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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 487 records · Page 27
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Predicting RNA structure and dynamics with deep learning and solution scattering

Advanced deep learning and statistical methods can predict structural models for RNA molecules. However, RNAs are flexible, and it remains difficult to describe their macromolecular conformations in solutions where varying conditions can induce conformational changes. Small-angle x-ray scattering (SAXS) in solution is an efficient technique to validate structural predictions by comparing the experimental SAXS profile with those calculated from predicted structures. There are two main challenges in comparing SAXS profiles to RNA structures: the absence of cations essential for stability and charge neutralization in predicted structures and the inadequacy of a single structure to represent RNA’s conformational plasticity. We introduce a solution conformation predictor for RNA (SCOPER) to address these challenges. This pipeline integrates kinematics-based conformational sampling with the innovative deep learning model, IonNet, designed for predicting Mg 2+ ion binding sites. Validated through benchmarking against 14 experimental data sets, SCOPER significantly improved the quality of SAXS profile fits by including Mg 2+ ions and sampling of conformational plasticity. We observe that an increased content of monovalent and bivalent ions leads to decreased RNA plasticity. Therefore, carefully adjusting the plasticity and ion density is crucial to avoid overfitting experimental SAXS data. SCOPER is an efficient tool for accurately validating the solution state of RNAs given an initial, sufficiently accurate structure and provides the corrected atomistic model, including ions.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

A dynamic interaction between CD19 and the tetraspanin CD81 controls B cell co-receptor trafficking

CD81 and its binding partner CD19 are core subunits of the B cell co-receptor complex. While CD19 belongs to the extensively studied Ig superfamily, CD81 belongs to a poorly understood family of four-pass transmembrane proteins called tetraspanins. Tetraspanins play important physiological roles by controlling protein trafficking and other processes. Here, we show that CD81 relies on its ectodomain to traffic CD19 to the cell surface. Moreover, the anti-CD81 antibody 5A6, which binds selectively to activated B cells, recognizes a conformational epitope on CD81 that is masked when CD81 is bound to CD19. Mutations of CD81 in this interface suppress its CD19 export activity. These data indicate that the CD81 - CD19 interaction is dynamically regulated upon B cell activation and this dynamism can be exploited to regulate B cell function. These results are not only valuable for understanding B cell biology, but also have important implications for understanding tetraspanin function generally.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Casein kinase 1 dynamics underlie substrate selectivity and the PER2 circadian phosphoswitch

Post-translational control of PERIOD stability by Casein Kinase 1δ and ε (CK1) plays a key regulatory role in metazoan circadian rhythms. Despite the deep evolutionary conservation of CK1 in eukaryotes, little is known about its regulation and the factors that influence substrate selectivity on functionally antagonistic sites in PERIOD that directly control circadian period. Here we describe a molecular switch involving a highly conserved anion binding site in CK1. This switch controls conformation of the kinase activation loop and determines which sites on mammalian PER2 are preferentially phosphorylated, thereby directly regulating PER2 stability. Integrated experimental and computational studies shed light on the allosteric linkage between two anion binding sites that dynamically regulate kinase activity. We show that period-altering kinase mutations from humans to Drosophila differentially modulate this activation loop switch to elicit predictable changes in PER2 stability, providing a foundation to understand and further manipulate CK1 regulation of circadian rhythms.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

The quantum p -spin glass model: a user manual for holographers

We study a large-N bosonic quantum mechanical sigma-model with a spherical target space subject to disordered interactions, more colloquially known as the p-spin spherical model. Replica symmetry is broken at low temperatures and for sufficiently weak quantum fluctuations, which drives the system into a spin glass (SG) phase. The first half of this paper is dedicated to a discussion of this model's thermodynamics, with particular emphasis on the marginally stable SG. This phase exhibits an emergent conformal symmetry in the strong coupling regime, which dictates its thermodynamic properties. It is associated with an extensive number of nearby states in the free energy landscape. We discuss in detail an elegant approximate solution to the SG equations, which interpolates between the conformal regime and an ultraviolet-complete short distance solution. In the second half of this paper we explore the real-time dynamics of the model and uncover quantum chaos as measured by out-of-time-order four-point functions, both numerically and analytically. We find exponential Lyapunov growth, which intricately depends on the model's couplings and becomes strongest in the quantum critical regime. We emphasize that the SG phase also exhibits quantum chaos, albeit with parametrically smaller Lyapunov exponent than in the replica symmetric phase. An analytical calculation in the marginal SG phase suggests that this Lyapunov exponent vanishes in a particular infinite coupling limit. Finally, we comment on the potential meaning of these observations from the perspective of holography.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2025

Effect of Crystallinity on Polymer Chain Compression in Polyethylene Dynamically Loaded with In-Situ X-Ray Diffraction

Abstract Polyethylene (PE) is a polymer widely used in commercial applications, where the properties of PE can be altered based on the molecular conformation. In this study, shock compression experiments with in-situ x-ray diffraction were conducted on two conformations of PE– low density polyethylene (LDPE) and ultra-high molecular weight polyethylene (UHMWPE). Encouragingly, X-ray diffraction patterns were easily observed in LDPE, which is only 25% crystalline. In agreement with a previous study on HDPE, LDPE exhibited a phase transition at 7.7 GPa. Lower pressure experiments on UHMWPE and LDPE exhibited polymer chain compression, but no occurrence of a phase transition.

36 MATERIALS SCIENCE↗
DOE OSTI2024

Microwave-Absorbing Foams with Adjustable Absorption Frequency and Structural Coloration

Microwave-absorbing materials with regulatable absorption frequency and optical camouflage hold great significance in intelligent electronic devices and advanced stealth technology. Herein, we present an innovative microwave-absorbing foam that can dynamically tune microwave absorption frequencies via a simple mechanical compression while in parallel enabling optical camouflage over broad spectral ranges by adjusting the structural colors. In this study, the vivid colors spanning different color categories generated from thin-film interference can be precisely regulated by adjusting the thickness of the conformal TiO 2 coatings on Ni/melamine foam. Enhanced interfacial and defect-induced polarizations resulting from the introduction of TiO 2 coating synergistically contribute to the dielectric attenuation performance. Consequently, such a foam exhibits exceptional microwave absorption capabilities, and the absorption frequency can be dynamically tuned from the S band to the Ku band by manipulating its compression ratio. Additionally, simulation calculations validate the adjustable electromagnetic wave loss behavior, offering valuable insights for the development of next-generation intelligent electromagnetic devices across diverse fields.

36 MATERIALS SCIENCE↗
DOE OSTI2026

Conserved Macromolecular Architecture of Poplar Secondary Cell Walls Revealed by ssNMR and Atomistic Modeling

The macromolecular architecture of plant secondary cell walls governs wood's mechanical and biochemical properties, yet its natural intra-species variability remains poorly characterized. Here, we combined 13C solid-state NMR (ssNMR), multivariate statistical analysis, and molecular modeling to profile nanoscale structure across 13 genetically diverse Populus trichocarpa genotypes grown in 13C-enriched atmospheres. SsNMR-derived phenotypes spanning composition, structure, mobility, and inter-polymer proximities reveal a conserved architecture, with a subtle yet coordinated variation organizing into dominant structural and secondary mobility axes. A representative atomistic model captures these features and reproduces experimental metrics. Molecular dynamics simulations support a weak but consistent positive correlation between cellulose abundance and crystalline-like order, with interior cellulose chains enriched in tg (trans-gauche) conformations without expanding crystalline cores. Together, experiment and simulation reveal a genetically buffered, broadly conserved nanoscale architecture across genotypes, where subtle fine-tuning of cellulose bundling and matrix packing balances mechanical performance with biological function.

09 BIOMASS FUELS↗
DOE OSTI2023

Disruption of Z-Disc Function Promotes Mechanical Dysfunction in Human Myocardium: Evidence for a Dual Myofilament Modulatory Role by Alpha-Actinin 2

The ACTN2 gene encodes α-actinin 2, located in the Z-disc of the sarcomeres in striated muscle. In this study, we sought to investigate the effects of an ACTN2 missense variant of unknown significance (p.A868T) on cardiac muscle structure and function. Left ventricular free wall samples were obtained at the time of cardiac transplantation from a heart failure patient with the ACTN2 A868T heterozygous variant. This variant is in the EF 3–4 domain known to interact with titin and α-actinin. At the ultrastructural level, ACTN2 A868T cardiac samples presented small structural changes in cardiomyocytes when compared to healthy donor samples. However, contractile mechanics of permeabilized ACTN2 A868T variant cardiac tissue displayed higher myofilament Ca 2+ sensitivity of isometric force, reduced sinusoidal stiffness, and faster rates of tension redevelopment at all Ca 2+ levels. Small-angle X-ray diffraction indicated increased separation between thick and thin filaments, possibly contributing to changes in muscle kinetics. Molecular dynamics simulations indicated that while the mutation does not significantly impact the structure of α-actinin on its own, it likely alters the conformation associated with titin binding. Our results can be explained by two Z-disc mediated communication pathways: one pathway that involves α-actinin’s interaction with actin, affecting thin filament regulation, and the other pathway that involves α-actinin’s interaction with titin, affecting thick filament activation. This work establishes the role of α-actinin 2 in modulating cross-bridge kinetics and force development in the human myocardium as well as how it can be involved in the development of cardiac disease.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Is a Malleable Active Site Loop the Key to High Substrate Promiscuity? Hybrid, Biocatalytic Route to Structurally Diverse Taxoid Side Chains with Remarkable Dual Stereocontrol

Abstract These studies reveal the first structure ofClostridium acetobutylicumalcohol dehydrogenase (CaADH), a protein exhibiting remarkable substrate promiscuity and stereochemical fidelity. The CaADH enzyme is utilized here for synthesizing 20 potential aryl isoserine side chains for the Taxotere family of tubulin‐binding chemotherapeutics. The approach involves dynamic reductive kinetic resolution (DYRKR) upon the corresponding α‐chloro‐β‐keto esters, showing high D‐synstereoselectivity, including those leading to the clinically relevant milataxel (Ar = 2‐furyl) and simotaxel (Ar = 2‐thienyl) side chains. Furthermore, various cross‐coupling chemistries performed on thep‐bromophenyl isoserine side chain significantly enhance the structural diversity of the taxoid side chain library obtained (16 additional taxoid side chains). The CaADH structure is notable: (i) the nicotinamide cofactor is bound in ananti‐conformation, with the amide carbonyl occupying the ketone binding pocket, and (ii) a flexible loop near the active site likely contributes to the remarkable substrate promiscuity observed in CaADH. We present our perspective on the dynamic nature of the CaADH active site through molecular dynamics simulation, proposing a halogen bonding model as a potential mechanism for the remarkable selectivity for an (S)‐configured C─Cl bond, in addition to the D‐facial selectivity, demonstrated across 20 diverse substrates by this remarkable short‐chain dehydrogenase enzyme.

Chemistry↗
DOE OSTI2020

Bottom-Up Meets Top-Down: The Crossroads of Multiscale Chromatin Modeling

Chromatin can be viewed as a hierarchically structured fiber that regulates gene expression. It consists of a complex network of DNA and proteins whose characteristic dynamical modes facilitate compaction and rearrangement in the cell nucleus. These modes stem from chromatin's fundamental unit, the nucleosome, and their effects are propagated across length scales. Understanding the effects of nucleosome dynamics on the chromatin fiber, primarily through post-translational modifications that occur on the histones, is of central importance to epigenetics. Within the last decade, imaging and chromosome conformation capture techniques have revealed a number of structural and statistical features of the packaged chromatin fiber at a hitherto unavailable level of resolution. Such experiments have led to increased efforts to develop polymer models that aim to reproduce, explain, and predict the contact probability scaling and density heterogeneity. At nanometer scales, available models have focused on the role of the nucleosome and epigenetic marks on local chromatin structure. At micrometer scales, existing models have sought to explain scaling laws and density heterogeneity. Less work, however, has been done to reconcile these two approaches: bottom-up and top-down models of chromatin. Here, we highlight the multiscale simulation models that are driving toward an understanding of chromatin structure and function, from the nanometer to the micron scale, and we highlight areas of opportunity and some of the prospects for new frameworks that bridge these two scales. Taken together, experimental and modeling advances over the last few years have established a robust platform for the study of chromatin fiber structure and dynamics, which will be of considerable use to the chromatin community in developing an understanding of the interplay between epigenomic regulation and molecular structure.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Molecular basis for lipid recognition by the prostaglandin D 2 receptor CRTH2

Significance Many amphipathic lipids, including cannabinoids, lysophospholipids, prostanoids, and leukotrienes, bind to G protein–coupled receptors (GPCRs) through the lipid bilayer. How these lipid ligands get anchored to their receptors and enter ligand-binding pockets is largely elusive. Our results revealed a distinctive lipid recognition mechanism for the prostaglandin D 2 (PGD 2 ) receptor CRTH2 that is not shared by other prostanoid receptors. Based on the structural analysis, we propose two representative binding modes of lipids in GPCRs. We also identified critical structural motifs and conformational changes of CRTH2 for capturing lipids from the lipidic environment and lipid transition to the binding pocket, thereby offering unprecedented molecular insight into the dynamic lipid-binding processes for GPCRs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Cryo-EM structures of Escherichia coli cytochrome bo 3 reveal bound phospholipids and ubiquinone-8 in a dynamic substrate binding site

Two independent structures of the proton-pumping, respiratory cytochrome bo3 ubiquinol oxidase (cyt bo 3 ) have been determined by cryogenic electron microscopy (cryo-EM) in styrene–maleic acid (SMA) copolymer nanodiscs and in membrane scaffold protein (MSP) nanodiscs to 2.55- and 2.19-Å resolution, respectively. The structures include the metal redox centers (heme b, heme o 3 , and Cu B ), the redox-active cross-linked histidine–tyrosine cofactor, and the internal water molecules in the proton-conducting D channel. Each structure also contains one equivalent of ubiquinone-8 (UQ8) in the substrate binding site as well as several phospholipid molecules. The isoprene side chain of UQ8 is clamped within a hydrophobic groove in subunit I by transmembrane helix TM0, which is only present in quinol oxidases and not in the closely related cytochrome c oxidases. Both structures show carbonyl O1 of the UQ8 headgroup hydrogen bonded to D75I and R71 I . In both structures, residue H98 I occupies two conformations. In conformation 1, H98 I forms a hydrogen bond with carbonyl O4 of the UQ8 headgroup, but in conformation 2, the imidazole side chain of H98 I has flipped to form a hydrogen bond with E14 I at the N-terminal end of TM0. We propose that H98 I dynamics facilitate proton transfer from ubiquinol to the periplasmic aqueous phase during oxidation of the substrate. Computational studies show that TM0 creates a channel, allowing access of water to the ubiquinol headgroup and to H98 I .

bioenergetics↗
DOE OSTI2021

Three-state harmonic models for photoinduced charge transfer

A widely used strategy for simulating the charge transfer between donor and acceptor electronic states in an all-atom anharmonic condensedphase system is based on invoking linear response theory to describe the system in terms of an effective spin-boson model Hamiltonian. Extending this strategy to photoinduced charge transfer processes requires also taking into consideration the ground electronic state in addition to the excited donor and acceptor electronic states. In this paper, we revisit the problem of describing such nonequilibrium processes in terms of an effective three-state harmonic model. We do so within the framework of nonequilibrium Fermi’s golden rule (NE-FGR) in the context of photoinduced charge transfer in the carotenoid–porphyrin–C 60 (CPC 60 ) molecular triad dissolved in explicit tetrahydrofuran (THF). To this end, we consider different ways for obtaining a three-state harmonic model from the equilibrium autocorrelation functions of the donor–acceptor, donor–ground, and acceptor–ground energy gaps, as obtained from all-atom molecular dynamics simulations of the CPC 60 /THF system. The quantum-mechanically exact time-dependent NE-FGR rate coefficients for two different charge transfer processes in two different triad conformations are then calculated using the effective three-state model Hamiltonians as well as a hierarchy of more approximate expressions that lead to the instantaneous Marcus theory limit. Our results show that the photoinduced charge transfer in CPC 60 /THF can be described accurately by the effective harmonic three-state models and that nuclear quantum effects are small in this system.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2022

Monitoring Carbon Storage Sites with Time-Lapse Gravity Surveys

Monitoring technologies are deployed on carbon storage sites to demonstrate that the injected CO2 is contained within the storage complex during and long after the active life of the project and that the CO2 behavior is conforming to expectations. Detection of gravity variations accompanying mass redistributions in the subsurface caused by fluid movements in reservoirs provides a unique means for monitoring the dynamics of a carbon sequestration site. Time-lapse gravity surveys have a long history of effectively monitoring temporal density changes in the subsurface. However, monitoring of carbon storage sites with time-lapse gravity surveys using surface or borehole measurements remains limited, although it gained more attention during the last decade. With the recent progresses in instrument capabilities, and the increased number of fluid storage sites (e.g., wastewater, CO2, natural gas, etc.), the gravity method (with its unique ability to remotely estimate both the mass of an injected fluid and its location) has a promising future in monitoring. This chapter provides background information regarding the gravity method and discusses its modeling and application to various carbon storage sites.

Carbon Sequestration, time-lapse gravity, monitori↗
DOE OSTI2023

Intergranular Hotspots: A Molecular Dynamics Study on the Influence of Compressive and Shear Work

Numerous crystal- and microstructural-level mechanisms are at play in the formation of hotspots, which are known to govern high explosives initiation behavior. Most of these mechanisms, including pore collapse, interfacial friction, and shear banding, involve both compressive and shear work done within the material and have thus far remained difficult to separate. Here, we assess hotspots formed at shocked crystal–crystal interfaces using quasi-1D molecular dynamics simulations that isolate effects due to compression and shear. Two high explosive materials are considered (TATB and PETN) that exhibit distinctly different levels of molecular conformational flexibility and crystal packing anisotropy. Temperature and intramolecular strain energy localization in the hotspot are assessed through parametric variation of the crystal orientation and two velocity components that respectively modulate compression and shear work. The resulting hotspots are found to be highly localized to a region within 5–20 nm of the crystal–crystal interface. Compressive work plays a considerably larger role in localizing temperature and intramolecular strain energy for both materials and all crystal orientations considered. Shear induces a moderate increase in energy localization relative to unsheared cases only for relatively weak compressive shock pressures of approximately 10 GPa. These results help isolate and rank the relative importance of hotspot generation mechanisms and are anticipated to guide the treatment of crystal–crystal interfaces in coarse-grained models of polycrystalline high-explosive materials.

36 MATERIALS SCIENCE↗
DOE OSTI2022

Source of Rate Acceleration for Carbocation Cyclization in Biomimetic Supramolecular Cages

The results of quantum chemical and molecular dynamics calculations reveal that polyanionic gallium-based cages accelerate cyclization reactions of pentadienyl alcohols as a result of substrate cage interactions, preferential binding of reactive conformations of substrate/H 3 O + pairs, and increased substrate basicity. However, the increase in basicity dominates. Here, experimental structure–activity relationship studies in which the metal vertices and overall charge of the cage are varied confirm the model derived via calculations.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2025

Structural determinants for pH-dependent activation of a plant metacaspase

Arabidopsis thaliana metacaspase 9 (AtMC9) plays roles in clearing dead cells, forming xylem vessels, and regulating immunity and programmed cell death in plants. The protease's activation is controlled by pH levels, but the exact structural mechanism behind this has not been elucidated. In this work, high-resolution crystal structures for AtMC9 at active (pH 5.5 and pH 4.2) and inactive (pH 7.5) conditions are reported. The three structures are similar except for local conformations where their hydrogen bonding interactions with solvents are mediated through the protonation of specific titratable amino acid residues' side chains. By combining structural analysis, molecular dynamics simulations under constant pHs, and biochemical assays coupled with site-directed mutagenesis, we show that the regulation of AtMC9 activation involves multiple titratable glutamate and histidine residues across the three domains of p20, linker, and p10. Specifically, deprotonated Glu112, His193, and His208 can suppress AtMC9 proteolytic activity, while protonation of Glu255 and His307 at acidic pH may promote it. This study provides valuable insights into the pH-dependent activation of AtMC9 and could potentially lead to improving crops with enhanced immunity and controlled cell death, ultimately increasing agricultural productivity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Going around the Kok cycle of the water oxidation reaction with femtosecond X-ray crystallography

The water oxidation reaction in photosystem II (PS II) produces most of the molecular oxygen in the atmosphere, which sustains life on Earth, and in this process releases four electrons and four protons that drive the downstream process of CO 2 fixation in the photosynthetic apparatus. The catalytic center of PS II is an oxygen-bridged Mn 4 Ca complex (Mn 4 CaO 5 ) which is progressively oxidized upon the absorption of light by the chlorophyll of the PS II reaction center, and the accumulation of four oxidative equivalents in the catalytic center results in the oxidation of two waters to dioxygen in the last step. The recent emergence of X-ray free-electron lasers (XFELs) with intense femtosecond X-ray pulses has opened up opportunities to visualize this reaction in PS II as it proceeds through the catalytic cycle. In this review, we summarize our recent studies of the catalytic reaction in PS II by following the structural changes along the reaction pathway via room-temperature X-ray crystallography using XFELs. The evolution of the electron density changes at the Mn complex reveals notable structural changes, including the insertion of O X from a new water molecule, which disappears on completion of the reaction, implicating it in the O—O bond formation reaction. We were also able to follow the structural dynamics of the protein coordinating with the catalytic complex and of channels within the protein that are important for substrate and product transport, revealing well orchestrated conformational changes in response to the electronic changes at the Mn 4 Ca cluster.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗