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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 937 records · Page 52
All sourcesNASA NTRSDOE OSTI
DOE OSTI2014

Ligand placement based on prior structures: the guided ligand-replacement method

A new module, Guided Ligand Replacement (GLR), has been developed in Phenix to increase the ease and success rate of ligand placement when prior protein-ligand complexes are available. The process of iterative structure-based drug design involves the X-ray crystal structure determination of upwards of 100 ligands with the same general scaffold (i.e. chemotype) complexed with very similar, if not identical, protein targets. In conjunction with insights from computational models and assays, this collection of crystal structures is analyzed to improve potency, to achieve better selectivity and to reduce liabilities such as absorption, distribution, metabolism, excretion and toxicology. Current methods for modeling ligands into electron-density maps typically do not utilize information on how similar ligands bound in related structures. Even if the electron density is of sufficient quality and resolution to allow de novo placement, the process can take considerable time as the size, complexity and torsional degrees of freedom of the ligands increase. A new module, Guided Ligand Replacement (GLR), was developed in Phenix to increase the ease and success rate of ligand placement when prior protein–ligand complexes are available. At the heart of GLR is an algorithm based on graph theory that associates atoms in the target ligand with analogous atoms in the reference ligand. Based on this correspondence, a set of coordinates is generated for the target ligand. GLR is especially useful in two situations: (i) modeling a series of large, flexible, complicated or macrocyclic ligands in successive structures and (ii) modeling ligands as part of a refinement pipeline that can automatically select a reference structure. Even in those cases for which no reference structure is available, if there are multiple copies of the bound ligand per asymmetric unit GLR offers an efficient way to complete the model after the first ligand has been placed. In all of these applications, GLR leverages prior knowledge from earlier structures to facilitate ligand placement in the current structure.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2015

Risk Informed Design and Analysis Criteria for Nuclear Structures

Target performance can be achieved by defining design basis ground motion from results of a probabilistic seismic hazards assessment, and introducing known levels of conservatism in the design above the DBE. ASCE 4, 43, DOE-STD-1020 defined the DBE at 4x10-4 and introduce only slight levels of conservatism in response. ASCE 4, 43, DOE-STD-1020 assume code capacities shoot for about 98% NEP. There is a need to have a uniform target (98% NEP) for code developers (ACI, AISC, etc.) to aim for. In considering strengthening options, one must also consider cost/risk reduction achieved.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗
DOE OSTI2019

The simulation on absorption properties of metamaterial/GaAs/electrode layer hybrid structure based Terahertz photoconductive detector

Terahertz (THz) photodetectors have attracted great attention from scientists worldwide for their application in security checking, biomedical treatment and astronomical observation of remote stars and distant galaxies. As a typical THz detector, extrinsic GaAs based photoconductive detector is facing critical technical bottlenecks in the epitaxial growth of sufficiently thick and high-quality GaAs absorption layer. In this work, a novel THz photoconductive detector based on metamaterial/GaAs/electrode layer hybrid structure was designed and simulated. By setting the periodic split ring resonator (SRR) structure as 88 μm pitch with 8 μm width, the absorption peaks exist at the wavelength of about 142 and 367 μm, which originate from the resonant cavity and the SRR dipole resonance effect, and the novel device shows a significant enhancement compared with the conventional GaAs photoconductive detector. Thus, the necessary thickness of GaAs absorption-layer is largely reduced, and the resonant absorption peak can be modulated by changing the thickness of absorption layer. This work provides a novel device structure which can solve the critical epitaxial growth bottleneck of GaAs photoconductive detector and used for the astronomical observation, security check, etc.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2015

Improved DC Gun and Insulator Assembly

Many user facilities such as synchrotron radiation light sources and free electron lasers rely on DC high voltage photoguns with internal field gradients as high as 10 to 15 MV/m. These high gradients often lead to field emission which poses serious problems for the photocathode used to generate the electron beam and the ceramic insulators used to bias the photocathode at high voltage. Ceramic insulators are difficult to manufacture, require long commissioning times, and have poor reliability, in part because energetic electrons bury themselves in the ceramic causing a buildup of charge and eventual puncture, and also because large diameter ceramics are difficult to braze reliably. The lifetimes of photo cathodes inside high current DC guns exhibiting field emission are limited to less than a hundred hours. Reducing the surface gradients on the metals reduces the field emission, which serves to maintain the required ultrahigh vacuum condition. A novel gun design with gradients around 5 MV/m and operating at 350 kV, a major improvement over existing designs, was proposed that allows for the in-situ replacement of photo cathodes in axially symmetric designs using inverted ceramics. In this project, the existing JLAB CEBAF asymmetric gun design with an inverted ceramic support was modeled and the beam dynamics characterized. An improved structure was designed that reduces the surface gradients and improves the beam optics. To minimize the surface gradients, a number of electrostatic gun designs were studied to determine the optimum configuration of the critical electrodes within the gun structure. Coating experiments were carried out to create a charge dissipative coating for cylindrical ceramics. The phase II proposal, which was not granted, included the design and fabrication of an axially symmetric DC Gun with an inverted ceramic that would operate with less than 5 MV/m at 350 kV and would be designed with an in-situ replaceable photo-cathode.

43 PARTICLE ACCELERATORS↗
DOE OSTI2017

Potent peptidic fusion inhibitors of influenza virus

Influenza therapeutics with new targets and mechanisms of action are urgently needed to combat potential pandemics, emerging viruses, and constantly mutating strains in circulation. We report here on the design and structural characterization of potent peptidic inhibitors of influenza hemagglutinin. The peptide design was based on complementarity-determining region loops of human broadly neutralizing antibodies against the hemagglutinin (FI6v3 and CR9114). The optimized peptides exhibit nanomolar affinity and neutralization against influenza A group 1 viruses, including the 2009 H1N1 pandemic and avian H5N1 strains. The peptide inhibitors bind to the highly conserved stem epitope and block the low pH–induced conformational rearrangements associated with membrane fusion. These peptidic compounds and their advantageous biological properties should accelerate the development of new small molecule– and peptide-based therapeutics against influenza virus.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Design and analysis of photonic crystal micro-cavity based optical sensor platform

In this paper, the design of a two-dimensional photonic crystal micro-cavity based integrated-optic sensor platform is proposed. The behaviour of designed cavity is analyzed using two-dimensional Finite Difference Time Domain (FDTD) method. The structure is designed by deliberately inserting some defects in a photonic crystal waveguide structure. Proposed structure shows a quality factor (Q) of about 1e5 and the average sensitivity of 500nm/RIU in the wavelength range of 1450 – 1580 nm. Sensing technique is based on the detection of shift in upper-edge cut-off wavelength for a reference signal strength of –10 dB in accordance with the change in refractive index of analyte.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2014

Design of gem -Difluoro- bis -Tetrahydrofuran as P2 Ligand for HIV-1 Protease Inhibitors to Improve Brain Penetration: Synthesis, X-ray Studies, and Biological Evaluation

The structure–based design, synthesis, biological evaluation, and X–ray structural studies of fluorine–containing HIV–1 protease inhibitors are described. The synthesis of both enantiomers of the gem–difluoro–bis–THF ligands was carried out in a stereoselective manner using a Reformatskii–Claisen reaction as the key step. Optically active ligands were converted into protease inhibitors. Two of these inhibitors, (3R,3aS,6aS)–4,4–difluorohexahydrofuro[2,3–b]furan–3–yl(2S,3R)–3–hydroxy–4–((N–isobutyl–4–methoxyphenyl)sulfonamido)–1–phenylbutan–2–yl) carbamate (3) and (3R,3aS,6aS)–4,4–difluorohexahydrofuro[2,3–b]furan–3–yl(2S,3R)–3–hydroxy–4–((N–isobutyl–4–aminophenyl)sulfonamido)phenylbutan–2–yl) carbamate (4), exhibited HIV–1 protease inhibitory K i values in the picomolar range. Both 3 and 4 showed very potent antiviral activity, with respective EC 50 values of 0.8 and 3.1 nM against the laboratory strain HIV–1 LAI . The two inhibitors exhibited better lipophilicity profiles than darunavir, and also showed much improved blood–brain barrier permeability in an in vitro model. A high–resolution X–ray structure of inhibitor 4 in complex with HIV–1 protease was determined, revealing that the fluorinated ligand makes extensive interactions with the S2 subsite of HIV–1 protease, including hydrogen bonding interactions with the protease backbone atoms. Moreover, both fluorine atoms on the bis–THF ligand formed strong interactions with the flap Gly 48 carbonyl oxygen atom.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2012

Structure of a 16-nm Cage Designed by Using Protein Oligomers

Designing protein molecules that will assemble into various kinds of ordered materials represents an important challenge in nanotechnology. We report the crystal structure of a 12-subunit protein cage that self-assembles by design to form a tetrahedral structure roughly 16 nanometers in diameter. The strategy of fusing together oligomeric protein domains can be generalized to produce other kinds of cages or extended materials.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2012

Advanced, High Power, Next Scale, Wave Energy Conversion Device

The project conducted under DOE contract DE-EE0002649 is defined as the Advanced, High Power, Next Scale, Wave Energy Converter. The overall project is split into a seven-stage, gated development program. The work conducted under the DOE contract is OPT Stage Gate III work and a portion of Stage Gate IV work of the seven stage product development process. The project effort includes Full Concept Design & Prototype Assembly Testing building on our existing PowerBuoy technology to deliver a device with much increased power delivery. Scaling-up from 150kW to 500kW power generating capacity required changes in the PowerBuoy design that addressed cost reduction and mass manufacturing by implementing a Design for Manufacturing (DFM) approach. The design changes also focused on reducing PowerBuoy Installation, Operation and Maintenance (IO&M) costs which are essential to reducing the overall cost of energy. In this design, changes to the core PowerBuoy technology were implemented to increase capability and reduce both CAPEX and OPEX costs. OPT conceptually envisaged moving from a floating structure to a seabed structure. The design change from a floating structure to seabed structure would provide the implementation of stroke unlimited Power Take-Off (PTO) which has a potential to provide significant power delivery improvement and transform the wave energy industry if proven feasible.

16 TIDAL AND WAVE POWER↗
DOE OSTI2022

Bio-inspired non self-similar hierarchical elastic metamaterials

Hierarchy provides unique opportunities for the design of advanced materials with superior properties that arise from architecture, rather than from constitutive material response. Contrary to the quasi-static regime, where the potential of hierarchy has been largely explored, its role in vibration mitigation and wave manipulation remains elusive. So far, the majority of the studies concerning hierarchical elastic metamaterials have proposed a self-similar repetition of a specific unit cell at multiple scale levels, leading to the activation of the same bandgap mechanism at different frequencies. On the contrary, here, we show that by designing non self-similar hierarchical geometries allows us to create periodic structures supporting multiple, highly attenuative and broadband bandgaps involving (independently or simultaneously) different scattering mechanisms, namely, Bragg scattering, local resonance and/or inertial amplification, at different frequencies. The type of band gap mechanism is identified and discussed by examining the vibrational mode shapes and the imaginary component of the wavenumber in the dispersion diagram of the unit cell. Finally, we also experimentally confirm this by performing measurements in the lowest frequency regime on a 3D printed structure. Hierarchical design strategies may find application in vibration mitigation for civil, aerospace and mechanical engineering.

36 MATERIALS SCIENCE↗
DOE OSTI2025

Lattice Structured Lightweight Structural Materials

The development of lightweight structural materials is crucial for enhancing the performance and deployment feasibility of fission batteries. This study aims to produce lightweight structural materials whose strength-to-weight ratios exceed those of current widely used structural materials. To achieve this, advanced modeling and simulation tools were employed to design lattice structures with different lattice parameters and different lattice types. A process was successfully developed for transforming lattice-structured models into Multiphysics Object Oriented Simulation Environment (MOOSE) inputs. Finite element modeling (FEM) was used to simulate the uniaxial tensile testing of the lattice-structured parts to investigate the stress distribution at a given displacement. The modeling results showed that the lattice-structured sample displayed a lower Young’s modulus in comparison to the solid material; the increase in solid shell thickness and blend radius enhances the mechanical performance; and the effect of unit cell size on macro scale stress is minimal. Tensile testing was conducted on the solid and lattice-structured materials fabricated by laser powder bed fusion (LPBF) additive manufacturing. The experimental results agreed well with the model prediction. The approach of using modeling as a guiding tool for preliminary material design can significantly save time and cost for new material development.

lightweight material↗
DOE OSTI2019

Simplified 2D Skin Lattice Models for Multi-Axial Camber Morphing Wing Aircraft

Conventional fixed wing aircraft require a selection of certain thickness of skin material that guarantees structural strength for aerodynamic loadings in various flight modes. However, skin structures of morphing wings are expected to be flexible as well as stiff to structural and coupled aerodynamic loadings from geometry change. Many works in the design of skin structures for morphing wings consider only geometric compliance. Among many morphing classifications, we consider camber rate change as airfoil morphing that changes its rate of the airfoil that induces warping, twisting, and bending in multi-axial directions, which makes compliant skin design for morphing a challenging task. It is desired to design a 3D skin structure for a morphing wing; however, it is a computationally challenging task in the design stage to optimize the design parameters. Therefore, it is of interest to establish the structure design process in rapid approaches. As a first step, the main theme of this study is to numerically validate and suggest simplified 2D plate models that fully represents multi-axial 3D camber morphing. In addition to that, the authors show the usage of lattice structures for the 2D plate models’ skin that will lead to on-demand design of advanced structure through the modification of selected structure.

Alsaidi, Bashir↗
DOE OSTI2019

Development of Potent and Selective Pyrazolopyrimidine IRAK4 Inhibitors

In this work, a series of pyrazolopyrimidine inhibitors of IRAK4 were developed from a high-throughput screen (HTS). Modification of an HTS hit led to a series of bicyclic heterocycles with improved potency and kinase selectivity but lacking sufficient solubility to progress in vivo. Structure-based drug design, informed by cocrystal structures with the protein and small-molecule crystal structures, yielded a series of dihydrobenzofurans. This semisaturated bicycle provided superior druglike properties while maintaining excellent potency and selectivity. Improved physicochemical properties allowed for progression into in vivo experiments, where lead molecules exhibited low clearance and showed target-based inhibition of IRAK4 signaling in an inflammation-mediated PK/PD mouse model.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2018

Dopamine D3 receptor antagonist reveals a cryptic pocket in aminergic GPCRs

The recent increase in the number of X-ray crystal structures of G-protein coupled receptors (GPCRs) has been enabling for structure-based drug design (SBDD) efforts. These structures have revealed that GPCRs are highly dynamic macromolecules whose function is dependent on their intrinsic flexibility. Unfortunately, the use of static structures to understand ligand binding can potentially be misleading, especially in systems with an inherently high degree of conformational flexibility. Here, we show that docking a set of dopamine D3 receptor compounds into the existing eticlopride-bound dopamine D3 receptor (D3R) X-ray crystal structure resulted in poses that were not consistent with results obtained from site-directed mutagenesis experiments. We overcame the limitations of static docking by using large-scale high-throughput molecular dynamics (MD) simulations and Markov state models (MSMs) to determine an alternative pose consistent with the mutation data. The new pose maintains critical interactions observed in the D3R/eticlopride X-ray crystal structure and suggests that a cryptic pocket forms due to the shift of a highly conserved residue, F 6.52 . Our study highlights the importance of GPCR dynamics to understand ligand binding and provides new opportunities for drug discovery.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

Equivalent circuit for VO{sub 2} phase change material film in reconfigurable frequency selective surfaces

We developed equivalent circuits of phase change materials based on vanadium dioxide (VO{sub 2}) thin films. These circuits are used to model VO{sub 2} thin films for reconfigurable frequency selective surfaces (FSSs). This is important as it provides a way for designing complex structures. A reconfigurable FSS filter using VO{sub 2} ON/OFF switches is designed demonstrating −60 dB isolation between the states. This filter is used to provide the transmission and reflection responses of the FSS in the frequency range of 0.1–0.6 THz. The comparison between equivalent circuit and full-wave simulation shows excellent agreement.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2023

Identification of small-molecule protein–protein interaction inhibitors for NKG2D

NKG2D (natural-killer group 2, member D) is a homodimeric transmembrane receptor that plays an important role in NK, γδ + , and CD8 + T cell-mediated immune responses to environmental stressors such as viral or bacterial infections and oxidative stress. However, aberrant NKG2D signaling has also been associated with chronic inflammatory and autoimmune diseases, and as such NKG2D is thought to be an attractive target for immune intervention. Here, in this study, we describe a comprehensive small-molecule hit identification strategy and two distinct series of protein–protein interaction inhibitors of NKG2D. Although the hits are chemically distinct, they share a unique allosteric mechanism of disrupting ligand binding by accessing a cryptic pocket and causing the two monomers of the NKG2D dimer to open apart and twist relative to one another. Leveraging a suite of biochemical and cell-based assays coupled with structure-based drug design, we established tractable structure–activity relationships with one of the chemical series and successfully improved both the potency and physicochemical properties. Together, we demonstrate that it is possible, albeit challenging, to disrupt the interaction between NKG2D and multiple protein ligands with a single molecule through allosteric modulation of the NKG2D receptor dimer/ligand interface.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Volumetric Segmentation via Neural Networks Improves Neutron Crystallography Data Analysis

Crystallography is the powerhouse technique for molecular structure determination, with applications in fields ranging from energy storage to drug design. Accurate structure determination, however, relies partly on determining the precise locations and integrated intensities of Bragg peaks in the resulting data. Here, we describe a method for Bragg peak integration that is accomplished using neural networks. The network is based on a U-Net and identifies peaks in three-dimensional reciprocal space through segmentation, allowing prediction of the full 3D peak shape from noisy data that is commonly difficult to process. The procedure for generating appropriate training sets is detailed. Trained networks achieve Dice coefficients of 0.82 and mean IoUs of 0.69. Carrying out integration over entire datasets, it is demonstrated that integrating neural network-predicted peaks results in improved intensity statistics. Furthermore, using a second dataset, the possibility of transfer learning between datasets is shown. Given the ubiquity and growing complexity of crystallography, we anticipate integration by machine learning to play an increasingly important role across the physical sciences. These early results demonstrate the applicability of deep learning techniques for integrating crystallography data and suggest a possible role in the next generation of crystallography experiments.

Sullivan, Brendan T.↗
DOE OSTI2024

Numerical Simulation of Irradiation Induced Swelling for STAR 4.1 Blanket

Here, this article presents the preliminary results of FEM implementation of irradiation-induced swelling, hardening, and creep effect using ANSYS user programmable features (UPFs) applied to material properties. The first liquid metal breeding blanket model for STAR 4.1 tokamak as a part of the virtual prototyping system is under development at Princeton Plasma Physics Laboratory (PPPL). Intense neutron irradiation produces significant changes in the physical and mechanical properties of Fe-(8%–9%)Cr-based reduced activation ferritic martensitic (RAFM) steels. An ANSYS model of the breeding blanket was built to involve these irradiation-induced material property changes with neutron fluence distribution mapped from the MCNP model. Simulation results show that significant structure deformation forms from nuclear swelling, stress, and plastic strain arising from DPA gradient through wall thickness. The material degradation effect is not negligible. This modeling feature can either assist in analyzing the structural behaviors with the influence of nuclear swelling or provide guidance to design the structure to withstand irradiation.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗