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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 649 records · Page 36

Reagent-free Hyperspectral Diagnosis of SARS-CoV-2 Infection in Saliva Samples

Rapid, reagent-free pathogen-agnostic diagnostics that can be performed at the point of need are vital for preparedness against future outbreaks. Yet, many current strategies are pathogen-specific and require several reagents. We present hyperspectral sensing, using light to non-invasively measure the composition of several molecules to form a spectral signature, to overcome these barriers. To generate these spectral signatures, we present the ProSpectral TM V1, a novel, miniaturized hyperspectral platform with high spectral resolution with two mini-spectrometers. Furthermore, we developed state-of-the-art ML pipelines for near real-time analysis of spectral signatures in saliva samples. We found that we could accurately identify SARS-CoV-2 infection status in double-blinded saliva samples and demonstrate 100% accuracy on a hold out test dataset. To our knowledge, this establishes the fastest hyperspectral diagnostic platform and in a small form factor, and executable with liquid samples, without ligands or reagents, all while maintaining PCR level specificity and sensitivity.

59 BASIC BIOLOGICAL SCIENCES↗

Sensitivity of Next-Generation CMB Surveys to Neutrinos and Other Light Relics

Neutrinos and other light relics leave characteristic imprints in the cosmic microwave background anisotropies, making their observation a sensitive probe of the particle content and thermal history of the early universe. The energy density in these relativistic species is parameterized by their effective number $N_\mathrm{eff}$. Measuring this parameter at the percent level, which is a long-standing science goal of CMB-S4 and other experiments, would test a wide range of well-motivated physics within and beyond the Standard Model of particle physics. In this paper, we present Fisher-matrix forecasts of the projected sensitivity to $N_\mathrm{eff}$ of several CMB-S4 survey configurations considered during its extensive design phase. The conceptual design reaches $σ(N_\mathrm{eff}) < 0.03$ over its seven-year observing period, while the revised configuration achieves the same precision over a longer timescale. We complement these results with a cosmic-variance-limited survey over the same multipole range to quantify the room for improvement accessible with additional instrumental, observational, and theoretical efforts. Finally, we discuss the broad implications of precise $N_\mathrm{eff}$ measurements for the radiation sector, big bang nucleosynthesis, light thermal relics, and other early-universe physics. The forecasts presented in this work are performed with the publicly released DRAFT (Dark Radiation Anisotropy Flowdown Team) tool. It provides an end-to-end pipeline from simulated foreground maps and component separation to delensing and projected sensitivities for any cosmological parameter, and it can be directly applied to other cosmic microwave background survey designs.

Trendafilova, Cynthia [Case Western Reserve U., CE↗

Relating Molecular Properties to the Persistence of Marine Dissolved Organic Matter with Liquid Chromatography–Ultrahigh-Resolution Mass Spectrometry

Marine dissolved organic matter (DOM) contains a complex mixture of small molecules that eludes rapid biological degradation. Spatial and temporal variations in the abundance of DOM reflect the existence of fractions that are removed from the ocean over different time scales, ranging from seconds to millennia. However, it remains unknown whether the intrinsic chemical properties of these organic components relate to their persistence. Here, we elucidate and compare the molecular compositions of distinct DOM fractions with different lability along a water column in the North Atlantic Gyre. Our analysis utilized ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry at 21 T coupled to liquid chromatography and a novel data pipeline developed in CoreMS that generates molecular formula assignments and metrics of isomeric complexity. Clustering analysis binned 14 857 distinct molecular components into groups that correspond to the depth distribution of semilabile, semirefractory, and refractory fractions of DOM. The more labile fractions were concentrated near the ocean surface and contained more aliphatic, hydrophobic, and reduced molecules than the refractory fraction, which occurred uniformly throughout the water column. These findings suggest that processes that selectively remove hydrophobic compounds, such as aggregation and particle sorption, contribute to variable removal rates of marine DOM.

54 ENVIRONMENTAL SCIENCES↗

Integration of machine learning with neutron scattering for the Hamiltonian tuning of spin ice under pressure

Quantum materials research requires co-design of theory with experiments and involves demanding simulations and the analysis of vast quantities of data, usually including pattern recognition and clustering. Artificial intelligence is a natural route to optimise these processes and bring theory and experiments together. Here, we propose a scheme that integrates machine learning with high-performance simulations and scattering measurements, covering the pipeline of typical neutron experiments. Our approach uses nonlinear autoencoders trained on realistic simulations along with a fast surrogate for the calculation of scattering in the form of a generative model. We demonstrate this approach in a highly frustrated magnet, Dy 2 Ti 2 O 7 , using machine learning predictions to guide the neutron scattering experiment under hydrostatic pressure, extract material parameters and construct a phase diagram. Our scheme provides a comprehensive set of capabilities that allows direct integration of theory along with automated data processing and provides on a rapid timescale direct insight into a challenging condensed matter system.

36 MATERIALS SCIENCE↗

CAHS: Context-Aware Homology Search

Protein homology search is foundational to bioinformatics: it supports annotation transfer, structure/function inference, and evolutionary analysis over rapidly expanding sequence repositories (e.g., UniProtKB). Profile hidden Markov models (pHMMs), as implemented in HMMER, remain the most widely trusted approach because they provide statistically calibrated E-values; however, their gap behavior is fixed once a profile is trained, despite biological evidence that insertion/deletion tolerance varies across flexible loops and intrinsically disordered regions. We present CAHS (Context-Aware Homology Search), a lightweight query-time adapter for pHMM search that incorporates learned and biologically motivated signals without changing HMMER's downstream search pipeline or its calibrated E-value reporting. Given a query sequence, CAHS computes per-residue representations from a protein language model and a disorder predictor, maps these to profile coordinates, and modulates only match-state transition rows (gap-open and gap-extension probabilities) while preserving Plan7 constraints. We comprehensively evaluate CAHS across six structurally diverse protein families and multi-domain architectures against a 570k-sequence target corpus. CAHS expands detection capability, retrieving thousands of additional remote homologs at relaxed thresholds by maintaining alignment quality through flexible regions. For multi-domain proteins, context-aware modulation resolves 94% of fragmented alignments. Crucially, CAHS preserves hit-set invariance at stringent operating points (E<10-10), demonstrating increased statistical confidence without inflating false positives. Furthermore, sharper statistical distinction between homologs and background noise during early filter stages yields up to a 3.87× acceleration in end-to-end wall-clock time on high-performance computing clusters. Overall, CAHS illustrates a practical AI-for-science design pattern: augmenting a trusted probabilistic model with query-specific learned signals to improve interpretable, reproducible inference in data-rich biology.

Bhattaram, Swethasree [Georgia Institute of Techno↗

Describing Point Defect Topology in 2D Energy Materials Through Computer Vision

Point defects such as vacancies and impurity atoms strongly impact the performance of 2D materials. Traditional efforts often rely on manual detection, a process that is time-intensive, prone to human error, and challenging to scale. Here we leverage machine learning (ML) methods to identify and quantify vacancies within 2D transition metal carbides (Ti3C2, MXenes), aiming to expedite detection while improving accuracy. MXenes exhibit valuable defect-defined electrochemical properties, but we currently lack statistical understanding of defect topology needed to fully harness these materials. Here we employ a convolutional neural network for semantic segmentation of experimental MXene images, opening an opportunity to conduct a rigorous statistical study on defect hierarchy while investigating local relaxation in the lattice. We show how the integration of ML can yield fundamental insight into point defects, providing a powerful tool that will play an increasingly crucial role in the future of materials science. ML is often not just a matter of straightforward application, and pretrained models proved ineffective in this case. Instead, we trained our own neural network (NN) and applied data augmentation techniques and fine-tuning to the training dataset. Since labeled microscopy data is often scarce, we developed training data from a previously published wide-frame MXene image, using customized Gaussian fitting to locate atomic positions. Our trained model was then applied to a large dataset of experimental images, enabling a statistical study of defect configurations across three samples prepared with different HF etchant concentrations (5%, 9.1%, and 12.5%), as shown in Fig. 1. This also allowed us to investigate local strain around vacancies, though we find that we are limited by the precision of measurements using high-angle annular dark field (HAADF) images, as shown in Fig. 2. This study demonstrates how ML enables large-scale, quantitative analysis of atomic defects - an otherwise infeasible task with traditional methods. While our NN was specialized for Ti3C2 MXenes, the pipeline we developed provides a foundation for future ML models tailored to other materials. Ultimately, we envision embedding the NN onto the microscope to give real-time feedback to the user. To make this a reality, continued work is necessary to fully understand the NN's capabilities and limitations. This study gets one step closer to our goals of automated experimentation moving away from traditional methods of manual labeling. As ML capabilities advance, we hope to continue adapting and applying these techniques in microscopy.

2D materials↗

The Future of a Myriad of Accelerated Biodiscoveries Lies in AI‐Powered Mass Spectrometry and Multiomics Integration

The intersection of modern artificial intelligence (AI) and mass spectrometry (MS) is set to transform the MS‐based “omics” research fields, particularly proteomics, metabolomics, lipidomics, and glycomics, enabling advancements across a wide range of domains, from health to environment and industrial biotechnology. Beginning with an overview of key challenges inherent in MS software pipelines, this personal perspective explores how AI‐driven solutions can address them to enhance data processing, integration and interpretation. It proposes a paradigm shift in molecular identification and quantitation algorithms, leveraging AI to enable holistic interpretation of MS‐based multiomics data. While centered on MS‐based omics, this holistic AI‐driven paradigm is also critical for connecting dynamic biochemical changes to genomics and transcriptomics contexts, reinforcing the integrative value of MS in multiomics research. Ultimately, this AI‐driven approach could enhance efficiency, accuracy, and molecular breadth of coverage, deepening our systems‐level understanding of biological processes and accelerating a myriad of biodiscoveries.

47 OTHER INSTRUMENTATION↗

Irradiation Testing of Sensors - ASI Program Review 2022

This is a powerpoint presentation for the annual Advanced Sensors and Instrumentation (ASI) program webinar. The following is a summary of the presentation. Advanced instrumentation enables testing of nuclear fuels and materials in support of the US advanced nuclear technology industry. A number of promising sensor technologies are in the pipeline. The early part of sensor development can be done outside of the reactor environment, but full technical readiness requires experience gained from in-core performance testing. Customers usually have only one shot to conduct their irradiation experiments. Because of the high costs test sponsors are frequently reluctant to incorporate unproven technologies in reactor experiments. Therefore, it is vital to demonstrate newly-developed sensors in operational conditions, prior to incorporating them into long-term high-value experiments. Successful completion of these activities will create new monitoring capabilities in high-power test reactors (such as ATR) as well as specialty reactors such as TREAT.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

The SPAN512 mid-latitude pulsar survey at the Nançay Radio Telescope

The large number of ongoing surveys for pulsars and transients at various radio observatories is motivated by the science obtained from these sources. Timing and polarisation analysis of relativistic binaries can place strong constraints on theories of gravity. The observation of a growing number of millisecond pulsars (MSPs) spread over the celestial sphere may allow the detection of a stochastic gravitational wave background arising from supermassive black hole binaries. A more complete sample of young pulsars improves our knowledge of neutron star birth and evolution. Transients such as fast radio bursts can serve to probe the intergalactic medium. The SPAN512 pulsar survey covers intermediate Galactic latitudes using the L-band receiver of the Nançay Radio Telescope (NRT). The survey covers 224 sq. deg. of the sky for a total exposure time of 2200 h. Population syntheses predict the discovery of 3 to 19 new normal pulsars and a few MSPs. We present detailed modelling of the NRT beam with its L-band receiver and its sensitivity which we used to precisely assess the expected survey yield. We used the flexible Pulsar Arecibo L-band Feed Array data processing pipeline to search the 47 TB of SPAN512 data for pulsars and transients. The SPAN512 survey discovered two new MSPs and one new middle-aged pulsar. We focus on the analysis of the 2.4-ms spin period pulsar J2205+6012 for which we also report the detection of gamma-ray pulsations. Its narrow pulse width (35µs at an observing frequency of 2.55 GHz) allows for sub-microsecond timing precision over 8 yr, with exciting prospects for pulsar timing array programs.

79 ASTRONOMY AND ASTROPHYSICS↗

Enhanced polymorph metastability drives glycine nucleation in aqueous salt solutions

Crystal nucleation from aqueous solutions influences countless geological, biochemical, astrophysical, environmental, and materials science–related phenomena, including ice formation, the manufacturing of active pharmaceutical ingredients, development of diseases such as Alzheimer’s and the origin of life itself. Understanding and controlling nucleation is essential for designing materials with specific properties, developing strategies to inhibit or promote crystallization in various contexts and preventing pathological aggregation in neurodegenerative diseases. Similar to the protein structure prediction problem—where a single amino acid sequence can in theory adopt one most stable conformation but in practice may sample multiple competing conformations—crystal nucleation faces a parallel challenge: the same chemical species can form diverse polymorphs under different environmental conditions (e.g., temperature, pressure, solvent). Each polymorph presents its own set of physical and chemical properties, highlighting the importance of understanding and controlling polymorph selection in fields ranging from pharmaceuticals to materials design. Despite advances in experimental and computational methods for studying phase transitions and polymorph stability, nucleation remains challenging due to its nanoscale nature. Furthermore, in practical settings, salts and impurities can further influence crystal nucleation in diverse contexts, from scaling in pipelines and desalination plants to the durability of concrete and the efficiency of battery materials. This can lead to the formation of polymorphs that may differ from the most stable phase in pure solutions. Or, even though the final structure might appear same irrespective of whether the environment contained impurities or not, the mechanism through which it was formed might be completely different and not intuitive.

Wang, Ruiyu [University of Maryland, College Park,↗

The Geothermal Data Repository: Ten Years of Supporting the Geothermal Industry with Open Access to Geothermal Data

The Department of Energy's (DOE) Geothermal Data Repository (GDR) is celebrating its tenth anniversary! Over the last decade it has grown from the simple idea of storing public data in a centralized location to a valuable tool at the center of the US geothermal scientific community and an integral part of the DOE Geothermal Technologies Office (DOE GTO) project management strategy. Researchers funded by the DOE GTO have contributed over 1,300 data submissions to the GDR. These data have been used to further advancements in geothermal science, economic analysis, exploration, research, development, and operational efficiency. The adoption of open data methodologies and a data management strategy that prioritizes universal open access and standardized, interoperable data have further increased the value of GDR data, making them available across a distributed network of data sharing partners and improving their utility to other industries and related fields, including material science and space exploration. Incorporating feedback from users has been critical to the GDR's success, allowing it to grow over the years to meet the evolving needs of the geothermal community. This paper will explore some of many changes that occurred throughout the GDRs tenure and the lessons learned along the way, as well as highlight some of the new features and recent improvements that been implemented to support innovation, reduce duplication of effort, and advance the geothermal industry as a whole.

access↗

NanoPSD: A software for automatic detection of Nano-Particle Shape Distribution in electron microscopy images

Accurate quantification of the size and morphology of nanoparticles from electron microscopy (EM) images is essential to understand growth mechanisms, surface reactivity, and functional behavior in nanoscale materials. Manual analysis remains slow, subjective, and difficult to reproduce in large datasets. We introduce NanoPSD (Nano-Particle Shape Distribution), an open-source and fully automated framework for quantitative particle detection and morphology analysis from EM images. NanoPSD integrates adaptive contrast enhancement, polarity-agnostic scale-bar detection, Optical Character Recognition (OCR)-based calibration, and classical segmentation via Otsu thresholding with morphological refinement. Particle contours are used to extract geometric descriptors, including equivalent circular diameter, aspect ratio, circularity, and solidity, enabling automated classification into spherical, rod-like, and aggregate morphologies. The framework supports both single-image and batch processing, generating publication-quality visualizations, LaTeX-ready tables, and structured comma-separated values (CSV) datasets. As a demonstration, we applied NanoPSD to plasma-synthesized nanoparticle samples diagnosed via transmission electron microscopy (TEM). The code produced statistically robust size and morphology distributions spanning a few to tens of nanometers with minimal user supervision. The pipeline demonstrates high reproducibility and scalability, processing large image collections with consistent calibration and output formatting. Its modular design enables seamless integration of future deep-learning-based segmentation models, providing a pathway toward intelligent, data-driven electron microscopy analysis.

36 MATERIALS SCIENCE↗

Space Communications Responsive to Events Across Missions (SCREAM): An Investigation of Network Solutions for Transient Science Space Systems

Space Communications Responsive to Events Across Missions (SCREAM): An Investigation of Network Solutions for Transient Science Space Systems The National Academies have prioritized the pursuit of new scientific discoveries using diverse and temporally coordinated measurements from multiple ground and space-based observatories. Networked communications can enable such measurements by connecting individual observatories and allowing them to operate as a cohesive and purposefully designed system. Timely data flows across terrestrial and space communications networks are required to observe transient scientific events and processes. Currently, communications to space-based observatories experience large latencies due to manual service reservation and scheduling procedures, intermittent signal coverage, and network capacity constraints. If space communications network latencies could be reduced, new discoveries about dynamic scientific processes could be realized. However, science mission and network planners lack a systematic framework for defining, quantifying and evaluating timely space data flow implementation options for transient scientific observation scenarios involving multiple ground and space-based observatories. This dissertation presents a model-based systems engineering approach to investigate and develop network solutions to meet the needs of transient science space systems. First, a systematic investigation of the current transient science operations of the National Aeronautics and Space Administration’s (NASA) Tracking and Data Relay Satellite (TDRS) space data network and the Neil Gehrels Swift Observatory resulted in a formal architectural model for transient science space systems. Two methods individual missions may use to achieve timely network services were defined, quantitatively modeled, and experimentally compared. Next, the architectural model was extended to describe two alternative ways to achieve timely and autonomous space data flows to multiple space-based observatories within the context of a purposefully designed transient science observation scenario. A quantitative multipoint space data flow modeling method based in queueing theory was defined. General system suitability metrics for timeliness, throughput, and capacity were specified to support the evaluation of alternative network data flow implementations. A hypothetical design study was performed to demonstrate the multipoint data flow modeling method and to evaluate alternative data flow implementations using TDRS. The merits of a proposed future TDRS broadcast service to implement multipoint data flows were quantified and compared to expected outcomes using the as-built TDRS network. Then, the architectural model was extended to incorporate commercial network service providers. Quantitative models for Globalstar and Iridium short messaging data services were developed based on publicly available sources. Financial cost was added to the set of system suitability metrics. The hypothetical design study was extended to compare the relative suitability of the as-built TDRS network with the commercial Globalstar and Iridium networks. Finally, results from this research are being applied by NASA missions and network planners. In 2020, Swift implemented the first automated command pipeline, increasing its expected gravitational wave follow-up detection rate by greater than 400%. Current NASA technology initiatives informed by this research will enable future space-based observatories to become interoperable sensing devices connected by a diverse ecosystem of network service providers.

Christopher J. Roberts↗

Advancing AI-Driven Analysis in X-ray Absorption Spectroscopy: Spectral Domain Mapping and Universal Models

In recent years, rapid progress has been made in developing artificial intelligence (AI) and machine learning (ML) methods for X-ray absorption spectroscopy (XAS) analysis. Compared to traditional XAS analysis methods, AI/ML approaches offer dramatic improvements in efficiency and help eliminate human bias. To advance this field, we advocate an AI-driven XAS analysis pipeline that features several interconnected key building blocks: benchmarks, workflows, databases, and AI/ML models. Specifically, we present two case studies for XAS ML. In the first study, we demonstrate the importance of reconciling the discrepancies between simulation and experiment using spectral domain mapping (SDM). Our ML model, which is trained solely on simulated spectra, predicts an incorrect oxidation state trend for Ti atoms in a combinatorial zinc titanate film. After transforming the experimental spectra into a simulation-like representation using SDM, the same model successfully recovers the correct oxidation state trend. In the second study, we explore the development of universal XAS ML models that are trained on the entire periodic table, which enables them to leverage common trends across elements. Looking ahead, we envision that an AI-driven pipeline can unlock the potential of real-time XAS analysis to accelerate scientific discovery.

36 MATERIALS SCIENCE↗

Large Scale MD to Predict Epitope Regions in HIV Env [Slides]

Highly dense carbohydrates located on the surface of the HIV Env protein play a key role in immune evasion. Such evolutionary adaptation hampers any attempt to obtain a full mechanistic understanding of the role played by the glycans in protecting the virus against an effective immune response. Moreover, and due to their chemical variability, an accurate molecular understanding of the so called “glycan shield” is still limited by the lack of effective resolution of state-of-the-art experimental technics. Here, we have used extensive computational modelling in order to fill this gap, addressing the presence of a large glycan variability as observed experimentally. Based on an automated pipeline, we were able to assemble, set-up and simulate via Molecular dynamics hundreds of different glycosylated Env variants at nearly atomic resolution, recapitulating the glycosylation distributions observed experimentally. Results from these simulations were subjected to machine learning and very accurate prediction of simulation derived glycan shielding areas of each glycan as a function of static sequence features. Such predictive models of per-glycan shielding, incorporating both glycan dynamics and heterogeneity, were used to develop a novel sequence-based glycan shield mapping strategy. Parallel to these studies, we also developed an accurate machine learning approach to predict glycan heterogeneity data using sequence features and found good prediction accuracy.

59 BASIC BIOLOGICAL SCIENCES↗

Track Seeding and Labelling with Embedded-space Graph Neural Networks

To address the unprecedented scale of HL-LHC data, the Exa.TrkX project is investigating a variety of machine learning approaches to particle track reconstruction. The most promising of these solutions, graph neural networks (GNN), process the event as a graph that connects track measurements (detector hits corresponding to nodes) with candidate line segments between the hits (corresponding to edges). Detector information can be associated with nodes and edges, enabling a GNN to propagate the embedded parameters around the graph and predict node-, edge- and graph-level observables. Previously, message-passing GNNs have shown success in predicting doublet likelihood, and we here report updates on the state-of-the-art architectures for this task. In addition, the Exa.TrkX project has investigated innovations in both graph construction, and embedded representations, in an effort to achieve fully learned end-to-end track finding. Hence, we present a suite of extensions to the original model, with encouraging results for hitgraph classification. In addition, we explore increased performance by constructing graphs from learned representations which contain non-linear metric structure, allowing for efficient clustering and neighborhood queries of data points. We demonstrate how this framework fits in with both traditional clustering pipelines, and GNN approaches. The embedded graphs feed into high-accuracy doublet and triplet classifiers, or can be used as an end-to-end track classifier by clustering in an embedded space. A set of post-processing methods improve performance with knowledge of the detector physics. Finally, we present numerical results on the TrackML particle tracking challenge dataset, where our framework shows favorable results in both seeding and track finding.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

OrthoPhyl—streamlining large-scale, orthology-based phylogenomic studies of bacteria at broad evolutionary scales

Abstract There are a staggering number of publicly available bacterial genome sequences (at writing, 2.0 million assemblies in NCBI's GenBank alone), and the deposition rate continues to increase. This wealth of data begs for phylogenetic analyses to place these sequences within an evolutionary context. A phylogenetic placement not only aids in taxonomic classification but informs the evolution of novel phenotypes, targets of selection, and horizontal gene transfer. Building trees from multi-gene codon alignments is a laborious task that requires bioinformatic expertise, rigorous curation of orthologs, and heavy computation. Compounding the problem is the lack of tools that can streamline these processes for building trees from large-scale genomic data. Here we present OrthoPhyl, which takes bacterial genome assemblies and reconstructs trees from whole genome codon alignments. The analysis pipeline can analyze an arbitrarily large number of input genomes (>1200 tested here) by identifying a diversity-spanning subset of assemblies and using these genomes to build gene models to infer orthologs in the full dataset. To illustrate the versatility of OrthoPhyl, we show three use cases: E. coli/Shigella, Brucella/Ochrobactrum and the order Rickettsiales. We compare trees generated with OrthoPhyl to trees generated with kSNP3 and GToTree along with published trees using alternative methods. We show that OrthoPhyl trees are consistent with other methods while incorporating more data, allowing for greater numbers of input genomes, and more flexibility of analysis.

59 BASIC BIOLOGICAL SCIENCES↗

Label-free affinity screening, design and synthesis of inhibitors targeting the Mycobacterium tuberculosis L-alanine dehydrogenase

The ability of Mycobacterium tuberculosis (Mtb) to persist in its host may enable an evolutionary advantage for drug resistant variants to emerge. A potential strategy to prevent persistence and gain drug efficacy is to directly target the activity of enzymes that are crucial for persistence. We present a method for expedited discovery and structure-based design of lead compounds by targeting the hypoxia-associated enzyme L-alanine dehydrogenase (AlaDH). Biochemical and structural analyses of AlaDH confirmed binding of nucleoside derivatives and showed a site adjacent to the nucleoside binding pocket that can confer specificity to putative inhibitors. Using a combination of dye-ligand affinity chromatography, enzyme kinetics and protein crystallographic studies, we show the development and validation of drug prototypes. Crystal structures of AlaDH-inhibitor complexes with variations at the N6 position of the adenyl-moiety of the inhibitor provide insight into the molecular basis for the specificity of these compounds. We describe a drug-designing pipeline that aims to block Mtb to proliferate upon re-oxygenation by specifically blocking NAD accessibility to AlaDH. The collective approach to drug discovery was further evaluated through in silico analyses providing additional insight into an efficient drug development strategy that can be further assessed with the incorporation of in vivo studies.

60 APPLIED LIFE SCIENCES↗