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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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260 records · Page 15
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

Cryo-EM Visualization of Intermolecular π-Electron Interactions within π-Conjugated Peptidic Supramolecular Polymers

The self-assembly of “π-peptides” – molecules with π-electron cores substituted with two or more oligopeptide chains – brings organic electronic function into biologically relevant nanomaterials. π-Peptides assemble into fibrillar nanomaterials as driven by enthalpic peptide-based hydrogen bonding networks and pi-core-based quadrupolar interactions. A large body of spectroscopic, morphological and computational studies informs on the nature of the self-assembly process and the resulting nanostructures, but detailed structural information has remained elusive. Here, inspired by the recent use of cryogenic electron microscopy (cryo-EM) to provide high-resolution structures for synthetic peptide nanomaterials, we present here the use of cryo-EM to offer ca. 3 Å resolution of π-peptide nanomaterial assemblies, visualizing for the first time the nature of the intermolecular π-core electronic interactions responsible for energy transport through these supramolecular materials.

Group theory↗
NASA NTRSDate not supplied

Cardiovascular Responses to Simulated Spaceflight: Molecular Signatures and Surrogate Outputs to Measure CVD Risk

During extended space missions beyond low Earth orbit, astronauts will encounter prolonged periods of weightlessness and low dose space radiation. Previous studies have shown that exposure to small doses of high LET radiation (< 50 cGy) can lead to both short-term and long-term alterations in heart function, structure and underlying molecular mechanisms. In this study, we aim to identify the molecular signature associated with the cardiovascular response to simulated galactic cosmic radiation (5-ion GCR) alone or in combination with simulated weightlessness at time intervals relevant to mission length and recovery. Additionally, we aim to determine whether sex impacts cardiovascular responses to these spaceflight factors. Our overarching goal is to enhance our understanding of the cardiovascular risks associated with extended space missions and the clinical endpoints they suggest. We hypothesize that exposure to simulated space radiation leads to enduring alterations in the transcriptome, redox signaling and cytokine environment of cardiovascular tissue, some which have known links with reduced cardiovascular performance, aging, and increased risk of cardiovascular disease (CVD). Furthermore, we posit that simulated space radiation exposure in combination with simulated microgravity exacerbates cardiovascular deficits compared to single factor exposure. Female and male C57BL/6J mice, aged 23-24 weeks, were exposed to a single dose of 5, 15, or 50 cGy of 5-ion GCR, or sham-treated (0 cGy). Euthanasia was performed at 14 days and ~4 months post-irradiation. Hearts, aorta and blood plasma were collected shortly thereafter. RNA-sequencing of left ventricles at ~4 months post-GCR exposure revealed sex differences in the heart transcriptome with a few genes showing radiation-dependent changes in expression levels. Notably, some of the differentially expressed genes in 15 and 50 cGy GCR groups are known to play roles in the development of CVD. Analysis of protein levels of a subset of inflammatory cytokines in the heart indicated sex differences but no differences between sham and 50 cGy groups. Results also showed correlations among differentially expressed genes and a subset of inflammatory cytokines, with some correlations altered by GCR exposure. These findings suggest that GCR exposure can modify protein and gene networks linked to inflammation and CVD progression. In the aorta, telomere lengths were comparable across treatment groups sexes. Mitochondrial copy number is a biomarker for mitochondrial function with decreased copy numbers associated with cardiometabolic disease traits. Mitochondrial copy numbers of aorta also showed no sex nor dose differences. In a second study, mice underwent one week of simulated microgravity by hindlimb unloading (HU) and then exposed to a single dose of 15 cGy of 5-ion GCR. HU was conducted for an additional two weeks following GCR exposure. Single factor exposure groups (HU or GCR only) also were included in the study. Euthanasia was then performed and the same tissues were collected. Protein levels of select inflammatory cytokines in the heart showed sex-dependent differences in expression. In the aorta, telomere lengths and mitochondrial copy number also showed sex differences. In summary, our results indicate differences between sexes in biomarkers related to cardiovascular health. Exposure to 5-ion GCR or HU, alone or in combination, did not result in changes in most of the cardiovascular biomarkers that were examined. However, in the heart, simulated space radiation at doses of 15 and 50 cGy led to long-term alterations in the expression levels of a small group of genes known to be associated with the progression of CVD. The long-term transcriptomic changes resulting from exposure to simulated space radiation should be carefully investigated to mitigate adverse cardiovascular events during and after deep space missions. Our results also highlight the importance of sex-specific strategies in monitoring and maintaining cardiovascular health during and after deep space missions.

cardiovascular↗
DOE OSTI2021

All-Atom Molecular Dynamics Simulations of the Temperature Response of Densely Grafted Polyelectrolyte Brushes

Water acts a “good” solvent for most polyelectrolyte (PE) systems due to its high dielectric strength. Theoretical and experimental studies have highlighted some remarkably unconventional properties of strongly water-swollen PE brushes such as a reduction in brush height with increase in temperature. However, an understanding of the atomistic-scale response of the grafted PE chains as well as the local arrangement and organization of the brush-supported counterions and water molecules to changes in temperature is missing. Here, we conduct an all-atom molecular dynamics (MD) study to probe the influence of temperature on the “microstructure” of densely grafted, fully ionized polyacrylic acid (PAA) brushes. The atomistic insights obtained from our study shed light on prior experimental observations and elucidate the key role played by changes in hydrogen bonding network in dictating the hydrophilicity of the brushes. In addition to the temperature-mediated reduction in height of the PE brush layer, we study the influence of temperature on several properties of the brush-supported water molecules such as the number distribution and kinetics of water-water and water-PE hydrogen bonds (HBs), mass density, orientational tetrahedral order parameter, and the activation energy associated with the self-diffusion of water. The effect of temperature on the properties of the brush-trapped counterions is also quantified via changes in their solvation structure, counterion-water radial distribution function (RDF), and the translational mobility. Our findings unravel several hitherto unknown phenomena such as the enhanced propensity for attaining PE brush-induced “water-in-salt”-like scenarios at elevated temperatures, and an increase in the activation energy for the self-diffusion of water with increase in the degree of PE brush-induced nanoconfinement (from ‘bulk water’ to ‘sparsely grafted PE brushes’ to ‘densely grafted PE brushes’). Further, we anticipate that this work will be helpful in improving our predictive capabilities of the temperature response of water-swollen PE brushes, which would be instrumental for better design of several PE brush systems used in a multitude of applications.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Modeling of Peptides with Classical and Novel Machine Learning Force Fields: A Comparison

The replacement of classical force fields (FFs) with novel neural-network-based frameworks is an emergent topic in molecular dynamics (MD) simulations. In contrast to classical FFs, which have proven their capability to provide insights into complex soft matter systems at an atomistic resolution, the machine learning (ML) potentials have yet to demonstrate their applicability for soft materials. However, the underlying philosophy, which is learning the energy of an atom in its surrounding chemical environment, makes this approach a promising tool. In particular for the exploration of novel chemical compounds, which have not been considered in the original parametrization of classical FFs. In this article, we study the performance of the ANI-2x ML model and compare the results with those of two classical FFs, namely, CHARMM27 and the GROMOS96 43a1 FF. We explore the performance of these FFs for bulk water and two model peptides, trialanine and a 9-mer of the α-aminoisobutyric acid, in vacuum and water. The results for water describe a highly ordered water structure, with a structure similar to those using ab initio molecular dynamics simulations. The energy landscape of the peptides described by Ramachandran maps show secondary structure basins similar to those of the classical FFs but differ in the position and relative stability of the basins. Details of the sampled structures show a divergent performance of the different models, which can be related either to the short-ranged nature of the ML potentials or to shortcomings of the underlying data set used for training. These findings highlight the current state of the applicability of ANI-2x ML potential for MD simulations of soft matter systems. Simultaneously, they provide insights for future improvements of current ML potentials.

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

Leveraging structure-informed machine learning for fast steric zipper propensity prediction across whole proteomes

Predicting the amyloid fold and the propensity of peptide segments to adopt amyloid-like structures remain a challenge. However, recent progress has facilitated structure-based prediction of steric zipper propensity and the use of machine learning to accelerate the calculation of predictive models across many scientific areas. Leveraging these advances, we have developed a new approach for rapid proteome-wide assessment of zipper profiles that is informed by four million steric zipper predictions collected over ten years. This collection is used to build a machine learning model capable of rapidly predicting steric zipper propensity, and allowing for the assessment of zippers at both the protein and proteome level. Our predictions show enrichment for zipper forming segments in proteins involved in cell wall reorganization in yeast, highlighting a potential category of interest for experimental characterization. Overall, our predictive model allows for the exploration of amyloid formation across the tree of life and provides a tool for assessment of both novel and designed sequences for zipper density.

Biochemistry & Molecular Biology↗
DOE OSTI2026

Nicotine-Inspired, De Novo-Designed SARS-CoV-2 Main Protease Inhibitors Reveal Unique Chemistry for Covalently Conjugating Both Cysteine and Histidine Residues in the Catalytic Dyad

Anecdotal reports about smokers with low SARS-CoV-2 infection rates prompted a search for nicotine and its pyrolysis products as SARS-CoV-2 main protease (M Pro ) inhibitors. From this search, 3-vinylpyridine was discovered as a weak binder for the M Pro S1 subsite and was used subsequently as a de novo starting point for covalent inhibitor design that quickly yielded a highly potent inhibitor, SR-A-174, with an IC 50 value of 60 nM. Representing a novel class of M Pro inhibitors, SR-A-174 features an N,N -diaryl-α,α-dichloroacetamide scaffold that facilitated rapid exploration of alternative covalent warheads and various N-substituents, leading to the identification of multiple inhibitors with potent antiviral activity. Eight such M Pro inhibitor structures were determined, all demonstrating covalent binding to catalytic Cys145 of M Pro . In six determined structures, binding is dominated by the covalent bond plus van der Waals contacts, which contrasts with the extensive hydrogen bond networks formed with peptidomimetic inhibitors such as nirmatrelvir. Strikingly, two N,N -diaryl-α,α-dichloroacetamide inhibitors exhibit an unprecedented dual covalent modification mode of the catalytic dyad, forming bonds to both Cys145 and His41 with a concomitant loss of both chlorides and displacing the inhibitors from the S1 subsite. This dyad-targeting reactivity suggests a novel route for bioconjugation of both cysteine and histidine.

SARS-CoV-2↗
DOE OSTI2025

The architecture of resilience: a genome assembly of Myrothamnus flabellifolia sheds light on desiccation tolerance and sex determination

Myrothamnus flabellifolia is a dioecious resurrection plant endemic to southern Africa that has become an important model for understanding desiccation tolerance. Despite its ecological and medicinal significance, genomic and transcriptomic resources for the species are limited. We generated a chromosome-level, haplotype-resolved reference genome assembly and annotation for M. flabellifolia and conducted transcriptomic profiling across a natural dehydration–rehydration time course in the field. Genome architecture and sex determination were characterized, and co-expression network and cis-regulatory element (CRE) enrichment analyses were used to investigate dynamic responses to desiccation. The 1.28-Gb genome exhibits unusually consistent chromatin architecture with unique chromosome organization across highly divergent haplotypes. We identified an XY sexual system with a small sex-determining region on Chromosome 8. Transcriptomic responses varied with dehydration severity, pointing to early suppression of growth, progressive activation of protective mechanisms, and subsequent return to homeostasis upon rehydration. Late embryogenesis abundant and early light-induced protein transcripts were dynamically regulated and showed enrichment of abscisic acid and stress-responsive CREs pointing toward conserved responses. Together, this study provides foundational resources for understanding the genomic architecture and reproductive biology of M. flabellifolia and offers new insights into the mechanisms of desiccation tolerance.

chromosome structure↗
NASA NTRS2002

Trends in lignin modification: a comprehensive analysis of the effects of genetic manipulations/mutations on lignification and vascular integrity

A comprehensive assessment of lignin configuration in transgenic and mutant plants is long overdue. This review thus undertook the systematic analysis of trends manifested through genetic and mutational manipulations of the various steps associated with monolignol biosynthesis; this included consideration of the downstream effects on organized lignin assembly in the various cell types, on vascular function/integrity, and on plant growth and development. As previously noted for dirigent protein (homologs), distinct and sophisticated monolignol forming metabolic networks were operative in various cell types, tissues and organs, and form the cell-specific guaiacyl (G) and guaiacyl-syringyl (G-S) enriched lignin biopolymers, respectively. Regardless of cell type undergoing lignification, carbon allocation to the different monolignol pools is apparently determined by a combination of phenylalanine availability and cinnamate-4-hydroxylase/"p-coumarate-3-hydroxylase" (C4H/C3H) activities, as revealed by transcriptional and metabolic profiling. Downregulation of either phenylalanine ammonia lyase or cinnamate-4-hydroxylase thus predictably results in reduced lignin levels and impaired vascular integrity, as well as affecting related (phenylpropanoid-dependent) metabolism. Depletion of C3H activity also results in reduced lignin deposition, albeit with the latter being derived only from hydroxyphenyl (H) units, due to both the guaiacyl (G) and syringyl (S) pathways being blocked. Apparently the cells affected are unable to compensate for reduced G/S levels by increasing the amounts of H-components. The downstream metabolic networks for G-lignin enriched formation in both angiosperms and gymnosperms utilize specific cinnamoyl CoA O-methyltransferase (CCOMT), 4-coumarate:CoA ligase (4CL), cinnamoyl CoA reductase (CCR) and cinnamyl alcohol dehydrogenase (CAD) isoforms: however, these steps neither affect carbon allocation nor H/G designations, this being determined by C4H/C3H activities. Such enzymes thus fulfill subsidiary processing roles, with all (except CCOMT) apparently being bifunctional for both H and G substrates. Their severe downregulation does, however, predictably result in impaired monolignol biosynthesis, reduced lignin deposition/vascular integrity, (upstream) metabolite build-up and/or shunt pathway metabolism. There was no evidence for an alternative acid/ester O-methyltransferase (AEOMT) being involved in lignin biosynthesis.The G/S lignin pathway networks are operative in specific cell types in angiosperms and employ two additional biosynthetic steps to afford the corresponding S components, i.e. through introduction of an hydroxyl group at C-5 and its subsequent O-methylation. [These enzymes were originally classified as ferulate-5-hydroxylase (F5H) and caffeate O-methyltransferase (COMT), respectively.] As before, neither step has apparently any role in carbon allocation to the pathway; hence their individual downregulation/manipulation, respectively, gives either a G enriched lignin or formation of the well-known S-deficient bm3 "lignin" mutant, with cell walls of impaired vascular integrity. In the latter case, COMT downregulation/mutation apparently results in utilization of the isoelectronic 5-hydroxyconiferyl alcohol species albeit in an unsuccessful attempt to form G-S lignin proper. However, there is apparently no effect on overall G content, thereby indicating that deposition of both G and S moieties in the G/S lignin forming cells are kept spatially, and presumably temporally, fully separate. Downregulation/mutation of further downstream steps in the G/S network [i.e. utilizing 4CL, CCR and CAD isoforms] gives predictable effects in terms of their subsidiary processing roles: while severe downregulation of 4CL gave phenotypes with impaired vascular integrity due to reduced monolignol supply, there was no evidence in support of increased growth and/or enhanced cellulose biosynthesis. CCR and CAD downregulation/mutations also established that a depletion in monolignol supply reduced both lignin contents supply reduced both lignin contents and vascular integrity, with a concomitant shift towards (upstream) metabolite build-up and/or shunting.The extraordinary claims of involvement of surrogate monomers (2-methoxybenzaldehyde, feruloyl tyramine, vanillic acid, etc.) in lignification were fully disproven and put to rest, with the investigators themselves having largely retracted former claims. Furthermore analysis of the well-known bm1 mutation, a presumed CAD disrupted system, apparently revealed that both G and S lignin components were reduced. This seems to imply that there is no monolignol specific dehydrogenase, such as the recently described sinapyl alcohol dehydrogenase (SAD) for sinapyl alcohol formation. Nevertheless, different CAD isoforms of differing homology seem to be operative in different lignifying cell types, thereby giving the G-enriched and G/S-enriched lignin biopolymers, respectively. For the G-lignin forming network, however, the CAD isoform is apparently catalytically less efficient with all three monolignols than that additionally associated with the corresponding G/S lignin forming network(s), which can more efficiently use all three monolignols. However, since CAD does not determine either H, G, or S designation, it again serves in a subsidiary role-albeit using different isoforms for different cell wall developmental and cell wall type responses.The results from this analysis contrasts further with speculations of some early investigators, who had viewed lignin assembly as resulting from non-specific oxidative coupling of monolignols and subsequent random polymerization. At that time, though, the study of the complex biological (biochemical) process of lignin assembly had begun without any of the (bio)chemical tools to either address or answer the questions posed as to how its formation might actually occur. Today, by contrast, there is growing recognition of both sophisticated and differential control of monolignol biosynthetic networks in different cell types, which serve to underscore the fact that complexity of assembly need not be confused any further with random formation. Moreover, this analysis revealed another factor which continues to cloud interpretations of lignin downregulation/mutational analyses, namely the serious technical problems associated with all aspects of lignin characterization, whether for lignin quantification, isolation of lignin-enriched preparations and/or in determining monomeric compositions. For example, in the latter analyses, some 50-90% of the lignin components still cannot be detected using current methodologies, e.g. by thioacidolysis cleavage and nitrobenzene oxidative cleavage. This deficiency in lignin characterization thus represents one of the major hurdles remaining in delineating how lignin assembly (in distinct cell types) and their configuration actually occurs.

Review, Academic↗