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DOE OSTI2021

Majorana zero modes in impurity-assisted vortex of LiFeAs superconductor

The iron-based superconductor is emerging as a promising platform for Majorana zero mode, which can be used to implement topological quantum computation. One of the most significant advances of this platform is the appearance of large vortex level spacing that strongly protects Majorana zero mode from other low-lying quasiparticles. Despite the advantages in the context of physics research, the inhomogeneity of various aspects hampers the practical construction of topological qubits in the compounds studied so far. Here we show that the stoichiometric superconductor LiFeAs is a good candidate to overcome this obstacle. By using scanning tunneling microscopy, we discover that the Majorana zero modes, which are absent on the natural clean surface, can appear in vortices influenced by native impurities. Our detailed analysis reveals a new mechanism for the emergence of those Majorana zero modes, i.e. native tuning of bulk Dirac fermions. The discovery of Majorana zero modes in this homogeneous material, with a promise of tunability, offers an ideal material platform for manipulating and braiding Majorana zero modes, pushing one step forward towards topological quantum computation.

36 MATERIALS SCIENCE↗

NASA NTRSDate not supplied

Aviary: An Open-Source Multidisciplinary Design, Analysis, and Optimization Tool for Modeling Aircraft with Analytic Gradients

In recent years demands on aircraft design methods have begun to require higher degrees of coupling between disciplines and optimization in order to satisfy competing objectives involving large numbers of design parameters that define unconventional configurations. These expanding requirements have amplified a need for new and improved aircraft design, analysis, and optimization codes that are capable of performing coupled design and exploiting analytic gradients to perform gradient-based optimization where possible. To address this need, a new multidisciplinary design optimization and analysis tool called Aviary is presented. This tool, built on OpenMDAO, allows for tightly coupled, simultaneous aircraft and subsystem design using analytic gradients. Aviary includes methods from two NASA developed legacy aircraft analysis tools and provides native analytically differentiated calculations for five different disciplines (weights and sizing, aerodynamics, geometry, propulsion, and mission analysis), while also allowing external discipline analysis tools to be coupled, regardless of whether those tools can provide analytic gradients. Verification and preliminary examples and modeling efforts show Aviary’s ability to effectively model novel concepts and explore large and non-intuitive design spaces. Additionally, a multi-level user interface in Aviary creates an easy entry point for users with any level of multidisciplinary design, analysis, and optimization experience.

optimization↗

NASA NTRSDate not supplied

Aviary: An Open-Source Multidisciplinary Design, Analysis, and Optimization Tool for Modeling Aircraft With Analytic Gradients

Demands on aircraft design methods in recent years have begun to require increasingly higher amounts of coupling between disciplines and have also begun to require optimization in order to satisfy competing objectives involving large numbers of parameters that define unconventional configurations. These expanding requirements have amplified a need for new and improved aircraft design, analysis, and optimization codes that are capable of performing coupled design exploiting analytic gradients where possible. Aviary is a multidisciplinary design optimization and analysis framework which allows for tightly coupled simultaneous aircraft and subsystem design using analytic gradients. Aviary has employed the methods of two legacy aircraft analysis tools to provide native analytically differentiated calculations for five different disciplines, and it also has the ability to couple in external discipline analysis tools, whether or not those tools can provide analytic gradients. Preliminary examples and modeling efforts have shown Aviary’s ability to effectively model novel concepts and explore large and non-intuitive design spaces. Finally, a multi-level user interface in Aviary creates an easy entry point for users with any level of multidisciplinary design, analysis, and optimization experience.

multidisciplinary↗

DOE OSTI2024

eagles-project/asediag

Aerosol process analysis in model-native Spectral Element (SE) grid. Aerosol Diagnostics on Model Native Grid is a Python-based tool designed for diagnosing aerosol processes in E3SM. It is particularly designed to analyze simulation data on the model-native spectral element (SE) grid, soit is also known as Aerosol SE Diagnostics or “asediag”

Hassan, Taufiq↗

NASA NTRS2014

Focal Gray Matter Plasticity as a Function of Long Duration Head Down Tilted Bed Rest: Preliminary Results

Long duration spaceflight (i.e., 22 days or longer) has been associated with changes in sensorimotor systems, resulting in difficulties that astronauts experience with posture control, locomotion, and manual control. The microgravity environment is an important causal factor for spaceflight induced sensorimotor changes. Whether these sensorimotor changes are solely related to peripheral changes from reduced vestibular stimulation, body unloading, body fluid shifts or that they may be related to structural and functional brain changes is yet unknown. However, a recent study reported associations between microgravity and flattening of the posterior eye globe and protrusion of the optic nerve [1] possibly as the result of increased intracranial pressure due to microgravity induced bodily fluid shifts [3]. Moreover, elevated intracranial pressure has been related to white matter microstructural damage [2]. Thus, it is possible that spaceflight may affect brain structure and thereby cognitive functioning. Long duration head down tilt bed rest has been suggested as an exclusionary analog to study microgravity effects on the sensorimotor system [4]. Bed rest mimics microgravity in body unloading and bodily fluid shifts. In consideration of the health and performance of crewmembers both in- and post-flight, we are conducting a prospective longitudinal 70-day bed rest study as an analog to investigate the effects of microgravity on brain structure [5]. Here we present results of the first six subjects. Six subjects were assessed at 12 and 7 days before-, at 7, 30, and ~70 days in-, and at 8 and 12 days post 70 days of bed rest at the NASA bed rest facility in UTMB, Galveston, TX, USA. At each time point structural MRI scans (i.e., high resolution T1-weighted imaging and Diffusion Tensor Imaging (DTI)) were obtained using a 3T Siemens scanner. Focal changes over time in gray matter density were assessed using the voxel based morphometry 8 (VBM8) toolbox under SPM. Longitudinal processing in VBM8 includes linear registration of each scan to the mean of the subject and subsequently transforming all scans in to MNI space by applying the warp from the mean subject to MNI to the individual gray matter segmentations. Modulation was applied so that all images represented the volume of the original structure in native space. Voxel wise analysis was carried out on the gray matter images after smoothing, using a flexible factorial design with family wise error correction. Focal changes in white matter microstructural integrity were assessed using tract based spatial statistics (TBSS) as part of FMRIB software library (FSL). TBSS registers all DTI scans to standard space. It subsequently creates a study specific white matter skeleton of the major white matter tracts. For each subject, for each DTI metric (i.e. fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD)), the maximum value in a line perpendicular to the skeleton tract is projected to the skeleton. Non-parametric permutation based t-tests and ANOVA's were used for voxel-wise comparison of the skeletons. For both VBM and TBSS, comparison of pre bed rest measurements did not show significant differences. VBM analysis revealed decreased gray matter density in bilateral areas including the frontal medial cortex, the insular cortex and the caudate (see Figure) from 'pre to in bed rest'. Over the same time period, there was an increase in gray matter density in the cerebellum, occipital-, and parietal cortex, including the precuneus (see Figure). The majority of these changes did not recover from 'during to post bed rest'. TBSS analysis did not reveal significant changes in white matter microstructural integrity after correction for multiple comparisons. Uncorrected analyses (p<.015) revealed an increase in RD in the cerebellum and brainstem from pre bed rest to the first week in bed rest that did not recover post bed rest. Extended bed rest, which is an analog for microgravity, can result in gray matter changes and potentially in microstructural white matter changes in areas that are important for neuro motor behavior and cognition. These changes did not recover at two weeks post bed rest. Whether the effects of bed rest wear off at longer times post bed rest, and if they are associated with behavior are important questions that warrant further research.

Koppelmans, V.↗

DOE OSTI2026

Automated Bacterial Identification and Morphological Feature Analysis in Low‐Dose Cryo‐EM Using YOLOv11

Bacteria rapidly adapt to environmental cues through morphological and ultrastructural changes that correlate with physiology and behavior. Cryogenic transmission electron microscopy (cryo‐TEM) can capture these phenotypic changes in near‐native, vitrified states, but manual analysis of low‐dose micrographs is labor intensive and limits throughput. Here, we present an end‐to‐end workflow that combines low‐dose cryo‐TEM imaging with a YOLOv11‐based instance‐segmentation model to automatically identify bacteria and quantify key structural features directly from the micrographs. This workflow enables (i) robust bacterial localization and counting from low‐magnification atlas/montage images, (ii) automated measurements of cell‐envelope (outer–inner membrane) thickness and anisotropy from higher‐magnification views, and (iii) detection and quantification of bacteria–flagella interactions, including overlap length and curvature metrics for interacting versus noninteracting flagella. Using Pantoea sp. YR343 grown under distinct media conditions, we show that the automated measurements agree with manual annotations while substantially reducing analysis time. Together, these tools provide a practical framework for scalable bacterial identification and quantitative phenotyping in low‐dose cryo‐TEM datasets and establish a foundation for extending cryo‐TEM image analysis toward higher‐throughput studies of microbial heterogeneity and biointerfaces.

YOLOv11↗

DOE OSTI2024

Mechanisms of Low-Level Jet Formation in the U.S. Mid-Atlantic Offshore

Abstract Low-level jets (LLJs), in which the wind speed attains a local maximum at low altitudes, have been found to occur in the U.S. mid-Atlantic offshore, a region of active wind energy deployment as of 2023. In contrast to widely studied regions such as the U.S. southern Great Plains and the California coastline, the mechanisms that underlie LLJs in the U.S. mid-Atlantic are poorly understood. This work analyzes floating lidar data from buoys deployed in the New York Bight to understand the characteristics and causes of coastal LLJs in the region. Application of the Hilbert–Huang transform, a frequency analysis technique, to LLJ case studies reveals that mid-Atlantic jets frequently occur during times of adjustment in synoptic-scale motions, such as large-scale temperature and pressure gradients or frontal passages, and that they do not coincide with motions at the native inertial oscillation frequency. Subsequent analysis with theoretical models of inertial oscillation and thermal winds further reveals that these jets can form in the stationary geostrophic wind profile from horizontal temperature gradients alone—in contrast to canonical LLJs, which arise from low-level inertial motions. Here, inertial oscillation can further modulate the intensity and altitude of the wind speed maximum. Statistical evidence indicates that these oscillations arise from stable stratification and the associated frictional decoupling due to warmer air flowing over a cold sea surface during the springtime land–sea breeze. These results improve our conceptual understanding of mid-Atlantic jets and may be used to better predict low-level wind speed maxima. Significance Statement The purpose of this work is to identify and characterize the atmospheric mechanisms that result in an occasional low-level maximum in the wind speed off the U.S. mid-Atlantic coastline. Our findings show that these low-level jets form due to horizontal temperature gradients arising from fronts and synoptic systems, as well as from the land–sea breeze that forces warmer air over the cold ocean surface. This work aids predictability of such jets, improves our understanding of this coastal environment, and has implications for future deployment of offshore wind energy in this region.

17 WIND ENERGY↗

DOE OSTI2022

Towards Fully Secure 5G Ultra-Low Latency Communications: A Cost-Security Functions Analysis

Future components to enhance the basic, native security of 5G networks are either complex mechanisms whose impact in the requiring 5G communications are not considered, or lightweight solutions adapted to ultra-reliable low-latency communications (URLLC) but whose security properties remain under discussion. Although different 5G network slices may have different requirements, in general, both visions seem to fall short at provisioning secure URLLC in the future. In this work we address this challenge, by introducing cost-security functions as a method to evaluate the performance and adequacy of most developed and employed non-native enhanced security mechanisms in 5G networks. We categorize those new security components into different groups according to their purpose and deployment scope. We propose to analyze them in the context of existing 5G architectures using two different approaches. First, using model checking techniques, we will evaluate the probability of an attacker to be successful against each security solution. Second, using analytical models, we will analyze the impact of these security mechanisms in terms of delay, throughput consumption, and reliability. Finally, we will combine both approaches using stochastic cost-security functions and the PRISM model checker to create a global picture. Our results are first evidence of how a 5G network that covers and strengthened all security areas through enhanced, dedicated non-native mechanisms could only guarantee secure URLLC with a probability of ~55%.

5G networks↗

DOE OSTI2023

The first two chromosome‐scale genome assemblies of American hazelnut enable comparative genomic analysis of the genus Corylus

Summary The native, perennial shrub American hazelnut ( Corylus americana ) is cultivated in the Midwestern United States for its significant ecological benefits, as well as its high‐value nut crop. Implementation of modern breeding methods and quantitative genetic analyses of C. americana requires high‐quality reference genomes, a resource that is currently lacking. We therefore developed the first chromosome‐scale assemblies for this species using the accessions ‘Rush’ and ‘Winkler’. Genomes were assembled using HiFi PacBio reads and Arima Hi‐C data, and Oxford Nanopore reads and a high‐density genetic map were used to perform error correction. N50 scores are 31.9 Mb and 35.3 Mb, with 90.2% and 97.1% of the total genome assembled into the 11 pseudomolecules, for ‘Rush’ and ‘Winkler’, respectively. Gene prediction was performed using custom RNAseq libraries and protein homology data. ‘Rush’ has a BUSCO score of 99.0 for its assembly and 99.0 for its annotation, while ‘Winkler’ had corresponding scores of 96.9 and 96.5, indicating high‐quality assemblies. These two independent assemblies enable unbiased assessment of structural variation within C. americana , as well as patterns of syntenic relationships across the Corylus genus. Furthermore, we identified high‐density SNP marker sets from genotyping‐by‐sequencing data using 1343 C. americana , C. avellana and C. americana × C. avellana hybrids, in order to assess population structure in natural and breeding populations. Finally, the transcriptomes of these assemblies, as well as several other recently published Corylus genomes, were utilized to perform phylogenetic analysis of sporophytic self‐incompatibility (SSI) in hazelnut, providing evidence of unique molecular pathways governing self‐incompatibility in Corylus .

54 ENVIRONMENTAL SCIENCES↗

DOE OSTI2020

Uncertainty analysis of correlated parameters in automated reaction mechanism generation

Abstract Uncertainty analysis is a useful tool for inspecting and improving detailed kinetic mechanisms because it can identify the greatest sources of model output error. Owing to the very nonlinear relationship between kinetic and thermodynamic parameters and computed concentrations, model predictions can be extremely sensitive to uncertainties in some parameters while uncertainties in other parameters can be irrelevant. Error propagation becomes even more convoluted in automatically generated kinetic models, where input uncertainties are correlated through kinetic rate rules and thermodynamic group values. Local and global uncertainty analyses were implemented and used to analyze error propagation in Reaction Mechanism Generator (RMG), an open‐source software for generating kinetic models. A framework for automatically assigning parameter uncertainties to estimated thermodynamics and kinetics was created, enabling tracking of correlated uncertainties. Local first‐order uncertainty propagation was implemented using sensitivities computed natively within RMG. Global uncertainty analysis was implemented using adaptive Smolyak pseudospectral approximations as implemented in the MIT Uncertainty Quantification Library to efficiently compute and construct polynomial chaos expansions to approximate the dependence of outputs on a subset of uncertain inputs. Cantera was used as a backend for simulating the reactor system in the global analysis. Analyses were performed for a phenyldodecane pyrolysis model. Local and global methods demonstrated similar trends; however, many uncertainties were significantly overestimated by the local analysis. Both local and global analyses show that correlated uncertainties based on kinetic rate rules and thermochemical groups drastically reduce a model's degrees of freedom and have a large impact on the determination of the most influential input parameters. These results highlight the necessity of incorporating uncertainty analysis in the mechanism generation workflow.

Gao, Connie W.↗

DOE OSTI2020

(S)TEM/EDS study of native precipitates and irradiation induced Nb-rich platelets in high-burnup M5®

We have investigated microstructure and microchemistry of precipitates and dislocation loops in high-burnup M5® using (scanning) transmission electron microscopy ((S)TEM) equipped with energy dispersive X-ray spectroscopy (EDS). Two (S)TEM lamellae were made by cryo-FIB from the same cladding sample. The Nb-rich native precipitates were found in the metal, in the suboxide and in the oxide. Upon diffraction analysis, most of the Nb-rich native precipitates in the metal matrix remain as β-Nb phase, while no β-Nb native precipitates were found in the oxide. Nearby the oxide and metal (O/M) interface, the native precipitates in the oxide were already oxidized into t-NbO2 phase. At further distance away from the O/M interface, the Nb-rich native precipitates were gradually oxidized and became amorphous. Besides the native precipitates, Nb-rich irradiation induced precipitates (IIPs) were found in the metal matrix. Using g = <0002> vector for imaging, the length of the IIPs was aligned with dislocation loops. However, no Nb segregation to the dislocation loops themselves was observed. For the first time, we report that IIPs indeed exist in the oxide but only within about 1.5 µm away from O/M interface. However, the oxidation state of the IIPs in the oxide is still unclear. The presence of both native precipitates and IIPs in the oxide may indicate the Nb concentration in the oxide solid solution remain low nearby the O/M interface, which may explain the reduced corrosion kinetics of in-pile M5®. On the other hand, no IIPs were observed in the oxide at further distance and this may indicate that they have eventually dissolved back into the oxide. A few mechanisms related to IIPs stability in the oxide are presented.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

DOE OSTI2023

CRISPR/Cas9 Directed Reprogramming of iPSC for Accelerated Motor Neuron Differentiation Leads to Dysregulation of Neuronal Fate Patterning and Function

Neurodegeneration causes a significant disease burden and there are few therapeutic interventions available for reversing or slowing the disease progression. Induced pluripotent stem cells (iPSCs) hold significant potential since they are sourced from adult tissue and have the capacity to be differentiated into numerous cell lineages, including motor neurons. This differentiation process traditionally relies on cell lineage patterning factors to be supplied in the differentiation media. Genetic engineering of iPSC with the introduction of recombinant master regulators of motor neuron (MN) differentiation has the potential to shorten and streamline cell developmental programs. We have established stable iPSC cell lines with transient induction of exogenous LHX3 and ISL1 from the Tet-activator regulatory region and have demonstrated that induction of the transgenes is not sufficient for the development of mature MNs in the absence of neuron patterning factors. Comparative global transcriptome analysis of MN development from native and Lhx-ISL1 modified iPSC cultures demonstrated that the genetic manipulation helped to streamline the neuronal patterning process. However, leaky gene expression of the exogenous MN master regulators in iPSC resulted in the premature activation of genetic pathways characteristic of the mature MN function. Dysregulation of metabolic and regulatory pathways within the developmental process affected the MN electrophysiological responses.

59 BASIC BIOLOGICAL SCIENCES↗

NASA NTRS1990

Partial purification and characterization of a Ca(2+)-dependent protein kinase from the green alga, Dunaliella salina

A calcium-dependent protein kinase was partially purified and characterized from the green alga Dunaliella salina. The enzyme was activated at free Ca2+ concentrations above 10(-7) molar. and half-maximal activation was at about 3 x 10(-7) molar. The optimum pH for its Ca(2+)-dependent activity was 7.5. The addition of various phospholipids and diolein had no effects on enzyme activity and did not alter the sensitivity of the enzyme toward Ca2+. The enzyme was inhibited by calmodulin antagonists, N-(6-aminohexyl)-1-naphthalene sulfonamide and N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide in a dose-dependent manner while the protein kinase C inhibitor, sphingosine, had little effect on enzyme activity up to 800 micromolar. Immunoassay showed some calmodulin was present in the kinase preparations. However, it is unlikely the kinase was calmodulin regulated, since it still showed stimulation by Ca2+ in gel assays after being electrophoretically separated from calmodulin by two different methods. This gel method of detection of the enzyme indicated that a protein band with an apparent molecular weight of 40,000 showed protein kinase activity at each one of the several steps in the purification procedure. Gel assay analysis also showed that after native gel isoelectric focusing the partially purified kinase preparations had two bands with calcium-dependent activity, at isoelectric points 6.7 and 7.1. By molecular weight, by isoelectric point, and by a comparative immunoassay, the Dunaliella kinase appears to differ from at least some of the calcium-dependent, but calmodulin and phospholipid independent kinases described from higher plants.

Non-NASA Center↗

NASA NTRS2009

Spectroscopic chemical analysis methods and apparatus

Spectroscopic chemical analysis methods and apparatus are disclosed which employ deep ultraviolet (e.g. in the 200 nm to 300 nm spectral range) electron beam pumped wide bandgap semiconductor lasers, incoherent wide bandgap semiconductor light emitting devices, and hollow cathode metal ion lasers to perform non-contact, non-invasive detection of unknown chemical analytes. These deep ultraviolet sources enable dramatic size, weight and power consumption reductions of chemical analysis instruments. Chemical analysis instruments employed in some embodiments include capillary and gel plane electrophoresis, capillary electrochromatography, high performance liquid chromatography, flow cytometry, flow cells for liquids and aerosols, and surface detection instruments. In some embodiments, Raman spectroscopic detection methods and apparatus use ultra-narrow-band angle tuning filters, acousto-optic tuning filters, and temperature tuned filters to enable ultra-miniature analyzers for chemical identification. In some embodiments Raman analysis is conducted simultaneously with native fluorescence spectroscopy to provide high levels of sensitivity and specificity in the same instrument.

Hug, William F.↗

NASA NTRS2010

Spectroscopic chemical analysis methods and apparatus

Hug, William F.↗

NASA NTRS2015

Advanced Curation: Solving Current and Future Sample Return Problems

Advanced Curation is a wide-ranging and comprehensive research and development effort at NASA Johnson Space Center that identifies and remediates sample related issues. For current collections, Advanced Curation investigates new cleaning, verification, and analytical techniques to assess their suitability for improving curation processes. Specific needs are also assessed for future sample return missions. For each need, a written plan is drawn up to achieve the requirement. The plan draws while upon current Curation practices, input from Curators, the analytical expertise of the Astromaterials Research and Exploration Science (ARES) team, and suitable standards maintained by ISO, IEST, NIST and other institutions. Additionally, new technologies are adopted on the bases of need and availability. Implementation plans are tested using customized trial programs with statistically robust courses of measurement, and are iterated if necessary until an implementable protocol is established. Upcoming and potential NASA missions such as OSIRIS-REx, the Asteroid Retrieval Mission (ARM), sample return missions in the New Frontiers program, and Mars sample return (MSR) all feature new difficulties and specialized sample handling requirements. The Mars 2020 mission in particular poses a suite of challenges since the mission will cache martian samples for possible return to Earth. In anticipation of future MSR, the following problems are among those under investigation: What is the most efficient means to achieve the less than 1.0 ng/sq cm total organic carbon (TOC) cleanliness required for all sample handling hardware? How do we maintain and verify cleanliness at this level? The Mars 2020 Organic Contamination Panel (OCP) predicts that organic carbon, if present, will be present at the "one to tens" of ppb level in martian near-surface samples. The same samples will likely contain wt% perchlorate salts, or approximately 1,000,000x as much perchlorate oxidizer as organic carbon. The chemical kinetics of this reaction are poorly understood at present under the conditions of cached or curated martian samples. Among other parameters, what is the maximum temperature allowed during storage in order to preserve native martian organic compounds for analysis? What is the best means to collect headspace gases from cached martian (and other) samples? This gas will contain not only martian atmosphere but also off-gassed volatiles from the cached solids.

Fries, M.↗

NASA NTRS2019

VISAGE - A Visualization and Exploration Framework for Environmental Data

Diverse airborne and ground-based environmental observations are important technologies for disaster assessment and response, as well as for the validation of environmental satellite observations and atmospheric models which can improve forecasts. The VISAGE (Visualization for Integrated Satellite, Airborne and Ground-based data Exploration) project is working to provide three-dimensional visualization and basic analytics capabilities for such datasets in an interactive user interface. The use of cloud-native, server less technologies for analysis optimized data storage will position VISAGE for integration with other technologies into a Data Analytic Center Framework.

Conover, Helen↗

DOE OSTI2025

Covalent Drug Binding in Live Cells Monitored by Mid-Infrared Quantum Cascade Laser Spectroscopy: Photoactive Yellow Protein as a Model System

The detection of drug-target interactions in live cells enables analysis of therapeutic compounds in a native cellular environment. Recent advances in spectroscopy and molecular biology have facilitated the development of genetically encoded vibrational probes like nitriles that can sensitively report on molecular interactions. Nitriles are powerful tools for measuring electrostatic environments within condensed media like proteins, but such measurements in live cells have been hindered by low signal-to-noise ratios. In this study, we design a spectrometer based on a double-beam quantum cascade laser (QCL)-based transmission infrared (IR) source with balanced detection that can significantly enhance sensitivity to nitrile vibrational probes embedded in proteins within cells compared to a conventional FTIR spectrometer. Here, using this approach, we detect small-molecule binding in Escherichia coli, with particular focus on the interaction between para-Coumaric acid (pCA) and nitrile-incorporated photoactive yellow protein (PYP). This system effectively serves as a model for investigating covalent drug binding in a cellular environment. Notably, we observe large spectral shifts of up to 15 cm –1 for nitriles embedded in PYP between the unbound and drug-bound states directly within bacteria, in agreement with observations for purified proteins. Such large spectral shifts are ascribed to the changes in the hydrogen-bonding environment around the local environment of nitriles, accurately modeled through high-level molecular dynamics simulations using the AMOEBA force field. Our findings underscore the QCL spectrometer’s ability to enhance sensitivity for monitoring drug–protein interactions, offering new opportunities for advanced methodologies in drug development and biochemical research.

chromophores↗