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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 595 records · Page 33
All sourcesNASA NTRSDOE OSTI
DOE OSTI2014

Resonant-frequency discharge in a multi-cell radio frequency cavity

We are reporting experimental results on a microwave discharge operating at resonant frequency in a multi-cell radio frequency (RF) accelerator cavity. Although the discharge operated at room temperature, the setup was constructed so that it could be used for plasma generation and processing in fully assembled active superconducting radio-frequency cryo-module. This discharge offers a mechanism for removal of a variety of contaminants, organic or oxide layers, and residual particulates from the interior surface of RF cavities through the interaction of plasma-generated radicals with the cavity walls. We describe resonant RF breakdown conditions and address the issues related to resonant detuning due to sustained multi-cell cavity plasma. We have determined breakdown conditions in the cavity, which was acting as a plasma vessel with distorted cylindrical geometry. We discuss the spectroscopic data taken during plasma removal of contaminants and use them to evaluate plasma parameters, characterize the process, and estimate the volatile contaminant product removal.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2020

Molecular mechanism for the interaction between human CPSF30 and hFip1

Most eukaryotic pre-mRNAs must undergo 3'-end cleavage and polyadenylation prior to their export from the nucleus. A large number of proteins in several complexes participate in this 3'-end processing, including cleavage and polyadenylation specificity factor (CPSF) in mammals. The CPSF30 subunit contains five CCCH zinc fingers (ZFs), with ZF2–ZF3 being required for the recognition of the AAUAAA poly(A) signal. ZF4–ZF5 recruits the hFip1 subunit of CPSF, although the details of this interaction have not been characterized. Here we report the crystal structure of human CPSF30 ZF4–ZF5 in complex with residues 161–200 of hFip1 at 1.9 Å resolution, illuminating the molecular basis for their interaction. Unexpectedly, the structure reveals one hFip1 molecule binding to each ZF4 and ZF5, with a conserved mode of interaction. Our mutagenesis studies confirm that the CPSF30–hFip1 complex has 1:2 stoichiometry in vitro. Mutation of each binding site in CPSF30 still allows one copy of hFip1 to bind, while mutation of both sites abrogates binding. Our fluorescence polarization binding assays show that ZF4 has higher affinity for hFip1, with a K d of 1.8 nM. We also demonstrate that two copies of the catalytic module of poly(A) polymerase (PAP) are recruited by the CPSF30–hFip1 complex in vitro, and both hFip1 binding sites in CPSF30 can support polyadenylation.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1993

A residual flexibility approach to multibody dynamics

Many complex systems can be modeled as a collection of interacting bodies, where the relative motion of the bodies may be large. The dynamics of such systems are simulated using multibody dynamic formulations. Many of these treat each body as a rigid component, but recently the flexibility of the components has been incorporated. This paper presents a residual flexibility formulation of the multibody dynamics problem. The formulation is very simple and offers great computational efficiency since it treats each body as a free structure in space, interacting with other bodies only through interface forces. Each body's accelerations can be solved independently, as can each set of interface forces. We have applied the technique successfully to several special applications, and the initial implementation in a general mechanisms code has given excellent results in comparison to a direct finite element representation of flexibility.

Blelloch, Paul A.↗
DOE OSTI2018

Crystal structure of SSB complexed with inhibitor myricetin

Highlights: • The first inhibitor-complexed crystal structure of SSB was determined. • Two SSB-myricetin interaction modes were found. • Lys7, Arg62, Glu80, and Gly107 in PaSSB were found crucial for forming hydrogen bond to myricetin. Single-stranded DNA-binding protein (SSB) is essential for all DNA-dependent cellular processes. SSB inhibitors have been recently suggested as broad-spectrum antibacterial agents in antibiotic development. In this paper, we report the first inhibitor-complexed crystal structure of SSB from Pseudomonas aeruginosa PAO1 (PaSSB) at 2.68 Å resolution (PDB entry 5YUN). The inhibitor, myricetin, is a flavonol that possesses many pharmacological activities, such as anticancer, anti-inflammatory, and antibacterial properties, and is beneficial for humans. Four monomers of PaSSB and two of myricetins were found per asymmetric unit. Various interactions between myricetin and PaSSB were examined. Among these, four residues in PaSSB, Lys7, Arg62, Glu80, and Gly107 were found crucial for forming hydrogen bond to myricetin. These two myricetins occupy the grooves for ssDNA-binding of SSB that may prevent ssDNA-wrapping and ssDNA-binding stably from SSB. In addition to explaining how SSB can be inhibited, the myricetin–SSB interaction modes in this paper may also provide insights into how myricetin can bind and inhibit proteins on cancer-signaling pathways.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

A conserved epitope III on hepatitis C virus E2 protein has alternate conformations facilitating cell binding or virus neutralization

Epitope III, a highly conserved amino acid motif of 524 APTYSW 529 on the hepatitis C virus (HCV) E2 glycoprotein, resides in the critical loop that binds to the host receptor CD81, thus making it one of the most important antibody targets for blocking HCV infections. Here, we have determined the X-ray crystal structure of epitope III at a 2.0-Å resolution when it was captured by a site-specific neutralizing antibody, monoclonal antibody 1H8 (mAb1H8). The snapshot of this complex revealed that epitope III has a relatively rigid structure when confined in the binding grooves of mAb1H8, which confers the residue specificity at both ends of the epitope. Such a high shape complementarity is reminiscent of the “lock and key” mode of action, which is reinforced by the incompatibility of an antibody binding with an epitope bearing specific mutations. By subtly positioning the side chains on the three residues of Tyr 527 , Ser 528 , and Trp 529 while preserving the spatial rigidity of the rest, epitope III in this cocrystal complex adopts a unique conformation that is different from previously described E2 structures. With further analyses of molecular docking and phage display–based peptide interactions, we recognized that it is the arrangements of two separate sets of residues within epitope III that create these discrete conformations for the epitope to interact selectively with either mAb1H8 or CD81. These observations thus raise the possibility that local epitope III conformational dynamics, in conjunction with sequence variations, may act as a regulatory mechanism to coordinate “mAb1H8-like” antibody-mediated immune defenses with CD81-initiated HCV infections.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

Structural hierarchy controlling dimerization and target DNA recognition in the AHR transcriptional complex

The aryl hydrocarbon receptor (AHR) belongs to the PAS (PER-ARNT-SIM) family transcription factors and mediates broad responses to numerous environmental pollutants and cellular metabolites, modulating diverse biological processes from adaptive metabolism, acute toxicity, to normal physiology of vascular and immune systems. The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. We determined the crystal structure of the mammalian AHR–ARNT heterodimer in complex with the DRE, in which ARNT curls around AHR into a highly intertwined asymmetric architecture, with extensive heterodimerization interfaces and AHR interdomain interactions. Specific recognition of the DRE is determined locally by the DNA-binding residues, which discriminates it from the closely related hypoxia response element (HRE), and is globally affected by the dimerization interfaces and interdomain interactions. Changes at the interdomain interactions caused either AHR constitutive nuclear localization or failure to translocate to nucleus, underlying an allosteric structural pathway for mediating ligand-induced exposure of nuclear localization signal. Furthermore, these observations, together with the global higher flexibility of the AHR PAS-A and its loosely packed structural elements, suggest a dynamic structural hierarchy for complex scenarios of AHR activation induced by its diverse ligands.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Inhibitor-3 inhibits Protein Phosphatase 1 via a metal binding dynamic protein–protein interaction

To achieve substrate specificity, protein phosphate 1 (PP1) forms holoenzymes with hundreds of regulatory and inhibitory proteins. Inhibitor-3 (I3) is an ancient inhibitor of PP1 with putative roles in PP1 maturation and the regulation of PP1 activity. Here, we show that I3 residues 27–68 are necessary and sufficient for PP1 binding and inhibition. In addition to a canonical RVxF motif, which is shared by nearly all PP1 regulators and inhibitors, and a non-canonical SILK motif, I3 also binds PP1 via multiple basic residues that bind directly in the PP1 acidic substrate binding groove, an interaction that provides a blueprint for how substrates bind this groove for dephosphorylation. Unexpectedly, this interaction positions a CCC (cys-cys-cys) motif to bind directly across the PP1 active site. Using biophysical and inhibition assays, we show that the I3 CCC motif binds and inhibits PP1 in an unexpected dynamic, fuzzy manner, via transient engagement of the PP1 active site metals. Together, these data not only provide fundamental insights into the mechanisms by which IDP protein regulators of PP1 achieve inhibition, but also shows that fuzzy interactions between IDPs and their folded binding partners, in addition to enhancing binding affinity, can also directly regulate enzyme activity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

Fixed-node diffusion Monte Carlo description of nitrogen defects in zinc oxide

Using the fixed-node diffusion Monte Carlo (FN-DMC) method, we evaluate the formation energies and charge transition levels of substitutional nitrogen defects in the wide-band-gap semiconductor zinc oxide. The use of a direct-solution, many-body approach inherently secures a good description of electron-electron interactions, achieving high accuracy without adjustable parameters. According to FN-DMC nitrogen is a deep acceptor with a charge transition level 1.0(3) eV above the valence-band maximum when 72-atom supercells are used. This result falls on the lower end of typically reported hybrid density functional results for the same size supercells, which range from 1.0 to 1.8 eV. Further, residual finite-size effects due to charged defect image interactions in the 72-atom supercells are estimated by supercell extrapolation within hybrid density functional theory. When the finite-size correction is included, we obtain a deep acceptor at 1.6(3) eV. This result is in good agreement with recent experimental measurements. We also analyze the local compressibility of charge according to FN-DMC and common density functionals and find that the use of hybrid functionals obtains compressibilities in better agreement with the many-body theory. Our work illustrates the application of the FN-DMC method to a challenging point defect problem, demonstrating that uncertainties and approximations can be well controlled.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2024

Variable domain mutational analysis to probe the molecular mechanisms of high viscosity of an IgG 1 antibody

Subcutaneous injection is the preferred route of administration for many antibody therapeutics for reasons that include its speed and convenience. However, the small volume limit (typically ≤2 mL) for subcutaneous delivery often necessitates antibody formulations at high concentrations (commonly ≥100 mg/mL), which may lead to physicochemical problems. For example, antibodies with large hydrophobic or charged patches can be prone to self-interaction giving rise to high viscosity. Here, we combined X-ray crystallography with computational modeling to predict regions of an anti-glucagon receptor (GCGR) IgG 1 antibody prone to self-interaction. An extensive mutational analysis was undertaken of the complementarity-determining region residues residing in hydrophobic surface patches predicted by spatial aggregation propensity, in conjunction with residue-level solvent accessibility, averaged over conformational ensembles from molecular dynamics simulations. Dynamic light scattering (DLS) was used as a medium throughput screen for self-interaction of ~200 anti-GCGR IgG 1 variants. A negative correlation was found between the viscosity determined at high concentration (180 mg/mL) and the DLS interaction parameter measured at low concentration (2–10 mg/mL). Additionally, anti-GCGR variants were readily identified with reduced viscosity and antigen-binding affinity within a few fold of the parent antibody, with no identified impact on overall developability. The methods described here may be useful in the optimization of other antibodies to facilitate their therapeutic administration at high concentration.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2012

In situ study of erosion and deposition of amorphous hydrogenated carbon films by exposure to a hydrogen atom beam

This paper reports on the first dual-beam experiment employing a hydrogen atom beam for sample exposure and an ion beam for analysis, enabling in situ and real-time studies of hydrogen atom interaction with materials. The erosion of an amorphous hydrogenated carbon (a-C:H) layer by deuterium atoms at 580 K sample temperature was studied and the uptake of deuterium during the erosion process was measured in real time. The deuterium areal density increased at the beginning to 7.3 Multiplication-Sign 10{sup 15} D cm{sup -2}, but then stabilized at a constant value of 5.5 Multiplication-Sign 10{sup 15} D cm{sup -2}. Formation of a polymer-like deposit on an a-C:H layer held at room temperature and subjected to the deuterium atom beam was observed and also studied in situ. For both erosion and deposition studies an a-{sup 13}C:H layer on top of an Si substrate was used as a sample, making the experiments isotopically fully specified and thereby differentiating the deposited from the original layer and the interacting D atoms from H atoms present in the layer and in the residual vacuum. From the deposition study it was shown that carbon in the deposited layer originates from carbon-carrying species in the background vacuum that interact with hydrogen atoms. The areal density of the carbon at the surface was determined from the energy shift of the Si edge in the Rutherford backscattering spectrum. The cross section for {sup 7}Li on D at 4.3 MeV Li ion energy and at a recoil angle of 30 Degree-Sign was also determined to be (236 {+-} 16) Multiplication-Sign 10{sup -27} cm{sup 2}/sr. This is a factor of 3 {+-} 0.2 times higher than the Rutherford elastic cross section.

36 MATERIALS SCIENCE↗
DOE OSTI2021

Effect of the scanning strategy on the formation of residual stresses in additively manufactured Ti-6Al-4V

During the laser-powder bed fusion (L-PBF) process, high laser intensities, short interaction times and highly localized heat input drive large thermal gradients that result in a state of high residual stresses. Generally, the residual stresses that develop during the L-PBF process can compromise the performance of the component. Up to now, the literature has indicated that the magnitude of the residual stresses can be affected by various process parameters. In this study, all process parameters such as laser power and speed are held fixed and the focus is solely on the effect of the laser scan strategy on the three-dimensional residual stress state of L-PBF metallic components. Four Ti-6Al-4V bridge shaped components were built using island and continuous scanning patterns parallel and offset 45° from the sample axes. High-energy X-ray diffraction was used to determine the residual stress field in each of the components. Two of them were re-measured after being partially removed from the build plate. The assumptions implicit in diffraction measurements of stress are reviewed and discussed in depth because the unique microstructure associated with L-PBF Ti-6Al-4V renders the validity of those assumptions uncertain. Specifically, additional data was collected and analyzed to evaluate the relationship between grain scale and macroscopic scale stresses. The observed residual stresses were large, ½ to ¾ of the yield strength, particularly the build direction stresses near the lateral edges of the bridges. Here in this work, the higher stresses were observed in the bridges built via the island scan strategies, chiefly near the edges of the parts.

36 MATERIALS SCIENCE↗
DOE OSTI2014

The cataract-associated V41M mutant of human γS-crystallin shows specific structural changes that directly enhance local surface hydrophobicity

Highlights: •We present NMR analysis of V41M, a cataract-causing mutant of human γS-crystallin. •Mutation alters strand–strand interactions throughout the N-terminal domain. •Mutation directly affects Trp46 due to key Met41-S–Trp46-pi interactions. •We identify the basis of the surface hydrophobicity increase and residues involved. -- Abstract: The major crystallins expressed in the human lens are γS-, γC- and γD-crystallins. Several mutations in γS-crystallin are associated with hereditary cataracts, one of which involves the substitution of a highly conserved Valine at position 41 to Methionine. According to a recent report, the mutant protein, V41M, shows lower stability and increased surface hydrophobicity compared to the wild-type, and a propensity for self-aggregation. Here we address the structural differences between the two proteins, with residue-level specificity using NMR spectroscopy. Based on the structural model of the mutant protein, our results clearly show that the mutation creates a major local perturbation almost at the junction of the first and second “Greek-key” motifs in the N-terminal domain. A larger section of the second motif (residues 44–86) appears to be mainly affected. Based on the sizeable chemical shift of the imino proton of the indole side-chain of Trp46 in V41M, we suggest that the sulphur atom of Met41 is involved in an S–π interaction with Trp46. This interaction would bring the last β-strand of the first “Greek-key” motif closer to the first β-strand of the second motif. This appears to lead to a domino effect, towards both the N- and C-terminal ends, even as it decays off substantially beyond the domain interface. During this process discreet hydrophobic surface patches are created, as revealed by ANS-binding. Such changes would not affect the secondary structure or cause a major change in the tertiary structure, but can lead to self-aggregation or aberrant binding interactions of the mutant protein in vivo, and lead to lens opacity or cataract.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1987

Low-field magnetoacoustic residual stress measurement in steel

Much of the recent development of the magnetoacoustic technique has been devoted to refine this technique as a reliable and practical tool for measuring bulk residual stress in steel components. For this, the effects of structural and metallurgical properties on the magnetoacoustic interaction have been studied for various types of steel samples. Also, progress is being made to obtain quantitative residual stress measurements in railroad wheels. This paper reviews the physical basis and the experimental results of the magnetoacoustic stress measurements in steels.

Namkung, M.↗
DOE OSTI2025

Binding and Translocation of Substrate Allosterically Promotes Functional Interactions Within the AlkB–AlkG Electron Transfer Complex

The alkane monooxygenase AlkB and rubredoxin AlkG form an electron transfer complex that hydroxylates terminal alkanes to produce alcohols. The recent cryoEM study of Fontimonas thermophila AlkB-AlkG complex revealed its architecture, including a dodecane (D12) substrate at the active site. However, FtAlkBG molecular mechanism of action of remains unknown. Here, in this study, we examined its dynamics and interactions by multiscale computations, including molecular dynamics simulations, elastic network models, and QM/MM of the oxygen activation mechanism at the AlkB catalytic site. D12 maintained stable interactions within the catalytic site during two MD runs, coordinated by hydrophobic residues L263-L264, I267, I133. A third extended run revealed that D12 could translocate to a membrane-exposed site near S49/F46 along a hydrophobic channel gated by I54. During this translocation, D12 was temporarily stabilized at intermediate sites IS1 (lined by I27/L30-G31/G50/L53-I54/P59/S124/A127-V128) and IS2 (I33-G34/L37/L45-F46/S49) before nearly exiting the protein, and diffused back to the active site, assisted by L30. Substrate binding and translocation across those intermediate sites affects the coupling between the iron centers in AlkBG, and interfacial interactions between AlkB-AlkG. The channel was further connected to the cytosol, near two surface-exposed arginines, potentially allowing for O 2 passage. The allosteric effects between D12 putative entry site, catalytic site and AlkB-AlkG interface were analyzed by ENM-based methods which confirmed the cooperative perturbation-responses and strongly correlated movements of residues belonging to those distal regions. Our study provides new mechanistic insights into key sites and their interactions that could be targeted for developing AlkB-variants with desirable alkane conversion functions.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Correction to “COCOMO2: A Coarse-Grained Model for Interacting Folded and Disordered Proteins”

Biomolecular interactions are essential in many biological processes, including complex formation and phase separation processes. Coarse-grained computational models are especially valuable for studying such processes via simulation. Here, we present COCOMO2, an updated residue-based coarse-grained model that extends its applicability from intrinsically disordered peptides to folded proteins. This is accomplished with the introduction of a surface exposure scaling factor, which adjusts interaction strengths based on solvent accessibility, to enable the more realistic modeling of interactions involving folded domains without additional computational costs. COCOMO2 was parametrized directly with solubility and phase separation data to improve its performance on predicting concentration-dependent phase separation for a broader range of biomolecular systems compared to the original version. COCOMO2 enables new applications including the study of condensates that involve IDPs together with folded domains and the study of complex assembly processes. COCOMO2 also provides an expanded foundation for the development of multiscale approaches for modeling biomolecular interactions that span from residue-level to atomistic resolution.

Molecular interactions↗
DOE OSTI2019

On the Contribution of the Long-Range Scattering Potential in the Process of Multiphoton Above-Threshold Ionization of Atoms in the Laser Field

Using the quantum mechanical analysis of stimulated bremsstrahlung of an electron on an electrostatic potential in the field of a strong electromagnetic wave in the generalized eikonal approximation, the simplified formula for the probability of multiphoton above-threshold ionization of a hydrogen-like atom in the laser field is obtained, taking into account the interaction of the photoelectron with the long-range Coulomb field of the residual ion.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗