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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 415 records · Page 23
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Protein3D: Enabling analysis and extraction of metal‐containing sites from the Protein Data Bank with molSimplify

Abstract Metalloenzymes catalyze a wide range of chemical transformations, with the active site residues playing a key role in modulating chemical reactivity and selectivity. Unlike smaller synthetic catalysts, a metalloenzyme active site is embedded in a larger protein, which makes interrogation of electronic properties and geometric features with quantum mechanical calculations challenging. Here we implement the ability to fetch crystallographic structures from the Protein Data Bank and analyze the metal binding sites in the program molSimplify. We show the usefulness of the newly created protein3D class to extract the local environment around non‐heme iron enzymes containing a two histidine motif and prepare 372 structures for quantum mechanical calculations. Our implementation of protein3D serves to expand the range of systems molSimplify can be used to analyze and will enable high‐throughput study of metal‐containing active sites in proteins.

Edholm, Freya↗
DOE OSTI2025

Influence of Steric and Electronic Properties of P2 Groups on Covalent Inhibitor Binding to SARS-CoV-2 Main Protease

The main protease (MPro) of SARS-CoV-2 is a critical enzyme required for viral replication, making it a prime target for antiviral drug development. Covalent inhibitors, which form a stable interaction with the catalytic C145, have demonstrated strong inhibition of MPro, but the influence of steric and electronic properties of P2 substituents, designed to engage the S2 substrate-binding subsite within the MPro active site, on inhibitor binding affinity remains underexplored. Here, in this study, we design and characterize two hybrid covalent inhibitors, BBH-3 and BBH-4, and present their X-ray crystallographic structures in complex with MPro, providing molecular insights into how their distinct P2 groups, a dichlorobenzyl moiety in BBH-3 and an adamantyl substituent in BBH-4, affect binding conformation and active site adaptability. Comparative structural analyses with previously characterized inhibitors, including BBH-2 and Mcule-5948770040, reveal how the P2 bulkiness and electronic properties influence active site dynamics, particularly through interactions with the S2 and S5 subsites. The P2 group of BBH-3 induces conformational shifts in the S2 helix and the S5 loop, while BBH-4 displaces M49, stabilizing its binding through hydrophobic interactions. Isothermal titration calorimetry further elucidates the impact of P2 modifications on inhibitor affinity, revealing a delicate balance between enthalpic and entropic contributions. The data demonstrate that BBH-3 exhibits less favorable binding, affirming that dichlorobenzyl substitution at the P2 position has a more negative impact on the affinity for MPro than bulky saturated cyclic groups. This underscores the feature that MPro active site malleability may be accompanied by a conformational strain.

SARS-CoV-2↗
DOE OSTI2024

Cascade CO 2 Insertion in Carbanion Ionic Liquids Driven by Structure Rearrangement

The CO 2 chemisorption in state-of-the-art sorbents based on oxide/hydroxide/amine moieties is driven by strong chemical bonding formation in the carbonate/bicarbonate/carbamate products, which in turn leads to high energy input in sorbent regeneration. In addition, the CO 2 uptake capacity was limited by the active sites’ utilization efficiency, with each active site incorporating one CO 2 molecule or less. In this work, a new concept and generation of sorbent was developed to achieve cascade insertion of multiple CO 2 molecules by leveraging structure rearrangement as the driving force, leading to in situ generation of extra CO 2 -binding sites and significantly reduced energy input for CO 2 release. The designed ionic liquids (ILs) containing carbanions with conjugated and asymmetric structure, deprotonated (methylsulfonyl)acetonitrile ([MSA]) anion, allowed the cascade insertion of two CO 2 molecules via consecutive C–C and O–C bond formations. The proton transfer and structure rearrangement of the carboxylic acid intermediates played critical roles in stabilizing the first integrated CO 2 and generating extra electron-rich oxygen sites for the insertion of the second CO 2 . The structure variation and reaction pathway were confirmed by operando spectroscopy, magnetic resonance spectroscopy (NMR), mass spectroscopy, and computational chemistry. The energy input in sorbent regeneration could be further reduced by harnessing the phase-changing behavior of the carbanion salts in ether solutions upon reacting with CO 2 , avoiding the energy consumption in heating the solvent. In conclusion, the fundamental insights obtained herein provide a promising approach to greatly improve the CO 2 sorption performance via sophisticated molecular-scale structural engineering of the sorbents.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2024

Mechanistic study of direct coupling of CO 2 and C 2 H 4 over atomically dispersed metal at graphene edges

Direct coupling of CO 2 and ethylene (hereinafter DCCE) to acrylic acid is valuable for valorizing CO 2 to manufacture acrylate-derived products. However, previous studies in DCCE have been limited on molecular catalysts with challenges in improving catalytic performance. In this work, we employed density functional theory calculations and ab initio molecular dynamics simulations to investigate the heterogeneous catalysis of DCCE over atomically dispersed metal centers at nitrogen-doped zigzag edge of graphene. Based on competitive adsorption and structural stability, Mo, Cr, V, Ru, and Ni active sites are chosen to explore the reaction kinetics. Here, we find that the activation barriers are determined by the charge redistribution at transition states, which explains the trend of activity for the C-C coupling and the hydrogen transfer, two key steps in DCCE. Furthermore, we show that the intramolecular hydrogen transfer (rate-limiting step) is hindered due to the lack of local coordinate at the active sites. We thus propose to use co-adsorbed water as a “proton-exchanger” following a water-assisted route, and show that the activation barriers are reduced over all metal centers. Particularly, water promotes the hydrogen transfer over metals with strong CO 2 -ethylene co-activation and facile C-C coupling kinetics, which could be considered promising for DCCE. In both mechanisms, the stability of metallactone intermediate can be used to predict the catalytic activity. It is anticipated that the insights from this work can provide guidelines for mimicking well-defined multifunctional active sites in molecular catalysts to design heterogeneous catalysts for such C-C coupling, which advances catalytic utilization of CO 2 .

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

Tunable Oxygen Reduction Electrocatalysis by Phenazine-Modified Carbons (Final Report)

This project aims to systematically investigate the fundamental interfacial chemistry that underlies the four-electron, four-proton oxygen reduction reaction (ORR) mediated by heteroatom-doped graphitic carbon electrodes. Heteroatom-doped (Fe, N, etc.) graphitic carbons have emerged as a rich class of materials that are promising ORR catalysts in low temperature fuel cells because of their earth-abundant elements, extremely low cost, environmental harmlessness, and high tolerance to impurities in the fuel stream. However, despite decades of research, systematic efforts to improve the activity, selectivity, and durability of these catalysts has been hampered both by a complex heterogeneous distribution of potential N- and Fe-dopant active sites and by the inability to tune the local electronic structure and environment of the active site with molecular precision. Understanding the fundamental chemistry that influences the turnover-limiting and selectivity determining steps for ORR and other multielectron/multiproton electrocatalytic transformations requires new and innovative methods to prepare heteroatom active sites with molecular precision on carbon surfaces.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
NASA NTRS1985

Method for measuring surface activity of silicon nitride powder

Amorphous, alpha-, and beta-Si3N4 powders were activated by vibration ball milling in purified MeOH, and the surface activity of ground powders was determined by the temperature programmed desorption (TPD) method using NH3 gas. The concentration of active sites with a potential energy equivalent to the peak temperature in the spectrum increased was markedly by ball milling the amorphous Si3N4. The alpha- and beta-Si3N4 also had active sites produced by ball milling. The concentration of active site increased with increased ball milling time. A method for measuring surface activity of ceramic raw materials by TPD is proposed.

Kanno, Y.↗
DOE OSTI2021

Increasing the Hot‐Electron Driven Hydrogen Evolution Reaction Rate on a Metal‐Free Graphene Electrode

Abstract Recently, it has been shown that a semiconductor–insulator–graphene device can drive the hydrogen evolution reaction (HER) at the graphene surface with a reduced onset potential by injecting hot electrons into graphene. However, the catalytic properties of graphene are limited by the large hydrogen adsorption energy and lack of electrochemically active sites. To address these limitations, a n ‐silicon/insulator/plasma etched graphene device is investigated, where a dry etch process is used to increase the number of active sites on the graphene by creating a greater number of active edge sites, increasing hydrogen adsorption at a given potential. This has been shown to improve the properties of devices with cold electrons. However, here it is shown that this approach can improve the HER rate with hot electrons. The electrons injected into the graphene from the silicon shift the onset potential of HER by as high as ≈0.8 V reaching a current density of 90 mA cm −2 at an overpotential of ‐0.5 V versus RHE. Furthermore, the comparison between device with pristine graphene shows a ≈2X improvement in current density at high overpotentials. This result shows that hot‐electron devices can be improved by modifying the catalytically active sites without metal catalysts.

Chae, Hyun Uk↗
DOE OSTI2025

High-resolution X-ray structure of Gln143Asn manganese superoxide dismutase captures multiple hydrogen peroxide-binding sites

Human mitochondrial manganese superoxide dismutase (MnSOD) converts superoxide into hydrogen peroxide and molecular oxygen, serving as a key defence against oxidative damage. Despite extensive studies, the full structural characterization of H 2 O 2 -binding sites in MnSOD remains largely unexplored. Previous H 2 O 2 -soaked MnSOD structures have identified two distinct H 2 O 2 -binding sites: one directly ligated to the catalytic manganese (LIG position) and another at the active-site gateway (PEO position) between the second-shell residues Tyr34 and His30. In this study, a kinetically impaired Gln143Asn MnSOD variant is used to trap and explore additional H 2 O 2 -binding sites beyond the second-shell solvent gate. In the wild-type enzyme, Gln143 mediates proton transfers with the manganese-bound solvent (WAT1) to drive redox cycling of the metal, which is necessary for effective superoxide dismutation. Substitution with Asn stalls catalysis because the increased distance from WAT1 disrupts critical proton-coupled electron-transfer (PCET) events, and the redox cycling of the active-site metal is impaired. This, in turn, stalls the electrostatic cycling of positive charge on the enzyme surface and enhances the likelihood of trapping transient H 2 O 2 -bound states in this variant. The results reveal several H 2 O 2 molecules leading up to the active site, in addition to the canonical LIG and PEO positions.

Dasgupta, Medhanjali [University of Nebraska Medic↗
NASA NTRSDate not supplied

Computational Investigation of Oxidative Etch Pitting in FiberForm and Its Impact on Material Properties

Oxidation-driven carbon erosion does not occur uniformly but rather through the development of localized etch pits at active surface sites. These active sites form due to atomic defects on the carbon surface, making them significantly more reactive than the surrounding, non-defective areas. As a result, these sites are the first to react during ablation, leading to their removal. This process creates new defects in neighboring atoms, increasing their reactivity and causing localized carbon removal around these active sites. In this way, the highly reactive defective areas serve as nucleation points for the formation and growth of etch pits, which can have adverse effects on structural integrity of FiberForm. To better understand how these etch pits impact the material properties of carbon fiber microstructures, we have developed a new capability within the direct simulation Monte Carlo (DSMC) framework to capture the etch pit formation process. This capability, integrated into the DSMC code SPARTA (Stochastic Parallel Rarefied-gas Time-accurate Analyzer), models material removal in the presence of active sites, leading to the formation of etch pits. The current work focuses on studying the effects of these etch pits on the material properties of FiberForm, a widely used base material in thermal protection systems (TPS). The microstructure of virgin FiberForm, obtained via X-ray microtomography, is imported into SPARTA to generate the ablated geometries with etch pits. These modified microstructures are then analyzed using the Porous Microstructure Analysis (PuMA) software to compute various material properties, including elasticity, thermal conductivity, and permeability. We investigate the variation of these properties due to the complex surface topology changes caused by etch pit formation. Additionally, we compare the effects of pitting with the conventional model of shrinking fibers, traditionally used to simulate the ablation of carbon structures. Significant differences emerge between the two approaches. Consequently, this physically realistic model of material removal through etch pit formation offers improved accuracy in predicting the degradation of carbon-based TPS during oxidation. It also provides insights into other mechanisms, such as spallation, where chunks of material are removed into the flow due to etch pit growth. Ultimately, this model enhances our understanding of failure modes in these materials during ablation.

PuMA↗
DOE OSTI2022

Explaining the structure sensitivity of Pt and Rh for aqueous-phase hydrogenation of phenol

Phenol is an important model compound to understand the thermocatalytic (TCH) and electrocatalytic hydrogenation (ECH) of biomass to biofuels. Although Pt and Rh are among the most studied catalysts for aqueous-phase phenol hydrogenation, the reason why certain facets are active for ECH and TCH is not fully understood. Herein, we identify the active facet of Pt and Rh catalysts for aqueous-phase hydrogenation of phenol and explain the origin of the size-dependent activity trends of Pt and Rh nanoparticles. Phenol adsorption energies extracted on the active sites of Pt and Rh nanoparticles on carbon by fitting kinetic data show that the active sites adsorb phenol weakly. We predict that the turnover frequencies (TOFs) for the hydrogenation of phenol to cyclohexanone on Pt(111) and Rh(111) terraces are higher than those on (221) stepped facets based on density functional theory modeling and mean-field microkinetic simulations. The higher activities of the (111) terraces are due to lower activation energies and weaker phenol adsorption, preventing high coverages of phenol from inhibiting hydrogen adsorption. We measure that the TOF for ECH of phenol increases as the Rh nanoparticle diameter increases from 2 to 10 nm at 298 K and -0.1 V vs the reversible hydrogen electrode, qualitatively matching prior reports for Pt nanoparticles. The increase in experimental TOFs as Pt and Rh nanoparticle diameters increase is due to a larger fraction of terraces on larger particles. These findings clarify the structure sensitivity and active site of Pt and Rh for the hydrogenation of phenol and will inform the catalyst design for the hydrogenation of bio-oils.

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

Diversity in the Common Fold: Structural Insights into Class D β-Lactamases from Gram-Negative Pathogens

Class D β-lactamases (DBLs) represent a major threat to antibiotic efficacy by hydrolyzing β-lactam drugs, including last-resort carbapenems, thereby driving antimicrobial resistance in Gram-negative bacteria. The enzymes share a structurally conserved two-domain α/β architecture with seven active-site motifs and three flexible extended loops (the P-loop, Ω-loop, and newly designated B-loop) that surround the active site. While each of these loops is known to influence enzyme function, their coordinated roles have not been fully elucidated. To investigate the significance of their interplay, we compared the sequences and crystal structures of 40 DBLs from clinically relevant Gram-negative pathogens and performed molecular dynamics simulations on selected representatives. Combined structural and dynamical analyses revealed a strong correlation between B-loop architecture and carbapenemase activity in the pathogens Klebsiella and Acinetobacter, particularly regarding loop length and spatial organization. These findings emphasize the B-loop’s critical contribution, in concert with the P- and Ω-loops, in tuning active site versatility, substrate recognition, catalytic activity, and structural stability. A deeper understanding of how these motifs and loops govern DBL function may inform the development of novel antibiotics and inhibitors targeting this class of enzymes.

antibiotic resistance↗
DOE OSTI2024

Structural and mechanistic insights into activation of the human RNA ligase RTCB by Archease

Abstract RNA ligases of the RTCB-type play an essential role in tRNA splicing, the unfolded protein response and RNA repair. RTCB is the catalytic subunit of the pentameric human tRNA ligase complex. RNA ligation by the tRNA ligase complex requires GTP-dependent activation of RTCB. This active site guanylylation reaction relies on the activation factor Archease. The mechanistic interplay between both proteins has remained unknown. Here, we report a biochemical and structural analysis of the human RTCB-Archease complex in the pre- and post-activation state. Archease reaches into the active site of RTCB and promotes the formation of a covalent RTCB-GMP intermediate through coordination of GTP and metal ions. During the activation reaction, Archease prevents futile RNA substrate binding to RTCB. Moreover, monomer structures of Archease and RTCB reveal additional states within the RNA ligation mechanism. Taken together, we present structural snapshots along the reaction cycle of the human tRNA ligase.

Science & Technology - Other Topics↗
DOE OSTI2021

Transformation of Highly Stable Pt Single Sites on Defect Engineered Ceria into Robust Pt Clusters for Vehicle Emission Control

Engineering surface defects on metal oxide supports could help promote the dispersion of active sites and catalytic performance of supported catalysts. Herein, a strategy of ZrO 2 doping was proposed to create rich surface defects on CeO 2 (CZO) and, with these defects, to improve Pt dispersion and enhance its affinity as single sites to the CZO support (Pt/CZO). The strongly anchored Pt single sites on CZO support were initially not efficient for catalytic oxidation of CO/C 3 H 6 . However, after a simple activation by H 2 reduction, the catalytic oxidation performance over Pt/CZO catalyst was significantly boosted and better than Pt/CeO 2 . Pt/CZO catalyst also exhibited much higher thermal stability. The structural evolution of Pt active sites by H 2 treatment was systematically investigated on aged Pt/CZO and Pt/CeO 2 catalysts. With H 2 reduction, ionic Pt single sites were transformed into active Pt clusters. Much smaller Pt clusters were created on CZO (ca. 1.2 nm) than on CeO 2 (ca. 1.8 nm) due to stronger Pt-CeO 2 interaction on aged Pt/CZO. Consequently, more exposed active Pt sites were obtained on the smaller clusters surrounded by more oxygen defects and Ce 3+ species, which directly translated to the higher catalytic oxidation performance of activated Pt/CZO catalyst in vehicle emission control applications.

36 MATERIALS SCIENCE↗
DOE OSTI2020

Visualizing group II intron dynamics between the first and second steps of splicing

Group II introns are ubiquitous self-splicing ribozymes and retrotransposable elements evolutionarily and chemically related to the eukaryotic spliceosome, with potential applications as gene-editing tools. Recent biochemical and structural data have captured the intron in multiple conformations at different stages of catalysis. Here, we employ enzymatic assays, X-ray crystallography, and molecular simulations to resolve the spatiotemporal location and function of conformational changes occurring between the first and the second step of splicing. We show that the first residue of the highly-conserved catalytic triad is protonated upon 5’-splice-site scission, promoting a reversible structural rearrangement of the active site (toggling). Protonation and active site dynamics induced by the first step of splicing facilitate the progression to the second step. Our insights into the mechanism of group II intron splicing parallels functional data on the spliceosome, thus reinforcing the notion that these evolutionarily-related molecular machines share the same enzymatic strategy.

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

Structural Insights into the Dynamics of Water in SOD1 Catalysis and Drug Interactions

Superoxide dismutase 1 (SOD1) is a crucial enzyme that protects cells from oxidative damage by converting superoxide radicals into H 2 O 2 and O 2 . This detoxification process, essential for cellular homeostasis, relies on a precisely orchestrated catalytic mechanism involving the copper cation, while the zinc cation contributes to the structural integrity of the enzyme. This study presents the 2.3 Å crystal structure of human SOD1 (PDB ID: 9IYK), revealing an assembly of six homodimers and twelve distinct active sites. The water molecules form a complex hydrogen-bonding network that drives proton transfer and sustains active site dynamics. Our structure also uncovers subtle conformational changes that highlight the intrinsic flexibility of SOD1, which is essential for its function. Additionally, we observe how these dynamic structural features may be linked to pathological mutations associated with amyotrophic lateral sclerosis (ALS). By advancing our understanding of hSOD1’s mechanistic intricacies and the influence of water coordination, this study offers valuable insights for developing therapeutic strategies targeting ALS. Our structure’s unique conformations and active site interactions illuminate new facets of hSOD1 function, underscoring the critical role of structural dynamics in enzyme catalysis. Moreover, we conducted a molecular docking analysis using SOD1 for potential radical scavengers and Abelson non-receptor tyrosine kinase (c-Abl, Abl1) inhibitors targeting misfolded SOD1 aggregation along with oxidative stress and apoptosis, respectively. The results showed that CHEMBL1075867, a free radical scavenger derivative, showed the most promising docking results and interactions at the binding site of hSOD1, highlighting its promising role for further studies against SOD1-mediated ALS.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Impact of microkinetic modeling assumptions on predicted kinetics and mechanisms over undercoordinated sites

Accurate modeling of catalytic reactions on undercoordinated sites requires accounting for the structural and ensemble-specific nature of the active sites. This study examines how common microkinetic modeling (MKM) assumptions affect predicted kinetics and mechanisms on the stepped Pt(211) facet for the ethane dehydrogenation (EDH) and the ethane hydrogenolysis (EH). Six (211) MKMs were developed, differing in (i) the number of active sites represented, (ii) adsorbate site occupancy treatment, and (iii) inclusion of cross-facet interactions. These models are benchmarked against a particle-based microkinetic model (PB-MKM), which best represents step-edge behavior. MKM assumptions caused deviations in turnover frequencies exceeding ten orders of magnitude and led to contrasting mechanistic and selectivity predictions. Multi-site MKMs overestimate activity by inflating free site availability, single-site models underestimate activity, and uniform occupancy models overpredict coverage of multi-dentate intermediates, leading to reaction-specific artifacts. Overall, the Combined Site Edge Model (CSEM), a single-site MKM accounting for site occupancy and cross-facet interactions, most closely approximates PB-MKM predictions. All models predict similar kinetics when surfaces are clean or primarily occupied by monodentate species. This work provides practical guidance for selecting MKM frameworks for undercoordinated catalytic surfaces and highlights the critical role of modeling assumptions in catalytic predictions.

(211) facet↗
DOE OSTI2022

Conserved conformational dynamics determine enzyme activity

Homologous enzymes often exhibit different catalytic rates despite a fully conserved active site. The canonical view is that an enzyme sequence defines its structure and function and, more recently, that intrinsic protein dynamics at different time scales enable and/or promote catalytic activity. Here, we show that, using the protein tyrosine phosphatase PTP1B, residues surrounding the PTP1B active site promote dynamically coordinated chemistry necessary for PTP1B function. However, residues distant to the active site also undergo distinct intermediate time scale dynamics and these dynamics are correlated with its catalytic activity and thus allow for different catalytic rates in this enzyme family. We identify these previously undetected motions using coevolutionary coupling analysis and nuclear magnetic resonance spectroscopy. Our findings strongly indicate that conserved dynamics drives the enzymatic activity of the PTP family. Characterization of these conserved dynamics allows for the identification of novel regulatory elements (therapeutic binding pockets) that can be leveraged for the control of enzymes.

59 BASIC BIOLOGICAL SCIENCES↗