Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “Direct Capture Component”

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 181 records · Page 10
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

First operation of a multi-channel Q-Pix prototype: measuring transverse electron diffusion in a gas time projection chamber

We report measurements of the transverse diffusion of electrons in P-10 gas (90% Ar, 10% CH 4 ) in a laboratory-scale time projection chamber (TPC) utilizing a novel pixelated signal capture and digitization technique known as Q-Pix. The Q-Pix method incorporates a precision switched integrating transimpedance amplifier whose output is compared to a threshold voltage. Upon reaching the threshold, a comparator sends a 'reset' signal, initiating a discharge of the integrating capacitor. The time difference between successive resets is inversely proportional to the average current at the pixel in that time interval, and the number of resets is directly proportional to the total collected charge. We developed a 16-channel Q-Pix prototype fabricated from commercial off-the-shelf components and coupled them to 16 concentric annular anode electrodes to measure the spatial extent of the electron swarm that reaches the anode after drifting through the uniform field of the TPC. The swarm is produced at a gold photocathode using pulsed UV light. The measured transverse diffusion agrees with simulations in PyBoltz across a range of operating pressures (200–1500 Torr). These results demonstrate that a Q-Pix readout can successfully reconstruct the ionization topology in a TPC.

47 OTHER INSTRUMENTATION↗
DOE OSTI2020

An updated estimate of the Mu2e experiment sensitivity

The Mu2e experiment at Fermilab will search for the conversion of a negative muon into an electron inside the field of a nucleus. This process does not conserve charged-lepton flavour and is heavily suppressed in the Standard Model (SM), with a branching ratio < 10-50. Any evidence of it would be an undeniable evidence of new physics beyond the SM. The project sets out to achieve a single event sensitivity of $\sim 3 × 10^{-17}$ on the ratio between the probability for a conversion of a negative muon into an electron and the one for a muon capture by the nucleus. Such a sensitivity would represent a 4 orders of magnitude improvement on the previous upper limit for the process, making possible to test predictions of different extensions of the SM. Mu2e uses three superconducting solenoids to produce and measure the muon conversions. In the first solenoid, the Production Solenoid, pions and kaons are produced, together with other secondary products, by 8 GeV kinetic energy proton interactions in a tungsten target. A gradient magnetic field is specifically designed to direct low momentum particles into the Transport Solenoid, an S-shaped magnet that filters out particles with unwanted charge and momentum. Muons, produced by pion and kaon decays, finally reach the aluminum Stopping Target in the Detector Solenoid, where they eventually stop and convert. The result of the conversion process is a monochromatic electron of ~105 MeV/c momentum. The Detector Solenoid also hosts the two main detectors: a straw tube tracker and two CsI calorimeter disks, both providing measurement of event kinematics. A germanium detector and a LaBr crystal are located downstream of the Detector Solenoid to measure the X and gamma rays produced by the muon captures in the Stopping Target. A veto system of scintillators covering the Detector Solenoid and half of the Transport Solenoid is used to identify and reject cosmic rays interactions. With respect to the initial project, the Mu2e running plan has evolved to a staged configuration with 2 years at reduced intensity before the 2025 accelerator shutdown for the neutrino beam upgrade and 2 or 3 years at full intensity after that. This, together with geometry changes and a better knowledge of detector performances obtained by the first slice tests, has required a full revision of the signal over background selection that is the subject of this thesis. In order to achieve a new estimate of Mu2e sensitivity, the simulation of the data corresponding to the first 2 years of data acquisition has been performed. This includes both conversion electrons (CE) and the main sources of background: cosmics, decay-in orbits (DIO), radiative pion captures (RPC) and antiprotons. The characteristics of the signal and of the main backgrounds have been studied to define the best selection variables for CE. A special effort has been devoted to the evaluation of the antiproton background. The lack of experimental data for antiproton production cross section makes the systematic uncertainty on this background significant. A new parameterization of the cross section has been developed to fit the existing data and to provide a more reliable estimate of the systematic uncertainty by comparing the results of the old and the new model. A special effort has been devoted to the optimization of the antiprotons Monte Carlo generator. This study has also revealed that the dominant component within this background is represented by antiprotons produced in the opposite direction with respect to the Transport Solenoid entrance and then redirected to it by back-scattering processes in the Production Target. This ultimately highlights the sensitivity of the background estimate to the G4 handling of antiproton interactions in the 1 to 3 GeV/c momentum range. Finally, the final experimental sensitivity has been studied. The momentum and time selection have been optimized to obtain the 5-sigma discovery reach or, in case of no signal, the upper limit on conversion probability. The results confirm that, in the firs t two years of data taking, Mu2e will be able to improve the current experimental sensitivity for muon-to-electron conversion in an atomic field by more than 3 order of magnitudes.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2025

Improved representation of black carbon mixing structures suggests stronger direct radiative heating

Black carbon significantly influences the Earth system because of its strong solar radiation absorption. However, its direct radiative effect remains poorly understood in current climate models, partly because current climate models oversimplify the diverse structures formed when black carbon mixes with other atmospheric components. Here we show that incorporating more realistic, multi-mixing-structure representations of black carbon increases the direct radiative effect. We find that aged black carbon particles, with thicker coatings and higher embedded fractions, enhance the direct radiative effect more efficiently. Using machine learning alongside the Community Earth System Model, we show that the direct radiative effect at the top of the atmosphere in regions with heavy black carbon pollution is 31.6% greater when multi-mixing structures are considered. These findings highlight the importance of modeling complex mixing structures of particle-resolved black carbon to accurately capture their warming impacts on global atmosphere, particularly in highly polluted regions.

54 ENVIRONMENTAL SCIENCES↗
NASA NTRS1992

Development of an integrated BEM approach for hot fluid structure interaction: BEST-FSI: Boundary Element Solution Technique for Fluid Structure Interaction

As part of the continuing effort at NASA LeRC to improve both the durability and reliability of hot section Earth-to-orbit engine components, significant enhancements must be made in existing finite element and finite difference methods, and advanced techniques, such as the boundary element method (BEM), must be explored. The BEM was chosen as the basic analysis tool because the critical variables (temperature, flux, displacement, and traction) can be very precisely determined with a boundary-based discretization scheme. Additionally, model preparation is considerably simplified compared to the more familiar domain-based methods. Furthermore, the hyperbolic character of high speed flow is captured through the use of an analytical fundamental solution, eliminating the dependence of the solution on the discretization pattern. The price that must be paid in order to realize these advantages is that any BEM formulation requires a considerable amount of analytical work, which is typically absent in the other numerical methods. All of the research accomplishments of a multi-year program aimed toward the development of a boundary element formulation for the study of hot fluid-structure interaction in Earth-to-orbit engine hot section components are detailed. Most of the effort was directed toward the examination of fluid flow, since BEM's for fluids are at a much less developed state. However, significant strides were made, not only in the analysis of thermoviscous fluids, but also in the solution of the fluid-structure interaction problem.

Dargush, G. F.↗
NASA NTRS2007

Using MODIS and GLAS Data to Develop Timber Volume Estimates in Central Siberia

The boreal forest is the Earth's largest terrestrial biome, covering some 12 million km2 and accounting for about one third of this planet's total forest area. Mapping of boreal forest's type, structure parameters and biomass are critical for understanding the boreal forest's significance in the carbon cycle, its response to and impact on global climate change. Ground based forest inventories, have much uncertainty in the inventory data, particularly in remote areas of Siberia where sampling is sparse and/or lacking. In addition, many of the forest inventories that do exist for Siberia are now a decade or more old. Thus, available forest inventories fail to capture the current conditions. Changes in forest structure in a particular forest-type and region can change significantly due to changing environment conditions, and natural and anthropogenic disturbance. Remote sensing methods can potentially overcome these problems. Multispectral sensors can be used to provide vegetation cover maps that show a timely and accurate geographic distribution of vegetation types rather than decade old ground based maps. Lidar sensors can be used to directly obtain measurements that can be used to derive critical forest structure information (e.g., height, density, and volume). These in turn can used to estimate biomass components using allometric equations without having to use out dated forest inventory. Finally, remote sensing data is ideally suited to provide a sampling basis for a rigorous statistical estimate of the variance and error bound on forest structure measures. In this study, new remote sensing methods were applied to develop estimates timber volume using NASA's MODerate resolution Imaging Spectroradiometer (MODIS) and unique waveform data of the geoscience laser altimeter system (GLAS) for a 10 deg x 10 deg area in central Siberia. Using MODIS and GLAS data, maps were produced for cover type and timber volume for 2003, and a realistic variance (error bound) for timber volume was calculated for the study area. In this 'study we used only GLAS footprints that had a slope value of less than 10 deg. This was done to avoid large errors due to the effect of slope on the GLAS models. The method requires the integration of new remote sensing methods with available ground studies of forest timber volume conducted in Russian forests. The results were compared to traditional ground forest inventory methods reported in the literature and to ground truth collected in the study area.

Ranson, K. Jon↗
DOE OSTI2020

In Vivo Molecular Insights into Syntrophic Geobacter Aggregates

Direct interspecies electron transfer (DIET) has been considered as a novel and highly efficient strategy in both natural anaerobic environments and artificial microbial fuel cells. A syntrophic model consisting of Geobacter metallireducens and Geobacter sulfurreducens was studied in this work. We conducted in vivo molecular mapping of the outer surface of the syntrophic community as the interface of nutrients and energy exchange. System for Analysis at the Liquid Vacuum Interface combined with time-of-flight secondary ion mass spectrometry was employed to capture the molecular distribution of syntrophic Geobacter communities in the living and hydrated state. Principal component analysis with selected peaks revealed that syntrophic Geobacter aggregates were well differentiated from other control samples, including syntrophic planktonic cells, pure cultured planktonic cells, and single population biofilms. Our in vivo imaging indicated that a unique molecular surface was formed. Specifically, aromatic amino acids, phosphatidylethanolamine components, and large water clusters were identified as key components that favored the DIET of syntrophic Geobacter aggregates. Moreover, the molecular changes in depths of the Geobacter aggregates were captured using dynamic depth profiling. Our findings shed new light on the interface components supporting electron transfer in syntrophic communities based on in vivo molecular imaging.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
NASA NTRS2010

CFD Assessment of Aerodynamic Degradation of a Subsonic Transport Due to Airframe Damage

A computational study is presented to assess the utility of two NASA unstructured Navier-Stokes flow solvers for capturing the degradation in static stability and aerodynamic performance of a NASA General Transport Model (GTM) due to airframe damage. The approach is to correlate computational results with a substantial subset of experimental data for the GTM undergoing progressive losses to the wing, vertical tail, and horizontal tail components. The ultimate goal is to advance the probability of inserting computational data into the creation of advanced flight simulation models of damaged subsonic aircraft in order to improve pilot training. Results presented in this paper demonstrate good correlations with slope-derived quantities, such as pitch static margin and static directional stability, and incremental rolling moment due to wing damage. This study further demonstrates that high fidelity Navier-Stokes flow solvers could augment flight simulation models with additional aerodynamic data for various airframe damage scenarios.

Frink, Neal T.↗
DOE OSTI2026

Integrated Strategies for Overcoming Resolution Limits in Electron Beam Lithography of Chemically Amplified Resists

Electron beam lithography (EBL) of chemically amplified resists (CARs) faces fundamental challenges, including stochastic electron scattering and acid diffusion, that limit resolution and reproducibility. Using SU-8 as a model CAR, this study systematically investigated complementary strategies to address these challenges, combining multipass exposure, proximity effect correction (PEC) with midrange correction factors, base quencher incorporation, and post-exposure bake (PEB) suppression. Monte Carlo simulations and calibrated PEC modeling revealed that extending the point spread function to include a midrange scattering component significantly improved critical dimension (CD) control across varying pattern densities, correcting deviations that conventional two-term PEC failed to capture. Multipass exposure, particularly 4-pass writing with a 25% offset, redistributed the dose to average stochastic beam and scattering fluctuations, reducing line-width roughness by more than 50% and yielding more uniform nanoscale features. Photoacid confinement was investigated by adding urea as a base quencher, which successfully reduced acid diffusion but introduced substantial sensitivity penalties without improving ultimate resolution or Z-factor performance, underscoring the trade-offs of chemical versus physical confinement. Suppressing PEB most directly minimized acid diffusion, resulting in improved Z-factors and reproducible 30 nm half-pitch dense line/space patterns. Overall, these results demonstrated that PEC with midrange correction, multipass strategies, quencher additives, and PEB-free processing addresses different aspects of the EBL process window and that their integration provides a comprehensive framework for managing stochastic scattering, diffusion, and chemical amplification effects. This framework advances dense nanoscale patterning in CARs and establishes guiding principles for optimizing resist design and process strategies in high-resolution EBL and potentially other advanced lithographies, such as extreme ultraviolet (EUV) lithography.

36 MATERIALS SCIENCE↗
DOE OSTI2025

Detailed Design and Cost Estimation of a 300 MWe Oxy-Fuel sCO2 Turbine

The detailed design of a 300 MWe, utility scale oxy-fuel turbine has been completed for purposed operation in the sCO2 direct fired Allam-Fetvedt cycle, targeting near-zero emissions and a 50% LHV system efficiency. The turbine and its supporting plant aim to offer a lower levelized cost of energy than a natural gas combined cycle plant employing carbon capture. The oxy-fuel turbine conditions include an inlet temperature of 1150°C and inlet pressure of 305 bar, representing temperatures near that of a gas turbine simultaneously with pressures near an ultra-supercritical steam turbine. The combustor housing and turbine designs were completed according to the ASME BPVC; the turbine case specifically incorporates a multi-body design with inner high-pressure barrel case and low-pressure (30 bar) horizontally split outer case of low-chromium steel material. Lateral rotordynamic evaluation demonstrated acceptable vibration response for a range of imbalance conditions per API standards. The cooling flow required in the six-stage turbine flowpath for 30,000 hr. blade and stator lifetime is predicted through thermal and structural modeling of the first stage. The provided cost estimate of the turbine is formed through a combination of scaled up-costs from procured 10 MWe scale sCO2 turbomachinery hardware, and vendor provided budgetary quotes of larger components including the turbine case requiring casting, welding, and final machining processes. The performance and cost estimation of the oxy-fuel turbine predicted for the completed detailed design provides important information towards future development needs for market penetration of utility scale direct fired sCO2 power cycles.

Marshall, Michael [Southwest Research Institute, S↗
NASA NTRS2014

Detailed Post-Soft Impact Progressive Damage Assessment for Hybrid Structure Jet Engines

Currently, certification of engine designs for resistance to bird strike is reliant on physical tests. Predictive modeling of engine structural damage has mostly been limited to evaluation of individual forward section components, such as fan blades within a fixed frame of reference, to direct impact with a bird. Such models must be extended to include interactions among engine components under operating conditions to evaluate the full extent of engine damage. This paper presents the results of a study aim to develop a methodology for evaluating bird strike damage in advanced propulsion systems incorporating hybrid composite/metal structures. The initial degradation and failure of individual fan blades struck by a bird were investigated. Subsequent damage to other fan blades and engine components due to resultant violent fan assembly vibrations and fragmentation was further evaluated. Various modeling parameters for the bird and engine components were investigated to determine guidelines for accurately capturing initial damage and progressive failure of engine components. Then, a novel hybrid structure modeling approach was investigated and incorporated into the crashworthiness methodology. Such a tool is invaluable to the process of design, development, and certification of future advanced propulsion systems.

bird strike↗
DOE OSTI2020

Non-autoregressive time-series methods for stable parametric reduced-order models

Advection-dominated dynamical systems, characterized by partial differential equations, are found in applications ranging from weather forecasting to engineering design where accuracy and robustness are crucial. There has been significant interest in the use of techniques borrowed from machine learning to reduce the computational expense and/or improve the accuracy of predictions for these systems. These rely on the identification of a basis that reduces the dimensionality of the problem and the subsequent use of time series and sequential learning methods to forecast the evolution of the reduced state. Often, however, machine-learned predictions after reduced-basis projection are plagued by issues of stability stemming from incomplete capture of multiscale processes as well as due to error growth for long forecast durations. To address these issues, we have developed a non-autoregressive time series approach for predicting linear reduced-basis time histories of forward models. In particular, we demonstrate that non-autoregressive counterparts of sequential learning methods such as long short-term memory (LSTM) considerably improve the stability of machine-learned reduced-order models. Further, we evaluate our approach on the inviscid shallow water equations and show that a non-autoregressive variant of the standard LSTM approach that is bidirectional in the principal component directions obtains the best accuracy for recreating the nonlinear dynamics of partial observations. Moreover-and critical for many applications of these surrogates-inference times are reduced by three orders of magnitude using our approach, compared with both the equation-based Galerkin projection method and the standard LSTM approach.

97 MATHEMATICS AND COMPUTING↗
NASA NTRS2016

A Method for Improving Hotspot Directional Signatures in BRDF Models Used for MODIS

The semi-empirical, kernel-driven, linear RossThick-LiSparseReciprocal (RTLSR) Bidirectional Reflectance Distribution Function (BRDF) model is used to generate the routine MODIS BRDFAlbedo product due to its global applicability and the underlying physics. A challenge of this model in regard to surface reflectance anisotropy effects comes from its underestimation of the directional reflectance signatures near the Sun illumination direction; also known as the hotspot effect. In this study, a method has been developed for improving the ability of the RTLSR model to simulate the magnitude and width of the hotspot effect. The method corrects the volumetric scattering component of the RTLSR model using an exponential approximation of a physical hotspot kernel, which recreates the hotspot magnitude and width using two free parameters (C(sub 1) and C(sub 2), respectively). The approach allows one to reconstruct, with reasonable accuracy, the hotspot effect by adjusting or using the prior values of these two hotspot variables. Our results demonstrate that: (1) significant improvements in capturing hotspot effect can be made to this method by using the inverted hotspot parameters; (2) the reciprocal nature allow this method to be more adaptive for simulating the hotspot height and width with high accuracy, especially in cases where hotspot signatures are available; and (3) while the new approach is consistent with the heritage RTLSR model inversion used to estimate intrinsic narrowband and broadband albedos, it presents some differences for vegetation clumping index (CI) retrievals. With the hotspot-related model parameters determined a priori, this method offers improved performance for various ecological remote sensing applications; including the estimation of canopy structure parameters.

airborne measurements↗
DOE OSTI2020

Netting and pan traps fail to identify the pollinator guild of an agricultural crop

Pollinator decline is expected to cause significant reductions in food production and plant reproduction. Quantifying the impact of pollinator decline on food production requires survey methods that can identify insect and bee species responsible for pollination of specific crops. To address this issue, we compared the effectiveness of two survey methods, netting and pan traps, at capturing the pollinators of alfalfa, Medicago sativa. Alfalfa is a major component of forage for cows and an important ingredient in chicken feed. We also examined bee species richness and diversity with these two survey methods, and compared these measures among three different colors of pan traps. Netting was more effective at capturing known pollinators of alfalfa, especially those belonging to the Bombus and Apis genera. Pan traps captured a higher bee diversity relative to netting and, like previous studies, each survey method and each trap color was more efficient at capturing certain bee genera. However, without a priori knowledge of pollinators, neither survey method could identify which of the bee species captured could pollinate alfalfa. We therefore recommend direct observations when the goal of a study is to identify pollinators or link pollinator decline to food production.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2020

Initial Engineering Design of a Post-Combustion CO 2 Capture (PCC) System for Duke Energy’s East Bend Station Using Membrane-Based Technology

The Electric Power Research Institute (EPRI) led a U.S. Department of Energy (DOE) funded study for a membrane-based post-combustion CO 2 capture (PCC) system retrofit to an existing U.S. coal power plant. EPRI teamed with technology suppliers, Membrane Technology and Research (MTR), engineering consultants Nexant, Trimeric Corporation and Bechtel Power Corporation, to develop a first-of-a-kind initial design and cost estimate for a PCC system at Duke Energy’s East Bend Station (EBS) in Kentucky. This project provides a comprehensive overview of the plant design proposed and develops estimated costs to within +/- 30% accuracy for retrofitting the existing EBS coal-fired power plant with the latest MTR’s second-generation Polaris™ membrane technology for CO 2 flue gas removal. The projects primary objective was to develop a design for Duke Energy that will require “minimally invasive surgery” on their existing 600-MWe coal-fired power plant, located on the Ohio River in Boone County, Kentucky. Unlike the current commercially available solvent-based capture systems that require a reliable source of steam to operate, the MTR membrane-based capture system is driven primarily by electric power. This direct, bolt-on approach to retrofitting carbon capture could potentially reduce the impact on the existing power plant, by minimal disruption of the existing facility’s infrastructure and operating procedures. This may also reduce the amount of retrofit downtime before the power plant can resume normal operations. A second objective was to reduce the cost of each ton of captured CO 2 while maintaining the existing 600 MW net output of the East Bend Station. With this aim in mind, various options to provide the necessary auxiliary power for the capture system were evaluated for the site. The full report describes in detail the overall design, layout and components of the entire EBS membrane capture system. The equipment and sizes, the capital cost estimate encompassing both engineering design and construction for the carbon capture process and balance of plant systems is presented. A detailed techno-economic analysis is also undertaken to examine the business case for capture.

01 COAL, LIGNITE, AND PEAT↗
DOE OSTI2021

Maturation of Rhodobacter capsulatus Multicopper Oxidase CutO Depends on the CopA Copper Efflux Pathway and Requires the cutF Product (Final Report)

The goal is to achieve a comprehensive understanding of the nature, mechanism of function and biogenesis of c-type cytochromes and their oligomeric complexes. These cytochrome are ubiquitous heme proteins that are required for cellular bioenergetics, including photosynthesis (Ps) and respiration (Res), which are central to chemical energy (ATP) production by oxidative- and photophosphorylation. We contribute to the molecular characterization of individual and membrane-integral cytochromes as parts of Ps and Res electron transport (ET) pathways, using the facultative phototrophic bacteria of as excellent models for multidisciplinary investigations. Supported by this grant we discovered novel membrane-bound cytochromes and cyts c complexes that are important for Ps- and Res-ET. We worked out their biogenesis including maturation (covalent heme addition) and assembly of mature subunits into complexes. These involve fundamental process found virtually in all organisms and are fundamental processes with major significance to the “Photosynthetic Systems” program of DOE-BES, because the cytochromes are integral components of natural energy production systems. Elucidation of basic principles, and the knowledge gained by their study greatly impact on our ability to design, engineer, and create new natural, bio-hybrid, bio-inspired and artificial systems to better capture light, transduce and store its energy with improved efficacy and are of broad significance.

14 SOLAR ENERGY↗
NASA NTRS2004

Measurement of Turbulent Pressure and Temperature Fluctuations in a Gas Turbine Combustor

The report summarizes the results of the redesign efforts directed towards the gas-turbine combustor rapid-injector flow diagnostic probe developed under sponsorship of NASA-GRC and earlier reported in NASA-CR-2003-212540. Lessons learned during the theoretical development, developmental testing and field-testing in the previous phase of this research were applied to redesign of both the probe sensing elements and of the rapid injection device. This redesigned probe (referred to herein as Turboprobe) has been fabricated and is ready, along with the new rapid injector, for field-testing. The probe is now designed to capture both time-resolved and mean total temperatures, total pressures and, indirectly, one component of turbulent fluctuations.

Povinelli, Louis↗
NASA NTRS2003

MOS Circuitry Would Detect Low-Energy Charged Particles

Metal oxide semiconductor (MOS) circuits for measuring spatially varying intensities of beams of low-energy charged particles have been developed. These circuits are intended especially for use in measuring fluxes of ions with spatial resolution along the focal planes of mass spectrometers. Unlike prior mass spectrometer focal-plane detectors, these MOS circuits would not be based on ion-induced generation of electrons, and photons; instead, they would be based on direct detection of the electric charges of the ions. Hence, there would be no need for microchannel plates (for ion-to-electron conversion), phosphors (for electron-to-photon conversion), and photodetectors (for final detection) -- components that degrade spatial resolution and contribute to complexity and size. The developmental circuits are based on linear arrays of charge-coupled devices (CCDs) with associated readout circuitry (see figure). They resemble linear CCD photodetector arrays, except that instead of a photodetector, each pixel contains a capacitive charge sensor. The capacitor in each sensor comprises two electrodes (typically made of aluminum) separated by a layer of insulating material. The exposed electrode captures ions and accumulates their electric charges during signal-integration periods.

Sinha, Mahadeva↗
DOE OSTI2026

Free Energy and Flexibility Analysis of Autoinhibited Human BRAF

The RAF serine/threonine protein kinases function as direct effectors of RAS in the intracellular transmission of extracellular growth signals, and they are key targets for drug discovery, given the high incidence of oncogenic mutations in RAF and other components of this signaling pathway. In its inactive state, RAF is held in an autoinhibited conformation in the cytosol through a combination of intramolecular interactions and binding to a regulatory 14−3−3 protein dimer. Activation of RAF is initiated by its interaction with membrane-localized GTP-bound RAS, which induces conformational changes that release RAF from its autoinhibited state. However, the molecular mechanisms governing RAF activation remain incomplete, largely due to the challenges in experimentally capturing the intermediate conformational states in this process. To address this gap, we developed a comprehensive all-atom model of BRAF based on existing cryo-EM structures. Using this model, we performed extensive molecular dynamics simulations to evaluate the stability and free energy landscape of autoinhibited BRAF in solution. Our analysis reveals conformational flexibility within the autoinhibited complex, suggesting that this dynamic behavior may play a role in facilitating BRAF activation upon engagement with the membrane-bound RAS.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗