetwise models are developed, which incorporate the combined effects of model accuracy, decision making, and sub-structure supply, as well as the effect of niching on the population sizing, to predict a limit on the growth rate of a maximum number of sub-structures that can compete in the two objectives to circumvent the failure of the niching method. The results show that if the number of competing building blocks between multiple objectives is less than the proposed limit, multiobjective GAs scale-up polynomially with the problem size on boundedly-difficult problems.

Molecular Sieve Bench Testing and Computer Modeling

NASA Technical Reports Server (NTRS)

Mohamadinejad, Habib; DaLee, Robert C.; Blackmon, James B.

1995-01-01

The design of an efficient four-bed molecular sieve (4BMS) CO2 removal system for the International Space Station depends on many mission parameters, such as duration, crew size, cost of power, volume, fluid interface properties, etc. A need for space vehicle CO2 removal system models capable of accurately performing extrapolated hardware predictions is inevitable due to the change of the parameters which influences the CO2 removal system capacity. The purpose is to investigate the mathematical techniques required for a model capable of accurate extrapolated performance predictions and to obtain test data required to estimate mass transfer coefficients and verify the computer model. Models have been developed to demonstrate that the finite difference technique can be successfully applied to sorbents and conditions used in spacecraft CO2 removal systems. The nonisothermal, axially dispersed, plug flow model with linear driving force for 5X sorbent and pore diffusion for silica gel are then applied to test data. A more complex model, a non-darcian model (two dimensional), has also been developed for simulation of the test data. This model takes into account the channeling effect on column breakthrough. Four FORTRAN computer programs are presented: a two-dimensional model of flow adsorption/desorption in a packed bed; a one-dimensional model of flow adsorption/desorption in a packed bed; a model of thermal vacuum desorption; and a model of a tri-sectional packed bed with two different sorbent materials. The programs are capable of simulating up to four gas constituents for each process, which can be increased with a few minor changes.

Molecular modeling of calmodulin: a comparison with crystallographic data

NASA Technical Reports Server (NTRS)

McDonald, J. J.; Rein, R.

1989-01-01

Two methods of side-chain placement on a modeled protein have been examined. Two molecular models of calmodulin were constructed that differ in the treatment of side chains prior to optimization of the molecule. A virtual bond analysis program developed by Purisima and Scheraga was used to determine the backbone conformation based on 2.2 angstroms resolution C alpha coordinates for the molecules. In the first model, side chains were initially constructed in an extended conformation. In the second model, a conformational grid search technique was employed. Calcium ions were treated explicitly during energy optimization using CHARMM. The models are compared to a recently published refined crystal structure of calmodulin. The results indicate that the initial choices for side-chains, but also significant effects on the main-chain conformation and supersecondary structure. The conformational differences are discussed. Analysis of these and other methods makes possible the formulation of a methodology for more appropriate side-chain placement in modeled proteins.

Molecular Rift: Virtual Reality for Drug Designers.

PubMed

Norrby, Magnus; Grebner, Christoph; Eriksson, Joakim; Boström, Jonas

2015-11-23

Recent advances in interaction design have created new ways to use computers. One example is the ability to create enhanced 3D environments that simulate physical presence in the real world--a virtual reality. This is relevant to drug discovery since molecular models are frequently used to obtain deeper understandings of, say, ligand-protein complexes. We have developed a tool (Molecular Rift), which creates a virtual reality environment steered with hand movements. Oculus Rift, a head-mounted display, is used to create the virtual settings. The program is controlled by gesture-recognition, using the gaming sensor MS Kinect v2, eliminating the need for standard input devices. The Open Babel toolkit was integrated to provide access to powerful cheminformatics functions. Molecular Rift was developed with a focus on usability, including iterative test-group evaluations. We conclude with reflections on virtual reality's future capabilities in chemistry and education. Molecular Rift is open source and can be downloaded from GitHub.

Virtual Ligand Screening Using PL-PatchSurfer2, a Molecular Surface-Based Protein-Ligand Docking Method.

PubMed

Shin, Woong-Hee; Kihara, Daisuke

2018-01-01

Virtual screening is a computational technique for predicting a potent binding compound for a receptor protein from a ligand library. It has been a widely used in the drug discovery field to reduce the efforts of medicinal chemists to find hit compounds by experiments.Here, we introduce our novel structure-based virtual screening program, PL-PatchSurfer, which uses molecular surface representation with the three-dimensional Zernike descriptors, which is an effective mathematical representation for identifying physicochemical complementarities between local surfaces of a target protein and a ligand. The advantage of the surface-patch description is its tolerance on a receptor and compound structure variation. PL-PatchSurfer2 achieves higher accuracy on apo form and computationally modeled receptor structures than conventional structure-based virtual screening programs. Thus, PL-PatchSurfer2 opens up an opportunity for targets that do not have their crystal structures. The program is provided as a stand-alone program at http://kiharalab.org/plps2 . We also provide files for two ligand libraries, ChEMBL and ZINC Drug-like.

The Art of Molecular Dynamics Simulation (by D. C. Rapaport)

NASA Astrophysics Data System (ADS)

Molner, Stephen P.

1999-02-01

Cambridge University Press: New York, 1996. 400 pp. ISBN 0 521 44561 2. $74.95. This book describes the extremely powerful techniques of molecular dynamics simulation. The techniques involve solving the classical many-body problems in contexts relevant to the study of matter at the atomic level. The method allows the prediction of static and dynamics properties of substances directly from the underlying interactions between molecules. This is, of course, a very broad subject and the author has adopted a dual approach in that the text is partly tutorial and also contains a large number of computer programs for practical use. Rapaport has adopted the attitude of trying the simplest method first. Atoms are modeled as point particles interacting through point potentials. Molecules are represented by atoms with orientation dependent forces, or as extended structures each containing several interaction sites. The molecules may be rigid, flexible, or somewhere in between, and if there are internal degrees of freedom there will be internal forces as well. The intent of the book is not to discuss the design of molecular models, but rather to make use of existing models, and from a pedagogical viewpoint the simpler the model the better. The aim of the book is to demonstrate the general methodology of molecular dynamics simulation by example, not to review the large body of literature covering the many different kinds of models developed for specific applications. The text is partly tutorial, but also contains a large number of computer programs for practical use. This volume will serve as an introduction to the subject for beginners and as a reference manual for the more experienced practitioner. The material covers a wide range of practical methods and real applications and is organized as a series of case studies. The typical case study includes a summary of the theoretical background used for the formulation of the computational approach. That is described by either a complete program listing or a series of modifications or additions to a program from an earlier case study. The initial conditions of the model, organization of the input and output, accuracy, convergence, and efficiency are also addressed for each case and, of course, the results of the computation are given and discussed. The book begins with the simplest case of basic molecular dynamics, a sift-disk fluid. The development is discussed in considerable depth to set the tone of the work. Later chapters extend the basic model in various directions, deal with various types of measurements, improve the computational methods, and introduce new models for more complex problems. These chapters also discuss the methodology for simulating monatomic systems and focus on measuring the thermodynamic and structural properties of systems in equilibrium. Consideration is given to the dynamical properties of equilibrium systems, including transport coefficients and the correlation functions that characterize space- and time-dependent properties. Chapters are devoted to the study of systems under constant temperature and pressure and the dynamics of rigid systems. It is difficult to cover all aspects of such a broad topic as the subject of this book; and the author has not attempted an exhaustive or encyclopedic coverage, but has produced an excellent introduction to the subject. The publisher has made the implementation of the numerous programs essentially painless by making them available via browser and the World Wide Web. The easy availability of the software, written in C, was welcomed by this old Fortran programmer. It is to be hoped that this service is representative of a trend in technical publishing. Overall this work is a pleasure to read and study and would be a valuable addition to the library of both the beginner and the experienced practitioner of the art.

An Introduction to Computational Physics

NASA Astrophysics Data System (ADS)

Pang, Tao

2010-07-01

Preface to first edition; Preface; Acknowledgements; 1. Introduction; 2. Approximation of a function; 3. Numerical calculus; 4. Ordinary differential equations; 5. Numerical methods for matrices; 6. Spectral analysis; 7. Partial differential equations; 8. Molecular dynamics simulations; 9. Modeling continuous systems; 10. Monte Carlo simulations; 11. Genetic algorithm and programming; 12. Numerical renormalization; References; Index.

In silico study of in vitro GPCR assays by QSAR modeling

EPA Science Inventory

The U.S. EPA is screening thousands of chemicals of environmental interest in hundreds of in vitro high-throughput screening (HTS) assays (the ToxCast program). One goal is to prioritize chemicals for more detailed analyses based on activity in molecular initiating events (MIE) o...

Calculations of Young's moduli for cellulose Iß

USDA-ARS?s Scientific Manuscript database

Young's modulus is a measure of a material’s resistance to deformation as the material is forced to elongate. Modulus values for cotton can be determined by performing tension tests experiments on cotton fibers or, as in this study, by stretching molecular models in a computer program. However, repo...

Homology Modeling and Molecular Docking for the Science Curriculum

ERIC Educational Resources Information Center

McDougal, Owen M.; Cornia, Nic; Sambasivarao, S. V.; Remm, Andrew; Mallory, Chris; Oxford, Julia Thom; Maupin, C. Mark; Andersen, Tim

2014-01-01

DockoMatic 2.0 is a powerful open source software program (downloadable from sourceforge.net) that allows users to utilize a readily accessible computational tool to explore biomolecules and their interactions. This manuscript describes a practical tutorial for use in the undergraduate curriculum that introduces students to macromolecular…

WORKSHOP REPORT: COMPUTATIONAL TOXICOLOGY: FRAMEWORK, PARTNERSHIPS, AND PROGRAM DEVELOPMENT, SEPTEMBER 29-30, 2003, RESEARCH TRIANGLE PARK, NORTH CAROLINA

EPA Science Inventory

Computational toxicology is a new research initiative being developed within the Office of Research and Development (ORD) of the US Environmental Protection Agency (EPA). Operationally, it is defined as the application of mathematical and computer models together with molecular c...

Validation, acceptance, and extension of a predictive model of reproductive toxicity using ToxCast data

EPA Science Inventory

The EPA ToxCast research program uses a high-throughput screening (HTS) approach for predicting the toxicity of large numbers of chemicals. Phase-I tested 309 well-characterized chemicals (mostly pesticides) in over 500 assays of different molecular targets, cellular responses an...

Predictive Model of Rat Reproductive Toxicity from ToxCast High Throughput Screening

EPA Science Inventory

The EPA ToxCast research program uses high throughput screening for bioactivity profiling and predicting the toxicity of large numbers of chemicals. ToxCast Phase‐I tested 309 well‐characterized chemicals in over 500 assays for a wide range of molecular targets and cellular respo...

Predictive Signatures from ToxCast Data for Chronic, Developmental and Reproductive Toxicity Endpoints

EPA Science Inventory

The EPA ToxCast program is using in vitro assay data and chemical descriptors to build predictive models for in vivo toxicity endpoints. In vitro assays measure activity of chemicals against molecular targets such as enzymes and receptors (measured in cell-free and cell-based sys...

Predictive Signatures of Developmental Toxicity Modeled with HTS Data from ToxCast™ Bioactivity Profiles

EPA Science Inventory

The EPA ToxCast™ research program uses a high-throughput screening (HTS) approach for predicting the toxicity of large numbers of chemicals. Phase-I contains 309 well-characterized chemicals which are mostly pesticides tested in over 600 assays of different molecular targets, cel...

A Molecular atlas of Xenopus respiratory system development.

PubMed

Rankin, Scott A; Thi Tran, Hong; Wlizla, Marcin; Mancini, Pamela; Shifley, Emily T; Bloor, Sean D; Han, Lu; Vleminckx, Kris; Wert, Susan E; Zorn, Aaron M

2015-01-01

Respiratory system development is regulated by a complex series of endoderm-mesoderm interactions that are not fully understood. Recently Xenopus has emerged as an alternative model to investigate early respiratory system development, but the extent to which the morphogenesis and molecular pathways involved are conserved between Xenopus and mammals has not been systematically documented. In this study, we provide a histological and molecular atlas of Xenopus respiratory system development, focusing on Nkx2.1+ respiratory cell fate specification in the developing foregut. We document the expression patterns of Wnt/β-catenin, fibroblast growth factor (FGF), and bone morphogenetic protein (BMP) signaling components in the foregut and show that the molecular mechanisms of respiratory lineage induction are remarkably conserved between Xenopus and mice. Finally, using several functional experiments we refine the epistatic relationships among FGF, Wnt, and BMP signaling in early Xenopus respiratory system development. We demonstrate that Xenopus trachea and lung development, before metamorphosis, is comparable at the cellular and molecular levels to embryonic stages of mouse respiratory system development between embryonic days 8.5 and 10.5. This molecular atlas provides a fundamental starting point for further studies using Xenopus as a model to define the conserved genetic programs controlling early respiratory system development. © 2014 Wiley Periodicals, Inc.

Optimizing legacy molecular dynamics software with directive-based offload

DOE PAGES

Michael Brown, W.; Carrillo, Jan-Michael Y.; Gavhane, Nitin; ...

2015-05-14

The directive-based programming models are one solution for exploiting many-core coprocessors to increase simulation rates in molecular dynamics. They offer the potential to reduce code complexity with offload models that can selectively target computations to run on the CPU, the coprocessor, or both. In our paper, we describe modifications to the LAMMPS molecular dynamics code to enable concurrent calculations on a CPU and coprocessor. We also demonstrate that standard molecular dynamics algorithms can run efficiently on both the CPU and an x86-based coprocessor using the same subroutines. As a consequence, we demonstrate that code optimizations for the coprocessor also resultmore » in speedups on the CPU; in extreme cases up to 4.7X. We provide results for LAMMAS benchmarks and for production molecular dynamics simulations using the Stampede hybrid supercomputer with both Intel (R) Xeon Phi (TM) coprocessors and NVIDIA GPUs: The optimizations presented have increased simulation rates by over 2X for organic molecules and over 7X for liquid crystals on Stampede. The optimizations are available as part of the "Intel package" supplied with LAMMPS. (C) 2015 Elsevier B.V. All rights reserved.« less

New experimental models of skin homeostasis and diseases.

PubMed

Larcher, F; Espada, J; Díaz-Ley, B; Jaén, P; Juarranz, A; Quintanilla, M

2015-01-01

Homeostasis, whose regulation at the molecular level is still poorly understood, is intimately related to the functions of epidermal stem cells. Five research groups have been brought together to work on new in vitro and in vivo skin models through the SkinModel-CM program, under the auspices of the Spanish Autonomous Community of Madrid. This project aims to analyze the functions of DNA methyltransferase 1, endoglin, and podoplanin in epidermal stem cell activity, homeostasis, and skin cancer. These new models include 3-dimensional organotypic cultures, immunodeficient skin-humanized mice, and genetically modified mice. Another aim of the program is to use skin-humanized mice to model dermatoses such as Gorlin syndrome and xeroderma pigmentosum in order to optimize new protocols for photodynamic therapy. Copyright © 2013 Elsevier España, S.L.U. and AEDV. All rights reserved.

Basic Modeling of the Solar Atmosphere and Spectrum

NASA Technical Reports Server (NTRS)

Avrett, Eugene H.; Wagner, William J. (Technical Monitor)

2000-01-01

During the last three years we have continued the development of extensive computer programs for constructing realistic models of the solar atmosphere and for calculating detailed spectra to use in the interpretation of solar observations. This research involves two major interrelated efforts: work by Avrett and Loeser on the Pandora computer program for optically thick non-LTE modeling of the solar atmosphere including a wide range of physical processes, and work by Kurucz on the detailed high-resolution synthesis of the solar spectrum using data for over 58 million atomic and molecular lines. Our objective is to construct atmospheric models from which the calculated spectra agree as well as possible with high-and low-resolution observations over a wide wavelength range. Such modeling leads to an improved understanding of the physical processes responsible for the structure and behavior of the atmosphere.

[Screen potential CYP450 2E1 inhibitors from Chinese herbal medicine based on support vector regression and molecular docking method].

PubMed

Chen, Xi; Lu, Fang; Jiang, Lu-di; Cai, Yi-Lian; Li, Gong-Yu; Zhang, Yan-Ling

2016-07-01

Inhibition of cytochrome P450 (CYP450) enzymes is the most common reasons for drug interactions, so the study on early prediction of CYPs inhibitors can help to decrease the incidence of adverse reactions caused by drug interactions.CYP450 2E1(CYP2E1), as a key role in drug metabolism process, has broad spectrum of drug metabolism substrate. In this study, 32 CYP2E1 inhibitors were collected for the construction of support vector regression (SVR) model. The test set data were used to verify CYP2E1 quantitative models and obtain the optimal prediction model of CYP2E1 inhibitor. Meanwhile, one molecular docking program, CDOCKER, was utilized to analyze the interaction pattern between positive compounds and active pocket to establish the optimal screening model of CYP2E1 inhibitors.SVR model and molecular docking prediction model were combined to screen traditional Chinese medicine database (TCMD), which could improve the calculation efficiency and prediction accuracy. 6 376 traditional Chinese medicine (TCM) compounds predicted by SVR model were obtained, and in further verification by using molecular docking model, 247 TCM compounds with potential inhibitory activities against CYP2E1 were finally retained. Some of them have been verified by experiments. The results demonstrated that this study could provide guidance for the virtual screening of CYP450 inhibitors and the prediction of CYPs-mediated DDIs, and also provide references for clinical rational drug use. Copyright© by the Chinese Pharmaceutical Association.

Advances in molecular quantum chemistry contained in the Q-Chem 4 program package

NASA Astrophysics Data System (ADS)

Shao, Yihan; Gan, Zhengting; Epifanovsky, Evgeny; Gilbert, Andrew T. B.; Wormit, Michael; Kussmann, Joerg; Lange, Adrian W.; Behn, Andrew; Deng, Jia; Feng, Xintian; Ghosh, Debashree; Goldey, Matthew; Horn, Paul R.; Jacobson, Leif D.; Kaliman, Ilya; Khaliullin, Rustam Z.; Kuś, Tomasz; Landau, Arie; Liu, Jie; Proynov, Emil I.; Rhee, Young Min; Richard, Ryan M.; Rohrdanz, Mary A.; Steele, Ryan P.; Sundstrom, Eric J.; Woodcock, H. Lee, III; Zimmerman, Paul M.; Zuev, Dmitry; Albrecht, Ben; Alguire, Ethan; Austin, Brian; Beran, Gregory J. O.; Bernard, Yves A.; Berquist, Eric; Brandhorst, Kai; Bravaya, Ksenia B.; Brown, Shawn T.; Casanova, David; Chang, Chun-Min; Chen, Yunqing; Chien, Siu Hung; Closser, Kristina D.; Crittenden, Deborah L.; Diedenhofen, Michael; DiStasio, Robert A., Jr.; Do, Hainam; Dutoi, Anthony D.; Edgar, Richard G.; Fatehi, Shervin; Fusti-Molnar, Laszlo; Ghysels, An; Golubeva-Zadorozhnaya, Anna; Gomes, Joseph; Hanson-Heine, Magnus W. D.; Harbach, Philipp H. P.; Hauser, Andreas W.; Hohenstein, Edward G.; Holden, Zachary C.; Jagau, Thomas-C.; Ji, Hyunjun; Kaduk, Benjamin; Khistyaev, Kirill; Kim, Jaehoon; Kim, Jihan; King, Rollin A.; Klunzinger, Phil; Kosenkov, Dmytro; Kowalczyk, Tim; Krauter, Caroline M.; Lao, Ka Un; Laurent, Adèle D.; Lawler, Keith V.; Levchenko, Sergey V.; Lin, Ching Yeh; Liu, Fenglai; Livshits, Ester; Lochan, Rohini C.; Luenser, Arne; Manohar, Prashant; Manzer, Samuel F.; Mao, Shan-Ping; Mardirossian, Narbe; Marenich, Aleksandr V.; Maurer, Simon A.; Mayhall, Nicholas J.; Neuscamman, Eric; Oana, C. Melania; Olivares-Amaya, Roberto; O'Neill, Darragh P.; Parkhill, John A.; Perrine, Trilisa M.; Peverati, Roberto; Prociuk, Alexander; Rehn, Dirk R.; Rosta, Edina; Russ, Nicholas J.; Sharada, Shaama M.; Sharma, Sandeep; Small, David W.; Sodt, Alexander; Stein, Tamar; Stück, David; Su, Yu-Chuan; Thom, Alex J. W.; Tsuchimochi, Takashi; Vanovschi, Vitalii; Vogt, Leslie; Vydrov, Oleg; Wang, Tao; Watson, Mark A.; Wenzel, Jan; White, Alec; Williams, Christopher F.; Yang, Jun; Yeganeh, Sina; Yost, Shane R.; You, Zhi-Qiang; Zhang, Igor Ying; Zhang, Xing; Zhao, Yan; Brooks, Bernard R.; Chan, Garnet K. L.; Chipman, Daniel M.; Cramer, Christopher J.; Goddard, William A., III; Gordon, Mark S.; Hehre, Warren J.; Klamt, Andreas; Schaefer, Henry F., III; Schmidt, Michael W.; Sherrill, C. David; Truhlar, Donald G.; Warshel, Arieh; Xu, Xin; Aspuru-Guzik, Alán; Baer, Roi; Bell, Alexis T.; Besley, Nicholas A.; Chai, Jeng-Da; Dreuw, Andreas; Dunietz, Barry D.; Furlani, Thomas R.; Gwaltney, Steven R.; Hsu, Chao-Ping; Jung, Yousung; Kong, Jing; Lambrecht, Daniel S.; Liang, WanZhen; Ochsenfeld, Christian; Rassolov, Vitaly A.; Slipchenko, Lyudmila V.; Subotnik, Joseph E.; Van Voorhis, Troy; Herbert, John M.; Krylov, Anna I.; Gill, Peter M. W.; Head-Gordon, Martin

2015-01-01

A summary of the technical advances that are incorporated in the fourth major release of the Q-Chem quantum chemistry program is provided, covering approximately the last seven years. These include developments in density functional theory methods and algorithms, nuclear magnetic resonance (NMR) property evaluation, coupled cluster and perturbation theories, methods for electronically excited and open-shell species, tools for treating extended environments, algorithms for walking on potential surfaces, analysis tools, energy and electron transfer modelling, parallel computing capabilities, and graphical user interfaces. In addition, a selection of example case studies that illustrate these capabilities is given. These include extensive benchmarks of the comparative accuracy of modern density functionals for bonded and non-bonded interactions, tests of attenuated second order Møller-Plesset (MP2) methods for intermolecular interactions, a variety of parallel performance benchmarks, and tests of the accuracy of implicit solvation models. Some specific chemical examples include calculations on the strongly correlated Cr2 dimer, exploring zeolite-catalysed ethane dehydrogenation, energy decomposition analysis of a charged ter-molecular complex arising from glycerol photoionisation, and natural transition orbitals for a Frenkel exciton state in a nine-unit model of a self-assembling nanotube.

Development of New Treatments for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

DiPaola, R. S.; Abate-Shen, C.; Hait, W. N.

2005-02-01

The Dean and Betty Gallo Prostate Cancer Center (GPCC) was established with the goal of eradicating prostate cancer and improving the lives of men at risk for the disease through research, treatment, education and prevention. GPCC was founded in the memory of Dean Gallo, a beloved New Jersey Congressman who died tragically of prostate cancer diagnosed at an advanced stage. GPCC unites a team of outstanding researchers and clinicians who are committed to high-quality basic research, translation of innovative research to the clinic, exceptional patient care, and improving public education and awareness of prostate cancer. GPCC is a center ofmore » excellence of The Cancer Institute of New Jersey, which is the only NCI-designated comprehensive cancer center in the state. GPCC efforts are now integrated well as part of our Prostate Program at CINJ, in which Dr. Robert DiPaola and Dr. Cory Abate-Shen are co-leaders. The Prostate Program unites 19 investigators from 10 academic departments who have broad and complementary expertise in prostate cancer research. The overall goal and unifying theme is to elucidate basic mechanisms of prostate growth and oncogenesis, with the ultimate goal of promoting new and effective strategies for the eradication of prostate cancer. Members' wide range of research interests collectively optimize the chances of providing new insights into normal prostate biology and unraveling the molecular pathophysiology of prostate cancer. Cell culture and powerful animal models developed by program members recapitulate the various stages of prostate cancer progression, including prostatic intraepithelial neoplasia, adenocarcinoma, androgen-independence, invasion and metastases. These models promise to further strengthen an already robust program of investigator-initiated therapeutic clinical trials, including studies adopted by national cooperative groups. Efforts to translate laboratory results into clinical studies of early detection and chemoprevention are underway. The specific goals of this program are: (1) To investigate the molecular mechanisms underlying normal prostate growth and differentiation and elucidate the molecular mechanisms underlying prostate oncogenesis. (2) To build on fundamental knowledge to develop effective therapeutic approaches for the treatment of prostate cancer. (3) To improve the control of prostate cancer through early detection, chemoprevention, and outreach and education. This new disease-based program is structured to improve interdisciplinary interactions and translational results. Already, through the dynamic leadership of Drs. Cory Abate-Shen and Robert DiPaola, new investigators were attracted to the field, new collaborations engendered, and numerous investigator-initiated trials implemented. Progress in GPCC and the program overall has been outstanding. The Center has success in uniting investigators with broad and complementary expertise in prostate cancer research. The overall goal and unifying theme is to elucidate basic mechanisms of prostate growth and oncogenesis, with the ultimate goal of promoting new and effective strategies for the eradication of prostate cancer in patients and populations at risk. Members wide range of research interests collectively optimize the chances of providing new insights into normal prostate biology and unraveling the molecular pathophysiology of prostate cancer. Studies in cell culture and powerful animal models developed recapitulate the various stages of prostate cancer progression, including prostatic intraepithelial neoplasia, adenocarcinoma, androgen-independence, invasion and metastases. These models promise to further strengthen an already robust program of investigator-initiated therapeutic clinical trials, including studies adopted by national cooperative groups. Efforts to translate laboratory results into clinical studies of early detection and chemoprevention are underway.« less

RAMBAs for Breast Cancer Prevention and Treatment

DTIC Science & Technology

2009-01-01

activated by CYPs only in cancer cells. Finally, the expression of CYPs within tumors has been utilized in the development of bioreductive molecules...enable us to utilize the Catalyst molecular modeling program to create a general phar- macophore model that can differentiate compounds as active or...the discovery and char- acterization of retinoid receptor and the realization of these compounds as nonsteroidal small-molecule hor- mones .1 All-trans

Structure-biodegradability study and computer-automated prediction of aerobic biodegradation of chemicals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klopman, G.; Tu, M.

1997-09-01

It is shown that a combination of two programs, MultiCASE and META, can help assess the biodegradability of industrial organic materials in the ecosystem. MultiCASE is an artificial intelligence computer program that had been trained to identify molecular substructures believed to cause or inhibit biodegradation and META is an expert system trained to predict the aerobic biodegradation products of organic molecules. These two programs can be used to help evaluate the fate of disposed chemicals by estimating their biodegradability and the nature of their biodegradation products under conditions that may model the environment.

Identification of tumor evolution patterns by means of inductive logic programming.

PubMed

Bevilacqua, Vitoantonio; Chiarappa, Patrizia; Mastronardi, Giuseppe; Menolascina, Filippo; Paradiso, Angelo; Tommasi, Stefania

2008-06-01

In considering key events of genomic disorders in the development and progression of cancer, the correlation between genomic instability and carcinogenesis is currently under investigation. In this work, we propose an inductive logic programming approach to the problem of modeling evolution patterns for breast cancer. Using this approach, it is possible to extract fingerprints of stages of the disease that can be used in order to develop and deliver the most adequate therapies to patients. Furthermore, such a model can help physicians and biologists in the elucidation of molecular dynamics underlying the aberrations-waterfall model behind carcinogenesis. By showing results obtained on a real-world dataset, we try to give some hints about further approach to the knowledge-driven validations of such hypotheses.

Learning reduced kinetic Monte Carlo models of complex chemistry from molecular dynamics.

PubMed

Yang, Qian; Sing-Long, Carlos A; Reed, Evan J

2017-08-01

We propose a novel statistical learning framework for automatically and efficiently building reduced kinetic Monte Carlo (KMC) models of large-scale elementary reaction networks from data generated by a single or few molecular dynamics simulations (MD). Existing approaches for identifying species and reactions from molecular dynamics typically use bond length and duration criteria, where bond duration is a fixed parameter motivated by an understanding of bond vibrational frequencies. In contrast, we show that for highly reactive systems, bond duration should be a model parameter that is chosen to maximize the predictive power of the resulting statistical model. We demonstrate our method on a high temperature, high pressure system of reacting liquid methane, and show that the learned KMC model is able to extrapolate more than an order of magnitude in time for key molecules. Additionally, our KMC model of elementary reactions enables us to isolate the most important set of reactions governing the behavior of key molecules found in the MD simulation. We develop a new data-driven algorithm to reduce the chemical reaction network which can be solved either as an integer program or efficiently using L1 regularization, and compare our results with simple count-based reduction. For our liquid methane system, we discover that rare reactions do not play a significant role in the system, and find that less than 7% of the approximately 2000 reactions observed from molecular dynamics are necessary to reproduce the molecular concentration over time of methane. The framework described in this work paves the way towards a genomic approach to studying complex chemical systems, where expensive MD simulation data can be reused to contribute to an increasingly large and accurate genome of elementary reactions and rates.

Learning reduced kinetic Monte Carlo models of complex chemistry from molecular dynamics

PubMed Central

Sing-Long, Carlos A.

2017-01-01

We propose a novel statistical learning framework for automatically and efficiently building reduced kinetic Monte Carlo (KMC) models of large-scale elementary reaction networks from data generated by a single or few molecular dynamics simulations (MD). Existing approaches for identifying species and reactions from molecular dynamics typically use bond length and duration criteria, where bond duration is a fixed parameter motivated by an understanding of bond vibrational frequencies. In contrast, we show that for highly reactive systems, bond duration should be a model parameter that is chosen to maximize the predictive power of the resulting statistical model. We demonstrate our method on a high temperature, high pressure system of reacting liquid methane, and show that the learned KMC model is able to extrapolate more than an order of magnitude in time for key molecules. Additionally, our KMC model of elementary reactions enables us to isolate the most important set of reactions governing the behavior of key molecules found in the MD simulation. We develop a new data-driven algorithm to reduce the chemical reaction network which can be solved either as an integer program or efficiently using L1 regularization, and compare our results with simple count-based reduction. For our liquid methane system, we discover that rare reactions do not play a significant role in the system, and find that less than 7% of the approximately 2000 reactions observed from molecular dynamics are necessary to reproduce the molecular concentration over time of methane. The framework described in this work paves the way towards a genomic approach to studying complex chemical systems, where expensive MD simulation data can be reused to contribute to an increasingly large and accurate genome of elementary reactions and rates. PMID:28989618

Learning reduced kinetic Monte Carlo models of complex chemistry from molecular dynamics

DOE PAGES

Yang, Qian; Sing-Long, Carlos A.; Reed, Evan J.

2017-06-19

Here, we propose a novel statistical learning framework for automatically and efficiently building reduced kinetic Monte Carlo (KMC) models of large-scale elementary reaction networks from data generated by a single or few molecular dynamics simulations (MD). Existing approaches for identifying species and reactions from molecular dynamics typically use bond length and duration criteria, where bond duration is a fixed parameter motivated by an understanding of bond vibrational frequencies. Conversely, we show that for highly reactive systems, bond duration should be a model parameter that is chosen to maximize the predictive power of the resulting statistical model. We demonstrate our methodmore » on a high temperature, high pressure system of reacting liquid methane, and show that the learned KMC model is able to extrapolate more than an order of magnitude in time for key molecules. Additionally, our KMC model of elementary reactions enables us to isolate the most important set of reactions governing the behavior of key molecules found in the MD simulation. We develop a new data-driven algorithm to reduce the chemical reaction network which can be solved either as an integer program or efficiently using L1 regularization, and compare our results with simple count-based reduction. For our liquid methane system, we discover that rare reactions do not play a significant role in the system, and find that less than 7% of the approximately 2000 reactions observed from molecular dynamics are necessary to reproduce the molecular concentration over time of methane. Furthermore, we describe a framework in this work that paves the way towards a genomic approach to studying complex chemical systems, where expensive MD simulation data can be reused to contribute to an increasingly large and accurate genome of elementary reactions and rates.« less

New solution decomposition and minimization schemes for Poisson-Boltzmann equation in calculation of biomolecular electrostatics

NASA Astrophysics Data System (ADS)

Xie, Dexuan

2014-10-01

The Poisson-Boltzmann equation (PBE) is one widely-used implicit solvent continuum model in the calculation of electrostatic potential energy for biomolecules in ionic solvent, but its numerical solution remains a challenge due to its strong singularity and nonlinearity caused by its singular distribution source terms and exponential nonlinear terms. To effectively deal with such a challenge, in this paper, new solution decomposition and minimization schemes are proposed, together with a new PBE analysis on solution existence and uniqueness. Moreover, a PBE finite element program package is developed in Python based on the FEniCS program library and GAMer, a molecular surface and volumetric mesh generation program package. Numerical tests on proteins and a nonlinear Born ball model with an analytical solution validate the new solution decomposition and minimization schemes, and demonstrate the effectiveness and efficiency of the new PBE finite element program package.

Computationally Efficient Multiconfigurational Reactive Molecular Dynamics

PubMed Central

Yamashita, Takefumi; Peng, Yuxing; Knight, Chris; Voth, Gregory A.

2012-01-01

It is a computationally demanding task to explicitly simulate the electronic degrees of freedom in a system to observe the chemical transformations of interest, while at the same time sampling the time and length scales required to converge statistical properties and thus reduce artifacts due to initial conditions, finite-size effects, and limited sampling. One solution that significantly reduces the computational expense consists of molecular models in which effective interactions between particles govern the dynamics of the system. If the interaction potentials in these models are developed to reproduce calculated properties from electronic structure calculations and/or ab initio molecular dynamics simulations, then one can calculate accurate properties at a fraction of the computational cost. Multiconfigurational algorithms model the system as a linear combination of several chemical bonding topologies to simulate chemical reactions, also sometimes referred to as “multistate”. These algorithms typically utilize energy and force calculations already found in popular molecular dynamics software packages, thus facilitating their implementation without significant changes to the structure of the code. However, the evaluation of energies and forces for several bonding topologies per simulation step can lead to poor computational efficiency if redundancy is not efficiently removed, particularly with respect to the calculation of long-ranged Coulombic interactions. This paper presents accurate approximations (effective long-range interaction and resulting hybrid methods) and multiple-program parallelization strategies for the efficient calculation of electrostatic interactions in reactive molecular simulations. PMID:25100924

A Review of the Molecular Mechanisms of Chemically-Induced Neoplasia in Rat and Mouse Models in National Toxicology Program Bioassays and Their Relevance to Human Cancer

PubMed Central

Hoenerhoff, Mark J.; Hong, Hue Hua; Ton, Tai-Vu; Lahousse, Stephanie A.; Sills, Robert C.

2012-01-01

Tumor response in the B6C3F1 mouse, F344 rat, and other animal models following exposure to various compounds provides evidence that people exposed to these or similar compounds may be at risk for developing cancer. Although tumors in rodents and humans are often morphologically similar, underlying mechanisms of tumorigenesis are often unknown and may be different between the species. Therefore, the relevance of an animal tumor response to human health would be better determined if the molecular pathogenesis were understood. The underlying molecular mechanisms leading to carcinogenesis are complex and involve multiple genetic and epigenetic events and other factors. To address the molecular pathogenesis of environmental carcinogens, we examine rodent tumors (e.g., lung, colon, mammary gland, skin, brain, mesothelioma) for alterations in cancer genes and epigenetic events that are associated with human cancer. Our NTP studies have identified several genetic alterations in chemically induced rodent neoplasms that are important in human cancer. Identification of such alterations in rodent models of chemical carcinogenesis caused by exposure to environmental contaminants, occupational chemicals, and other compounds lends further support that they are of potential human health risk. These studies also emphasize the importance of molecular evaluation of chemically induced rodent tumors for providing greater public health significance for NTP evaluated compounds. PMID:19846892

A new biodegradation prediction model specific to petroleum hydrocarbons.

PubMed

Howard, Philip; Meylan, William; Aronson, Dallas; Stiteler, William; Tunkel, Jay; Comber, Michael; Parkerton, Thomas F

2005-08-01

A new predictive model for determining quantitative primary biodegradation half-lives of individual petroleum hydrocarbons has been developed. This model uses a fragment-based approach similar to that of several other biodegradation models, such as those within the Biodegradation Probability Program (BIOWIN) estimation program. In the present study, a half-life in days is estimated using multiple linear regression against counts of 31 distinct molecular fragments. The model was developed using a data set consisting of 175 compounds with environmentally relevant experimental data that was divided into training and validation sets. The original fragments from the Ministry of International Trade and Industry BIOWIN model were used initially as structural descriptors and additional fragments were then added to better describe the ring systems found in petroleum hydrocarbons and to adjust for nonlinearity within the experimental data. The training and validation sets had r2 values of 0.91 and 0.81, respectively.

ms2: A molecular simulation tool for thermodynamic properties

NASA Astrophysics Data System (ADS)

Deublein, Stephan; Eckl, Bernhard; Stoll, Jürgen; Lishchuk, Sergey V.; Guevara-Carrion, Gabriela; Glass, Colin W.; Merker, Thorsten; Bernreuther, Martin; Hasse, Hans; Vrabec, Jadran

2011-11-01

This work presents the molecular simulation program ms2 that is designed for the calculation of thermodynamic properties of bulk fluids in equilibrium consisting of small electro-neutral molecules. ms2 features the two main molecular simulation techniques, molecular dynamics (MD) and Monte-Carlo. It supports the calculation of vapor-liquid equilibria of pure fluids and multi-component mixtures described by rigid molecular models on the basis of the grand equilibrium method. Furthermore, it is capable of sampling various classical ensembles and yields numerous thermodynamic properties. To evaluate the chemical potential, Widom's test molecule method and gradual insertion are implemented. Transport properties are determined by equilibrium MD simulations following the Green-Kubo formalism. ms2 is designed to meet the requirements of academia and industry, particularly achieving short response times and straightforward handling. It is written in Fortran90 and optimized for a fast execution on a broad range of computer architectures, spanning from single processor PCs over PC-clusters and vector computers to high-end parallel machines. The standard Message Passing Interface (MPI) is used for parallelization and ms2 is therefore easily portable to different computing platforms. Feature tools facilitate the interaction with the code and the interpretation of input and output files. The accuracy and reliability of ms2 has been shown for a large variety of fluids in preceding work. Program summaryProgram title:ms2 Catalogue identifier: AEJF_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEJF_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Special Licence supplied by the authors No. of lines in distributed program, including test data, etc.: 82 794 No. of bytes in distributed program, including test data, etc.: 793 705 Distribution format: tar.gz Programming language: Fortran90 Computer: The simulation tool ms2 is usable on a wide variety of platforms, from single processor machines over PC-clusters and vector computers to vector-parallel architectures. (Tested with Fortran compilers: gfortran, Intel, PathScale, Portland Group and Sun Studio.) Operating system: Unix/Linux, Windows Has the code been vectorized or parallelized?: Yes. Message Passing Interface (MPI) protocol Scalability. Excellent scalability up to 16 processors for molecular dynamics and >512 processors for Monte-Carlo simulations. RAM:ms2 runs on single processors with 512 MB RAM. The memory demand rises with increasing number of processors used per node and increasing number of molecules. Classification: 7.7, 7.9, 12 External routines: Message Passing Interface (MPI) Nature of problem: Calculation of application oriented thermodynamic properties for rigid electro-neutral molecules: vapor-liquid equilibria, thermal and caloric data as well as transport properties of pure fluids and multi-component mixtures. Solution method: Molecular dynamics, Monte-Carlo, various classical ensembles, grand equilibrium method, Green-Kubo formalism. Restrictions: No. The system size is user-defined. Typical problems addressed by ms2 can be solved by simulating systems containing typically 2000 molecules or less. Unusual features: Feature tools are available for creating input files, analyzing simulation results and visualizing molecular trajectories. Additional comments: Sample makefiles for multiple operation platforms are provided. Documentation is provided with the installation package and is available at http://www.ms-2.de. Running time: The running time of ms2 depends on the problem set, the system size and the number of processes used in the simulation. Running four processes on a "Nehalem" processor, simulations calculating VLE data take between two and twelve hours, calculating transport properties between six and 24 hours.

Building an International Initiative to Infuse Novel Cancer Models into the Research Community | Office of Cancer Genomics

Cancer.gov

My name is Caitlyn Barrett and I am the Scientific Program Manager for the Human Cancer Model Initiative (HCMI) in the Office of Cancer Genomics (OCG). In my role within the HCMI, I am helping to establish communication pathways and build the foundation for collaboration that will enable the completion of the Initiative’s aim to develop as many as 1000 next-generation cancer models, established from patient tumors and accompanied by clinical and molecular data.

Paternal obesity, interventions, and mechanistic pathways to impaired health in offspring.

PubMed

McPherson, Nicole O; Fullston, Tod; Aitken, R John; Lane, Michelle

2014-01-01

The global rates of male overweight/obesity are rising, approaching 70% of the total adult population in Western nations. Overweight/obesity increases the risk of chronic diseases; however, there is increasing awareness that male obesity negatively impacts fertility, subsequent pregnancy, and the offspring health burden. Developmental programming is well defined in mothers; however, it is becoming increasingly evident that developmental programming can be paternally initiated and mediated through paternal obesity. Both human and rodent models have established that paternal obesity impairs sex hormones, basic sperm function, and molecular composition. This results in perturbed embryo development and health and an increased subsequent offspring disease burden in both sexes. The reversibility of obesity-induced parental programming has only recently received attention. Promising results in animal models utilizing diet and exercise interventions have shown improvements in sperm function and molecular composition, resulting in restorations of both embryo and fetal health and subsequent male offspring fertility. The direct mode for paternal inheritance is likely mediated via spermatozoa. We propose two main theories for the origin of male obesity-induced paternal programming: (1) accumulation of sperm DNA damage resulting in de novo mutations in the embryo and (2) changes in sperm epigenetic marks (microRNA, methylation, or acetylation) altering the access, transcription, and translation of paternally derived genes during early embryogenesis. Paternal overweight/obesity induces paternal programming of offspring phenotypes likely mediated through genetic and epigenetic changes in spermatozoa. These programmed changes to offspring health appear to be partially restored via diet/exercise interventions in obese fathers preconception, which have been shown to improve aspects of sperm DNA integrity. However, the majority of data surrounding paternal obesity and offspring phenotypes have come from rodent models; therefore, we contend that it will be increasingly important to study population-based data to determine the likely mode of inheritance in humans. © 2014 S. Karger AG, Basel.

Theoretical Modeling of Molecular and Electron Kinetic Processes. Volume I. Theoretical Formulation of Analysis and Description of Computer Program.

DTIC Science & Technology

1979-01-01

syn- thesis proceed s by ignoring unacceptable syntax or other errors , pro- tection against subsequent execution of a faulty reaction scheme can be...resulting TAPE9 . During subroutine syn thesis and reaction processing, a search is made (fo r each secondary electron collision encountered) to...program library, which can be cat- alogued and saved if any future specialized modifications (beyond the scope of the syn thesis capability of LASER

A COMPUTER MODELING STUDY OF BINDING PROPERTIES OF CHIRAL NUCLEOPEPTIDE FOR BIOMEDICAL APPLICATIONS.

PubMed

Pirtskhalava, M; Egoyan, A; Mirtskhulava, M; Roviello, G

2017-12-01

Nucleopeptides often show interesting properties of molecular binding that render them good candidates for development of innovative drugs for anticancer and antiviral therapies. In this work we present results of computer modeling of interactions between the molecules of hexathymine nucleopeptide (T6) and poly rA RNA (A18). The results of geometry optimization calculated using Hyperchem software and our own computer program for molecular docking show that molecules establish stable complexes due to the complementary-nucleobase interaction and the electrostatic interaction between the negative phosphate group of poly rA and the positively-charged residues present in the cationic nucleopeptide structure. Computer modeling makes it possible to find the optimal binding configuration of the molecules of a nucleopeptide and poly rA RNA and to estimate the binding energy between the molecules.

ECUT: Energy Conversion and Utilization Technologies program - Biocatalysis research activity

NASA Technical Reports Server (NTRS)

Wilcox, R.

1984-01-01

The activities of the Biocatalysis Research Activity are organized into the Biocatalysis and Molecular Modeling work elements and a supporting planning and analysis function. In the Biocatalysis work element, progress is made in developing a method for stabilizing genetically engineered traits in microorganisms, refining a technique for monitoring cells that are genetically engineered, and identifying strains of fungi for highly efficient preprocessing of biomass for optimizing the efficiency of bioreactors. In the Molecular Modeling work element, a preliminary model of the behavior of enzymes is developed. A preliminary investigation of the potential for synthesizing enzymes for use in electrochemical processes is completed. Contact with industry and universities is made to define key biocatalysis technical issues and to broaden the range of potential participants in the activity. Analyses are conducted to identify and evaluate potential concepts for future research funding.

Physics Computing '92: Proceedings of the 4th International Conference

NASA Astrophysics Data System (ADS)

de Groot, Robert A.; Nadrchal, Jaroslav

1993-04-01

The Table of Contents for the book is as follows: * Preface * INVITED PAPERS * Ab Initio Theoretical Approaches to the Structural, Electronic and Vibrational Properties of Small Clusters and Fullerenes: The State of the Art * Neural Multigrid Methods for Gauge Theories and Other Disordered Systems * Multicanonical Monte Carlo Simulations * On the Use of the Symbolic Language Maple in Physics and Chemistry: Several Examples * Nonequilibrium Phase Transitions in Catalysis and Population Models * Computer Algebra, Symmetry Analysis and Integrability of Nonlinear Evolution Equations * The Path-Integral Quantum Simulation of Hydrogen in Metals * Digital Optical Computing: A New Approach of Systolic Arrays Based on Coherence Modulation of Light and Integrated Optics Technology * Molecular Dynamics Simulations of Granular Materials * Numerical Implementation of a K.A.M. Algorithm * Quasi-Monte Carlo, Quasi-Random Numbers and Quasi-Error Estimates * What Can We Learn from QMC Simulations * Physics of Fluctuating Membranes * Plato, Apollonius, and Klein: Playing with Spheres * Steady States in Nonequilibrium Lattice Systems * CONVODE: A REDUCE Package for Differential Equations * Chaos in Coupled Rotators * Symplectic Numerical Methods for Hamiltonian Problems * Computer Simulations of Surfactant Self Assembly * High-dimensional and Very Large Cellular Automata for Immunological Shape Space * A Review of the Lattice Boltzmann Method * Electronic Structure of Solids in the Self-interaction Corrected Local-spin-density Approximation * Dedicated Computers for Lattice Gauge Theory Simulations * Physics Education: A Survey of Problems and Possible Solutions * Parallel Computing and Electronic-Structure Theory * High Precision Simulation Techniques for Lattice Field Theory * CONTRIBUTED PAPERS * Case Study of Microscale Hydrodynamics Using Molecular Dynamics and Lattice Gas Methods * Computer Modelling of the Structural and Electronic Properties of the Supported Metal Catalysis * Ordered Particle Simulations for Serial and MIMD Parallel Computers * "NOLP" -- Program Package for Laser Plasma Nonlinear Optics * Algorithms to Solve Nonlinear Least Square Problems * Distribution of Hydrogen Atoms in Pd-H Computed by Molecular Dynamics * A Ray Tracing of Optical System for Protein Crystallography Beamline at Storage Ring-SIBERIA-2 * Vibrational Properties of a Pseudobinary Linear Chain with Correlated Substitutional Disorder * Application of the Software Package Mathematica in Generalized Master Equation Method * Linelist: An Interactive Program for Analysing Beam-foil Spectra * GROMACS: A Parallel Computer for Molecular Dynamics Simulations * GROMACS Method of Virial Calculation Using a Single Sum * The Interactive Program for the Solution of the Laplace Equation with the Elimination of Singularities for Boundary Functions * Random-Number Generators: Testing Procedures and Comparison of RNG Algorithms * Micro-TOPIC: A Tokamak Plasma Impurities Code * Rotational Molecular Scattering Calculations * Orthonormal Polynomial Method for Calibrating of Cryogenic Temperature Sensors * Frame-based System Representing Basis of Physics * The Role of Massively Data-parallel Computers in Large Scale Molecular Dynamics Simulations * Short-range Molecular Dynamics on a Network of Processors and Workstations * An Algorithm for Higher-order Perturbation Theory in Radiative Transfer Computations * Hydrostochastics: The Master Equation Formulation of Fluid Dynamics * HPP Lattice Gas on Transputers and Networked Workstations * Study on the Hysteresis Cycle Simulation Using Modeling with Different Functions on Intervals * Refined Pruning Techniques for Feed-forward Neural Networks * Random Walk Simulation of the Motion of Transient Charges in Photoconductors * The Optical Hysteresis in Hydrogenated Amorphous Silicon * Diffusion Monte Carlo Analysis of Modern Interatomic Potentials for He * A Parallel Strategy for Molecular Dynamics Simulations of Polar Liquids on Transputer Arrays * Distribution of Ions Reflected on Rough Surfaces * The Study of Step Density Distribution During Molecular Beam Epitaxy Growth: Monte Carlo Computer Simulation * Towards a Formal Approach to the Construction of Large-scale Scientific Applications Software * Correlated Random Walk and Discrete Modelling of Propagation through Inhomogeneous Media * Teaching Plasma Physics Simulation * A Theoretical Determination of the Au-Ni Phase Diagram * Boson and Fermion Kinetics in One-dimensional Lattices * Computational Physics Course on the Technical University * Symbolic Computations in Simulation Code Development and Femtosecond-pulse Laser-plasma Interaction Studies * Computer Algebra and Integrated Computing Systems in Education of Physical Sciences * Coordinated System of Programs for Undergraduate Physics Instruction * Program Package MIRIAM and Atomic Physics of Extreme Systems * High Energy Physics Simulation on the T_Node * The Chapman-Kolmogorov Equation as Representation of Huygens' Principle and the Monolithic Self-consistent Numerical Modelling of Lasers * Authoring System for Simulation Developments * Molecular Dynamics Study of Ion Charge Effects in the Structure of Ionic Crystals * A Computational Physics Introductory Course * Computer Calculation of Substrate Temperature Field in MBE System * Multimagnetical Simulation of the Ising Model in Two and Three Dimensions * Failure of the CTRW Treatment of the Quasicoherent Excitation Transfer * Implementation of a Parallel Conjugate Gradient Method for Simulation of Elastic Light Scattering * Algorithms for Study of Thin Film Growth * Algorithms and Programs for Physics Teaching in Romanian Technical Universities * Multicanonical Simulation of 1st order Transitions: Interface Tension of the 2D 7-State Potts Model * Two Numerical Methods for the Calculation of Periodic Orbits in Hamiltonian Systems * Chaotic Behavior in a Probabilistic Cellular Automata? * Wave Optics Computing by a Networked-based Vector Wave Automaton * Tensor Manipulation Package in REDUCE * Propagation of Electromagnetic Pulses in Stratified Media * The Simple Molecular Dynamics Model for the Study of Thermalization of the Hot Nucleon Gas * Electron Spin Polarization in PdCo Alloys Calculated by KKR-CPA-LSD Method * Simulation Studies of Microscopic Droplet Spreading * A Vectorizable Algorithm for the Multicolor Successive Overrelaxation Method * Tetragonality of the CuAu I Lattice and Its Relation to Electronic Specific Heat and Spin Susceptibility * Computer Simulation of the Formation of Metallic Aggregates Produced by Chemical Reactions in Aqueous Solution * Scaling in Growth Models with Diffusion: A Monte Carlo Study * The Nucleus as the Mesoscopic System * Neural Network Computation as Dynamic System Simulation * First-principles Theory of Surface Segregation in Binary Alloys * Data Smooth Approximation Algorithm for Estimating the Temperature Dependence of the Ice Nucleation Rate * Genetic Algorithms in Optical Design * Application of 2D-FFT in the Study of Molecular Exchange Processes by NMR * Advanced Mobility Model for Electron Transport in P-Si Inversion Layers * Computer Simulation for Film Surfaces and its Fractal Dimension * Parallel Computation Techniques and the Structure of Catalyst Surfaces * Educational SW to Teach Digital Electronics and the Corresponding Text Book * Primitive Trinomials (Mod 2) Whose Degree is a Mersenne Exponent * Stochastic Modelisation and Parallel Computing * Remarks on the Hybrid Monte Carlo Algorithm for the ∫4 Model * An Experimental Computer Assisted Workbench for Physics Teaching * A Fully Implicit Code to Model Tokamak Plasma Edge Transport * EXPFIT: An Interactive Program for Automatic Beam-foil Decay Curve Analysis * Mapping Technique for Solving General, 1-D Hamiltonian Systems * Freeway Traffic, Cellular Automata, and Some (Self-Organizing) Criticality * Photonuclear Yield Analysis by Dynamic Programming * Incremental Representation of the Simply Connected Planar Curves * Self-convergence in Monte Carlo Methods * Adaptive Mesh Technique for Shock Wave Propagation * Simulation of Supersonic Coronal Streams and Their Interaction with the Solar Wind * The Nature of Chaos in Two Systems of Ordinary Nonlinear Differential Equations * Considerations of a Window-shopper * Interpretation of Data Obtained by RTP 4-Channel Pulsed Radar Reflectometer Using a Multi Layer Perceptron * Statistics of Lattice Bosons for Finite Systems * Fractal Based Image Compression with Affine Transformations * Algorithmic Studies on Simulation Codes for Heavy-ion Reactions * An Energy-Wise Computer Simulation of DNA-Ion-Water Interactions Explains the Abnormal Structure of Poly[d(A)]:Poly[d(T)] * Computer Simulation Study of Kosterlitz-Thouless-Like Transitions * Problem-oriented Software Package GUN-EBT for Computer Simulation of Beam Formation and Transport in Technological Electron-Optical Systems * Parallelization of a Boundary Value Solver and its Application in Nonlinear Dynamics * The Symbolic Classification of Real Four-dimensional Lie Algebras * Short, Singular Pulses Generation by a Dye Laser at Two Wavelengths Simultaneously * Quantum Monte Carlo Simulations of the Apex-Oxygen-Model * Approximation Procedures for the Axial Symmetric Static Einstein-Maxwell-Higgs Theory * Crystallization on a Sphere: Parallel Simulation on a Transputer Network * FAMULUS: A Software Product (also) for Physics Education * MathCAD vs. FAMULUS -- A Brief Comparison * First-principles Dynamics Used to Study Dissociative Chemisorption * A Computer Controlled System for Crystal Growth from Melt * A Time Resolved Spectroscopic Method for Short Pulsed Particle Emission * Green's Function Computation in Radiative Transfer Theory * Random Search Optimization Technique for One-criteria and Multi-criteria Problems * Hartley Transform Applications to Thermal Drift Elimination in Scanning Tunneling Microscopy * Algorithms of Measuring, Processing and Interpretation of Experimental Data Obtained with Scanning Tunneling Microscope * Time-dependent Atom-surface Interactions * Local and Global Minima on Molecular Potential Energy Surfaces: An Example of N3 Radical * Computation of Bifurcation Surfaces * Symbolic Computations in Quantum Mechanics: Energies in Next-to-solvable Systems * A Tool for RTP Reactor and Lamp Field Design * Modelling of Particle Spectra for the Analysis of Solid State Surface * List of Participants

Engineering solid-state materials. Strategies for modeling and packing control of molecular assemblies into 3-D networks

NASA Astrophysics Data System (ADS)

Videnova-Adrabinska, V.; Etter, M. C.; Ward, M. D.

1993-04-01

The crystal structure and properties of a number of urea cocrystals are studied with regard to symmetry of the hydrogen-bonded molecular assemblies. The logical consequences of hydrogen bonding interactions are followed step-by-step. The problems of aggregate formation, nucleation, and crystal growth are also elucidated. Endeavor is made to envisage the 2-D and 3-D hydrogen bond network in a manageable way by exploiting graph set short hand. Strategies of how to control the symmetry of molecular packing are still to be elaborated. In our strategy, the programmed self-assembly has been based on the principle of molecular recognition of self- and hetero-complementary functional groups. However, the main focus for pre-organizational control has been put on the two-fold axis estimator of the urea molecule.

Molecular Phylogenetics: Concepts for a Newcomer.

PubMed

Ajawatanawong, Pravech

Molecular phylogenetics is the study of evolutionary relationships among organisms using molecular sequence data. The aim of this review is to introduce the important terminology and general concepts of tree reconstruction to biologists who lack a strong background in the field of molecular evolution. Some modern phylogenetic programs are easy to use because of their user-friendly interfaces, but understanding the phylogenetic algorithms and substitution models, which are based on advanced statistics, is still important for the analysis and interpretation without a guide. Briefly, there are five general steps in carrying out a phylogenetic analysis: (1) sequence data preparation, (2) sequence alignment, (3) choosing a phylogenetic reconstruction method, (4) identification of the best tree, and (5) evaluating the tree. Concepts in this review enable biologists to grasp the basic ideas behind phylogenetic analysis and also help provide a sound basis for discussions with expert phylogeneticists.

PLUMED-GUI: An environment for the interactive development of molecular dynamics analysis and biasing scripts

NASA Astrophysics Data System (ADS)

Giorgino, Toni

2014-03-01

PLUMED-GUI is an interactive environment to develop and test complex PLUMED scripts within the Visual Molecular Dynamics (VMD) environment. Computational biophysicists can take advantage of both PLUMED’s rich syntax to define collective variables (CVs) and VMD’s chemically-aware atom selection language, while working within a natural point-and-click interface. Pre-defined templates and syntax mnemonics facilitate the definition of well-known reaction coordinates. Complex CVs, e.g. involving reference snapshots used for RMSD or native contacts calculations, can be built through dialogs that provide a synoptic view of the available options. Scripts can be either exported for use in simulation programs, or evaluated on the currently loaded molecular trajectories. Script development takes place without leaving VMD, thus enabling an incremental try-see-modify development model for molecular metrics.

Molecular modelling studies on the ORL1-receptor and ORL1-agonists

NASA Astrophysics Data System (ADS)

Bröer, Britta M.; Gurrath, Marion; Höltje, Hans-Dieter

2003-11-01

The ORL1 ( opioid receptor like 1)- receptor is a member of the family of rhodopsin-like G protein-coupled receptors (GPCR) and represents an interesting new therapeutical target since it is involved in a variety of biomedical important processes, such as anxiety, nociception, feeding, and memory. In order to shed light on the molecular basis of the interactions of the GPCR with its ligands, the receptor protein and a dataset of specific agonists were examined using molecular modelling methods. For that purpose, the conformational space of a very potent non-peptide ORL1-receptor agonist (Ro 64-6198) with a small number of rotatable bonds was analysed in order to derive a pharmacophoric arrangement. The conformational analyses yielded a conformation that served as template for the superposition of a set of related analogues. Structural superposition was achieved by employing the program FlexS. Using the experimental binding data and the superposition of the ligands, a 3D-QSAR analysis applying the GRID/GOLPE method was carried out. After the ligand-based modelling approach, a 3D model of the ORL1-receptor has been constructed using homology modelling methods based on the crystal structure of bovine rhodopsin. A representative structure of the model taken from molecular dynamics simulations was used for a manual docking procedure. Asp-130 and Thr-305 within the ORL1-receptor model served as important hydrophilic interaction partners. Furthermore, a hydrophobic cavity was identified stabilizing the agonists within their binding site. The manual docking results were supported using FlexX, which identified the same protein-ligand interaction points.

Goals and objectives for molecular pathology education in residency programs. The Association for Molecular Pathology Training and Education Committee.

PubMed

1999-11-01

Increasing knowledge of the molecular basis of disease and advances in technology for analyzing nucleic acids and gene products are changing pathology practice. The explosion of information regarding inherited susceptibility to disease is an important aspect of this transformation. Pathology residency programs are incorporating molecular pathology education into their curricula to prepare newly trained pathologists for the future, yet little guidance has been available regarding the important components of molecular pathology training. We present general goals for pathology training programs for molecular pathology education. These include recommendations to pathology residents for the acquisition of both basic knowledge in human genetics and molecular biology and specific skills relevant to microbiology, molecular oncology, genetics, histocompatibility, and identity determination. The importance of residents gaining facility in integrating data gained via nucleic acid based-technology with other laboratory and clinical information available in the care of patients is emphasized.

Guidelines on the use of molecular genetics in reintroduction programs

Treesearch

Michael K. Schwartz

2005-01-01

The use of molecular genetics can play a key role in reintroduction efforts. Prior to the introduction of any individuals, molecular genetics can be used to identify the most appropriate source population for the reintroduction, ensure that no relic populations exist in the reintroduction area, and guide captive breeding programs. The use of molecular genetics post-...

Use of molecular modeling aided design to dial out hERG liability in adenosine A(2A) receptor antagonists.

PubMed

Deng, Qiaolin; Lim, Yeon-Hee; Anand, Rajan; Yu, Younong; Kim, Jae-hun; Zhou, Wei; Zheng, Junying; Tempest, Paul; Levorse, Dorothy; Zhang, Xiaoping; Greene, Scott; Mullins, Deborra; Culberson, Chris; Sherborne, Brad; Parker, Eric M; Stamford, Andrew; Ali, Amjad

2015-08-01

Molecular modeling was performed on a triazolo quinazoline lead compound to help develop a series of adenosine A2A receptor antagonists with improved hERG profile. Superposition of the lead compound onto MK-499, a benchmark hERG inhibitor, combined with pKa calculations and measurement, identified terminal fluorobenzene to be responsible for hERG activity. Docking of the lead compound into an A2A crystal structure suggested that this group is located at a flexible, spacious, and solvent-exposed opening of the binding pocket, making it possible to tolerate various functional groups. Transformation analysis (MMP, matched molecular pair) of in-house available experimental data on hERG provided suggestions for modifications in order to mitigate this liability. This led to the synthesis of a series of compounds with significantly reduced hERG activity. The strategy used in the modeling work can be applied to other medicinal chemistry programs to help improve hERG profile. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluating the solution from MrBUMP and BALBES

PubMed Central

Keegan, Ronan M.; Long, Fei; Fazio, Vincent J.; Winn, Martyn D.; Murshudov, Garib N.; Vagin, Alexei A.

2011-01-01

Molecular replacement is one of the key methods used to solve the problem of determining the phases of structure factors in protein structure solution from X-ray image diffraction data. Its success rate has been steadily improving with the development of improved software methods and the increasing number of structures available in the PDB for use as search models. Despite this, in cases where there is low sequence identity between the target-structure sequence and that of its set of possible homologues it can be a difficult and time-consuming chore to isolate and prepare the best search model for molecular replacement. MrBUMP and BALBES are two recent developments from CCP4 that have been designed to automate and speed up the process of determining and preparing the best search models and putting them through molecular replacement. Their intention is to provide the user with a broad set of results using many search models and to highlight the best of these for further processing. An overview of both programs is presented along with a description of how best to use them, citing case studies and the results of large-scale testing of the software. PMID:21460449

An Introduction to Computational Physics - 2nd Edition

NASA Astrophysics Data System (ADS)

Pang, Tao

2006-01-01

Preface to first edition; Preface; Acknowledgements; 1. Introduction; 2. Approximation of a function; 3. Numerical calculus; 4. Ordinary differential equations; 5. Numerical methods for matrices; 6. Spectral analysis; 7. Partial differential equations; 8. Molecular dynamics simulations; 9. Modeling continuous systems; 10. Monte Carlo simulations; 11. Genetic algorithm and programming; 12. Numerical renormalization; References; Index.

Self-Regulation: An Unexplored Learning Model in Biochemistry and Molecular Biology

ERIC Educational Resources Information Center

Costa, Manuel Joao; Sandars, John

2012-01-01

The ultimate goal of "student-centered" education is to empower students to learn beyond educational programs. This means nurturing students' autonomy and fostering the development of their own motivation and mechanisms to become self-directed learners. This idea has been embodied in the "lifelong learning" mantra that pervades contemporary views…

Computer-Based Exercises To Supplement the Teaching of Stereochemical Aspects of Drug Action.

ERIC Educational Resources Information Center

Harrold, Marc W.

1995-01-01

At the Duquesne University (PA) school of pharmacy, five self-paced computer exercises using a molecular modeling program have been implemented to teach stereochemical concepts. The approach, designed for small-group learning, has been well received and found effective in enhancing students' understanding of the concepts. (Author/MSE)

Estimation of the Young’s modulus of cellulose Iß by MM3 and quantum mechanics

USDA-ARS?s Scientific Manuscript database

Young’s modulus provides a measure of the resistance to deformation of an elastic material. In this study, modulus estimations for models of cellulose Iß relied on calculations performed with molecular mechanics (MM) and quantum mechanics (QM) programs. MM computations used the second generation emp...

Structural Analysis Of CD59 Of Chinese Tree Shrew: A New Reference Molecule For Human Immune System Specific CD59 Drug Discovery.

PubMed

Panda, Subhamay; Kumari, Leena; Panda, Santamay

2017-11-17

Chinese tree shrews (Tupaia belangeri chinensis) bear several characteristics that are considered to be very crucial for utilizing in animal experimental models in biomedical research. Subsequent to the identification of key aspects and signaling pathways in nervous and immune systems, it is revealed that tree shrews acquires shared common as well as unique characteristics, and hence offers a genetic basis for employing this animal as a prospective model for biomedical research. CD59 glycoprotein, commonly referred to as MAC-inhibitory protein (MAC-IP), membrane inhibitor of reactive lysis (MIRL), or protectin, is encoded by the CD59 gene in human beings. It is the member of the LY6/uPAR/alpha-neurotoxin protein family. With this initial point the objective of this study was to determine a comparative composite based structure of CD59 of Chinese tree shrew. The additional objective of this study was to examine the distribution of negatively and positively charged amino acid over molecular modeled structure, distribution of secondary structural elements, hydrophobicity molecular surface analysis and electrostatic potential analysis with the assistance of several bioinformatical analytical tools. CD59 Amino acid sequence of Chinese tree shrew collected from the online database system of National Centre for Biotechnology Information. SignalP 4.0 online server was employed for detection of signal peptide instance within the protein sequence of CD59. Molecular model structure of CD59 protein was generated by the Iterative Threading ASSEmbly Refinement (I-TASSER) suite. The confirmation for three-dimensional structural model was evaluated by structure validation tools. Location of negatively and positively charged amino acid over molecular modeled structure, distribution of secondary structural elements, and hydrophobicity molecular surface analysis was performed with the help of Chimera tool. Electrostatic potential analysis was carried out with the adaptive Poisson-Boltzmann solver package. Subsequently validated model was used for the functionally critical amino acids and active site prediction. The functionally critical amino acids and ligand- binding site (LBS) of the proteins (modeled) was determined using the COACH program. Analysis of Ramachandran plot for Chinese tree shrew depicted that overall, 100% of the residues in homology model were observed in allowed and favored regions, sequentially leading to the validation of the standard of generated protein structural model. In case of CD59 of Chinese tree shrew, the total score of G-factor was found to be -0.66 that was generally larger than the acceptable value. This approach suggests the significance and acceptability of the modeled structure of CD59 of Chinese tree shrew. The molecular model data in cooperation to other relevant post model analysis data put forward molecular insight to protecting activity of CD59 protein molecule of Chinese tree shrew. In the present study, we have proposed the first molecular model structure of uncharted CD59 of Chinese tree shrew by significantly utilizing the comparative composite modeling approach. Therefore, the development of a structural model of the CD59 protein was carried out and analyzed further for deducing molecular enrichment technique. The collaborative effort of molecular model and other relevant data of post model analysis carry forward molecular understanding to protecting activity of CD59 functions towards better insight of features of this natural lead compound. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

DTIC Science & Technology

2011-09-01

Simulator ( LAMMPS ). This report presents a theory overview and a manual how to use the method. 15. SUBJECT TERMS Ammunition, coarse-grained model...polymer builder, LAMMPS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT UU 18. NUMBER OF PAGES 26 19a. NAME OF RESPONSIBLE PERSON...scale Atomic/Molecular Massively Parallel Simulator ( LAMMPS ). Gel is an in house written C program of coarse- grained polymer builder, and LAMMPS is

Evaluation of reduced point charge models of proteins through Molecular Dynamics simulations: application to the Vps27 UIM-1-Ubiquitin complex.

PubMed

Leherte, Laurence; Vercauteren, Daniel P

2014-02-01

Reduced point charge models of amino acids are designed, (i) from local extrema positions in charge density distribution functions built from the Poisson equation applied to smoothed molecular electrostatic potential (MEP) functions, and (ii) from local maxima positions in promolecular electron density distribution functions. Corresponding charge values are fitted versus all-atom Amber99 MEPs. To easily generate reduced point charge models for protein structures, libraries of amino acid templates are built. The program GROMACS is used to generate stable Molecular Dynamics trajectories of an Ubiquitin-ligand complex (PDB: 1Q0W), under various implementation schemes, solvation, and temperature conditions. Point charges that are not located on atoms are considered as virtual sites with a nul mass and radius. The results illustrate how the intra- and inter-molecular H-bond interactions are affected by the degree of reduction of the point charge models and give directions for their implementation; a special attention to the atoms selected to locate the virtual sites and to the Coulomb-14 interactions is needed. Results obtained at various temperatures suggest that the use of reduced point charge models allows to probe local potential hyper-surface minima that are similar to the all-atom ones, but are characterized by lower energy barriers. It enables to generate various conformations of the protein complex more rapidly than the all-atom point charge representation. Copyright © 2013 Elsevier Inc. All rights reserved.

mrtailor: a tool for PDB-file preparation for the generation of external restraints.

PubMed

Gruene, Tim

2013-09-01

Model building starting from, for example, a molecular-replacement solution with low sequence similarity introduces model bias, which can be difficult to detect, especially at low resolution. The program mrtailor removes low-similarity regions from a template PDB file according to sequence similarity between the target sequence and the template sequence and maps the target sequence onto the PDB file. The modified PDB file can be used to generate external restraints for low-resolution refinement with reduced model bias and can be used as a starting point for model building and refinement. The program can call ProSMART [Nicholls et al. (2012), Acta Cryst. D68, 404-417] directly in order to create external restraints suitable for REFMAC5 [Murshudov et al. (2011), Acta Cryst. D67, 355-367]. Both a command-line version and a GUI exist.

Optimization and benchmarking of a perturbative Metropolis Monte Carlo quantum mechanics/molecular mechanics program

NASA Astrophysics Data System (ADS)

Feldt, Jonas; Miranda, Sebastião; Pratas, Frederico; Roma, Nuno; Tomás, Pedro; Mata, Ricardo A.

2017-12-01

In this work, we present an optimized perturbative quantum mechanics/molecular mechanics (QM/MM) method for use in Metropolis Monte Carlo simulations. The model adopted is particularly tailored for the simulation of molecular systems in solution but can be readily extended to other applications, such as catalysis in enzymatic environments. The electrostatic coupling between the QM and MM systems is simplified by applying perturbation theory to estimate the energy changes caused by a movement in the MM system. This approximation, together with the effective use of GPU acceleration, leads to a negligible added computational cost for the sampling of the environment. Benchmark calculations are carried out to evaluate the impact of the approximations applied and the overall computational performance.

Optimization and benchmarking of a perturbative Metropolis Monte Carlo quantum mechanics/molecular mechanics program.

PubMed

Feldt, Jonas; Miranda, Sebastião; Pratas, Frederico; Roma, Nuno; Tomás, Pedro; Mata, Ricardo A

2017-12-28

In this work, we present an optimized perturbative quantum mechanics/molecular mechanics (QM/MM) method for use in Metropolis Monte Carlo simulations. The model adopted is particularly tailored for the simulation of molecular systems in solution but can be readily extended to other applications, such as catalysis in enzymatic environments. The electrostatic coupling between the QM and MM systems is simplified by applying perturbation theory to estimate the energy changes caused by a movement in the MM system. This approximation, together with the effective use of GPU acceleration, leads to a negligible added computational cost for the sampling of the environment. Benchmark calculations are carried out to evaluate the impact of the approximations applied and the overall computational performance.

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

NASA Astrophysics Data System (ADS)

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 system and runtime parameters Classification: 16.5 Catalogue identifier of previous version: ADMG_v2_0 Journal reference of previous version: Comput. Phys. Comm. 162 (2004) 51 External routines: CUDA libraries (SDK V2.x). Does the new version supersede the previous version?: Yes Nature of problem: In this set of codes an efficient procedure is implemented to describe the wavefunction and related molecular properties of a polyatomic molecular system within the Single Center of Expansion (SCE) approximation. The resulting SCE wavefunction, electron density, electrostatic and correlation/polarization potentials can then be used in a wide variety of applications, such as electron-molecule scattering calculations, quantum chemistry studies, biomodelling and drug design. Solution method: The polycentre Hartree-Fock solution for a molecule of arbitrary geometry, based on linear combination of Gaussian-Type Orbital (GTO), is expanded over a single center, typically the Center Of Mass (C.O.M.), by means of a Gauss Legendre/Chebyschev quadrature over the θ,φ angular coordinates. The resulting SCE numerical wavefunction is then used to calculate the one-particle electron density, the electrostatic potential and two different models for the correlation/polarization potentials induced by the impinging electron, which have the correct asymptotic behavior for the leading dipole molecular polarizabilities. Reasons for new version: The present release of SCELib allows the study of larger molecular systems with respect to the previous versions by means of theoretical and technological advances, with the first implementation of the code over a many-core computing system. Summary of revisions: The major features added with respect to SCELib Version 2.0 are molecular wavefunctions obtained via the Los Alamos (Hay and Wadt) LAN ECP plus DZ description of the inner-shell electrons (on Na-La, Hf-Bi elements) [1] can now be single-center-expanded; the addition required modifications of: (i) the filtering code readgau, (ii) the main reading function setinp, (iii) the sphint code (including changes to the CalcMO code), (iv) the densty code, (v) the vst code; the classes of platforms supported now include two more architectures based on accelerated coprocessors (Nvidia GSeries GPGPU and ClearSpeed e720 (ClearSpeed version, experimental; initial preliminary porting of the sphint() function not for production runs - see the code documentation for additional detail). A single-precision representation for real numbers in the SCE mapping of the GTOs ( sphint code), has been implemented into the new code; the I h symmetry point group for the molecular systems has been added to those already allowed in the SCE procedure; the orientation of the molecular axis system for the Cs (planar) symmetry has been changed in accord with the standard orientation adopted by the latest version of the quantum chemistry code (Gaussian C03 [2]), which is used to generate the input multi-centre molecular wavefunctions ( z-axis perpendicular to the symmetry plane); the abelian subgroup for the Cs point group has been changed from C 1 to Cs; atomic basis functions including g-type GTOs can now be single-center-expanded. Restrictions: Depending on the molecular system under study and on the operating conditions the program may or may not fit into available RAM memory. In this case a feature of the program is to memory map a disk file in order to efficiently access the memory data through a disk device. The parallel GP-GPU implementation limits the number of CPU threads to the number of GPU cores present. Running time: The execution time strongly depends on the molecular target description and on the hardware/OS chosen, it is directly proportional to the ( r,θ,φ) grid size and to the number of angular basis functions used. Thus, from the program printout of the main arrays memory occupancy, the user can approximately derive the expected computer time needed for a given calculation executed in serial mode. For parallel executions the overall efficiency must be further taken into account, and this depends on the no. of processors used as well as on the parallel architecture chosen, so a simple general law is at present not determinable. References:[1] P.J. Hay, W.R. Wadt, J. Chem. Phys. 82 (1985) 270; W.R. Wadt, P.J. Hay, J. Chem. Phys. 284 (1985);P.J. Hay, W.R. Wadt, J. Chem. Phys. 299 (1985). [2] M.J. Frisch et al., Gaussian 03, revision C.02, Gaussian, Inc., Wallingford, CT, 2004.

Molecular and mathematical modeling analyses of inter-island transmission of rabies into a previously rabies-free island in the Philippines.

PubMed

Tohma, Kentaro; Saito, Mariko; Demetria, Catalino S; Manalo, Daria L; Quiambao, Beatriz P; Kamigaki, Taro; Oshitani, Hitoshi

2016-03-01

Rabies is endemic in the Philippines and dog bites are a major cause of rabies cases in humans. The rabies control program has not been successful in eliminating rabies because of low vaccination coverage among dogs. Therefore, more effective and feasible strategies for rabies control are urgently required in the country. To control rabies, it is very important to know if inter-island transmission can occur because rabies can become endemic once the virus is introduced in areas that previously had no reported cases. Our molecular epidemiological study suggests that inter-island transmission events can occur; therefore, we further investigated these inter-island transmission using phylogenetic and modeling approaches. We investigate inter-island transmission between Luzon and Tablas Islands in the Philippines. Phylogenetic analysis and mathematical modeling demonstrate that there was a time lag of several months to a year from rabies introduction to initial case detection, indicating the difficulties in recognizing the initial rabies introductory event. There had been no rabies cases reported in Tablas Island; however, transmission chain was sustained on this island after the introduction of rabies virus because of low vaccination coverage among dogs. Across the islands, a rabies control program should include control of inter-island dog transportation and rabies vaccination to avoid viral introduction from the outside and to break transmission chains after viral introduction. However, this program has not yet been completely implemented and transmission chains following inter-island virus transmission are still observed. Local government units try to control dog transport; however, it should be more strictly controlled, and a continuous rabies control program should be implemented to prevent rabies spread even in rabies-free areas. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

MacSyFinder: A Program to Mine Genomes for Molecular Systems with an Application to CRISPR-Cas Systems

PubMed Central

Abby, Sophie S.; Néron, Bertrand; Ménager, Hervé; Touchon, Marie; Rocha, Eduardo P. C.

2014-01-01

Motivation Biologists often wish to use their knowledge on a few experimental models of a given molecular system to identify homologs in genomic data. We developed a generic tool for this purpose. Results Macromolecular System Finder (MacSyFinder) provides a flexible framework to model the properties of molecular systems (cellular machinery or pathway) including their components, evolutionary associations with other systems and genetic architecture. Modelled features also include functional analogs, and the multiple uses of a same component by different systems. Models are used to search for molecular systems in complete genomes or in unstructured data like metagenomes. The components of the systems are searched by sequence similarity using Hidden Markov model (HMM) protein profiles. The assignment of hits to a given system is decided based on compliance with the content and organization of the system model. A graphical interface, MacSyView, facilitates the analysis of the results by showing overviews of component content and genomic context. To exemplify the use of MacSyFinder we built models to detect and class CRISPR-Cas systems following a previously established classification. We show that MacSyFinder allows to easily define an accurate “Cas-finder” using publicly available protein profiles. Availability and Implementation MacSyFinder is a standalone application implemented in Python. It requires Python 2.7, Hmmer and makeblastdb (version 2.2.28 or higher). It is freely available with its source code under a GPLv3 license at https://github.com/gem-pasteur/macsyfinder. It is compatible with all platforms supporting Python and Hmmer/makeblastdb. The “Cas-finder” (models and HMM profiles) is distributed as a compressed tarball archive as Supporting Information. PMID:25330359

CAMD studies of coal structure and coal liquefaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Faulon, J.L.; Carlson, G.A.

The macromolecular structure of coal is essential to understand the mechanisms occurring during coal liquefaction. Many attempts to model coal structure can be found in the literature. More specifically for high volatile bituminous coal, the subject of interest the most commonly quoted models are the models of Given, Wiser, Solomon, and Shinn. In past work, the authors`s have used computer-aided molecular design (CAMD) to develop three-dimensional representations for the above coal models. The three-dimensional structures were energy minimized using molecular mechanics and molecular dynamics. True density and micopore volume were evaluated for each model. With the exception of Given`s model,more » the computed density values were found to be in agreement with the corresponding experimental results. The above coal models were constructed by a trial and error technique consisting of a manual fitting of the-analytical data. It is obvious that for each model the amount of data is small compared to the actual complexity of coal, and for all of the models more than one structure can be built. Hence, the process by which one structure is chosen instead of another is not clear. In fact, all the authors agree that the structure they derived was only intended to represent an {open_quotes}average{close_quotes} coal model rather than a unique correct structure. The purpose of this program is further develop CAMD techniques to increase the understanding of coal structure and its relationship to coal liquefaction.« less

Prediction on the inhibition ratio of pyrrolidine derivatives on matrix metalloproteinase based on gene expression programming.

PubMed

Li, Yuqin; You, Guirong; Jia, Baoxiu; Si, Hongzong; Yao, Xiaojun

2014-01-01

Quantitative structure-activity relationships (QSAR) were developed to predict the inhibition ratio of pyrrolidine derivatives on matrix metalloproteinase via heuristic method (HM) and gene expression programming (GEP). The descriptors of 33 pyrrolidine derivatives were calculated by the software CODESSA, which can calculate quantum chemical, topological, geometrical, constitutional, and electrostatic descriptors. HM was also used for the preselection of 5 appropriate molecular descriptors. Linear and nonlinear QSAR models were developed based on the HM and GEP separately and two prediction models lead to a good correlation coefficient (R (2)) of 0.93 and 0.94. The two QSAR models are useful in predicting the inhibition ratio of pyrrolidine derivatives on matrix metalloproteinase during the discovery of new anticancer drugs and providing theory information for studying the new drugs.

Final Technical Report for SISGR: Ultrafast Molecular Scale Chemical Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hersam, Mark C.; Guest, Jeffrey R.; Guisinger, Nathan P.

2017-04-10

The Northwestern-Argonne SISGR program utilized newly developed instrumentation and techniques including integrated ultra-high vacuum tip-enhanced Raman spectroscopy/scanning tunneling microscopy (UHV-TERS/STM) and surface-enhanced femtosecond stimulated Raman scattering (SE-FSRS) to advance the spatial and temporal resolution of chemical imaging for the study of photoinduced dynamics of molecules on plasmonically active surfaces. An accompanying theory program addressed modeling of charge transfer processes using constrained density functional theory (DFT) in addition to modeling of SE-FSRS, thereby providing a detailed description of the excited state dynamics. This interdisciplinary and highly collaborative research resulted in 62 publications with ~ 48% of them being co-authored by multiplemore » SISGR team members. A summary of the scientific accomplishments from this SISGR program is provided in this final technical report.« less

Goals and Objectives for Molecular Pathology Education in Residency Programs

PubMed Central

1999-01-01

Increasing knowledge of the molecular basis of disease and advances in technology for analyzing nucleic acids and gene products are changing pathology practice. The explosion of information regarding inherited susceptibility to disease is an important aspect of this transformation. Pathology residency programs are incorporating molecular pathology education into their curricula to prepare newly trained pathologists for the future, yet little guidance has been available regarding the important components of molecular pathology training. We present general goals for pathology training programs for molecular pathology education. These include recommendations to pathology residents for the acquisition of both basic knowledge in human genetics and molecular biology and specific skills relevant to microbiology, molecular oncology, genetics, histocompatibility, and identity determination. The importance of residents gaining facility in integrating data gained via nucleic acid based-technology with other laboratory and clinical information available in the care of patients is emphasized. PMID:11272908

Senescence and programmed cell death in plants: polyamine action mediated by transglutaminase

PubMed Central

Del Duca, Stefano; Serafini-Fracassini, Donatella; Cai, Giampiero

2014-01-01

Research on polyamines (PAs) in plants laps a long way of about 50 years and many roles have been discovered for these aliphatic cations. PAs regulate cell division, differentiation, organogenesis, reproduction, dormancy-break and senescence, homeostatic adjustments in response to external stimuli and stresses. Nevertheless, the molecular mechanisms of their multiple activities are still matter of research. PAs are present in free and bound forms and interact with several important cell molecules; some of these interactions may occur by covalent linkages catalyzed by transglutaminase (TGase), giving rise to “cationization” or cross-links among specific proteins. Senescence and programmed cell death (PCD) can be delayed by PAs; in order to re-interpret some of these effects and to obtain new insights into their molecular mechanisms, their conjugation has been revised here. The TGase-mediated interactions between proteins and PAs are the main target of this review. After an introduction on the characteristics of this enzyme, on its catalysis and role in PCD in animals, the plant senescence and PCD models in which TGase has been studied, are presented: the corolla of naturally senescing or excised flowers, the leaves senescing, either excised or not, the pollen during self-incompatible pollination, the hypersensitive response and the tuber storage parenchyma during dormancy release. In all the models examined, TGase appears to be involved by a similar molecular mechanism as described during apoptosis in animal cells, even though several substrates are different. Its effect is probably related to the type of PCD, but mostly to the substrate to be modified in order to achieve the specific PCD program. As a cross-linker of PAs and proteins, TGase is an important factor involved in multiple, sometimes controversial, roles of PAs during senescence and PCD. PMID:24778637

Teaching Molecular Biology with Microcomputers.

ERIC Educational Resources Information Center

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)

Current Status of Human Resource Training Program for Fostering RIBiomics Professionals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Dong-Eun; Jang, Beom-Su; Choi, Dae Seong

RI-Biomics is a state-of-the-art radiation fusion technology for evaluating in-vivo dynamics such as absorption, distribution, metabolism and excretion (ADME) of new drug candidates and biomaterials using radioisotope (RI), and quantitative evaluation of their efficacy via molecular imaging techniques and animal models. The RI-Biomics center is the sole comprehensive research and experiment complex in Korea that can simultaneously perform the radio-synthesis of drug candidate with radioisotope, analysis, and molecular imaging evaluation with animal model. Molecular imaging techniques, including nuclear imaging (SPECT and PET), near-infrared fluorescent (NIRF) imaging, and magnetic resonance imaging (MRI), are the cutting-edge technologies for evaluating drug candidates. Sincemore » they allow in vivo real-time imaging of the diseased site, monitoring the biodistribution of drug and determining the optimal therapeutic efficacy following treatments, we have integrated RI-ADME and molecular imaging to provide useful information for drug evaluation and to accelerate the development of new drugs and biomaterials. The RI-Biomics center was established with total investment of 18 million $ during four years from 2009 to 2012 in order to develop a comprehensive analyzing system using RI for new drug development as an axis for national growth in the next generation. The RI-Biomics center has labeling synthesis facility for the radiosynthesis of drug candidate with radioisotope such as Tc-99m, I-125, I-131, F-18, H-3 and C-14 using hot cell. It also includes RI-general analysis facilities, such as Radio-HPLC, LC/MS, GC/MS, gamma counter that can analyzing the radio-synthesized materials, and animal image analysis facilities that developed small animal imaging equipment such as SPECT/PET/CT, 7 T MRI, in-vivo optical imaging system and others. In order to achieve the system to verify safety and effectiveness of the new drugs using RI, it is necessary to establish a human resource training program for fostering RI-Biomics professionals in the following key fields; (1) Radio-pharmaceuticals synthesis and labeled compound development, (2) Development of RI-ADME in the living object and image assessment technology. Personnel training program that carries out theoretical education and practical training in the field related to RI-Biomics in parallel is being conducted. Internship training for university students has been administered twice already while educational program for the existing professionals in the RI-Biomics field will be carried out during the summer of 2014. The human resource training program for combination of RIADME and different molecular imaging techniques can offer synergistic advantages to facilitate understanding RIADME and fostering RI-ADME professionals. (authors)« less

Molecular beam epitaxy growth method for vertical-cavity surface-emitting laser resonators based on substrate thermal emission

NASA Astrophysics Data System (ADS)

Talghader, J. J.; Hadley, M. A.; Smith, J. S.

1995-12-01

A molecular beam epitaxy growth monitoring method is developed for distributed Bragg reflectors and vertical-cavity surface-emitting laser (VCSEL) resonators. The wavelength of the substrate thermal emission that corresponds to the optical cavity resonant wavelength is selected by a monochromator and monitored during growth. This method allows VCSEL cavities of arbitrary design wavelength to be grown with a single control program. This letter also presents a theoretical model for the technique which is based on transmission matrices and simple thermal emission properties. Demonstrated reproducibility of the method is well within 0.1%.

Program review. Challenges and opportunities for training the next generation of biophysicists: perspectives of the directors of the Molecular Biophysics Training Program at Northwestern University.

PubMed

Neuhaus, Francis; Widom, Jonathan; MacDonald, Robert; Jardetzky, Theodore; Radhakrishnan, Ishwar

2008-04-01

Molecular biophysics is a broad, diverse, and dynamic field that has presented a variety of unique challenges and opportunities for training future generations of investigators. Having been or currently being intimately associated with the Molecular Biophysics Training Program at Northwestern, we present our perspectives on various issues that we have encountered over the years. We propose no cookie-cutter solutions, as there is no consensus on what constitutes the "ideal" program. However, there is uniformity in opinion on some key issues that might be useful to those interested in establishing a biophysics training program.

Molecular Modeling of Ammonium, Calcium, Sulfur, and Sodium Lignosulphonates in Acid and Basic Aqueous Environments

NASA Astrophysics Data System (ADS)

Salazar Valencia, P. J.; Bolívar Marinez, L. E.; Pérez Merchancano, S. T.

2015-12-01

Lignosulphonates (LS), also known as lignin sulfonates or sulfite lignin, are lignins in sulfonated forms, obtained from the "sulfite liquors," a residue of the wood pulp extraction process. Their main utility lies in its wide range of properties, they can be used as additives, dispersants, binders, fluxing, binder agents, etc. in fields ranging from food to fertilizer manufacture and even as agents in the preparation of ion exchange membranes. Since they can be manufactured relatively easy and quickly, and that its molecular size can be manipulated to obtain fragments of very low molecular weight, they are used as transport agents in the food industry, cosmetics, pharmaceutical and drug development, and as molecular elements for the treatment of health problems. In this paper, we study the electronic structural and optical characteristics of LS incorporating ammonium, sulfur, calcium, and sodium ions in acidic and basic aqueous media in order to gain a better understanding of their behavior and the very interesting properties exhibit. The studies were performed using the molecular modeling program HyperChem 5 using the semiempirical method PM3 of the NDO Family (neglect of differential overlap), to calculate the structural properties. We calculated the electronic and optical properties using the semiempirical method ZINDO / CI.

Biotechnology and genetic engineering in the new drug development. Part III. Biocatalysis, metabolic engineering and molecular modelling.

PubMed

Stryjewska, Agnieszka; Kiepura, Katarzyna; Librowski, Tadeusz; Lochyński, Stanisław

2013-01-01

Industrial biotechnology has been defined as the use and application of biotechnology for the sustainable processing and production of chemicals, materials and fuels. It makes use of biocatalysts such as microbial communities, whole-cell microorganisms or purified enzymes. In the review these processes are described. Drug design is an iterative process which begins when a chemist identifies a compound that displays an interesting biological profile and ends when both the activity profile and the chemical synthesis of the new chemical entity are optimized. Traditional approaches to drug discovery rely on a stepwise synthesis and screening program for large numbers of compounds to optimize activity profiles. Over the past ten to twenty years, scientists have used computer models of new chemical entities to help define activity profiles, geometries and relativities. This article introduces inter alia the concepts of molecular modelling and contains references for further reading.

Faunus: An object oriented framework for molecular simulation

PubMed Central

Lund, Mikael; Trulsson, Martin; Persson, Björn

2008-01-01

Background We present a C++ class library for Monte Carlo simulation of molecular systems, including proteins in solution. The design is generic and highly modular, enabling multiple developers to easily implement additional features. The statistical mechanical methods are documented by extensive use of code comments that – subsequently – are collected to automatically build a web-based manual. Results We show how an object oriented design can be used to create an intuitively appealing coding framework for molecular simulation. This is exemplified in a minimalistic C++ program that can calculate protein protonation states. We further discuss performance issues related to high level coding abstraction. Conclusion C++ and the Standard Template Library (STL) provide a high-performance platform for generic molecular modeling. Automatic generation of code documentation from inline comments has proven particularly useful in that no separate manual needs to be maintained. PMID:18241331

Structure simulation with calculated NMR parameters - integrating COSMOS into the CCPN framework.

PubMed

Schneider, Olaf; Fogh, Rasmus H; Sternberg, Ulrich; Klenin, Konstantin; Kondov, Ivan

2012-01-01

The Collaborative Computing Project for NMR (CCPN) has build a software framework consisting of the CCPN data model (with APIs) for NMR related data, the CcpNmr Analysis program and additional tools like CcpNmr FormatConverter. The open architecture allows for the integration of external software to extend the abilities of the CCPN framework with additional calculation methods. Recently, we have carried out the first steps for integrating our software Computer Simulation of Molecular Structures (COSMOS) into the CCPN framework. The COSMOS-NMR force field unites quantum chemical routines for the calculation of molecular properties with a molecular mechanics force field yielding the relative molecular energies. COSMOS-NMR allows introducing NMR parameters as constraints into molecular mechanics calculations. The resulting infrastructure will be made available for the NMR community. As a first application we have tested the evaluation of calculated protein structures using COSMOS-derived 13C Cα and Cβ chemical shifts. In this paper we give an overview of the methodology and a roadmap for future developments and applications.

Electron tunneling in proteins program.

PubMed

Hagras, Muhammad A; Stuchebrukhov, Alexei A

2016-06-05

We developed a unique integrated software package (called Electron Tunneling in Proteins Program or ETP) which provides an environment with different capabilities such as tunneling current calculation, semi-empirical quantum mechanical calculation, and molecular modeling simulation for calculation and analysis of electron transfer reactions in proteins. ETP program is developed as a cross-platform client-server program in which all the different calculations are conducted at the server side while only the client terminal displays the resulting calculation outputs in the different supported representations. ETP program is integrated with a set of well-known computational software packages including Gaussian, BALLVIEW, Dowser, pKip, and APBS. In addition, ETP program supports various visualization methods for the tunneling calculation results that assist in a more comprehensive understanding of the tunneling process. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A Virtual Laboratory for the 4 Bed Molecular Sieve of the Carbon Dioxide Removal Assembly

NASA Technical Reports Server (NTRS)

Coker, Robert; Knox, James; O'Connor, Brian

2016-01-01

Ongoing work to improve water and carbon dioxide separation systems to be used on crewed space vehicles combines sub-scale systems testing and multi-physics simulations. Thus, as part of NASA's Advanced Exploration Systems (AES) program and the Life Support Systems Project (LSSP), fully predictive COMSOL Multiphysics models of the Four Bed Molecular Sieve (4BMS) of the Carbon Dioxide Removal Assembly (CDRA) on the International Space Station (ISS) have been developed. This Virtual Laboratory is being used to help reduce mass, power, and volume requirements for exploration missions. In this paper we describe current and planned modeling developments in the area of carbon dioxide removal to support future missions as well as the resolution of anomalies observed in the ISS CDRA.

ATK-ForceField: a new generation molecular dynamics software package

NASA Astrophysics Data System (ADS)

Schneider, Julian; Hamaekers, Jan; Chill, Samuel T.; Smidstrup, Søren; Bulin, Johannes; Thesen, Ralph; Blom, Anders; Stokbro, Kurt

2017-12-01

ATK-ForceField is a software package for atomistic simulations using classical interatomic potentials. It is implemented as a part of the Atomistix ToolKit (ATK), which is a Python programming environment that makes it easy to create and analyze both standard and highly customized simulations. This paper will focus on the atomic interaction potentials, molecular dynamics, and geometry optimization features of the software, however, many more advanced modeling features are available. The implementation details of these algorithms and their computational performance will be shown. We present three illustrative examples of the types of calculations that are possible with ATK-ForceField: modeling thermal transport properties in a silicon germanium crystal, vapor deposition of selenium molecules on a selenium surface, and a simulation of creep in a copper polycrystal.

MTOR-driven quasi-programmed aging as a disposable soma theory

PubMed Central

2013-01-01

If life were created by intelligent design, we would indeed age from accumulation of molecular damage. Repair is costly and limited by energetic resources, and we would allocate resources rationally. But, albeit elegant, this design is fictional. Instead, nature blindly selects for short-term benefits of robust developmental growth. “Quasi-programmed” by the blind watchmaker, aging is a wasteful and aimless continuation of developmental growth, driven by nutrient-sensing, growth-promoting signaling pathways such as MTOR (mechanistic target of rapamycin). A continuous post-developmental activity of such gerogenic pathways leads to hyperfunctions (aging), loss of homeostasis, age-related diseases, non-random organ damage and death. This model is consistent with a view that (1) soma is disposable, (2) aging and menopause are not programmed and (3) accumulation of random molecular damage is not a cause of aging as we know it. PMID:23708516

Strategies For Clinical Implementation: Precision Oncology At Three Distinct Institutions.

PubMed

Nadauld, Lincoln D; Ford, James M; Pritchard, Daryl; Brown, Thomas

2018-05-01

Despite rapid advances in molecular diagnostics and targeted therapeutics, the adoption of precision medicine into clinical oncology workflows has been slow. Questions about clinical utility, inconsistent reimbursement for molecular diagnostics, and limited access to targeted therapies are some of the major hurdles that have hampered clinical adoption. Despite these challenges, providers have invested in precision medicine programs in an ongoing search for innovative care models to deliver improved patient outcomes and achieve economic gains. We describe the precision oncology medicine programs implemented by an integrated delivery system, a community care center, and an academic medical center, to demonstrate the approaches and challenges associated with clinical implementation efforts designed to advance this treatment paradigm. Payer policies that include coverage for broad genomic testing panels would support the broader application of precision medicine, deepen research benefits, and bring targeted therapies to more patients with advanced cancer.

Pyrite: A blender plugin for visualizing molecular dynamics simulations using industry-standard rendering techniques.

PubMed

Rajendiran, Nivedita; Durrant, Jacob D

2018-05-05

Molecular dynamics (MD) simulations provide critical insights into many biological mechanisms. Programs such as VMD, Chimera, and PyMOL can produce impressive simulation visualizations, but they lack many advanced rendering algorithms common in the film and video-game industries. In contrast, the modeling program Blender includes such algorithms but cannot import MD-simulation data. MD trajectories often require many gigabytes of memory/disk space, complicating Blender import. We present Pyrite, a Blender plugin that overcomes these limitations. Pyrite allows researchers to visualize MD simulations within Blender, with full access to Blender's cutting-edge rendering techniques. We expect Pyrite-generated images to appeal to students and non-specialists alike. A copy of the plugin is available at http://durrantlab.com/pyrite/, released under the terms of the GNU General Public License Version 3. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

ScrubChem: Cleaning of PubChem Bioassay Data to Create Diverse and Massive Bioactivity Datasets for Use in Modeling Applications (SOT)

EPA Science Inventory

The PubChem Bioassay database is a non-curated public repository with bioactivity data from 64 sources, including: ChEMBL, BindingDb, DrugBank, Tox21, NIH Molecular Libraries Screening Program, and various academic, government, and industrial contributors. However, this data is d...

DREW-UCLA Breast Cancer Research and Training Program: Molecular/Cellular Pathogenesis Model

DTIC Science & Technology

2007-03-01

system in bovine renal brush- border [13] and in a bovine renal epithelial cell line NBL -1 [14]. In order to highlight the substrate difference with an... NBL -1 expresses a broad specificity Na(+)-dependent neu- tral amino acid transport system (System B0) similar to that in bovine renal brush border

A study of lunar models based on Apollo and other data

NASA Technical Reports Server (NTRS)

1973-01-01

The research concerned with the interpretation of lunar data developed during the Apollo Program is reported. The areas of research include: X-ray emission spectra and molecular orbitals of lunar materials, magnetic properties of lunar rock, lunar features, thermal history and evolution of the moon, and the internal constitution and evolution of the moon.

Predictive Modeling of the CDRA 4BMS

NASA Technical Reports Server (NTRS)

Coker, Robert F.; Knox, James C.

2016-01-01

As part of NASA's Advanced Exploration Systems (AES) program and the Life Support Systems Project (LSSP), fully predictive models of the Four Bed Molecular Sieve (4BMS) of the Carbon Dioxide Removal Assembly (CDRA) on the International Space Station (ISS) are being developed. This virtual laboratory will be used to help reduce mass, power, and volume requirements for future missions. In this paper we describe current and planned modeling developments in the area of carbon dioxide removal to support future crewed Mars missions as well as the resolution of anomalies observed in the ISS CDRA.

Accessible high-throughput virtual screening molecular docking software for students and educators.

PubMed

Jacob, Reed B; Andersen, Tim; McDougal, Owen M

2012-05-01

We survey low cost high-throughput virtual screening (HTVS) computer programs for instructors who wish to demonstrate molecular docking in their courses. Since HTVS programs are a useful adjunct to the time consuming and expensive wet bench experiments necessary to discover new drug therapies, the topic of molecular docking is core to the instruction of biochemistry and molecular biology. The availability of HTVS programs coupled with decreasing costs and advances in computer hardware have made computational approaches to drug discovery possible at institutional and non-profit budgets. This paper focuses on HTVS programs with graphical user interfaces (GUIs) that use either DOCK or AutoDock for the prediction of DockoMatic, PyRx, DockingServer, and MOLA since their utility has been proven by the research community, they are free or affordable, and the programs operate on a range of computer platforms.

Wallerian demyelination: chronicle of a cellular cataclysm.

PubMed

Tricaud, Nicolas; Park, Hwan Tae

2017-11-01

Wallerian demyelination is characteristic of peripheral nerve degeneration after traumatic injury. After axonal degeneration, the myelinated Schwann cell undergoes a stereotypical cellular program that results in the disintegration of the myelin sheath, a process termed demyelination. In this review, we chronologically describe this program starting from the late and visible features of myelin destruction and going backward to the initial molecular steps that trigger the nuclear reprogramming few hours after injury. Wallerian demyelination is a wonderful model for myelin degeneration occurring in the diverse forms of demyelinating peripheral neuropathies that plague human beings.

Spaceborne Photonics Institute

NASA Technical Reports Server (NTRS)

Venable, D. D.; Farrukh, U. O.; Han, K. S.; Hwang, I. H.; Jalufka, N. W.; Lowe, C. W.; Tabibi, B. M.; Lee, C. J.; Lyons, D.; Maclin, A.

1994-01-01

This report describes in chronological detail the development of the Spaceborne Photonics Institute as a sustained research effort at Hampton University in the area of optical physics. This provided the research expertise to initiate a PhD program in Physics. Research was carried out in the areas of: (1) modelling of spaceborne solid state laser systems; (2) amplified spontaneous emission in solar pumped iodine lasers; (3) closely simulated AM0 CW solar pumped iodine laser and repeatedly short pulsed iodine laser oscillator; (4) a materials spectroscopy and growth program; and (5) laser induced fluorescence and atomic and molecular spectroscopy.

Girsanov reweighting for path ensembles and Markov state models

NASA Astrophysics Data System (ADS)

Donati, L.; Hartmann, C.; Keller, B. G.

2017-06-01

The sensitivity of molecular dynamics on changes in the potential energy function plays an important role in understanding the dynamics and function of complex molecules. We present a method to obtain path ensemble averages of a perturbed dynamics from a set of paths generated by a reference dynamics. It is based on the concept of path probability measure and the Girsanov theorem, a result from stochastic analysis to estimate a change of measure of a path ensemble. Since Markov state models (MSMs) of the molecular dynamics can be formulated as a combined phase-space and path ensemble average, the method can be extended to reweight MSMs by combining it with a reweighting of the Boltzmann distribution. We demonstrate how to efficiently implement the Girsanov reweighting in a molecular dynamics simulation program by calculating parts of the reweighting factor "on the fly" during the simulation, and we benchmark the method on test systems ranging from a two-dimensional diffusion process and an artificial many-body system to alanine dipeptide and valine dipeptide in implicit and explicit water. The method can be used to study the sensitivity of molecular dynamics on external perturbations as well as to reweight trajectories generated by enhanced sampling schemes to the original dynamics.

φ-evo: A program to evolve phenotypic models of biological networks.

PubMed

Henry, Adrien; Hemery, Mathieu; François, Paul

2018-06-01

Molecular networks are at the core of most cellular decisions, but are often difficult to comprehend. Reverse engineering of network architecture from their functions has proved fruitful to classify and predict the structure and function of molecular networks, suggesting new experimental tests and biological predictions. We present φ-evo, an open-source program to evolve in silico phenotypic networks performing a given biological function. We include implementations for evolution of biochemical adaptation, adaptive sorting for immune recognition, metazoan development (somitogenesis, hox patterning), as well as Pareto evolution. We detail the program architecture based on C, Python 3, and a Jupyter interface for project configuration and network analysis. We illustrate the predictive power of φ-evo by first recovering the asymmetrical structure of the lac operon regulation from an objective function with symmetrical constraints. Second, we use the problem of hox-like embryonic patterning to show how a single effective fitness can emerge from multi-objective (Pareto) evolution. φ-evo provides an efficient approach and user-friendly interface for the phenotypic prediction of networks and the numerical study of evolution itself.

Early-life programming of susceptibility to dysregulation of glucose metabolism and the development of Type 2 diabetes mellitus.

PubMed Central

Holness, M J; Langdown, M L; Sugden, M C

2000-01-01

There is increasing epidemiological evidence in humans which associates low birthweight with later metabolic disorders, including insulin resistance and glucose intolerance. There is evidence that nutritional and hormonal factors (e.g. maternal protein restriction, exposure to excess maternal glucocorticoids) markedly influence intra-uterine growth and development. A picture is also emerging of the biochemical and physiological mechanisms that may underlie these effects. This review focuses on recent research directed towards understanding the molecular basis of the relationship between indices of poor early growth and the subsequent development of glucose intolerance and Type 2 diabetes mellitus using animal models that attempt to recreate the process of programming via an adverse intra-uterine or neonatal environment. Emphasis is on the chain of events and potential mechanisms by which adverse adaptations affect pancreatic-beta-cell insulin secretion and the sensitivity to insulin of key metabolic processes, including hepatic glucose production, skeletal-muscle glucose disposal and adipose-tissue lipolysis. Unravelling the molecular details involved in metabolic programming may provide new insights into the pathogenesis of impaired glucoregulation and Type 2 diabetes. PMID:10903125

Altered Placental Tryptophan Metabolism: A Crucial Molecular Pathway for the Fetal Programming of Neurodevelopmental Disorders

DTIC Science & Technology

2015-07-01

Programming of Neurodevelopmental Disorders PRINCIPAL INVESTIGATOR: Alexandre Bonnin, PhD CONTRACTING ORGANIZATION: University of Southern...Molecular Pathway for the Fetal Programming of Neurodevelopmental Disorders 5a. CONTRACT NUMBER W81XWH-13-1-0135 Pathway for the Fetal Programming of... Neurodevelopmental Disorders 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Alexandre Bonnin, PhD; 5d. PROJECT NUMBER Nick Goeden

Algorithms of GPU-enabled reactive force field (ReaxFF) molecular dynamics.

PubMed

Zheng, Mo; Li, Xiaoxia; Guo, Li

2013-04-01

Reactive force field (ReaxFF), a recent and novel bond order potential, allows for reactive molecular dynamics (ReaxFF MD) simulations for modeling larger and more complex molecular systems involving chemical reactions when compared with computation intensive quantum mechanical methods. However, ReaxFF MD can be approximately 10-50 times slower than classical MD due to its explicit modeling of bond forming and breaking, the dynamic charge equilibration at each time-step, and its one order smaller time-step than the classical MD, all of which pose significant computational challenges in simulation capability to reach spatio-temporal scales of nanometers and nanoseconds. The very recent advances of graphics processing unit (GPU) provide not only highly favorable performance for GPU enabled MD programs compared with CPU implementations but also an opportunity to manage with the computing power and memory demanding nature imposed on computer hardware by ReaxFF MD. In this paper, we present the algorithms of GMD-Reax, the first GPU enabled ReaxFF MD program with significantly improved performance surpassing CPU implementations on desktop workstations. The performance of GMD-Reax has been benchmarked on a PC equipped with a NVIDIA C2050 GPU for coal pyrolysis simulation systems with atoms ranging from 1378 to 27,283. GMD-Reax achieved speedups as high as 12 times faster than Duin et al.'s FORTRAN codes in Lammps on 8 CPU cores and 6 times faster than the Lammps' C codes based on PuReMD in terms of the simulation time per time-step averaged over 100 steps. GMD-Reax could be used as a new and efficient computational tool for exploiting very complex molecular reactions via ReaxFF MD simulation on desktop workstations. Copyright © 2013 Elsevier Inc. All rights reserved.

Implementation and Assessment of a Molecular Biology and Bioinformatics Undergraduate Degree Program

ERIC Educational Resources Information Center

Pham, Daphne Q. -D.; Higgs, David C.; Statham, Anne; Schleiter, Mary Kay

2008-01-01

The Department of Biological Sciences at the University of Wisconsin-Parkside has developed and implemented an innovative, multidisciplinary undergraduate curriculum in Molecular Biology and Bioinformatics (MBB). The objective of the MBB program is to give students a hands-on facility with molecular biology theories and laboratory techniques, an…

Incorporating Molecular and Cellular Biology into a Chemical Engineering Degree Program

ERIC Educational Resources Information Center

O'Connor, Kim C.

2005-01-01

There is a growing need for a workforce that can apply engineering principles to molecular based discovery and product development in the biological sciences. To this end, Tulane University established a degree program that incorporates molecular and cellular biology into the chemical engineering curriculum. In celebration of the tenth anniversary…

Program Review Challenges and Opportunities for Training the Next Generation of Biophysicists: Perspectives of the Directors of the Molecular Biophysics Training Program at Northwestern University

PubMed Central

Neuhaus, Francis; Widom, Jonathan; MacDonald, Robert; Jardetzky, Theodore; Radhakrishnan, Ishwar

2009-01-01

Molecular biophysics is a broad, diverse, and dynamic field that has presented a variety of unique challenges and opportunities for training future generations of investigators. Having been or currently being intimately associated with the Molecular Biophysics Training Program at Northwestern, we present our perspectives on various issues that we have encountered over the years. We propose no cookie-cutter solutions, as there is no consensus on what constitutes the “ideal” program. However, there is uniformity in opinion on some key issues that might be useful to those interested in establishing a biophysics training program. PMID:18293401

QSAR Study and Molecular Design of Open-Chain Enaminones as Anticonvulsant Agents

PubMed Central

Garro Martinez, Juan C.; Duchowicz, Pablo R.; Estrada, Mario R.; Zamarbide, Graciela N.; Castro, Eduardo A.

2011-01-01

Present work employs the QSAR formalism to predict the ED50 anticonvulsant activity of ringed-enaminones, in order to apply these relationships for the prediction of unknown open-chain compounds containing the same types of functional groups in their molecular structure. Two different modeling approaches are applied with the purpose of comparing the consistency of our results: (a) the search of molecular descriptors via multivariable linear regressions; and (b) the calculation of flexible descriptors with the CORAL (CORrelation And Logic) program. Among the results found, we propose some potent candidate open-chain enaminones having ED50 values lower than 10 mg·kg−1 for corresponding pharmacological studies. These compounds are classified as Class 1 and Class 2 according to the Anticonvulsant Selection Project. PMID:22272137

Fullrmc, a rigid body Reverse Monte Carlo modeling package enabled with machine learning and artificial intelligence.

PubMed

Aoun, Bachir

2016-05-05

A new Reverse Monte Carlo (RMC) package "fullrmc" for atomic or rigid body and molecular, amorphous, or crystalline materials is presented. fullrmc main purpose is to provide a fully modular, fast and flexible software, thoroughly documented, complex molecules enabled, written in a modern programming language (python, cython, C and C++ when performance is needed) and complying to modern programming practices. fullrmc approach in solving an atomic or molecular structure is different from existing RMC algorithms and software. In a nutshell, traditional RMC methods and software randomly adjust atom positions until the whole system has the greatest consistency with a set of experimental data. In contrast, fullrmc applies smart moves endorsed with reinforcement machine learning to groups of atoms. While fullrmc allows running traditional RMC modeling, the uniqueness of this approach resides in its ability to customize grouping atoms in any convenient way with no additional programming efforts and to apply smart and more physically meaningful moves to the defined groups of atoms. In addition, fullrmc provides a unique way with almost no additional computational cost to recur a group's selection, allowing the system to go out of local minimas by refining a group's position or exploring through and beyond not allowed positions and energy barriers the unrestricted three dimensional space around a group. © 2016 Wiley Periodicals, Inc.

Fullrmc, a rigid body reverse monte carlo modeling package enabled with machine learning and artificial intelligence

DOE PAGES

Aoun, Bachir

2016-01-22

Here, a new Reverse Monte Carlo (RMC) package ‘fullrmc’ for atomic or rigid body and molecular, amorphous or crystalline materials is presented. fullrmc main purpose is to provide a fully modular, fast and flexible software, thoroughly documented, complex molecules enabled, written in a modern programming language (python, cython ,C and C++ when performance is needed) and complying to modern programming practices. fullrmc approach in solving an atomic or molecular structure is different from existing RMC algorithms and software. In a nutshell, traditional RMC methods and software randomly adjust atom positions until the whole system has the greatest consistency with amore » set of experimental data. In contrast, fullrmc applies smart moves endorsed with reinforcement machine learning to groups of atoms. While fullrmc allows running traditional RMC modelling, the uniqueness of this approach resides in its ability to customize grouping atoms in any convenient way with no additional programming efforts and to apply smart and more physically meaningful moves to the defined groups of atoms. Also fullrmc provides a unique way with almost no additional computational cost to recur a group’s selection, allowing the system to go out of local minimas by refining a group’s position or exploring through and beyond not allowed positions and energy barriers the unrestricted three dimensional space around a group.« less

Fullrmc, a rigid body reverse monte carlo modeling package enabled with machine learning and artificial intelligence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aoun, Bachir

Here, a new Reverse Monte Carlo (RMC) package ‘fullrmc’ for atomic or rigid body and molecular, amorphous or crystalline materials is presented. fullrmc main purpose is to provide a fully modular, fast and flexible software, thoroughly documented, complex molecules enabled, written in a modern programming language (python, cython ,C and C++ when performance is needed) and complying to modern programming practices. fullrmc approach in solving an atomic or molecular structure is different from existing RMC algorithms and software. In a nutshell, traditional RMC methods and software randomly adjust atom positions until the whole system has the greatest consistency with amore » set of experimental data. In contrast, fullrmc applies smart moves endorsed with reinforcement machine learning to groups of atoms. While fullrmc allows running traditional RMC modelling, the uniqueness of this approach resides in its ability to customize grouping atoms in any convenient way with no additional programming efforts and to apply smart and more physically meaningful moves to the defined groups of atoms. Also fullrmc provides a unique way with almost no additional computational cost to recur a group’s selection, allowing the system to go out of local minimas by refining a group’s position or exploring through and beyond not allowed positions and energy barriers the unrestricted three dimensional space around a group.« less

A Suggested Molecular Pathology Curriculum for Residents: A Report of the Association for Molecular Pathology.

PubMed

Aisner, Dara L; Berry, Anna; Dawson, D Brian; Hayden, Randall T; Joseph, Loren; Hill, Charles E

2016-03-01

Molecular pathology is an essential element of pathology training. As more molecular tests have become available, there is an increasing need for pathology trainees to receive a strong foundation in molecular pathology. Appointed by the Training and Education Committee of the Association for Molecular Pathology, the Molecular Curriculum Task Force has developed a suggested curriculum in molecular pathology for residents. The foundations of molecular pathology are presented as a series of goals and objectives that residency programs can use to develop their educational programs. As pathologists continue to expand their roles to include regular clinical consultations in the realm of molecular testing, a strong foundation in molecular pathology and genomic medicine has become essential to the practice of pathology. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Multi-scale strategies for dealing with moving contact lines

NASA Astrophysics Data System (ADS)

Smith, Edward R.; Theodorakis, Panagiotis; Craster, Richard V.; Matar, Omar K.

2017-11-01

Molecular dynamics (MD) has great potential to elucidate the dynamics of the moving contact line. As a more fundamental model, it can provide a priori results for fluid-liquid interfaces, surface tension, viscosity, phase change, and near wall stick-slip behaviour which typically show very good agreement to experimental results. However, modelling contact line motion combines all this complexity in a single problem. In this talk, MD simulations of the contact line are compared to the experimental results obtained from studying the dynamics of a sheared liquid bridge. The static contact angles are correctly matched to the experimental data for a range of different electro-wetting results. The moving contact line results are then compared for each of these electro-wetting values. Despite qualitative agreement, there are notable differences between the simulation and experiments. Many MD simulation have studied contact lines, and the sheared liquid bridge, so it is of interest to review the limitations of this setup in light of this discrepancy. A number of factors are discussed, including the inter-molecular interaction model, molecular-scale surface roughness, model of electro-wetting and, perhaps most importantly, the limited system sizes possible using MD simulation. EPSRC, UK, MEMPHIS program Grant (EP/K003976/1), RAEng Research Chair (OKM).

Programming with models: modularity and abstraction provide powerful capabilities for systems biology

PubMed Central

Mallavarapu, Aneil; Thomson, Matthew; Ullian, Benjamin; Gunawardena, Jeremy

2008-01-01

Mathematical models are increasingly used to understand how phenotypes emerge from systems of molecular interactions. However, their current construction as monolithic sets of equations presents a fundamental barrier to progress. Overcoming this requires modularity, enabling sub-systems to be specified independently and combined incrementally, and abstraction, enabling generic properties of biological processes to be specified independently of specific instances. These, in turn, require models to be represented as programs rather than as datatypes. Programmable modularity and abstraction enables libraries of modules to be created, which can be instantiated and reused repeatedly in different contexts with different components. We have developed a computational infrastructure that accomplishes this. We show here why such capabilities are needed, what is required to implement them and what can be accomplished with them that could not be done previously. PMID:18647734

Programming with models: modularity and abstraction provide powerful capabilities for systems biology.

PubMed

Mallavarapu, Aneil; Thomson, Matthew; Ullian, Benjamin; Gunawardena, Jeremy

2009-03-06

Mathematical models are increasingly used to understand how phenotypes emerge from systems of molecular interactions. However, their current construction as monolithic sets of equations presents a fundamental barrier to progress. Overcoming this requires modularity, enabling sub-systems to be specified independently and combined incrementally, and abstraction, enabling generic properties of biological processes to be specified independently of specific instances. These, in turn, require models to be represented as programs rather than as datatypes. Programmable modularity and abstraction enables libraries of modules to be created, which can be instantiated and reused repeatedly in different contexts with different components. We have developed a computational infrastructure that accomplishes this. We show here why such capabilities are needed, what is required to implement them and what can be accomplished with them that could not be done previously.

Treatment Algorithms Based on Tumor Molecular Profiling: The Essence of Precision Medicine Trials.

PubMed

Le Tourneau, Christophe; Kamal, Maud; Tsimberidou, Apostolia-Maria; Bedard, Philippe; Pierron, Gaëlle; Callens, Céline; Rouleau, Etienne; Vincent-Salomon, Anne; Servant, Nicolas; Alt, Marie; Rouzier, Roman; Paoletti, Xavier; Delattre, Olivier; Bièche, Ivan

2016-04-01

With the advent of high-throughput molecular technologies, several precision medicine (PM) studies are currently ongoing that include molecular screening programs and PM clinical trials. Molecular profiling programs establish the molecular profile of patients' tumors with the aim to guide therapy based on identified molecular alterations. The aim of prospective PM clinical trials is to assess the clinical utility of tumor molecular profiling and to determine whether treatment selection based on molecular alterations produces superior outcomes compared with unselected treatment. These trials use treatment algorithms to assign patients to specific targeted therapies based on tumor molecular alterations. These algorithms should be governed by fixed rules to ensure standardization and reproducibility. Here, we summarize key molecular, biological, and technical criteria that, in our view, should be addressed when establishing treatment algorithms based on tumor molecular profiling for PM trials. © The Author 2015. Published by Oxford University Press.

Research on Spectroscopy, Opacity, and Atmospheres

NASA Technical Reports Server (NTRS)

Kurucz, Robert L.

1999-01-01

A web site has been set up to make the calculations accessible; (i.e., cfakus.harvard.edu) This data can also be accessed by FTP. It has all of the atomic and diatomic molecular data, tables of distribution function opacities, grids of model atmospheres, colors, fluxes, etc, programs that are ready for distribution, and most of recent papers developed during this grant. Atlases and computed spectra will be added as they are completed. New atomic and molecular calculations will be added as they are completed. The atomic programs that had been running on a Cray at the San Diego Supercomputer Center can now run on the Vaxes and Alpha. The work started with Ni and Co because there were new laboratory analyses that included isotopic and hyperfine splitting. Those calculations are described in the appended abstract for the 6th Atomic Spectroscopy and oscillator Strengths meeting in Victoria last summer. A surprising finding is that quadrupole transitions have been grossly in error because mixing with higher levels has not been included. All levels up through n=9 for Fe I and II, the spectra for which the most information is available, are now included. After Fe I and Fe II, all other spectra are "easy". ATLAS12, the opacity sampling program for computing models with arbitrary abundances, has been put on the web server. A new distribution function opacity program for workstations that replaces the one used on the Cray at the San Diego Supercomputer Center has been written. Each set of abundances would take 100 Cray hours costing $100,000.

Calculation of diagnostic parameters of advanced serological and molecular tissue-print methods for detection of Citrus tristeza virus. A model for other plant pathogens

USDA-ARS?s Scientific Manuscript database

Citrus tristeza virus (CTV) is one of the most important virus diseases which affect citrus. Control of CTV in Spain and central California is achieved by planting virus-free citrus on CTV-tolerant or -resistant rootstocks. Quarantine and certification programs remain essential to avoid importation ...

Annual Progress Report, FY 1980, 1 October 1979 - 30 September 1980,

DTIC Science & Technology

1980-10-01

coordinating an integrated pest management program, and constructing initial pilot prototypes, test models, and pro- ducing limited quantities of medical...Screening Test Based on the Ventilatory Responses of Fish . . . . . . . a & a . . . . 25 Chemistry and Molecular Biology of the Disinfection Process...Sink Unit, Surgical, Field (NSN 6545-00-935-4056), Engineering Evaluation of . . . . . . . . . . . . . . . . . . 69 Technical Feasibility Testing (TFT

A Case Study of the Introduction of RISC-based Computing and a Telecommunications Link to a Suburban High School.

ERIC Educational Resources Information Center

Hakerem, Gita; And Others

This study reports the efforts of the Water and Molecular Networks Project (WAMNet), a program in which high school chemistry students use computer simulations developed at Boston University (Massachusetts) to model the three-dimensional structure of molecules and the hydrogen bond network that holds water molecules together. This case study…

Applications of genetic programming in cancer research.

PubMed

Worzel, William P; Yu, Jianjun; Almal, Arpit A; Chinnaiyan, Arul M

2009-02-01

The theory of Darwinian evolution is the fundamental keystones of modern biology. Late in the last century, computer scientists began adapting its principles, in particular natural selection, to complex computational challenges, leading to the emergence of evolutionary algorithms. The conceptual model of selective pressure and recombination in evolutionary algorithms allow scientists to efficiently search high dimensional space for solutions to complex problems. In the last decade, genetic programming has been developed and extensively applied for analysis of molecular data to classify cancer subtypes and characterize the mechanisms of cancer pathogenesis and development. This article reviews current successes using genetic programming and discusses its potential impact in cancer research and treatment in the near future.

Models@Home: distributed computing in bioinformatics using a screensaver based approach.

PubMed

Krieger, Elmar; Vriend, Gert

2002-02-01

Due to the steadily growing computational demands in bioinformatics and related scientific disciplines, one is forced to make optimal use of the available resources. A straightforward solution is to build a network of idle computers and let each of them work on a small piece of a scientific challenge, as done by Seti@Home (http://setiathome.berkeley.edu), the world's largest distributed computing project. We developed a generally applicable distributed computing solution that uses a screensaver system similar to Seti@Home. The software exploits the coarse-grained nature of typical bioinformatics projects. Three major considerations for the design were: (1) often, many different programs are needed, while the time is lacking to parallelize them. Models@Home can run any program in parallel without modifications to the source code; (2) in contrast to the Seti project, bioinformatics applications are normally more sensitive to lost jobs. Models@Home therefore includes stringent control over job scheduling; (3) to allow use in heterogeneous environments, Linux and Windows based workstations can be combined with dedicated PCs to build a homogeneous cluster. We present three practical applications of Models@Home, running the modeling programs WHAT IF and YASARA on 30 PCs: force field parameterization, molecular dynamics docking, and database maintenance.

Molecular Mechanisms Modulating the Phenotype of Macrophages and Microglia

PubMed Central

Amici, Stephanie A.; Dong, Joycelyn; Guerau-de-Arellano, Mireia

2017-01-01

Macrophages and microglia play crucial roles during central nervous system development, homeostasis and acute events such as infection or injury. The diverse functions of tissue macrophages and microglia are mirrored by equally diverse phenotypes. A model of inflammatory/M1 versus a resolution phase/M2 macrophages has been widely used. However, the complexity of macrophage function can only be achieved by the existence of varied, plastic and tridimensional macrophage phenotypes. Understanding how tissue macrophages integrate environmental signals via molecular programs to define pathogen/injury inflammatory responses provides an opportunity to better understand the multilayered nature of macrophages, as well as target and modulate cellular programs to control excessive inflammation. This is particularly important in MS and other neuroinflammatory diseases, where chronic inflammatory macrophage and microglial responses may contribute to pathology. Here, we perform a comprehensive review of our current understanding of how molecular pathways modulate tissue macrophage phenotype, covering both classic pathways and the emerging role of microRNAs, receptor-tyrosine kinases and metabolism in macrophage phenotype. In addition, we discuss pathway parallels in microglia, novel markers helpful in the identification of peripheral macrophages versus microglia and markers linked to their phenotype. PMID:29176977

Molecular pathogenesis of emphysema

PubMed Central

Taraseviciene-Stewart, Laimute; Voelkel, Norbert F.

2008-01-01

Emphysema is one manifestation of a group of chronic, obstructive, and frequently progressive destructive lung diseases. Cigarette smoking and air pollution are the main causes of emphysema in humans, and cigarette smoking causes emphysema in rodents. This review examines the concept of a homeostatically active lung structure maintenance program that, when attacked by proteases and oxidants, leads to the loss of alveolar septal cells and airspace enlargement. Inflammatory and noninflammatory mechanisms of disease pathogenesis, as well as the role of the innate and adaptive immune systems, are being explored in genetically altered animals and in exposure models of this disease. These recent scientific advances support a model whereby alveolar destruction resulting from a coalescence of mechanical forces, such as hyperinflation, and more recently recognized cellular and molecular events, including apoptosis, cellular senescence, and failed lung tissue repair, produces the clinically recognized syndrome of emphysema. PMID:18246188

Rosetta3: An Object-Oriented Software Suite for the Simulation and Design of Macromolecules

PubMed Central

Leaver-Fay, Andrew; Tyka, Michael; Lewis, Steven M.; Lange, Oliver F.; Thompson, James; Jacak, Ron; Kaufman, Kristian; Renfrew, P. Douglas; Smith, Colin A.; Sheffler, Will; Davis, Ian W.; Cooper, Seth; Treuille, Adrien; Mandell, Daniel J.; Richter, Florian; Ban, Yih-En Andrew; Fleishman, Sarel J.; Corn, Jacob E.; Kim, David E.; Lyskov, Sergey; Berrondo, Monica; Mentzer, Stuart; Popović, Zoran; Havranek, James J.; Karanicolas, John; Das, Rhiju; Meiler, Jens; Kortemme, Tanja; Gray, Jeffrey J.; Kuhlman, Brian; Baker, David; Bradley, Philip

2013-01-01

We have recently completed a full re-architecturing of the Rosetta molecular modeling program, generalizing and expanding its existing functionality. The new architecture enables the rapid prototyping of novel protocols by providing easy to use interfaces to powerful tools for molecular modeling. The source code of this rearchitecturing has been released as Rosetta3 and is freely available for academic use. At the time of its release, it contained 470,000 lines of code. Counting currently unpublished protocols at the time of this writing, the source includes 1,285,000 lines. Its rapid growth is a testament to its ease of use. This document describes the requirements for our new architecture, justifies the design decisions, sketches out central classes, and highlights a few of the common tasks that the new software can perform. PMID:21187238

ReaDDy - A Software for Particle-Based Reaction-Diffusion Dynamics in Crowded Cellular Environments

PubMed Central

Schöneberg, Johannes; Noé, Frank

2013-01-01

We introduce the software package ReaDDy for simulation of detailed spatiotemporal mechanisms of dynamical processes in the cell, based on reaction-diffusion dynamics with particle resolution. In contrast to other particle-based reaction kinetics programs, ReaDDy supports particle interaction potentials. This permits effects such as space exclusion, molecular crowding and aggregation to be modeled. The biomolecules simulated can be represented as a sphere, or as a more complex geometry such as a domain structure or polymer chain. ReaDDy bridges the gap between small-scale but highly detailed molecular dynamics or Brownian dynamics simulations and large-scale but little-detailed reaction kinetics simulations. ReaDDy has a modular design that enables the exchange of the computing core by efficient platform-specific implementations or dynamical models that are different from Brownian dynamics. PMID:24040218

77 FR 40072 - Assessment of the Program for Enhanced Review Transparency and Communication for New Molecular...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0603] Assessment of the Program for Enhanced Review Transparency and Communication for New Molecular Entity New... statement of work for an assessment of the Program for Enhanced Review Transparency and Communication for...

From Mice to Men: research models of developmental programming

PubMed Central

Rabadán-Diehl, C.; Nathanielsz, P.

2012-01-01

Developmental programming can be defined as a response to a specific challenge to the mammalian organism during a critical developmental time window that alters the trajectory of development with persistent effects on offspring phenotype and predisposition to future illness. We focus on the need for studies in relevant, well-characterized animal models in the context of recent research discoveries on the challenges, mechanisms and outcomes of developmental programming. We discuss commonalities and differences in general principles of developmental programming as they apply to several species, including humans. The consequences of these differences are discussed. Obesity, metabolic disorders and cardiovascular diseases are associated with the highest percentage of morbidity and mortality worldwide. Although many of the causes are associated with lifestyle, high-energy diets and lack of physical activity, recent evidence has linked developmental programming to the epidemic of metabolic diseases. A better understanding of comparative systems physiology of mother, fetus and neonate using information provided by rapid advances in molecular biology has the potential to improve the lifetime health of future generations by providing better women’s health, diagnostic tools and preventative and therapeutic interventions in individuals exposed during their development to programming influences. PMID:23525085

Potential energy hypersurface and molecular flexibility

NASA Astrophysics Data System (ADS)

Koča, Jaroslav

1993-02-01

The molecular flexibility phenomenon is discussed from the conformational potential energy(hyper) surface (PES) point of view. Flexibility is considered as a product of three terms: thermodynamic, kinetic and geometrical. Several expressions characterizing absolute and relative molecular flexibility are introduced, depending on a subspace studied of the entire conformational space, energy level E of PES as well as absolute temperature. Results obtained by programs DAISY, CICADA and PANIC in conjunction with molecular mechanics program MMX for flexibility analysis of isopentane, 2,2-dimethylpentane and isohexane molecules are introduced.

Quantum chemical approach for condensed-phase thermochemistry (V): Development of rigid-body type harmonic solvation model

NASA Astrophysics Data System (ADS)

Tarumi, Moto; Nakai, Hiromi

2018-05-01

This letter proposes an approximate treatment of the harmonic solvation model (HSM) assuming the solute to be a rigid body (RB-HSM). The HSM method can appropriately estimate the Gibbs free energy for condensed phases even where an ideal gas model used by standard quantum chemical programs fails. The RB-HSM method eliminates calculations for intra-molecular vibrations in order to reduce the computational costs. Numerical assessments indicated that the RB-HSM method can evaluate entropies and internal energies with the same accuracy as the HSM method but with lower calculation costs.

Molecular model of cannabis sensitivity in developing neuronal circuits

PubMed Central

Keimpema, Erik; Mackie, Ken; Harkany, Tibor

2011-01-01

Prenatal cannabis exposure can complicate in utero development of the nervous system. Cannabis impacts the formation and functions of neuronal circuitries by targeting cannabinoid receptors. Endocannabinoid signaling emerges as a signaling cassette to orchestrate neuronal differentiation programs through the precisely timed interaction of endocannabinoid ligands with their cognate cannabinoid receptors. By indiscriminately prolonging the ‘switched-on’ period of cannabinoid receptors, cannabis can hijack endocannabinoid signals to evoke molecular rearrangements, leading to the erroneous wiring of neuronal networks. Here, we formulate a hierarchical network design necessary and sufficient to describe molecular underpinnings of cannabis-induced neural growth defects. We integrate signalosome components deduced from genome- and proteome-wide arrays and candidate analyses to propose a mechanistic hypothesis on how cannabis-induced ectopic cannabinoid receptor activity overrides physiological neurodevelopmental endocannabinoid signals, affecting the timely formation of synapses. PMID:21757242

SMMP v. 3.0—Simulating proteins and protein interactions in Python and Fortran

NASA Astrophysics Data System (ADS)

Meinke, Jan H.; Mohanty, Sandipan; Eisenmenger, Frank; Hansmann, Ulrich H. E.

2008-03-01

We describe a revised and updated version of the program package SMMP. SMMP is an open-source FORTRAN package for molecular simulation of proteins within the standard geometry model. It is designed as a simple and inexpensive tool for researchers and students to become familiar with protein simulation techniques. SMMP 3.0 sports a revised API increasing its flexibility, an implementation of the Lund force field, multi-molecule simulations, a parallel implementation of the energy function, Python bindings, and more. Program summaryTitle of program:SMMP Catalogue identifier:ADOJ_v3_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADOJ_v3_0.html Program obtainable from: CPC Program Library, Queen's University of Belfast, N. Ireland Licensing provisions:Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html Programming language used:FORTRAN, Python No. of lines in distributed program, including test data, etc.:52 105 No. of bytes in distributed program, including test data, etc.:599 150 Distribution format:tar.gz Computer:Platform independent Operating system:OS independent RAM:2 Mbytes Classification:3 Does the new version supersede the previous version?:Yes Nature of problem:Molecular mechanics computations and Monte Carlo simulation of proteins. Solution method:Utilizes ECEPP2/3, FLEX, and Lund potentials. Includes Monte Carlo simulation algorithms for canonical, as well as for generalized ensembles. Reasons for new version:API changes and increased functionality. Summary of revisions:Added Lund potential; parameters used in subroutines are now passed as arguments; multi-molecule simulations; parallelized energy calculation for ECEPP; Python bindings. Restrictions:The consumed CPU time increases with the size of protein molecule. Running time:Depends on the size of the simulated molecule.

First Detection of Near-infrared Line Emission from Organics in Young Circumstellar Disks

NASA Astrophysics Data System (ADS)

Mandell, Avi M.; Bast, Jeanette; van Dishoeck, Ewine F.; Blake, Geoffrey A.; Salyk, Colette; Mumma, Michael J.; Villanueva, Geronimo

2012-03-01

We present an analysis of high-resolution spectroscopy of several bright T Tauri stars using the CRIRES spectrograph on the Very Large Telescope and NIRSPEC spectrograph on the Keck Telescope, revealing the first detections of emission from HCN and C2H2 in circumstellar disks at near-infrared wavelengths. Using advanced data reduction techniques, we achieve a dynamic range with respect to the disk continuum of ~500 at 3 μm, revealing multiple emission features of H2O, OH, HCN, and C2H2. We also present stringent upper limits for two other molecules thought to be abundant in the inner disk, CH4 and NH3. Line profiles for the different detected molecules are broad but centrally peaked in most cases, even for disks with previously determined inclinations of greater than 20°, suggesting that the emission has both a Keplerian and non-Keplerian component as observed previously for CO emission. We apply two different modeling strategies to constrain the molecular abundances and temperatures: we use a simplified single-temperature local thermal equilibrium (LTE) slab model with a Gaussian line profile to make line identifications and determine a best-fit temperature and initial abundance ratios, and we compare these values with constraints derived from a detailed disk radiative transfer model assuming LTE excitation but utilizing a realistic temperature and density structure. Abundance ratios from both sets of models are consistent with each other and consistent with expected values from theoretical chemical models, and analysis of the line shapes suggests that the molecular emission originates from within a narrow region in the inner disk (R < 1 AU). Based partially on observations collected at the European Southern Observatory Very Large Telescope under program ID 179.C-0151, program ID 283.C-5016, and program ID 082.C-0432 (P.I.: Pontopiddan).

High Molecular Weight Polymers in the New Chemicals Program

EPA Pesticide Factsheets

There are three categories or types of High Molecular Weight (HMW, 10,000 daltons) polymers typically reviewed by the New Chemicals Program: Soluble, insoluble, and water absorbing. Each of the three types are treated differently.

A Simple Huckel Molecular Orbital Plotter

ERIC Educational Resources Information Center

Ramakrishnan, Raghunathan

2013-01-01

A program is described and presented to readily plot the molecular orbitals from a Huckel calculation. The main features of the program and the scope of its applicability are discussed through some example organic molecules. (Contains 2 figures.)

ProbeZT: Simulation of transport coefficients of molecular electronic junctions under environmental effects using Büttiker's probes

NASA Astrophysics Data System (ADS)

Korol, Roman; Kilgour, Michael; Segal, Dvira

2018-03-01

We present our in-house quantum transport package, ProbeZT. This program provides linear response coefficients: electrical and electronic thermal conductances, as well as the thermopower of molecular junctions in which electrons interact with the surrounding thermal environment. Calculations are performed based on the Büttiker probe method, which introduces decoherence, energy exchange and dissipation effects phenomenologically using virtual electrode terminals called probes. The program can realize different types of probes, each introducing various environmental effects, including elastic and inelastic scattering of electrons. The molecular system is described by an arbitrary tight-binding Hamiltonian, allowing the study of different geometries beyond simple one-dimensional wires. Applications of the program to study the thermoelectric performance of molecular junctions are illustrated. The program also has a built-in functionality to simulate electron transport in double-stranded DNA molecules based on a tight-binding (ladder) description of the junction.

Use of Mutated Self-Cleaving 2A Peptides as a Molecular Rheostat to Direct Simultaneous Formation of Membrane and Secreted Anti-HIV Immunoglobulins

PubMed Central

Yu, Kenneth K.; Aguilar, Kiefer; Tsai, Jonathan; Galimidi, Rachel; Gnanapragasam, Priyanthi; Yang, Lili; Baltimore, David

2012-01-01

In nature, B cells produce surface immunoglobulin and secreted antibody from the same immunoglobulin gene via alternative splicing of the pre-messenger RNA. Here we present a novel system for genetically programming B cells to direct the simultaneous formation of membrane-bound and secreted immunoglobulins that we term a “Molecular Rheostat”, based on the use of mutated “self-cleaving” 2A peptides. The Molecular Rheostat is designed so that the ratio of secreted to membrane-bound immunoglobulins can be controlled by selecting appropriate mutations in the 2A peptide. Lentiviral transgenesis of Molecular Rheostat constructs into B cell lines enables the simultaneous expression of functional b12-based IgM-like BCRs that signal to the cells and mediate the secretion of b12 IgG broadly neutralizing antibodies that can bind and neutralize HIV-1 pseudovirus. We show that these b12-based Molecular Rheostat constructs promote the maturation of EU12 B cells in an in vitro model of B lymphopoiesis. The Molecular Rheostat offers a novel tool for genetically manipulating B cell specificity for B-cell based gene therapy. PMID:23209743

A Selected Library of Transport Coefficients for Combustion and Plasma Physics Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cloutman, L.D.

2000-08-01

COYOTE and similar combustion programs based on the multicomponent Navier-Stokes equations require the mixture viscosity, thermal conductivity, and species transport coefficients as input. This report documents a model of these molecular transport coefficients that is simpler than the general theory, but which provides adequate accuracy for many purposes. This model leads to a computationally convenient, self-contained, and easy-to-use source of such data in a format suitable for use by such programs. We present the data for various neutral species in two forms. The first form is a simple functional fit to the transport coefficients. The second form is the usemore » of tabulated Lennard-Jones parameters in simple theoretical expressions for the gas-phase transport coefficients. The model then is extended to the case of a two-temperature plasma. Lennard-Jones parameters are given for a number of chemical species of interest in combustion research.« less

Solvation Structure and Thermodynamic Mapping (SSTMap): An Open-Source, Flexible Package for the Analysis of Water in Molecular Dynamics Trajectories.

PubMed

Haider, Kamran; Cruz, Anthony; Ramsey, Steven; Gilson, Michael K; Kurtzman, Tom

2018-01-09

We have developed SSTMap, a software package for mapping structural and thermodynamic water properties in molecular dynamics trajectories. The package introduces automated analysis and mapping of local measures of frustration and enhancement of water structure. The thermodynamic calculations are based on Inhomogeneous Fluid Solvation Theory (IST), which is implemented using both site-based and grid-based approaches. The package also extends the applicability of solvation analysis calculations to multiple molecular dynamics (MD) simulation programs by using existing cross-platform tools for parsing MD parameter and trajectory files. SSTMap is implemented in Python and contains both command-line tools and a Python module to facilitate flexibility in setting up calculations and for automated generation of large data sets involving analysis of multiple solutes. Output is generated in formats compatible with popular Python data science packages. This tool will be used by the molecular modeling community for computational analysis of water in problems of biophysical interest such as ligand binding and protein function.

Molecular diagnostics of Galactic star-formation regions

NASA Astrophysics Data System (ADS)

Loenen, Edo; Baan, Willem; Spaans, Marco

2007-10-01

We propose a sensitive spectral survey of Galactic star-formation regions. Using the broadband correlator at two different frequencies, we expect to detect the (1-0) transition of CO, CN, HNC, HCN, HCO+, and HCO and various of their isotopes lines, as well as the (12-11) and (10-9) transitions of HC3N. The purpose of these observations is to create a consistent (public) database of molecular emission from galactic star-formation regions. The data will be interpreted using extensive physical and chemical modeling of the whole ensemble of lines, in order to get an accurate description of the molecular environment of these regions. In particular, this diagnostic approach will describe the optical depths, the densities, and the radiation fields in the medium and will allow the establishment of dominant temperature gradients. These observations are part of a program to study molecular emission on all scales, going from individual Galactic star-formation regions, through resolved nearby galaxies, to unresolved extra-galactic emission.

A machine learning approach to computer-aided molecular design

NASA Astrophysics Data System (ADS)

Bolis, Giorgio; Di Pace, Luigi; Fabrocini, Filippo

1991-12-01

Preliminary results of a machine learning application concerning computer-aided molecular design applied to drug discovery are presented. The artificial intelligence techniques of machine learning use a sample of active and inactive compounds, which is viewed as a set of positive and negative examples, to allow the induction of a molecular model characterizing the interaction between the compounds and a target molecule. The algorithm is based on a twofold phase. In the first one — the specialization step — the program identifies a number of active/inactive pairs of compounds which appear to be the most useful in order to make the learning process as effective as possible and generates a dictionary of molecular fragments, deemed to be responsible for the activity of the compounds. In the second phase — the generalization step — the fragments thus generated are combined and generalized in order to select the most plausible hypothesis with respect to the sample of compounds. A knowledge base concerning physical and chemical properties is utilized during the inductive process.

VLTI/AMBER spectro-interferometric imaging of VX Sagittarii's inhomogenous outer atmosphere

NASA Astrophysics Data System (ADS)

Chiavassa, A.; Lacour, S.; Millour, F.; Driebe, T.; Wittkowski, M.; Plez, B.; Thiébaut, E.; Josselin, E.; Freytag, B.; Scholz, M.; Haubois, X.

2010-02-01

Aims: We aim to explore the photosphere of the very cool late-type star VX Sgr and in particular the characterization of molecular layers above the continuum forming photosphere. Methods: We obtained interferometric observations with the VLTI/AMBER interferometer using the fringe tracker FINITO in the spectral domain 1.45-2.50 μm with a spectral resolution of ≈35 and baselines ranging from 15 to 88 m. We performed independent image reconstruction for different wavelength bins and fit the interferometric data with a geometrical toy model. We also compared the data to 1D dynamical models of Miras atmosphere and to 3D hydrodynamical simulations of red supergiant (RSG) and asymptotic giant branch (AGB) stars. Results: Reconstructed images and visibilities show a strong wavelength dependence. The H-band images display two bright spots whose positions are confirmed by the geometrical toy model. The inhomogeneities are qualitatively predicted by 3D simulations. At ≈2.00 μm and in the region 2.35-2.50 μm, the photosphere appears extended and the radius is larger than in the H band. In this spectral region, the geometrical toy model locates a third bright spot outside the photosphere that can be a feature of the molecular layers. The wavelength dependence of the visibility can be qualitatively explained by 1D dynamical models of Mira atmospheres. The best-fitting photospheric models show a good match with the observed visibilities and give a photospheric diameter of Theta=8.82 ± 0.50 mas. The H2O molecule seems to be the dominant absorber in the molecular layers. Conclusions: We show that the atmosphere of VX Sgr seems to resemble Mira/AGB star model atmospheres more closely than do RSG model atmospheres. In particular, we see molecular (water) layers that are typical of Mira stars. Based on the observations made with VLTI-ESO Paranal, Chile under the programs IDs 081.D-0005(A, B, C, D, E, F, G, H).

Orientation distribution and process modeling of thermotropic liquid crystalline copolyester (TLCP) injection-moldings

NASA Astrophysics Data System (ADS)

Bubeck, Robert; Fang, Jun; Burghardt, Wesley; Burgard, Susan; Fischer, Daniel

2009-03-01

The influence of melt processing conditions upon mechanical properties and degrees of compound molecular orientation have been thoroughly studied for a series of well-defined injection molded samples fabricated from VECTRA (TM) A950 and 4,4'-dihydroxy-a-methylstilbene TLCPs. Fracture and tensile data were correlated with processing conditions, orientation, and molecular weight. Mechanical properties for both TLCPs were found to follow a ``universal'' Anisotropy Factor (AF) associated with the bimodal orientation states in the plaques determined from 2-D WAXS. Surface orientations were globally surveyed using Attenuated Total Reflectance -- Fourier Transform Infrared (ATR-FTIR) spectroscopy and C K edge Near-Edge X-ray Absorption Fine Structure (NEXAFS). The results derived from the two spectroscopy techniques confirmed each other well. These results along with those from 2-D WAXS in transmission were compared with the results of process modeling using a commercial program, MOLDFLOW(TM). The agreement between model predictions and the measured orientation states was gratifyingly good.

Results from the Biology Concept Inventory (BCI), and what they mean for biogeoscience literacy.

NASA Astrophysics Data System (ADS)

Garvin-Doxas, K.; Klymkowsky, M.

2008-12-01

While researching the Biology Concept Inventory (BCI) we found that a wide class of student difficulties in genetics and molecular biology can be traced to deep-seated misconceptions about random processes and molecular interactions. Students believe that random processes are inefficient, while biological systems are very efficient, and are therefore quick to propose their own rational explanations for various processes (from diffusion to evolution). These rational explanations almost always make recourse to a driver (natural selection in genetics, or density gradients in molecular biology) with the process only taking place when the driver is present. The concept of underlying random processes that are taking place all the time giving rise to emergent behaviour is almost totally absent. Even students who have advanced or college physics, and can discuss diffusion correctly in that context, cannot make the transfer to biological processes. Furthermore, their understanding of molecular interactions is purely geometric, with a lock-and-key model (rather than an energy minimization model) that does not allow for the survival of slight variations of the "correct" molecule. Together with the dominant misconception about random processes, this results in a strong conceptual barrier in understanding evolutionary processes, and can frustrate the success of education programs.

An autonomous molecular computer for logical control of gene expression.

PubMed

Benenson, Yaakov; Gil, Binyamin; Ben-Dor, Uri; Adar, Rivka; Shapiro, Ehud

2004-05-27

Early biomolecular computer research focused on laboratory-scale, human-operated computers for complex computational problems. Recently, simple molecular-scale autonomous programmable computers were demonstrated allowing both input and output information to be in molecular form. Such computers, using biological molecules as input data and biologically active molecules as outputs, could produce a system for 'logical' control of biological processes. Here we describe an autonomous biomolecular computer that, at least in vitro, logically analyses the levels of messenger RNA species, and in response produces a molecule capable of affecting levels of gene expression. The computer operates at a concentration of close to a trillion computers per microlitre and consists of three programmable modules: a computation module, that is, a stochastic molecular automaton; an input module, by which specific mRNA levels or point mutations regulate software molecule concentrations, and hence automaton transition probabilities; and an output module, capable of controlled release of a short single-stranded DNA molecule. This approach might be applied in vivo to biochemical sensing, genetic engineering and even medical diagnosis and treatment. As a proof of principle we programmed the computer to identify and analyse mRNA of disease-related genes associated with models of small-cell lung cancer and prostate cancer, and to produce a single-stranded DNA molecule modelled after an anticancer drug.

MCPB.py: A Python Based Metal Center Parameter Builder.

PubMed

Li, Pengfei; Merz, Kenneth M

2016-04-25

MCPB.py, a python based metal center parameter builder, has been developed to build force fields for the simulation of metal complexes employing the bonded model approach. It has an optimized code structure, with far fewer required steps than the previous developed MCPB program. It supports various AMBER force fields and more than 80 metal ions. A series of parametrization schemes to derive force constants and charge parameters are available within the program. We give two examples (one metalloprotein example and one organometallic compound example), indicating the program's ability to build reliable force fields for different metal ion containing complexes. The original version was released with AmberTools15. It is provided via the GNU General Public License v3.0 (GNU_GPL_v3) agreement and is free to download and distribute. MCPB.py provides a bridge between quantum mechanical calculations and molecular dynamics simulation software packages thereby enabling the modeling of metal ion centers. It offers an entry into simulating metal ions in a number of situations by providing an efficient way for researchers to handle the vagaries and difficulties associated with metal ion modeling.

Peptoid Backbone Flexibilility Dictates Its Interaction with Water and Surfaces: A Molecular Dynamics Investigation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prakash, Arushi; Baer, Marcel D.; Mundy, Christopher J.

Peptoids are peptide-mimetic biopolymers that are easy-to-synthesize and adaptable for use in drugs, chemical scaffolds, and coatings. However, there is insufficient information about their structural preferences and interactions with the environment in various applications. We conducted a study to understand the fundamental differences between peptides and peptoids using molecular dynamics simulations with semi-empirical (PM6) and empirical (AMBER) potentials, in conjunction with metadynamics enhanced sampling. From studies of single molecules in water and on surfaces, we found that sarcosine (model peptoid) is much more flexible than alanine (model peptide) in different environments. However, the sarcosine and alanine interact similarly with amore » hydrophobic or a hydrophilic. Finally, this study highlights the conformational landscape of peptoids and the dominant interactions that drive peptoids towards these conformations. ACKNOWLEDGMENT: MD simulations and manuscript preparation were supported by the MS3 (Materials Synthesis and Simulation Across Scales) Initiative at Pacific Northwest National Laboratory (PNNL), a multi-program national laboratory operated by Battelle for the U.S. Department of Energy. CJM was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences Division of Chemical Sciences, Geosciences, and Biosciences. MDB was supported by the US Department of Energy, Office of Basic Energy Sciences, Biomolecular Materials Program at PNNL. Computing resources were generously allocated by University of Washington's IT department and PNNL's Institutional Computing program. The authors greatly acknowledge conversations with Dr. Kayla Sprenger, Josh Smith, and Dr. Yeneneh Yimer.« less

CADRE-SS, an in Silico Tool for Predicting Skin Sensitization Potential Based on Modeling of Molecular Interactions.

PubMed

Kostal, Jakub; Voutchkova-Kostal, Adelina

2016-01-19

Using computer models to accurately predict toxicity outcomes is considered to be a major challenge. However, state-of-the-art computational chemistry techniques can now be incorporated in predictive models, supported by advances in mechanistic toxicology and the exponential growth of computing resources witnessed over the past decade. The CADRE (Computer-Aided Discovery and REdesign) platform relies on quantum-mechanical modeling of molecular interactions that represent key biochemical triggers in toxicity pathways. Here, we present an external validation exercise for CADRE-SS, a variant developed to predict the skin sensitization potential of commercial chemicals. CADRE-SS is a hybrid model that evaluates skin permeability using Monte Carlo simulations, assigns reactive centers in a molecule and possible biotransformations via expert rules, and determines reactivity with skin proteins via quantum-mechanical modeling. The results were promising with an overall very good concordance of 93% between experimental and predicted values. Comparison to performance metrics yielded by other tools available for this endpoint suggests that CADRE-SS offers distinct advantages for first-round screenings of chemicals and could be used as an in silico alternative to animal tests where permissible by legislative programs.

QSPR models of n-octanol/water partition coefficients and aqueous solubility of halogenated methyl-phenyl ethers by DFT method.

PubMed

Zeng, Xiao-Lan; Wang, Hong-Jun; Wang, Yan

2012-02-01

The possible molecular geometries of 134 halogenated methyl-phenyl ethers were optimized at B3LYP/6-31G(*) level with Gaussian 98 program. The calculated structural parameters were taken as theoretical descriptors to establish two new novel QSPR models for predicting aqueous solubility (-lgS(w,l)) and n-octanol/water partition coefficient (lgK(ow)) of halogenated methyl-phenyl ethers. The two models achieved in this work both contain three variables: energy of the lowest unoccupied molecular orbital (E(LUMO)), most positive atomic partial charge in molecule (q(+)), and quadrupole moment (Q(yy) or Q(zz)), of which R values are 0.992 and 0.970 respectively, their standard errors of estimate in modeling (SD) are 0.132 and 0.178, respectively. The results of leave-one-out (LOO) cross-validation for training set and validation with external test sets both show that the models obtained exhibited optimum stability and good predictive power. We suggests that two QSPR models derived here can be used to predict S(w,l) and K(ow) accurately for non-tested halogenated methyl-phenyl ethers congeners. Copyright © 2011 Elsevier Ltd. All rights reserved.

Estimating SIT-driven population reduction in the Mediterranean fruit fly, Ceratitis capitata, from sterile mating.

PubMed

Juan-Blasco, M; Sabater-Muñoz, B; Pla, I; Argilés, R; Castañera, P; Jacas, J A; Ibáñez-Gual, M V; Urbaneja, A

2014-04-01

Area-wide sterile insect technique (SIT) programs assume that offspring reduction of the target population correlates with the mating success of the sterile males released. However, there is a lack of monitoring tools to prove the success of these programs in real-time. Field-cage tests were conducted under the environmental conditions of the Mediterranean coast of Spain to estimate: (a) the mating success of sterile Vienna-8 (V8) Ceratitis capitata males using molecular markers and (b) their efficacy to reduce C. capitata populations under six release ratios of wild females to wild males to V8 males (1:0:0, 1:1:0, 1:1:1, 1:1:5, 1:1:10, and 1:1:20). Statistical models were developed to predict: (a) the number of females captured in traps, (b) sperm ID (sterile or not) in spermathecae of the trapped females, and (c) the viable offspring produced, using release ratio and temperature as predictors. The number of females captured was affected by relative humidity. However, its influence in the model was low. Female captures were significantly higher in ratios 1:0:0 compared to ratios where V8 males were released. The proportion of V8 sperm in spermathecae increased with temperature and with the number of V8 males released, but leveled off between ratios 1:1:10 and 1:1:20. In all seasons, except winter (no offspring), viable offspring increased with temperature and was lowest for ratio 1:1:20. For the first time, a strong negative relationship between proportion of V8 sperm detected by molecular tools and C. capitata offspring was established. The models obtained should contribute to enhance the efficacy of SIT programs against this pest.

Effective electron-density map improvement and structure validation on a Linux multi-CPU web cluster: The TB Structural Genomics Consortium Bias Removal Web Service.

PubMed

Reddy, Vinod; Swanson, Stanley M; Segelke, Brent; Kantardjieff, Katherine A; Sacchettini, James C; Rupp, Bernhard

2003-12-01

Anticipating a continuing increase in the number of structures solved by molecular replacement in high-throughput crystallography and drug-discovery programs, a user-friendly web service for automated molecular replacement, map improvement, bias removal and real-space correlation structure validation has been implemented. The service is based on an efficient bias-removal protocol, Shake&wARP, and implemented using EPMR and the CCP4 suite of programs, combined with various shell scripts and Fortran90 routines. The service returns improved maps, converted data files and real-space correlation and B-factor plots. User data are uploaded through a web interface and the CPU-intensive iteration cycles are executed on a low-cost Linux multi-CPU cluster using the Condor job-queuing package. Examples of map improvement at various resolutions are provided and include model completion and reconstruction of absent parts, sequence correction, and ligand validation in drug-target structures.

The Evolution of Interstellar Gas: Massive Stars and the Dispersal of Neutral Material

NASA Technical Reports Server (NTRS)

Federman, Steven R.

2003-01-01

We studied the effects of newly formed O and B stars on their surrounding interstellar material through a combination of observations and theoretical modeling. The observational data came from measurements of absorption seen in the spectra of background, newly formed stars. Particular attention was given to stellar radiation which converts molecular to atomic material. Laboratory data on absorption cross sections relevant to the analysis and interpretation of carbon monoxide formed part of the effort. The grant supported Postdoctoral Fellows, Drs. Min Yan and Yaron Sheffer, and a laboratory technician. Though the students themselves were not supported. one M.S. Thesis and two Ph.D. dissertations from the University of Toledo were based on the research done under the grant. The research accomplished under this grant led directly to other funded programs. An observing proposal to study the chemistry of diffuse molecular clouds in the Large and Small Magellanic Clouds with ESO s Very Large Telescope was another example of a successful outcome of my LTSA program.

DNA Replication Control During Drosophila Development: Insights into the Onset of S Phase, Replication Initiation, and Fork Progression

PubMed Central

Hua, Brian L.; Orr-Weaver, Terry L.

2017-01-01

Proper control of DNA replication is critical to ensure genomic integrity during cell proliferation. In addition, differential regulation of the DNA replication program during development can change gene copy number to influence cell size and gene expression. Drosophila melanogaster serves as a powerful organism to study the developmental control of DNA replication in various cell cycle contexts in a variety of differentiated cell and tissue types. Additionally, Drosophila has provided several developmentally regulated replication models to dissect the molecular mechanisms that underlie replication-based copy number changes in the genome, which include differential underreplication and gene amplification. Here, we review key findings and our current understanding of the developmental control of DNA replication in the contexts of the archetypal replication program as well as of underreplication and differential gene amplification. We focus on the use of these latter two replication systems to delineate many of the molecular mechanisms that underlie the developmental control of replication initiation and fork elongation. PMID:28874453

Frequency analysis of stress relaxation dynamics in model asphalts

NASA Astrophysics Data System (ADS)

Masoori, Mohammad; Greenfield, Michael L.

2014-09-01

Asphalt is an amorphous or semi-crystalline material whose mechanical performance relies on viscoelastic responses to applied strain or stress. Chemical composition and its effect on the viscoelastic properties of model asphalts have been investigated here by computing complex modulus from molecular dynamics simulation results for two different model asphalts whose compositions each resemble the Strategic Highway Research Program AAA-1 asphalt in different ways. For a model system that contains smaller molecules, simulation results for storage and loss modulus at 443 K reach both the low and high frequency scaling limits of the Maxwell model. Results for a model system composed of larger molecules (molecular weights 300-900 g/mol) with longer branches show a quantitatively higher complex modulus that decreases significantly as temperature increases over 400-533 K. Simulation results for its loss modulus approach the low frequency scaling limit of the Maxwell model at only the highest temperature simulated. A Black plot or van Gurp-Palman plot of complex modulus vs. phase angle for the system of larger molecules suggests some overlap among results at different temperatures for less high frequencies, with an interdependence consistent with the empirical Christensen-Anderson-Marasteanu model. Both model asphalts are thermorheologically complex at very high frequencies, where they show a loss peak that appears to be independent of temperature and density.

Model Stellar Atmospheres and Real Stellar Atmospheres and Status of the ATLAS12 Opacity Sampling Program and of New Programs for Rosseland and for Distribution Function Opacity

NASA Technical Reports Server (NTRS)

Kurucz, Robert L.

1996-01-01

I discuss errors in theory and in interpreting observations that are produced by the failure to consider resolution in space, time, and energy. I discuss convection in stellar model atmospheres and in stars. Large errors in abundances are possible such as the factor of ten error in the Li abundance for extreme Population II stars. Finally I discuss the variation of microturbulent velocity with depth, effective temperature, gravity, and abundance. These variations must be dealt with in computing models and grids and in any type of photometric calibration. I have also developed a new opacity-sampling version of my model atmosphere program called ATLAS12. It recognizes more than 1000 atomic and molecular species, each in up to 10 isotopic forms. It can treat all ions of the elements up through Zn and the first 5 ions of heavier elements up through Es. The elemental and isotopic abundances are treated as variables with depth. The fluxes predicted by ATLAS12 are not accurate in intermediate or narrow bandpass intervals because the sample size is too small. A special stripped version of the spectrum synthesis program SYNTHE is used to generate the surface flux for the converged model using the line data on CD-ROMs 1 and 15. ATLAS12 can be used to produce improved models for Am and Ap stars. It should be very useful for investigating diffusion effects in atmospheres. It can be used to model exciting stars for H II regions with abundances consistent with those of the H II region. These programs and line files will be distributed on CD-ROMs.

POLYANA-A tool for the calculation of molecular radial distribution functions based on Molecular Dynamics trajectories

NASA Astrophysics Data System (ADS)

Dimitroulis, Christos; Raptis, Theophanes; Raptis, Vasilios

2015-12-01

We present an application for the calculation of radial distribution functions for molecular centres of mass, based on trajectories generated by molecular simulation methods (Molecular Dynamics, Monte Carlo). When designing this application, the emphasis was placed on ease of use as well as ease of further development. In its current version, the program can read trajectories generated by the well-known DL_POLY package, but it can be easily extended to handle other formats. It is also very easy to 'hack' the program so it can compute intermolecular radial distribution functions for groups of interaction sites rather than whole molecules.

Estimation of maximum tolerated dose for long-term bioassays from acute lethal dose and structure by QSAR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gombar, V.K.; Enslein, K.; Hart, J.B.

1991-09-01

A quantitative structure-activity relationship (QSAR) model has been developed to estimate maximum tolerated doses (MTD) from structural features of chemicals and the corresponding oral acute lethal doses (LD50) as determined in male rats. The model is based on a set of 269 diverse chemicals which have been tested under the National Cancer Institute/National Toxicology Program (NCI/NTP) protocols. The rat oral LD50 value was the strongest predictor. Additionally, 22 structural descriptors comprising nine substructural MOLSTAC(c) keys, three molecular connectivity indices, and sigma charges on 10 molecular fragments were identified as endpoint predictors. The model explains 76% of the variance and ismore » significant (F = 35.7) at p less than 0.0001 with a standard error of the estimate of 0.40 in the log (1/mol) units used in Hansch-type equations. Cross-validation showed that the difference between the average deleted residual square (0.179) and the model residual square (0.160) was not significant (t = 0.98).« less

Evidence for Decay of Turbulence by MHD Shocks in the ISM via CO Emission

NASA Astrophysics Data System (ADS)

Larson, Rebecca L.; Evans, Neal J., II; Green, Joel D.; Yang, Yao-Lun

2015-06-01

We utilize observations of sub-millimeter rotational transitions of CO from a Herschel Cycle 2 open time program (“COPS”, PI: J. Green) to identify previously predicted turbulent dissipation by magnetohydrodynamic (MHD) shocks in molecular clouds. We find evidence of the shocks expected for dissipation of MHD turbulence in material not associated with any protostar. Two models fit about equally well: model 1 has a density of 103 cm-3, a shock velocity of 3 km s-1, and a magnetic field strength of 4 μG model 2 has a density of 103.5 cm-3, a shock velocity of 2 km s-1, and a magnetic field strength of 8 μG. Timescales for decay of turbulence in this region are comparable to crossing times. Transitions of CO up to J of 8, observed close to active sites of star formation, but not within outflows, can trace turbulent dissipation of shocks stirred by formation processes. Although the transitions are difficult to detect at individual positions, our Herschel-SPIRE survey of protostars provides a grid of spatially distributed spectra within molecular clouds. We averaged all spatial positions away from known outflows near seven protostars. We find significant agreement with predictions of models of turbulent dissipation in slightly denser (103.5 cm-3) material with a stronger magnetic field (24 μG) than in the general molecular cloud.

Critical Evaluation of Chemical Reaction Rates and Collision Cross Sections of Importance in the Earth's Upper Atmosphere and the Atmospheres of Other Planets, Moons, and Comets

NASA Technical Reports Server (NTRS)

Huestis, David L.

2006-01-01

We propose to establish a long-term program of critical evaluation by domain experts of the rates and cross sections for atomic and molecular processes that are needed for understanding and modeling the atmospheres in the solar system. We envision data products resembling those of the JPL/NASA Panel for Data Evaluation and the similar efforts of the international combustion modeling community funded by US DoE and its European counterpart.

Use of Laboratory Data to Model Interstellar Chemistry

NASA Technical Reports Server (NTRS)

Vidali, Gianfranco; Roser, J. E.; Manico, G.; Pirronello, V.

2006-01-01

Our laboratory research program is about the formation of molecules on dust grains analogues in conditions mimicking interstellar medium environments. Using surface science techniques, in the last ten years we have investigated the formation of molecular hydrogen and other molecules on different types of dust grain analogues. We analyzed the results to extract quantitative information on the processes of molecule formation on and ejection from dust grain analogues. The usefulness of these data lies in the fact that these results have been employed by theoreticians in models of the chemical evolution of ISM environments.

Reproducing Quantum Probability Distributions at the Speed of Classical Dynamics: A New Approach for Developing Force-Field Functors.

PubMed

Sundar, Vikram; Gelbwaser-Klimovsky, David; Aspuru-Guzik, Alán

2018-04-05

Modeling nuclear quantum effects is required for accurate molecular dynamics (MD) simulations of molecules. The community has paid special attention to water and other biomolecules that show hydrogen bonding. Standard methods of modeling nuclear quantum effects like Ring Polymer Molecular Dynamics (RPMD) are computationally costlier than running classical trajectories. A force-field functor (FFF) is an alternative method that computes an effective force field that replicates quantum properties of the original force field. In this work, we propose an efficient method of computing FFF using the Wigner-Kirkwood expansion. As a test case, we calculate a range of thermodynamic properties of Neon, obtaining the same level of accuracy as RPMD, but with the shorter runtime of classical simulations. By modifying existing MD programs, the proposed method could be used in the future to increase the efficiency and accuracy of MD simulations involving water and proteins.

Quality Assurance Program for Molecular Medicine Laboratories

PubMed Central

Hajia, M; Safadel, N; Samiee, S Mirab; Dahim, P; Anjarani, S; Nafisi, N; Sohrabi, A; Rafiee, M; Sabzavi, F; Entekhabi, B

2013-01-01

Background: Molecular diagnostic methods have played and continuing to have a critical role in clinical laboratories in recent years. Therefore, standardization is an evolutionary process that needs to be upgrade with increasing scientific knowledge, improvement of the instruments and techniques. The aim of this study was to design a quality assurance program in order to have similar conditions for all medical laboratories engaging with molecular tests. Methods: We had to design a plan for all four elements; required space conditions, equipments, training, and basic guidelines. Necessary guidelines was prepared and confirmed by the launched specific committee at the Health Reference Laboratory. Results: Several workshops were also held for medical laboratories directors and staffs, quality control manager of molecular companies, directors and nominees from universities. Accreditation of equipments and molecular material was followed parallel with rest of program. Now we are going to accredit medical laboratories and to evaluate the success of the program. Conclusion: Accreditation of medical laboratory will be succeeding if its basic elements are provided in advance. Professional practice guidelines, holding training and performing accreditation the molecular materials and equipments ensured us that laboratories are aware of best practices, proper interpretation, limitations of techniques, and technical issues. Now, active external auditing can improve the applied laboratory conditions toward the defined standard level. PMID:23865028

Quality assurance program for molecular medicine laboratories.

PubMed

Hajia, M; Safadel, N; Samiee, S Mirab; Dahim, P; Anjarani, S; Nafisi, N; Sohrabi, A; Rafiee, M; Sabzavi, F; Entekhabi, B

2013-01-01

Molecular diagnostic methods have played and continuing to have a critical role in clinical laboratories in recent years. Therefore, standardization is an evolutionary process that needs to be upgrade with increasing scientific knowledge, improvement of the instruments and techniques. The aim of this study was to design a quality assurance program in order to have similar conditions for all medical laboratories engaging with molecular tests. We had to design a plan for all four elements; required space conditions, equipments, training, and basic guidelines. Necessary guidelines was prepared and confirmed by the launched specific committee at the Health Reference Laboratory. Several workshops were also held for medical laboratories directors and staffs, quality control manager of molecular companies, directors and nominees from universities. Accreditation of equipments and molecular material was followed parallel with rest of program. Now we are going to accredit medical laboratories and to evaluate the success of the program. Accreditation of medical laboratory will be succeeding if its basic elements are provided in advance. Professional practice guidelines, holding training and performing accreditation the molecular materials and equipments ensured us that laboratories are aware of best practices, proper interpretation, limitations of techniques, and technical issues. Now, active external auditing can improve the applied laboratory conditions toward the defined standard level.

Slip of grip of a molecular motor on a crowded track: Modeling shift of reading frame of ribosome on RNA template

NASA Astrophysics Data System (ADS)

Mishra, Bhavya; Schütz, Gunter M.; Chowdhury, Debashish

2016-06-01

We develop a stochastic model for the programmed frameshift of ribosomes synthesizing a protein while moving along a mRNA template. Normally the reading frame of a ribosome decodes successive triplets of nucleotides on the mRNA in a step-by-step manner. We focus on the programmed shift of the ribosomal reading frame, forward or backward, by only one nucleotide which results in a fusion protein; it occurs when a ribosome temporarily loses its grip to its mRNA track. Special “slippery” sequences of nucleotides and also downstream secondary structures of the mRNA strand are believed to play key roles in programmed frameshift. Here we explore the role of an hitherto neglected parameter in regulating -1 programmed frameshift. Specifically, we demonstrate that the frameshift frequency can be strongly regulated also by the density of the ribosomes, all of which are engaged in simultaneous translation of the same mRNA, at and around the slippery sequence. Monte Carlo simulations support the analytical predictions obtained from a mean-field analysis of the stochastic dynamics.

Developmental programming of hypothalamic neuronal circuits: impact on energy balance control

PubMed Central

Gali Ramamoorthy, Thanuja; Begum, Ghazala; Harno, Erika; White, Anne

2015-01-01

The prevalence of obesity in adults and children has increased globally at an alarming rate. Mounting evidence from both epidemiological studies and animal models indicates that adult obesity and associated metabolic disorders can be programmed by intrauterine and early postnatal environment- a phenomenon known as “fetal programming of adult disease.” Data from nutritional intervention studies in animals including maternal under- and over-nutrition support the developmental origins of obesity and metabolic syndrome. The hypothalamic neuronal circuits located in the arcuate nucleus controlling appetite and energy expenditure are set early in life and are perturbed by maternal nutritional insults. In this review, we focus on the effects of maternal nutrition in programming permanent changes in these hypothalamic circuits, with experimental evidence from animal models of maternal under- and over-nutrition. We discuss the epigenetic modifications which regulate hypothalamic gene expression as potential molecular mechanisms linking maternal diet during pregnancy to the offspring's risk of obesity at a later age. Understanding these mechanisms in key metabolic genes may provide insights into the development of preventative intervention strategies. PMID:25954145

An undergraduate laboratory activity on molecular dynamics simulations.

PubMed

Spitznagel, Benjamin; Pritchett, Paige R; Messina, Troy C; Goadrich, Mark; Rodriguez, Juan

2016-01-01

Vision and Change [AAAS, 2011] outlines a blueprint for modernizing biology education by addressing conceptual understanding of key concepts, such as the relationship between structure and function. The document also highlights skills necessary for student success in 21st century Biology, such as the use of modeling and simulation. Here we describe a laboratory activity that allows students to investigate the dynamic nature of protein structure and function through the use of a modeling technique known as molecular dynamics (MD). The activity takes place over two lab periods that are 3 hr each. The first lab period unpacks the basic approach behind MD simulations, beginning with the kinematic equations that all bioscience students learn in an introductory physics course. During this period students are taught rudimentary programming skills in Python while guided through simple modeling exercises that lead up to the simulation of the motion of a single atom. In the second lab period students extend concepts learned in the first period to develop skills in the use of expert MD software. Here students simulate and analyze changes in protein conformation resulting from temperature change, solvation, and phosphorylation. The article will describe how these activities can be carried out using free software packages, including Abalone and VMD/NAMD. © 2016 The International Union of Biochemistry and Molecular Biology.

A Combined Experimental and Computational Study on the Stability of Nanofluids Containing Metal Organic Frameworks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Annapureddy, Harsha Vardhan Reddy; Nune, Satish K.; Motkuri, Radha K.

2015-01-08

Computational studies on nanofluids composed of metal organic frameworks (MOFs) were performed using molecular modeling techniques. Grand Canonical Monte Carlo (GCMC) simulations were used to study adsorption behavior of 1,1,1,3,3-pentafluoropropane (R-245fa) in a MIL-101 MOF at various temperatures. To understand the stability of the nanofluid composed of MIL-101 particles, we performed molecular dynamics simulations to compute potentials of mean force between hypothetical MIL-101 fragments terminated with two different kinds of modulators in R-245fa and water. Our computed potentials of mean force results indicate that the MOF particles tend to disperse better in water than in R-245fa. The reasons for thismore » observation were analyzed and discussed. Our results agree with experimental results indicating that the employed potential models and modeling approaches provide good description of molecular interactions and the reliabilities. Work performed by LXD was supported by the U.S. Department of Energy (DOE), Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences, and Biosciences. Work performed by HVRA, SKN, RKM, and PBM was supported by the Office of Energy Efficiency and Renewable Energy, Geothermal Technologies Program. Pacific Northwest National Laboratory is a multiprogram national laboratory operated for DOE by Battelle.« less

Dependence of the rate of LiF ion pairing on the description of molecular interaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pluharova, Eva; Baer, Marcel D.; Schenter, Gregory K.

2016-03-03

We present an analysis of the dynamics of ion-pairing of Lithium Fluoride (LiF) in aqueous solvent using both detailed molecular simulation as well as reduced models within a Gener- alized Langevin Equation (GLE) framework. We explored the sensitivity of the ion-pairing phenomena to the details of descriptions of molecular interaction, comparing two empirical potentials to explicit quantum based density functional theory. We find quantitative differences in the potentials of mean force for ion-pairing as well as time dependent frictions that lead to variations in the rate constant and reactive flux correlation functions. These details reflect differences in solvent response tomore » ion-pairing between different representations of molecular interaction and influence anharmonicity of the dynamic response. We find that the short time anharmonic response is recovered with a GLE parameterization. Recovery of the details of long time response may require extensions to the reduced model. We show that the utility of using a reduced model leads to a straight forward application of variational transition state the- ory concepts to the condensed phase system. The significance of this is reflected in the analysis of committor distributions and the variation of planar hypersurfaces, leading to an improved understanding of factors that determine the rate of LiF ion-pairing. CJM and GKS are supported by the U.S. Department of Energy‘s (DOE) Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences and Biosciences. Pacific Northwest Na- tional Laboratory (PNNL) is operated for the Department of Energy by Battelle. MDB is grateful for the support of Laboratory Directed Research and Development funding under the auspices of PNNL’s Laboratory Initiative Materials Synthesis and Simulation across Scales (MS3). Additional computing resources were generously allocated by PNNL’s Institutional Computing program. EP acknowledges support from PNNL’s Alternate Sponsored Fellowship program and IMPRS Dres- den.Support to P.J. from the Czech Science Foundation (grant P208/12/G016) and the Academy of Sciences (Praemium Academie award) is gratefully acknowledged.« less

RECENT ADVANCES IN MACROMOLECULAR HYDRODYNAMIC MODELING

PubMed Central

Aragon, Sergio R.

2010-01-01

The modern implementation of the boundary element method (S.R. Aragon, J. Comput. Chem. 25(2004)1191–12055) has ushered unprecedented accuracy and precision for the solution of the Stokes equations of hydrodynamics with stick boundary conditions. This article begins by reviewing computations with the program BEST of smooth surface objects such as ellipsoids, the dumbbell, and cylinders that demonstrate that the numerical solution of the integral equation formulation of hydrodynamics yields very high precision and accuracy. When BEST is used for macromolecular computations, the limiting factor becomes the definition of the molecular hydrodynamic surface and the implied effective solvation of the molecular surface. Studies on 49 different proteins, ranging in molecular weight from 9 to over 400 kDa, have shown that a model using a 1.1 A thick hydration layer describes all protein transport properties very well for the overwhelming majority of them. In addition, this data implies that the crystal structure is an excellent representation of the average solution structure for most of them. In order to investigate the origin of a handful of significant discrepancies in some multimeric proteins (over −20% observed in the intrinsic viscosity), the technique of Molecular Dynamics simulation (MD) has been incorporated into the research program. A preliminary study of dimeric α-chymotrypsin using approximate implicit water MD is presented. In addition I describe the successful validation of modern protein force fields, ff03 and ff99SB, for the accurate computation of solution structure in explicit water simulation by comparison of trajectory ensemble average computed transport properties with experimental measurements. This work includes small proteins such as lysozyme, ribonuclease and ubiquitin using trajectories around 10 ns duration. We have also studied a 150 kDa flexible monoclonal IgG antibody, trastuzumab, with multiple independent trajectories encompassing over 320 ns of simulation. The close agreement within experimental error of the computed and measured properties allows us to conclude that MD does produce structures typical of those in solution, and that flexible molecules can be properly described using the method of ensemble averaging over a trajectory. We review similar work on the study of a transfer RNA molecule and DNA oligomers that demonstrate that within 3% a simple uniform hydration model 1.1 A thick provides agreement with experiment for these nucleic acids. In the case of linear oligomers, the precision can be improved close to 1% by a non-uniform hydration model that hydrates mainly in the DNA grooves, in agreement with high resolution x-ray diffraction. We conclude with a vista on planned improvements for the BEST program to decrease its memory requirements and increase its speed without sacrificing accuracy. PMID:21073955

Molecular model of cannabis sensitivity in developing neuronal circuits.

PubMed

Keimpema, Erik; Mackie, Ken; Harkany, Tibor

2011-09-01

Prenatal cannabis exposure can complicate in utero development of the nervous system. Cannabis impacts the formation and functions of neuronal circuitries by targeting cannabinoid receptors. Endocannabinoid signaling emerges as a signaling cassette that orchestrates neuronal differentiation programs through the precisely timed interaction of endocannabinoid ligands with their cognate cannabinoid receptors. By indiscriminately prolonging the 'switched-on' period of cannabinoid receptors, cannabis can hijack endocannabinoid signals to evoke molecular rearrangements, leading to the erroneous wiring of neuronal networks. Here, we formulate a hierarchical network design necessary and sufficient to describe the molecular underpinnings of cannabis-induced neural growth defects. We integrate signalosome components, deduced from genome- and proteome-wide arrays and candidate analyses, to propose a mechanistic hypothesis of how cannabis-induced ectopic cannabinoid receptor activity overrides physiological neurodevelopmental endocannabinoid signals, affecting the timely formation of synapses. Copyright © 2011 Elsevier Ltd. All rights reserved.

Designing of phenol-based β-carbonic anhydrase1 inhibitors through QSAR, molecular docking, and MD simulation approach.

PubMed

Ahamad, Shahzaib; Hassan, Md Imtaiyaz; Dwivedi, Neeraja

2018-05-01

Tuberculosis (Tb) is an airborne infectious disease caused by Mycobacterium tuberculosis. Beta-carbonic anhydrase 1 ( β-CA1 ) has emerged as one of the potential targets for new antitubercular drug development. In this work, three-dimensional quantitative structure-activity relationships (3D-QSAR), molecular docking, and molecular dynamics (MD) simulation approaches were performed on a series of natural and synthetic phenol-based β-CA1 inhibitors. The developed 3D-QSAR model ( r 2  = 0.94, q 2  = 0.86, and pred_r 2  = 0.74) indicated that the steric and electrostatic factors are important parameters to modulate the bioactivity of phenolic compounds. Based on this indication, we designed 72 new phenolic inhibitors, out of which two compounds (D25 and D50) effectively stabilized β-CA1 receptor and, thus, are potential candidates for new generation antitubercular drug discovery program.

Transcriptional and post-transcriptional regulation of NK cell development and function

PubMed Central

Leong, Jeffrey W.; Wagner, Julia A.; Ireland, Aaron R.; Fehniger, Todd A.

2016-01-01

Natural killer (NK) cells are specialized innate lymphoid cells that survey against viral infections and malignancy. Numerous advances have improved our understanding of the molecular mechanisms that control NK cell development and function over the past decade. These include both studies on the regulatory effects of transcription factors and translational repression via microRNAs. In this review, we summarize our current knowledge of DNA-binding transcription factors that regulate gene expression and thereby orchestrate NK cell development and activation, with an emphasis on recent discoveries. Additionally, we highlight our understanding of how RNA-bindings microRNAs fine tune the NK cell molecular program. We also underscore the large number of open questions in field that are now being addressed using new technological approaches and genetically engineered model organisms. Ultimately, a deeper understanding of the basic molecular biology of NK cells will facilitate new strategies to manipulate NK cells for the treatment of human disease. PMID:26948928

KinImmerse: Macromolecular VR for NMR ensembles

PubMed Central

Block, Jeremy N; Zielinski, David J; Chen, Vincent B; Davis, Ian W; Vinson, E Claire; Brady, Rachael; Richardson, Jane S; Richardson, David C

2009-01-01

Background In molecular applications, virtual reality (VR) and immersive virtual environments have generally been used and valued for the visual and interactive experience – to enhance intuition and communicate excitement – rather than as part of the actual research process. In contrast, this work develops a software infrastructure for research use and illustrates such use on a specific case. Methods The Syzygy open-source toolkit for VR software was used to write the KinImmerse program, which translates the molecular capabilities of the kinemage graphics format into software for display and manipulation in the DiVE (Duke immersive Virtual Environment) or other VR system. KinImmerse is supported by the flexible display construction and editing features in the KiNG kinemage viewer and it implements new forms of user interaction in the DiVE. Results In addition to molecular visualizations and navigation, KinImmerse provides a set of research tools for manipulation, identification, co-centering of multiple models, free-form 3D annotation, and output of results. The molecular research test case analyzes the local neighborhood around an individual atom within an ensemble of nuclear magnetic resonance (NMR) models, enabling immersive visual comparison of the local conformation with the local NMR experimental data, including target curves for residual dipolar couplings (RDCs). Conclusion The promise of KinImmerse for production-level molecular research in the DiVE is shown by the locally co-centered RDC visualization developed there, which gave new insights now being pursued in wider data analysis. PMID:19222844

Aerospace Power Scholarly Research Program. Delivery Order 0011: Modeling Lithium-Ion Conducting Channel

DTIC Science & Technology

2005-12-01

Brinkmann, D. NMR, DSC, and conductivity study of a poly (ethylene oxide) complex electrolyte: PEO(LiClO4)x, Sol. St. Ionics 1986, 18-19, 295. (27...Electrochemical Characterizations of Dilithium Octacyanophthalocyanine Langmuir - Blodgett films, Langmuir 2002, 18, 2223. 20 ...phthalocyanine (Li2Pc) has been used in this development since it can undergo molecular self-assembly to form the ionic ally conducting channel. The

Neuronal substrates and functional consequences of prenatal cannabis exposure.

PubMed

Calvigioni, Daniela; Hurd, Yasmin L; Harkany, Tibor; Keimpema, Erik

2014-10-01

Cannabis remains one of the world's most widely used substance of abuse amongst pregnant women. Trends of the last 50 years show an increase in popularity in child-bearing women together with a constant increase in cannabis potency. In addition, potent herbal "legal" highs containing synthetic cannabinoids that mimic the effects of cannabis with unknown pharmacological and toxicological effects have gained rapid popularity amongst young adults. Despite the surge in cannabis use during pregnancy, little is known about the neurobiological and psychological consequences in the exposed offspring. In this review, we emphasize the importance of maternal programming, defined as the intrauterine presentation of maternal stimuli to the foetus, in neurodevelopment. In particular, we focus on cannabis-mediated maternal adverse effects, resulting in direct central nervous system alteration or sensitization to late-onset chronic and neuropsychiatric disorders. We compare clinical and preclinical experimental studies on the effects of foetal cannabis exposure until early adulthood, to stress the importance of animal models that permit the fine control of environmental variables and allow the dissection of cannabis-mediated molecular cascades in the developing central nervous system. In sum, we conclude that preclinical experimental models confirm clinical studies and that cannabis exposure evokes significant molecular modifications to neurodevelopmental programs leading to neurophysiological and behavioural abnormalities.

Models and molecular approaches to assessing the effects of the microgravity environment on vertebrate development

NASA Technical Reports Server (NTRS)

Wolgemuth, D. J.; Murashov, A. K.

1995-01-01

The extent to which gravity, and especially the lack thereof, can affect normal development in higher organisms is poorly understood. Underlying this question is the assumption that normal development depends on the embryo's ability to maintain a programmed temporal and spatial coordination of morphogenetic events. There are several reports documenting the apparently normal development of several vertebrate species, including mammals, under conditions of exposure to space flight during various periods of the development process. Evidence to the contrary also exists and it is therefore likely that some alterations in morphology do occur in a microgravity environment. Although subsequent development may appear overtly normal, more subtle abnormalities result. In all studies, the evaluation is restricted by the few numbers of specimens that can be examined and the relatively insensitive techniques for assessing potentially subtle effects. In the present discussion, we summarize some observations of mammalian development made in microgravity and consider which stages might be expected to be differentially sensitive to altered gravity conditions. While we emphasize mammalian development, we discuss the suitability of another model system for examining such effects in a cross-species context. Furthermore, we consider recent developments in our understanding of the molecular genetic program regulating embryogenesis that could serve as markers for assessing perturbations of development.

HST/WFC3 Observations of Giant Hot Exoplanets

NASA Technical Reports Server (NTRS)

Deming, D.; Agol, E.; Burrows, A.; Charbonneau, D.; Clampin, M.; Desert, J.-M.; Gilliland, R.; Knutson, H.; Madhusudhan, N.; Mandell, A.;

Neuronal substrates and functional consequences of prenatal cannabis exposure

PubMed Central

Calvigioni, Daniela; Hurd, Yasmin L.; Keimpema, Erik

2015-01-01

Cannabis remains one of the world’s most widely used substance of abuse amongst pregnant women. Trends of the last 50 years show an increase in popularity in child-bearing women together with a constant increase in cannabis potency. In addition, potent herbal “legal” highs containing synthetic cannabinoids that mimic the effects of cannabis with unknown pharmacological and toxicological effects have gained rapid popularity amongst young adults. Despite the surge in cannabis use during pregnancy, little is known about the neurobiological and psychological consequences in the exposed offspring. In this review, we emphasize the importance of maternal programming, defined as the intrauterine presentation of maternal stimuli to the foetus, in neurodevelopment. In particular, we focus on cannabis-mediated maternal adverse effects, resulting in direct central nervous system alteration or sensitization to late-onset chronic and neuropsychiatric disorders. We compare clinical and preclinical experimental studies on the effects of foetal cannabis exposure until early adulthood, to stress the importance of animal models that permit the fine control of environmental variables and allow the dissection of cannabis-mediated molecular cascades in the developing central nervous system. In sum, we conclude that preclinical experimental models confirm clinical studies and that cannabis exposure evokes significant molecular modifications to neurodevelopmental programs leading to neurophysiological and behavioural abnormalities. PMID:24793873

Molecular markers: a potential resource for ginger genetic diversity studies.

PubMed

Ismail, Nor Asiah; Rafii, M Y; Mahmud, T M M; Hanafi, M M; Miah, Gous

2016-12-01

Ginger is an economically important and valuable plant around the world. Ginger is used as a food, spice, condiment, medicine and ornament. There is available information on biochemical aspects of ginger, but few studies have been reported on its molecular aspects. The main objective of this review is to accumulate the available molecular marker information and its application in diverse ginger studies. This review article was prepared by combing material from published articles and our own research. Molecular markers allow the identification and characterization of plant genotypes through direct access to hereditary material. In crop species, molecular markers are applied in different aspects and are useful in breeding programs. In ginger, molecular markers are commonly used to identify genetic variation and classify the relatedness among varieties, accessions, and species. Consequently, it provides important input in determining resourceful management strategies for ginger improvement programs. Alternatively, a molecular marker could function as a harmonizing tool for documenting species. This review highlights the application of molecular markers (isozyme, RAPD, AFLP, SSR, ISSR and others such as RFLP, SCAR, NBS and SNP) in genetic diversity studies of ginger species. Some insights on the advantages of the markers are discussed. The detection of genetic variation among promising cultivars of ginger has significance for ginger improvement programs. This update of recent literature will help researchers and students select the appropriate molecular markers for ginger-related research.

FEL (Free Electron Laser) Optics Coating Test Program (Design Phase of Sample Introduction Chamber)

DTIC Science & Technology

1986-02-01

is the photon energy dependent on the molecular species? - does the saturation depend on the UV photon energy? 3. Examine the rapid, saturating...can also be determined if the active photon energy range depends significantly on the molecular species. In a six month program, the first three...determine if the deposition rate depends #significantly on the species. The photon energy dependence of the deposition rate on the molecular species

Interaction of D2 with H2O amorphous ice studied by temperature-programmed desorption experiments.

PubMed

Amiaud, L; Fillion, J H; Baouche, S; Dulieu, F; Momeni, A; Lemaire, J L

2006-03-07

The gas-surface interaction of molecular hydrogen D2 with a thin film of porous amorphous solid water (ASW) grown at 10 K by slow vapor deposition has been studied by temperature-programmed-desorption (TPD) experiments. Molecular hydrogen diffuses rapidly into the porous network of the ice. The D2 desorption occurring between 10 and 30 K is considered here as a good probe of the effective surface of ASW interacting with the gas. The desorption kinetics have been systematically measured at various coverages. A careful analysis based on the Arrhenius plot method has provided the D2 binding energies as a function of the coverage. Asymmetric and broad distributions of binding energies were found, with a maximum population peaking at low energy. We propose a model for the desorption kinetics that assumes a complete thermal equilibrium of the molecules with the ice film. The sample is characterized by a distribution of adsorption sites that are filled according to a Fermi-Dirac statistic law. The TPD curves can be simulated and fitted to provide the parameters describing the distribution of the molecules as a function of their binding energy. This approach contributes to a correct description of the interaction of molecular hydrogen with the surface of possibly porous grain mantles in the interstellar medium.

Theoretical research program to study chemical reactions in AOTV bow shock tubes

NASA Technical Reports Server (NTRS)

Taylor, Peter R.

1993-01-01

The main focus was the development, implementation, and calibration of methods for performing molecular electronic structure calculations to high accuracy. These various methods were then applied to a number of chemical reactions and species of interest to NASA, notably in the area of combustion chemistry. Among the development work undertaken was a collaborative effort to develop a program to efficiently predict molecular structures and vibrational frequencies using energy derivatives. Another major development effort involved the design of new atomic basis sets for use in chemical studies: these sets were considerably more accurate than those previously in use. Much effort was also devoted to calibrating methods for computing accurate molecular wave functions, including the first reliable calibrations for realistic molecules using full CI results. A wide variety of application calculations were undertaken. One area of interest was the spectroscopy and thermochemistry of small molecules, including establishing small molecule binding energies to an accuracy rivaling, or even on occasion surpassing, the experiment. Such binding energies are essential input to modeling chemical reaction processes, such as combustion. Studies of large molecules and processes important in both hydrogen and hydrocarbon combustion chemistry were also carried out. Finally, some effort was devoted to the structure and spectroscopy of small metal clusters, with applications to materials science problems.

Predicting the activity of drugs for a group of imidazopyridine anticoccidial compounds.

PubMed

Si, Hongzong; Lian, Ning; Yuan, Shuping; Fu, Aiping; Duan, Yun-Bo; Zhang, Kejun; Yao, Xiaojun

2009-10-01

Gene expression programming (GEP) is a novel machine learning technique. The GEP is used to build nonlinear quantitative structure-activity relationship model for the prediction of the IC(50) for the imidazopyridine anticoccidial compounds. This model is based on descriptors which are calculated from the molecular structure. Four descriptors are selected from the descriptors' pool by heuristic method (HM) to build multivariable linear model. The GEP method produced a nonlinear quantitative model with a correlation coefficient and a mean error of 0.96 and 0.24 for the training set, 0.91 and 0.52 for the test set, respectively. It is shown that the GEP predicted results are in good agreement with experimental ones.

Knowledge discovery and system biology in molecular medicine: an application on neurodegenerative diseases.

PubMed

Fattore, Matteo; Arrigo, Patrizio

2005-01-01

The possibility to study an organism in terms of system theory has been proposed in the past, but only the advancement of molecular biology techniques allow us to investigate the dynamical properties of a biological system in a more quantitative and rational way than before . These new techniques can gave only the basic level view of an organisms functionality. The comprehension of its dynamical behaviour depends on the possibility to perform a multiple level analysis. Functional genomics has stimulated the interest in the investigation the dynamical behaviour of an organism as a whole. These activities are commonly known as System Biology, and its interests ranges from molecules to organs. One of the more promising applications is the 'disease modeling'. The use of experimental models is a common procedure in pharmacological and clinical researches; today this approach is supported by 'in silico' predictive methods. This investigation can be improved by a combination of experimental and computational tools. The Machine Learning (ML) tools are able to process different heterogeneous data sources, taking into account this peculiarity, they could be fruitfully applied to support a multilevel data processing (molecular, cellular and morphological) that is the prerequisite for the formal model design; these techniques can allow us to extract the knowledge for mathematical model development. The aim of our work is the development and implementation of a system that combines ML and dynamical models simulations. The program is addressed to the virtual analysis of the pathways involved in neurodegenerative diseases. These pathologies are multifactorial diseases and the relevance of the different factors has not yet been well elucidated. This is a very complex task; in order to test the integrative approach our program has been limited to the analysis of the effects of a specific protein, the Cyclin dependent kinase 5 (CDK5) which relies on the induction of neuronal apoptosis. The system has a modular structure centred on a textual knowledge discovery approach. The text mining is the only way to enhance the capability to extract ,from multiple data sources, the information required for the dynamical simulator. The user may access the publically available modules through the following site: http://biocomp.ge.ismac.cnr.it.

Las Palmeras Molecular Dynamics: A flexible and modular molecular dynamics code

NASA Astrophysics Data System (ADS)

Davis, Sergio; Loyola, Claudia; González, Felipe; Peralta, Joaquín

2010-12-01

Las Palmeras Molecular Dynamics (LPMD) is a highly modular and extensible molecular dynamics (MD) code using interatomic potential functions. LPMD is able to perform equilibrium MD simulations of bulk crystalline solids, amorphous solids and liquids, as well as non-equilibrium MD (NEMD) simulations such as shock wave propagation, projectile impacts, cluster collisions, shearing, deformation under load, heat conduction, heterogeneous melting, among others, which involve unusual MD features like non-moving atoms and walls, unstoppable atoms with constant-velocity, and external forces like electric fields. LPMD is written in C++ as a compromise between efficiency and clarity of design, and its architecture is based on separate components or plug-ins, implemented as modules which are loaded on demand at runtime. The advantage of this architecture is the ability to completely link together the desired components involved in the simulation in different ways at runtime, using a user-friendly control file language which describes the simulation work-flow. As an added bonus, the plug-in API (Application Programming Interface) makes it possible to use the LPMD components to analyze data coming from other simulation packages, convert between input file formats, apply different transformations to saved MD atomic trajectories, and visualize dynamical processes either in real-time or as a post-processing step. Individual components, such as a new potential function, a new integrator, a new file format, new properties to calculate, new real-time visualizers, and even a new algorithm for handling neighbor lists can be easily coded, compiled and tested within LPMD by virtue of its object-oriented API, without the need to modify the rest of the code. LPMD includes already several pair potential functions such as Lennard-Jones, Morse, Buckingham, MCY and the harmonic potential, as well as embedded-atom model (EAM) functions such as the Sutton-Chen and Gupta potentials. Integrators to choose include Euler (if only for demonstration purposes), Verlet and Velocity Verlet, Leapfrog and Beeman, among others. Electrostatic forces are treated as another potential function, by default using the plug-in implementing the Ewald summation method. Program summaryProgram title: LPMD Catalogue identifier: AEHG_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEHG_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: GNU General Public License version 3 No. of lines in distributed program, including test data, etc.: 509 490 No. of bytes in distributed program, including test data, etc.: 6 814 754 Distribution format: tar.gz Programming language: C++ Computer: 32-bit and 64-bit workstation Operating system: UNIX RAM: Minimum 1024 bytes Classification: 7.7 External routines: zlib, OpenGL Nature of problem: Study of Statistical Mechanics and Thermodynamics of condensed matter systems, as well as kinetics of non-equilibrium processes in the same systems. Solution method: Equilibrium and non-equilibrium molecular dynamics method, Monte Carlo methods. Restrictions: Rigid molecules are not supported. Polarizable atoms and chemical bonds (proteins) either. Unusual features: The program is able to change the temperature of the simulation cell, the pressure, cut regions of the cell, color the atoms by properties, even during the simulation. It is also possible to fix the positions and/or velocity of groups of atoms. Visualization of atoms and some physical properties during the simulation. Additional comments: The program does not only perform molecular dynamics and Monte Carlo simulations, it is also able to filter and manipulate atomic configurations, read and write different file formats, convert between them, evaluate different structural and dynamical properties. Running time: 50 seconds on a 1000-step simulation of 4000 argon atoms, running on a single 2.67 GHz Intel processor.

Toward a molecular programming language for algorithmic self-assembly

NASA Astrophysics Data System (ADS)

Patitz, Matthew John

Self-assembly is the process whereby relatively simple components autonomously combine to form more complex objects. Nature exhibits self-assembly to form everything from microscopic crystals to living cells to galaxies. With a desire to both form increasingly sophisticated products and to understand the basic components of living systems, scientists have developed and studied artificial self-assembling systems. One such framework is the Tile Assembly Model introduced by Erik Winfree in 1998. In this model, simple two-dimensional square 'tiles' are designed so that they self-assemble into desired shapes. The work in this thesis consists of a series of results which build toward the future goal of designing an abstracted, high-level programming language for designing the molecular components of self-assembling systems which can perform powerful computations and form into intricate structures. The first two sets of results demonstrate self-assembling systems which perform infinite series of computations that characterize computably enumerable and decidable languages, and exhibit tools for algorithmically generating the necessary sets of tiles. In the next chapter, methods for generating tile sets which self-assemble into complicated shapes, namely a class of discrete self-similar fractal structures, are presented. Next, a software package for graphically designing tile sets, simulating their self-assembly, and debugging designed systems is discussed. Finally, a high-level programming language which abstracts much of the complexity and tedium of designing such systems, while preventing many of the common errors, is presented. The summation of this body of work presents a broad coverage of the spectrum of desired outputs from artificial self-assembling systems and a progression in the sophistication of tools used to design them. By creating a broader and deeper set of modular tools for designing self-assembling systems, we hope to increase the complexity which is attainable. These tools provide a solid foundation for future work in both the Tile Assembly Model and explorations into more advanced models.

How molecular epidemiology studies can support the National Malaria Control Program in Papua New Guinea.

PubMed

Koepfli, Cristian; Barry, Alyssa; Javati, Sarah; Timinao, Lincoln; Nate, Elma; Mueller, Ivo; Barnadas, Celine

2014-01-01

Papua New Guinea (PNG) is undertaking intensified efforts to control malaria. The National Malaria Control Program aims to reduce the burden of disease by large-scale distribution of insecticide-treated bednets, improved diagnosis and implementation of new treatments. A scientific program monitoring the effect of these interventions, including molecular epidemiology studies, closely accompanies the program. Laboratory assays have been developed in (or transferred to) PNG to measure prevalence of infection and intensity of transmission as well as potential resistance to currently used drugs. These assays help to assess the impact of the National Malaria Control Program, and they reveal a much clearer picture of malaria epidemiology in PNG. In addition, analysis of the geographical clustering of parasites aids in selecting areas where intensified control will be most successful. This paper gives an overview of current research and recently completed studies in the molecular epidemiology of malaria conducted in Papua New Guinea.

Planetary Biology and Microbial Ecology: Molecular Ecology and the Global Nitrogen cycle

NASA Technical Reports Server (NTRS)

Nealson, Molly Stone (Editor); Nealson, Kenneth H. (Editor)

1993-01-01

This report summarizes the results of the Planetary Biology and Molecular Ecology's summer 1991 program, which was held at the Marine Biological Laboratory in Woods Hole, Massachusetts. The purpose of the interdisciplinary PBME program is to integrate, via lectures and laboratory work, the contributions of university and NASA scientists and student interns. The goals of the 1991 program were to examine several aspects of the biogeochemistry of the nitrogen cycle and to teach the application of modern methods of molecular genetics to field studies of organisms. Descriptions of the laboratory projects and protocols and abstracts and references of the lectures are presented.

Predicting Quantitative Traits With Regression Models for Dense Molecular Markers and Pedigree

PubMed Central

de los Campos, Gustavo; Naya, Hugo; Gianola, Daniel; Crossa, José; Legarra, Andrés; Manfredi, Eduardo; Weigel, Kent; Cotes, José Miguel

2009-01-01

The availability of genomewide dense markers brings opportunities and challenges to breeding programs. An important question concerns the ways in which dense markers and pedigrees, together with phenotypic records, should be used to arrive at predictions of genetic values for complex traits. If a large number of markers are included in a regression model, marker-specific shrinkage of regression coefficients may be needed. For this reason, the Bayesian least absolute shrinkage and selection operator (LASSO) (BL) appears to be an interesting approach for fitting marker effects in a regression model. This article adapts the BL to arrive at a regression model where markers, pedigrees, and covariates other than markers are considered jointly. Connections between BL and other marker-based regression models are discussed, and the sensitivity of BL with respect to the choice of prior distributions assigned to key parameters is evaluated using simulation. The proposed model was fitted to two data sets from wheat and mouse populations, and evaluated using cross-validation methods. Results indicate that inclusion of markers in the regression further improved the predictive ability of models. An R program that implements the proposed model is freely available. PMID:19293140

Molecular Signatures Discriminating the Male and the Female Sexual Pathways in the Pearl Oyster Pinctada margaritifera

PubMed Central

Teaniniuraitemoana, Vaihiti; Huvet, Arnaud; Levy, Peva; Gaertner-Mazouni, Nabila; Gueguen, Yannick; Le Moullac, Gilles

2015-01-01

The genomics of economically important marine bivalves is studied to provide better understanding of the molecular mechanisms underlying their different reproductive strategies. The recently available gonad transcriptome of the black-lip pearl oyster Pinctada margaritifera is a novel and powerful resource to study these mechanisms in marine mollusks displaying hermaphroditic features. In this study, RNAseq quantification data of the P. margaritifera gonad transcriptome were analyzed to identify candidate genes in histologically-characterized gonad samples to provide molecular signatures of the female and male sexual pathway in this pearl oyster. Based on the RNAseq data set, stringent expression analysis identified 1,937 contigs that were differentially expressed between the gonad histological categories. From the hierarchical clustering analysis, a new reproduction model is proposed, based on a dual histo-molecular analytical approach. Nine candidate genes were identified as markers of the sexual pathway: 7 for the female pathway and 2 for the male one. Their mRNA levels were assayed by real-time PCR on a new set of gonadic samples. A clustering method revealed four principal expression patterns based on the relative gene expression ratio. A multivariate regression tree realized on these new samples and validated on the previously analyzed RNAseq samples showed that the sexual pathway of P. margaritifera can be predicted by a 3-gene-pair expression ratio model of 4 different genes: pmarg-43476, pmarg-foxl2, pmarg-54338 and pmarg-fem1-like. This 3-gene-pair expression ratio model strongly suggests only the implication of pmarg-foxl2 and pmarg-fem1-like in the sex inversion of P. margaritifera. This work provides the first histo-molecular model of P. margaritifera reproduction and a gene expression signature of its sexual pathway discriminating the male and female pathways. These represent useful tools for understanding and studying sex inversion, sex differentiation and sex determinism in this species and other related species for aquaculture purposes such as genetic selection programs. PMID:25815473

Molecular systems biology of ErbB1 signaling: bridging the gap through multiscale modeling and high-performance computing.

PubMed

Shih, Andrew J; Purvis, Jeremy; Radhakrishnan, Ravi

2008-12-01

The complexity in intracellular signaling mechanisms relevant for the conquest of many diseases resides at different levels of organization with scales ranging from the subatomic realm relevant to catalytic functions of enzymes to the mesoscopic realm relevant to the cooperative association of molecular assemblies and membrane processes. Consequently, the challenge of representing and quantifying functional or dysfunctional modules within the networks remains due to the current limitations in our understanding of mesoscopic biology, i.e., how the components assemble into functional molecular ensembles. A multiscale approach is necessary to treat a hierarchy of interactions ranging from molecular (nm, ns) to signaling (microm, ms) length and time scales, which necessitates the development and application of specialized modeling tools. Complementary to multiscale experimentation (encompassing structural biology, mechanistic enzymology, cell biology, and single molecule studies) multiscale modeling offers a powerful and quantitative alternative for the study of functional intracellular signaling modules. Here, we describe the application of a multiscale approach to signaling mediated by the ErbB1 receptor which constitutes a network hub for the cell's proliferative, migratory, and survival programs. Through our multiscale model, we mechanistically describe how point-mutations in the ErbB1 receptor can profoundly alter signaling characteristics leading to the onset of oncogenic transformations. Specifically, we describe how the point mutations induce cascading fragility mechanisms at the molecular scale as well as at the scale of the signaling network to preferentially activate the survival factor Akt. We provide a quantitative explanation for how the hallmark of preferential Akt activation in cell-lines harboring the constitutively active mutant ErbB1 receptors causes these cell-lines to be addicted to ErbB1-mediated generation of survival signals. Consequently, inhibition of ErbB1 activity leads to a remarkable therapeutic response in the addicted cell lines.

Innovative Molecular Analysis Technologies Program Funding Opportunities | Office of Cancer Clinical Proteomics Research

Cancer.gov

The NCI is very pleased to announce that the Innovative Molecular Analysis Technologies (IMAT) program funding opportunity announcements have been posted for calendar year (CY) 2013. Please visit this website for more information on these announcements. For your convenience, a link to each solicitation is provided below with associated submission deadlines for new applications and resubmissions. Please contact the NCI IMAT program director, Dr.

Prediction of atmospheric degradation data for POPs by gene expression programming.

PubMed

Luan, F; Si, H Z; Liu, H T; Wen, Y Y; Zhang, X Y

2008-01-01

Quantitative structure-activity relationship models for the prediction of the mean and the maximum atmospheric degradation half-life values of persistent organic pollutants were developed based on the linear heuristic method (HM) and non-linear gene expression programming (GEP). Molecular descriptors, calculated from the structures alone, were used to represent the characteristics of the compounds. HM was used both to pre-select the whole descriptor sets and to build the linear model. GEP yielded satisfactory prediction results: the square of the correlation coefficient r(2) was 0.80 and 0.81 for the mean and maximum half-life values of the test set, and the root mean square errors were 0.448 and 0.426, respectively. The results of this work indicate that the GEP is a very promising tool for non-linear approximations.

Millimeter and submillimeter spectra of hot cores and diffuse clouds: comparing IRAM and Herschel spectra with CASSIS simulations.

NASA Astrophysics Data System (ADS)

de Luca, Massimo

The primary goal of the PRISMAS Herschel key program is the spectroscopic study of key molecular lines towards bright Galactic star-forming regions and the diffuse interstellar clouds distributed along the lines of sight. Models of the source emission and absorption spectra have been constructed with CASSIS, based on 1) observational evidence in comparable environments, 2) warm-up chemical models with gas-grain networks, and 3) ground-based spectra of various molecules in the target sources obtained at the IRAM 30m telescope. These models include contributions from the hot core, its parental molecular cloud and the foreground diffuse inter-stellar matter. The considerable complexity of the hot core chemistry, together with the huge amount of information buried in the spectra, often prevents a straightforward interpretation of the data without the help simulations. This is particularly true for the largely unexplored wavelength range of HIFI. In this contribution, we compare HIFI and IRAM observations to our models, in order to either consolidate present day assumptions and knowledge of these environments, or to highlight the model limitations, poorly understood physical and chemical conditions or unexpected abundances. We pay particular attention to the ground state tran-sitions of the most important hydrides, which the PRISMAS program has been designed for, though the HIFI spectra are expected to be rich in other molecules as well. List of Authors De Luca, M., Observatoire de Paris, Ecole Normale Supérieure and CNRS, FRANCE; Bell, T., CalTech, UNITED STATES; Coutens, A., CESR, FRANCE; Godard, B., IAS, FRANCE; Gupta, H., JPL, UNITED STATES; Mook-erjea, B., Tata Institute for Fundamental Research, INDIA; and the PRISMAS consortium, PRISMAS, FRANCE

Quantum probability ranking principle for ligand-based virtual screening.

PubMed

Al-Dabbagh, Mohammed Mumtaz; Salim, Naomie; Himmat, Mubarak; Ahmed, Ali; Saeed, Faisal

2017-04-01

Chemical libraries contain thousands of compounds that need screening, which increases the need for computational methods that can rank or prioritize compounds. The tools of virtual screening are widely exploited to enhance the cost effectiveness of lead drug discovery programs by ranking chemical compounds databases in decreasing probability of biological activity based upon probability ranking principle (PRP). In this paper, we developed a novel ranking approach for molecular compounds inspired by quantum mechanics, called quantum probability ranking principle (QPRP). The QPRP ranking criteria would make an attempt to draw an analogy between the physical experiment and molecular structure ranking process for 2D fingerprints in ligand based virtual screening (LBVS). The development of QPRP criteria in LBVS has employed the concepts of quantum at three different levels, firstly at representation level, this model makes an effort to develop a new framework of molecular representation by connecting the molecular compounds with mathematical quantum space. Secondly, estimate the similarity between chemical libraries and references based on quantum-based similarity searching method. Finally, rank the molecules using QPRP approach. Simulated virtual screening experiments with MDL drug data report (MDDR) data sets showed that QPRP outperformed the classical ranking principle (PRP) for molecular chemical compounds.

Quantum probability ranking principle for ligand-based virtual screening

NASA Astrophysics Data System (ADS)

Al-Dabbagh, Mohammed Mumtaz; Salim, Naomie; Himmat, Mubarak; Ahmed, Ali; Saeed, Faisal

2017-04-01

Chemical libraries contain thousands of compounds that need screening, which increases the need for computational methods that can rank or prioritize compounds. The tools of virtual screening are widely exploited to enhance the cost effectiveness of lead drug discovery programs by ranking chemical compounds databases in decreasing probability of biological activity based upon probability ranking principle (PRP). In this paper, we developed a novel ranking approach for molecular compounds inspired by quantum mechanics, called quantum probability ranking principle (QPRP). The QPRP ranking criteria would make an attempt to draw an analogy between the physical experiment and molecular structure ranking process for 2D fingerprints in ligand based virtual screening (LBVS). The development of QPRP criteria in LBVS has employed the concepts of quantum at three different levels, firstly at representation level, this model makes an effort to develop a new framework of molecular representation by connecting the molecular compounds with mathematical quantum space. Secondly, estimate the similarity between chemical libraries and references based on quantum-based similarity searching method. Finally, rank the molecules using QPRP approach. Simulated virtual screening experiments with MDL drug data report (MDDR) data sets showed that QPRP outperformed the classical ranking principle (PRP) for molecular chemical compounds.

ENABLE 2017, the First EUROPEAN PhD and Post-Doc Symposium. Session 3: In Vitro to In Vivo: Modeling Life in 3D.

PubMed

Di Mauro, Gianmarco; Dondi, Ambra; Giangreco, Giovanni; Hogrebe, Alexander; Louer, Elja; Magistrati, Elisa; Mullari, Meeli; Turon, Gemma; Verdurmen, Wouter; Cortada, Helena Xicoy; Zivanovic, Sanja

2018-05-22

The EUROPEAN ACADEMY FOR BIOMEDICAL SCIENCE (ENABLE) is an initiative funded by the European Union Horizon 2020 program involving four renowned European research institutes (Institute for Research in Biomedicine-IRB Barcelona, Spain; Radboud Institute for Molecular Life Sciences-RIMLS, the Netherlands; Novo Nordisk Foundation Center for Protein Research-NNF CPR, Denmark; European School of Molecular Medicine-SEMM, Italy) and an innovative science communication agency (Scienseed). With the aim to promote biomedical science of excellence in Europe, ENABLE organizes an annual three-day international event. This gathering includes a top-level scientific symposium bringing together leading scientists, PhD students, and post-doctoral fellows; career development activities supporting the progression of young researchers and fostering discussion about opportunities beyond the bench; outreach activities stimulating the interaction between science and society. The first European PhD and Postdoc Symposium, entitled "Breaking Down Complexity: Innovative models and techniques in biomedicine", was hosted by the vibrant city of Barcelona. The scientific program of the conference was focused on the most recent advances and applications of modern techniques and models in biomedical research and covered a wide range of topics, from synthetic biology to translational medicine. Overall, the event was a great success, with more than 200 attendees from all over Europe actively participating in the symposium by presenting their research and exchanging ideas with their peers and world-renowned scientists.

Repeated short climatic change affects the epidermal differentiation program and leads to matrix remodeling in a human organotypic skin model.

PubMed

Boutrand, Laetitia-Barbollat; Thépot, Amélie; Muther, Charlotte; Boher, Aurélie; Robic, Julie; Guéré, Christelle; Vié, Katell; Damour, Odile; Lamartine, Jérôme

2017-01-01

Human skin is subject to frequent changes in ambient temperature and humidity and needs to cope with these environmental modifications. To decipher the molecular response of human skin to repeated climatic change, a versatile model of skin equivalent subject to "hot-wet" (40°C, 80% relative humidity [RH]) or "cold-dry" (10°C, 40% RH) climatic stress repeated daily was used. To obtain an exhaustive view of the molecular mechanisms elicited by climatic change, large-scale gene expression DNA microarray analysis was performed and modulated function was determined by bioinformatic annotation. This analysis revealed several functions, including epidermal differentiation and extracellular matrix, impacted by repeated variations in climatic conditions. Some of these molecular changes were confirmed by histological examination and protein expression. Both treatments (hot-wet and cold-dry) reduced the expression of genes encoding collagens, laminin, and proteoglycans, suggesting a profound remodeling of the extracellular matrix. Strong induction of the entire family of late cornified envelope genes after cold-dry exposure, confirmed at protein level, was also observed. These changes correlated with an increase in epidermal differentiation markers such as corneodesmosin and a thickening of the stratum corneum, indicating possible implementation of defense mechanisms against dehydration. This study for the first time reveals the complex pattern of molecular response allowing adaption of human skin to repeated change in its climatic environment.

An autonomous molecular computer for logical control of gene expression

PubMed Central

Benenson, Yaakov; Gil, Binyamin; Ben-Dor, Uri; Adar, Rivka; Shapiro, Ehud

2013-01-01

Early biomolecular computer research focused on laboratory-scale, human-operated computers for complex computational problems1–7. Recently, simple molecular-scale autonomous programmable computers were demonstrated8–15 allowing both input and output information to be in molecular form. Such computers, using biological molecules as input data and biologically active molecules as outputs, could produce a system for ‘logical’ control of biological processes. Here we describe an autonomous biomolecular computer that, at least in vitro, logically analyses the levels of messenger RNA species, and in response produces a molecule capable of affecting levels of gene expression. The computer operates at a concentration of close to a trillion computers per microlitre and consists of three programmable modules: a computation module, that is, a stochastic molecular automaton12–17; an input module, by which specific mRNA levels or point mutations regulate software molecule concentrations, and hence automaton transition probabilities; and an output module, capable of controlled release of a short single-stranded DNA molecule. This approach might be applied in vivo to biochemical sensing, genetic engineering and even medical diagnosis and treatment. As a proof of principle we programmed the computer to identify and analyse mRNA of disease-related genes18–22 associated with models of small-cell lung cancer and prostate cancer, and to produce a single-stranded DNA molecule modelled after an anticancer drug. PMID:15116117

[A contribution safety on using low molecular weight heparin in patients with renal failure].

PubMed

Gea Rodríguez, E; Barral Viñals, N; Manso Mardones, P; Indo Berges, O

2004-01-01

1. To promote safe and appropriate use of low molecular weight heparins in patients with renal failure. 2. To analyze results from a pharmaceutical intervention program. Data from a prospective, 16-month study are presented. The entire adult population of a general hospital with 41,792 stays/year is included. An intensive monitoring program for low molecular weight heparin prescriptions in patients with renal failure is implemented. This program identifies patients using a computerized unit dose system, and is aided by a software able to calculate creatinine clearance using the Cockroft-Gault formula from an interphase between laboratory, pharmacy and admissions data, and by an algorithm to establish a recommended pharmaceutical intervention according to renal failure severity and low molecular weight heparin indication, either with prophylactic or therapeutic purposes. In all, 221 patients were identified, corresponding to 2.9% of admitted patients and 25.5% of patients with renal failure. Answers were assessable for 128 patients (61%). Extent of program acceptance according to physician-accepted pharmaceutical interventions was proportional to renal failure severity and therapy intensiveness. An acceptance of 70% was obtained for treatments with clearance < 30 mL/min, of 41.8% for treatments with 30-60 mL/min, of 31.5% for prophylaxis, and of 21.4% for low-risk patients. 1. Program repercussions improve prescription safety. 2. Scarce literature and a belief in low molecular weight heparin safety account for responses regarding pharmaceutical intervention. 3. Integrated computerized systems are essential for the implementation of intensive pharmaceutical care programs.

Kakusan4 and Aminosan: two programs for comparing nonpartitioned, proportional and separate models for combined molecular phylogenetic analyses of multilocus sequence data.

PubMed

Tanabe, Akifumi S

2011-09-01

Proportional and separate models able to apply different combination of substitution rate matrix (SRM) and among-site rate variation model (ASRVM) to each locus are frequently used in phylogenetic studies of multilocus data. A proportional model assumes that branch lengths are proportional among partitions and a separate model assumes that each partition has an independent set of branch lengths. However, the selection from among nonpartitioned (i.e., a common combination of models is applied to all-loci concatenated sequences), proportional and separate models is usually based on the researcher's preference rather than on any information criteria. This study describes two programs, 'Kakusan4' (for DNA sequences) and 'Aminosan' (for amino-acid sequences), which allow the selection of evolutionary models based on several types of information criteria. The programs can handle both multilocus and single-locus data, in addition to providing an easy-to-use wizard interface and a noninteractive command line interface. In the case of multilocus data, SRMs and ASRVMs are compared at each locus and at all-loci concatenated sequences, after which nonpartitioned, proportional and separate models are compared based on information criteria. The programs also provide model configuration files for mrbayes, paup*, phyml, raxml and Treefinder to support further phylogenetic analysis using a selected model. When likelihoods are optimized by Treefinder, the best-fit models were found to differ depending on the data set. Furthermore, differences in the information criteria among nonpartitioned, proportional and separate models were much larger than those among the nonpartitioned models. These findings suggest that selecting from nonpartitioned, proportional and separate models results in a better phylogenetic tree. Kakusan4 and Aminosan are available at http://www.fifthdimension.jp/. They are licensed under gnugpl Ver.2, and are able to run on Windows, MacOS X and Linux. © 2011 Blackwell Publishing Ltd.

Molecular Probes in Marine Ecology: Concepts, Techniques and Applications.

DTIC Science & Technology

1991-08-16

AD-A240 938 FINAL TECNCAL REPORT Title: Molecular Probes In Marine Ecology: Concepts, Techniques and Applications Office of Naval Research Program ...Contact: Leslie D. Garrick, Office of Sponsored Programs (508) 548-3705, ext. 218 Date: August 16, 1991 91-11818 DISCLAIMER NOTICE THIS DOCUMENT IS BEST...disguise, embi-aces the many questions and seeks workable solutions. The 1990 MBL marine ecology course, entered into its second year of a program in

Glaucoma Symptoms

MedlinePlus

... Alzheimer’s Disease Research Program Macular Degeneration Research Program National Glaucoma Research Program Molecular Neurodegeneration ... Foundation BrightFocus Foundation 22512 Gateway Center Drive Clarksburg, MD ...

The origin and evolution of dust in interstellar and circumstellar environments

NASA Technical Reports Server (NTRS)

Whittet, Douglas C. B.; Leung, Chun M.

1993-01-01

This status report covers the period from the commencement of the research program on 1 Jul. 1992 through 30 Apr. 1993. Progress is reported for research in the following areas: (1) grain formation in circumstellar envelopes; (2) photochemistry in circumstellar envelopes; (3) modeling ice features in circumstellar envelopes; (4) episodic dust formation in circumstellar envelopes; (5) grain evolution in the diffuse interstellar medium; and (6) grain evolution in dense molecular clouds.

ECUT: Energy Conversion and Utilization Technologies program. Biocatalysis project

NASA Technical Reports Server (NTRS)

1990-01-01

The Biocatalysis Project is a mission-oriented, applied research and exploratory development activity directed toward resolution of the major generic technical barriers that impede the development of biologically catalyzed commercial chemical production. The approach toward achieving project objectives involves an integrated participation of Universities, Industrial Companies and Government Research Laboratories. The Project's technical activities were organized into three work elements: molecular modeling and applied genetics; bioprocess engineering; and bioprocess design and assessment.

Molecular Marker Systems for Oenothera Genetics

PubMed Central

Rauwolf, Uwe; Golczyk, Hieronim; Meurer, Jörg; Herrmann, Reinhold G.; Greiner, Stephan

2008-01-01

The genus Oenothera has an outstanding scientific tradition. It has been a model for studying aspects of chromosome evolution and speciation, including the impact of plastid nuclear co-evolution. A large collection of strains analyzed during a century of experimental work and unique genetic possibilities allow the exchange of genetically definable plastids, individual or multiple chromosomes, and/or entire haploid genomes (Renner complexes) between species. However, molecular genetic approaches for the genus are largely lacking. In this study, we describe the development of efficient PCR-based marker systems for both the nuclear genome and the plastome. They allow distinguishing individual chromosomes, Renner complexes, plastomes, and subplastomes. We demonstrate their application by monitoring interspecific exchanges of genomes, chromosome pairs, and/or plastids during crossing programs, e.g., to produce plastome–genome incompatible hybrids. Using an appropriate partial permanent translocation heterozygous hybrid, linkage group 7 of the molecular map could be assigned to chromosome 9·8 of the classical Oenothera map. Finally, we provide the first direct molecular evidence that homologous recombination and free segregation of chromosomes in permanent translocation heterozygous strains is suppressed. PMID:18791241

Molecular marker systems for Oenothera genetics.

PubMed

Rauwolf, Uwe; Golczyk, Hieronim; Meurer, Jörg; Herrmann, Reinhold G; Greiner, Stephan

2008-11-01

The genus Oenothera has an outstanding scientific tradition. It has been a model for studying aspects of chromosome evolution and speciation, including the impact of plastid nuclear co-evolution. A large collection of strains analyzed during a century of experimental work and unique genetic possibilities allow the exchange of genetically definable plastids, individual or multiple chromosomes, and/or entire haploid genomes (Renner complexes) between species. However, molecular genetic approaches for the genus are largely lacking. In this study, we describe the development of efficient PCR-based marker systems for both the nuclear genome and the plastome. They allow distinguishing individual chromosomes, Renner complexes, plastomes, and subplastomes. We demonstrate their application by monitoring interspecific exchanges of genomes, chromosome pairs, and/or plastids during crossing programs, e.g., to produce plastome-genome incompatible hybrids. Using an appropriate partial permanent translocation heterozygous hybrid, linkage group 7 of the molecular map could be assigned to chromosome 9.8 of the classical Oenothera map. Finally, we provide the first direct molecular evidence that homologous recombination and free segregation of chromosomes in permanent translocation heterozygous strains is suppressed.

Temperature specification in atomistic molecular dynamics and its impact on simulation efficacy

NASA Astrophysics Data System (ADS)

Ocaya, R. O.; Terblans, J. J.

2017-10-01

Temperature is a vital thermodynamical function for physical systems. Knowledge of system temperature permits assessment of system ergodicity, entropy, system state and stability. Rapid theoretical and computational developments in the fields of condensed matter physics, chemistry, material science, molecular biology, nanotechnology and others necessitate clarity in the temperature specification. Temperature-based materials simulations, both standalone and distributed computing, are projected to grow in prominence over diverse research fields. In this article we discuss the apparent variability of temperature modeling formalisms used currently in atomistic molecular dynamics simulations, with respect to system energetics,dynamics and structural evolution. Commercial simulation programs, which by nature are heuristic, do not openly discuss this fundamental question. We address temperature specification in the context of atomistic molecular dynamics. We define a thermostat at 400K relative to a heat bath at 300K firstly using a modified ab-initio Newtonian method, and secondly using a Monte-Carlo method. The thermostatic vacancy formation and cohesion energies, equilibrium lattice constant for FCC copper is then calculated. Finally we compare and contrast the results.

Initiative for Molecular Profiling and Advanced Cancer Therapy and challenges in the implementation of precision medicine.

PubMed

Tsimberidou, Apostolia-Maria

In the last decade, breakthroughs in technology have improved our understanding of genomic, transcriptional, proteomic, epigenetic aberrations and immune mechanisms in carcinogenesis. Genomics and model systems have enabled the validation of novel therapeutic strategies. Based on these developments, in 2007, we initiated the IMPACT (Initiative for Molecular Profiling and Advanced Cancer Therapy) study, the first personalized medicine program for patients with advanced cancer at The University of Texas MD Anderson Cancer Center. We demonstrated that in patients referred for Phase I clinical trials, the use of tumor molecular profiling and treatment with matched targeted therapy was associated with encouraging rates of response, progression-free survival and overall survival compared to non-matched therapy. We are currently conducting IMPACT2, a randomized study evaluating molecular profiling and targeted agents in patients with metastatic cancer. Optimization of innovative biomarker-driven clinical trials that include targeted therapy and/or immunotherapeutic approaches for carefully selected patients will accelerate the development of novel drugs and the implementation of precision medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

High performance computing in biology: multimillion atom simulations of nanoscale systems

PubMed Central

Sanbonmatsu, K. Y.; Tung, C.-S.

2007-01-01

Computational methods have been used in biology for sequence analysis (bioinformatics), all-atom simulation (molecular dynamics and quantum calculations), and more recently for modeling biological networks (systems biology). Of these three techniques, all-atom simulation is currently the most computationally demanding, in terms of compute load, communication speed, and memory load. Breakthroughs in electrostatic force calculation and dynamic load balancing have enabled molecular dynamics simulations of large biomolecular complexes. Here, we report simulation results for the ribosome, using approximately 2.64 million atoms, the largest all-atom biomolecular simulation published to date. Several other nanoscale systems with different numbers of atoms were studied to measure the performance of the NAMD molecular dynamics simulation program on the Los Alamos National Laboratory Q Machine. We demonstrate that multimillion atom systems represent a 'sweet spot' for the NAMD code on large supercomputers. NAMD displays an unprecedented 85% parallel scaling efficiency for the ribosome system on 1024 CPUs. We also review recent targeted molecular dynamics simulations of the ribosome that prove useful for studying conformational changes of this large biomolecular complex in atomic detail. PMID:17187988

Multiscale Computation. Needs and Opportunities for BER Science

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scheibe, Timothy D.; Smith, Jeremy C.

2015-01-01

The Environmental Molecular Sciences Laboratory (EMSL), a scientific user facility managed by Pacific Northwest National Laboratory for the U.S. Department of Energy, Office of Biological and Environmental Research (BER), conducted a one-day workshop on August 26, 2014 on the topic of “Multiscale Computation: Needs and Opportunities for BER Science.” Twenty invited participants, from various computational disciplines within the BER program research areas, were charged with the following objectives; Identify BER-relevant models and their potential cross-scale linkages that could be exploited to better connect molecular-scale research to BER research at larger scales and; Identify critical science directions that will motivate EMSLmore » decisions regarding future computational (hardware and software) architectures.« less

O-desmethylquinine as a cyclooxygenase-2 (COX-2) inhibitors using AutoDock Vina

NASA Astrophysics Data System (ADS)

Damayanti, Sophi; Mahardhika, Andhika Bintang; Ibrahim, Slamet; Chong, Wei Lim; Lee, Vannajan Sanghiran; Tjahjono, Daryono Hadi

2014-10-01

Computational approach was employed to evaluate the biological activity of novel cyclooxygenase-2 COX-2 inhibitor, O-desmethylquinine, in comparison to quinine as common inhibitor which can also be used an agent of antipyretic, antimalaria, analgesic and antiinflamation. The molecular models of the compound were constructed and optimized with the density function theory with at the B3LYP/6-31G (d,p) level using Gaussian 09 program. Molecular docking studies of the compounds were done to obtain the COX-2 complex structures and their binding energies were analyzed using the AutoDock Vina. The results of docking of the two ligands were comparable and cannot be differentiated from the energy scoring function with AutoDock Vina.

Synthetic Molecular Machines for Active Self-Assembly: Prototype Algorithms, Designs, and Experimental Study

NASA Astrophysics Data System (ADS)

Dabby, Nadine L.

Computer science and electrical engineering have been the great success story of the twentieth century. The neat modularity and mapping of a language onto circuits has led to robots on Mars, desktop computers and smartphones. But these devices are not yet able to do some of the things that life takes for granted: repair a scratch, reproduce, regenerate, or grow exponentially fast--all while remaining functional. This thesis explores and develops algorithms, molecular implementations, and theoretical proofs in the context of "active self-assembly" of molecular systems. The long-term vision of active self-assembly is the theoretical and physical implementation of materials that are composed of reconfigurable units with the programmability and adaptability of biology's numerous molecular machines. En route to this goal, we must first find a way to overcome the memory limitations of molecular systems, and to discover the limits of complexity that can be achieved with individual molecules. One of the main thrusts in molecular programming is to use computer science as a tool for figuring out what can be achieved. While molecular systems that are Turing-complete have been demonstrated [Winfree, 1996], these systems still cannot achieve some of the feats biology has achieved. One might think that because a system is Turing-complete, capable of computing "anything," that it can do any arbitrary task. But while it can simulate any digital computational problem, there are many behaviors that are not "computations" in a classical sense, and cannot be directly implemented. Examples include exponential growth and molecular motion relative to a surface. Passive self-assembly systems cannot implement these behaviors because (a) molecular motion relative to a surface requires a source of fuel that is external to the system, and (b) passive systems are too slow to assemble exponentially-fast-growing structures. We call these behaviors "energetically incomplete" programmable behaviors. This class of behaviors includes any behavior where a passive physical system simply does not have enough physical energy to perform the specified tasks in the requisite amount of time. As we will demonstrate and prove, a sufficiently expressive implementation of an "active" molecular self-assembly approach can achieve these behaviors. Using an external source of fuel solves part of the problem, so the system is not "energetically incomplete." But the programmable system also needs to have sufficient expressive power to achieve the specified behaviors. Perhaps surprisingly, some of these systems do not even require Turing completeness to be sufficiently expressive. Building on a large variety of work by other scientists in the fields of DNA nanotechnology, chemistry and reconfigurable robotics, this thesis introduces several research contributions in the context of active self-assembly. We show that simple primitives such as insertion and deletion are able to generate complex and interesting results such as the growth of a linear polymer in logarithmic time and the ability of a linear polymer to treadmill. To this end we developed a formal model for active-self assembly that is directly implementable with DNA molecules. We show that this model is computationally equivalent to a machine capable of producing strings that are stronger than regular languages and, at most, as strong as context-free grammars. This is a great advance in the theory of active self-assembly as prior models were either entirely theoretical or only implementable in the context of macro-scale robotics. We developed a chain reaction method for the autonomous exponential growth of a linear DNA polymer. Our method is based on the insertion of molecules into the assembly, which generates two new insertion sites for every initial one employed. The building of a line in logarithmic time is a first step toward building a shape in logarithmic time. We demonstrate the first construction of a synthetic linear polymer that grows exponentially fast via insertion. We show that monomer molecules are converted into the polymer in logarithmic time via spectrofluorimetry and gel electrophoresis experiments. We also demonstrate the division of these polymers via the addition of a single DNA complex that competes with the insertion mechanism. This shows the growth of a population of polymers in logarithmic time. We characterize the DNA insertion mechanism that we utilize in Chapter 4. We experimentally demonstrate that we can control the kinetics of this reaction over at least seven orders of magnitude, by programming the sequences of DNA that initiate the reaction. In addition, we review co-authored work on programming molecular robots using prescriptive landscapes of DNA origami; this was the first microscopic demonstration of programming a molecular robot to walk on a 2-dimensional surface. We developed a snapshot method for imaging these random walking molecular robots and a CAPTCHA-like analysis method for difficult-to-interpret imaging data.

Molecular Cooperativity Governs Diverse and Monoallelic Olfactory Receptor Expression

NASA Astrophysics Data System (ADS)

Xing, Jianhua; Tian, Xiaojun; Zhang, Hang; Sannerud, Jens

Multiple-objective optimization is common in biological systems. In the mammalian olfactory system, each sensory neuron stochastically expresses only one out of up to thousands of olfactory receptor (OR) gene alleles; at organism level the types of expressed ORs need to be maximized. The molecular mechanism of this Nobel-Prize winning puzzle remains unresolved after decades of extensive studies. Existing models focus only on monoallele activation, and cannot explain recent observations in mutants, especially the reduced global diversity of expressed ORs in G9a/GLP knockouts. In this work we integrated existing information on OR expression, and proposed an evolutionarily optimized three-layer regulation mechanism, which includes zonal segregation, epigenetic and enhancer competition coupled to a negative feedback loop. This model not only recapitulates monoallelic OR expression, but also elucidates how the olfactory system maximizes and maintains the diversity of OR expression. The model is validated by several experimental results, and particularly underscores cooperativity and synergy as a general design principle of multi-objective optimization in biology. The work is supported by the NIGMS/DMS Mathematical Biology program.

A National Comparison of Biochemistry and Molecular Biology Capstone Experiences

ERIC Educational Resources Information Center

Aguanno, Ann; Mertz, Pamela; Martin, Debra; Bell, Ellis

2015-01-01

Recognizing the increasingly integrative nature of the molecular life sciences, the "American Society for Biochemistry and Molecular Biology" (ASBMB) recommends that Biochemistry and Molecular Biology (BMB) programs develop curricula based on concepts, content, topics, and expected student outcomes, rather than courses. To that end,…

Avogadro: an advanced semantic chemical editor, visualization, and analysis platform

PubMed Central

2012-01-01

Background The Avogadro project has developed an advanced molecule editor and visualizer designed for cross-platform use in computational chemistry, molecular modeling, bioinformatics, materials science, and related areas. It offers flexible, high quality rendering, and a powerful plugin architecture. Typical uses include building molecular structures, formatting input files, and analyzing output of a wide variety of computational chemistry packages. By using the CML file format as its native document type, Avogadro seeks to enhance the semantic accessibility of chemical data types. Results The work presented here details the Avogadro library, which is a framework providing a code library and application programming interface (API) with three-dimensional visualization capabilities; and has direct applications to research and education in the fields of chemistry, physics, materials science, and biology. The Avogadro application provides a rich graphical interface using dynamically loaded plugins through the library itself. The application and library can each be extended by implementing a plugin module in C++ or Python to explore different visualization techniques, build/manipulate molecular structures, and interact with other programs. We describe some example extensions, one which uses a genetic algorithm to find stable crystal structures, and one which interfaces with the PackMol program to create packed, solvated structures for molecular dynamics simulations. The 1.0 release series of Avogadro is the main focus of the results discussed here. Conclusions Avogadro offers a semantic chemical builder and platform for visualization and analysis. For users, it offers an easy-to-use builder, integrated support for downloading from common databases such as PubChem and the Protein Data Bank, extracting chemical data from a wide variety of formats, including computational chemistry output, and native, semantic support for the CML file format. For developers, it can be easily extended via a powerful plugin mechanism to support new features in organic chemistry, inorganic complexes, drug design, materials, biomolecules, and simulations. Avogadro is freely available under an open-source license from http://avogadro.openmolecules.net. PMID:22889332

Avogadro: an advanced semantic chemical editor, visualization, and analysis platform.

PubMed

Hanwell, Marcus D; Curtis, Donald E; Lonie, David C; Vandermeersch, Tim; Zurek, Eva; Hutchison, Geoffrey R

2012-08-13

The Avogadro project has developed an advanced molecule editor and visualizer designed for cross-platform use in computational chemistry, molecular modeling, bioinformatics, materials science, and related areas. It offers flexible, high quality rendering, and a powerful plugin architecture. Typical uses include building molecular structures, formatting input files, and analyzing output of a wide variety of computational chemistry packages. By using the CML file format as its native document type, Avogadro seeks to enhance the semantic accessibility of chemical data types. The work presented here details the Avogadro library, which is a framework providing a code library and application programming interface (API) with three-dimensional visualization capabilities; and has direct applications to research and education in the fields of chemistry, physics, materials science, and biology. The Avogadro application provides a rich graphical interface using dynamically loaded plugins through the library itself. The application and library can each be extended by implementing a plugin module in C++ or Python to explore different visualization techniques, build/manipulate molecular structures, and interact with other programs. We describe some example extensions, one which uses a genetic algorithm to find stable crystal structures, and one which interfaces with the PackMol program to create packed, solvated structures for molecular dynamics simulations. The 1.0 release series of Avogadro is the main focus of the results discussed here. Avogadro offers a semantic chemical builder and platform for visualization and analysis. For users, it offers an easy-to-use builder, integrated support for downloading from common databases such as PubChem and the Protein Data Bank, extracting chemical data from a wide variety of formats, including computational chemistry output, and native, semantic support for the CML file format. For developers, it can be easily extended via a powerful plugin mechanism to support new features in organic chemistry, inorganic complexes, drug design, materials, biomolecules, and simulations. Avogadro is freely available under an open-source license from http://avogadro.openmolecules.net.

Physiological, Molecular and Genetic Mechanisms of Long-Term Habituation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Calin-Jageman, Robert J

Work funded on this grant has explored the mechanisms of long-term habituation, a ubiquitous form of learning that plays a key role in basic cognitive functioning. Specifically, behavioral, physiological, and molecular mechanisms of habituation have been explored using a simple model system, the tail-elicited siphon-withdrawal reflex (T-SWR) in the marine mollusk Aplysia californica. Substantial progress has been made on the first and third aims, providing some fundamental insights into the mechanisms by which memories are stored. We have characterized the physiological correlates of short- and long-term habituation. We found that short-term habituation is accompanied by a robust sensory adaptation, whereasmore » long-term habituation is accompanied by alterations in sensory and interneuron synaptic efficacy. Thus, our data indicates memories can be shifted between different sites in a neural network as they are consolidated from short to long term. At the molecular level, we have accomplished microarray analysis comparing gene expression in both habituated and control ganglia. We have identified a network of putatively regulated transcripts that seems particularly targeted towards synaptic changes (e.g. SNAP25, calmodulin) . We are now beginning additional work to confirm regulation of these transcripts and build a more detailed understanding of the cascade of molecular events leading to the permanent storage of long-term memories. On the third aim, we have fostered a nascent neuroscience program via a variety of successful initiatives. We have funded over 11 undergraduate neuroscience scholars, several of whom have been recognized at national and regional levels for their research. We have also conducted a pioneering summer research program for community college students which is helping enhance access of underrepresented groups to life science careers. Despite minimal progress on the second aim, this project has provided a) novel insight into the network mechanisms by which short-term memories are permanently stored, and b) a strong foundation for continued growth of an excellent undergraduate neuroscience program.« less

Understanding the structural and energetic basis of PD-1 and monoclonal antibodies bound to PD-L1: A molecular modeling perspective.

PubMed

Shi, Danfeng; Zhou, Shuangyan; Liu, Xuewei; Zhao, Chenxi; Liu, Huanxiang; Yao, Xiaojun

2018-03-01

The inhibitors blocking the interaction between programmed cell death protein 1(PD-1) and programmed death-ligand 1(PD-L1) can activate the immune response of T cell and eliminate cancer cells. The crystallographic studies have provided structural insights of the interactive interfaces between PD-L1 and its protein ligands. However, the hotspot residues on PD-L1 as well as structural and energetic basis for different protein ligands still need to be further investigated. Molecular modeling methods including molecular dynamics simulation, per-residue free energy decomposition, virtual alanine scanning mutagenesis and residue-residue contact analysis were used to qualitatively and quantitatively analyze the interactions between PD-L1 and different protein ligands. The results of virtual alanine scanning mutagenesis suggest that Y56, Q66, M115, D122, Y123, R125 are the hotspot residues on PD-L1. The residue-residue contact analysis further shows that PD-1 interacts with PD-L1 mainly by F and G strands while monoclonal antibodies like avelumab and BMS-936559 mainly interact with PD-L1 by CDR2 and CDR3 loops of the heavy chain. A structurally similar β-hairpin peptide with 13 or 14 residues was extracted from each protein ligand and these β-hairpin peptides were found tightly binding to the putative hotspot residues on PD-L1. This study recognizes the hotspot residues on PD-L1 and uncovers the common structural and energetic basis of different protein ligands binding to PD-L1. These results will be valuable for the design of small molecule or peptide inhibitors targeting on PD-L1. Copyright © 2017 Elsevier B.V. All rights reserved.

Studies for the Loss of Atomic and Molecular Species from IO

NASA Technical Reports Server (NTRS)

Combi, Michael R.

1999-01-01

The general objective of this project has been to advance our theoretical understanding of lo's atmosphere and how various atomic and molecular species are lost from this atmosphere and are distributed in the circumplanetary environment of Jupiter. This grant has provided support for the activities of Dr. Michael Combi at the University of Michigan to serve as a small part in collaboration with a larger project awarded to Atmospheric & Environmental Research, Inc., with primary principal investigator Dr. William H. Smyth. Dr. Combi is the Principal Investigator and Project Manager for the Michigan grant NAG5-6187. This Michigan grant has provided for a continuation of a collaboration between Drs. Smyth and Combi in related efforts beginning in 1981, and with the object to develop and apply sophisticated theoretical models to interpret and to relate a number of new and exciting observations for the atmospheric gases of the satellite. The ability to interpret and then to relate through the theoretical fabric a number of these otherwise independent observations are a central strength of this program. This comprehensive approach provides a collective power, extracting more from the sum of the parts and seeing beyond various limitations that are inherent in any one observation. Although the approach is designed to unify, the program is divided into well-defined studies for the likely dominant atmospheric gases involving species of the SO2 family (SO2, SO, O2, S and O) and for the trace atmospheric gas atomic sodium and a likely escaping molecular ion NaX(+) (where Na(X) is the atmospheric molecule and X represents one or more atoms).Attachments: IO's sodium corona and spatially cloud: a consistent flux speed distribution. and Io's plasma environment during the Galileo flyby: global three-dimensional MHD modeling with adaptive mesh refinement.

Four-component relativistic calculations in solution with the polarizable continuum model of solvation: theory, implementation, and application to the group 16 dihydrides H2X (X = O, S, Se, Te, Po).

PubMed

Remigio, Roberto Di; Bast, Radovan; Frediani, Luca; Saue, Trond

2015-05-28

We present a formulation of four-component relativistic self-consistent field (SCF) theory for a molecular solute described within the framework of the polarizable continuum model (PCM) for solvation. The linear response function for a four-component PCM-SCF state is also derived, as well as the explicit form of the additional contributions to the first-order response equations. The implementation of such a four-component PCM-SCF model, as carried out in a development version of the DIRAC program package, is documented. In particular, we present the newly developed application programming interface PCMSolver used in the actual implementation with DIRAC. To demonstrate the applicability of the approach, we present and analyze calculations of solvation effects on the geometries, electric dipole moments, and static electric dipole polarizabilities for the group 16 dihydrides H2X (X = O, S, Se, Te, Po).

Towards a molecular logic machine

NASA Astrophysics Data System (ADS)

Remacle, F.; Levine, R. D.

2001-06-01

Finite state logic machines can be realized by pump-probe spectroscopic experiments on an isolated molecule. The most elaborate setup, a Turing machine, can be programmed to carry out a specific computation. We argue that a molecule can be similarly programmed, and provide examples using two photon spectroscopies. The states of the molecule serve as the possible states of the head of the Turing machine and the physics of the problem determines the possible instructions of the program. The tape is written in an alphabet that allows the listing of the different pump and probe signals that are applied in a given experiment. Different experiments using the same set of molecular levels correspond to different tapes that can be read and processed by the same head and program. The analogy to a Turing machine is not a mechanical one and is not completely molecular because the tape is not part of the molecular machine. We therefore also discuss molecular finite state machines, such as sequential devices, for which the tape is not part of the machine. Nonmolecular tapes allow for quite long input sequences with a rich alphabet (at the level of 7 bits) and laser pulse shaping experiments provide concrete examples. Single molecule spectroscopies show that a single molecule can be repeatedly cycled through a logical operation.

Evolution of apoptosis-like programmed cell death in unicellular protozoan parasites.

PubMed

Kaczanowski, Szymon; Sajid, Mohammed; Reece, Sarah E

2011-03-25

Apoptosis-like programmed cell death (PCD) has recently been described in multiple taxa of unicellular protists, including the protozoan parasites Plasmodium, Trypanosoma and Leishmania. Apoptosis-like PCD in protozoan parasites shares a number of morphological features with programmed cell death in multicellular organisms. However, both the evolutionary explanations and mechanisms involved in parasite PCD are poorly understood. Explaining why unicellular organisms appear to undergo 'suicide' is a challenge for evolutionary biology and uncovering death executors and pathways is a challenge for molecular and cell biology. Bioinformatics has the potential to integrate these approaches by revealing homologies in the PCD machinery of diverse taxa and evaluating their evolutionary trajectories. As the molecular mechanisms of apoptosis in model organisms are well characterised, and recent data suggest similar mechanisms operate in protozoan parasites, key questions can now be addressed. These questions include: which elements of apoptosis machinery appear to be shared between protozoan parasites and multicellular taxa and, have these mechanisms arisen through convergent or divergent evolution? We use bioinformatics to address these questions and our analyses suggest that apoptosis mechanisms in protozoan parasites and other taxa have diverged during their evolution, that some apoptosis factors are shared across taxa whilst others have been replaced by proteins with similar biochemical activities.

Evolution of apoptosis-like programmed cell death in unicellular protozoan parasites

PubMed Central

2011-01-01

Apoptosis-like programmed cell death (PCD) has recently been described in multiple taxa of unicellular protists, including the protozoan parasites Plasmodium, Trypanosoma and Leishmania. Apoptosis-like PCD in protozoan parasites shares a number of morphological features with programmed cell death in multicellular organisms. However, both the evolutionary explanations and mechanisms involved in parasite PCD are poorly understood. Explaining why unicellular organisms appear to undergo 'suicide' is a challenge for evolutionary biology and uncovering death executors and pathways is a challenge for molecular and cell biology. Bioinformatics has the potential to integrate these approaches by revealing homologies in the PCD machinery of diverse taxa and evaluating their evolutionary trajectories. As the molecular mechanisms of apoptosis in model organisms are well characterised, and recent data suggest similar mechanisms operate in protozoan parasites, key questions can now be addressed. These questions include: which elements of apoptosis machinery appear to be shared between protozoan parasites and multicellular taxa and, have these mechanisms arisen through convergent or divergent evolution? We use bioinformatics to address these questions and our analyses suggest that apoptosis mechanisms in protozoan parasites and other taxa have diverged during their evolution, that some apoptosis factors are shared across taxa whilst others have been replaced by proteins with similar biochemical activities. PMID:21439063

Session 6: Infant nutrition: future research developments in Europe EARNEST, the early nutrition programming project: EARly Nutrition programming - long-term Efficacy and Safety Trials and integrated epidemiological, genetic, animal, consumer and economic research.

PubMed

Fewtrell, M S

2007-08-01

Increasing evidence from lifetime experimental studies in animals and observational and experimental studies in human subjects suggests that pre- and postnatal nutrition programme long-term health. However, key unanswered questions remain on the extent of early-life programming in contemporary European populations, relevant nutritional exposures, critical time periods, mechanisms and the effectiveness of interventions to prevent or reverse programming effects. The EARly Nutrition programming - long-term Efficacy and Safety Trials and integrated epidemiological, genetic, animal, consumer and economic research (EARNEST) consortium brings together a multi-disciplinary team of scientists from European research institutions in an integrated programme of work that includes experimental studies in human subjects, modern prospective observational studies and mechanistic animal work including physiological studies, cell-culture models and molecular techniques. Theme 1 tests early nutritional programming of disease in human subjects, measuring disease markers in childhood and early adulthood in nineteen randomised controlled trials of nutritional interventions in pregnancy and infancy. Theme 2 examines associations between early nutrition and later outcomes in large modern European population-based prospective studies, with detailed measures of diet in pregnancy and early life. Theme 3 uses animal, cellular and molecular techniques to study lifetime effects of early nutrition. Biomedical studies are complemented by studies of the social and economic importance of programming (themes 4 and 5), and themes encouraging integration, communication, training and wealth creation. The project aims to: help formulate policies on the composition and testing of infant foods; improve the nutritional value of infant formulas; identify interventions to prevent and reverse adverse early nutritional programming. In addition, it has the potential to develop new products through industrial partnerships, generate information on the social and economic cost of programming in Europe and help maintain Europe's lead in this critical area of research.

Massively parallel implementation of 3D-RISM calculation with volumetric 3D-FFT.

PubMed

Maruyama, Yutaka; Yoshida, Norio; Tadano, Hiroto; Takahashi, Daisuke; Sato, Mitsuhisa; Hirata, Fumio

2014-07-05

A new three-dimensional reference interaction site model (3D-RISM) program for massively parallel machines combined with the volumetric 3D fast Fourier transform (3D-FFT) was developed, and tested on the RIKEN K supercomputer. The ordinary parallel 3D-RISM program has a limitation on the number of parallelizations because of the limitations of the slab-type 3D-FFT. The volumetric 3D-FFT relieves this limitation drastically. We tested the 3D-RISM calculation on the large and fine calculation cell (2048(3) grid points) on 16,384 nodes, each having eight CPU cores. The new 3D-RISM program achieved excellent scalability to the parallelization, running on the RIKEN K supercomputer. As a benchmark application, we employed the program, combined with molecular dynamics simulation, to analyze the oligomerization process of chymotrypsin Inhibitor 2 mutant. The results demonstrate that the massive parallel 3D-RISM program is effective to analyze the hydration properties of the large biomolecular systems. Copyright © 2014 Wiley Periodicals, Inc.

Developing QSPR model of gas/particle partition coefficients of neutral poly-/perfluoroalkyl substances

NASA Astrophysics Data System (ADS)

Yuan, Quan; Ma, Guangcai; Xu, Ting; Serge, Bakire; Yu, Haiying; Chen, Jianrong; Lin, Hongjun

2016-10-01

Poly-/perfluoroalkyl substances (PFASs) are a class of synthetic fluorinated organic substances that raise increasing concern because of their environmental persistence, bioaccumulation and widespread presence in various environment media and organisms. PFASs can be released into the atmosphere through both direct and indirect sources, and the gas/particle partition coefficient (KP) is an important parameter that helps us to understand their atmospheric behavior. In this study, we developed a temperature-dependent predictive model for log KP of PFASs and analyzed the molecular mechanism that governs their partitioning equilibrium between gas phase and particle phase. All theoretical computation was carried out at B3LYP/6-31G (d, p) level based on neutral molecular structures by Gaussian 09 program package. The regression model has a good statistical performance and robustness. The application domain has also been defined according to OECD guidance. The mechanism analysis shows that electrostatic interaction and dispersion interaction play the most important role in the partitioning equilibrium. The developed model can be used to predict log KP values of neutral fluorotelomer alcohols and perfluor sulfonamides/sulfonamidoethanols with different substitutions at nitrogen atoms, providing basic data for their ecological risk assessment.

Molecular-Beam-Epitaxy Program

NASA Technical Reports Server (NTRS)

Sparks, Patricia D.

1988-01-01

Molecular Beam Epitaxy (MBE) computer program developed to aid in design of single- and double-junction cascade cells made of silicon. Cascade cell has efficiency 1 or 2 percent higher than single cell, with twice the open-circuit voltage. Input parameters include doping density, diffusion lengths, thicknesses of regions, solar spectrum, absorption coefficients of silicon (data included for 101 wavelengths), and surface recombination velocities. Results include maximum power, short-circuit current, and open-circuit voltage. Program written in FORTRAN IV.

Studies for the Loss of Atomic and Molecular Species from Io

NASA Technical Reports Server (NTRS)

Combi, Michael R.

1997-01-01

The general objective of this project has been to advance our theoretical understanding of Io's atmosphere and how various atomic and molecular species are lost from this atmosphere and are distributed in the circumplanetary environment of Jupiter. The scientific objectives of the larger collaborative program between AER, Inc., and the University of Michigan have been to undertake theoretical modeling studies to simulate the distributions of the exospheric gases in Io's corona and extended clouds, to investigate the importance of the various physical processes that shape their relative abundances, and with these tools to analyze observations of O, S and Na obtained by four observers: M.A. McGrath of the Space Telescope Science Institute and G.E. Ballester of the University of Michigan who each have obtained Hubble Space Telescope observations of O and S near Io, F. Scherb who continues an effort to obtain 6300 A OI observations as part of the University of Wisconsin Fabry-Perot program, and N.M. Schneider of the University of Colorado who obtained an extensive set of spectral and spatial observations of the Na emission near Io in the D-lines.

Representation of molecular structure using quantum topology with inductive logic programming in structure-activity relationships.

PubMed

Buttingsrud, Bård; Ryeng, Einar; King, Ross D; Alsberg, Bjørn K

2006-06-01

The requirement of aligning each individual molecule in a data set severely limits the type of molecules which can be analysed with traditional structure activity relationship (SAR) methods. A method which solves this problem by using relations between objects is inductive logic programming (ILP). Another advantage of this methodology is its ability to include background knowledge as 1st-order logic. However, previous molecular ILP representations have not been effective in describing the electronic structure of molecules. We present a more unified and comprehensive representation based on Richard Bader's quantum topological atoms in molecules (AIM) theory where critical points in the electron density are connected through a network. AIM theory provides a wealth of chemical information about individual atoms and their bond connections enabling a more flexible and chemically relevant representation. To obtain even more relevant rules with higher coverage, we apply manual postprocessing and interpretation of ILP rules. We have tested the usefulness of the new representation in SAR modelling on classifying compounds of low/high mutagenicity and on a set of factor Xa inhibitors of high and low affinity.

Radiobiological modeling with MarCell software

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hasan, J.S.; Jones, T.D.

1999-01-01

A nonlinear system of differential equations that models the bone marrow cellular kinetics associated with radiation injury, molecular repair, and compensatory cell proliferation has been extensively documented. Recently, that model has been implemented as MarCell, a user-friendly MS-DOS computer program that allows users with little knowledge of the original model to evaluate complex radiation exposure scenarios. The software allows modeling with the following radiations: tritium beta, 100 kVp X, 250 kVp X, 22 MV X, {sup 60}Co, {sup 137}Cs, 2 MeV electrons, triga neutrons, D-T neutrons, and 3 blends of mixed-field fission radiations. The possible cell lineages are stem, stroma,more » and leukemia/lymphoma, and the available species include mouse, rat, dog, sheep, swine, burro, and man. An attractive mathematical feature is that any protracted protocol can be expressed as an equivalent prompt dose for either the source used or for a reference, such as 250 kVp X rays or {sup 60}Co. Output from MarCell includes: risk of 30-day mortality; risk of cancer and leukemia based either on cytopenia or compensatory cell proliferation; cell survival plots as a function of time or dose; and 4-week recovery kinetics following treatment. In this article, the program`s applicability and ease of use are demonstrated by evaluating a medical total body irradiation protocol and a nuclear fallout scenario.« less

Molecular implementation of simple logic programs.

PubMed

Ran, Tom; Kaplan, Shai; Shapiro, Ehud

2009-10-01

Autonomous programmable computing devices made of biomolecules could interact with a biological environment and be used in future biological and medical applications. Biomolecular implementations of finite automata and logic gates have already been developed. Here, we report an autonomous programmable molecular system based on the manipulation of DNA strands that is capable of performing simple logical deductions. Using molecular representations of facts such as Man(Socrates) and rules such as Mortal(X) <-- Man(X) (Every Man is Mortal), the system can answer molecular queries such as Mortal(Socrates)? (Is Socrates Mortal?) and Mortal(X)? (Who is Mortal?). This biomolecular computing system compares favourably with previous approaches in terms of expressive power, performance and precision. A compiler translates facts, rules and queries into their molecular representations and subsequently operates a robotic system that assembles the logical deductions and delivers the result. This prototype is the first simple programming language with a molecular-scale implementation.

CHARMM-GUI 10 Years for Biomolecular Modeling and Simulation

PubMed Central

Jo, Sunhwan; Cheng, Xi; Lee, Jumin; Kim, Seonghoon; Park, Sang-Jun; Patel, Dhilon S.; Beaven, Andrew H.; Lee, Kyu Il; Rui, Huan; Roux, Benoît; MacKerell, Alexander D.; Klauda, Jeffrey B.; Qi, Yifei

2017-01-01

CHARMM-GUI, http://www.charmm-gui.org, is a web-based graphical user interface that prepares complex biomolecular systems for molecular simulations. CHARMM-GUI creates input files for a number of programs including CHARMM, NAMD, GROMACS, AMBER, GENESIS, LAMMPS, Desmond, OpenMM, and CHARMM/OpenMM. Since its original development in 2006, CHARMM-GUI has been widely adopted for various purposes and now contains a number of different modules designed to set up a broad range of simulations: (1) PDB Reader & Manipulator, Glycan Reader, and Ligand Reader & Modeler for reading and modifying molecules; (2) Quick MD Simulator, Membrane Builder, Nanodisc Builder, HMMM Builder, Monolayer Builder, Micelle Builder, and Hex Phase Builder for building all-atom simulation systems in various environments; (3) PACE CG Builder and Martini Maker for building coarse-grained simulation systems; (4) DEER Facilitator and MDFF/xMDFF Utilizer for experimentally guided simulations; (5) Implicit Solvent Modeler, PBEQ-Solver, and GCMC/BD Ion Simulator for implicit solvent related calculations; (6) Ligand Binder for ligand solvation and binding free energy simulations; and (7) Drude Prepper for preparation of simulations with the CHARMM Drude polarizable force field. Recently, new modules have been integrated into CHARMM-GUI, such as Glycolipid Modeler for generation of various glycolipid structures, and LPS Modeler for generation of lipopolysaccharide structures from various Gram-negative bacteria. These new features together with existing modules are expected to facilitate advanced molecular modeling and simulation thereby leading to an improved understanding of the molecular details of the structure and dynamics of complex biomolecular systems. Here, we briefly review these capabilities and discuss potential future directions in the CHARMM-GUI development project. PMID:27862047

A Model Program for Translational Medicine in Epilepsy Genetics

PubMed Central

Smith, Lacey A.; Ullmann, Jeremy F. P.; Olson, Heather E.; El Achkar, Christelle M.; Truglio, Gessica; Kelly, McKenna; Rosen-Sheidley, Beth; Poduri, Annapurna

2017-01-01

Recent technological advances in gene sequencing have led to a rapid increase in gene discovery in epilepsy. However, the ability to assess pathogenicity of variants, provide functional analysis, and develop targeted therapies has not kept pace with rapid advances in sequencing technology. Thus, although clinical genetic testing may lead to a specific molecular diagnosis for some patients, test results often lead to more questions than answers. As the field begins to focus on therapeutic applications of genetic diagnoses using precision medicine, developing processes that offer more than equivocal test results is essential. The success of precision medicine in epilepsy relies on establishing a correct genetic diagnosis, analyzing functional consequences of genetic variants, screening potential therapeutics in the preclinical laboratory setting, and initiating targeted therapy trials for patients. We describe the structure of a comprehensive, pediatric Epilepsy Genetics Program that can serve as a model for translational medicine in epilepsy. PMID:28056630

uPy: a ubiquitous CG Python API with biological-modeling applications.

PubMed

Autin, Ludovic; Johnson, Graham; Hake, Johan; Olson, Arthur; Sanner, Michel

2012-01-01

The uPy Python extension module provides a uniform abstraction of the APIs of several 3D computer graphics programs (called hosts), including Blender, Maya, Cinema 4D, and DejaVu. A plug-in written with uPy can run in all uPy-supported hosts. Using uPy, researchers have created complex plug-ins for molecular and cellular modeling and visualization. uPy can simplify programming for many types of projects (not solely science applications) intended for multihost distribution. It's available at http://upy.scripps.edu. The first featured Web extra is a video that shows interactive analysis of a calcium dynamics simulation. YouTube URL: http://youtu.be/wvs-nWE6ypo. The second featured Web extra is a video that shows rotation of the HIV virus. YouTube URL: http://youtu.be/vEOybMaRoKc.

View How Glaucoma May Affect Vision

MedlinePlus

... Alzheimer’s Disease Research Program Macular Degeneration Research Program National Glaucoma Research Program Molecular Neurodegeneration ... Foundation BrightFocus Foundation 22512 Gateway Center Drive Clarksburg, MD ...

Orchestrating liver development.

PubMed

Gordillo, Miriam; Evans, Todd; Gouon-Evans, Valerie

2015-06-15

The liver is a central regulator of metabolism, and liver failure thus constitutes a major health burden. Understanding how this complex organ develops during embryogenesis will yield insights into how liver regeneration can be promoted and how functional liver replacement tissue can be engineered. Recent studies of animal models have identified key signaling pathways and complex tissue interactions that progressively generate liver progenitor cells, differentiated lineages and functional tissues. In addition, progress in understanding how these cells interact, and how transcriptional and signaling programs precisely coordinate liver development, has begun to elucidate the molecular mechanisms underlying this complexity. Here, we review the lineage relationships, signaling pathways and transcriptional programs that orchestrate hepatogenesis. © 2015. Published by The Company of Biologists Ltd.

Oxidative Stress and Programmed Cell Death in Yeast

PubMed Central

Farrugia, Gianluca; Balzan, Rena

2012-01-01

Yeasts, such as Saccharomyces cerevisiae, have long served as useful models for the study of oxidative stress, an event associated with cell death and severe human pathologies. This review will discuss oxidative stress in yeast, in terms of sources of reactive oxygen species (ROS), their molecular targets, and the metabolic responses elicited by cellular ROS accumulation. Responses of yeast to accumulated ROS include upregulation of antioxidants mediated by complex transcriptional changes, activation of pro-survival pathways such as mitophagy, and programmed cell death (PCD) which, apart from apoptosis, includes pathways such as autophagy and necrosis, a form of cell death long considered accidental and uncoordinated. The role of ROS in yeast aging will also be discussed. PMID:22737670

Competency-Based Education for the Molecular Genetic Pathology Fellow

PubMed Central

Talbert, Michael L.; Dunn, S. Terence; Hunt, Jennifer; Hillyard, David R.; Mirza, Imran; Nowak, Jan A.; Van Deerlin, Vivianna; Vnencak-Jones, Cindy L.

2009-01-01

The following report represents guidelines for competency-based fellowship training in Molecular Genetic Pathology (MGP) developed by the Association for Molecular Pathology Training and Education Committee and Directors of MGP Programs in the United States. The goals of the effort were to describe each of the Accreditation Council for Graduate Medical Education competencies as they apply to MGP fellowship training, provide a summary of goals and objectives, and recommend assessment tools. These guidelines are particularly pertinent to MGP training, which is a relatively new specialty that operates within a rapidly changing scientific and technological arena. It is hoped that this document will provide additional material for directors of existing MGP programs to consider for improvement of program objectives and enhancement of evaluation tools already in place. In addition, the guidelines should provide a valuable framework for the development of new MGP programs. PMID:19797613

CAST: a new program package for the accurate characterization of large and flexible molecular systems.

PubMed

Grebner, Christoph; Becker, Johannes; Weber, Daniel; Bellinger, Daniel; Tafipolski, Maxim; Brückner, Charlotte; Engels, Bernd

2014-09-15

The presented program package, Conformational Analysis and Search Tool (CAST) allows the accurate treatment of large and flexible (macro) molecular systems. For the determination of thermally accessible minima CAST offers the newly developed TabuSearch algorithm, but algorithms such as Monte Carlo (MC), MC with minimization, and molecular dynamics are implemented as well. For the determination of reaction paths, CAST provides the PathOpt, the Nudge Elastic band, and the umbrella sampling approach. Access to free energies is possible through the free energy perturbation approach. Along with a number of standard force fields, a newly developed symmetry-adapted perturbation theory-based force field is included. Semiempirical computations are possible through DFTB+ and MOPAC interfaces. For calculations based on density functional theory, a Message Passing Interface (MPI) interface to the Graphics Processing Unit (GPU)-accelerated TeraChem program is available. The program is available on request. Copyright © 2014 Wiley Periodicals, Inc.

Yeast as a model to study apoptosis?

PubMed

Fleury, Christophe; Pampin, Mathieu; Tarze, Agathe; Mignotte, Bernard

2002-02-01

Programmed cell death (PCD) serves as a major mechanism for the precise regulation of cell numbers, and as a defense mechanism to remove unwanted and potentially dangerous cells. Despite the striking heterogeneity of cell death induction pathways, the execution of the death program is often associated with characteristic morphological and biochemical changes termed apoptosis. Although for a long time the absence of mitochondrial changes was considered as a hallmark of apoptosis, mitochondria appear today as the central executioner of programmed cell death. This crucial position of mitochondria in programmed cell death control is not due to a simple loss of function (deficit in energy supplying), but rather to an active process in the regulation of effector mechanisms. The large diversity of regulators of apoptosis in mammals and their numerous interactions complicate the analysis of their individual functions. Yeast, eukaryotic but unicellular organism, lack the main regulators of apoptosis (caspases, Bcl-2 family members, ...) found in mammals. This absence render them a powerful tool for heterologous expression, functional studies, and even cloning of new regulators of apoptosis. Great advances have thus been made in our understanding of the molecular mechanisms of Bcl-2 family members interactions with themselves and other cellular proteins, specially thanks to the two hybrid system and the easy manipulation of yeast (molecular biology and genetics). This review will focus on the use of yeast as a tool to identify new regulators and study function of mammalian apoptosis regulators.

Senior Computational Scientist | Center for Cancer Research

Cancer.gov

The Basic Science Program (BSP) pursues independent, multidisciplinary research in basic and applied molecular biology, immunology, retrovirology, cancer biology, and human genetics. Research efforts and support are an integral part of the Center for Cancer Research (CCR) at the Frederick National Laboratory for Cancer Research (FNLCR). The Cancer & Inflammation Program (CIP), Basic Science Program, HLA Immunogenetics Section, under the leadership of Dr. Mary Carrington, studies the influence of human leukocyte antigens (HLA) and specific KIR/HLA genotypes on risk of and outcomes to infection, cancer, autoimmune disease, and maternal-fetal disease. Recent studies have focused on the impact of HLA gene expression in disease, the molecular mechanism regulating expression levels, and the functional basis for the effect of differential expression on disease outcome. The lab’s further focus is on the genetic basis for resistance/susceptibility to disease conferred by immunogenetic variation. KEY ROLES/RESPONSIBILITIES The Senior Computational Scientist will provide research support to the CIP-BSP-HLA Immunogenetics Section performing bio-statistical design, analysis and reporting of research projects conducted in the lab. This individual will be involved in the implementation of statistical models and data preparation. Successful candidate should have 5 or more years of competent, innovative biostatistics/bioinformatics research experience, beyond doctoral training Considerable experience with statistical software, such as SAS, R and S-Plus Sound knowledge, and demonstrated experience of theoretical and applied statistics Write program code to analyze data using statistical analysis software Contribute to the interpretation and publication of research results

Grid-Based Surface Generalized Born Model for Calculation of Electrostatic Binding Free Energies.

PubMed

Forouzesh, Negin; Izadi, Saeed; Onufriev, Alexey V

2017-10-23

Fast and accurate calculation of solvation free energies is central to many applications, such as rational drug design. In this study, we present a grid-based molecular surface implementation of "R6" flavor of the generalized Born (GB) implicit solvent model, named GBNSR6. The speed, accuracy relative to numerical Poisson-Boltzmann treatment, and sensitivity to grid surface parameters are tested on a set of 15 small protein-ligand complexes and a set of biomolecules in the range of 268 to 25099 atoms. Our results demonstrate that the proposed model provides a relatively successful compromise between the speed and accuracy of computing polar components of the solvation free energies (ΔG pol ) and binding free energies (ΔΔG pol ). The model tolerates a relatively coarse grid size h = 0.5 Å, where the grid artifact error in computing ΔΔG pol remains in the range of k B T ∼ 0.6 kcal/mol. The estimated ΔΔG pol s are well correlated (r 2 = 0.97) with the numerical Poisson-Boltzmann reference, while showing virtually no systematic bias and RMSE = 1.43 kcal/mol. The grid-based GBNSR6 model is available in Amber (AmberTools) package of molecular simulation programs.

The Molecular Biology Capstone Assessment: A Concept Assessment for Upper-Division Molecular Biology Students

ERIC Educational Resources Information Center

Couch, Brian A.; Wood, William B.; Knight, Jennifer K.

2015-01-01

Measuring students' conceptual understandings has become increasingly important to biology faculty members involved in evaluating and improving departmental programs. We developed the Molecular Biology Capstone Assessment (MBCA) to gauge comprehension of fundamental concepts in molecular and cell biology and the ability to apply these concepts in…

A mechanism-mediated model for carcinogenicity: Model content and prediction of the outcome of rodent carcinogenicity bioassays currently being conducted on 25 organic chemicals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Purdy, R.

A hierarchical model consisting of quantitative structure-activity relationships based mainly on chemical reactivity was developed to predict the carcinogenicity of organic chemicals to rodents. The model is comprised of quantitative structure-activity relationships, QSARs based on hypothesized mechanisms of action, metabolism, and partitioning. Predictors included octanol/water partition coefficient, molecular size, atomic partial charge, bond angle strain, atomic acceptor delocalizibility, atomic radical superdelocalizibility, the lowest unoccupied molecular orbital (LUMO) energy of hypothesized intermediate nitrenium ion of primary aromatic amines, difference in charge of ionized and unionized carbon-chlorine bonds, substituent size and pattern on polynuclear aromatic hydrocarbons, the distance between lone electron pairsmore » over a rigid structure, and the presence of functionalities such as nitroso and hydrazine. The model correctly classified 96% of the carcinogens in the training set of 306 chemicals, and 90% of the carcinogens in the test set of 301 chemicals. The test set by chance contained 84% of the positive thiocontaining chemicals. A QSAR for these chemicals was developed. This posttest set modified model correctly predicted 94% of the carcinogens in the test set. This model was used to predict the carcinogenicity of the 25 organic chemicals the U.S. National Toxicology Program was testing at the writing of this article. 12 refs., 3 tabs.« less

The calculation of theoretical chromospheric models and the interpretation of the solar spectrum

NASA Technical Reports Server (NTRS)

Avrett, Eugene H.

1994-01-01

Since the early 1970s we have been developing the extensive computer programs needed to construct models of the solar atmosphere and to calculate detailed spectra for use in the interpretation of solar observations. This research involves two major related efforts: work by Avrett and Loeser on the Pandora computer program for non-LTE modeling of the solar atmosphere including a wide range of physical processes, and work by Kurucz on the detailed synthesis of the solar spectrum based on opacity data for over 58 million atomic and molecular lines. Our goals are to determine models of the various features observed on the sun (sunspots, different components of quiet and active regions, and flares) by means of physically realistic models, and to calculate detailed spectra at all wavelengths that match observations of those features. These two goals are interrelated: discrepancies between calculated and observed spectra are used to determine improvements in the structure of the models, and in the detailed physical processes used in both the model calculations and the spectrum calculations. The atmospheric models obtained in this way provide not only the depth variation of various atmospheric parameters, but also a description of the internal physical processes that are responsible for nonradiative heating, and for solar activity in general.

The calculation of theoretical chromospheric models and the interpretation of solar spectra from rockets and spacecraft

NASA Technical Reports Server (NTRS)

Avrett, Eugene H.

1993-01-01

Since the early 1970s we have been developing the extensive computer programs needed to construct models of the solar atmosphere and to calculate detailed spectra for use in the interpretation of solar observations. This research involves two major related efforts: work by Avrett and Loeser on the Pandora computer program for non-LTE modeling of the solar atmosphere including a wide range of physical processes, and work by Kurucz on the detailed synthesis of the solar spectrum based on opacity data for over 58 million atomic and molecular lines. Our goals are to determine models of the various features observed on the Sun (sunspots, different components of quiet and active regions, and flares) by means of physically realistic models, and to calculate detailed spectra at all wavelengths that match observations of those features. These two goals are interrelated: discrepancies between calculated and observed spectra are used to determine improvements in the structure of the models, and in the detailed physical processes used in both the model calculations and the spectrum calculations. The atmospheric models obtained in this way provide not only the depth variation of various atmospheric parameters, but also a description of the internal physical processes that are responsible for non-radiative heating, and for solar activity in general.

Event simulation based on three-fluid hydrodynamics for collisions at energies available at the Dubna Nuclotron-based Ion Collider Facility and at the Facility for Antiproton and Ion Research in Darmstadt

NASA Astrophysics Data System (ADS)

Batyuk, P.; Blaschke, D.; Bleicher, M.; Ivanov, Yu. B.; Karpenko, Iu.; Merts, S.; Nahrgang, M.; Petersen, H.; Rogachevsky, O.

2016-10-01

We present an event generator based on the three-fluid hydrodynamics approach for the early stage of the collision, followed by a particlization at the hydrodynamic decoupling surface to join to a microscopic transport model, ultrarelativistic quantum molecular dynamics, to account for hadronic final-state interactions. We present first results for nuclear collisions of the Facility for Antiproton and Ion Research-Nuclotron-based Ion Collider Facility energy scan program (Au+Au collisions, √{sN N}=4 -11 GeV ). We address the directed flow of protons and pions as well as the proton rapidity distribution for two model equations of state, one with a first-order phase transition and the other with a crossover-type softening at high densities. The new simulation program has the unique feature that it can describe a hadron-to-quark matter transition which proceeds in the baryon stopping regime that is not accessible to previous simulation programs designed for higher energies.

Molecular mechanisms involved in Bacillus subtilis biofilm formation

PubMed Central

Mielich-Süss, Benjamin; Lopez, Daniel

2014-01-01

Summary Biofilms are the predominant lifestyle of bacteria in natural environments, and they severely impact our societies in many different fashions. Therefore, biofilm formation is a topic of growing interest in microbiology, and different bacterial models are currently studied to better understand the molecular strategies that bacteria undergo to build biofilms. Among those, biofilms of the soil-dwelling bacterium Bacillus subtilis are commonly used for this purpose. Bacillus subtilis biofilms show remarkable architectural features that are a consequence of sophisticated programs of cellular specialization and cell-cell communication within the community. Many laboratories are trying to unravel the biological role of the morphological features of biofilms, as well as exploring the molecular basis underlying cellular differentiation. In this review, we present a general perspective of the current state of knowledge of biofilm formation in B. subtilis. In particular, a special emphasis is placed on summarizing the most recent discoveries in the field and integrating them into the general view of these truly sophisticated microbial communities. PMID:24909922

Mass-spectrometric analysis of hydroperoxy- and hydroxy-derivatives of cardiolipin and phosphatidylserine in cells and tissues induced by pro-apoptotic and pro-inflammatory stimuli

PubMed Central

Tyurin, Vladimir A.; Tyurina, Yulia Y.; Jung, Mi-Yeon; Tungekar, Muhammad A.; Wasserloos, Karla J.; Bayir, Hülya; Greenberger, Joel S.; Kochanek, Patrick M.; Shvedova, Anna A.; Pitt, Bruce; Kagan, Valerian E.

2009-01-01

Oxidation of two anionic phospholipids - cardiolipin (CL) in mitochondria and phosphatidylserine (PS) in extramitochondrial compartments - are important signaling events, particularly during the execution of programmed cell death and clearance of apoptotic cells. Quantitative analysis of CL and PS oxidation products is central to understanding their molecular mechanisms of action. We combined the identification of diverse phospholipid molecular species by ESI-MS with quantitative assessments of lipid hydroperoxides using a fluorescence HPLC-based protocol. We characterized CL and PS oxidation products formed in a model system (cyt c/H2O2), in apoptotic cells (neurons, pulmonary artery endothelial cells) and mouse lung under inflammatory/oxidative stress conditions (hyperoxia, inhalation of single walled carbon nanotubes). Our results demonstrate the usefulness of this approach for quantitative assessments, identification of individual molecular species and structural characterization of anionic phospholipids that are involved in oxidative modification in cells and tissues. PMID:19328050

Density functional theory for molecular and periodic systems using density fitting and continuous fast multipole method: Analytical gradients.

PubMed

Łazarski, Roman; Burow, Asbjörn Manfred; Grajciar, Lukáš; Sierka, Marek

2016-10-30

A full implementation of analytical energy gradients for molecular and periodic systems is reported in the TURBOMOLE program package within the framework of Kohn-Sham density functional theory using Gaussian-type orbitals as basis functions. Its key component is a combination of density fitting (DF) approximation and continuous fast multipole method (CFMM) that allows for an efficient calculation of the Coulomb energy gradient. For exchange-correlation part the hierarchical numerical integration scheme (Burow and Sierka, Journal of Chemical Theory and Computation 2011, 7, 3097) is extended to energy gradients. Computational efficiency and asymptotic O(N) scaling behavior of the implementation is demonstrated for various molecular and periodic model systems, with the largest unit cell of hematite containing 640 atoms and 19,072 basis functions. The overall computational effort of energy gradient is comparable to that of the Kohn-Sham matrix formation. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Classical Molecular Dynamics with Mobile Protons.

PubMed

Lazaridis, Themis; Hummer, Gerhard

2017-11-27

An important limitation of standard classical molecular dynamics simulations is the inability to make or break chemical bonds. This restricts severely our ability to study processes that involve even the simplest of chemical reactions, the transfer of a proton. Existing approaches for allowing proton transfer in the context of classical mechanics are rather cumbersome and have not achieved widespread use and routine status. Here we reconsider the combination of molecular dynamics with periodic stochastic proton hops. To ensure computational efficiency, we propose a non-Boltzmann acceptance criterion that is heuristically adjusted to maintain the correct or desirable thermodynamic equilibria between different protonation states and proton transfer rates. Parameters are proposed for hydronium, Asp, Glu, and His. The algorithm is implemented in the program CHARMM and tested on proton diffusion in bulk water and carbon nanotubes and on proton conductance in the gramicidin A channel. Using hopping parameters determined from proton diffusion in bulk water, the model reproduces the enhanced proton diffusivity in carbon nanotubes and gives a reasonable estimate of the proton conductance in gramicidin A.

FlaME: Flash Molecular Editor - a 2D structure input tool for the web.

PubMed

Dallakian, Pavel; Haider, Norbert

2011-02-01

So far, there have been no Flash-based web tools available for chemical structure input. The authors herein present a feasibility study, aiming at the development of a compact and easy-to-use 2D structure editor, using Adobe's Flash technology and its programming language, ActionScript. As a reference model application from the Java world, we selected the Java Molecular Editor (JME). In this feasibility study, we made an attempt to realize a subset of JME's functionality in the Flash Molecular Editor (FlaME) utility. These basic capabilities are: structure input, editing and depiction of single molecules, data import and export in molfile format. The result of molecular diagram sketching in FlaME is accessible in V2000 molfile format. By integrating the molecular editor into a web page, its communication with the HTML elements on this page is established using the two JavaScript functions, getMol() and setMol(). In addition, structures can be copied to the system clipboard. A first attempt was made to create a compact single-file application for 2D molecular structure input/editing on the web, based on Flash technology. With the application examples presented in this article, it could be demonstrated that the Flash methods are principally well-suited to provide the requisite communication between the Flash object (application) and the HTML elements on a web page, using JavaScript functions.

Standards-based metadata procedures for retrieving data for display or mining utilizing persistent (data-DOI) identifiers.

PubMed

Harvey, Matthew J; Mason, Nicholas J; McLean, Andrew; Rzepa, Henry S

2015-01-01

We describe three different procedures based on metadata standards for enabling automated retrieval of scientific data from digital repositories utilising the persistent identifier of the dataset with optional specification of the attributes of the data document such as filename or media type. The procedures are demonstrated using the JSmol molecular visualizer as a component of a web page and Avogadro as a stand-alone modelling program. We compare our methods for automated retrieval of data from a standards-compliant data repository with those currently in operation for a selection of existing molecular databases and repositories. Our methods illustrate the importance of adopting a standards-based approach of using metadata declarations to increase access to and discoverability of repository-based data. Graphical abstract.

Coding considerations for standalone molecular dynamics simulations of atomistic structures

NASA Astrophysics Data System (ADS)

Ocaya, R. O.; Terblans, J. J.

2017-10-01

The laws of Newtonian mechanics allow ab-initio molecular dynamics to model and simulate particle trajectories in material science by defining a differentiable potential function. This paper discusses some considerations for the coding of ab-initio programs for simulation on a standalone computer and illustrates the approach by C language codes in the context of embedded metallic atoms in the face-centred cubic structure. The algorithms use velocity-time integration to determine particle parameter evolution for up to several thousands of particles in a thermodynamical ensemble. Such functions are reusable and can be placed in a redistributable header library file. While there are both commercial and free packages available, their heuristic nature prevents dissection. In addition, developing own codes has the obvious advantage of teaching techniques applicable to new problems.

Multi-scale Visualization of Molecular Architecture Using Real-Time Ambient Occlusion in Sculptor.

PubMed

Wahle, Manuel; Wriggers, Willy

2015-10-01

The modeling of large biomolecular assemblies relies on an efficient rendering of their hierarchical architecture across a wide range of spatial level of detail. We describe a paradigm shift currently under way in computer graphics towards the use of more realistic global illumination models, and we apply the so-called ambient occlusion approach to our open-source multi-scale modeling program, Sculptor. While there are many other higher quality global illumination approaches going all the way up to full GPU-accelerated ray tracing, they do not provide size-specificity of the features they shade. Ambient occlusion is an aspect of global lighting that offers great visual benefits and powerful user customization. By estimating how other molecular shape features affect the reception of light at some surface point, it effectively simulates indirect shadowing. This effect occurs between molecular surfaces that are close to each other, or in pockets such as protein or ligand binding sites. By adding ambient occlusion, large macromolecular systems look much more natural, and the perception of characteristic surface features is strongly enhanced. In this work, we present a real-time implementation of screen space ambient occlusion that delivers realistic cues about tunable spatial scale characteristics of macromolecular architecture. Heretofore, the visualization of large biomolecular systems, comprising e.g. hundreds of thousands of atoms or Mega-Dalton size electron microscopy maps, did not take into account the length scales of interest or the spatial resolution of the data. Our approach has been uniquely customized with shading that is tuned for pockets and cavities of a user-defined size, making it useful for visualizing molecular features at multiple scales of interest. This is a feature that none of the conventional ambient occlusion approaches provide. Actual Sculptor screen shots illustrate how our implementation supports the size-dependent rendering of molecular surface features.

Formal linguistics as a cue to demographic history.

PubMed

Longobardi, Giuseppe; Ceolin, Andrea; Ecay, Aaron; Ghirotto, Silvia; Guardiano, Cristina; Irimia, Monica-Alexandrina; Michelioudakis, Dimitris; Radkevich, Nina; Pettener, Davide; Luiselli, Donata; Barbujani, Guido

2016-06-20

Beyond its theoretical success, the development of molecular genetics has brought about the possibility of extraordinary progress in the study of classification and in the inference of the evolutionary history of many species and populations. A major step forward was represented by the availability of extremely large sets of molecular data suited to quantitative and computational treatments. In this paper, we argue that even in cognitive sciences, purely theoretical progress in a discipline such as linguistics may have analogous impact. Thus, exactly on the model of molecular biology, we propose to unify two traditionally unrelated lines of linguistic investigation: 1) the formal study of syntactic variation (parameter theory) in the biolinguistic program; 2) the reconstruction of relatedness among languages (phylogenetic taxonomy). The results of our linguistic analysis have thus been plotted against data from population genetics and the correlations have turned out to be largely significant: given a non-trivial set of languages/populations, the description of their variation provided by the comparison of systematic parametric analysis and molecular anthropology informatively recapitulates their history and relationships. As a result, we can claim that the reality of some parametric model of the language faculty and language acquisition/transmission (more broadly of generative grammar) receives strong and original support from its historical heuristic power. Then, on these grounds, we can begin testing Darwin's prediction that, when properly generated, the trees of human populations and of their languages should eventually turn out to be significantly parallel.

Using Symmetry Group Correlation Tables to Explain why Erham (and Other Programs) cannot BE Used to Analyze Torsional Splittings of Some Molecules

NASA Astrophysics Data System (ADS)

Groner, Peter

2016-06-01

ERHAM has been used to analyze rotational spectra of many molecules with torsional splitting caused by one or two internal rotors. The gauche form of dimethyl ether-d1 whose equilibrium structure has C1 symmetry is an example of a molecule for which ERHAM could not model additional small splittings resolvable for many transitions, whereas the spectrum of the symmetric (anti, trans) form with a C{_s} equilibrium structure could be analyzed successfully with ERHAM. A more recent example where ERHAM failed is pinacolone CH_3-CO-C(CH_3)_3. In this case, the barriers to internal rotation of the methyl groups within the -C(CH_3)_3 unit are too high to produce observable internal rotation splittings, but the splittings due to the CH_3-CO methyl group could not be modeled correctly with ERHAM nor with any other available program (XIAM, BELGI-Cs, BELGI-C1, RAM36). In the paper, it was speculated that BELGI-Cs-2tops might be able to the job, but arguments against this possibility have also been put forward. The correlation between irreducible representations of groups and their subgroups according to Watson can be used not only to determine the total number of substates (components) to be expected but also to help decide which particular program has a chance for a successful analysis. As it turns out, the number of components of split lines depends on the molecular symmetry at equilibrium in relation to the highest possible symmetry for a given molecular symmetry group. Therefore, for pinacolone, the vibrational ground state is split into 10 torsional substates. P. Groner, J. Mol. Spectrosc. 278 (2012) 52-67. C. Richard et al. A&A 552 (2013), A117. Y. Zhao et al., J. Mol. Spectrosc. 318 (2015) 91-100, with references to all other programs mentioned in the abstract. J. K. G. Watson, Can. J. Physics 43 (1965) 1996-2007.

Xylogenesis in zinnia (Zinnia elegans) cell cultures: unravelling the regulatory steps in a complex developmental programmed cell death event.

PubMed

Iakimova, Elena T; Woltering, Ernst J

2017-04-01

Physiological and molecular studies support the view that xylogenesis can largely be determined as a specific form of vacuolar programmed cell death (PCD). The studies in xylogenic zinnia cell culture have led to many breakthroughs in xylogenesis research and provided a background for investigations in other experimental models in vitro and in planta . This review discusses the most essential earlier and recent findings on the regulation of xylem elements differentiation and PCD in zinnia and other xylogenic systems. Xylogenesis (the formation of water conducting vascular tissue) is a paradigm of plant developmental PCD. The xylem vessels are composed of fused tracheary elements (TEs)-dead, hollow cells with patterned lignified secondary cell walls. They result from the differentiation of the procambium and cambium cells and undergo cell death to become functional post-mortem. The TE differentiation proceeds through a well-coordinated sequence of events in which differentiation and the programmed cellular demise are intimately connected. For years a classical experimental model for studies on xylogenesis was the xylogenic zinnia (Zinnia elegans) cell culture derived from leaf mesophyll cells that, upon induction by cytokinin and auxin, transdifferentiate into TEs. This cell system has been proven very efficient for investigations on the regulatory components of xylem differentiation which has led to many discoveries on the mechanisms of xylogenesis. The knowledge gained from this system has potentiated studies in other xylogenic cultures in vitro and in planta. The present review summarises the previous and latest findings on the hormonal and biochemical signalling, metabolic pathways and molecular and gene determinants underlying the regulation of xylem vessels differentiation in zinnia cell culture. Highlighted are breakthroughs achieved through the use of xylogenic systems from other species and newly introduced tools and analytical approaches to study the processes. The mutual dependence between PCD signalling and the differentiation cascade in the program of TE development is discussed.

Transcriptomic evidence for the evolution of shoot meristem function in sporophyte-dominant land plants through concerted selection of ancestral gametophytic and sporophytic genetic programs.

PubMed

Frank, Margaret H; Scanlon, Michael J

2015-02-01

Alternation of generations, in which the haploid and diploid stages of the life cycle are each represented by multicellular forms that differ in their morphology, is a defining feature of the land plants (embryophytes). Anciently derived lineages of embryophytes grow predominately in the haploid gametophytic generation from apical cells that give rise to the photosynthetic body of the plant. More recently evolved plant lineages have multicellular shoot apical meristems (SAMs), and photosynthetic shoot development is restricted to the sporophyte generation. The molecular genetic basis for this evolutionary shift from gametophyte-dominant to sporophyte-dominant life cycles remains a major question in the study of land plant evolution. We used laser microdissection and next generation RNA sequencing to address whether angiosperm meristem patterning genes expressed in the sporophytic SAM of Zea mays are expressed in the gametophytic apical cells, or in the determinate sporophytes, of the model bryophytes Marchantia polymorpha and Physcomitrella patens. A wealth of upregulated genes involved in stem cell maintenance and organogenesis are identified in the maize SAM and in both the gametophytic apical cell and sporophyte of moss, but not in Marchantia. Significantly, meiosis-specific genetic programs are expressed in bryophyte sporophytes, long before the onset of sporogenesis. Our data suggest that this upregulated accumulation of meiotic gene transcripts suppresses indeterminate cell fate in the Physcomitrella sporophyte, and overrides the observed accumulation of meristem patterning genes. A model for the evolution of indeterminate growth in the sporophytic generation through the concerted selection of ancestral meristem gene programs from gametophyte-dominant lineages is proposed. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

3D QSAR studies on binding affinities of coumarin natural products for glycosomal GAPDH of Trypanosoma cruzi

NASA Astrophysics Data System (ADS)

Menezes, Irwin R. A.; Lopes, Julio C. D.; Montanari, Carlos A.; Oliva, Glaucius; Pavão, Fernando; Castilho, Marcelo S.; Vieira, Paulo C.; Pupo, M.^onica T.

2003-05-01

Drug design strategies based on Comparative Molecular Field Analysis (CoMFA) have been used to predict the activity of new compounds. The major advantage of this approach is that it permits the analysis of a large number of quantitative descriptors and uses chemometric methods such as partial least squares (PLS) to correlate changes in bioactivity with changes in chemical structure. Because it is often difficult to rationalize all variables affecting the binding affinity of compounds using CoMFA solely, the program GRID was used to describe ligands in terms of their molecular interaction fields, MIFs. The program VolSurf that is able to compress the relevant information present in 3D maps into a few descriptors can treat these GRID fields. The binding affinities of a new set of compounds consisting of 13 coumarins, for one of which the three-dimensional ligand-enzyme bound structure is known, were studied. A final model based on the mentioned programs was independently validated by synthesizing and testing new coumarin derivatives. By relying on our knowledge of the real physical data (i.e., combining crystallographic and binding affinity results), it is also shown that ligand-based design agrees with structure-based design. The compound with the highest binding affinity was the coumarin chalepin, isolated from Rutaceae species, with an IC50 value of 55.5 μM towards the enzyme glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) from glycosomes of the parasite Trypanosoma cruzi, the causative agent of Chagas' disease. The proposed models from GRID MIFs have revealed the importance of lipophilic interactions in modulating the inhibition, but without excluding the dependence on stereo-electronic properties as found from CoMFA fields.

MLP Tools: a PyMOL plugin for using the molecular lipophilicity potential in computer-aided drug design

NASA Astrophysics Data System (ADS)

Oberhauser, Nils; Nurisso, Alessandra; Carrupt, Pierre-Alain

2014-05-01

The molecular lipophilicity potential (MLP) is a well-established method to calculate and visualize lipophilicity on molecules. We are here introducing a new computational tool named MLP Tools, written in the programming language Python, and conceived as a free plugin for the popular open source molecular viewer PyMOL. The plugin is divided into several sub-programs which allow the visualization of the MLP on molecular surfaces, as well as in three-dimensional space in order to analyze lipophilic properties of binding pockets. The sub-program Log MLP also implements the virtual log P which allows the prediction of the octanol/water partition coefficients on multiple three-dimensional conformations of the same molecule. An implementation on the recently introduced MLP GOLD procedure, improving the GOLD docking performance in hydrophobic pockets, is also part of the plugin. In this article, all functions of the MLP Tools will be described through a few chosen examples.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ibrahim, Khaled Z.; Epifanovsky, Evgeny; Williams, Samuel W.

Coupled-cluster methods provide highly accurate models of molecular structure by explicit numerical calculation of tensors representing the correlation between electrons. These calculations are dominated by a sequence of tensor contractions, motivating the development of numerical libraries for such operations. While based on matrix-matrix multiplication, these libraries are specialized to exploit symmetries in the molecular structure and in electronic interactions, and thus reduce the size of the tensor representation and the complexity of contractions. The resulting algorithms are irregular and their parallelization has been previously achieved via the use of dynamic scheduling or specialized data decompositions. We introduce our efforts tomore » extend the Libtensor framework to work in the distributed memory environment in a scalable and energy efficient manner. We achieve up to 240 speedup compared with the best optimized shared memory implementation. We attain scalability to hundreds of thousands of compute cores on three distributed-memory architectures, (Cray XC30&XC40, BlueGene/Q), and on a heterogeneous GPU-CPU system (Cray XK7). As the bottlenecks shift from being compute-bound DGEMM's to communication-bound collectives as the size of the molecular system scales, we adopt two radically different parallelization approaches for handling load-imbalance. Nevertheless, we preserve a uni ed interface to both programming models to maintain the productivity of computational quantum chemists.« less

eSBMTools 1.0: enhanced native structure-based modeling tools.

PubMed

Lutz, Benjamin; Sinner, Claude; Heuermann, Geertje; Verma, Abhinav; Schug, Alexander

2013-11-01

Molecular dynamics simulations provide detailed insights into the structure and function of biomolecular systems. Thus, they complement experimental measurements by giving access to experimentally inaccessible regimes. Among the different molecular dynamics techniques, native structure-based models (SBMs) are based on energy landscape theory and the principle of minimal frustration. Typically used in protein and RNA folding simulations, they coarse-grain the biomolecular system and/or simplify the Hamiltonian resulting in modest computational requirements while achieving high agreement with experimental data. eSBMTools streamlines running and evaluating SBM in a comprehensive package and offers high flexibility in adding experimental- or bioinformatics-derived restraints. We present a software package that allows setting up, modifying and evaluating SBM for both RNA and proteins. The implemented workflows include predicting protein complexes based on bioinformatics-derived inter-protein contact information, a standardized setup of protein folding simulations based on the common PDB format, calculating reaction coordinates and evaluating the simulation by free-energy calculations with weighted histogram analysis method or by phi-values. The modules interface with the molecular dynamics simulation program GROMACS. The package is open source and written in architecture-independent Python2. http://sourceforge.net/projects/esbmtools/. alexander.schug@kit.edu. Supplementary data are available at Bioinformatics online.

Comparative simulation study of chemical synthesis of functional DADNE material.

PubMed

Liu, Min Hsien; Liu, Chuan Wen

2017-01-01

Amorphous molecular simulation to model the reaction species in the synthesis of chemically inert and energetic 1,1-diamino-2,2-dinitroethene (DADNE) explosive material was performed in this work. Nitromethane was selected as the starting reactant to undergo halogenation, nitration, deprotonation, intermolecular condensation, and dehydration to produce the target DADNE product. The Materials Studio (MS) forcite program allowed fast energy calculations and reliable geometric optimization of all aqueous molecular reaction systems (0.1-0.5 M) at 283 K and 298 K. The MS forcite-computed and Gaussian polarizable continuum model (PCM)-computed results were analyzed and compared in order to explore feasible reaction pathways under suitable conditions for the synthesis of DADNE. Through theoretical simulation, the findings revealed that synthesis was possible, and a total energy barrier of 449.6 kJ mol -1 needed to be overcome in order to carry out the reaction according to MS calculation of the energy barriers at each stage at 283 K, as shown by the reaction profiles. Local analysis of intermolecular interaction, together with calculation of the stabilization energy of each reaction system, provided information that can be used as a reference regarding molecular integrated stability. Graphical Abstract Materials Studio software has been suggested for the computation and simulation of DADNE synthesis.

Kinematical calculations of RHEED intensity oscillations during the growth of thin epitaxial films

NASA Astrophysics Data System (ADS)

Daniluk, Andrzej

2005-08-01

A practical computing algorithm working in real time has been developed for calculating the reflection high-energy electron diffraction (RHEED) from the molecular beam epitaxy (MBE) growing surface. The calculations are based on the use of kinematical diffraction theory. Simple mathematical models are used for the growth simulation in order to investigate the fundamental behaviors of reflectivity change during the growth of thin epitaxial films prepared using MBE. Program summaryTitle of program:GROWTH Catalogue identifier:ADVL Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADVL Program obtainable from: CPC Program Library, Queen's University of Belfast, N. Ireland Distribution format: tar.gz Computer for which the program is designed and others on which is has been tested:Pentium-based PC Operating systems or monitors under which the program has been tested:Windows 9x, XP, NT Programming language used:Object Pascal Memory required to execute with typical data:more than 1 MB Number of bits in a word: 64 bits Number of processors used: 1 Number of lines in distributed program, including test data, etc.: 10 989 Number of bytes in distributed program, including test data, etc.:103 048 Nature of the physical problem:Reflection high-energy electron diffraction (RHEED) is a very useful technique for studying growth and surface analysis of thin epitaxial structures prepared using the molecular beam epitaxy (MBE). The simplest approach to calculating the RHEED intensity during the growth of thin epitaxial films is the kinematical diffraction theory (often called kinematical approximation), in which only a single scattering event is taken into account. The biggest advantage of this approach is that we can calculate RHEED intensity in real time. Also, the approach facilitates intuitive understanding of the growth mechanism and surface morphology [P.I. Cohen, G.S. Petrich, P.R. Pukite, G.J. Whaley, A.S. Arrott, Surf. Sci. 216 (1989) 222]. Method of solution:Epitaxial growth of thin films is modeled by a set of non-linear differential equations [P.I. Cohen, G.S. Petrich, P.R. Pukite, G.J. Whaley, A.S. Arrott, Surf. Sci. 216 (1989) 222]. The Runge-Kutta method with adaptive stepsize control was used for solving initial value problem for non-linear differential equations [W.H. Press, B.P. Flannery, S.A. Teukolsky, W.T. Vetterling, Numerical Recipes in Pascal: The Art of Scientific Computing; first ed., Cambridge University Press, 1989; See also: Numerical Recipes in C++, second ed., Cambridge University Press, 1992]. Typical running time: The typical running time is machine and user-parameters dependent. Unusual features of the program: The program is distributed in the form of a main project Growth.dpr file and an independent Rhd.pas file and should be compiled using Object Pascal compilers, including Borland Delphi.

A Web interface generator for molecular biology programs in Unix.

PubMed

Letondal, C

2001-01-01

Almost all users encounter problems using sequence analysis programs. Not only are they difficult to learn because of the parameters, syntax and semantic, but many are different. That is why we have developed a Web interface generator for more than 150 molecular biology command-line driven programs, including: phylogeny, gene prediction, alignment, RNA, DNA and protein analysis, motif discovery, structure analysis and database searching programs. The generator uses XML as a high-level description language of the legacy software parameters. Its aim is to provide users with the equivalent of a basic Unix environment, with program combination, customization and basic scripting through macro registration. The program has been used for three years by about 15000 users throughout the world; it has recently been installed on other sites and evaluated as a standard user interface for EMBOSS programs.

EVIDENCE FOR DECAY OF TURBULENCE BY MHD SHOCKS IN THE ISM VIA CO EMISSION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larson, Rebecca L.; Evans II, Neal J.; Green, Joel D.

2015-06-10

We utilize observations of sub-millimeter rotational transitions of CO from a Herschel Cycle 2 open time program (“COPS”, PI: J. Green) to identify previously predicted turbulent dissipation by magnetohydrodynamic (MHD) shocks in molecular clouds. We find evidence of the shocks expected for dissipation of MHD turbulence in material not associated with any protostar. Two models fit about equally well: model 1 has a density of 10{sup 3} cm{sup −3}, a shock velocity of 3 km s{sup −1}, and a magnetic field strength of 4 μG; model 2 has a density of 10{sup 3.5} cm{sup −3}, a shock velocity of 2more » km s{sup −1}, and a magnetic field strength of 8 μG. Timescales for decay of turbulence in this region are comparable to crossing times. Transitions of CO up to J of 8, observed close to active sites of star formation, but not within outflows, can trace turbulent dissipation of shocks stirred by formation processes. Although the transitions are difficult to detect at individual positions, our Herschel-SPIRE survey of protostars provides a grid of spatially distributed spectra within molecular clouds. We averaged all spatial positions away from known outflows near seven protostars. We find significant agreement with predictions of models of turbulent dissipation in slightly denser (10{sup 3.5} cm{sup −3}) material with a stronger magnetic field (24 μG) than in the general molecular cloud.« less

CPFP Summer Curriculum: Molecular Prevention Course | Division of Cancer Prevention

Cancer.gov

This Cancer Prevention Fellowship Program (CPFP) one-week course on molecular aspects of cancer prevention follows the Principles and Practice of Cancer Prevention and Control course. It provides a strong background about molecular biology and genetics of cancer, and an overview of cutting-edge research and techniques in the fields of molecular epidemiology, biomarkers,

Shuttle optical environment; Proceedings of the Meeting, Washington, DC, April 23, 24, 1981

NASA Technical Reports Server (NTRS)

Miller, E. R. (Editor); Fazio, G. G.

1982-01-01

The numerical modeling, instrumentation, identification, and procedures to characterize and/or control contamination hazards to equipment used on the Shuttle are discussed. On-orbit pollutants include molecular offgassing and outgassing, particulate material, and substances from thrusters, vents, and leaks. Clean-rooms are being implemented in ground assembly and integration facilities. Attention is given to an upgraded SPACE program for numerically modeling contamination pathways and appropriate procedures to protect instrumentation from film and particulate deposition. Finally, attention is given to military cryogenic IR detectors being employed to quantify the Shuttle thermal and solid pollutant environment on-orbit as a prelude to future operational IR sensors.

Designing DNA nanodevices for compatibility with the immune system of higher organisms

NASA Astrophysics Data System (ADS)

Surana, Sunaina; Shenoy, Avinash R.; Krishnan, Yamuna

2015-09-01

DNA is proving to be a powerful scaffold to construct molecularly precise designer DNA devices. Recent trends reveal their ever-increasing deployment within living systems as delivery devices that not only probe but also program and re-program a cell, or even whole organisms. Given that DNA is highly immunogenic, we outline the molecular, cellular and organismal response pathways that designer nucleic acid nanodevices are likely to elicit in living systems. We address safety issues applicable when such designer DNA nanodevices interact with the immune system. In light of this, we discuss possible molecular programming strategies that could be integrated with such designer nucleic acid scaffolds to either evade or stimulate the host response with a view to optimizing and widening their applications in higher organisms.

A predictive model for failure properties of thermoset resins

NASA Technical Reports Server (NTRS)

Caruthers, James M.; Bowles, Kenneth J.

1989-01-01

A predictive model for the three-dimensional failure behavior of engineering polymers has been developed in a recent NASA-sponsored research program. This model acknowledges the underlying molecular deformation mechanisms and thus accounts for the effects of different chemical compositions, crosslink density, functionality of the curing agent, etc., on the complete nonlinear stress-strain response including yield. The material parameters required by the model can be determined from test-tube quantities of a new resin in only a few days. Thus, we can obtain a first-order prediction of the applicability of a new resin for an advanced aerospace application without synthesizing the large quantities of material needed for failure testing. This technology will effect order-of-magnitude reductions in the time and expense required to develop new engineering polymers.

Organizing the Cellular and Molecular Heterogeneity in High-Grade Serous Ovarian Cancer by Mass Cytometry

DTIC Science & Technology

2013-10-01

5b. GRANT NUMBER W81XWH-12-1-0591 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Garry P. Nolan, Ph.D. 5d. PROJECT NUMBER Wendy J . Fantl...viable HG-SOC single cells prepared from clinically anno - tated samples where the parameters measured at the single-cell level will provide critical...models by comparison of genomic profiles. Nat Commun, 2013. 4: p. 2126. 2. Coticchia, C.M., J . Yang, and M.A. Moses, Ovarian cancer biomarkers: current

[Programmed necrosis and necroptosis - molecular mechanisms].

PubMed

Giżycka, Agata; Chorostowska-Wynimko, Joanna

2015-12-16

Programmed necrosis has been proven vital for organism development and homeostasis maintenance. Its regulatory effects on functional activity of the immune system, as well as on pathways regulating the death mechanisms in cells with diminished apoptotic activity, including malignant cells, have been confirmed. There is also increasing evidence indicating necrosis involvement in many human pathologies. Contrary to previous beliefs, necrosis is not only a passive, pathological, gene-independent process. However, the current knowledge regarding molecular regulation of programmed necrosis is scarce. In part this is due to the multiplicity and complexity of signaling pathways involved in programmed necrosis, as well as the absence of specific cellular markers identifying this process, but also the ambiguous and imprecise international terminology. This review presents the current state of the art on molecular mechanisms of programmed necrosis. In particular, its specific and frequent form, necroptosis, is discussed. The role of RIP1 and RIP3 kinases in this process is presented, as well as the diverse pathways induced by ligation of tumor necrosis factor α, to its receptor, TNFR1, i.e. cell survival, apoptosis or necroptosis.

How the Build Up of Aqueous Humor Can Damage the Optic Nerve

MedlinePlus

... Alzheimer’s Disease Research Program Macular Degeneration Research Program National Glaucoma Research Program Molecular Neurodegeneration ... Foundation BrightFocus Foundation 22512 Gateway Center Drive Clarksburg, MD ...

Quantitative structure-activity relationships (QSAR) of some 2,2-diphenyl propionate (DPP) derivatives of muscarinic antagonists

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gordon, R.K.; Breuer, E.; Padilla, F.N.

1987-05-01

QSAR between biological activities and molecular-chemical properties were investigated to aid in designing more effective and potent antimuscarinic pharmacophores. A molecular modeling program was used to calculate geometrical and topological values of a series of DPP pharmacophores. The newly synthesized pharmacophores were tested for their antagonist activities by: (1) inhibition of (N-methyl-/sup 3/H)scopolamine binding assay to the muscarinic receptors of N4TG1 neuroblastoma cells; (2) blocking of acetylcholine-induced contraction of guinea pig ileum; and (3) inhibition of carbachol-induced ..cap alpha..-amylase release from rat pancreas. The differences in the log of these biological activities were directly and significantly related to the distancesmore » between the carbonyl oxygen of the DPP and the quaternary nitrogen of the modified pharmacophores. The biological activities, while depending on each particular assay, varied between three and four logs of activity. The charge remained the same in all the pharmacophores. There were no QSAR correlations between molecular volume, molecular connectivity, or principle moments and their antagonistic activities, although multivariate QSAR was not employed. Thus, based on distance geometry, potent muscarinic pharmacophores can be predicted.« less

Modeling, molecular dynamics, and docking assessment of transcription factor rho: a potential drug target in Brucella melitensis 16M

PubMed Central

Pradeepkiran, Jangampalli Adi; Kumar, Konidala Kranthi; Kumar, Yellapu Nanda; Bhaskar, Matcha

2015-01-01

The zoonotic disease brucellosis, a chronic condition in humans affecting renal and cardiac systems and causing osteoarthritis, is caused by Brucella, a genus of Gram-negative, facultative, intracellular pathogens. The mode of transmission and the virulence of the pathogens are still enigmatic. Transcription regulatory elements, such as rho proteins, play an important role in the termination of transcription and/or the selection of genes in Brucella. Adverse effects of the transcription inhibitors play a key role in the non-successive transcription challenges faced by the pathogens. In the investigation presented here, we computationally predicted the transcription termination factor rho (TtFRho) inhibitors against Brucella melitensis 16M via a structure-based method. In view the unknown nature of its crystal structure, we constructed a robust three-dimensional homology model of TtFRho’s structure by comparative modeling with the crystal structure of the Escherichia coli TtFRho (Protein Data Bank ID: 1PVO) as a template in MODELLER (v 9.10). The modeled structure was optimized by applying a molecular dynamics simulation for 2 ns with the CHARMM (Chemistry at HARvard Macromolecular Mechanics) 27 force field in NAMD (NAnoscale Molecular Dynamics program; v 2.9) and then evaluated by calculating the stereochemical quality of the protein. The flexible docking for the interaction phenomenon of the template consists of ligand-related inhibitor molecules from the ZINC (ZINC Is Not Commercial) database using a structure-based virtual screening strategy against minimized TtFRho. Docking simulations revealed two inhibitors compounds – ZINC24934545 and ZINC72319544 – that showed high binding affinity among 2,829 drug analogs that bind with key active-site residues; these residues are considered for protein-ligand binding and unbinding pathways via steered molecular dynamics simulations. Arg215 in the model plays an important role in the stability of the protein-ligand complex via a hydrogen bonding interaction by aromatic-π contacts, and the ADMET (absorption, distribution, metabolism, and excretion) analysis of best leads indicate nontoxic in nature with good potential for drug development. PMID:25848225

Molecular Dynamics Simulations of Simple Liquids

ERIC Educational Resources Information Center

Speer, Owner F.; Wengerter, Brian C.; Taylor, Ramona S.

2004-01-01

An experiment, in which students were given the opportunity to perform molecular dynamics simulations on a series of molecular liquids using the Amber suite of programs, is presented. They were introduced to both physical theories underlying classical mechanics simulations and to the atom-atom pair distribution function.

Quality assurance and quality improvement in U.S. clinical molecular genetic laboratories.

PubMed

Chen, Bin; Richards, C Sue; Wilson, Jean Amos; Lyon, Elaine

2011-04-01

A robust quality-assurance program is essential for laboratories that perform molecular genetic testing to maintain high-quality testing and be able to address challenges associated with performance or delivery of testing services as the use of molecular genetic tests continues to expand in clinical and public health practice. This unit discusses quality-assurance and quality-improvement considerations that are critical for molecular genetic testing performed for heritable diseases and conditions. Specific discussion is provided on applying regulatory standards and best practices in establishing/verifying test performance, ensuring quality of the total testing process, monitoring and maintaining personnel competency, and continuing quality improvement. The unit provides a practical reference for laboratory professionals to use in recognizing and addressing essential quality-assurance issues in human molecular genetic testing. It should also provide useful information for genetics researchers, trainees, and fellows in human genetics training programs, as well as others who are interested in quality assurance and quality improvement for molecular genetic testing. 2011 by John Wiley & Sons, Inc.

Growth versus immunity--a redirection of the cell cycle?

PubMed

Eichmann, Ruth; Schäfer, Patrick

2015-08-01

Diseases caused by plant pathogens significantly reduce growth and yield in agricultural crop production. Raising immunity in crops is therefore a major aim in breeding programs. However, efforts to enhance immunity are challenged by the occurrence of growth inhibition triggered by immunity that can be as detrimental as diseases. In this review, we will propose molecular models to explain the inhibitory growth-immunity crosstalk. We will briefly discuss why the resource reallocation model might not represent the driving force for the observed growth-immunity trade-offs. We suggest a model in which immunity redirects and initiates hormone signalling activities that can impair plant growth by antagonising cell cycle regulation and meristem activities. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Research on Spectroscopy, Opacity, and Atmospheres

NASA Technical Reports Server (NTRS)

Kurucz, Robert L.

1999-01-01

To make my calculations more readily accessible I have set up a web site cfaku5.harvard.edu that can also be accessed by FTP. it has 5 9GB disks that hold all of my atomic and diatomic molecular data, my tables of distribution function opacities, my grids of model atmospheres, colors, fluxes, etc, my program that are ready for distribution, most of my recent papers. Atlases and computed spectra will be added as they are completed. New atomic and molecular calculations will be added as they are completed. I got my atomic programs that had been running on a Cray at the San Diego Supercomputer Center to run on my Vaxes and Alpha. I started with Ni and Co because there were new laboratory analyses that included isotopic and hyperfine splitting. Those calculations are described in the appended abstract for the 6th Atomic Spectroscopy and oscillator Strengths meeting in Victoria last summer. A surprising finding is that quadrupole transitions have been grossly in error because mixing with higher levels has not been included. I now have enough memory in my Alpha to treat 3000 x 3000 matrices. I now include all levels up through n=9 for Fe I and 11, the spectra for which the most information is available. I am finishing those calculations right now. After Fe I and Fe 11, all other spectra are "easy", and I will be in mass production. ATL;LS12, my opacity sampling program for computing models with arbitrary abundances, has been put on the web server. I wrote a new distribution function opacity program for workstations that replaces the one I used on the Cray at the San Diego Supercomputer Center. Each set of abundances would take 100 Cray hours costing $100,000. 1 ran 25 cases. Each of my opacity CDs contains three abundances. I have a new program -iinning on the Alpha that takes about a week. I am going to have to get a faster processor or I will have to dedicate a whole workstation just to opacities.

Multidrug resistance in parasites: ABC transporters, P-glycoproteins and molecular modelling.

PubMed

Jones, P M; George, A M

2005-04-30

Parasitic diseases, caused by protozoa, helminths and arthropods, rank among the most important problems in human and veterinary medicine, and in agriculture, leading to debilitating sicknesses and loss of life. In the absence of vaccines and with the general failure of vector eradication programs, drugs are the main line of defence, but the newest drugs are being tracked by the emergence of resistance in parasites, sharing ominous parallels with multidrug resistance in bacterial pathogens. Any of a number of mechanisms will elicit a drug resistance phenotype in parasites, including: active efflux, reduced uptake, target modification, drug modification, drug sequestration, by-pass shunting, or substrate competition. The role of ABC transporters in parasitic multidrug resistance mechanisms is being subjected to more scrutiny, due in part to the established roles of certain ABC transporters in human diseases, and also to an increasing portfolio of ABC transporters from parasite genome sequencing projects. For example, over 100 ABC transporters have been identified in the Escherichia coli genome, but to date only about 65 in all parasitic genomes. Long established laboratory investigations are now being assisted by molecular biology, bioinformatics, and computational modelling, and it is in these areas that the role of ABC transporters in parasitic multidrug resistance mechanisms may be defined and put in perspective with that of other proteins. We discuss ABC transporters in parasites, and conclude with an example of molecular modelling that identifies a new interaction between the structural domains of a parasite P-glycoprotein.

MOLECULAR DESIGNER: an interactive program for the display of protein structure on the IBM-PC.

PubMed

Hannon, G J; Jentoft, J E

1985-09-01

A BASIC interactive graphics program has been developed for the IBM-PC which utilizes the graphics capabilities of that computer to display and manipulate protein structure from coordinates. Structures may be generated from typed files, or from Brookhaven National Laboratories' Protein Data Bank data tapes. Once displayed, images may be rotated, translated and expanded to any desired size. Figures may be viewed as ball-and-stick or space-filling models. Calculated multiple-point perspective may also be added to the display. Docking manipulations are possible since more than a single figure may be displayed and manipulated simultaneously. Further, stereo images and red/blue three-dimensional images may be generated using the accompanying DESIPLOT program and an HP-7475A plotter. A version of the program is also currently available for the Apple Macintosh. Full implementation on the Macintosh requires 512 K and at least one disk drive. Otherwise this version is essentially identical to the IBM-PC version described herein.

The Alberta Hereditary Diseases Program: a regional model for delivery of genetic services.

PubMed Central

Lowry, R B; Bowen, P

1990-01-01

Genetic counselling and related services are generally provided at major university medical centres because they are very specialized. The need for rurally based genetic services prompted the inclusion of an outreached program in the Alberta Hereditary Diseases Program (AHDP), which was established in 1979; the AHDP was designed to provide services to the entire province through two regional centres and seven outreach clinics. There is a community health nurse in almost every health unit whose duties are either totally or partially devoted to the AHDP; thus, genetic help and information are as close as a rural health unit. The AHDP is designed to provide complete clinical (diagnostic, counselling and some management) services and laboratory (cytogenetic, biochemical and molecular) services for genetic disorders. In addition, the program emphasizes education and publishes a quarterly bulletin, which is sent free of charge to all physicians, hospitals, public health units, social service units, major radio and television stations, newspapers and public libraries and to selected individuals and groups in Alberta. PMID:2302614

PyContact: Rapid, Customizable, and Visual Analysis of Noncovalent Interactions in MD Simulations.

PubMed

Scheurer, Maximilian; Rodenkirch, Peter; Siggel, Marc; Bernardi, Rafael C; Schulten, Klaus; Tajkhorshid, Emad; Rudack, Till

2018-02-06

Molecular dynamics (MD) simulations have become ubiquitous in all areas of life sciences. The size and model complexity of MD simulations are rapidly growing along with increasing computing power and improved algorithms. This growth has led to the production of a large amount of simulation data that need to be filtered for relevant information to address specific biomedical and biochemical questions. One of the most relevant molecular properties that can be investigated by all-atom MD simulations is the time-dependent evolution of the complex noncovalent interaction networks governing such fundamental aspects as molecular recognition, binding strength, and mechanical and structural stability. Extracting, evaluating, and visualizing noncovalent interactions is a key task in the daily work of structural biologists. We have developed PyContact, an easy-to-use, highly flexible, and intuitive graphical user interface-based application, designed to provide a toolkit to investigate biomolecular interactions in MD trajectories. PyContact is designed to facilitate this task by enabling identification of relevant noncovalent interactions in a comprehensible manner. The implementation of PyContact as a standalone application enables rapid analysis and data visualization without any additional programming requirements, and also preserves full in-program customization and extension capabilities for advanced users. The statistical analysis representation is interactively combined with full mapping of the results on the molecular system through the synergistic connection between PyContact and VMD. We showcase the capabilities and scientific significance of PyContact by analyzing and visualizing in great detail the noncovalent interactions underlying the ion permeation pathway of the human P2X 3 receptor. As a second application, we examine the protein-protein interaction network of the mechanically ultrastable cohesin-dockering complex. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Rapid Detection of Pathogens

DOE Office of Scientific and Technical Information (OSTI.GOV)

David Perlin

2005-08-14

Pathogen identification is a crucial first defense against bioterrorism. A major emphasis of our national biodefense strategy is to establish fast, accurate and sensitive assays for diagnosis of infectious diseases agents. Such assays will ensure early and appropriate treatment of infected patients. Rapid diagnostics can also support infection control measures, which monitor and limit the spread of infectious diseases agents. Many select agents are highly transmissible in the early stages of disease, and it is critical to identify infected patients and limit the risk to the remainder of the population and to stem potential panic in the general population. Nucleicmore » acid-based molecular approaches for identification overcome many of the deficiencies associated with conventional culture methods by exploiting both large- and small-scale genomic differences between organisms. PCR-based amplification of highly conserved ribosomal RNA (rRNA) genes, intergenic sequences, and specific toxin genes is currently the most reliable approach for bacterial, fungal and many viral pathogenic agents. When combined with fluorescence-based oligonucleotide detection systems, this approach provides real-time, quantitative, high fidelity analysis capable of single nucleotide allelic discrimination (4). These probe systems offer rapid turn around time (<2 h) and are suitable for high throughput, automated multiplex operations that are critical for clinical diagnostic laboratories. In this pilot program, we have used molecular beacon technology invented at the Public health Research Institute to develop a new generation of molecular probes to rapidly detect important agents of infectious diseases. We have also developed protocols to rapidly extract nucleic acids from a variety of clinical specimen including and blood and tissue to for detection in the molecular assays. This work represented a cooperative research development program between the Kramer-Tyagi/Perlin labs on probe development and the Perlin lab in sample preparation and testing in animal models.« less

Stress and the Emerging Roles of Chromatin Remodeling in Signal Integration and Stable Transmission of Reversible Phenotypes

PubMed Central

Weaver, Ian C. G.; Korgan, Austin C.; Lee, Kristen; Wheeler, Ryan V.; Hundert, Amos S.; Goguen, Donna

2017-01-01

The influence of early life experience and degree of parental-infant attachment on emotional development in children and adolescents has been comprehensively studied. Structural and mechanistic insight into the biological foundation and maintenance of mammalian defensive systems (metabolic, immune, nervous and behavioral) is slowly advancing through the emerging field of developmental molecular (epi)genetics. Initial evidence revealed that differential nurture early in life generates stable differences in offspring hypothalamic-pituitary-adrenal (HPA) regulation, in part, through chromatin remodeling and changes in DNA methylation of specific genes expressed in the brain, revealing physical, biochemical and molecular paths for the epidemiological concept of gene-environment interactions. Herein, a primary molecular mechanism underpinning the early developmental programming and lifelong maintenance of defensive (emotional) responses in the offspring is the alteration of chromatin domains of specific genomic regions from a condensed state (heterochromatin) to a transcriptionally accessible state (euchromatin). Conversely, DNA methylation promotes the formation of heterochromatin, which is essential for gene silencing, genomic integrity and chromosome segregation. Therefore, inter-individual differences in chromatin modifications and DNA methylation marks hold great potential for assessing the impact of both early life experience and effectiveness of intervention programs—from guided psychosocial strategies focused on changing behavior to pharmacological treatments that target chromatin remodeling and DNA methylation enzymes to dietary approaches that alter cellular pools of metabolic intermediates and methyl donors to affect nutrient bioavailability and metabolism. In this review article, we discuss the potential molecular mechanism(s) of gene regulation associated with chromatin modeling and programming of endocrine (e.g., HPA and metabolic or cardiovascular) and behavioral (e.g., fearfulness, vigilance) responses to stress, including alterations in DNA methylation and the role of DNA repair machinery. From parental history (e.g., drugs, housing, illness, nutrition, socialization) to maternal-offspring exchanges of nutrition, microbiota, antibodies and stimulation, the nature of nurture provides not only mechanistic insight into how experiences propagate from external to internal variables, but also identifies a composite therapeutic target, chromatin modeling, for gestational/prenatal stress, adolescent anxiety/depression and adult-onset neuropsychiatric disease. PMID:28360846

Teaching Ionic Solvation Structure with a Monte Carlo Liquid Simulation Program

ERIC Educational Resources Information Center

Serrano, Agostinho; Santos, Flavia M. T.; Greca, Ileana M.

2004-01-01

The use of molecular dynamics and Monte Carlo methods has provided efficient means to stimulate the behavior of molecular liquids and solutions. A Monte Carlo simulation program is used to compute the structure of liquid water and of water as a solvent to Na(super +), Cl(super -), and Ar on a personal computer to show that it is easily feasible to…

Primer on Molecular Genetics; DOE Human Genome Program

DOE R&D Accomplishments Database

1992-04-01

This report is taken from the April 1992 draft of the DOE Human Genome 1991--1992 Program Report, which is expected to be published in May 1992. The primer is intended to be an introduction to basic principles of molecular genetics pertaining to the genome project. The material contained herein is not final and may be incomplete. Techniques of genetic mapping and DNA sequencing are described.

Assessment of Molecular Modeling & Simulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 materialsmore » 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.« less

Conformational, vibrational spectroscopic and quantum chemical studies on 5-methoxyindole-3-carboxaldehyde: A DFT approach

NASA Astrophysics Data System (ADS)

Jeyaseelan, S. Christopher; Hussain, Shamima; Premkumar, R.; Rekha, T. N.; Benial, A. Milton Franklin

2018-04-01

Indole and its derivatives are considered as good ligands for various disease causing proteins in human because of presence of the single nitrogen atom. In the present study, the potential energy surface scan was performed for the most stable molecular structure of the 5-Methoxyindole-3-carboxaldehyde (MICA) molecule. The most stable molecular structure was optimized by DFT/B3LYP method with 6-311G++ (d, p) basis set using Gaussian 09 program package. The vibrational frequencies were calculated and assigned on the basis of potential energy distribution calculations using VEDA 4.0 program. The Frontier molecular orbitals analysis was performed and related molecular propertieswere calculated. The possible electrophilic and nucleophilic reactive sites of the molecule were studied using molecular electrostatic potential analysis, which confirms the bioactivity of the molecule. The natural bond orbital analysis was also performed to confirm the bioactivity of the title molecule.

ISO Key Project: Exploring the Full Range of Quasar/Agn Properties

NASA Technical Reports Server (NTRS)

Wilkes, Belinda; Oliversen, Ronald J. (Technical Monitor)

2003-01-01

While most of the work on this program has been completed, as previously reported, the portion of the program dealing with the subtopic of ISO LWS data analysis and reduction for the LWS Extragalactic Science Team and its leader, Dr. Howard Smith, is still active. This program in fact continues to generate results, and newly available computer modeling has extended the value of the datasets. As a result the team requests a one-year no-cost extension to this program, through 31 December 2004. The essence of the proposal is to perform ISO spectroscopic studies, including data analysis and modeling, of star-formation regions using an ensemble of archival space-based data from the Infrared Space Observatory's Long Wavelength Spectrometer and Short Wavelength Spectrometer, but including as well some other spectroscopic databases. Four kinds of regions are considered in the studies: (1) disks around more evolved objects; (2) young, low or high mass pre-main sequence stars in star-formation regions; (3) star formation in external, bright IR galaxies; and (4) the galactic center. One prime focus of the program is the OH lines in the far infrared. The program has the following goals: 1) Refine the data analysis of ISO observations to obtain deeper and better SNR results on selected sources. The ISO data itself underwent 'pipeline 10' reductions in early 2001, and additional 'hands-on data reduction packages' were supplied by the ISO teams in 2001. The Fabry-Perot database is particularly sensitive to noise and slight calibration errors; 2) Model the atomic and molecular line shapes, in particular the OH lines, using revised Monte-Carlo techniques developed by the SWAS team at the Center for Astrophysics; 3) Attend scientific meetings and workshops; 4) Perform E&PO activities related to infrared astrophysics and/or spectroscopy.

GLOBEC (Global Ocean Ecosystems Dynamics: Northwest Atlantic program

NASA Technical Reports Server (NTRS)

1991-01-01

The specific objective of the meeting was to plan an experiment in the Northwestern Atlantic to study the marine ecosystem and its role, together with that of climate and physical dynamics, in determining fisheries recruitment. The underlying focus of the GLOBEC initiative is to understand the marine ecosystem as it related to marine living resources and to understand how fluctuation in these resources are driven by climate change and exploitation. In this sense the goal is a solid scientific program to provide basic information concerning major fisheries stocks and the environment that sustains them. The plan is to attempt to reach this understanding through a multidisciplinary program that brings to bear new techniques as disparate as numerical fluid dynamic models of ocean circulation, molecular biology and modern acoustic imaging. The effort will also make use of the massive historical data sets on fisheries and the state of the climate in a coordinated manner.

Sex differences in prenatal epigenetic programming of stress pathways.

PubMed

Bale, Tracy L

2011-07-01

Maternal stress experience is associated with neurodevelopmental disorders including schizophrenia and autism. Recent studies have examined mechanisms by which changes in the maternal milieu may be transmitted to the developing embryo and potentially translated into programming of the epigenome. Animal models of prenatal stress have identified important sex- and temporal-specific effects on offspring stress responsivity. As dysregulation of stress pathways is a common feature in most neuropsychiatric diseases, molecular and epigenetic analyses at the maternal-embryo interface, especially in the placenta, may provide unique insight into identifying much-needed predictive biomarkers. In addition, as most neurodevelopmental disorders present with a sex bias, examination of sex differences in the inheritance of phenotypic outcomes may pinpoint gene targets and specific windows of vulnerability in neurodevelopment, which have been disrupted. This review discusses the association and possible contributing mechanisms of prenatal stress in programming offspring stress pathway dysregulation and the importance of sex.

BioRuby: bioinformatics software for the Ruby programming language.

PubMed

Goto, Naohisa; Prins, Pjotr; Nakao, Mitsuteru; Bonnal, Raoul; Aerts, Jan; Katayama, Toshiaki

2010-10-15

The BioRuby software toolkit contains a comprehensive set of free development tools and libraries for bioinformatics and molecular biology, written in the Ruby programming language. BioRuby has components for sequence analysis, pathway analysis, protein modelling and phylogenetic analysis; it supports many widely used data formats and provides easy access to databases, external programs and public web services, including BLAST, KEGG, GenBank, MEDLINE and GO. BioRuby comes with a tutorial, documentation and an interactive environment, which can be used in the shell, and in the web browser. BioRuby is free and open source software, made available under the Ruby license. BioRuby runs on all platforms that support Ruby, including Linux, Mac OS X and Windows. And, with JRuby, BioRuby runs on the Java Virtual Machine. The source code is available from http://www.bioruby.org/. katayama@bioruby.org

Genome-Enabled Molecular Tools for Reductive Dehalogenation

DTIC Science & Technology

2011-11-01

Genome-Enabled Molecular Tools for Reductive Dehalogenation - A Shift in Paradigm for Bioremediation - Alfred M. Spormann Departments of Chemical...Genome-Enabled Molecular Tools for Reductive Dehalogenation 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...Applications Technical Session No. 3D C-77 GENOME-ENABLED MOLECULAR TOOLS FOR REDUCTIVE DEHALOGENATION PROFESSOR ALFRED SPORMANN Stanford

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

PubMed

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.

Resolving asymmetries along the pulsation cycle of the Mira star X Hydrae

NASA Astrophysics Data System (ADS)

Haubois, X.; Wittkowski, M.; Perrin, G.; Kervella, P.; Mérand, A.; Thiébaut, E.; Ridgway, S. T.; Ireland, M.; Scholz, M.

2015-10-01

Context. The mass-loss process in Mira stars probably occurs in an asymmetric way where dust can form in inhomogeneous circumstellar molecular clumps. Following asymmetries along the pulsation cycle can give us clues about these mass-loss processes. Aims: We imaged the Mira star X Hya and its environnement at different epochs to follow the evolution of the morphology in the continuum and in the molecular bands. Methods: We observed X Hya with AMBER in J-H-K at low resolution at two epochs. We modelled squared visibilities with geometrical and physical models. We also present imaging reconstruction results obtained with MiRA and based on the physical a priori images. Results: We report on the angular scale change of X Hya between the two epochs. 1D CODEX profiles allowed us to understand and model the spectral variation of squared visibilities and constrain the stellar parameters. Reconstructed model-dependent images enabled us to reproduce closure phase signals and the azimuthal dependence of squared visibilities. They show evidence for material inhomogeneities located in the immediate environment of the star. Based on observations obtained with the ESO VLTI/ATs telescopes under the program ID 084.D-0326. Figures 7-12 are available in electronic form at http://www.aanda.org

Alkaloids and leishmania donovani UDP-galactopyarnose mutase: Anovel approach in drug designing against Visceral leishmaniasis.

PubMed

Srivastava, Ankita; Chandra, Deepak

2017-06-05

The unsatisfactory treatment options for Visceral Leishmaniasis (VL), needs identification of new drug targets. Among natural products, Alkaloids have been proved to be highly effective against number of diseases. In Leishmania UDP-galactopyranose mutase (UGM) is a critical enzyme required for cell wall synthesis and thus a drug target for structure based drug designing against L. donovani. To build the homology model of UDP galactopyranse mutase and investigate the interaction of selected alkaloids with this modeled UDP galactopyranose mutase by molecular docking. Since there is no crystal structure record has been found with this protein, a homology modeling was performed and a three dimensional structure of L. donovani UGM was created using MODELLER v9.9, structure quality was validated using PROCHECK and QMEAN programs which confirms that the structure is reliable. Further Molecular docking was performed with previously reported 15 alkaloids. It was found that Protopine shows a binding energy of -12.39Kcal/mole, binds at Flavin adenine dinucleotide (FAD) biding site. Concluding that Protopine, an alkaloid could interrupt the functional aspect of L. donovani UGM and thus may be useful for drug designing studies. These finding would contribute to the understanding of effect of drug on the parasite. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Outpatient treatment of deep venous thrombosis in diverse inner-city patients.

PubMed

Dunn, A S; Schechter, C; Gotlin, A; Vomvolakis, D; Jacobs, E; Sacks, H S; Coller, B

2001-04-15

We sought to describe the development and outcomes of a hospital-based program designed to provide safe and effective outpatient treatment to a diverse group of patients with acute deep venous thrombosis. Patients enrolled in the program were usually discharged on the day of or the day after presentation. Low- molecular-weight heparin was administered for a minimum of 5 days and warfarin was given for a minimum of 3 months. The hospital provided low-molecular-weight heparin free of charge to patients. Patients received daily home nursing visits to monitor the prothrombin time, assess compliance, and detect complications. The inpatient and outpatient records of the first 89 consecutive patients enrolled in the program were reviewed. Patients were observed for a 3-month period after enrollment. The median length of stay was 1 day. Low-molecular-weight heparin was administered for a mean (+/- standard deviation [SD]) of 4.7 +/- 2.4 days at home. Recurrent thromboembolism was noted in 1 patient (1%), major bleeding in 2 patients (2%), and minor bleeding in 2 patients (2%). No patients died or developed thrombocytopenia. Assuming that patients would have been hospitalized for the duration of treatment with low-molecular-weight heparin, the program eliminated a mean of 4.7 days of hospitalization, with an estimated reduction of $1,645 in total health care costs per patient. This hospital-based program to provide outpatient treatment of deep venous thrombosis to a diverse group of inner-city patients achieved a low incidence of adverse events and substantial health care cost savings. Specific strategies, including providing low-molecular-weight heparin free of charge and daily home nursing visits, can be utilized to facilitate access to outpatient treatment and ensure high-quality care.

The role of inhibition by phosphocitrate and its analogue in chondrocyte differentiation and subchondral bone advance in Hartley guinea pigs

PubMed Central

Sun, Yubo; Kiraly, Alex J.; Cox, Michael; Mauerhan, David R.; Hanley, Edward N.

2018-01-01

Phosphocitrate (PC) and its analogue, PC-β ethyl ester, inhibit articular cartilage degeneration in Hartley guinea pigs. However, the underlying molecular mechanisms remain unclear. The present study aimed to investigate the hypothesis that PC exerted its disease-modifying effect on osteoarthritis (OA), in part, by inhibiting a molecular program similar to that in the endochondral pathway of ossification. The results demonstrated that severe proteoglycan loss occurred in the superficial and middle zones, as well as in the calcified zone of articular cartilage in the Hartley guinea pigs. Subchondral bone advance was greater in the control Hartley guinea pigs compared with PC- or PC analogue-treated guinea pigs. Resorption of cartilage bars or islands and vascular invasion in the growth plate were also greater in the control guinea pigs compared with the PC- or PC analogue-treated guinea pigs. The levels of matrix metalloproteinase-13 and type X collagen within the articular cartilage and growth plate were significantly increased in the control guinea pigs compared with PC-treated guinea pigs (P<0.05). These results indicated that articular chondrocytes in Hartley guinea pigs exhibited a hypertrophic phenotype and recapitulated a developmental molecular program similar to the endochondral pathway of ossification. Activation of this molecular program resulted in resorption of calcified articular cartilage and subchondral bone advance. This suggests that PC and PC analogues exerted their OA disease-modifying activity, in part, by inhibiting this molecular program. PMID:29545850

Evolutionary Models of Cold, Magnetized, Interstellar Clouds

NASA Technical Reports Server (NTRS)

Gammie, Charles F.; Ostriker, Eve; Stone, James M.

2004-01-01

We modeled the long-term and small-scale evolution of molecular clouds using direct 2D and 3D magnetohydrodynamic (MHD) simulations. This work followed up on previous research by our group under auspices of the ATP in which we studied the energetics of turbulent, magnetized clouds and their internal structure on intermediate scales. Our new work focused on both global and smallscale aspects of the evolution of turbulent, magnetized clouds, and in particular studied the response of turbulent proto-cloud material to passage through the Galactic spiral potential, and the dynamical collapse of turbulent, magnetized (supercritical) clouds into fragments to initiate the formation of a stellar cluster. Technical advances under this program include developing an adaptive-mesh MHD code as a successor to ZEUS (ATHENA) in order to follow cloud fragmentation, developing a shearing-sheet MHD code which includes self-gravity and externally-imposed gravity to follow the evolution of clouds in the Galactic potential, and developing radiative transfer models to evaluate the internal ionization of clumpy clouds exposed to external photoionizing UV and CR radiation. Gammie's work at UIUC focused on the radiative transfer aspects of this program.

ECUT (Energy Conversion and Utilization Technologies Program). Biocatalysis Project

NASA Technical Reports Server (NTRS)

1986-01-01

Presented are the FY 1985 accomplishments, activities, and planned research efforts of the Biocatalysis Project of the U.S. Department of Energy, Energy Conversion and Utilization Technologies (ECUT) Program. The Project's technical activities were organized as follows: In the Molecular Modeling and Applied Genetics work element, research focused on (1) modeling and simulation studies to establish the physiological basis of high temperature tolerance in a selected enzyme and the catalytic mechanisms of three species of another enzyme, and (2) determining the degree of plasmid amplification and stability of several DNA bacterial strains. In the Bioprocess Engineering work element, research focused on (1) studies of plasmid propagation and the generation of models, (2) developing methods for preparing immobilized biocatalyst beads, and (3) developing an enzyme encapsulation method. In the Process Design and Analysis work element, research focused on (1) further refinement of a test case simulation of the economics and energy efficiency of alternative biocatalyzed production processes, (2) developing a candidate bioprocess to determine the potential for reduced energy consumption and facility/operating costs, and (3) a techno-economic assessment of potential advancements in microbial ammonia production.

The MOLDY short-range molecular dynamics package

NASA Astrophysics Data System (ADS)

Ackland, G. J.; D'Mellow, K.; Daraszewicz, S. L.; Hepburn, D. J.; Uhrin, M.; Stratford, K.

2011-12-01

We describe a parallelised version of the MOLDY molecular dynamics program. This Fortran code is aimed at systems which may be described by short-range potentials and specifically those which may be addressed with the embedded atom method. This includes a wide range of transition metals and alloys. MOLDY provides a range of options in terms of the molecular dynamics ensemble used and the boundary conditions which may be applied. A number of standard potentials are provided, and the modular structure of the code allows new potentials to be added easily. The code is parallelised using OpenMP and can therefore be run on shared memory systems, including modern multicore processors. Particular attention is paid to the updates required in the main force loop, where synchronisation is often required in OpenMP implementations of molecular dynamics. We examine the performance of the parallel code in detail and give some examples of applications to realistic problems, including the dynamic compression of copper and carbon migration in an iron-carbon alloy. Program summaryProgram title: MOLDY Catalogue identifier: AEJU_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEJU_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: GNU General Public License version 2 No. of lines in distributed program, including test data, etc.: 382 881 No. of bytes in distributed program, including test data, etc.: 6 705 242 Distribution format: tar.gz Programming language: Fortran 95/OpenMP Computer: Any Operating system: Any Has the code been vectorised or parallelized?: Yes. OpenMP is required for parallel execution RAM: 100 MB or more Classification: 7.7 Nature of problem: Moldy addresses the problem of many atoms (of order 10 6) interacting via a classical interatomic potential on a timescale of microseconds. It is designed for problems where statistics must be gathered over a number of equivalent runs, such as measuring thermodynamic properities, diffusion, radiation damage, fracture, twinning deformation, nucleation and growth of phase transitions, sputtering etc. In the vast majority of materials, the interactions are non-pairwise, and the code must be able to deal with many-body forces. Solution method: Molecular dynamics involves integrating Newton's equations of motion. MOLDY uses verlet (for good energy conservation) or predictor-corrector (for accurate trajectories) algorithms. It is parallelised using open MP. It also includes a static minimisation routine to find the lowest energy structure. Boundary conditions for surfaces, clusters, grain boundaries, thermostat (Nose), barostat (Parrinello-Rahman), and externally applied strain are provided. The initial configuration can be either a repeated unit cell or have all atoms given explictly. Initial velocities are generated internally, but it is also possible to specify the velocity of a particular atom. A wide range of interatomic force models are implemented, including embedded atom, Morse or Lennard-Jones. Thus the program is especially well suited to calculations of metals. Restrictions: The code is designed for short-ranged potentials, and there is no Ewald sum. Thus for long range interactions where all particles interact with all others, the order- N scaling will fail. Different interatomic potential forms require recompilation of the code. Additional comments: There is a set of associated open-source analysis software for postprocessing and visualisation. This includes local crystal structure recognition and identification of topological defects. Running time: A set of test modules for running time are provided. The code scales as order N. The parallelisation shows near-linear scaling with number of processors in a shared memory environment. A typical run of a few tens of nanometers for a few nanoseconds will run on a timescale of days on a multiprocessor desktop.

Molecular Mechanics: The Method and Its Underlying Philosophy.

ERIC Educational Resources Information Center

Boyd, Donald B.; Lipkowitz, Kenny B.

1982-01-01

Molecular mechanics is a nonquantum mechanical method for solving problems concerning molecular geometries and energy. Methodology based on: the principle of combining potential energy functions of all structural features of a particular molecule into a total force field; derivation of basic equations; and use of available computer programs is…

Molecular Mechanisms That Underlie the Dynamic Adaptation of Innate Monocyte Memory to Varying Stimulant Strength of TLR Ligands.

PubMed

Yuan, Ruoxi; Geng, Shuo; Li, Liwu

2016-01-01

In adaptation to rising stimulant strength, innate monocytes can be dynamically programed to preferentially express either pro- or anti-inflammatory mediators. Such dynamic innate adaptation or programing may bear profound relevance in host health and disease. However, molecular mechanisms that govern innate adaptation to varying strength of stimulants are not well understood. Using lipopolysaccharide (LPS), the model stimulant of toll-like-receptor 4 (TLR4), we reported that the expressions of pro-inflammatory mediators are preferentially sustained in monocytes adapted by lower doses of LPS, and suppressed/tolerized in monocytes adapted by higher doses of LPS. Mechanistically, monocytes adapted by super-low dose LPS exhibited higher levels of transcription factor, interferon regulatory factor 5 (IRF5), and reduced levels of transcriptional modulator B lymphocyte-induced maturation protein-1 (Blimp-1). Intriguingly, the inflammatory monocyte adaptation by super-low dose LPS is dependent upon TRAM/TRIF but not MyD88. Similar to LPS, we also observed biphasic inflammatory adaptation and tolerance in monocytes challenged with varying dosages of TLR7 agonist. In sharp contrast, rising doses of TLR3 agonist preferentially caused inflammatory adaptation without inducing tolerance. At the molecular level, the differential regulation of IRF5 and Blimp-1 coincides with unique monocyte adaptation dynamics by TLR4/7 and TLR3 agonists. Our study provides novel clue toward the understanding of monocyte adaptation and memory toward distinct TLR ligands.

A Training Program in Breast Cancer Research Using NMR Techniques

DTIC Science & Technology

2005-07-01

to explore the application NMR molecular imaging techniques developed in this program in detection of amyloid plaques in the Alzheimer diseased mouse...one is to utilize the molecular imaging technique to exploit new application in imaging of amyloid plaques in Alzheimer disease. A abridge of each...matched, non-demented elderly suggests that volumetric studies of ante-mortem neuroimages may provide an early marker of AD in aging populations. In

World Wide Web-based system for the calculation of substituent parameters and substituent similarity searches.

PubMed

Ertl, P

1998-02-01

Easy to use, interactive, and platform-independent WWW-based tools are ideal for development of chemical applications. By using the newly emerging Web technologies such as Java applets and sophisticated scripting, it is possible to deliver powerful molecular processing capabilities directly to the desk of synthetic organic chemists. In Novartis Crop Protection in Basel, a Web-based molecular modelling system has been in use since 1995. In this article two new modules of this system are presented: a program for interactive calculation of important hydrophobic, electronic, and steric properties of organic substituents, and a module for substituent similarity searches enabling the identification of bioisosteric functional groups. Various possible applications of calculated substituent parameters are also discussed, including automatic design of molecules with the desired properties and creation of targeted virtual combinatorial libraries.

Regulation of gene transcription by Polycomb proteins

PubMed Central

Aranda, Sergi; Mas, Gloria; Di Croce, Luciano

2015-01-01

The Polycomb group (PcG) of proteins defines a subset of factors that physically associate and function to maintain the positional identity of cells from the embryo to adult stages. PcG has long been considered a paradigmatic model for epigenetic maintenance of gene transcription programs. Despite intensive research efforts to unveil the molecular mechanisms of action of PcG proteins, several fundamental questions remain unresolved: How many different PcG complexes exist in mammalian cells? How are PcG complexes targeted to specific loci? How does PcG regulate transcription? In this review, we discuss the diversity of PcG complexes in mammalian cells, examine newly identified modes of recruitment to chromatin, and highlight the latest insights into the molecular mechanisms underlying the function of PcGs in transcription regulation and three-dimensional chromatin conformation. PMID:26665172

Molecular genetic approaches to the study of cellular senescence.

PubMed

Goletz, T J; Smith, J R; Pereira-Smith, O M

1994-01-01

Cellular senescence is an inability of cells to synthesize DNA and divide, which results in a terminal loss of proliferation despite the maintenance of basic metabolic processes. Senescence has been proposed as a model for the study of aging at the cellular level, and the basis for this model system and its features have been summarized. Although strong experimental evidence exists to support the hypothesis that cellular senescence is a dominant active process, the mechanisms responsible for this phenomenon remain a mystery. Investigators have taken several approaches to gain a better understanding of senescence. Several groups have documented the differences between young and senescent cells, and others have identified changes that occur during the course of a cell's in vitro life span. Using molecular and biochemical approaches, important changes in gene expression and function of cell-cycle-associated products have been identified. The active production of an inhibitor of DNA synthesis has been demonstrated. This may represent the final step in a cascade of events governing senescence. The study of immortal cells which have escaped senescence has also provided useful information, particularly with regard to the genes governing the senescence program. These studies have identified four complementation groups for indefinite division, which suggests that there are at least four genes or gene pathways in the senescence program. Through the use of microcell-mediated chromosome transfer, chromosomes encoding senescence genes have been identified; efforts to clone these genes are ongoing.(ABSTRACT TRUNCATED AT 250 WORDS)

ENABLE 2017, the First EUROPEAN PhD and Post-Doc Symposium. Session 4: From Discovery to Cure: The Future of Therapeutics.

PubMed

Di Mauro, Gianmarco; Dondi, Ambra; Giangreco, Giovanni; Hogrebe, Alexander; Louer, Elja; Magistrati, Elisa; Mullari, Meeli; Turon, Gemma; Verdurmen, Wouter; Xicoy Cortada, Helena; Zivanovic, Sanja

2018-05-28

The EUROPEAN ACADEMY FOR BIOMEDICAL SCIENCE (ENABLE) is an initiative funded by the European Union Horizon 2020 program involving four renowned European Research Institutes (Institute for Research in Biomedicine-IRB Barcelona, Spain; Radboud Institute for Molecular Life Sciences-RIMLS, the Netherlands; Novo Nordisk Foundation Center for Protein Research-NNF CPR, Denmark; European School of Molecular Medicine-SEMM, Italy) and an innovative science communication agency (Scienseed). With the aim of promoting biomedical science of excellence in Europe, ENABLE organizes an annual three-day international event. This gathering includes a top-level scientific symposium bringing together leading scientists, PhD students, and post-doctoral fellows; career development activities supporting the progression of young researchers and fostering discussion about opportunities beyond the bench; and outreach activities stimulating the interaction between science and society. The first European PhD and Postdoc Symposium, entitled "Breaking Down Complexity: Innovative Models and Techniques in Biomedicine", was hosted by the vibrant city of Barcelona. The scientific program of the conference was focused on the most recent advances and applications of modern techniques and models in biomedical research and covered a wide range of topics, from synthetic biology to translational medicine. Overall, the event was a great success, with more than 200 attendees from all over Europe actively participating in the symposium by presenting their research and exchanging ideas with their peers and world-renowned scientists.

Incorporation of autopsy case-based learning into PhD graduate education: a novel approach to bridging the "bench-to-bedside" gap.

PubMed

Brooks, Erin G; Thornton, Joanne M; Ranheim, Erik A; Fabry, Zsuzsanna

2017-10-01

Given the current rapid expansion of biological knowledge and the challenges of translating that knowledge into clinical practice, finding effective methods of teaching graduate students clinical medicine concepts has become even more critical. The utility of autopsy in medical student and resident education has been well established. Multiple studies have reported it to be a helpful means of teaching anatomy, pathophysiology, clinical problem-solving skills, and medical diagnostic techniques. Although various models of training PhD candidates in clinical medicine have been reported, an autopsy-based curriculum has not been previously described. For over 4 years, our pathology department has offered a novel semester-long autopsy-based course to educate future Cellular and Molecular Pathology scientists about clinical medicine. Our results indicate that this "hands-on" approach is a popular as well as effective means of teaching the pathogenesis of disease at the level of the cell, organ, and patient. The course reputation has recently led to requests to open registration to graduate students from other university programs as well as undergraduate students. Additionally, it has played an important role in our Cellular and Molecular Pathology program's recent receipt of a 5-year renewal National Institutes of Health-funded T32 award. Overall, this course model has been successful at our own institution and could provide a useful template for other institutions seeking to provide graduate investigators with in-depth exposure to clinical medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

FlaME: Flash Molecular Editor - a 2D structure input tool for the web

PubMed Central

2011-01-01

Background So far, there have been no Flash-based web tools available for chemical structure input. The authors herein present a feasibility study, aiming at the development of a compact and easy-to-use 2D structure editor, using Adobe's Flash technology and its programming language, ActionScript. As a reference model application from the Java world, we selected the Java Molecular Editor (JME). In this feasibility study, we made an attempt to realize a subset of JME's functionality in the Flash Molecular Editor (FlaME) utility. These basic capabilities are: structure input, editing and depiction of single molecules, data import and export in molfile format. Implementation The result of molecular diagram sketching in FlaME is accessible in V2000 molfile format. By integrating the molecular editor into a web page, its communication with the HTML elements on this page is established using the two JavaScript functions, getMol() and setMol(). In addition, structures can be copied to the system clipboard. Conclusion A first attempt was made to create a compact single-file application for 2D molecular structure input/editing on the web, based on Flash technology. With the application examples presented in this article, it could be demonstrated that the Flash methods are principally well-suited to provide the requisite communication between the Flash object (application) and the HTML elements on a web page, using JavaScript functions. PMID:21284863

Dynamic Structure-Based Pharmacophore Model Development: A New and Effective Addition in the Histone Deacetylase 8 (HDAC8) Inhibitor Discovery

PubMed Central

Thangapandian, Sundarapandian; John, Shalini; Lee, Yuno; Kim, Songmi; Lee, Keun Woo

2011-01-01

Histone deacetylase 8 (HDAC8) is an enzyme involved in deacetylating the amino groups of terminal lysine residues, thereby repressing the transcription of various genes including tumor suppressor gene. The over expression of HDAC8 was observed in many cancers and thus inhibition of this enzyme has emerged as an efficient cancer therapeutic strategy. In an effort to facilitate the future discovery of HDAC8 inhibitors, we developed two pharmacophore models containing six and five pharmacophoric features, respectively, using the representative structures from two molecular dynamic (MD) simulations performed in Gromacs 4.0.5 package. Various analyses of trajectories obtained from MD simulations have displayed the changes upon inhibitor binding. Thus utilization of the dynamically-responded protein structures in pharmacophore development has the added advantage of considering the conformational flexibility of protein. The MD trajectories were clustered based on single-linkage method and representative structures were taken to be used in the pharmacophore model development. Active site complimenting structure-based pharmacophore models were developed using Discovery Studio 2.5 program and validated using a dataset of known HDAC8 inhibitors. Virtual screening of chemical database coupled with drug-like filter has identified drug-like hit compounds that match the pharmacophore models. Molecular docking of these hits reduced the false positives and identified two potential compounds to be used in future HDAC8 inhibitor design. PMID:22272142

LAMMPS framework for dynamic bonding and an application modeling DNA

NASA Astrophysics Data System (ADS)

Svaneborg, Carsten

2012-08-01

We have extended the Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) to support directional bonds and dynamic bonding. The framework supports stochastic formation of new bonds, breakage of existing bonds, and conversion between bond types. Bond formation can be controlled to limit the maximal functionality of a bead with respect to various bond types. Concomitant with the bond dynamics, angular and dihedral interactions are dynamically introduced between newly connected triplets and quartets of beads, where the interaction type is determined from the local pattern of bead and bond types. When breaking bonds, all angular and dihedral interactions involving broken bonds are removed. The framework allows chemical reactions to be modeled, and use it to simulate a simplistic, coarse-grained DNA model. The resulting DNA dynamics illustrates the power of the present framework. Catalogue identifier: AEME_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEME_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: GNU General Public Licence No. of lines in distributed program, including test data, etc.: 2 243 491 No. of bytes in distributed program, including test data, etc.: 771 Distribution format: tar.gz Programming language: C++ Computer: Single and multiple core servers Operating system: Linux/Unix/Windows Has the code been vectorized or parallelized?: Yes. The code has been parallelized by the use of MPI directives. RAM: 1 Gb Classification: 16.11, 16.12 Nature of problem: Simulating coarse-grain models capable of chemistry e.g. DNA hybridization dynamics. Solution method: Extending LAMMPS to handle dynamic bonding and directional bonds. Unusual features: Allows bonds to be created and broken while angular and dihedral interactions are kept consistent. Additional comments: The distribution file for this program is approximately 36 Mbytes and therefore is not delivered directly when download or E-mail is requested. Instead an html file giving details of how the program can be obtained is sent. Running time: Hours to days. The examples provided in the distribution take just seconds to run.

Force Field for Peptides and Proteins based on the Classical Drude Oscillator

PubMed Central

Lopes, Pedro E.M.; Huang, Jing; Shim, Jihyun; Luo, Yun; Li, Hui; Roux, Benoît; MacKerell, Alexander D.

2013-01-01

Presented is a polarizable force field based on a classical Drude oscillator framework, currently implemented in the programs CHARMM and NAMD, for modeling and molecular dynamics (MD) simulation studies of peptides and proteins. Building upon parameters for model compounds representative of the functional groups in proteins, the development of the force field focused on the optimization of the parameters for the polypeptide backbone and the connectivity between the backbone and side chains. Optimization of the backbone electrostatic parameters targeted quantum mechanical conformational energies, interactions with water, molecular dipole moments and polarizabilities and experimental condensed phase data for short polypeptides such as (Ala)5. Additional optimization of the backbone φ, ψ conformational preferences included adjustments of the tabulated two-dimensional spline function through the CMAP term. Validation of the model included simulations of a collection of peptides and proteins. This 1st generation polarizable model is shown to maintain the folded state of the studied systems on the 100 ns timescale in explicit solvent MD simulations. The Drude model typically yields larger RMS differences as compared to the additive CHARMM36 force field (C36) and shows additional flexibility as compared to the additive model. Comparison with NMR chemical shift data shows a small degradation of the polarizable model with respect to the additive, though the level of agreement may be considered satisfactory, while for residues shown to have significantly underestimated S2 order parameters in the additive model, improvements are calculated with the polarizable model. Analysis of dipole moments associated with the peptide backbone and tryptophan side chains show the Drude model to have significantly larger values than those present in C36, with the dipole moments of the peptide backbone enhanced to a greater extent in sheets versus helices and the dipoles of individual moieties observed to undergo significant variations during the MD simulations. Although there are still some limitations, the presented model, termed Drude-2013, is anticipated to yield a molecular picture of peptide and protein structure and function that will be of increased physical validity and internal consistency in a computationally accessible fashion. PMID:24459460

Structure, Function, and Applications of the Georgetown-Einstein (GE) Breast Cancer Simulation Model.

PubMed

Schechter, Clyde B; Near, Aimee M; Jayasekera, Jinani; Chandler, Young; Mandelblatt, Jeanne S

2018-04-01

The Georgetown University-Albert Einstein College of Medicine breast cancer simulation model (Model GE) has evolved over time in structure and function to reflect advances in knowledge about breast cancer, improvements in early detection and treatment technology, and progress in computing resources. This article describes the model and provides examples of model applications. The model is a discrete events microsimulation of single-life histories of women from multiple birth cohorts. Events are simulated in the absence of screening and treatment, and interventions are then applied to assess their impact on population breast cancer trends. The model accommodates differences in natural history associated with estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) biomarkers, as well as conventional breast cancer risk factors. The approach for simulating breast cancer natural history is phenomenological, relying on dates, stage, and age of clinical and screen detection for a tumor molecular subtype without explicitly modeling tumor growth. The inputs to the model are regularly updated to reflect current practice. Numerous technical modifications, including the use of object-oriented programming (C++), and more efficient algorithms, along with hardware advances, have increased program efficiency permitting simulations of large samples. The model results consistently match key temporal trends in US breast cancer incidence and mortality. The model has been used in collaboration with other CISNET models to assess cancer control policies and will be applied to evaluate clinical trial design, recurrence risk, and polygenic risk-based screening.

Quantum Mechanical Study of Atoms and Molecules

NASA Technical Reports Server (NTRS)

Sahni, R. C.

1961-01-01

This paper, following a brief introduction, is divided into five parts. Part I outlines the theory of the molecular orbital method for the ground, ionized and excited states of molecules. Part II gives a brief summary of the interaction integrals and their tabulation. Part III outlines an automatic program designed for the computation of various states of molecules. Part IV gives examples of the study of ground, ionized and excited states of CO, BH and N2 where the program of automatic computation and molecular integrals have been utilized. Part V enlists some special problems of Molecular Quantum Mechanics are being tackled at New York University.

A complete catalog of stellar mass maps for PHANGS

NASA Astrophysics Data System (ADS)

Munoz-Mateos, Juan-Carlos; Querejeta, Miguel; Schinnerer, Eva; Leroy, Adam; Sun, Jiayi; Blanc, Guillermo; Kruijssen, Diederik; Emsellem, Eric; Bigiel, Frank

2018-05-01

We request IRAC 3.6 and 4.5 um imaging of four galaxies that have been mapped in molecular gas by ALMA as part of its first large program targeting nearby galaxies (PHANGS: Physics at High Angular resolution in Nearby GalaxieS). IRAC provides a uniquely robust view of the stellar mass distribution, which in turn plays a key role in regulating the properties and behavior of the molecular gas. These are the only targets of our ALMA large program without such imaging. A modest investment of Spitzer time will allow us to measure the drivers of molecular cloud and star formation in these targets.

Halogen occultation experiment (HALOE) optical witness-plate program

NASA Technical Reports Server (NTRS)

Harvey, Gale A.; Raper, James L.

1989-01-01

An optical witness plate program was implemented to monitor buildup of molecular contamination in the clean room during the assembly and testing of the Halogen Occulation Experiment (HALOE) instrument. Travel plates to monitor molecular contamination when the instrument is not in the clean room are also measured. The instrument technique is high-resolution transmission spectroscopy in the 3 micron spectral region using a Fourier transform spectrometer. Witness specimens of low index of refraction, infrared transmitting material are used for contaminant monitoring and for spectral signature analysis. Spectral signatures of possible molecular contamination are presented. No condensible volatile material contamination of HALOE optical witness specimens have yet been found.

Between destiny and disease: genetics and molecular pathways of human central nervous system aging.

PubMed

Glorioso, Christin; Sibille, Etienne

2011-02-01

Aging of the human brain is associated with "normal" functional, structural, and molecular changes that underlie alterations in cognition, memory, mood and motor function, amongst other processes. Normal aging also imposes a robust constraint on the onset of many neurological diseases, ranging from late onset neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's diseases (PD), to early onset psychiatric disorders, such as bipolar disorder (BPD) and schizophrenia (SCZ). The molecular mechanisms and genetic underpinnings of age-related changes in the brain are understudied, and, while they share some overlap with peripheral mechanisms of aging, many are unique to the largely non-mitotic brain. Hence, understanding mechanisms of brain aging and identifying associated modulators may have profound consequences for the prevention and treatment of age-related impairments and diseases. Here we review current knowledge on age-related functional and structural changes, their molecular and genetic underpinnings, and discuss how these pathways may contribute to the vulnerability to develop age-related neurological diseases. We highlight recent findings from human post-mortem brain microarray studies, which we hypothesize, point to a potential genetically controlled transcriptional program underlying molecular changes and age-gating of neurological diseases. Finally, we discuss the implications of this model for understanding basic mechanisms of brain aging and for the future investigation of therapeutic approaches. Copyright © 2010 Elsevier Ltd. All rights reserved.

Estimation of mechanical properties of nanomaterials using artificial intelligence methods

NASA Astrophysics Data System (ADS)

Vijayaraghavan, V.; Garg, A.; Wong, C. H.; Tai, K.

2014-09-01

Computational modeling tools such as molecular dynamics (MD), ab initio, finite element modeling or continuum mechanics models have been extensively applied to study the properties of carbon nanotubes (CNTs) based on given input variables such as temperature, geometry and defects. Artificial intelligence techniques can be used to further complement the application of numerical methods in characterizing the properties of CNTs. In this paper, we have introduced the application of multi-gene genetic programming (MGGP) and support vector regression to formulate the mathematical relationship between the compressive strength of CNTs and input variables such as temperature and diameter. The predictions of compressive strength of CNTs made by these models are compared to those generated using MD simulations. The results indicate that MGGP method can be deployed as a powerful method for predicting the compressive strength of the carbon nanotubes.

An enhanced Petri-net model to predict synergistic effects of pairwise drug combinations from gene microarray data.

PubMed

Jin, Guangxu; Zhao, Hong; Zhou, Xiaobo; Wong, Stephen T C

2011-07-01

Prediction of synergistic effects of drug combinations has traditionally been relied on phenotypic response data. However, such methods cannot be used to identify molecular signaling mechanisms of synergistic drug combinations. In this article, we propose an enhanced Petri-Net (EPN) model to recognize the synergistic effects of drug combinations from the molecular response profiles, i.e. drug-treated microarray data. We addressed the downstream signaling network of the targets for the two individual drugs used in the pairwise combinations and applied EPN to the identified targeted signaling network. In EPN, drugs and signaling molecules are assigned to different types of places, while drug doses and molecular expressions are denoted by color tokens. The changes of molecular expressions caused by treatments of drugs are simulated by two actions of EPN: firing and blasting. Firing is to transit the drug and molecule tokens from one node or place to another, and blasting is to reduce the number of molecule tokens by drug tokens in a molecule node. The goal of EPN is to mediate the state characterized by control condition without any treatment to that of treatment and to depict the drug effects on molecules by the drug tokens. We applied EPN to our generated pairwise drug combination microarray data. The synergistic predictions using EPN are consistent with those predicted using phenotypic response data. The molecules responsible for the synergistic effects with their associated feedback loops display the mechanisms of synergism. The software implemented in Python 2.7 programming language is available from request. stwong@tmhs.org.

Molecular Modeling, de novo Design and Synthesis of a Novel, Extracellular Binding Fibroblast Growth Factor Receptor 2 Inhibitor Alofanib (RPT835).

PubMed

Tsimafeyeu, Ilya; Daeyaert, Frits; Joos, Jean-Baptiste; Aken, Koen V; Ludes-Meyers, John; Byakhov, Mikhail; Tjulandin, Sergei

2016-01-01

Fibroblast growth factor (FGF) receptors (FGFRs) play a key role in tumor growth and angiogenesis. The present report describes our search for an extracellularly binding FGFR inhibitor using a combined molecular modeling and de novo design strategy. Based upon crystal structures of the receptor with its native ligand and knowledge of inhibiting peptides, we have developed a computational protocol that predicts the putative binding of a molecule to the extracellular domains of the receptor. This protocol, or scoring function, was used in combination with the de novo synthesis program 'SYNOPSIS' to generate high scoring and synthetically accessible compounds. Eight compounds belonging to 3 separate chemical classes were synthesized. One of these compounds, alofanib (RPT835), was found to be an effective inhibitor of the FGF/FGFR2 pathway. The preclinical in vitro data support an allosteric inhibition mechanism of RPT835. RPT835 potently inhibited growth of KATO III gastric cancer cells expressing FGFR2, with GI50 value of 10 nmol/L. These results provide strong rationale for the evaluation of compound in advanced cancers.

Solution influence on biomolecular equilibria - Nucleic acid base associations

NASA Technical Reports Server (NTRS)

Pohorille, A.; Pratt, L. R.; Burt, S. K.; Macelroy, R. D.

1984-01-01

Various attempts to construct an understanding of the influence of solution environment on biomolecular equilibria at the molecular level using computer simulation are discussed. First, the application of the formal statistical thermodynamic program for investigating biomolecular equilibria in solution is presented, addressing modeling and conceptual simplications such as perturbative methods, long-range interaction approximations, surface thermodynamics, and hydration shell. Then, Monte Carlo calculations on the associations of nucleic acid bases in both polar and nonpolar solvents such as water and carbon tetrachloride are carried out. The solvent contribution to the enthalpy of base association is positive (destabilizing) in both polar and nonpolar solvents while negative enthalpies for stacked complexes are obtained only when the solute-solute in vacuo energy is added to the total energy. The release upon association of solvent molecules from the first hydration layer around a solute to the bulk is accompanied by an increase in solute-solvent energy and decrease in solvent-solvent energy. The techniques presented are expectd to displace less molecular and more heuristic modeling of biomolecular equilibria in solution.

Structure-based design and biological evaluation of novel 2-(indol-2-yl) thiazole derivatives as xanthine oxidase inhibitors.

PubMed

Song, Jeong Uk; Jang, Jae Wan; Kim, Tae Hun; Park, Heuisul; Park, Wan Su; Jung, Sang-Hun; Kim, Geun Tae

2016-02-01

Inhibition of xanthine oxidase (XO) has obviously been a central concept for controlling hyperuricemia, which causes serious and painful inflammatory arthritis disease such as gout. We discovered a series of novel 2-(indol-2-yl)thiazole derivatives as XO inhibitors at the level of nanomolar activity. Structure-guided design using molecular modeling program (Accelrys Software program) provided an excellent basis for optimization of 2-(indol-2-yl)thiazole compounds. Structure-activity relationship indicated that hydrophobic alkoxy group (isopropoxy, cyclopentoxy) at 5-position and hydrogen binding acceptor (NO2, CN) at 7-position of indole ring appear as critical functional groups. Among the compounds, 2-(7-nitro-5-isopropoxy-indol-2-yl)-4-methylthiazole-5-carboxylic acid (9m) exhibits the most potent XO inhibitory activity (IC50 value: 5.1 nM) and the excellent uric acid lowering activity in potassium oxonate induced hyperuricemic rat model. Copyright © 2016. Published by Elsevier Ltd.

Analysis of ISO Data

NASA Technical Reports Server (NTRS)

Lambert, David L.

2003-01-01

A block grant supported several astronomers who executed observing programs using the Infrared Space Observatory (ISO). The ISO project in which Harriet Dinerstein participated was a study of sulfur and neon abundances in extragalactic H II regions using the ISO Short Wavelength Spectrometer (SWS). Evans and Jaffe, along with collaborators Ewine van Dishoeck and Wing-Fai Thi, and then graduate student Wenbin Li, carried out an in-depth study of the peripheral region of the molecular cloud L1204/S140, where the far ultraviolet radiation and the density are relatively low. Their observations test theories of photon-dominated regions (PDRs) in a regime that has been little explored. One ISO program was involved with PHT-32 observations of about a dozen young stars to search for extended emission that could be modeled with our dust-modeling-code at UT. The document reports on preliminary analysis of PHT 32 scanning of 10 pre-main-sequence stars at 50 and 100 microns. A small sample of R Coronae Borealis stars was observed with the SWS.

An argument for mechanism-based statistical inference in cancer

PubMed Central

Ochs, Michael; Price, Nathan D.; Tomasetti, Cristian; Younes, Laurent

2015-01-01

Cancer is perhaps the prototypical systems disease, and as such has been the focus of extensive study in quantitative systems biology. However, translating these programs into personalized clinical care remains elusive and incomplete. In this perspective, we argue that realizing this agenda—in particular, predicting disease phenotypes, progression and treatment response for individuals—requires going well beyond standard computational and bioinformatics tools and algorithms. It entails designing global mathematical models over network-scale configurations of genomic states and molecular concentrations, and learning the model parameters from limited available samples of high-dimensional and integrative omics data. As such, any plausible design should accommodate: biological mechanism, necessary for both feasible learning and interpretable decision making; stochasticity, to deal with uncertainty and observed variation at many scales; and a capacity for statistical inference at the patient level. This program, which requires a close, sustained collaboration between mathematicians and biologists, is illustrated in several contexts, including learning bio-markers, metabolism, cell signaling, network inference and tumorigenesis. PMID:25381197

Feasibility of quasi-random band model in evaluating atmospheric radiance

NASA Technical Reports Server (NTRS)

Tiwari, S. N.; Mirakhur, N.

1980-01-01

The use of the quasi-random band model in evaluating upwelling atmospheric radiation is investigated. The spectral transmittance and total band adsorptance are evaluated for selected molecular bands by using the line by line model, quasi-random band model, exponential sum fit method, and empirical correlations, and these are compared with the available experimental results. The atmospheric transmittance and upwelling radiance were calculated by using the line by line and quasi random band models and were compared with the results of an existing program called LOWTRAN. The results obtained by the exponential sum fit and empirical relations were not in good agreement with experimental results and their use cannot be justified for atmospheric studies. The line by line model was found to be the best model for atmospheric applications, but it is not practical because of high computational costs. The results of the quasi random band model compare well with the line by line and experimental results. The use of the quasi random band model is recommended for evaluation of the atmospheric radiation.

The MOLGENIS toolkit: rapid prototyping of biosoftware at the push of a button.

PubMed

Swertz, Morris A; Dijkstra, Martijn; Adamusiak, Tomasz; van der Velde, Joeri K; Kanterakis, Alexandros; Roos, Erik T; Lops, Joris; Thorisson, Gudmundur A; Arends, Danny; Byelas, George; Muilu, Juha; Brookes, Anthony J; de Brock, Engbert O; Jansen, Ritsert C; Parkinson, Helen

2010-12-21

There is a huge demand on bioinformaticians to provide their biologists with user friendly and scalable software infrastructures to capture, exchange, and exploit the unprecedented amounts of new *omics data. We here present MOLGENIS, a generic, open source, software toolkit to quickly produce the bespoke MOLecular GENetics Information Systems needed. The MOLGENIS toolkit provides bioinformaticians with a simple language to model biological data structures and user interfaces. At the push of a button, MOLGENIS' generator suite automatically translates these models into a feature-rich, ready-to-use web application including database, user interfaces, exchange formats, and scriptable interfaces. Each generator is a template of SQL, JAVA, R, or HTML code that would require much effort to write by hand. This 'model-driven' method ensures reuse of best practices and improves quality because the modeling language and generators are shared between all MOLGENIS applications, so that errors are found quickly and improvements are shared easily by a re-generation. A plug-in mechanism ensures that both the generator suite and generated product can be customized just as much as hand-written software. In recent years we have successfully evaluated the MOLGENIS toolkit for the rapid prototyping of many types of biomedical applications, including next-generation sequencing, GWAS, QTL, proteomics and biobanking. Writing 500 lines of model XML typically replaces 15,000 lines of hand-written programming code, which allows for quick adaptation if the information system is not yet to the biologist's satisfaction. Each application generated with MOLGENIS comes with an optimized database back-end, user interfaces for biologists to manage and exploit their data, programming interfaces for bioinformaticians to script analysis tools in R, Java, SOAP, REST/JSON and RDF, a tab-delimited file format to ease upload and exchange of data, and detailed technical documentation. Existing databases can be quickly enhanced with MOLGENIS generated interfaces using the 'ExtractModel' procedure. The MOLGENIS toolkit provides bioinformaticians with a simple model to quickly generate flexible web platforms for all possible genomic, molecular and phenotypic experiments with a richness of interfaces not provided by other tools. All the software and manuals are available free as LGPLv3 open source at http://www.molgenis.org.

Molecular modeling study of the differential ligand-receptor interaction at the μ, δ and κ opioid receptors

NASA Astrophysics Data System (ADS)

Filizola, Marta; Carteni-Farina, Maria; Perez, Juan J.

1999-07-01

3D models of the opioid receptors μ, δ and κ were constructed using BUNDLE, an in-house program to build de novo models of G-protein coupled receptors at the atomic level. Once the three opioid receptors were constructed and before any energy refinement, models were assessed for their compatibility with the results available from point-site mutations carried out on these receptors. In a subsequent step, three selective antagonists to each of three receptors (naltrindole, naltrexone and nor-binaltorphamine) were docked onto each of the three receptors and subsequently energy minimized. The nine resulting complexes were checked for their ability to explain known results of structure-activity studies. Once the models were validated, analysis of the distances between different residues of the receptors and the ligands were computed. This analysis permitted us to identify key residues tentatively involved in direct interaction with the ligand.

Early patterning in a chondrichthyan model, the small spotted dogfish: towards the gnathostome ancestral state

PubMed Central

Godard, B G; Mazan, S

2013-01-01

In the past few years, the small spotted dogfish has become the primary model for analyses of early development in chondrichthyans. Its phylogenetic position makes it an ideal outgroup to reconstruct the ancestral gnathostome state by comparisons with established vertebrate model organisms. It is also a suitable model to address the molecular bases of lineage-specific diversifications such as the rise of extraembryonic tissues, as it is endowed with a distinct extraembryonic yolk sac and yolk duct ensuring exchanges between the embryo and a large undivided vitelline mass. Experimental or functional approaches such as cell marking or in ovo pharmacological treatments are emerging in this species, but recent analyses of early development in this species have primarily concentrated on molecular descriptions. These data show the dogfish embryo exhibits early polarities reflecting the dorso-ventral axis of amphibians and teleosts at early blastula stages and an atypical anamniote molecular pattern during gastrulation, independently of the presence of extraembryonic tissues. They also highlight unexpected relationships with amniotes, with a strikingly similar Nodal-dependent regional pattern in the extraembryonic endoderm. In this species, extraembryonic cell fates seem to be determined by differential cell behaviors, which lead to cell allocation in extraembryonic and embryonic tissues, rather than by cell regional identity. We suggest that this may exemplify an early evolutionary step in the rise of extraembryonic tissues, possibly related to quantitative differences in the signaling activities, which shape the early embryo. These results highlight the conservation across gnathostomes of a highly constrained core genetic program controlling early patterning. This conservation may be obscured in some lineages by taxa-specific diversifications such as specializations of extraembryonic nutritive tissues. PMID:22905913

A Simple and Accurate Method To Calculate Free Energy Profiles and Reaction Rates from Restrained Molecular Simulations of Diffusive Processes.

PubMed

Ovchinnikov, Victor; Nam, Kwangho; Karplus, Martin

2016-08-25

A method is developed to obtain simultaneously free energy profiles and diffusion constants from restrained molecular simulations in diffusive systems. The method is based on low-order expansions of the free energy and diffusivity as functions of the reaction coordinate. These expansions lead to simple analytical relationships between simulation statistics and model parameters. The method is tested on 1D and 2D model systems; its accuracy is found to be comparable to or better than that of the existing alternatives, which are briefly discussed. An important aspect of the method is that the free energy is constructed by integrating its derivatives, which can be computed without need for overlapping sampling windows. The implementation of the method in any molecular simulation program that supports external umbrella potentials (e.g., CHARMM) requires modification of only a few lines of code. As a demonstration of its applicability to realistic biomolecular systems, the method is applied to model the α-helix ↔ β-sheet transition in a 16-residue peptide in implicit solvent, with the reaction coordinate provided by the string method. Possible modifications of the method are briefly discussed; they include generalization to multidimensional reaction coordinates [in the spirit of the model of Ermak and McCammon (Ermak, D. L.; McCammon, J. A. J. Chem. Phys. 1978, 69, 1352-1360)], a higher-order expansion of the free energy surface, applicability in nonequilibrium systems, and a simple test for Markovianity. In view of the small overhead of the method relative to standard umbrella sampling, we suggest its routine application in the cases where umbrella potential simulations are appropriate.

DnaSAM: Software to perform neutrality testing for large datasets with complex null models.

PubMed

Eckert, Andrew J; Liechty, John D; Tearse, Brandon R; Pande, Barnaly; Neale, David B

2010-05-01

Patterns of DNA sequence polymorphisms can be used to understand the processes of demography and adaptation within natural populations. High-throughput generation of DNA sequence data has historically been the bottleneck with respect to data processing and experimental inference. Advances in marker technologies have largely solved this problem. Currently, the limiting step is computational, with most molecular population genetic software allowing a gene-by-gene analysis through a graphical user interface. An easy-to-use analysis program that allows both high-throughput processing of multiple sequence alignments along with the flexibility to simulate data under complex demographic scenarios is currently lacking. We introduce a new program, named DnaSAM, which allows high-throughput estimation of DNA sequence diversity and neutrality statistics from experimental data along with the ability to test those statistics via Monte Carlo coalescent simulations. These simulations are conducted using the ms program, which is able to incorporate several genetic parameters (e.g. recombination) and demographic scenarios (e.g. population bottlenecks). The output is a set of diversity and neutrality statistics with associated probability values under a user-specified null model that are stored in easy to manipulate text file. © 2009 Blackwell Publishing Ltd.

National Toxicology Program

MedlinePlus

... develops and applies tools of modern toxicology and molecular biology to identify substances in the environment that may ... application of new technologies for modern toxicology and molecular biology. A world leader in toxicology research, NTP has ...

Automatic search for maximum similarity between molecular electrostatic potential distributions

NASA Astrophysics Data System (ADS)

Manaut, Francesc; Sanz, Ferran; José, Jaume; Milesi, Massimo

1991-08-01

A new computer program has been developed to automatically obtain the relative position of two molecules in which the similarity between molecular electrostatic-potential distributions is greatest. These distributions are considered in a volume around the molecules, and the similarity is measured by the Spearman rank coefficient. The program has been tested using several pairs of molecules: water vs. water; phenylethylamine and phenylpropylamine vs. benzylamine; and methotrexate vs. dihydrofolic acid.

ParFit: A Python-Based Object-Oriented Program for Fitting Molecular Mechanics Parameters to ab Initio Data.

PubMed

Zahariev, Federico; De Silva, Nuwan; Gordon, Mark S; Windus, Theresa L; Dick-Perez, Marilu

2017-03-27

A newly created object-oriented program for automating the process of fitting molecular-mechanics parameters to ab initio data, termed ParFit, is presented. ParFit uses a hybrid of deterministic and stochastic genetic algorithms. ParFit can simultaneously handle several molecular-mechanics parameters in multiple molecules and can also apply symmetric and antisymmetric constraints on the optimized parameters. The simultaneous handling of several molecules enhances the transferability of the fitted parameters. ParFit is written in Python, uses a rich set of standard and nonstandard Python libraries, and can be run in parallel on multicore computer systems. As an example, a series of phosphine oxides, important for metal extraction chemistry, are parametrized using ParFit. ParFit is in an open source program available for free on GitHub ( https://github.com/fzahari/ParFit ).

The Distributed Diagonal Force Decomposition Method for Parallelizing Molecular Dynamics Simulations

PubMed Central

Boršnik, Urban; Miller, Benjamin T.; Brooks, Bernard R.; Janežič, Dušanka

2011-01-01

Parallelization is an effective way to reduce the computational time needed for molecular dynamics simulations. We describe a new parallelization method, the distributed-diagonal force decomposition method, with which we extend and improve the existing force decomposition methods. Our new method requires less data communication during molecular dynamics simulations than replicated data and current force decomposition methods, increasing the parallel efficiency. It also dynamically load-balances the processors' computational load throughout the simulation. The method is readily implemented in existing molecular dynamics codes and it has been incorporated into the CHARMM program, allowing its immediate use in conjunction with the many molecular dynamics simulation techniques that are already present in the program. We also present the design of the Force Decomposition Machine, a cluster of personal computers and networks that is tailored to running molecular dynamics simulations using the distributed diagonal force decomposition method. The design is expandable and provides various degrees of fault resilience. This approach is easily adaptable to computers with Graphics Processing Units because it is independent of the processor type being used. PMID:21793007

New synthetic thrombin inhibitors: molecular design and experimental verification.

PubMed

Sinauridze, Elena I; Romanov, Alexey N; Gribkova, Irina V; Kondakova, Olga A; Surov, Stepan S; Gorbatenko, Aleksander S; Butylin, Andrey A; Monakov, Mikhail Yu; Bogolyubov, Alexey A; Kuznetsov, Yuryi V; Sulimov, Vladimir B; Ataullakhanov, Fazoyl I

2011-01-01

The development of new anticoagulants is an important goal for the improvement of thromboses treatments. The design, synthesis and experimental testing of new safe and effective small molecule direct thrombin inhibitors for intravenous administration. Computer-aided molecular design of new thrombin inhibitors was performed using our original docking program SOL, which is based on the genetic algorithm of global energy minimization in the framework of a Merck Molecular Force Field. This program takes into account the effects of solvent. The designed molecules with the best scoring functions (calculated binding energies) were synthesized and their thrombin inhibitory activity evaluated experimentally in vitro using a chromogenic substrate in a buffer system and using a thrombin generation test in isolated plasma and in vivo using the newly developed model of hemodilution-induced hypercoagulation in rats. The acute toxicities of the most promising new thrombin inhibitors were evaluated in mice, and their stabilities in aqueous solutions were measured. New compounds that are both effective direct thrombin inhibitors (the best K(I) was <1 nM) and strong anticoagulants in plasma (an IC(50) in the thrombin generation assay of approximately 100 nM) were discovered. These compounds contain one of the following new residues as the basic fragment: isothiuronium, 4-aminopyridinium, or 2-aminothiazolinium. LD(50) values for the best new inhibitors ranged from 166.7 to >1111.1 mg/kg. A plasma-substituting solution supplemented with one of the new inhibitors prevented hypercoagulation in the rat model of hemodilution-induced hypercoagulation. Activities of the best new inhibitors in physiological saline (1 µM solutions) were stable after sterilization by autoclaving, and the inhibitors remained stable at long-term storage over more than 1.5 years at room temperature and at 4°C. The high efficacy, stability and low acute toxicity reveal that the inhibitors that were developed may be promising for potential medical applications.

Diffusion in liquid Germanium using ab initio molecular dynamics

NASA Astrophysics Data System (ADS)

Kulkarni, R. V.; Aulbur, W. G.; Stroud, D.

1996-03-01

We describe the results of calculations of the self-diffusion constant of liquid Ge over a range of temperatures. The calculations are carried out using an ab initio molecular dynamics scheme which combines an LDA model for the electronic structure with the Bachelet-Hamann-Schlüter norm-conserving pseudopotentials^1. The energies associated with electronic degrees of freedom are minimized using the Williams-Soler algorithm, and ionic moves are carried out using the Verlet algorithm. We use an energy cutoff of 10 Ry, which is sufficient to give results for the lattice constant and bulk modulus of crystalline Ge to within 1% and 12% of experiment. The program output includes not only the self-diffusion constant but also the structure factor, electronic density of states, and low-frequency electrical conductivity. We will compare our results with other ab initio and semi-empirical calculations, and discuss extension to impurity diffusion. ^1 We use the ab initio molecular dynamics code fhi94md, developed at 1cm the Fritz-Haber Institute, Berlin. ^2 Work supported by NASA, Grant NAG3-1437.

Developmental origins of cardiovascular disease: Impact of early life stress in humans and rodents.

PubMed

Murphy, M O; Cohn, D M; Loria, A S

2017-03-01

The Developmental Origins of Health and Disease (DOHaD) hypothesizes that environmental insults during childhood programs the individual to develop chronic disease in adulthood. Emerging epidemiological data strongly supports that early life stress (ELS) given by the exposure to adverse childhood experiences is regarded as an independent risk factor capable of predicting future risk of cardiovascular disease. Experimental animal models utilizing chronic behavioral stress during postnatal life, specifically maternal separation (MatSep) provides a suitable tool to elucidate molecular mechanisms by which ELS increases the risk to develop cardiovascular disease, including hypertension. The purpose of this review is to highlight current epidemiological studies linking ELS to the development of cardiovascular disease and to discuss the potential molecular mechanisms identified from animal studies. Overall, this review reveals the need for future investigations to further clarify the molecular mechanisms of ELS in order to develop more personalized therapeutics to mitigate the long-term consequences of chronic behavioral stress including cardiovascular and heart disease in adulthood. Copyright © 2016 Elsevier Ltd. All rights reserved.

Molecular Identification of the Schwannomatosis Locus

DTIC Science & Technology

2005-07-01

AD Award Number: DAMD17-03-1-0445 TITLE: Molecular Identification of the Schwannomatosis Locus PRINCIPAL INVESTIGATOR: Mia M. MacCollin, M.D...NUMBER Molecular Identification of the Schwannomatosis Locus 5b. GRANT NUMBER DAMD17-03-1-0445 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER...can be found on next page. 15. SUBJECT TERMS schwannomatosis , tumor suppressor gene, NF2, molecular genetics 16. SECURITY CLASSIFICATION OF: 17

Membrane Insertion Profiles of Peptides Probed by Molecular Dynamics Simulations

DTIC Science & Technology

2008-07-17

Membrane insertion profiles of peptides probed by molecular dynamics simulations In-Chul Yeh,* Mark A. Olson,# Michael S. Lee,*#§ and Anders...a methodology based on molecular dynamics simulation techniques to probe the insertion profiles of small peptides across the membrane interface. The...profiles of peptides probed by molecular dynamics simulations 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d

Minority undergraduate programs intended to increase participation in biomedical careers.

PubMed

MacLachlan, Anne J

2012-01-01

This article reviews a selection of undergraduate programs intended to increase successful minority participation in science, technology, engineering, and mathematics majors, potentially leading to biomedical careers. The object is to examine their structure, consider how well they address the issues of the target population, and assess the extent to which they have met/meet their goals. As a means of conducting this review, the first step is to examine the concepts used as the building blocks for program design. These concepts are found in a shared, yet often undefined, vocabulary used in most undergraduate programs for minority students. The hypothesis is that a shared vocabulary obscures a broad range of meaning and interpretation that has serious ramifications affecting student success. How these building blocks are understood and implemented strongly reflects the institution where the program is housed. The discussion further considers the nature of a number of programs created by the National Science Foundation and the National Institutes of Health specifically for underrepresented minority students and examines one program in detail, the University of California Berkeley's National Science Foundation Research Experience for Undergraduates Program in Molecular, Cell, and Evolutionary Biology. The characteristics of federally organized programs and the Research Experience for Undergraduates are contrasted with 2 very successful student-centered local programs based on a different conceptual model. © 2012 Mount Sinai School of Medicine.

Symbolic programming language in molecular multicenter integral problem

NASA Astrophysics Data System (ADS)

Safouhi, Hassan; Bouferguene, Ahmed

It is well known that in any ab initio molecular orbital (MO) calculation, the major task involves the computation of molecular integrals, among which the computation of three-center nuclear attraction and Coulomb integrals is the most frequently encountered. As the molecular system becomes larger, computation of these integrals becomes one of the most laborious and time-consuming steps in molecular systems calculation. Improvement of the computational methods of molecular integrals would be indispensable to further development in computational studies of large molecular systems. To develop fast and accurate algorithms for the numerical evaluation of these integrals over B functions, we used nonlinear transformations for improving convergence of highly oscillatory integrals. These methods form the basis of new methods for solving various problems that were unsolvable otherwise and have many applications as well. To apply these nonlinear transformations, the integrands should satisfy linear differential equations with coefficients having asymptotic power series in the sense of Poincaré, which in their turn should satisfy some limit conditions. These differential equations are very difficult to obtain explicitly. In the case of molecular integrals, we used a symbolic programming language (MAPLE) to demonstrate that all the conditions required to apply these nonlinear transformation methods are satisfied. Differential equations are obtained explicitly, allowing us to demonstrate that the limit conditions are also satisfied.

GeneLab for High Schools: Data Mining for the Next Generation

NASA Technical Reports Server (NTRS)

Blaber, Elizabeth A.; Ly, Diana; Sato, Kevin Y.; Taylor, Elizabeth

2016-01-01

Modern biological sciences have become increasingly based on molecular biology and high-throughput molecular techniques, such as genomics, transcriptomics, and proteomics. NASA Scientists and the NASA Space Biology Program have aimed to examine the fundamental building blocks of life (RNA, DNA and protein) in order to understand the response of living organisms to space and aid in fundamental research discoveries on Earth. In an effort to enable NASA funded science to be available to everyone, NASA has collected the data from omics studies and curated them in a data system called GeneLab. Whilst most college-level interns, academics and other scientists have had some interaction with omics data sets and analysis tools, high school students often have not. Therefore, the Space Biology Program is implementing a new Summer Program for high-school students that aims to inspire the next generation of scientists to learn about and get involved in space research using GeneLabs Data System. The program consists of three main components core learning modules, focused on developing students knowledge on the Space Biology Program and Space Biology research, Genelab and the data system, and previous research conducted on model organisms in space; networking and team work, enabling students to interact with guest lecturers from local universities and their fellow peers, and also enabling them to visit local universities and genomics centers around the Bay area; and finally an independent learning project, whereby students will be required to form small groups, analyze a dataset on the Genelab platform, generate a hypothesis and develop a research plan to test their hypothesis. This program will not only help inspire high-school students to become involved in space-based research but will also help them develop key critical thinking and bioinformatics skills required for most college degrees and furthermore, will enable them to establish networks with their peers and connections with university Professors that may help them achieve their educational goals.

Pedagogical view of model metabolic cycles.

PubMed

García-Herrero, Victor; Sillero, Antonio

2015-01-01

The main purpose of this study was to present a simplified view of model metabolic cycles. Although the models have been elaborated with the Mathematica Program, and using a system of differential equations, the main conclusions were presented in a rather intuitive way, easily understandable by students of general courses of Biochemistry, and without any need of mathematical support. A change in any kinetic constant (Km or Vmax) of only one enzyme affected the metabolic profile of all the substrates of the cycle. In addition, it is shown how an increase in the Km or a decrease in the Vmax values of any particular enzyme promoted an increase of its substrate; the contrary occurred decreasing the Km or increasing the Vmax values. © 2015 The International Union of Biochemistry and Molecular Biology.

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

PubMed

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.

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

PubMed

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.

Population Structure, Genetic Diversity and Molecular Marker-Trait Association Analysis for High Temperature Stress Tolerance in Rice

PubMed Central

Barik, Saumya Ranjan; Sahoo, Ambika; Mohapatra, Sudipti; Nayak, Deepak Kumar; Mahender, Anumalla; Meher, Jitandriya; Anandan, Annamalai

2016-01-01

Rice exhibits enormous genetic diversity, population structure and molecular marker-traits associated with abiotic stress tolerance to high temperature stress. A set of breeding lines and landraces representing 240 germplasm lines were studied. Based on spikelet fertility percent under high temperature, tolerant genotypes were broadly classified into four classes. Genetic diversity indicated a moderate level of genetic base of the population for the trait studied. Wright’s F statistic estimates showed a deviation of Hardy-Weinberg expectation in the population. The analysis of molecular variance revealed 25 percent variation between population, 61 percent among individuals and 14 percent within individuals in the set. The STRUCTURE analysis categorized the entire population into three sub-populations and suggested that most of the landraces in each sub-population had a common primary ancestor with few admix individuals. The composition of materials in the panel showed the presence of many QTLs representing the entire genome for the expression of tolerance. The strongly associated marker RM547 tagged with spikelet fertility under stress and the markers like RM228, RM205, RM247, RM242, INDEL3 and RM314 indirectly controlling the high temperature stress tolerance were detected through both mixed linear model and general linear model TASSEL analysis. These markers can be deployed as a resource for marker-assisted breeding program of high temperature stress tolerance. PMID:27494320

Population Structure, Genetic Diversity and Molecular Marker-Trait Association Analysis for High Temperature Stress Tolerance in Rice.

PubMed

Pradhan, Sharat Kumar; Barik, Saumya Ranjan; Sahoo, Ambika; Mohapatra, Sudipti; Nayak, Deepak Kumar; Mahender, Anumalla; Meher, Jitandriya; Anandan, Annamalai; Pandit, Elssa

2016-01-01

Rice exhibits enormous genetic diversity, population structure and molecular marker-traits associated with abiotic stress tolerance to high temperature stress. A set of breeding lines and landraces representing 240 germplasm lines were studied. Based on spikelet fertility percent under high temperature, tolerant genotypes were broadly classified into four classes. Genetic diversity indicated a moderate level of genetic base of the population for the trait studied. Wright's F statistic estimates showed a deviation of Hardy-Weinberg expectation in the population. The analysis of molecular variance revealed 25 percent variation between population, 61 percent among individuals and 14 percent within individuals in the set. The STRUCTURE analysis categorized the entire population into three sub-populations and suggested that most of the landraces in each sub-population had a common primary ancestor with few admix individuals. The composition of materials in the panel showed the presence of many QTLs representing the entire genome for the expression of tolerance. The strongly associated marker RM547 tagged with spikelet fertility under stress and the markers like RM228, RM205, RM247, RM242, INDEL3 and RM314 indirectly controlling the high temperature stress tolerance were detected through both mixed linear model and general linear model TASSEL analysis. These markers can be deployed as a resource for marker-assisted breeding program of high temperature stress tolerance.

Molecular Genetics Information System (MOLGENIS): alternatives in developing local experimental genomics databases.

PubMed

Swertz, Morris A; De Brock, E O; Van Hijum, Sacha A F T; De Jong, Anne; Buist, Girbe; Baerends, Richard J S; Kok, Jan; Kuipers, Oscar P; Jansen, Ritsert C

2004-09-01

Genomic research laboratories need adequate infrastructure to support management of their data production and research workflow. But what makes infrastructure adequate? A lack of appropriate criteria makes any decision on buying or developing a system difficult. Here, we report on the decision process for the case of a molecular genetics group establishing a microarray laboratory. Five typical requirements for experimental genomics database systems were identified: (i) evolution ability to keep up with the fast developing genomics field; (ii) a suitable data model to deal with local diversity; (iii) suitable storage of data files in the system; (iv) easy exchange with other software; and (v) low maintenance costs. The computer scientists and the researchers of the local microarray laboratory considered alternative solutions for these five requirements and chose the following options: (i) use of automatic code generation; (ii) a customized data model based on standards; (iii) storage of datasets as black boxes instead of decomposing them in database tables; (iv) loosely linking to other programs for improved flexibility; and (v) a low-maintenance web-based user interface. Our team evaluated existing microarray databases and then decided to build a new system, Molecular Genetics Information System (MOLGENIS), implemented using code generation in a period of three months. This case can provide valuable insights and lessons to both software developers and a user community embarking on large-scale genomic projects. http://www.molgenis.nl

g_contacts: Fast contact search in bio-molecular ensemble data

NASA Astrophysics Data System (ADS)

Blau, Christian; Grubmuller, Helmut

2013-12-01

Short-range interatomic interactions govern many bio-molecular processes. Therefore, identifying close interaction partners in ensemble data is an essential task in structural biology and computational biophysics. A contact search can be cast as a typical range search problem for which efficient algorithms have been developed. However, none of those has yet been adapted to the context of macromolecular ensembles, particularly in a molecular dynamics (MD) framework. Here a set-decomposition algorithm is implemented which detects all contacting atoms or residues in maximum O(Nlog(N)) run-time, in contrast to the O(N2) complexity of a brute-force approach. Catalogue identifier: AEQA_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEQA_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.: 8945 No. of bytes in distributed program, including test data, etc.: 981604 Distribution format: tar.gz Programming language: C99. Computer: PC. Operating system: Linux. RAM: ≈Size of input frame Classification: 3, 4.14. External routines: Gromacs 4.6[1] Nature of problem: Finding atoms or residues that are closer to one another than a given cut-off. Solution method: Excluding distant atoms from distance calculations by decomposing the given set of atoms into disjoint subsets. Running time:≤O(Nlog(N)) References: [1] S. Pronk, S. Pall, R. Schulz, P. Larsson, P. Bjelkmar, R. Apostolov, M. R. Shirts, J.C. Smith, P. M. Kasson, D. van der Spoel, B. Hess and Erik Lindahl, Gromacs 4.5: a high-throughput and highly parallel open source molecular simulation toolkit, Bioinformatics 29 (7) (2013).

A research project-based and self-determined teaching system of molecular biology techniques for undergraduates.

PubMed

Zhang, Shuping

2008-05-01

Molecular biology techniques play a very important role in understanding the biological activity. Students who major in biology should know not only how to perform experiments, but also the reasons for performing them. Having the concept of conducting research by integrating various techniques is especially important. This paper introduces a research project-based and self-determined teaching system of molecular biology techniques for undergraduates. Its aim is to create an environment mimicking real research programs and to help students build up confidence in their research skills. The students are allowed to explore a set of commonly used molecular biology techniques to solve some fundamental problems about genes on their own. They find a gene of interest, write a mini-proposal, and give an oral presentation. This course provides students a foundation before entering the research laboratory and allows them to adapt easily to real research programs. Copyright © 2008 International Union of Biochemistry and Molecular Biology, Inc.

Keeping up with the times: revising the dermatology residency curriculum in the era of molecular diagnostics and personalized medicine.

PubMed

LaChance, Avery; Murphy, Michael J

2014-11-01

The clinical use of molecular diagnostics, genomics, and personalized medicine is increasing and improving rapidly over time. However, medical education incorporating the practical application of these techniques is lagging behind. Although instruction in these areas should be expanded upon and improved at all levels of training, residency provides a concentrated period of time in which to hone in on skills that are practically applicable to a trainee's specialty of choice. Although residencies in some fields, such as pathology, have begun to incorporate practical molecular diagnostics training, this area remains a relative gap in dermatology residency programs. Herein, we advocate for the incorporation of training in molecular diagnostics and personalized medicine into dermatology residency programs and propose a basic curriculum template for how to begin approaching these topics. By incorporating molecular diagnostics into dermatology residency training, dermatologists have the opportunity to lead the way and actively shape the specialty's transition into the era of personalized medicine. © 2014 The International Society of Dermatology.

A consistent transported PDF model for treating differential molecular diffusion

NASA Astrophysics Data System (ADS)

Wang, Haifeng; Zhang, Pei

2016-11-01

Differential molecular diffusion is a fundamentally significant phenomenon in all multi-component turbulent reacting or non-reacting flows caused by the different rates of molecular diffusion of energy and species concentrations. In the transported probability density function (PDF) method, the differential molecular diffusion can be treated by using a mean drift model developed by McDermott and Pope. This model correctly accounts for the differential molecular diffusion in the scalar mean transport and yields a correct DNS limit of the scalar variance production. The model, however, misses the molecular diffusion term in the scalar variance transport equation, which yields an inconsistent prediction of the scalar variance in the transported PDF method. In this work, a new model is introduced to remedy this problem that can yield a consistent scalar variance prediction. The model formulation along with its numerical implementation is discussed, and the model validation is conducted in a turbulent mixing layer problem.

HOBYS and W43-HERO: Two more steps toward a Galaxy-wide understanding of high-mass star formation

NASA Astrophysics Data System (ADS)

Motte, Frédérique; Bontemps, Sylvain; Tigé, Jérémy

The Herschel/HOBYS key program allows to statistically study the formation of 10-20 M ⊙ stars. The IRAM/W43-HERO large program is itself dedicated to the much more extreme W43 molecular complex, which forms stars up to 50 M ⊙. Both reveal high-density cloud filaments of several pc3, which are forming clusters of OB-type stars. Given their activity, these so-called mini-starburst cloud ridges could be seen as ``miniature and instant models'' of starburst galaxies. Both surveys also strongly suggest that high-mass prestellar cores do not exist, in agreement with the dynamical formation of cloud ridges. The HOBYS and W43 surveys are necessary steps towards Galaxy-wide studies of high-mass star formation.

IMGui-A Desktop GUI Application for Isolation with Migration Analyses.

PubMed

Knoblauch, Jared; Sethuraman, Arun; Hey, Jody

2017-02-01

The Isolation with Migration (IM) programs (e.g., IMa2) have been utilized extensively by evolutionary biologists for model-based inference of demographic parameters including effective population sizes, migration rates, and divergence times. Here, we describe a graphical user interface for the latest IM program. IMGui provides a comprehensive set of tools for performing demographic analyses, tracking progress of runs, and visualizing results. Developed using node. js and the Electron framework, IMGui is an application that runs on any desktop operating system, and is available for download at https://github.com/jaredgk/IMgui-electron-packages. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Single-Cell RNA-Seq Reveals Dynamic Early Embryonic-like Programs during Chemical Reprogramming.

PubMed

Zhao, Ting; Fu, Yao; Zhu, Jialiang; Liu, Yifang; Zhang, Qian; Yi, Zexuan; Chen, Shi; Jiao, Zhonggang; Xu, Xiaochan; Xu, Junquan; Duo, Shuguang; Bai, Yun; Tang, Chao; Li, Cheng; Deng, Hongkui

2018-06-12

Chemical reprogramming provides a powerful platform for exploring the molecular dynamics that lead to pluripotency. Although previous studies have uncovered an intermediate extraembryonic endoderm (XEN)-like state during this process, the molecular underpinnings of pluripotency acquisition remain largely undefined. Here, we profile 36,199 single-cell transcriptomes at multiple time points throughout a highly efficient chemical reprogramming system using RNA-sequencing and reconstruct their progression trajectories. Through identifying sequential molecular events, we reveal that the dynamic early embryonic-like programs are key aspects of successful reprogramming from XEN-like state to pluripotency, including the concomitant transcriptomic signatures of two-cell (2C) embryonic-like and early pluripotency programs and the epigenetic signature of notable genome-wide DNA demethylation. Moreover, via enhancing the 2C-like program by fine-tuning chemical treatment, the reprogramming process is remarkably accelerated. Collectively, our findings offer a high-resolution dissection of cell fate dynamics during chemical reprogramming and shed light on mechanistic insights into the nature of induced pluripotency. Copyright © 2018 Elsevier Inc. All rights reserved.

Radiative and convective heating during Venus entry.

NASA Technical Reports Server (NTRS)

Page, W. A.; Woodward, H. T.

1972-01-01

Determination of the stagnation region heating of probes entering the Venusian atmosphere. Both convective and radiative heat-transfer rates are predicted, and account is taken of the important effects of radiative transport in the vehicle shock layer. A nongray radiative transport model is utilized which parallels a four-band treatment previously developed for air (Page et al., 1969), but includes two additional bands to account for the important CO(4+) molecular band system. Some comparisons are made between results for Venus entry and results for earth entry obtained using a viscous earth entry program.

Solving coiled-coil protein structures

DOE PAGES

Dauter, Zbigniew

2015-02-26

With the availability of more than 100,000 entries stored in the Protein Data Bank (PDB) that can be used as search models, molecular replacement (MR) is currently the most popular method of solving crystal structures of macromolecules. Significant methodological efforts have been directed in recent years towards making this approach more powerful and practical. This resulted in the creation of several computer programs, highly automated and user friendly, that are able to successfully solve many structures even by researchers who, although interested in structures of biomolecules, are not very experienced in crystallography.

Epigenetic Mediation of Endocrine and Immune Response in an Animal Model of Gulf War Illness

DTIC Science & Technology

2016-10-01

Illness 5b. GRANT NUMBER W81XWH-14-1-0550 5c. PROGRAM ELEMENT NUMBER Patrick O. McGowan, PhD, Gordon Broderick , PhD, James O’Callaghan, PhD...Nova Southeastern) as part of IAME/CFS meeting, hosted by Nova, to meet with Drs. Broderick (Co-PI) Oct 27- 2016. Co-PI and PI arranged to meet with...project. Direct supervision of molecular biology studies related to epigenetics data. Funding Support: Name: Gordon Broderick , PhD Project Role: Co

New aspects relating to the behaviour of composites and adhesives in space

NASA Technical Reports Server (NTRS)

Carpenter, A.

1991-01-01

Some of the specialized testing procedures performed at the JPL Molecular Contamination Investigation Facility for the WideField Planetary Camera II (WFPC II) program for the screening of polymeric materials for outgassing properties are described. For WFPC II, a science performance goal of 1-percent photometric accuracy at 1470 A over an extended time (at least 30 days) has been established. Utilization of the newest technology using CCD detectors poses even more stringent requirements. Test results are presented, and data reduction and modeling techniques are discussed.

Applications of SHAPES screening in drug discovery.

PubMed

Lepre, Christopher A; Peng, Jeffrey; Fejzo, Jasna; Abdul-Manan, Norzehan; Pocas, Jennifer; Jacobs, Marc; Xie, Xiaoling; Moore, Jonathan M

2002-12-01

The SHAPES strategy combines nuclear magnetic resonance (NMR) screening of a library of small drug-like molecules with a variety of complementary methods, such as virtual screening, high throughput enzymatic assays, combinatorial chemistry, X-ray crystallography, and molecular modeling, in a directed search for new medicinal chemistry leads. In the past few years, the SHAPES strategy has found widespread utility in pharmaceutical research. To illustrate a variety of different implementations of the method, we will focus in this review on recent applications of the SHAPES strategy in several drug discovery programs at Vertex Pharmaceuticals.

On the Relationship between Molecular Hit Rates in High-Throughput Screening and Molecular Descriptors.

PubMed

Hansson, Mari; Pemberton, John; Engkvist, Ola; Feierberg, Isabella; Brive, Lars; Jarvis, Philip; Zander-Balderud, Linda; Chen, Hongming

2014-06-01

High-throughput screening (HTS) is widely used in the pharmaceutical industry to identify novel chemical starting points for drug discovery projects. The current study focuses on the relationship between molecular hit rate in recent in-house HTS and four common molecular descriptors: lipophilicity (ClogP), size (heavy atom count, HEV), fraction of sp(3)-hybridized carbons (Fsp3), and fraction of molecular framework (f(MF)). The molecular hit rate is defined as the fraction of times the molecule has been assigned as active in the HTS campaigns where it has been screened. Beta-binomial statistical models were built to model the molecular hit rate as a function of these descriptors. The advantage of the beta-binomial statistical models is that the correlation between the descriptors is taken into account. Higher degree polynomial terms of the descriptors were also added into the beta-binomial statistic model to improve the model quality. The relative influence of different molecular descriptors on molecular hit rate has been estimated, taking into account that the descriptors are correlated to each other through applying beta-binomial statistical modeling. The results show that ClogP has the largest influence on the molecular hit rate, followed by Fsp3 and HEV. f(MF) has only a minor influence besides its correlation with the other molecular descriptors. © 2013 Society for Laboratory Automation and Screening.

College Summer Programs for High School Students: Outreach, Recruitment, Enrichment.

ERIC Educational Resources Information Center

Nusbaum, Kenneth E.

1998-01-01

Describes an Auburn University (Alabama) summer program that brings high school students into the veterinary medicine and molecular biology programs, focusing on recruitment and selection of students, aspects of faculty participation, parent involvement, orientation, laboratory work, and student grouping and mentoring. Results of the program to…

Task 6 - Subtask 1: PNNL Visit by JAEA Researchers to Evaluate the Feasibility of the FLESCOT Code for the Future JAEA Use for the Fukushima Surface Water Environmental Assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Onishi, Yasuo

Four Japan Atomic Energy Agency (JAEA) researchers visited Pacific Northwest National Laboratory (PNNL) for seven working days and have evaluated the suitability and adaptability of FLESCOT to a JAEA’s supercomputer system to effectively simulate cesium behavior in dam reservoirs, river mouths, and coastal areas in Fukushima contaminated by the Fukushima Daiichi nuclear accident. PNNL showed the following to JAEA visitors during the seven-working day period: FLESCOT source code; User’s manual; FLESCOT description – Program structure – Algorism – Solver – Boundary condition handling – Data definition – Input and output methods – How to run. During the visit, JAEA hadmore » access to FLESCOT to run with an input data set to evaluate the capacity and feasibility of adapting it to a JAEA super computer with massive parallel processors. As a part of this evaluation, PNNL ran FLESCOT for sample cases of the contaminant migration simulation to further describe FLESCOT in action. JAEA and PNNL researchers also evaluated time spent for each subroutine of FLESCOT, and the JAEA researcher implemented some initial parallelization schemes to FLESCOT. Based on this code evaluation, JAEA and PNNL determined that FLESCOT is: applicable to Fukushima lakes/dam reservoirs, river mouth areas, and coastal water; and feasible to implement parallelization for the JAEA supercomputer. In addition, PNNL and JAEA researchers discussed molecular modeling approaches on cesium adsorption mechanisms to enhance the JAEA molecular modeling activities. PNNL and JAEA also discussed specific collaboration of molecular and computational modeling activities.« less

Chromosomal abnormalities and molecular landscape of metastasizing mucinous salivary adenocarcinoma

PubMed Central

Panaccione, Alex; Zhang, Yi; Mi, Yanfang; Mitani, Yoshitsugu; Yan, Guo; Prasad, Manju L.; McDonald, W. Hayes; El-Naggar, Adel K.; Yarbrough, Wendell G.; Ivanov, Sergey V.

2017-01-01

Background Mucinous adenocarcinoma of the salivary gland (MAC) is a lethal cancer with unknown molecular etiology and a high propensity to lymph node metastasis. Mostly due to its orphan status, MAC remains one of the least explored cancers that lacks cell lines and mouse models that could help translational and pre-clinical studies. Surgery with or without radiation remains the only treatment modality but poor overall survival (10-year, 44%) underscores the urgent need for mechanism-based therapies. Methods We developed the first patient-derived xenograft (PDX) model for pre-clinical MAC studies and a cell line that produces aggressively growing tumors after subcutaneous injection into nude mice. We performed cytogenetic, exome, and proteomic profiling of MAC to identify driving mutations, therapeutic targets, and pathways involved in aggressive cancers based on TCGA database mining and GEO analysis. Results: We identified in MAC KRAS (G13D) and TP53 (R213X) mutations that have been previously reported as drivers in a variety of highly aggressive cancers. Somatic mutations were also found in KDM6A, KMT2D, and other genes frequently mutated in colorectal and other cancers: FAT1, NBEA, RELN, RLP1B, and ZFHX3. Proteomic analysis of MAC implied epigenetic up-regulation of a genetic program involved in proliferation and cancer stem cell maintenance. Conclusion Genomic and proteomic analyses provided the first insight into potential molecular drivers of MAC metastases pointing at common mechanisms of CSC propagation in aggressive cancers. The in vitro/in vivo models that we created should aid in the development and validation of new treatment strategies against MAC. PMID:28249646

Computational identification of potential multi-drug combinations for reduction of microglial inflammation in Alzheimer disease

PubMed Central

Anastasio, Thomas J.

2015-01-01

Like other neurodegenerative diseases, Alzheimer Disease (AD) has a prominent inflammatory component mediated by brain microglia. Reducing microglial inflammation could potentially halt or at least slow the neurodegenerative process. A major challenge in the development of treatments targeting brain inflammation is the sheer complexity of the molecular mechanisms that determine whether microglia become inflammatory or take on a more neuroprotective phenotype. The process is highly multifactorial, raising the possibility that a multi-target/multi-drug strategy could be more effective than conventional monotherapy. This study takes a computational approach in finding combinations of approved drugs that are potentially more effective than single drugs in reducing microglial inflammation in AD. This novel approach exploits the distinct advantages of two different computer programming languages, one imperative and the other declarative. Existing programs written in both languages implement the same model of microglial behavior, and the input/output relationships of both programs agree with each other and with data on microglia over an extensive test battery. Here the imperative program is used efficiently to screen the model for the most efficacious combinations of 10 drugs, while the declarative program is used to analyze in detail the mechanisms of action of the most efficacious combinations. Of the 1024 possible drug combinations, the simulated screen identifies only 7 that are able to move simulated microglia at least 50% of the way from a neurotoxic to a neuroprotective phenotype. Subsequent analysis shows that of the 7 most efficacious combinations, 2 stand out as superior both in strength and reliability. The model offers many experimentally testable and therapeutically relevant predictions concerning effective drug combinations and their mechanisms of action. PMID:26097457

Rosetta Structure Prediction as a Tool for Solving Difficult Molecular Replacement Problems.

PubMed

DiMaio, Frank

2017-01-01

Molecular replacement (MR), a method for solving the crystallographic phase problem using phases derived from a model of the target structure, has proven extremely valuable, accounting for the vast majority of structures solved by X-ray crystallography. However, when the resolution of data is low, or the starting model is very dissimilar to the target protein, solving structures via molecular replacement may be very challenging. In recent years, protein structure prediction methodology has emerged as a powerful tool in model building and model refinement for difficult molecular replacement problems. This chapter describes some of the tools available in Rosetta for model building and model refinement specifically geared toward difficult molecular replacement cases.

Multiscale geometric modeling of macromolecules II: Lagrangian representation

PubMed Central

Feng, Xin; Xia, Kelin; Chen, Zhan; Tong, Yiying; Wei, Guo-Wei

2013-01-01

Geometric modeling of biomolecules plays an essential role in the conceptualization of biolmolecular structure, function, dynamics and transport. Qualitatively, geometric modeling offers a basis for molecular visualization, which is crucial for the understanding of molecular structure and interactions. Quantitatively, geometric modeling bridges the gap between molecular information, such as that from X-ray, NMR and cryo-EM, and theoretical/mathematical models, such as molecular dynamics, the Poisson-Boltzmann equation and the Nernst-Planck equation. In this work, we present a family of variational multiscale geometric models for macromolecular systems. Our models are able to combine multiresolution geometric modeling with multiscale electrostatic modeling in a unified variational framework. We discuss a suite of techniques for molecular surface generation, molecular surface meshing, molecular volumetric meshing, and the estimation of Hadwiger’s functionals. Emphasis is given to the multiresolution representations of biomolecules and the associated multiscale electrostatic analyses as well as multiresolution curvature characterizations. The resulting fine resolution representations of a biomolecular system enable the detailed analysis of solvent-solute interaction, and ion channel dynamics, while our coarse resolution representations highlight the compatibility of protein-ligand bindings and possibility of protein-protein interactions. PMID:23813599

Targeted Cancer Therapy Systems: An In Silico Study of Radiohalogenated Ligands in the Estrogen Receptor and the Synthesis of a Molecular Toolkit for the Fabrication of Customizable Nanoparticles

NASA Astrophysics Data System (ADS)

Barnsley, Kelton K.

Chemotherapy is often limited by off-target toxicity and the development of multi-drug resistance in response to treatment. Strategies which reduce off-target toxicity by passively or actively targeting cancer cells may improve the efficacy of chemotherapy. Herein, two projects relating to targeted therapy are described. In the first project, the binding modes of 1,1-bis(4-hydroxyphenyl)-2-phenylethylenes (THPEs), a class of synthetic estrogens previously developed by our group, in the human estrogen receptor alpha-ligand binding domain were studied using molecular modeling programs YASARA AutoDock and Schrodinger Glide. The results were internally consistent and supported the observation that a bromine or iodine atom at the 2-position of the THPEs contributes positively to their binding in the estrogen receptor. In the second project, a "molecular toolkit" approach to the synthesis of multifunctional nanoparticles was envisioned. Our hypothesis was that the physical and chemical properties of the final product could be defined by controlling the types and relative amounts of prefunctionalized polymer units (PPUs) as well as the emulsification conditions. The design and syntheses of heterobifunctional linkers and other components for a preliminary molecular toolkit are reported, and the literature on select heterobifunctional aliphatic linkers is examined.

Computational approaches in the design of synthetic receptors - A review.

PubMed

Cowen, Todd; Karim, Kal; Piletsky, Sergey

2016-09-14

The rational design of molecularly imprinted polymers (MIPs) has been a major contributor to their reputation as "plastic antibodies" - high affinity robust synthetic receptors which can be optimally designed, and produced for a much reduced cost than their biological equivalents. Computational design has become a routine procedure in the production of MIPs, and has led to major advances in functional monomer screening, selection of cross-linker and solvent, optimisation of monomer(s)-template ratio and selectivity analysis. In this review the various computational methods will be discussed with reference to all the published relevant literature since the end of 2013, with each article described by the target molecule, the computational approach applied (whether molecular mechanics/molecular dynamics, semi-empirical quantum mechanics, ab initio quantum mechanics (Hartree-Fock, Møller-Plesset, etc.) or DFT) and the purpose for which they were used. Detailed analysis is given to novel techniques including analysis of polymer binding sites, the use of novel screening programs and simulations of MIP polymerisation reaction. The further advances in molecular modelling and computational design of synthetic receptors in particular will have serious impact on the future of nanotechnology and biotechnology, permitting the further translation of MIPs into the realms of analytics and medical technology. Copyright © 2016 Elsevier B.V. All rights reserved.