Search NASA⌕ Search

SEARCH · Search NASA

Results for “direct counts”

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.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Scalable self attraction and loading calculations for unstructured ocean tide models

Self attraction and earth-loading effects are important for accurately modeling global tides. A common approach of handling this forcing is to expand mass anomalies into spherical harmonics, which are scaled by load Love numbers to account for elastic earth deformation. We investigate two different approaches to perform these calculations for ocean models that employ unstructured meshes and distributed memory parallelization. The first approach leverages a highly efficient spherical harmonics library, but requires all-to-one and one-to-all communications and interpolation operations between the unstructured and a structured mesh. This approach is compared to a parallel algorithm that computes the spherical harmonic transformations directly on the unstructured mesh with an all-reduce communication. Here, our results show that although the unstructured mesh calculations are more expensive, the scalability of the unstructured mesh approach allows for more efficient spherical harmonics transforms for high-resolution meshes and large processor counts. This methodology enables the efficient inclusion of tidal dynamics large-scale Earth system model simulations.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2026

Identifying neutron sources using recoil and time-of-flight spectroscopy

Identification of neutron sources is central to nuclear physics and its applications, from planetary science to nuclear security, yet direct source discrimination from measured neutron spectra remains fundamentally elusive. Here, we introduce a Bayesian protocol that directly infers source ensembles from measured neutron spectra by combining full-spectrum template matching with probabilistic evidence evaluation. Applying this protocol to recoil and time-of-flight spectroscopy, we recover single- and two-source configurations with strong statistical significance (beyond 4⁢𝜎) at event counts as low as ∼10 3 . These results demonstrate that neutron spectral signatures can be leveraged for robust source identification, opening a new observational window for both fundamental research and operationally driven applications.

neutron physics↗
DOE OSTI2025

Discriminator Threshold Study for Scint 1

During electronics testing at NSRL, the fluence/spill is recorded from the QC1 chamber. This chamber, which is a permanent fixture on the NSRL beamline, requires calibration from an external radiation detector that can measure ion flux directly. A 1.0 × 1.0 × 0.5 cm 3 scintillator is used at the testing location to calibrate all NSRL beams for electronic experiments. A calibration factor is derived by comparing the ions observed by the scintillator and QC1 during an exposure of at least 10 5 scintillator counts or total ions.

43 PARTICLE ACCELERATORS↗
DOE OSTI2024

The 4D Camera: An 87 kHz Direct Electron Detector for Scanning/Transmission Electron Microscopy

We describe the development, operation, and application of the 4D Camera—a 576 by 576 pixel active pixel sensor for scanning/transmission electron microscopy which operates at 87,000 Hz. The detector generates data at ~480 Gbit/s which is captured by dedicated receiver computers with a parallelized software infrastructure that has been implemented to process the resulting 10–700 Gigabyte-sized raw datasets. The back illuminated detector provides the ability to detect single electron events at accelerating voltages from 30 to 300 kV. Through electron counting, the resulting sparse data sets are reduced in size by 10--300× compared to the raw data, and open-source sparsity-based processing algorithms offer rapid data analysis. The high frame rate allows for large and complex scanning diffraction experiments to be accomplished with typical scanning transmission electron microscopy scanning parameters.

47 OTHER INSTRUMENTATION↗
DOE OSTI2020

Economic Model for Estimation of GDP Losses in the MACCS Offsite Consequence Analysis Code

The MACCS (MELCOR Accident Consequence Code System) code is the U.S. Nuclear Regulatory Commission (NRC) tool used to perform probabilistic health and economic consequence assessments for atmospheric releases of radionuclides. It is also used by international organizations, both reactor owners and regulators. It is intended and most commonly used for hypothetical accidents that could potentially occur in the future rather than to evaluate past accidents or to provide emergency response during an ongoing accident. It is designed to support probabilistic risk and consequence analyses and is used by the NRC, U.S. nuclear licensees, the Department of Energy, and international vendors, licensees, and regulators. This report describes the modeling framework, implementation, verification, and benchmarking of a GDP-based model for economic losses that has recently been developed as an alternative to the original cost-based economic loss model in MACCS. The GDP-based model has its roots in a code developed by Sandia National Laboratories for the Department of Homeland Security to estimate short-term losses from natural and manmade accidents, called the Regional Economic Accounting analysis tool (REAcct). This model was adapted and modified for MACCS and is now called the Regional Disruption Economic Impact Model (RDEIM). It is based on input-output theory, which is widely used in economic modeling. It accounts for direct losses to a disrupted region affected by an accident, indirect losses to the national economy due to disruption of the supply chain, and induced losses from reduced spending by displaced workers. RDEIM differs from REAcct in its treatment and estimation of indirect loss multipliers, elimination of double counting associated with inter-industry trade in the affected area, and that it is designed to be used to estimate impacts for extended periods that can occur from a major nuclear reactor accident, such as the one that occurred at the Fukushima Daiichi site in Japan. Most input-output models do not account for economic adaptation and recovery, and in this regard RDEIM differs from its parent, REAcct, because it allows for a user-definable national recovery period. Implementation of a recovery period was one of several recommendations made by an independent peer review panel to ensure that RDEIM is state-of-practice. For this and several other reasons, RDEIM differs from REAcct. Both the original and the RDEIM economic loss models account for costs from evacuation and relocation, decontamination, depreciation, and condemnation. Where the original model accounts for an expected rate of return, based on the value of property, that is lost during interdiction, the RDEIM model instead accounts for losses of GDP based on the industrial sectors located within a county. The original model includes costs for disposal of crops and milk that the RDEIM model currently does not, but these costs tend to contribute insignificantly to the overall losses. This document discusses three verification exercises to demonstrate that the RDEIM model is implemented correctly in MACCS. It also describes a benchmark study at five nuclear power plants chosen to represent the spectrum of U.S. commercial sites. The benchmarks provide perspective on the expected differences between the RDEIM and the original cost-based economic loss models. The RDEIM model is shown to consistently predict larger losses than the original model, probably in part because it accounts for national losses by including indirect and induced losses; whereas, the original model only accounts for regional losses. Nonetheless, the RDEIM model predicts losses that are remarkably consistent with the original cost-based model, differing by 16% at most for the five sites combined with three source terms considered in this benchmark.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗
DOE OSTI2026

Digital Silicon Photomultiplier Chip Testing

Silicon Photomultipliers (SiPMs) are highly sensitive photodetectors. Traditional analog SiPMs require complex external readout electronics. Digital SiPMs (dSiPMs) include digital readout circuitry directly on-chip, offering superior timing resolution, reduced power consumption and compact size, pixel-level masking for active noise reduction. The primary objectives of this study are to, verify digital logic integrity of the shift registers used for controlling the pixel masking circuit, and determine the dark count rate of individual pixels as a function of bias voltage and clock frequency. I observe and explain behavior of the shift register and counting circuit.

Graham, Bennett [U. Chicago (main)]↗
DOE OSTI2021

Signature Analysis Utilizing a Dynamic Molten Salt Reactor Model for MC&A

Moving from traditional fixed fuel nuclear reactor systems to a mobile, dynamic fuel system that has dissolved special nuclear material in a molten salt is a paradigm shift in several respects. One major consideration is how to develop effective nuclear material controls and accounting for these novel reactor systems. The Molten Salt Reactor Experiment is one example of a critical molten salt system and provided a significant reference library based on the documented effort. But it was low thermal power that was not intended to reflect a commercial scale electricity production design. Therefore, to facilitate and assist vendors with domestic licensing considerations, research is underway to identify methods that could be used for domestic safeguards approaches for these novel reactor systems. This research presents the results of a signature analysis of data generated from three simulated scenarios using the molten salt demonstration reactor model defined in the Transient Simulation Framework of Reconfigurable Modules. Each scenario provides 1 hour isotope inventories over a 180 day period. The scenarios investigated provide test cases to examine if direct gamma-ray spectroscopy of the fuel can be used to identify changes comparing a base case (no reactivity control and fixed fission contribution) to an insertion of reactivity (10 pcm no change in fission composition) and a change in fission composition. The analysis demonstrates that monitoring the total count rate in a highly collimated high-resolution photon energy spectrum is sensitive to perturbations imposed into the reactor model. The total photon count rate changes ≈2% for the fission composition change and ≈4.5% for the reactivity insertion compared to the base case. However, both scenarios show an increase in the total photon count rate. The total photon count rate can be used to identify changes due to power (number of fissions) but not due to a change in the material undergoing fission. To distinguish between the two cases of increased power, the photon spectrum would require an intensive analysis technique. A photon peak count rate ratio analysis could be used to identify changes in the fissile material fission generation in the core through identification of a static peak that shows little variation to the source of fission and a highly varying peak. The photon peak strength will ultimately be determined by the isotope’s fission yield. A preliminary analysis investigating the coupling of the isotope’s fission yield and its concentration in the fuel salt derived from the modeling has been performed. A ratio analysis of the photon peak count rates of 140 La to 99 Mo demonstrated that the reactivity insertion creates a distinct difference in the ratio compared to the fission composition change scenario.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗
DOE OSTI2022

Updated Economic Model for Estimation of GDP Losses in the MACCS Offsite Consequence Analysis Code RDEIM Model Report for MACCS v4.2

This report updates the Regional Disruption Economic Impact Model (RDEIM) GDP-based model described in Bixler et al. (2020) used in the MACCS accident consequence analysis code. MACCS is the U.S. Nuclear Regulatory Commission (NRC) used to perform probabilistic health and economic consequence assessments for atmospheric releases of radionuclides. It is also used by international organizations, both reactor owners and regulators. It is intended and most commonly used for hypothetical accidents that could potentially occur in the future rather than to evaluate past accidents or to provide emergency response during an ongoing accident. It is designed to support probabilistic risk and consequence analyses and is used by the NRC, U.S. nuclear licensees, the Department of Energy, and international vendors, licensees, and regulators. The update of the RDEIM model in version 4.2 expresses the national recovery calculation explicitly, rather than implicitly as in the previous version. The calculation of the total national GDP losses remains unchanged. However, anticipated gains from recovery are now allocated across all the GDP loss types – direct, indirect, and induced – whereas in version 4.1, all recovery gains were accounted for in the indirect loss type. To achieve this, we’ve introduced new methodology to streamline and simplify the calculation of all types of losses and recovery. In addition, RDEIM includes other kinds of losses, including tangible wealth. This includes loss of tangible assets (e.g., depreciation) and accident expenditures (e.g., decontamination). This document describes the updated RDEIM economic model and provides examples of loss and recovery calculation, results analysis, and presentation. Changes to the tangible cost calculation and accident expenditures are described in section 2.2. The updates to the RDEIM input-output (I-O) model are not expected to affect the final benchmark results Bixler et al. (2020), as the RDEIM calculation for the total national GDP losses remains unchanged. The reader is referred to the MACCS revision history for other cost modelling changes since version 4.0 that may affect the benchmark. RDEIM has its roots in a code developed by Sandia National Laboratories for the Department of Homeland Security to estimate short-term losses from natural and manmade accidents, called the Regional Economic Accounting analysis tool (REAcct). This model was adapted and modified for MACCS. It is based on I-O theory, which is widely used in economic modeling. It accounts for direct losses to a disrupted region affected by an accident, indirect losses to the national economy due to disruption of the supply chain, and induced losses from reduced spending by displaced workers. RDEIM differs from REAcct in in its treatment and estimation of indirect loss multipliers, elimination of double-counting associated with inter-industry trade in the affected area, and that it is intended to be used for extended periods that can occur from a major nuclear reactor accident, such as the one that occurred at the Fukushima Daiichi site in Japan. Most input-output models do not account for economic adaptation and recovery, and in this regard RDEIM differs from its parent, REAcct, because it allows for a user-definable national recovery period. Implementation of a recovery period was one of several recommendations made by an independent peer review panel to ensure that RDEIM is state-of-practice. For this and several other reasons, RDEIM differs from REAcct.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗
DOE OSTI2022

A safeguards approach for molten salt reactors: Direct gamma-spectrometry of 233 U

Multidimensional gamma-spectrometry is a potential solution for safeguarding future thorium-fueled molten salt reactors (MSRs). A high-sensitivity system developed at Pacific Northwest National Laboratory (PNNL), the Advanced Radionuclide Gamma spectrOmeter (ARGO), has demonstrated direct 233 U assay in freshly irradiated fuel salt samples using a dual-detector configuration and the 97.1 keV gamma-emission. These measurements were made using 1.4 x 10 6 Bq of 233 U activity (at 1.4 x 10 8 fissions), at relatively high dead times (10.4%), and using short count durations of ~800 s. Other major emissions were also evaluated (42.5 keV, 54.7 keV, 146.4 keV), in additional to limited (1.96%) Compton suppression, but provided less consistent determination of the 233 U activity. Accurate 233 U measurement was also demonstrated using its four coincidence gamma-emissions (42.5 keV, 54.7 keV; 42.5 keV, 278.1 keV; 146.4 keV, 174.2 keV; 146.4 keV, 219 keV). Further improvements in coincidence measurements may be achievable with improvements in the detector configuration and nuclear data. Whilst this demonstration utilized the ARGO laboratory system, a similar dual-detector configuration could be utilized for online safeguards measurements.

Gamma-spectrometry↗
DOE OSTI2022

The ultrafast pixel array camera system and its applications in high energy density physics

Diagnostics in high energy density physics, shock physics, and related fields are primarily driven by a need to record rapidly time-evolving signals in single-shot events. These measurements are often limited by channel count and signal degradation issues on cable links between the detector and digitizer. Here we present the Ultrafast Pixel Array Camera (UPAC), a compact and flexible detector readout system with 32 waveform-recording channels at up to 10 Gsample/s and 1.8 GHz analog bandwidth. The compact footprint allows the UPAC to be directly embedded in the detector environment. A key enabling technology is the PSEC4A chip, an eight-channel switch-capacitor array sampling device with up to 1056 samples/channel. The UPAC system includes a high-density input connector that can plug directly into an application-specific detector board, programmable control, and serial readout, with less than 5 W of power consumption in full operation. We present the UPAC design and characterization, including a measured timing resolution of ~20 ps or better on acquisitions of sub-nanosecond pulses with minimal system calibrations. Example applications of the UPAC are also shown to demonstrate operation of a solid-state streak camera, an ultrafast imaging array, and a neutron time-of-flight spectrometer.

47 OTHER INSTRUMENTATION↗
DOE OSTI2026

Toward an AI-Powered Software Pipeline for Real-Time Tracking and Analysis of Wildfire and Smoke

Real-time tracking of wildfires and smoke is crucial for effective response, minimizing damage, protecting lives, and efficiently managing resources during fire emergencies. We develop a web-based AI-powered pipeline that detects wildfires in aerial video and estimates deployment-relevant behavior metrics, including cumulative burned area, burned-area growth rate, fire spread direction, and smoke dispersion. The system combines a YOLO-based detector with YCbCr-based fire segmentation, HSV-based smoke segmentation, Farneback optical flow, and centroid-based spatiotemporal tracking. Using ground sampling distance (GSD), pixel-level fire masks are converted to physical burned-area measurements by correlating fire pixel counts with camera altitude and tilt angle. We benchmark YOLO variants and non-YOLO baselines (GoogLeNet, CNN, DBN, Autoencoder, U-Net, and AlexNet) on the IEEE FLAME dataset and a newly created aerial frame dataset, Wildfire-DB. Cross-dataset evaluation uses a strict threshold-transfer protocol: decision thresholds are selected on FLAME validation and transferred unchanged to Wildfire-DB to quantify generalization under domain shift. YOLOv6 achieves the strongest cross-dataset frame-level fire detection on Wildfire-DB (ROC-AUC 0.8200, PR-AUC 0.8044, and transferred-threshold F1 0.7596). For tracking-oriented deployment requiring oriented localization, YOLO11-OBB provides the most reliable cross-dataset behavior among OBB-capable models while remaining computationally feasible. To analyze the feasibility of UAV deployment, we further measure inference efficiency using synchronized GPU and CPU power logs on a fixed workload of 1569 frames. YOLO-family models process the video in 5.73–12.47 seconds with net energy of 1247.28–1775.39 J, substantially lower latency and energy than heavier classification and reconstruction baselines. Overall, model optimality depends on operational objectives: YOLOv6 is best for cross-dataset detection robustness, whereas YOL...

Color segmentation↗
DOE OSTI2026

AQDrop Quantum Service (AQDrop) v1.0

AQDrop is a job management system designed to streamline access to the Advanced Quantum Testbed (AQT) at NERSC (National Energy Research Scientific Computing Center). It serves as a centralized middleware layer between researchers and quantum processing hardware. Key Features: AQDrop provides a FastAPI-based server backed by PostgreSQL for job submission, queue management, and role-based access control (members, operators, and administrators). Users submit Qiskit circuits via JSON payloads, which are queued, dispatched to the QPU through the Qubic API, and returned as measurement counts. A Python client library and web dashboard round out the interface options. Primary Use: Researchers submit quantum circuit jobs from a laptop or login node; an operator client executes those jobs on the AQT's physical QPU and returns results — all coordinated through the central API. Advantages: Compared to ad-hoc or direct hardware access, AQDrop adds structured queue management, auditable job-status tracking and OAuth2 authentication — reducing scheduling conflicts and unauthorized access. Its containerized deployment also improves reproducibility and scalability. Overall, AQDrop functions as a purpose-built quantum job broker tailored to NERSC's specific hardware and institutional access requirements.

Caplinger, Evan [Lawrence Berkeley National Labora↗
DOE OSTI2021

Development of a Miniaturized Mobile Mapping System for In-Row, Under-Canopy Phenotyping

This paper focuses on the development of a miniaturized mobile mapping platform with advantages over current agricultural phenotyping systems in terms of acquiring data that facilitate under-canopy plant trait extraction. The system is based on an unmanned ground vehicle (UGV) for in-row, under-canopy data acquisition to deliver accurately georeferenced 2D and 3D products. The paper addresses three main aspects pertaining to the UGV development: (a) architecture of the UGV mobile mapping system (MMS), (b) quality assessment of acquired data in terms of georeferencing information as well as derived 3D point cloud, and (c) ability to derive phenotypic plant traits using data acquired by the UGV MMS. The experimental results from this study demonstrate the ability of the UGV MMS to acquire dense and accurate data over agricultural fields that would facilitate highly accurate plant phenotyping (better than above-canopy platforms such as unmanned aerial systems and high-clearance tractors). Plant centers and plant count with an accuracy in the 90% range have been achieved.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2023

Conceptual design of DIII-D experiments to diagnose the lifetime of spin polarized fuel

Abstract In magnetic fusion experiments, the cross sections for the D-T and D- 3 He fusion reactions are increased by as much as 50% if the fuel remains spin polarized parallel to the magnetic field. The goal of this study is to assess the feasibility of lifetime measurements of spin polarization, in magnetic fusion relevant conditions, on the DIII-D tokamak using relative changes in charged fusion product (CFP) loss measurements that depend upon the differential fusion cross section d σ /dΩ. Relative measurements that capture changes in the escaping CFP pitch, poloidal, and energy distributions are studied in two realistic TRANSP calculated plasma scenarios: (a) vector-polarized 3 He and D pellets are injected into a hot hydrogen plasma to produce thermonuclear reactions, and (b) a tensor-polarized deuterium pellet is injected into an L-mode hydrogen background plasma that includes unpolarized 3 He neutral beam injection. Ideal CFP signals in both scenarios show substantial pitch sensitivity to polarization for 14.7 MeV proton detection at a poloidal angle of − 56 ∘ (on the outer wall in the ion ∇ B direction), and strong sensitivity to polarization for 3.6 MeV alpha flux detection by an array of poloidal detectors. Energy-resolved measurements of 14.7 MeV protons are also sensitive to the degree of polarization for the − 56 ∘ port in the beam-plasma scenario. A realistic assessment of CFP signals in the thermonuclear scenario show count rates in the range of 2 × 10 4 cps for pitch-resolved proton detection and 2 × 10 5 cps for alpha flux measurements. Reduced chi-squared χ r 2 calculations show polarization lifetime measurements are feasible for either proton or alpha detection of both enhanced or suppressed polarization for the thermonuclear scenario. Measurements of gamma rays produced in the weak D + 3 He → γ + 5 Li branch complement the CFP measurements.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2023

Measurements and computational analysis of the natural decay of 176 Lu

Background: Mainly because of its long half-life and despite its scientific relevance, spectroscopic measurements of 176 Lu forbidden β decays are very limited and lack formulation of shape factors. A direct precise measurement of its Q value is also presently unreported. In addition, the description of forbidden decays provides interesting challenges for nuclear theory. The comparison of precise experimental results with theoretical calculations for these decays can help to test underlying models and can aid the interpretation of data from other experiments. Purpose: Perform the first precision measurements of 176 Lu β-decay spectra and attempt the observation of its electron capture decays, as well as perform the first precision direct measurement of the 176 Lu β-decay Q value. Compare the shape of the precisely determined experimental β spectra to theoretical calculations, and compare the end point energy to that obtained from an independent Q value measurement. Method: Here, the 176 Lu β-decay spectra measurements and the search for electron capture decays were performed with an experimental setup that employed lutetium-containing scintillator crystals and a NaI(Tl) spectrometer for coincidence counting. The β decay Q value was determined via high-precision Penning trap mass spectrometry (PTMS) with the LEBIT facility at the National Superconducting Cyclotron Laboratory. The β-spectrum calculations were performed within the Fermi theory formalism with nuclear structure effects calculated using a shell model approach. Results: Both β transitions of 176 Lu were experimentally observed and corresponding shape factors formulated in their entire energy ranges. The search for electron capture decay branches led to an experimental upper limit of 6.3×10 –6 relative to its β decays. The 176 Lu β-decay and electron capture Q values were measured using PTMS to be 1193.0(6) and 108.9(8) keV, respectively. This enabled precise β end point energies of 596.2(6) and 195.3(6) keV to be determined for the primary and secondary β decays, respectively. The conserved vector current hypothesis was applied to calculate the relativistic vector matrix elements. The β-spectrum shape was shown to significantly depend on the Coulomb displacement energy and on the value of the axial vector coupling constant gA, which was extracted according to different assumptions. Conclusion: The implemented self-scintillation method has provided unmatched observations of 176 Lu, independently validated by the first direct measurements of its β-decay Q value by Penning trap mass spectrometry. Theoretical study of the main β transition led to the extraction of very different effective gA and log10f values, showing that a high-precision description of this transition would require a realistic nuclear structure with nucleus deformation.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2022

Alpha/beta-gated gamma–gamma spectroscopy of mixed fission products for trace analysis

This experiment demonstrated that some hard-to-detect fission products can be quantified directly from mixed fission product samples using advanced radio-emission spectroscopy techniques. A gamma/gamma coincidence detector was combined with a custom liquid scintillation counter to evaluate the benefits of alpha and beta coincident and anti-coincident analysis of mixed fission product samples. Reduction factors in the minimum detectable activity (MDA) relative to traditional gamma counting were quantified for a set of radionuclides. For isotopes like 91Y, 144Ce, 147Nd, and 153Sm MDA reductions of factors of 1-2 were observed using optimized beta thresholds. Using beta anti-coincidence counting reductions of factors 3-5 were observed for isotopes like 89Sr, 95mNb, 115Cd, and 137Cs and factors of 5-7 for isotopes like 235U using alpha coincidence counting. The selectivity of gamma/gamma coincidence and reduction in backgrounds using beta gating were also demonstrated with 136Cs and 153Sm. The improvements observed in the detection sensitivity of fission products and actinides achieved by combining time-correlated radiation signatures is significant and of value to applications such as nuclear fission physics, environmental monitoring for nuclear waste, reactor accidental releases, and nuclear forensics.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗
DOE OSTI2020

Molecular dynamics simulations of alkaline earth metal ions binding to DNA reveal ion size and hydration effects

The identity of metal ions surrounding DNA is key to its biological function and materials applications. In this work, we compare atomistic molecular dynamics simulations of double strand DNA (dsDNA) with four alkaline earth metal ions (Mg 2+ , Ca 2+ , Sr 2+ , and Ba 2+ ) to elucidate the physical interactions that govern DNA–ion binding. Simulations accurately model the ion–phosphate distance of Mg 2+ and reproduce ion counting experiments for Ca 2+ , Sr 2+ , and Ba 2+ . Our analysis shows that alkaline earth metal ions prefer to bind at the phosphate backbone compared to the major groove and negligible binding occurs in the minor groove. Larger alkaline earth metal ions with variable first solvation shells (Ca 2+ , Sr 2+ , and Ba 2+ ) show both direct and indirect binding, where indirect binding increases with ion size. Mg 2+ does not fit this trend because the strength of its first solvation shell predicts indirect binding only. Ions bound to the phosphate backbone form fewer contacts per ion compared to the major groove. Within the major groove, metal ions preferentially bind to guanine–cystosine base pairs and form simultaneous contacts with the N7 and O6 atoms of guanine. Overall, we find that the interplay among ion size, DNA–ion interaction, and the size and flexibility of the first solvation shell are key to predicting how alkaline earth metal ions interact with DNA.

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

Combining MicroED and native mass spectrometry for structural discovery of enzyme–small molecule complexes

With the goal of accelerating the discovery of small molecule–protein complexes, we leverage fast, low-dose, event-based electron counting microcrystal electron diffraction (MicroED) data collection and native mass spectrometry. This approach, which we term electron diffraction with native mass spectrometry (ED-MS), allows assignment of protein target structures bound to ligands with data obtained from crystal slurries soaked with mixtures of known inhibitors and crude biosynthetic reactions. This extends to libraries of printed ligands dispensed directly onto TEM grids for later soaking with microcrystal slurries, and complexes with noncovalent ligands. ED-MS resolves structures of the natural product, epoxide-based cysteine protease inhibitor E-64, and its biosynthetic analogs bound to the model cysteine protease, papain. It further identifies papain binding to its preferred natural products, by showing that two analogs of E-64 outcompete others in binding to papain crystals, and by detecting papain bound to E-64 and an analog from crude biosynthetic reactions, without purification. ED-MS also resolves binding of the CTX-M-14 β-lactamase, a target of active drug development, to the non-β-lactam inhibitor, avibactam, alone or in a cocktail of unrelated compounds. These results illustrate the utility of ED-MS for natural product ligand discovery and for structure-based screening of small molecule binders to macromolecular targets, promising utility for drug discovery.

MicroED↗